Med/surg Ii Exam Iv

Front 1

Pancreatic Anatomy

Back 1

-V-shaped
-Very thin organ, almost not even there
-Right lobe, left lobe, and body
-Right lobe is in the mesodeoudenum
-Left lobe is in the greater omentum, next to the stomach
-Clinical signs associated with pancreatic exocrine disease can affect both lower and upper GI
--pancreas sits right next to both duodenum and colon

Front 2

Pancreatic Histology

Back 2

-LOTS of exocrine pancreatic ducts
-Islets of Langerhans are embedded in exocrine pancreas

Front 3

Pancreas Exocrine Function

Back 3

-Digestive enzymes
-Bicarbonate
-Secretes through pancreatic ducts

Front 4

Pancreas Endocrine Function

Back 4

-Secretes hormones
-Insulin (Beta cells)
-Glucagon (Alpha cells)
-Somatostatin (Delta cells)
-Pancreatic polypeptide (F cells)
-Each hormone is secreted from a different cell type within the islet of langerhans

Front 5

Insulin Synthesis

Back 5

-Synthesized and Secreted from B-cells in endocrine pancreas
-2 introns and 3 exons
-A chain
-B chain
-C chain

Front 6

Insulin C peptide

Back 6

-“Connecting peptide”
-Connects A and B chains of insulin
-A and B chains are functional part of insulin
-C peptide is produced in the exact same amount as Insulin
-can trace C peptide to see how much endogenous insulin is produced
--gives idea about endogenous reserve of insulin
-Exogenous insulin does not have C peptide

Front 7

Function of Insulin on Carbohydrate metabolism

Back 7

-Anabolic Hormone
-Increases glucose entry into muscle and adipose tissue
--no insulin, blood glucose increases
-Increases glucagon synthesis in liver
-Decreases gluconeogenesis in liver

Front 8

Function of Insulin on Protein metabolism

Back 8

-Insulin is Anabolic
-Increases amino acid uptake in muscle
-Increases protein synthesis in muscle and liver
-Decreases protein catabolism in muscle

Front 9

Functions of Insulin on Fat metabolism

Back 9

-Insulin is Anabolic
-increases lipid synthesis in adipose tissue and liver
-Decreases ketogenesis
-Activates lipoprotein lipase
-Inhibits hormone-sensitive lipase

Front 10

Lipoprotein Lipase

Back 10

-Chops off fatty acids and stores in fatty tissue
-Anabolic process, activated by insulin

Front 11

Hormone Sensitive Lipase

Back 11

-Located within fat tissue
-When activated, lyses fat stores into fatty acids
-Catabolic activity
-Inhibited by insulin

Front 12

Other Actions of Insulin

Back 12

-Increases cell growth
-Increases K, Mg, and PO4 uptake into adipose tissue, muscle, and other cells
--K, Mg, and PO4 are co-factors
--Insulin pushes into cells to make sure they are available for metabolism

Front 13

Secretion of Insulin

Back 13

-Stimulated by:
--glucose, mannose, fructose
--amino acids
--Glucagon
--Intestinal hormones: gastrin, secretin, cholecystokinase

Front 14

Glucagon

Back 14

-Antagonistic to insulin
-breaks down glycogen to glucose
-Stimulates insulin secretion, if more glucose is made it needs to be transported into cells by insulin
-Inhibited by insulin

Front 15

Counter-regulatory hormones of Insulin

Back 15

-“Diabetogenic hormones”
-increase blood glucose concentration
-Glucocorticoids
-Glucagon
-Catecholamines
-Growth Hormone

Front 16

Actions of Glucagon

Back 16

-Catabolic action
-Increases glycogenolysis, breakdown of glycogen
-Increases lipolysis, breakdown of fats
--Increases ketone body formation
-Increases gluconeogenesis, formation of glucose

Front 17

Fed state

Back 17

-Insulin kicks in to store material just ate
--increased glucose oxidation
--increased glycogen synthesis
--increased fat synthesis
--Increased protein synthesis
-Anabolic state

Front 18

Fasted State

Back 18

-Glucagon kicks in and dominates
-Uses energy stores to give energy needed
-Catabolic state
--increased Ketogenesis
--Increased gluconeogenesis
--Increased glycogenolysis

Front 19

Actions of Somatostatin

Back 19

-Internal regulator of pancreatic hormone secretion
-Inhibits secretion of insulin, glucagon, pancreatic peptide secretion
-Slows gastric emptying
-Decreases gastric acid secretion

Front 20

Actions of Pancreatic Polypeptide

Back 20

-Very little is known
-Secreted from intestinal cells, not pancreas
-Slows absorption of food from GI tract
-Inhibits gallbladder secretions
-Inhibits intestinal motility
-Inhibits pancreatic secretion

Front 21

Glucose Transport into Cells

Back 21

-Na-glucose cotransporters
-Glucose transporters

Front 22

SGLT-2

Back 22

-in kidneys
-absorbs glucose from proximal renal tubules
-Takes glucose out of the kidney filtrate and back into body
-when overwhelmed, glucose ends up in urine
-High affinity for substrate

Front 23

SGLT-1

Back 23

-in intestine
-High affinity for substrate
-Genetic defect causes diarrhea, can be fatal if not corrected quickly
--glucose stays in intestine, acts as osmotic agent and pulls water into intestine
--causes diarrhea

Front 24

GLUT-2

Back 24

-Located in beta cells in pancreas
-Low affinity for glucose
--prevents aberrant secretion of insulin and hypoglycemia
-Increased expression with hyperglycemia
-Hyperinsulinemia decreases expression

Front 25

GLUT-1

Back 25

-HIGH affinity for glucose
-Located in RBCs, kidney, glial cells of BBB
-Also in fetal tissues
-In tissues that NEED glucose!

Front 26

GLUT-4

Back 26

-In skeletal muscle, hear tissue, fat tissue
-Expression is stimulated by insulin and exercise
--exercise increases GLUT-4
-High affinity for glucose

Front 27

Diabetes mellitus

Back 27

-Diabetes= polyuria
-Mellitus= sweet

Front 28

Type I diabetes mellitus

Back 28

-Insulin dependent Diabetes, need to give exogenous insulin
-Juvenile, affects children
--can also be latent autoimmune diabetes in adults (LADA)
-Immune mediated disease?
-most common form of diabetes mellitus in dogs and cats
--ALL dogs need exogenous insulin
--most cats need exogenous insulin
-Beta-cell destruction
-Impaired insulin secretion (hypoinsulinemia)
-Can be genetic, immune-mediated, infectious, toxic, or due to some other factor

Front 29

Type II diabetes mellitus

Back 29

-Non-insulin dependent diabetes
-Do not need to give exogenous insulin, can treat with other approaches
-Uncommon in cats, rare in dogs
-Insulin resistance and impaired insulin secretion
--may or may not have beta cell destruction
-Insulin concentration may vary, can be high, medium, or low
--if high, indicates type II
-Obesity, islet-cell amyloid deposition, genetic, other factors may be involved
-Older individuals are affected
-Associated with increased BMI in humans
--Now are starting to see in young children also

Front 30

Genetic component of human Type I diabetes mellitus

Back 30

-MHC genes
--code for human leukocyte antigen class II proteins
-HLA proteins present pancreatic peptide proteins to T-cells, T-cells destroy proteins

Front 31

Canine Diabetes

Back 31

-All are hypoinsulinemic
--all need insulin
-Some have anti-pancreatic beta cell antibodies when diagnosed
--not sure if antibodies have caused destruction or formed secondary to destruction via different mechanism
-Breed predisposition may imply genetic component

Front 32

Obesity and Insulin Resistance in cats

Back 32

-Obese cats are 4x as likely to develop diabetes
-Diabetic cats are considered to be THIN
--no anabolic protein, no storage of glucose
-Hyperglycemia and increased insulin secretion are associated with weight gain
-Cat may start out as obese, but due to lack of insulin will become thin
-Obesity in cats may be associated with insulin resistance
-Obesity induced insulin resistance may be reversible if body condition returns to normal

Front 33

Mechanisms for Obesity Associated Insulin Resistance

Back 33

-Down-regulation of GLUT-4
-Impaired binding to insulin receptor
-Impaired receptor phosphorylation, tyrosine kinase activation, and IRS phosphorylation
-Excess TNF-a secretion
-Decreased leptin secretion
-Increased number of insulin receptors

Front 34

Down-regulation of GLUT-4 and diabetes

Back 34

-Exercise and insulin concentration can increase expression of GLUT-4
--more able to transport glucose into cells
-In obesity, down-regulation of GLUT-4
-If cat is put on an exercise regime, can increase GLUT-4 and decrease insulin resistance

Front 35

Amyloid Deposition and Diabetes in Cats

Back 35

-Amyloids: synthesized from islet amyloid polypeptie
-Secreted with insulin
-Deposited in beta cells
--deposited in diabetic cats (70%) and non-diabetic cats (35%)
-Deposition in beta cells causes destruction of beta cells
-Decreases insulin secretion
-increases insulin resistance
-AA sequence that forms amyloid is important for deposition in beta cells
--Cats and humans: 25-29 sequence allows for reposition of amyloid in beta cells
--In rodents, has slightly different sequence that does not allow deposition
-Dogs have the same sequence as cats but do not get amyloid deposition because they do not have hyperinsulinemia with diabetes (hypoinsulinemia)
--only occurs with insulinoma

Front 36

Genetic components in Human Type II diabetes mellitus

Back 36

-Different from type I genetic predispositions
-Mutations in insulin genes, insulin receptor, IRS-1, Glucokinase, Glycogen synthase, Mitochondrial DNA

Front 37

Genetic component in feline Diabetes mellitus

Back 37

-Burmese cats in Australia are predisposed
--only in Australia

Front 38

Secondary Diabetes Mellitus

Back 38

-Secondary to progesterone concentrations
-Progesterone causes increased secretion of GH
-GH is diabetogenic, counter-regulatory for insulin
-In dogs:
--diestrus, Pregnancy
-In cats:
--megestrol acetate

Front 39

Transient Diabetes Mellitus

Back 39

-Diabetes that comes and goes
-Rare in dogs, uncommon in cats
-Can be due to treatment with drugs that cause hyperglycemia
-Subclinical diabetes mellitus that is complicated by concurrent disorder or drug
-Animal is “teetering on edge” of diabetes and drug administration “pushed into diabetes”
-Can be caused by any disease that causes stress and induces stress hormones
--glucocorticoids, glucagon, catecholamines, Growth hormone

Front 40

Concurrent Diseases and Diabetes

Back 40

-Any concurrent disease process causes stress
-Causes release of stress hormones
--glucocorticoids, glucagon, growth hormone, catecholamines
-Counter-regulatory for insulin, can push a pancreas into diabetic state for a while

Front 41

Glucose and Insulin secretion suppression

Back 41

-Glucose itself is toxic to the pancreas
-High amounts of glucose and suppress insulin secretion
-Stress or underlying disease can cause glucagon release and high glucose levels
--will inhibit insulin release from pancreas

Front 42

Clinical Presentation of Diabetes

Back 42

-Uncompilcated diabetes mellitus
-Diabetic ketoacidosis
-Hyperosmolar non-ketotic diabetes mellitus

Front 43

Uncomplicated diabetes

Back 43

-Office visit
-There is a problem, but there is time
-In dogs, occurs at 7-9 years
-In cats, 10 years
-Samoyeds and Australian shepherds are predisposed
-Burmese cats are at increased risk
-Pitts, goldens, and german shepherds are no disposed
-Keeshunds get genetic form of disease, autosomal dominant
-intact and neutered female dogs are at increased risk
-Neutered males are at increased risk

Front 44

History and Clinical signs of uncomplicated diabetes

Back 44

-PU/PD
-Weight loss
-Polyphagia
-Blindness (dogs)
-Plantigrade stance (cats)
-Anorexia
-Vomiting

Front 45

Cataracts and Hyperglycemia

Back 45

-Glucose and fructose diffuse into the lens
-Fructose is stuck in the lens, cannot get out
-Draws water into the lens, lens swells and damages lens fibers
-In dogs, high concentration of aldose reductase in lens
--causes conversion of glucose to fructose
-cats do not have high concentration of aldose reductase in lens, do not get cataracts so much

Front 46

Physical exam for uncomplicated diabetes

Back 46

-Vary from normal to severely compromised animals
-May be non-sepcific
-Variable body weight
--underweight, normal, or obese
--depends on stage of disease
-Variable hydration status, normal or dehydrated
-hepatomegaly due to fatty lipidosis
-Cataracts (dogs)
-Plantigrade stance (cats)
-Lethargy, weakness
-Acetone breath

Front 47

Plantigrade Stance and Diabetes

Back 47

-Common in Cats
-Fructose gets into nerves and cannot get out? Aldose reductase in nerves?

Front 48

History, clinical signs, and PE for uncomplicated diabetes are affected by concurrent disease

Back 48

-UTI
-Hyperadenocorticism
-Acute pancreatitis
-Hypothyroidism
-Neoplasia
-Other infections
-Look for these diseases when diabetes becomes dysregulated! Common cause of complications with diabetes

Front 49

UTI and Diabetes

Back 49

-Common finding that can complicate diabetes
-Glucose is excellent medium for bacterial growth
-When urine is dilute, preventative mechanisms for bacteria are gone
-Neutrophils in diabetic state are compromised
--cannot adhere to the antigen
-Most common reason an uncomplicated case of diabetes becomes complicated
-Infection can increase dysregulatory hormones and decrease insulin secretion

Front 50

Hyperadrenocorticism and Diabetes

Back 50

-Cushing’s disease and diabetes are not related pathophysiologically
-Related how they affect the body
-Both occur in middle-aged, older individuals
-Increased glucocorticoid secretion causes insulin resistance
-Clinical signs and parameters are very similar to each other

Front 51

Acute Pancreatitis

Back 51

-Occurs with diabetes, cushing’s and hypothyroidism
-All 3 cause hypercholesterolemia
-high-fat diet will induce pancreatitis
-Not sure that high cholesterol is the reason 3 diseases cause acute pancreatitis, but makes sense

Front 52

Hypothyroidism

Back 52

-Endocrine disease that does not cause PU/PD
-causes hypercholesterolemia
-Immune-mediated disease
-Commonly seen with diabetes

Front 53

Diagnosis of Diabetes mellitus

Back 53

-History and clinical signs
-Physical exam findings
-Persistent hyperglycemia
--cats can have hyperglycemia due to stress, need to make sure hyperglycemia is persistent!
-Glucosuria

Front 54

DDx for PU/PD

Back 54

-Renal disease
-Liver disease
-Diabetes mellitus
-Hyperadrenocorticism
-Hyperthyroidism
-Hypoadrenocorticism
-Hypercalcemia
-Hypokalemia
-Glucocorticoid administration
-Diuretics
-Anticonvulsants
-Fluid overload
-Pyometra
-Diabetes insipidus
-Psychogenic
-Polycythemia

Front 55

Renal disease and PU/PD

Back 55

-Tubular disease: tubules do not concentrate urine as they should
-Glomerular disease: small proteins leak through glomerulus
--specifically albumin
--act osmotically, draw water into tubule lumen

Front 56

Liver disease and PU/PD

Back 56

-Liver produces urea and BUN
-BUN is needed to concentrate urine across tubules

Front 57

Diabetes and PU/PD

Back 57

-Blood glucose spills over into renal tubules when elevated
-Acts as an osmotic agent

Front 58

Hyperadrenocorticism and PU/PD

Back 58

-Glucocorticoids bind ADH receptor in kidney
-Prevents ADH from binding to receptor
-no ADH binding, no ADH effect, diuresis results

Front 59

Hyperthyroidism and PU/PD

Back 59

-Thyroid hormone increases metabolic demand
-Increases O2 demand and O2 flow
-Increases blood flow throughout the body
-Increases blood flow to kidneys, causes increased GFR and PU/PD

Front 60

Addison’s disease and PU/PD

Back 60

-Hypoadrenocorticism
-Lack of glucocorticoids and aldosterone
-Na is secreted in excess in urine
-Na acts as osmotic agent and draws water into tubular lumen

Front 61

Hypercalcemia and PU/PD

Back 61

-Can develop as a result of many disorders
--primary hyperparathyroidism
--tumors
--fungal diseases
--idiopathic
-Ca binds to ADH receptors and prevents ADH binding
-No ADH effect

Front 62

Hypokalemia and PU/PD

Back 62

-K is needed for concentration across renal tubules
-No K, no concentration and PU/PD results

Front 63

Pyometra and PU/PD

Back 63

-E. coli endotoxin is toxic to renal tubules
-Causes polyuria

Front 64

Diabetes Insipidus and PU/PD

Back 64

-Primary: ADH is not secreted from pituitary
-Secondary: ADH is present but cannot bind to receptor in renal tubules
-Decreased ADH secretion from pituitary
-or ADH is not binding to its receptor because glucocorticoids block receptor

Front 65

Common DDx for weight loss in the face of polyphagia

Back 65

-Diabetes Mellitus
-Hyperthyroidism
-GI parasites
-Exocrine pancreas insufficiency
-Protein losing enteropathy
-Protein losing nephropathy

Front 66

Polypagia and Diabetes mellitus

Back 66

-Glucose does not enter into satiety center
-No signal is sent to stop eating
-Body is also in catabolic state, animal is losing weight

Front 67

Hyperthyroidism and Polyphagia

Back 67

-Thyroid hormone increases metabolic demands
-Cat is unable to eat enough to compensate for huge energetic demands

Front 68

Exocrine Pancreatic Insufficiency and Polyphagia

Back 68

-No digestive enzymes to digest food, food passes through GI without getting digested

Front 69

DDx for Hyperglycemia

Back 69

-Diabetes mellitus (really the only good differential)
-Stress (will be transient)
-Hyperadrenocorticism
-Glucocorticoid administration
-Progesterone administration
-Megestrol acetate
-TPN or other fluid administration
-Post-prandial
-Diestrus
-Pheochromocytoma
-Acromegaly (GH secretion)
-Acute pancreatitis
-Factitious measurement

Front 70

DDx for Glucosuria

Back 70

-Diabetes mellitus
-Primary renal glucosuria
--defect in Na/Glucose transporter
-Very few DDx!

Front 71

Acute pancreatitis and glucosuria

Back 71

-Causes high secretion of insulin counter-regulatory hormones
-Especially glucagon
-Will cause hyperglycemia

Front 72

Diagnostic Evaluation for Diabetes

Back 72

-CBC/Chem: usually normal
-Urinalysis
-Urine culture
-Serum insulin or C-peptide concentration

Front 73

CBC for patients with Diabetes

Back 73

-Usually normal
-Can tell if there is something ELSE wrong with patient
-Hematocrit may be normal, low, or high
-“Stress leukogram” may be present
--mature neutrophilia, monocytosis, lymphopenia, eosinopenia
-Neutrophilia with left shift may be present if there is an infection

Front 74

Chem screen for patients with Diabetes

Back 74

-Hyperglycemia
-Increases Alanine Aminotransferase activity (ALT)
-increased Aspartate aminotransferase activity (AST)
-increase alkaline phosphatase activity (ALP)
-Lipemia, fat is not being stored
-Hypercholesterolemia
-Elevated total bilirubin concentration
-Azotemia when PU exceeds PD

Front 75

Increase alkaline phosphatase activity with diabetes

Back 75

-in epithelial biliary cells
-increases with cholestasis
-Increases with stress situations via glucocorticoids

Front 76

Urinalysis for patient with Diabetes

Back 76

-Variable specific gravity
-Glucose interferes with USG measurement via spectrometer
-May see protein in urine
-Bacteriuria
-Ketonuria with DKA

Front 77

Urine culture and sensitivity for Diabetes

Back 77

-Bacteria and WBCs may not be apparent in urine sediment even if infection is present
-urine is dilute
-May not have white cells because WBCs have difficulty migrating to the site of infection and binding bacteria
-PU/PD can mask lower UTI signs

Front 78

C-peptide concentration in Diabetic patients

Back 78

-Type I: C-peptide is low
--cannot distinguish type I from type II with low C-peptide concentration
-Type II: C-peptide is variable

Front 79

Treatment of Diabetes Mellitus

Back 79

-Insulin
-Deit
-Exercise
-Oral hyperglycemics
-treatment of concurrent disease

Front 80

Goal of Insulin Treatment

Back 80

-Want to mimic physiologic action of insulin in the body
-Produce something similar to 1st phase and 2nd phase insulin secretion

Front 81

Normal insulin secretion

Back 81

-GLUT-2 recognizes glucose in blood when it is higher than 60mg/dL
-Glucose enters beta cell and is metabolized, forms ATP
-K channels close when glucose forms ATP
--Intracellular K concentration increases
--voltage of the cell increases
-Voltage-dependent Ca channels open
--Ca flows into the cell, concentration of Ca increases
-Causes Insulin exocytosis, secretion of Insulin

Front 82

Biphasic secretion of Insulin

Back 82

-1st phase: rapid and short
--Ready to release insulin granules, already adhered to beta cell membrane
--high magnitude
--5 minutes
--goal is to reach a steady state of insulin
-2nd phase is longer
--45-60 minutes
--Goal is to maintain steady state of insulin

Front 83

Ready to Secrete Insulin granules

Back 83

-Are embedded within the beta-cell membrane
-Ready to be secreted as soon as glucose enters the beta cell
-Allows 1st phase of insulin secretion to occur rapidly and end rapidly

Front 84

Basal-bolus insulin therapy in Humans

Back 84

-Humans administer basal insulin that mimics 2nd phase of insulin secretion
-Before meals, give boluses of rapid, short-acting insulin that mimics 1st phase

Front 85

Species variation in Insulin

Back 85

-Insulin between species is very similar
-Sub-species of insulin is based on species and duration of action
-Porcine insulin is identical to dog insulin
-Short, intermediate, and long acting insulin
-Human insulin is genetically engineered and modified to look different from human insulin

Front 86

Short-acting Insulins

Back 86

-Regular insulin
-Lispro insulin (Genetically modified insulin, position 28 and 29 switch)
-Aspart Insulin (Aspartic acid substitution for proline at position 28)
-Glulisine insulin (Glutamic acid at position 29 and lysine added at B3)
-All are genetically modified human analogs of insulin
-All are clear and colorless
-All have 100 units of insulin per ml (human insulin)
--veterinary insulin has 40 units per ml

Front 87

Onset and duration of short-acting insulins

Back 87

-Shorter and faster than natural insulin products
-5-15 onset of action compared to 30-60 minute onset
-4-6 hour duration compared to 8-10 hours duration
-have been specifically designed to be faster
--designed to be given just prior to the meal
-In vet medicine, short-acting insulin can be used for dogs with DKA
--faster resolution of DKA, glucose normalization, glucose plateau

Front 88

Fructosamine

Back 88

-Albumin bound to glucose
-Once glucose reaches a certain threshold, glucose binds to fructose and forms fructosamine

Front 89

Intermediate Acting Insulins

Back 89

-NPH
-Lente
-rPZI

Front 90

Neutral Protamine Hagedorn (NPH)

Back 90

-Produced by recombinant DNA technology
-Uses non-pathogenic laboratory strain of E. coli
-Identical to human insulin
--comes in 100 units of insulin per ml, human dosage
-Has been available for a long term, is in generic form
-Cheaper product
-Peaks at 2 hours but lasts much longer
-in well-regulated dogs intermediate insulin dose can be 0.6 units per kilo

Front 91

NPH in cats

Back 91

-Not well-reported
-Good for financial constraints

Front 92

Porcine Insulin Zinc

Back 92

-Lente in humans
-Vetsulin in animals
-produced from Pigs
-FDA approved for dogs and cats
-SHAKE well until homogenous before using
-Starting dose of 0.5 units per kg twice daily
-comes in pen form for easy injections

Front 93

Recombinant Protamine Zinc Insulin (rPZI)

Back 93

-Not produced from an animla
-Veterinary product, approved for use in dogs and cats
-Identically to human insulin
-0.5 units per kg 2x daily

Front 94

Long Acting Insulin

Back 94

-Glarginie
-Detemir
-Mimic basal insulin secretion
-Both marketed for humans, sold in 100 units per ml

Front 95

Glargine

Back 95

-Long-acting insulin
-Peakless insulin used in humans
-Asparagine at position A21 is replaced with Glycine
-2 Arginine residues added to C-terminal of the B-chain at position B30
-Injected in solution with pH of 4
--low pH is important for long duration of action
-Cannot be diluted or mixed with ANYTHING
-Mimics flat inter-parandial insulin secretion, peakless
-Onset in 2-4 hours
-Duration of 20-24 hours
-Supplemented with rapid and short-acting insulin at meal times
-Starting dose of 0.5 units per kg SQ twice per day

Front 96

Glargine in Dogs

Back 96

-Good for easy regulation
-Can be used when other insulin products have not worked well
-Peak-less insulin in dogs

Front 97

Detemir Insulin

Back 97

-“Levemir”
-Long-acting insulin
-Approved by FDA
-Commercially available in UK
-Injected or prepared in neutral pH
-Long mechanism of action because it binds to albumin, slowly released from albumin
-Usually given every 12 hours
-has been reported to cause anaphylactic and allergic reactions in humans
--causes local irritation and pain at site of injection
-Hard to monitor pain and inflammation in dogs, not worth using
-0.1-0.2 units per kg
--hard to draw up, has caused overdoses

Front 98

Which insulin is best?

Back 98

-The one that works best for the individual animal
-Glargine is best for cats
-NPH is most used in dogs
--when problems arise with NPH, switch to glargine

Front 99

Frequency of Insulin Therapy

Back 99

-Most dogs and cats need twice daily insulin treatment
-Successful treatment with once daily is rare in dog, uncommon in cat
-May change with increased use of glargine or detemir
-Intermediate acting insulin is given every 12 hours to start
-Long-acting insulin can try at 24 hours to start
-Initial dose is 0.5 units per kg
--except detemir, 0.1-0.2 units per kg
--glargine in dogs is 0.3 units per kg
-Dose of insulin is adjusted based on glucose curves

Front 100

40 units vs. 100 units

Back 100

-Need to look at “fine print” of the insulin syringe!
-If a 40 unit syringe is used with a 100 unit product, will overdose patient!
-ALWAYS give insulin in an insulin syringe!

Front 101

Dietary Management with Diabetes

Back 101

-Try to have food at a fixed time
-Fixed caloric intake based on fixed amount of insuli
-Give diet that will decrease post-prandial blood glucose fluctuations
-Weight reduction diet for obese patients
-Dietary management for dogs and cats is different
-Make sure the owner knows how crucial the diet is!

Front 102

Dietary management of diabetes in Dogs

Back 102

-High insoluble fiber diet
--weight loss
--slow carbohydrate absorption
--decreases post-prandial blood glucose fluctuations
--increases insulin sensitivity
-Rich in complex carbohydrates
--takes time to break down, more gradual glucose release
-Fixed protein and restricted fat content
-Fixed feeding schedule
-Give dogs that do not need to lose weight the same diet, helps regulate the diabetes
-Goal is diabetic regulation

Front 103

Details of the feline diet

Back 103

-Carnivores
--consume high protein and low carbohydrate diet
-Constant gluconeogenesis
--energentically expensive process
-Possibly no glucokinase in liver and pancreas?

Front 104

Guidelines for dietary management in Cats

Back 104

-Need to change diet to something the cat will eat
--if they don’t eat, get hepatic lipidosis
--try a variety of diets that the cat will eat
-Fixed caloric intake if possible
-Maintain optimal body condition
-Low carbohydrate diet
-High protein diet
-Most important is that the cat eats!

Front 105

Exercise management and Diabetes

Back 105

-Up-regulates GLUT-4
-Insulin sensitivity is increased with increased blood flow, glycogen synthase activity, and glucose storage as glycogen
-In humans increases insulin-stimulated glucose transport and glycogen synthesis

Front 106

Exercise in dogs and cats with Diabetes

Back 106

-Exercising cats is difficult
-Diabetic dogs can benefit from exercise
--promote weight loss in obese patients
--increase blood flow
--Possibly increases glucose transport and glycogen synthesis
-Need to build up to exercise gradually
--adjust food intake on the days that dog exercises
--want to avoid hypoglycemia on exercising days
--increase exercise 2 minutes every day

Front 107

Oral Hypoglycemics

Back 107

-Main use in humans for diabetes type II
-Rare in dogs and cats, not that helpful
-increases insulin secretion from beta cells
-Binds to GLUT2 receptor on beta cells
--causes metabolism and creation of ATP, shuts down K transporter, K builds up and changes charge of cell, Ca voltage-gated channels open, Ca floods into cell and causes release of insulin

Front 108

Sulfonylurea Mode of Action

Back 108

-Stimulates insulin secretion from pancreatic beta cells
-Binds to receptors on beta cell membranes and induces ATP-dependent K channels to close
-Only works if animal has some type of type II diabetes

Front 109

Adverse side effects of Sulfonylurea in Humans

Back 109

-Hypoglycemia
-Allergic reactions
-GI intolerance
-Hepatotoxicity
-Severe dermatitis
-Hemolytic anemia
-Thrombocytopenia
-Agranulocytosis
-Hyperinsulinemia and risk for atherosclerosis
-May be cardiotoxic

Front 110

Glipizide in Cats

Back 110

-Difficult to predict which cats will respond
-Decision to treat with glipizide is based on clinical presentation
-only try in cats that are relatively healthy
-meant to treat mild hyperglycemia in relatively stable animals
-2.5mg PO twice daily for 2 weeks
--if still hyperglycemic, increase to 5mg PO twice daily
--if still hyperglycemic at 4 weeks, discontinue and treat with insulin
-Give orally twice per day

Front 111

Cardiotoxicity of oral hypoglycemic

Back 111

-K channels need to be open during ischemic events to promote vasodilation
-If channels in heart stay closed, may worsen myocardial infarctions
-Unknown what it does in cats

Front 112

Transdermal Glipizide

Back 112

-Not recommended
-inconsistent absorption

Front 113

Adverse effects of Glipizide in cats

Back 113

-Vomiting after administration
-Hypoglycemia
-Increased serum hepatic enzyme activity
-Icterus
-Removing the drug causes issues to go away

Front 114

Glipizide in Dogs

Back 114

-Has not been reported

Front 115

Treatment of Diabetes mellitus

Back 115

-Insulin
-Diet
-Exercise
-Oral hypoglycemic (glipizide)
-Treatment of concurrent diseases

Front 116

Home care for the diabetic dog

Back 116

-VERY IMPORTANT! Crucial for care of a diabetic dog!
-Note changes in clinical signs, be very observant
-Monitor urine glucose twice daily before feeding
--ketonuria is an emergency
-Not presence or absence of ketones in urine 2x daily
-Feed 2x daily
-Administer insulin 2x daily after feeding
-If dog vomits or does not eat a meal, administer half insulin dose and seek veterinary advice
--do not skip insulin injection
-If animal seizures, weakness, or signs of hypoglycemia occur, give karo syrup to the gums (on finger onto gums)
--indicate hypoglycemia

Front 117

Concurrent diseases and Diabetes

Back 117

-Concurrent diseases cause STRESS
-Induces counter-regulatory hormones
--glucocorticoids
--catecholamines
--Growth Hormone
--Glucagon

Front 118

Home care for the Diabetic Cat

Back 118

-May require free choice food
-Cannot be fasted! Need to eat whatever they will
-Sampling urine at fixed times can be difficult
-Cats do not like exercise
-Monitoring the weight is the best indicator

Front 119

Monitoring response to treatment for Diabetes

Back 119

-Monitor clinical signs
--PU/PD
--polyphagia
--body weight
-Monitor glucosuria and ketonuria
-perform glucose curves
-Measure glycosylated Hb or fructosamine

Front 120

Glucose Curve

Back 120

-Needed to determine proper dose of insulin
-only really used if there is a problem with insulin dosage or long time since last glucose curve was done
-Measure every 2 hours for at least 12 hours in animals that get insulin daily
-Single measurement of blood glucose can not be used to determine dose of insulin

Front 121

Somogyi Effect

Back 121

-Only happens with exogenous insulin, when too much is given
-Catecholamines, glucocorticoids, glucagon, and growth hormone are secreted in response to severe insulin-induced hypoglycemia and cause pronounced hyperglycemia
--over-correct for hypoglycemia
-Body’s mechanism to counteract hyperinsulinemia and massive drop in glucose
-If glucose is too high, need to increase insulin
-If glucose is too low, need to decrease glucose

Front 122

Spot glucose measurements

Back 122

-Can be very misleading!
-Have no idea what the glucose was doing for the rest of the day

Front 123

Analyzing a glucose curve

Back 123

-Onset of action: From time 0, when the glucose levels start to decrease
--number of hours after time 0 it takes blood glucose decreases below 250
-Duration of action: Number of hours after time 0 it takes for glucose to return to 250 after it has decreased
-Peak action: Time of maximum effect
--time point when the blood glucose is the lowest

Front 124

Adequate Glycemic Control

Back 124

-Dogs: achieved when blood glucose concentration is between 100-250 mg/dL
-Cats: achieved when blood glucose concentration is between 100-300 mg/dL
--assume a cat has some level of stress going on all of the time

Front 125

Insulin Resistance

Back 125

-Suspected when hyperglycemia is present in the face of insulin therapy above 1.5 units/kg per injection
-Something is getting in the way on insulin action

Front 126

Reasons for Insulin Resistance

Back 126

-Improper handling of insulin
--keep in fridge
--can be left out overnight, but should not be left out for days
-Improper administration of Insulin
-Outdated or inactive insulin
--do not use if more than 6 months old or opened 6 months ago
--activity has probably worn off a little bit
-Improper dose or frequency of insulin administration
-Poor absorption of insulin
-Anti-insulin antibodies
-Somogyi effect

Front 127

Concurrent Disorders that can cause insulin resistance

Back 127

-UTI
-Pyoderma
-Pneumonia
-Ketoacidosis
-Hyperadrenocorticism (Cushing’s, similar clinical signs to diabetes)
-Hyperthyroidism
-Hypothyroidism
-Acute pancreatitis
-Exocrine pancreatic insufficiency
-Diestrus
-Acromegaly
-Renal, liver, cardiac insufficiency
-Obesity
-Drug induced (prednisone)

Front 128

Glycosylated Hemoglobin

Back 128

-Hb that is bound irreversibly to glucose
-Non-enzymatic insulin-dependent bond
-Reflects serum blood glucose concentrations over past 3-4 months
-If animal is hyperglycemic, will be high
-If animal is not hyperglycemic, will be normal

Front 129

Fructosamine

Back 129

-Non-reversible binding of glucose to albumin
-Reflects blood glucose concentration over past 1-3 weeks
-Non-enzymatic insulin-dependent bond of glucose to various serum proteins
-Use in cats that will not tolerate a blood-glucose curve
--not worth the cat freaking out
-Can be high with somogyi effect
--indicates animal is getting too much insulin
-Can also be high if animal is getting too little insulin

Front 130

Long-term Complications of Diabetes Mellitus

Back 130

-Cataracts
-Uveitis
-Retinopathy
-Neuropathy
-Nephropathy

Front 131

Diabetes Prognosis

Back 131

-generally good
-Animals do not die from Diabetes, die from other old-age problems
-Owner needs to be willing and able to take care of the animal
-Quality of life of the animal is good to excellent

Front 132

Diabetic Ketoacidosis (DKA)

Back 132

-Complicated diabetes mellitus
-Ketones are synthesized as a substitute form of energy
--glucose is not present
--body resorts to using fat, ketones are produced
-Too much keto-acids result in acidosis and severe electrolyte abnormalities
-Acidosis and electrolyte abnormalities can be life threatening

Front 133

Assessing ketones

Back 133

-Use keto-stix
-Sticks look for acetoacetate
--not the most common ketone body around
--most common is beta-hydroxybutyrate
-If keto-stix is netagive, does not mean the patient does not have ketones

Front 134

Development of DKA

Back 134

-Type I diabetics develop DKA when insulin is 0
-Type II diabetics will not develop DKA because they always have some reserve of insulin
-Not the whole story, some dogs with normal insulin will develop DKA

Front 135

DKA develops due to another disease

Back 135

-Other disease causes increase in glucocorticoids, glucagon, growth hormone, and catecholamines
-Cause insulin resistance
-Insulin resistance pushes patients into DKA
-Glucagon is most studied

Front 136

Glucagon and DKA

Back 136

-is secreted and remains high in the proper time interval
-Best catabolic hormone of counter-regulatory insulin hormones
-Catabolic for carbohydrates, protein, and fats
--best anti-insulin hormone
-Causes insulin dysregulation

Front 137

Concurrent disorders and DKA

Back 137

-70% of dogs with DKA have confirmed concurrent disorder
--acute pancreatitis
--UTI
--Hyperadrenocorticism (Cushing’s)
-55% of cats with DKA have confirmed concurrent disorder
--Acute pancreatitis
--Hepatic lipidosis
--Chronic renal failure
--UTI
-Numbers are probably much higher

Front 138

3 ketone bodies

Back 138

1. beta-hydroxybutyrate
--higher concentrations with increased available hydrogen ions
2. Acetoacetate
-Acetoacetate and beta-hydrocybutyrate are in opposite concentrations from each other
3. Acetone
--can be smelled on breath
Formation of ketone bodies

Hint 138

-Oxidation of fatty acids
-Made from 2 acetyl CoA or 3 acetyl CoA units

Front 139

2 Acetyl CoA unit Pathway

Back 139

-2 units of acetyl Co-A can condense to Acetoacetyl CoA in many organs
-Acetoacetyl CoA is converted into acetoacetate
--deacylase present in liver only
-Acetoacetate is converted to beta hydroxybutyrate and acetone in liver
-More acidic environment, more likely to form beta-hydroxybutyrate
--does not show up on keto-stick

Front 140

3 Acetyl CoA unit Pathway

Back 140

-Acetoacetyl CoA condenses with 3rd unit of acetyl-CoA
--forms 3-hydroxy-3-methylglutary CoA (HMG CoA)
-HMG CoA is metabolized to acetoacetate

Front 141

Acetyl CoA production

Back 141

-Formed with oxidation of a fatty acid
-Every catabolic action/degradation/oxidation of fat makes Acetyl CoA
-Assocaited with lipolysis

Front 142

Alteration of Acetyl CoA production in Diabetes mellitus

Back 142

-Decreased insulin action
-increased glucagon action
-Results in increased fatty acid oxidation
-Results in excess production of Acetyl CoA due to lipolysis
-Acetyl CoA should go into krebs cycle to produce energy
--needs amino acids, but are being used elsewhere to produce energy
-Less Acetyl Co enters krebs cycle
-Forming too much, and does not enter krebs cycle to be formed into ATP

Front 143

Acetyl CoA summary

Back 143

-Acetyl COA is the precursor for ketone body synthesis
-in Diabetes mellitus, excess synthesis of Acetyl CoA due to excess fatty acid oxidation
-Accumulation of Acetyl CoA due to lack of pyruvate synthesis
--Acetryl CoA is unable to enter the krebs cycle
-Excess synthesis and lack of Acetyl CoA use results in accumulation and conversion to ketone bodies

Front 144

Formation of ketone Bodies

Back 144

-Fasting
-Dehydration
-Insulin deficiency
-Excess diabetogenic hormones
--mostly glucagon
--catecholamines
--glucocorticoids
--growth hormone
-Excess diabetogenic hormones are due to concurrent disease or stress

Front 145

Metabolic Acidosis

Back 145

-Formation of keto-acids
-Exacerbated by vomiting, dehydration, and poor renal perfusion

Front 146

Clinical signs of DKA

Back 146

-Chronic untreated diabetes mellitus
--PU/PD, polyphagia, weight loss
-Concurrent disease
-Acute onset of DKA
-Owner will report clinical signs that “pushed the animal over the edge”

Front 147

DKA signalment in cats

Back 147

-Presents at a younger age
--presence of concurrent disease pushes pancreas into failure earlier
-Abyssinians and Siamese are over-represented
-Neutered males, and males in general
-Overweight body condition but thinner due to crisis

Front 148

Clinical signs of Dogs presenting with DKA

Back 148

-PU/PD
-Lethargy
-inappetence or anorexia
-Vomiting
-Weight loss

Front 149

Clinicals signs of cats presenting with DKA

Back 149

-Lethargy
-Inappetence
-Weight loss
-PU/PD
-Vomiting
-Diarrhea
-Polyphagia

Front 150

Physical exam of dog with DKA

Back 150

-Overweight or underweight body condition
-Dehydration
--most important, dangerous, and unspecific sign
-Cranial organomegaly
-Abdominal pain
-Cardiac murmur
-Mental dullness
-Dermatologic abnormalities
-Dyspnea, coughing, abnormal lung sounds
-Cataracts

Front 151

Physical exam of cat with DKA

Back 151

-Dehydration (most important!)
-Neurologic abnormalities
--dull mentation, obtunded, recumbent
-Plantigrade stance
-Underweight
-Overweight
-Obese

Front 152

Diagnostic Evaluation of animals with DKA

Back 152

-Complete diagnostic evalulation is recommended
-Need to find out what the other disease is that is causing DKA
-CBC/Chem
-Urinalysis
-Electrolytes

Front 153

CBC for animals with DKA

Back 153

-Anemia in 50% of dogs
-Anemia is unrelated to hypophosphatemia
-Left shift neutrophilia
-Normal platelet count in most cats, thrombocytosis in 10% and thrombocytopenia in 17%

Front 154

Chem screen for dogs with DKA

Back 154

-97% of dogs have high ALP activity
--much higher than ALT and AST
--produced in bile duct epithelium
--due to increased stress and concurrent pancreatitis
-50% have high cholesterol, hyperlipidemia

Front 155

Chem screen for Cats with DKA

Back 155

-54% have high ALT
-96% have high AST
--from hepatocytes and muscle lysis
--occurs with hepatic lipidosis
-59% have high bilirubin
-No steroid-induced ALP

Front 156

Urinalysis in animals with DKA

Back 156

-Glucose
-Ketones (acetoacetate)
-Proteinuria
-Sediment may not reveal infection, may need to do a culture

Front 157

Electrolyte abnormalities with DKA

Back 157

-Hypokalemia
-Hypophosphatemia
-Hyponatremia
-Hypomagnesia
-At the end of the day, all are decreased
-All are important, all can kill the patient!

Front 158

Potassium and DKA

Back 158

-Animal is in a state of acidosis, high concentration of H ions outside of the cell
-Push hydrogen ions into cell by trading with K ions
-K ions go out and are excreted in urine, vomiting
--can also bind to keto acids to form keto-salts
-Insulin is anabolic, pushes electrolyte cofactors into the cells
--shifts from extracellular fluid into cells very rapidly, dangerous!
-happens acutely

Front 159

Clinical significance of hypokalemia

Back 159

-Muscle weakness
-Paralysis
-Respiratory depression
-Cardiac electrical conduction abnormalities

Front 160

Hypokalemia in dogs with DKA

Back 160

-Initially low in half of dogs
-Eventually low in most dogs

Front 161

Hypokalemia in Cats with DKA

Back 161

-Initially half are low
-Eventually most become low

Front 162

Hypophosphatemia and DKA

Back 162

-High concentration of H ions, neutralize by pushing negatively charged PO4 out of the cell
-Intracellular store of phosphate is destroyed
-With animal on fluids, osmotic diuresis
-Insulin therapy moves phosphate back into cell
--dramatic shift from extracellular to intracellular space
-No exchange, just pushed out because it is negatively charged

Front 163

Clinical signs of Hypophosphatemia

Back 163

-Weakness
-Respiratory depression
-Hemolytic anemia
-Cardiac dysfunction
-Decreased 2,3-DPG and delivery of oxygen
-Seizures in dogs

Front 164

Hyponatremia and DKA

Back 164

-High concentration of hydrogen ions outside of cell causes activation of Na/H exchanger to correct pH
--H is brought into cell, Na goes out
-Na is flushed out with osmotic diuresis
-Hyperlipidemia causes fictitious hyponatremia and interferes with measurement

Front 165

Clinical significance of Hyponatremia

Back 165

-Relative Intracellular hypernatremia if extracellular Na is depleted
--Water flow into cells to osmotically balance
-Cerebral swelling and cell rupture
-Altered mental status

Front 166

Hypomagnesium and DKA

Back 166

-Insufficient dietary intake of Mg
-Increased renal excretion of Mg
-Increases risk of heart disease
-Get hypokalemia, hyponatremia
--exacerbates problems with other electrolytes
-Insulin resistance
0Hypertension, hyperlipidemia, and increased platelet aggregation

Front 167

Magnesium in cats with DKA

Back 167

-Total initial serum Mg concentration is positively correlated with creatinine concentration and ionized Mg concentration
-At risk for underlying renal disease
--more likely to leak Mg?

Front 168

Association between venous pH and discharge

Back 168

-low pH leads to less likely to be discharged
-More acidotic patients are less likely to go home

Front 169

Outcome of Cats with DKA

Back 169

-18% recurrence
-35% euthanized at median treatment
-12% euthanized after second or third episode of DKA
-3% died during initial 24 hours of treatment
-Creatinine, BUN, and Mg represent renal function and indicate outcome in cats
-Increased bilirubin concentration is associated with poor outcome

Front 170

Treatment of DKA

Back 170

-IV fluids
-Correction of electrolyte abnormalities
-Correction of hyperglycemia (insulin)
-Correction of acidosis
-Address concurrent disease
--if concurrent disease is not addressed, DKA will not go away

Front 171

Fluid therapy for DKA

Back 171

-IV fluid therapy is most important component of DKA therapy
--Dehydration can kill the animal!
-Helps control electrolytes
-Saline helps with Na
--add K
-Just giving fluids will bring down glucose levels
-DO NOT give insulin right when patient arrives! Will cause glucose to drop too quickly

Front 172

Correction of hypokalemia and DKA

Back 172

-Add K to 250 ml bag
-Administer at a rate that is not greater than 0.5 mEq/kg/hour
-Make sure Mg is normal and there are not other electrolyte abnormalities

Front 173

Correction of Hypophosphatemia in patients with DKA

Back 173

-Give potassium phosphate
--Administration of K must also be taken into account!

Front 174

Correction of hyponatremia in DKA patients

Back 174

-Give Na, saline diuresis

Front 175

Correction of hypomagnesia in DKA patients

Back 175

-Magnesium sulfate

Front 176

Correction of hyperglycemia in patients with DKA

Back 176

-Give fluids first
-After 6 hours, give insulin
--only give IV or IM, not SQ
--patients are too dehydrated, will not absorb anything from SQ
-Give 2.2 units/kg/250ml bag of NaCl to both dogs and cats

Front 177

Time to resolution of DKA

Back 177

-Regular insulin: 60 hours
-Lispro: 30 hours

Front 178

IM insulin Administration

Back 178

-Administer regular crystalline insulin IM every hour
-Begin with 0.2 units/kg IM
-Proceed with 0.1 units/kg 1 hour later
-Continue with 0.05, 0.1 or 0.2 units/kg depending on how fast glucose has dropped
--if glucose drops less, give more insulin
-Can also Use glargine insulin given IM

Front 179

Correction of Aicidosis in patients with DKA

Back 179

-Give Sodium Bicarbonate at 0.3x body weight * base excess
-Bicarbonate administration Can contribute to worsening of cerebral edema
--poor prognosis in humans
--Only consider if pH stays below 7 for more than 1 hour

Front 180

Address concurrent diseases in patients with DKA

Back 180

-Totally necessary!
-Treatment of concurrent diseases decreases secretion of diabetogenic hormones
--results in decreased insulin resistance

Front 181

Prognosis for DKA

Back 181

-70% of patients survived and were discharged
-Mean hospitalization time was 6 days
-7% develop recurring episodes
-Dogs with hyperadrenocorticism (cushing’s) are less likely to be discharged
-Degree of acidosis is associated with outcome

Front 182

Hyperosmolar Non-ketotic diabetes mellitus

Back 182

-Very very very rare, 1% of all diabetics
-Hyperosmolarity, greater than 325
-Severe hyperglycemia
-No ketosis because there is some residual insulin action
-Increased plasma osmolarity results in intracellular fluid moving to extracellular space
-Rapid correction of hyperosmolarity is potentially painful

Front 183

Insulinoma

Back 183

-Pancreatic beta cell tumor
-Most common pancreatic tumor in dogs
-Functional tumor, Secretes insulin without inhibition
-Excess insulin results in hypoglycemia
-In normal patients, insulin secretion is depressed when blood glucose is less than 60 mg/dl
-In patients with insulinoma, high concentrations of insulin are secreted independently of blood glucose concentration

Front 184

Excess insulin concentration

Back 184

-Results in decreased blood glucose concentration
-Increased glucose uptake from the blood into the tissue
-Decreased glucose is released from the liver into the blood
--decreased gluconeogenesis and glycogenolysis, no glucose is released into the blood

Front 185

Effects of low blood glucose concentration

Back 185

-Hypoxic damage to CNS
--first in cerebral cortex, then in metabolically slower areas
-PNS degeneration and demyelination can occur
-Release of diabetogenic hormones
--glucocorticoids, glucagon, growth hormone, catecholamines

Front 186

Insulinoma signalment

Back 186

-Develops in older patients
-Mostly a dog disease
--rare in cats, may have increased frequency of insulinoma
-Can effect many breeds
-No sex predilection

Front 187

History of Insulinoma

Back 187

-Initial signs can be mild, usually present for 6 months-1 year before owner does anything
-Critical signs may be episodic
--release of diabetogenic hormones temporarily resolves hypoglycemia
-Clinical signs are worsened by fasting, excitement, exercise, and eating
--Eating stimulates insulin secretion that results in post-prandial hypoglycemia

Front 188

Hypoglycemia clinical signs

Back 188

-Lethargy
-Weakness
-Ataxia
-Collapse
-Abnormal behavior or mentation
-Seizures
-Coma

Front 189

Clinical signs due to release of diabetogenic hormones

Back 189

-Tremors, muscle fasciculations
-Nervousness, restlessness
-Polyphagia
-PU/PD

Front 190

Effects of Hyerinsulinemia on protein and fat

Back 190

-Decreases mobilization of amino acids from muscle
-Decreases lipid mobilization from adipose tissue
-Decreases catabolic effects

Front 191

Physical exam for Insulinoma

Back 191

-Usually unremarkable
-Possible weight gain due to anabolic effect of insulin or athletic appearance
-Possible peripheral neuropathy

Front 192

Diagnostic work-up for insulinoma

Back 192

-CBC
-Chem screen
-Urinalysis
-Ultrasound
-Insulin concentration

Front 193

Abdominal Ultrasound for Insulinoma

Back 193

-Does not usually identify a pancreatic miss
-If it does, is very helpful!

Front 194

Definitive diagnosis for Insulinoma

Back 194

-High insulin concentration and low blood glucose
-Need to wait until blood glucose has gone down before measuring blood glucose

Front 195

Treatment options for Insulinoma

Back 195

-IV dextrose administration in acute stage
-Surgical excision is optimal but difficult
--most likely has metastasized
-Feed complex carbohydrates via canned or dry food
--feed frequently
-Avoid moist, soft foods
-Prednisone: catabolizes glycogen to carbohydrates
-Diazoxide
-Somatostatin
-Streptozocin

Front 196

Diazoxide as treatment for insulinoma

Back 196

-Treatment for insulinoma
-Activates ATP-sensitive K channels, opens channels
--decreases cell membrane potential, Ca channels do not open
-Inhibitis insulin secretion by decreasing intracellular Ca
-Stimulates hepatic gluconeogenesis and glycogenolysis
-Inhibits tissue uptake of glucose

Front 197

Prednisone as treatment for insulinoma

Back 197

-Increases gluconeogenesis
-Decreases peripheral glucose uptake

Front 198

Somatostatin as treatment for Insulinoma

Back 198

-Inhibits synthesis and secretion of insulin from normal and neoplastic beta cells

Front 199

Streptozocin

Back 199

-Nitrosurea antibiotic
-Derived from Streptomyces acromogenes
-Destroys beta cells in pancreas and metastatic lesions
--selectively affects beta cells in all mammalian cell cycle stages
-Alkylating agent
-Not myelosuppressive
-Used in humans with metastatic beta cell carcinoma

Front 200

Insulinoma Prognosis

Back 200

-Poor
-Mean survival time is 1 year from onset of clinical signs
-Only chance for a cure is surgery

Front 201

Rare Endocrine Pancreatic Diseases

Back 201

-Glucagonoma
-Gastrinoma
-Pancreatic polypeptidoma

Front 202

Glucagonoma

Back 202

-Pancreatic alpha cell tumor
-Rare in the dog
-Not yet reported in the cat

Front 203

Pathophysiology of Glucagonoma

Back 203

-Excess glucagon results in insulin resistance and diabetes mellitus
-Extremely catabolic
-profound deficiency in amino acids results in dermatologic issues
--necrolytic migratory eruthema in humans

Front 204

Necrolytic Migratory Erythema

Back 204

-AKA superficial necrolytic dermatitis, metabolic epidermal necrosis
-Seen in association with severe liver disease and diabetes mellitus
--in humans associated with glucagonoma
-Severe hyperkeratosis
-Skin erosions, ulcerations, alopecia, exudation, thick adherent crusts around mucocutaneous junctions, ears, and pressure points
-Secondary skin infections are common

Front 205

Clinical signs of Glucagonoma

Back 205

-Necrolytic migratory erythema
-Diabetes mellitus
-Small intestinal diarrhea

Front 206

Diagnosis of Glucagonoma

Back 206

-Necrolytic migratory erythema
-Diabetes mellitus
-Hyperglucagonemia
-presence of a pancreatic tumor containing glucagon
--biopsy pancreas

Front 207

Diagnosis of Hepato-cutaneous Syndrome vs. glucagonoma

Back 207

-Necrolytic migratory erythema
-Diabetes mellitus
-Severe liver disease
-No hyperglucagonemia
-No pancreatic tumor

Front 208

Treatment for Glucagonoma

Back 208

-Surgical excision
-Somatostatin
-Treat skin diseases with IV administration of amino acids
-Oral supplementation of amino acids via egg yolks
-Treat secondary infections

Front 209

Prognosis for glucagonoma

Back 209

-poor
-Quality of life is not good

Front 210

Gastrinoma

Back 210

-Pancreatic tumor
-Arises from residual fetal delta cells or delta cells that revert back to fetal function and secrete gastrin
-normal adult pancreas does not secrete gastrin
-Gastric secretion results in increased gastric acid (HCl) secretion
--causes GI ulceration, vomiting, diarrhea, anorexia, weight loss, lethargy, depression

Front 211

Clinical sigs of Gastrinoma

Back 211

-Vomiting, sometimes with blood
-Diarrhea, hematochezia, melena
-Weight loss
-Anorexia
-Abdominal pain
-PU
-Lethargy, depression
-Regurgitation

Front 212

Gastrinoma PE

Back 212

-Usually unremarkable
-Animal will be vomiting
-May see dehydration, abdominal pain, tachycardia, fever
-palpable abdominal pancreatic mass sometimes

Front 213

Diagnosis of Gastrinoma

Back 213

-Hypergastrinemia, high gastrin concentration
-Secretin or calcium stimulation test
-Pancreatic mass that contains gastrin

Front 214

Gastrinoma treatment

Back 214

-Surgical resection!
-Somatostatin
-Cometidine, ranitidine, omeprazole to reduce gastric acid secretion
-Sucralfate or misoprostol to treat GI ulceration

Front 215

Gastrinoma prognosis

Back 215

-Poor

Front 216

Pancreatic polypeptoma

Back 216

-reported in one dog

Front 217

Adrenal Anatomy

Back 217

-Craniomedial to the kidneys
-Weigh about 1 gram in adult dog
-Left adrenal is slightly larger and more caudal
-Composed of medulla and cortex
-Big important blood vessels travel across adrenal surface

Front 218

Layers of the Adrenal Cortex

Back 218

-Zona glumerulosa
-Zona fasciculate
-Zona reticularis

Front 219

Adrenal Medulla function

Back 219

-Not essential for life
-Secretes catecholamines in response to stress and sympathetic stimulation
-“Fight or flight” response
-Epi
-Norepi
-Dopamine

Front 220

Adrenal cortex function

Back 220

-Essential for life
-Secretes steroids
-Corticosterone is secreted from all 3 layers
-Cortisol is secreted from fasciculata and reticularis
-Sex hormones from Fasiculata and reticularis
-Mineralocorticoid from glomerulosa

Front 221

Synthesis of Catecholamines

Back 221

-Tyrosine is converted into Dopa (dihydroxyphenalanine)
-Dopa is converted to dopamine, then to norepi, then epi
-Norepi has negative feedback inhibition on tyrosine hydroxylase, decreases catecholamine production

Front 222

Catabolism of Catecholamines

Back 222

-Metabolized and secreted as Vanillylmandelic acid (VMA), normetanephrine, and metanephrine
-Half-life of catecholamines is very short
--hard to measure
--Easier to measure metabolites

Front 223

Steroid Synthesis

Back 223

-All are made from cholesterol
-Cholesterol is converted to pregnenolone via ACTH stimulation
-Same enzyme is used many times in pathway
--can inhibit one enzyme, will inhibit rest of the pathways
-Many enzymes are p450 enzymes
-Formation of steroids in layers depends on presence of enzymes in the layer
--if enzyme is not present, hormone will not be made in that layer

Front 224

Corticoids

Back 224

-Have both glucocorticoid and mineralocorticoid activity

Front 225

Affects of ACTH on steroid synthesis

Back 225

-Increase conversion of cholesteryl esters to free cholesterol and prengenolone
-Increases synthesis and p450 enzymes

Front 226

Affects of Angiotensin II on steroid synthesis

Back 226

-Increases conversion of cholesterol to pregnenolone
-Increases aldosterone synthase activity

Front 227

Actions of Catecholamines

Back 227

-Epi and NorEpi
-Stimulate alpha and beta adrenergic receptors
-Mimic effects of adrenergic nervous system
--increase HR< excitability, force contractility of heart
--decrease peripheral resistance
--increase alertness
-increase metabolic rate
-Increase glycogenolysis and lipolysis

Front 228

Actions of Dopamine

Back 228

-Mostly unknon
-Causes renal vasodilation and vasoconstriction elsewhere
-Increases systolic blood pressure
-increases force of cardiac contraction
-increases natiuresis

Front 229

Actions of Glucocorticoids

Back 229

-Sustain life!
-Bind intracellular receptors, promote DNA transcription and leads to enzyme synthesis that changes cell function
-Permissive effect on catecholamines, glucagon, and EPO
-Physiologic effects are different than pharmacologic and pathologic effects

Front 230

Specific Actions of Glucocorticoids

Back 230

-Increase protein catabolism
-increase hepatic uptake of amino acids
-Increase gluconeogenesis
-Increase formation of active form of glycogen synthase
-Increase glucose 6-phosphatase activity
--results in increased blood glucose concentration
-Decreases peripheral glucose utilization
-has anti-insulin effect, except in brain and heart
-Decrease hepatic lipogenesis
-increase plasma free fatty acids
-Causes hyperlipidemia and ketosis in diabetics
-Inhibits ACTH secretion
-Promotes vascular smooth muscle reactivity
-Increases GFR
-Increases number of circulating neutrophils, monocytes, platelets and RBCs
-Decreases number of circulating lymphocytes, eosinophils, and basophils
-Resists stress

Front 231

Actions of Mineralocorticoids

Back 231

-Bind intracellular receptors, promote DNA transcription
--leads to synthesis of Na and K channels and pumps
--changes Na and K absorption and secretion in the kidney
-Increase Na resorption from urine, sweat, saliva, gastric juices
-Promote secretion of H and K

Front 232

Regulation of Catecholamine secretion

Back 232

-Decreases during sleep
-increases in emergency situations
--hypoglycemia, hypothermia
-NorEpi inhibits tyrosine hydroxylase if too much catecholamines are produced

Front 233

Regulation of Glucocorticoid Secretion

Back 233

-CRH is secreted from hypothalamus
--stimulates secretion of ACTH from anterior pituitary
--CRH does not have effect on intermediate pituitary
-ACTH stimulates adrenal cortex to synthesize cortisol
-Cortisol negative feedback inhibits ACTH from anterior pituitary and CRH from hypothalamus

Front 234

Regulation of Mineralocorticoid Secretion

Back 234

-Aldosterone is secreted from cortex zona glomerulosa
--causes decreased Na excretion, increased Na retention
--Water follows Na, increases extracellular fluid volume
--increases BP
-Increased BP inhibits conversion of angiotensinogen to angiotensin I via renin
--Less angiotensin I converting to Angiotensin II, less angiotensin II to stimulate aldosterone secretion
-ACTH can bind to adrenal cortex and stimulate aldosterone secretion to a small extent

Front 235

Adrenal Diseases

Back 235

-Hyperadrenocorticism
-Primary hyperaldosteronim
-Hypoadrenocorticism
-Pheochromocytoma (adrenal medulla)

Front 236

Hyperadrenocorticism (Cushing’s disease)

Back 236

-Common disease in dogs
-not common in cats
-Pituitary dependent hyperadrenocorticism
-Adrenal tumor
-Iatrogenic
-All cause the exact same clinical signs!
--hard to know origin of issue
-Treatment modalities are different

Front 237

Pathophysiology of PDH

Back 237

-Likely due to a primary defect in the pituitary and not in the hypothalamus
-Chronic excess secrethion of ACTH
-90% are pituitary tumors
--70% in anterior lobe, pars distalis
--30% from intermediate lobe, pars intermedia
-Pharmacological intervention is different for the different lobes
--Anterior lobe, CRH and glucocorticoid negative feedback
--intermediate lobe, dopamine inhibits ACTH secretion

Front 238

Pathophysiology of Adrenal Tumors

Back 238

-Adrenal adenomas or carcinomas
-Secrete excess glucocorticoids, suppress CRH and ACTH
--go to pituitary and hypothalamus
-Less ACTH secretion, contralateral adrenal atrophies
-Also get atrophy of zona reticularis and zona fasciculate in adrenal with tumor
-Histological classification can be challenging

Front 239

PDH

Back 239

-80-85% of dogs with hyperadrenocorticism have PDH
-90% is pituitary adenoma
--70% anterior lobe adenoma
--30% intermediate lobe adenoma
-85-90% of pituitary adenomas are microadenomas, less than 1cm in diameter
-10-15% of pituitary adenomas are macroadenomas, more than 1cm in diameter
-Small % of dogs have pituitary hyperplasia or carcinoma instead of adenoma
-Anterior lobe pituitary microadenoma is most common

Front 240

Incidence of Adrenal tumor Types

Back 240

-50% adenomas
-50% carcinomas

Front 241

Signalment for Cushing’s disease

Back 241

-Older dogs, 10-11 years old
-Females may be slightly higher risk
-Smaller breeds develop PDH
-Larger dogs develop adrenal tumors

Front 242

Clinical signs of Cushing’s Disease

Back 242

-Look exactly the same regardless of the “type” of cushing’s
-PU/PD
--most profound
--too much glucocorticoids, bind ADH receptors and prevent ADH binding
-Polyphagia
--Glucocorticoids are catabolic, breaking down energy stores
-Abdominal enlargement
-Truncal obesity
-Muscle weakness, lethargy, possible lameness
--breakdown of connective tissue, predisposes to ligament and tendon tears
-Panting
-Testicular atrophy or failure to cycle
--glucocorticoids suppress LH and FAH secretion
-Myotonia

Front 243

Abdominal enlargement with Cushing’s disease

Back 243

-Liver enlargement due to glycogen accumulation in the liver
-Swollen hepatocytes
-Muscle and skin is broken down so liver “hangs out”
-Fat is re-distributed from limbs to trunk

Front 244

Panting and Cushing’s

Back 244

-Truncal obesity prevents chest expansion
-Breakdown of intercostal muscles make chest expansion difficult
-Pneumonia due to immune suppression from glucocorticoids
-Acute thromboembolic disease

Front 245

Thromboembolic Disease and Cushing’s

Back 245

-Too little trypsin
-Too much tissue plasminogen inhibitor
-Too little tissue plasminogen activator
-Decrease conversion of frbrin to fibrin-split products
-Dogs with cushing’s are hypocoagulytic, cannot break down clots
--“hypercoagulable” is not totally correct
--form clots normally but cannot break down clots

Front 246

Skin issues associated with Cushing’s disease

Back 246

-Alopecia
-Shaved hair will not regrow
-Thin skin (look in inguinal area)
--may see vasculature under skin
-Poyderma
-Bruising (more common in cats)
-Dehiscence of healing lesion
-Calcinosis cutis, deposition of Ca in the skin
-Recurrent infections due to immunosuppression

Front 247

Immunosuppression due to glucocorticoids

Back 247

-Lympholytic, fewer circulating antibodies
-Decrease expression of Fc receptors on macrophages
--no ability to bind antibodies
-Decrease chemotaxis of neutrophils and ability to adhere
-Causes recurrent infections, skin infections, and pneumonia

Front 248

Physical Exam findings of Cushing’s Patient

Back 248

-Abdominal enlargement
-Hepatomegaly
-Truncal obesity
-Muscle weakness and muscle wasting
-Lethargy and possible lameness
-Panting
-Alopecia
-Hyperpigmentation
-Failure to regrow shaved hair
-Thin skin
-Pyoderma
-Exophthalmos, breakdown of musculature and connective tissue around the eye
-Sudden Acute Retinal Degeneration (SARDS)

Front 249

Hyperpigmentation and Cushing’s disease

Back 249

-Melanin-stimulating hormone is produced from same peptide as ACTH
-Increased synthesis fo ACTH results in increased synthesis of MSH
--causes hyperpigmentation

Front 250

Concurrent conditions that can affect clinical signs of a Cushing’s patient

Back 250

-UTIs
-Cystic calculi, excess secretion of Ca in urine
-Glomerular disease
-Dermatitis or pyoderma
-Pneumonia
-Other infections
-Diabetes mellitus
-Acute pancreatitis
-Hypertension and CHF
--excess ACTH causes excess secretion of alosterone
-Pulmonary thromboembolism
-Sepsis
-CNS signs due to a macroadenoma (rare)acting as space-occupying lesion

Front 251

Conditions associated with high cholesterol concentration

Back 251

-Hyperthyroid
-Diabetes mellitus
-Cushing’s disease
-Causes increased risk for acute pancreatitis?

Front 252

Diagnosing Hyperadrenocorticism (Cushing’s)

Back 252

-History and Clinical signs
--MUST have classic history and clinical signs for diagnosis!
--tests are imperfect, give false positives and false negatives
-Physical exam findings
-Clinicopathologic findings consistent with a diagnosis
-Adrenal axis testing
--only do tests if you are sure that the dog has cushing’s and you want to treat!

Front 253

Initial diagnostic evaluation of Cushing’s

Back 253

-CBC
-Chem screen
-Urinalysis
-Urine culture
-Abdominal ultrasound

Front 254

CBC for Cushing’s

Back 254

-Can be normal
-Can have high hematocrit or normal
--Glucocorticoids induce EPO, makes more RBCs
-Can have thrombocytosis
-WBC “stress leukogram” may be present
-Neutrophilia with a left shift if there is an infection

Front 255

Chem screen for Cushing’s

Back 255

-High ALP due to excess steroid secretion
-high ALT and high AST
--due to glycogen accumulation in hepatocytes
-Lipema may be present
-Hypercholesteroemia may be present
-Hyperglycemia
-Mild hypopohsophatemia
-Looks like Diabetes mellutis chem screen
--treat diabetes first and hope it resolves
--if no resolution, test for cushing’s

Front 256

Urinalysis for Cushing’s

Back 256

-Hyposthenuria, dilute urine
-Pyuria
-Glucosuria

Front 257

Urine culture and sensitivity for Cushing’s

Back 257

-Should always be performed in dogs suspected of cushing’s even if WBCs are not present in urine sediment
-Dilute urine can mask presence of WBCs

Front 258

Abdominal Ultraound for Cushing’s

Back 258

-Can be helpful but does NOT diagnose cushing’s
-gives shape of the adrenals
-Does not tell anything about secretion of hormones or lack thereof
-Adrenals may be bilaterally plump with pituitary adenoma
-Adrenal tumor will have one large and one atrophied tumor
-adrenal mass and adrenal atrophy
-Diffusely enlarged, hyperechoic liver
-Metastasis
-concurrent disorders (cystic calculi)

Front 259

Adrenal Mass

Back 259

-Can invade caudal vena cava
-Look for metastasis to liver

Front 260

Abdominal and thoracic radiographs for Cushing’s

Back 260

-Hepatomegaly
-Good abdominal detail due to excess fat deposits
-Calcinosis cutis
-Ectopic calcification of the airways
-Adrenal mass
Radiographic findings are nonspecific, do not confirm a diagnosis

Front 261

Confirming Cushing’s

Back 261

-Adrenal axis testing
-Only in animals with clinical signs and clinicopathologic findings that indicate hyperadrenocorticism
-Only done in dogs that you want to treat
-Screening tests and differentiating tests

Front 262

Screening test vs. differentiating test for Cushing’s

Back 262

-Screening tests: indicates if the dog has Cushing’s
-Differentiating test: indicates what type of cushing’s
--only done if the screening test has confirmed cushing’s disease

Front 263

Screening tests for Cushing’s

Back 263

-Does the dog have cushing’s?
-ACTH stimulation test
-Low dose dexamethasone suppression test
-Urine cortisol to creatinine ratio
-Oral low dose dexamethasone suppression test (still in progress)

Front 264

ACTH stimulation test

Back 264

-Stimulates cortisol production
-Do when there are concurrent diseases
-Fast, 1 hour test
-Normal:
--pre-ACTH cortisol should be 0.5-6 ug/dl
--post ACTH cortisol should be less than 17
-PDH:
--pre-ACTH cortisol should be 0.5-6
--post ACTH cortisol should be more than 22, really high, more ability to make cortisol due to hypertrophy
-Adrenal tumor:
--post-ACTH cortisol should increase beyond what is expected to be normal, maintains some capacity to respond

Front 265

Low-dose dexamethasone suppression test

Back 265

-Suppresses cortisol production, dexamethasone acts like cortisol
-Do in dogs that are pretty stable, have PU/PD and polyphagia and no concurrent disorders
-8 hour test, longer test where animal needs to be left alone
-Normal: cortisol secretion should be suppressed, less than 1 at 4 and 8 hours after injection
-Adrenal Tumor: secretes glucocorticoids autonomously, un-regulated
--dexamethasone will not suppress cortisol levels, stays above 1.4
-Pituitary adenoma: autonomously secreting ACTH
--dexamethasone will not suppress cortisol levels, stays above 1.4

Front 266

Urine Cortisol Creatinine Ratio

Back 266

-Developed because measurement fo a single cortisol level in blood is unreliable
-Looks at cortisol in the urine, reflects cortisol in blood over past few hours
-Will have elevated urine cortisol: creatinine ratio
-Test is non-specific, cannot differentiate stress from hyperadrenocorticism
-Used to tell if dog does NOT have cushing’s
-If low or normal, can definitively say the animal does not have cushing’s

Front 267

Sensitivity and specificity of Cushing’s screening tests

Back 267

-ACTH stimulation test: specific
--if positive, know it really is positive
--possible that some positive patients are missed
-Low-dose dex test: sensitive
--will pick up cushing’s, but get false positives
--most common reason for false positives is stress (concurrent disorder or general stress)
-Urine cortisol:creatinine ratio: sensitive

Front 268

Differentiating Tests for Cushing’s

Back 268

-Do to figure out what type of cushing’s the dog has
-LDDS test
-Endogenous ACTH concentration
-High dose dexamethasone suppression test

Front 269

Low dose dexamethasone suppression test

Back 269

-Screening test AND differentiating test
-4 hour serum cortisol concentration should be less than 1.4 or less than 50% of baseline
-If cortisol stays high, cannot differentiate Pituitary adenoma from adrenal tumor
-40% of dogs with PDH have no suppression
-Sometimes get transient suppression of microadenoma in pituitary
--will stop secreting ACTH
--4 hours: suppression
--8 hours, goes back up
-Adrenal tumors DO NOT suppress

Front 270

Endogenous ACTH concentration differentiation test for Cushing’s

Back 270

-One measurement, likely to give yes/no answer
-Pituitary tumor: ACTH will be high (above 45)
-Adrenal tumor: ACTH will be low (below 10
-Gray zone between 45 and 10
-Blood draw goes into purple top, then removed from EDTA and placed in a plastic tube
--will adhere to glass, concentration goes down incorrectly

Front 271

High Dose dexamethasone suppression test for differentiating Cushing’s

Back 271

-8 hour test
-Give high dose of dexamethasone, want to suppress pituitary dependent ACTH production
-Will not suppress adrenal tumor
-Still have significant number of dogs with pituitary tumor that will not suppress
-Not the best test, does not always work

Front 272

Tests for Cushing’s that cannot be used to differentiate

Back 272

-Abdominal ultrasound
-CT
-MRI
-Supportive, but not diagnostic of disease

Front 273

Diagnosis of Iatrogenic Hyperadrenocorticism

Back 273

-History and clinical signs
--animal is on exogenous steroids
-Serum cortisol is expected to remain low after ACTH stimulation
-Differentiating test is not needed

Front 274

Treatment of Cushing’s Disease

Back 274

-Treatment is a big deal! Can kill the patient!
-medical treatment is most common
-Lysodren
-Trilostane
-Deprenyl
-Surgery
-Stereotactic radiation therapy
-Ketoconazole
-Photon irradiation

Front 275

Lysodren

Back 275

-Mitotane, Bristol-Myers Squibb
-Causes severe necrosis of zona fasciculate and zona reticularis, some necrosis of zona glomerulosa
-NOT FDA approved for dogs
-Only 500mg tab, inconvenient
-Induction phase and maintenance phase
-Need constant monitoring and adjustment of dose
--taper dose to each dog individually

Front 276

Lysodren induction phase

Back 276

-Goal is to destroy the adrenals, destroy cortisol secreting layers
-25-50 mg/kg for 7 consecutive days, give daily
--on last day do ACTH stimulation, if still high continue with induction phase
-May give prednisone also to prevent crisis
-Need to be careful to not give too much and kill adrenals completely

Front 277

Lysodren Maintenance phase

Back 277

-Retains destruction of cortisol secreting layers of the adrenal glands
-25-50 mg/kg per week, divided into 2 weekly doses
--daily dose becomes weekly dose

Front 278

Key things about Lysodren therapy

Back 278

-Excess lysodren can cause death! Do not give too much
-Monitor patient really well!
-Constant and excellent communication between vet and owner are essential
-Perfect dose is achieved by trial and error, practice
-Perfect dose changes over time

Front 279

Monitoring Lysodren treatment by owner

Back 279

-Decreased appetite
-Vomiting
-Decreaed water consumption
-Lethargy, weakness, ataxia
-Diarrhea

Front 280

Monitoring of Lysodren treatment by veterinarian

Back 280

-Clinical monitoring
-ACTH stimulation test if:
--lysodren overdose is suspected
--lysodren underdose is suspected
-End of every induction phase
-Before changing lysodren dose
-If complications occur (UTI or other infection)
-every 3-4 months when dog appears well-regulated

Front 281

Results of ACTH stimulation test in Lysodren treated dogs

Back 281

-Post- ACTH stimulation cortisol concentration should be less than 5ug/dL
--at VHUP, should be 2
-Not supported by studies!

Front 282

Lysodren Overdose

Back 282

-Common!
-Varies in severity
-Confirm with ACTH stimulation test
-May not need treatment, may need treatment with IV fluids, dex, correction of elextrolyte disturbances

Front 283

Trilostane

Back 283

-Treatment for Cushing’s
-Synthetic steroid analogue
-can bind enzymes that normally bind cortisol
-Specifically binds 3 beta hydroxysteroid dehydrogenase inhibitor
-Blocks many hormone pathways
--blocks production of cortisol and aldosterone
-FDA approved
-Can cause adrenal necrosis via unknown pathology
--occurs in first 4 weeks of treatment

Front 284

Trilostane and Potassium

Back 284

-Trilostane treatment results in increased serum potassium concentration
-Unknown cause
--causes cell nerosis, which causes release of intracellular K?
--aldosterone concentration is decreased?
-In addisonian crisis, will see increased K
--if dog is happy and not sick, not addisonian crisis
--if dog is sick, may be addisonian crisis

Front 285

Aldosterone and Trilostane

Back 285

-Aldosterone and Cortisol are not equally affected by trilostane
-Preferentially decreases cortisol and not aldosterone

Front 286

Alopecia X and Trilostane

Back 286

-Helpful for treating alopecia X condition
-May be due to increased 17-hydroxyprogesterone, trilostane decreases 17-OHP concentration
-Not cushinoid dogs, and do not become addisonian
--Dogs that do not have Cushing’s are less sensitive to drugs
-Breed related
--Alaskan Malamute
--Chow chow
--keeshond
--pomeranian
--Samoyed
--Siberian husky

Front 287

Trilostane and Adrenal gland size

Back 287

-Adrenal gland will be enlarged after treatment with trilostane
-Less glucocorticoids produced, less glucocorticoid inhibition of ACTH
--causes enlargement of pituitary
-Diffuse and quietly enlarged, not necrotic

Front 288

Survival of Cushinoid patients with Treatment

Back 288

-Do well, drugs work well

Front 289

Trilostane formulation

Back 289

-10, 30, 60 mg capsules
-Also 5 mg capsules by compounding pharmacies
--watch out for variability!
-Dose twice daily, 1-3mg/kg orally divided into 2 doses
-Dose can be increased up to 40-50mg/kg/day if needed
--Increase gradually within first few months of treatment
-May need to discontinue medication as hypoadrenocorticism develops
-Monitor based on stimulation tests
--test on days 10-14, 30, and 60, then every 3-4 months

Front 290

When to do an ACTH stimulation test?

Back 290

-Standard: 4-6 hours after trilostane administration
--time of peak action of enzyme
-Can also do stimulation tests 10-12 hours after administration
-Always interpret in light of the clinical signs

Front 291

Commonside effects of Trilostane

Back 291

-Lethargy
-Anorexia
-Hyperkalemia
-Hyponatremia
-Addisonian crisis
-Uncommon:
--adrenal necrosis
--irreversible hypoadrenocorticism
--death

Front 292

Trilostane vs. Lysodren

Back 292

-Same cost
-FDA approved vs. non FDA approved
-Reversible action sometimes
-Safer?

Front 293

L-Deprenyl / Selegiline / Anipryl

Back 293

-Irreversible monoamine oxidase inhibitor type B
-MAOb normally degrades dopamine
-Inhibition causes increased dopamine concentration
--High dopamine inhibits ACTH secretion from intermediate pituitary
-Only 30% of dogs have pars intermedia tumor
--beneficial for about 20% of dogs with Cushing’s
-Only FDA approved drug approved for treatment of hyperadrenocorticism
-Approved for cognitive dysfunction in dogs
-Used in addition to trilostane or lysodren

Front 294

Surgery for treatment of Cushing’s

Back 294

-Remove pituitary
-All hormones from pituitary are gone!
-Need to supplement animal with prednisone, thyroid hormone,
-Surgery is complicated, requires special training
--need a surgeon who can do it! Need to be really really good for success
-May be curative for adenoma, need to supplement with small amounts of mineralocorticoids and glucocorticoids for a few months
--contralateral adrenal will be shrunken, will grow back but takes time
-Higher success if intervened early

Front 295

Stereotactic Radiation Therapy for Adrenal Tumor Cushing’s

Back 295

-Highly focused dose of radiation to the tumor
-3 fractions of treatment
-less radiation to surrounding tissue
-Successful in alleviating clinical signs of adenoma

Front 296

Lysodren Treatment for Cushing’s caused by adrenal tumors

Back 296

-When surgery is not recommended due to metastasis
-Larger doses than for PDH
-Truly destroys the adrenal glands and possible metastasis

Front 297

Trilostane for Adrenal tumors

Back 297

-Will inhibit glucocorticoid synthesis but won’t do anything for the actual tumor

Front 298

Not recommended treatments for adrenal tumors

Back 298

-Ketoconazole
-Proton irradiation

Front 299

Atypical Cushing’s

Back 299

-Dog that presents with PU/PD, polyphagia, big liver, thin skin, collapsing trachea
-CBC looks like cushing’s
-Liver has glycogen accumulation
-All adrenal testing is negative, cannot confirm cushing’s disease
-Something else is binding the steroid and causing clinical signs?
--do not know what it is
-Treat with Lysodren, do not know what intermediary is causing issue
--Trilostane will cut off some hormones and increase synthesis of others

Front 300

Feline Hyperadrenocorticism

Back 300

-Rare
-over 90% of cushinoid cats are diabetic
-Thin skin results in skin tears, skin is paper-thin
-No steroid induced ALP, no elevated ALP
-Protocols for ACTH stimulation test, LDDS tests, and HDDS tests are different
-Different treatment: surgery and metyrapone (11-beta-hydroxylase inhibitor)
--no response to lysodren

Front 301

Metyrapone

Back 301

-11-beta-hydroxylase inhibitor
-Treatment for feline cushing’s

Front 302

Spontaneous skin tears in cats

Back 302

-Diabetic cat with cushing’s

Front 303

Treatment of cats with Cushing’s

Back 303

-Surgery!
-Hard to give cats mediations and meds are not that effective
--tastes bad, cats are grouchy
-Cats handle surgery better than dogs
-Retroperitoneal approach

Front 304

Prognosis for cats with Cushing’s

Back 304

-Variable
-Better with pituitary microadenomas than with adrenal carcinoma

Front 305

Primary Hyperaldosteronism

Back 305

-Rare, more common than cushing’s
-Mostly in cats
-Usually due to unilateral adrenal adenoma or carcinoma, bilateral adrenal hyperplasia
-Excess aldosterone secretion causes increased Na retention
--leads to increased extracellular plasma volumes, hypertension, and hypokalemia
-Will see elevated serum aldosterone concentration
-Clinical signs will be due to hypokalemia
-Surgical treatment, remove!

Front 306

Hypoadrenocorticism Addison’s Disease

Back 306

-Common in dogs, rare in cats
-Primary: adrenocortical failure, failure of adrenal glands
--more common
-Secondary: failure of the pituitary or hypothalamus

Front 307

Primary Adrenocortical Failure

Back 307

-Failure of the adrenal glands
-Occurs when more than 90% of adrenocortical cells are lost
--only need a small amount of cortex to be viable to mask clinical signs
-Characterized by a decreased glucocorticoid and mineralocorticoid secretion

Front 308

Causes of Primary Addision’s

Back 308

-Immune-mediated destruction of adrenal glands
-Genetic component
--poodles, portugese water dogs, labs
-Granulomatous disease
-Trauma
-Iatrogenic from lysodren treatment

Front 309

Secondary adrenocortical failure

Back 309

-Rare
-Due to failure of pituitary or hypothalamus
-Characterized by decreased glucocorticoid secretion
--mineralocorticoid secretion will be normal

Front 310

Causes of Secondary Addison’s

Back 310

-Neoplasia
-Inflammation
-Trauma
-Brain disease
-Iatrogenic due to abrupt discontinuation of chronic prednisone treatment

Front 311

Lack of Aldosterone

Back 311

-Hyponatremia, Na is excreted in urine
--no aldosterone to retain Na
-Hypochloremia (Na and Cl travel together)
-Reduced extracellular volume
--VERY dehydrated patient
-Dilute urine despite dehydration
-Hyperkalemia
-Acidosis

Front 312

Lack of glucocorticoids causes…

Back 312

-Anorexia
-Vomiting
-Abdominal pain
-Weight loss
-Fasting hypoglycemia, glucocorticoids are not metabolizing glucose stores to glycogen
-Lethargy due to hypoglycemia
-Impaired tolerance to stress

Front 313

Signalment of Addison’s disease

Back 313

-Young to middle aged dogs, 5 years old
-70% of affected dogs are female
-Poodles, Portuguese water dogs, and labs may be predisposed

Front 314

Clinical signs of Addison’s disease

Back 314

-Can be very mild
-Anorexia, weight loss or underweight body condition
-Vomiting, diarrhea
-Lethargy, weakness, PU/PD
-Painful abdomen
-Shaking/shivering due to hypoglycemia
-Collapse

Front 315

Physical exam of patient with Addison’s

Back 315

-Depression
-Underweight
-Weakness
-Dehydration can be mild or severe
-Bradycardia due to hyperkalemia
-Weak pulses
-Melena/hematochezia
-Abdominal pain
-Collapse

Front 316

Bradycardia due to hyperkalemia

Back 316

-K stays in the cell
-Increased K increases resting membrane potential

Front 317

Diagnosis of Hypoadrenocorticism (Addison’s)

Back 317

-History and clinical signs
--depression, weakness, vomiting
--hypotensive
-Physical exam findings
-Clinicopathologic findings
-Adrenal axis testing
--ACTH stimulation test is only test that proves presence or absence of Addison’s disease

Front 318

Addison’s disease and hypotension

Back 318

-Aldosterone is not produced
-No retention of Na and water
-No water in vasculature, hypotension

Front 319

Initial Diagnostic evalulation for Hypoadrenocorticism

Back 319

-CBC
-Chem
-Urinalysis
-Urine culture
-Fecal parasitic examination
-Fecal culture
-Abdominal radiographs

Front 320

CBC for dog with Addison’s Disease

Back 320

-CBC may be normal
-RBC: hematocrit is low, but may be normal or high
-WBC count is normally lower, but may be increased
-Eosinophils and lymphocytes may be observed

Front 321

WBCs and Addison’s disease

Back 321

-Steroids induce stress leukogram:
--neutrophilia, Monocytosis, lymphopenia, eosinopenia
-Without steroids, get reverse
--body does not mount appropriate stress response that we would get from a dog that has glucocorticoids
--lymphocytosis within the reference interval

Front 322

Chem screen for dogs with Addison’s disease

Back 322

-Na/K ratio is particularly important
--without aldosterone Na decreases and K increases
-Azotemia
-Hyponatremia
-Hyperkalemia
-Hypochloremia
-Mild metabolic acidosis
-Hypercalcemia
-Hypoglycemia
-Hypoalbuminemina
-Hypocholesterolemia

Front 323

Na/K ratio in Addison’s

Back 323

-Should be assessed together
-More than 27 Na:K in normal dogs
-Less than 27 Na:K in dogs with hypoadrenocorticism
-Should do a stimulation test on all dogs with a Na:K ratio of 30 or less
-Look at Na:K ratio in conjunction with lymphocyte count

Front 324

Lymphocyte count and Addison’s

Back 324

-Look at all dogs above 1.2 as potentially having Addison’s
-Dogs above 2.4 indicates very likely that the dog has addison’s disease
-Look at lymphocyte in conjunction with Na:K ratio

Front 325

Urinalysis and Addison’s Disease

Back 325

-Urine is dilute in the face of dehydration
-Looks like kidney or liver disease
-Do a urine culture due to PU/PD
--do not expect to see bacteria, no growth expected

Front 326

Fecal exam for Addison’s disease

Back 326

-Always do fecal parasitic exam and fecal culture in dogs with vomiting and diarrhea
-Normal results are expected with Addison’s disease
--negative for parasites and infection

Front 327

Abdominal radiographs in Addison’s disease

Back 327

-Always performed in dogs that are vomiting
--foreign body potential
-Should be normal in dogs with Addison’s disease
-May see microcardia secondary to dehydration
-May see megaesophagus secondary to immune-mediated destruction of esophagus

Front 328

Abdominal ultrasound with Addison’s disease

Back 328

-Adrenals will be shrunken

Front 329

ECG for Addison’s patients

Back 329

-Prolonged P-R interval
-Short or absent P waves
-Wide and short QRS complexes
-Possible ventricular fibrillation
-Consistent with hyperkalemia

Front 330

DDx for PU/PD in younger dogs

Back 330

-Kidney or liver disease
-Addison’s
-Everything else is also possible

Front 331

DDx for Eosinophilia

Back 331

-Parasitism (MAIN differential!!!)
-Non-parasitic skin disease
-Mast cell tumor
-Addison’s/hypoadrenocorticism
-Eosinophilic myositis, pneumonitis, enterocolitis
-Hypereosinophilic syndrome
-Eosinophilic leukemia
-Eosinophilic granuloma complex

Front 332

Pseudo Addison’s Disease

Back 332

-Eosinophilia
-Vomiting and diarrhea
-Low Na:K ratio
-Looks like an addison’s patient
-Can be caused by ANY severe GI disease
--treat any possible underlying conditions before testing for Addison’s disease

Front 333

DDx for Hyperkalemia and Hyponatremia

Back 333

-Any severe GI disease
-Hypoadrenocorticism/Addison’s
-Acute renal failure
-Severe liver disease
-Urethral obstruction
-Uroperitoneum
-Osmotic or diuretic induced diuresis
-Acidosis due to DKA
-Pleural effusion
-CHF
-Massive tissue destruction
-Polydipsia
-Artifact

Front 334

DDx for Hypoglycemia

Back 334

-Insulinoma
-Liver disease
-Toy breed
-Young animal
-Hypoadrenocorticism
-Sepsis
-Neoplasia
-Starvation
-Severe malabsorption or maldigestion
-Severe polycythemia
-Growth hormone deficiency
-Artifact

Front 335

Hypoglycemia and Addison’s disease

Back 335

-No glucocorticoids, body is not breaking down glycogen stores to glucose
-Usually mild, but can cause seizures

Front 336

DDx for Hypercalcemia

Back 336

-Hypoadrenocorticism/Addison’s
-Neoplasia
-Renal failure
-Granulomatous disease
-Osteolytic disease
-Hyperparathyroidism
-Vitamin D toxicosis
-Young animals
-Idiopathic in cats
-Acidosis, H ions displace Ca from albumin and Ca is free in blood
-Hypothermia

Front 337

Hypercalcemia and Addison’s disease

Back 337

-Hypercalcemia should be mild, not severe
-can be profound
-Without glucocorticoids, animals are unable to secrete Ca

Front 338

Adrenal Axis Testing for Addison’s

Back 338

-ACTH stimulation test is preferred test for hypoadrenocorticism/Addison’s
-Try to see if cortisol secretion can be stimulated from adrenal glands
-Normal: exogenous ACTH should increase cortisol production
--2 and above
-Addison’s: Exogenous ACTH does not increase cortisol production, no stimulation
--aldosterone concentration will also be low
-expensive test!

Front 339

Liver enzymes and Addison’s disease

Back 339

-Liver is ischemic, hepatocellular damage occurs
-ALT and AST are released from hepatocytes

Front 340

Aldosterone test for Addison’s disease

Back 340

-Measured after ACTH stimulation
-Primary: adrenals failed, should not have aldosterone
--Na:K ratio is low
-Secondary: pituitary/hypothalamus issue
-Not the best test, does not really diagnose or rule out anything

Front 341

Treatment of Acute Addison’s crisis

Back 341

-Fluid therapy and dextrose
--most important therapy! Will save lives!
--addresses acidosis
--Saline is fluid of choice, has Na
-Dexamethasone:
-IV glucose and insulin:
--insulin to push K into cells, but have to give glucose first
-Desoxycorticosterone pivalate (DOCP)

Front 342

Dexamethasone for Addison’s

Back 342

-Hold off because making a diagnosis is difficult if dex is given
-Can be given IV
-Does not interfere with cortisol assay
-Will suppress CRH and ACTH secretion for about 24 hours
--Best to give after ACTH stimulation test

Front 343

Desoxycorticosterone pivalate

Back 343

-DOCP
-Synthetic aldosterone
-Give in acute addisonian crisis
-Does not interfere with ACTH stimulation test
-Corrects Na:K ratio

Front 344

When to do ACTH stimulation test

Back 344

-Before glucocorticoid administration
-Dex will not interfere with cortisol assay, but will suppress adrenal axis

Front 345

Long-term treatment of Hypoadrenocorticism

Back 345

-Begins once animal is rehydrated, has normal electrolyte concentrations, no vomiting, diarrhea, or anorexia
-Oral supplementation of mineralocorticoid or glucocorticoid
-Mineralocorticoid supplementation:
--Fludrocortisone or DOCP
-Glucocorticoid supplementation:
--prednisone or Fludrocortisone

Front 346

Monitoring of Addison’s disease by owner

Back 346

-Can be too much or too little
-Decreased appetitie
-Decreased water consumption
-Lethargy, weakness, ataxia, shaking
-Vomiting
-Diarrhea
-PU/PD
-Polyphagia
-Panting
-Other signs of hyperadrenocorticism

Front 347

Veterinary monitoring of Addison’s

Back 347

-Physical exam
-Check response to therapy
-Do not do stimulation tests
-Look at Na:K ratio to see if aldosterone supplementation needs to be tweaked

Front 348

Addison’s Prognosis

Back 348

-Excellent once crisis is over
-Average length of hospitalization is 2 days

Front 349

Feline hypoadrenocorticism

Back 349

-Rare

Front 350

Diagnostic Imaging for Endocrine Diseases

Back 350

-Usually not used to definitively diagnos diseases
-Used more for support of a diagnosis
-Monitoring diseases over time

Front 351

Diagnostic imaging for Cushing’s disease

Back 351

-Pituitary dependent or adrenal tumor
-Pituitary gland imaging: CT or MRI
--microadenoma is most common, less than 1cm
--Macroadenoma in 15-20% of dogs, more than 1cm

Front 352

Imaging the pituitary gland

Back 352

-CT or MRI
-Only two modalities that can penetrate the skull
-MRI is better for brain imaging
-Hyperintense area in center represents vasopressin granules in posterior pituitary
-Small lesions that will not enlarge pituitary can be identified by lack of hyperintense center
--may be missed on CT, but will see on MRI

Front 353

Fluid on MRI

Back 353

-Dark on T1 image and light on T2 image
-Cavitated or cystic area

Front 354

Pituitary dependent Hyperadrenocorticism (PDH) CT imaging

Back 354

-Microadenomas are often not visible
-Macroadenomas expand dorsally from the sella turcia
--Do not cause bone destruction

Front 355

Imaging the Adrenals

Back 355

-Ultrasound is modality of choice
--does not need anesthesia or sedation ususally
-Cheaper
-More widely available

Front 356

Pituitary Dependent Hyperadrenocorticism Ultrasound imaging

Back 356

-Expect to see enlargement of both adrenal glands
--over-stimulation and over-production by pituitary tumor
-Adrenals may still be within normal range of size
-Should be relatively equal in size

Front 357

Adrenal Cortical Tumors on Ultrasound

Back 357

-One adrenal is large and the other is suppressed
-Can be benign (adenoma) or malignant (carcninoma)
--either can be mineralized, 50% of cases are mineralized
-Adenomas will be encapsulated, 1-6cm
-Carcinomas can invade along local structures
--metastasize hematogenously to liver and lungs

Front 358

Mineralization in Adrenal gland

Back 358

-Indicates a neoplastic process
-In cats, can have mineralization in adrenal as an incidental finding

Front 359

Adrenal tumors on Radiographs

Back 359

-Uncommon finding
--may not be big enough to see
-Will only see if mineralized
-Take thoracic radiographs to rule out metastatic disease

Front 360

Adrenal Tumor Ultrasound

Back 360

-Unilateral
-Abnormally enlarged
-Abnormally shaped
-Abnormally small contralateral adrenal
--suppressed by other adrenal
-Uncommonly can be bilateral tumors

Front 361

Vessels on Ultrasound

Back 361

-Should be anechoic, contain fluid
-If dark, indicates that there is something wrong
-With adrenal tumors, can see elongated neoplastic tissue occluding lumen of the vessel
--adrenal tumor invades the cava
-Can be a blood clot or something else

Front 362

Adrenal tumor invading the Vena Cava

Back 362

-If mass invades vessel, damages endothelial layer of the vessel wall
-Predisposes thrombus formation at site
-Makes surgery more complicated
-Prognosis is much more guarded
-Neoplastic tissue invades via phrenicoabdominal vein
-Can see invasion on CT

Front 363

MRI and adrenal gland imaging

Back 363

-Rare for adrenal gland issues
--usually ultrasound and CT give all the needed info
-MRI is more expensive and takes much longer, but is possible approach

Front 364

Adrenal tumors and Metastatic Disease

Back 364

-Always look at liver for neoplastic spread
-Look for evidence of invasion of the vena cava

Front 365

Cushing’s Disease Diagnosis

Back 365

-Should NEVER be diagnosed via imaging!
-Important tool for differentiating PDH vs. adrenocortical tumor once diagnosis has been made
-May see non-specific signs on radiographs also
--“pot belly”
--Hepatomegaly due to steroid hepatopathy and glycogen accumulation
--Calcinosis Cutis
--Excesive mineralization of bronchi and lungs
--urinary calculi

Front 366

Cushing’s Liver on Ultrasound

Back 366

-Will appear large and white due to glycogen accumulation
-Steroid hepatopathy
-Not pathognomonic or specific, but can support other findings

Front 367

Calcinosis Cutis on Radiograph

Back 367

-Can see in skin
-Indicates mineralization in the sub-cutis
-Indicates Cushing’s disease

Front 368

Non-specific diagnostic signs of Cushing’s disease on Radiographs

Back 368

-Pot belly
-Hepatomegaly
-Calcinosis Cutis
-Mineralization of bronchi and lungs
-Urinary calculi

Front 369

Addison’s Disease in Ultrasound

Back 369

-Slender adrenals, small adrenals
--depends on the size of the dog

Front 370

Addison’s disease on Radiographs

Back 370

-Hypovolemia due to small liver, vessels that are difficult to see and narrowed
-Microcardia
-Megaesophagus (rare)

Front 371

Hyperthyroid Radiographs

Back 371

-Hyper-inflated lungs: lungs will look darker than usual
-Hypertrophic Cardiomyopathy: Thyrotoxic Cardiomyopathy

Front 372

Hyper-inflated lungs on radiograph

Back 372

-Sign of hyperthyroidism in cats
-Lungs look darker than usual
-Extend more cranial than the thoracic inlet or more caudal than usual
-Increased distance between the heart and the diaphragm

Front 373

Thyrotoxic Cardiomyopathy

Back 373

-Cardiomyopathy due to thyroid disease
-Tends to be reversible, unless it has been going on for a long time
-Usually resolve with treatment of hyperthyroid disease

Front 374

Ultrasound of the Thyroid Gland

Back 374

-Start with a transverse image, identify the trachea
-Move from trachea to the carotid artery to find the thyroid
-Between Carotid artery and the trachea

Front 375

Thyroid gland on CT

Back 375

-Naturally thyroid contains Iodine, will be hyper-attenuating before contrast is added
-After contrast, carotid artery and branches enhance, look similar to the thyroid
-Easier on pre-contrast to evaluate the thyroid glands

Front 376

Scintigraphy for Hyperthyroidism

Back 376

-Can sometimes be done in hyperthyroid patient to identify function and hyperfunction
-Important if planning surgical removal
-Use radioactive Technetium injected into peripheral vein for contrast
-Technitium is similar radioactively to iodine, iodine pumps in thyroid gland actively trap Tch from circulation
-Normal cats: thyroid and salivary glands have similar size and intensity
-Hyperthyroid cats: thyroid lobes will have increased size and uptake compared to salivary glands
--If unilateral, contralateral lobe is suppressed
-Can identify ectopic thyroid tissue

Front 377

Uptake of Technetium

Back 377

-Should have uptake in:
--salivary glands
--Thyroid glands
--Stomach
-With hyperfunctioning thyroid, will have LOTS of uptake
--thyroid adenoma will show up

Front 378

Ectopic Thyroid Tissue

Back 378

-Can be identified with Scintigraphy

Front 379

Thyroid tumors in dogs

Back 379

-Very rare
-Dogs have malignant neoplasia that can result in hyperthyroidism
-Usually can palpate mass in neck area

Front 380

Parathyroid Disease Imaging

Back 380

-Whole body radiographs and abdominal ultrasound
-Need to rule out paraneoplastic syndrome as cause for hypercalcemia
-Rule out bladder stones secondary to hypercalcemia

Front 381

Cancers presenting with Hypercalcemia

Back 381

-Lymphoma, esp. with cranial mediastinal mass
-Anal sac carcinomas

Front 382

Neck Ultrasound for Parathyroid Tumors

Back 382

-Look for thyroid gland, then look for evidence of hypoechoic nodules
-Round/oval, well-marginated nodule
-More than 4-5mm, hypoechoic or anechoic comared to surrounding parenchyma
-High accuracy diagnosis

Front 383

Hyperparathyroidism secondary to Nutrition

Back 383

-Caused by diet that has low Ca:P ratio
-Decreases serum Ca levels, decreases PTH secretion
--Ca is removed from bone, causes diffuse osteopathic and pathologic fractures
-Will see thin cortices, double cortical lines, decreased bone opacity, or pathological fractures on radiographs

Front 384

Double Cortical Sign

Back 384

-Two lines in bone cortex with radiolucency in the center
-Indicates osteopenia, any type of osteopenia
-Bone resorption occurs around vessel first

Front 385

Secondary Hyperparathyroidism on ultrasound

Back 385

-Diffuse hyperplasia of ALL parathyroid glands
--All parathyroid glands will be visible due to enlargement

Front 386

Pancreatic Insulinoma on Radiographs

Back 386

-Abdomen is usually normal
-Thorax is usually normal, pulmonary metastasis is rare

Front 387

Pancreatic Insulinoma on Ultrasound

Back 387

-Look for mass lesion in the area of the pancreas
-Absence of mass does not rule out a tumor
--may be small or poorly visualized
--pancreas is surrounded by gas, can be hard to image
-May see peri-pancreatic metastatic lesions and liver metastasis

Front 388

Insulinoma on CT

Back 388

-Dual phase angiography study
-Image the pancreas pre and post contrast administration during arterial phase and venous phase
-If insulinoma is present, will see stronger arterial enhancement compared with normal pancreatic parenchyma
-Pre-contrast image is not that exciting, post-contrast image will show nodules no matter how small

Front 389

Imaging of Diabetes Mellitus

Back 389

-Not a disease that can be imaged well
-May see concurrent disease
--infection, pancreatitis, hepatomegaly due to hepatic lipidosis

Front 390

Important points of Endocrine Imaging

Back 390

-Endocrine disease diagnosis is usually not based on imaging
-Imaging can support a diagnosis
-Rule out other differentials
-Determine prognosis
-Identify concurrent diseases or complications
-Monitoring function, can see response to therapy

Front 391

Histology of the Thyroid Gland

Back 391

-Made of thyroid follicles
-One layer of cells surrounding protein-rich colloid that stains pink
-Colloid: mostly thyroglobulin

Front 392

Thyroglobulin

Back 392

-Precursor to Thyroid hormones

Front 393

Formation and Secretion of Thyroid Hormones

Back 393

-4 main steps:
--Iodide trapping
--Organification
--Coupling
--Hormone Secretion

Front 394

Thyroid Peroxidase

Back 394

-Main enzyme that is responsible for thyroid hormone production
-Treatments addressing thyroid issues inhibit Thyroid peroxidase function

Front 395

Steps in Thyroid Hormone Synthesis

Back 395

1. Iodide trapping and transport into the cell
2. Converting Iodide to Iodine
3. Incorporating Iodine with Tyrosine, tyrosine attached to thyroglobulin
-1 iodine: MIT
-2 iodine: DIT
3. Coupling of Tyrosine molecules within the thyroglobulin
-T4: 2 DIT coupled together
-T3: 1DIT and 1 MIT coupled together
4. T3 and T4 bud off from thyroglobulin in colloid vesicles, are exported from the cell membrane

Front 396

Transport and Metabolism of Thyroid Hormones

Back 396

-99% of T4 and T3 are transported in plasma bound to proteins
--Thyroid Hormone Binding Globulin, transthyretin, and albumin
--Serves as a reservoir for thyroid hormone
-Free T3 and T4 are physiologically active
-Most of T3 is made in periphery from T4
-T3 is more active than T4

Front 397

Formation of T3

Back 397

-T3 is made from T4 in the periphery
-T3 is more active than T4
-80-90% of T3 is formed by deiodination of T4 in peripheral tissues
--liver, kidney, muscle
-To measure thyroid gland function, need to measure T4

Front 398

Thyroid Hormone Regulation

Back 398

-TRH released from hypothalamus, acts on pituitary
-Pituitary secretes TSH that acts on thyroid gland
-Free Thyroid hormone T3 inhibits Pituitary

Front 399

Thyroid Hormone Actions

Back 399

-Increases metabolic rate
-REgultes mental awareness in nervous system
-Increases number and affinity of beta-adrenergic receptors in the heart
--can lead to hypertrophic cardiomyopathy
-Stimulates protein synthesis
-Stimulates carbohydrate and lipid metabolism
-Stimulates EPO
-Stimulates bone turnover during growth
-Stimulates neural and skeletal development

Front 400

Hyperthyroid Diseases

Back 400

-Clinical condition that results from excessive production and secretion of

Front 401

Hyperthyroid Diseases

Back 401

-Clinical condition that results from excessive production and secretion of Thyroxine T4 and Triiodothyronine T3 by thyroid gland
-Most common endocrine disorder seen in cats
-“New Disease,” first reported in 1979/1980
-Has become more common in last 15-20 years

Front 402

Pathogenesis of Hyperthyroid Disease

Back 402

-Adenomatous hyperplasia, benign hyperplasia
--Most common cause
-Can be small multi-focal nodules throughout the thyroid gland or generalized hyperplasia
-Similar to multi-nodular or toxic nodular goiter in humans
-Usually bilateral, 70%

Front 403

Histology of Adenomatous Hyperplasia of the Thyroid gland

Back 403

-have LOTS of cells where before there was only one cell layer
-Colloid gets smaller
-Lots more cellular function, lots more thyroid hormone produced

Front 404

Thyroid carcinoma

Back 404

-1-2% of cats with thyroid disease
-May or may not secrete excess thyroid hormone

Front 405

Etiology of Hyperthyroid diseases

Back 405

-Unknown!
-cat food additives?
-Abnormalities in cell regulation? G-protein issue?
-Circulating thyroid stimulators?
-Increased awareness among veterinarians?
-Probably multi-factorial

Front 406

Signalment for Hyperthyroid diseases

Back 406

-Middle aged to older cats, 4-22 years old
--most are more than 8 years, mean is 13
-No reported breed or gender predilection
-Less common in Persian and Himalayan

Front 407

Clinical signs of Hyperthyroid Diseases

Back 407

-Clinical signs can be ignored by the owner for a while
-Active, ravenous cat (appears “healthy”)
-Routine screening and veterinarian awareness
-Weight loss with polyphagia
-PU/PD
-Vomiting
-Diarrhea
-Unkempt hair coat or alopecia
-Behavior changes
-Shivering/tremors
-Weakness/lethargy
-Heat or stress intolerance
-Panting and respiratory distress
-Sudden onset blindness due to hypertension
-Heart failure due to up-regulation of beta-adrenergic receptors

Front 408

DDx for weight loss with polyphagia

Back 408

-Hyperthyroid disease
-Diabetes mellitus
-Neoplasia
-Protein-losing enteropathy
-Exocrine pancreatic insufficiency
-Parasites

Front 409

Physical Exam of animal with hyperthyroid disease

Back 409

-Hyperactive and difficult to exam
-Thin or cachectic
-Abnormal cardiac auscultation
--gallop rhythm
--cardiac murmurs (50%)
--tachycardia, more than 240 beats per minute
-Palpable thyroid gland, can be unilateral or bilateral

Front 410

CBC abnormalities in hyperthyroid animals

Back 410

-Mild elevation in PCV due to increased EPO
-Increased MCV
-Stress leukogram
-Increased platelet size

Front 411

Serum chemistry abnormalities in hyperthyroid animals

Back 411

-Mild to moderate elevation of ALP and ALT
--may be severe, may get fatty infiltration due to start of hepatic lipidosis
-Hyperglycemia due to stress
-BUN and creatinine may be elevate due to concurrent renal disease or dehydration
-Mild hyperphosphatemia
-Milk hypokalemia
-Creatine Kinase elevation due to muscle wasting (may be severe)

Front 412

Urinalysis in Hyperthyroid animals

Back 412

-Isosthenuria if there is renal insufficiency or PU

Front 413

Diagnostics to confirm hyperthyroid disease

Back 413

-Do not need nuclear scintigraphy!
-Look at total T4!!

Front 414

Total T4 concentration test

Back 414

-Normal is between 1 and 4
-Hyperthyroid is above 4
-Useful for diagnosing hyperthyroid disease in more than 90% of cases
-Should be elevated, above 4
-If lower or normal in a suspected animal, repeat in 1-2 weeks due to hormone fluctuations
-Can be affected by non-thyroid illnesses

Front 415

Free T4 concentration test

Back 415

-Good for diagnosing HYPO thyroid disease
-Not effected by thyroid hormone binding protein levels
-12-15% of normal vats with non-thyroidal illness had elevated free T4
-More sensitive and less soecific test
-Only use in combination with total T4 or after total T4
-Misleading if used as only diagnostic test

Front 416

T3 concentration

Back 416

-Not a good measure for diagnosis of hyperthyroidism
-Mostly formed by deiodination of T4 in the tissues
-T3 inhibits TSH secretion from the pituitary
--should decrease T4 secretion in a normal animal
-In abnormal thyroid gland, T3 will not suppress TSH release from pituitary

Front 417

Thyroid Scintigraphy

Back 417

-Identifies functional thyroid tissue
-Useful for finding ectopic thyroid tissue
--3-5% of cats have hyperactive secreting thyroid tissue in the mediastinum
-Useful to identify if one or both thyroid lobes are hyperfunctional
-Can see how much tissue in each thyroid is functional
-May help identify hyperthyroid cats with normal T4
-Do before sending animal to surgery

Front 418

Diagnosing Feline Hyperthyroidism

Back 418

-Clinical index of suspicion
-T4, CBC, chem, Urinalysis, chest rads, other ancillary tests if needed
-If T4 is in normal range, repeat in 1-2 weeks
--do T4 and free T4
-If T4 is still normal, screen for other diseases and perform T3 suppression test or scintigraphy

Front 419

Treatment for Hyperthyroid disease

Back 419

-Need to treat! Not treating is not an option, worst thing that can be done
-Medical treatment: anti-thyroid medications

Front 420

Why treat hyperthyroid disease

Back 420

-Elevated T4 increases GFR
--Can mask renal insufficiency
-Can lead to renal failure or heart failure
-Cats with overt renal failure at time of diagnosis must be managed carefully

Front 421

Medical treatment for Hyperthyroid disease

Back 421

-Anti-thyroid medications: Thiourelene compounds
-Inhibits thyroid peroxidase
-Prevent iodine incorporation into tyrosyl groups
-prevent coupling of MIT and DIT into T3 and T4
-Can directly interact with the thyroglobulin molecule

Front 422

Methimazole

Back 422

-Tapazole
-Main drug to use for hyperthyroid disease
-Very available and inexpensive
-Can control the amount of thyroid hormone produced
--important if there is a renal component, renal compromise
-Stabilize animals for surgery
-Owners have to pill the cat every day! VERY difficult!

Front 423

Methimazole Side effects

Back 423

-Usually appear within the first 3 months
-Transient anorexia, vomiting, lethargy
--Usually resolves quickly, can still use the drug
-Facial excoriations: resolves but need to stop the drug
-Hepatic toxicity: fairly rare but need to stop the drug before effects are permanent
-Immune-mediated issues

Front 424

Immune-mediated issues relating to methimazole

Back 424

-Hemolytic anemia
-Leukopenia
-Thrombocytopenia
-Usually resolve after stopping the drug
-Cannot use drug again if immune-mediated side effect arises

Front 425

Methimazole Preparations

Back 425

-Pill
-Liquid solutions, need to mix carefully
--dosing is not as accurate
-Transdermal preparation
--each compounding pharmacy will have a different version
--fewer GI side effects
--Variability in absorption

Front 426

Methimazole treatment regime

Back 426

-Check for renal disease before starting
-Monitor in 1-2 weeks to make dose adjustments
-Check CBC, chem, and T4
-Monitor every 2-3 weeks for first 3 months, the every 3-6 months as needed

Front 427

Surgery for Hyperthyroid disease

Back 427

-Usually need to remove both glands
-Surgery is curative
-Do not need lifelong administration of medication
-No monitoring of blood levels unless signs reoccur
-Very useful in cases of big or cystic thyroid mass

Front 428

Disadvantages of Thyroid surgery

Back 428

-VERY EXPENSIVE!
-Requires general anesthesia and hospitalization
-Very invasive surgery
-May result in hypocalcemia post-surgery if parathyroid glands are removed
-Hard to get ectopic hyperthyroid tissue
--Do Scintigraphy before surgery!
-Horner’s syndrome and laryngeal nerve damage may occur, but rare
-May lead to renal failure
-Hypothyroidism (rare)

Front 429

Radioactive treatment for Hyperthyroidism (I-131)

Back 429

-Take radioactive iodine I-131, give SQ
-Radioactive nucleus is unstable, undergoes decay
-Hyperfunctioning gland will collect radioactive iodine
--iodine concentrates in hyperfunctioning follicles
-I-131 is a beta-emitter, causes local tissue damage
--will kill hyperfunctional thyroid follicle cells
-Halflife of 8 days

Front 430

I-131 advantages

Back 430

-One SQ injection is curative in 95% of cats
-not invasive, do not need to repeat treatment
-Negligible side effects
-Not invasive
-Affects ectopic thyroid tissues
--affects any thyroid-secreting tissue
-Effective treatment for carcinoma, just need to give a high dose

Front 431

I-131 disadvantages

Back 431

-Need an authorized facility, regulated and licensed
-Cat needs to be hospitalized for radioactive clearance, away from owners
-High cost
--if animal lives for more than a year, becomes cost-effective
-May precipitate renal failure
-Cannot remove the treatment, one-shot deal
-Animals may become hypothyroid (Rare)

Front 432

Adjunct therapies for Hyperthyroid disease

Back 432

-Beta-blockers:
--propanolol or atenolol
--prevent heart failure
-Thiamine

Front 433

Prognosis for Hyperthyroid Disease

Back 433

-Survival is good with I-131 and Methimazole
-Renal disease significantly shortens survival time
-Methimazole alone: 2 years
-I-131 alone: 4 years
-Methimazole before I-131: 5.3 years

Front 434

Nutrition and Hyperthyroid disease

Back 434

-Y/d diet, new food from Hill’s
-Remove iodine from the diet
-Seems to work OK!
-Best in house with only 1 cat where diet can be strictly controlled

Front 435

Treatment for Hyperthyroidism in Cats

Back 435

-Do a treatment trial!
-I-131 treatment is best
--Fewer treatments and side effects
--need to make sure there is no renal disease
-Important to not get to hypothyroid state

Front 436

Canine Hyperthyroidism

Back 436

-VERY rare
-Usually a malignant carcinoma in the thyroid
--large and invasive
-5-10% of tumors are functional
-Most animals have large cervical masses at the time of presentation
-Prognosis is poor to grave

Front 437

Treatment for Canine hyperthyroidism

Back 437

-Surgery
-Radioiodine (harder, need to give very high doses)
-Chemotherapy
-Cobalt irradiation

Front 438

Hypothyroid Disease

Back 438

-Usually affects dogs, rare in cats
--Most commonly diagnosed endocrinopathy diagnosed in dogs
-LOTS of false diagnoses

Front 439

Pathogenesis of Hypothyroid disease

Back 439

-Immune-mediated
--lymphocytes infiltrate thyroid and cause inflammation, damage thyroid
--histologically, will see lymphocytic infiltration
-Progressive destruction of thyroid follicles
-May take years to complete destruction

Front 440

Thyroid Atrophy

Back 440

-Thyroid parenchyma is replaced by adipose tissue and no inflammatory cells
-Idiopathic
-End-stage lymphocytic thyroiditis?

Front 441

Neopastic destruction of the Thyroid

Back 441

-Carcinoma
-Squamous cell carcinoma

Front 442

Congenital Hypothyroid issues

Back 442

-Rare
-Thyroid agenesis
-Thyroid dysgenesis
-Dyshormonogenesis
--follicular cell hyperplasia
-Usually have other congenital issues as well
-Want to prevent at an early age

Front 443

Drug-induced hypothyroid disease

Back 443

-Trimethoprim-sulfadiazine induced hypothyroidism
--May directly interfere with thyroid peroxidase activity
--directly inhibits thyroid hormone synthesis
-Treatments for hyperthyroidism can cause hypothyroidism

Front 444

Secondary Disease of Hypothyroidism

Back 444

-Dysfunction within the pituitary thyrotropic cells
--less TSH is produced
--can be due to neoplasia or drugs
-Cystic Rathke’s pouch n German Shepherds

Front 445

Signalment for Hypothyroid dogs

Back 445

-Middle-aged, big dogs
--4-10 years old
-Golden retrievers, Dobermans, Labrador Retrievers
-Spayed females and castrated male dogs may be at an increased risk

Front 446

Clinical signs of Hypothyroidism in dogs

Back 446

-Often is subtle and gradual onset
--Important for diagnosis!
-Decreased cellular metabolism
-Lethargic, exercise intolerant
-Heat-seeking
-Weight gain
-Mental dullness, usually not obvious
-Constipated
-Decreased appetite with increased weight gain

Front 447

Dermatologic signs of Hypothyroid disease

Back 447

-Endocrine alopecia
--bilateral truncal alopecia, non-pruritic
-Alopecic on caudal thighs
-“Rat tail”
-Dull, dry, flaky hair coat
-Seborrhea, chronic otitis
-Hyperpigmentation
-Failure of hair growth
-Myxedema
-Secondary pyoderma

Front 448

Neuromuscular signs

Back 448

-Profound lethargy and muscle weakness
-Peripheral nerve paralysis
-Laryngeal paralysis
-Dragging feet
-Lameness
-Megaesophagus?
-Slow nerve conduction velocities
-Peripheral vestibular disease

Front 449

DDx for megaesophagus

Back 449

-Myasthenia gravis
-Addison’s disease
-Lead poisoning
-Idiopathic

Front 450

Reproductive signs of Hypothyroidism

Back 450

-Affects fertility of females, not male dogs
-Failure to cycle
-Prolonged interestrous intervals
-Lack of libido in the female
-Hyperprolactinemia

Front 451

Clinical signs of Congenital Hypothyroidism

Back 451

-Growth retardation
-Mental retardation
-disproportionately large heads
-Retention of the puppy coat
-Disproportionate dwarfism, retarded epiphyseal growth

Front 452

Cardiovascular signs associated with Hypothyroidism

Back 452

-Bradicardia
-Cardiac arrhythmias

Front 453

Myxedema Coma

Back 453

-Animal may present comatose
-Cerebral myxedema, swelling in the brain
-Central neurological signs and seizures

Front 454

Physical exam of a hypothyroid patient

Back 454

-Mildly overweight, or severely obese
-Lethargy
-Hypothermia
-Bradycardia
--sinus bradycardia
--decreased amplitude of P and R waves
-Skin disease, rat tail
-Myxedema of skin

Front 455

Diagnosis of Hypothyroid dogs

Back 455

-VERY over-diagnosed disease!
-Due to dilliculties of diagnostics

Front 456

Work-up for Hypothyroid disease

Back 456

-CBC/Chem:
--mild to moderate normocytic, normochromic non-regenerative anemia
--Fasting hypercholesterolemia can help identify the disease
-Fasting hypertriglyceridemia
-Urinalysis is usually normal

Front 457

T4 measurement for Hypothyroid disease

Back 457

-Measures totally T4 in the plasma
-Affected by MANY physiologic and pharmacologic factors
--affects T4 binding proteins and pituitary-thyroid axis
-Useful as a screening test, middle or high normal will reduce the chance of hypothyroidism

Front 458

Free T4 measurement

Back 458

-Free hormone
-If low, indicates hypothyroidism
-Separated by equilibrium dialysis and measured by RIA
-MUCH more sensitive

Front 459

TSH measurement

Back 459

-Used to diagnose hypothyroidism in people
-No good assays out there
-Very specific when combined with total T4
-Not a valid test on its own
--25-38% of hypothyroid dogs have normal TSH levels
-12-38% of euthyroid dogs with concurrent illnesses have high TSH levels

Front 460

Total T4 and TSH

Back 460

-Total T4 is low and TSH is high: suspicious for hypothyroidism
-Best test for hypothyroidism when combined

Front 461

TSH stimulation test

Back 461

-Gold standard for hypothyroid testing
-INjectible bovine TSH is off the market
--expensive test to run
--have to worry about anaphylactic reactions

Front 462

T3 measurement for hypothyroidism

Back 462

-Not useful
-T3 is formed by deiodination of T4 in the tissues
-Not indicative of thyroid activity

Front 463

Euthyroid Sick Syndrome

Back 463

-physiological adaptation to decrease cell metabolism during periods of stress
-concurrent illness
-Makes diagnosis of hypothyroidism difficult
-Can be due to changes in thyroid hormone binding proteins
--changes activation of 5-deiodinase enzymes
--changes TSH secretion
--Causes increased metabolism of thyroid hormone
-Free T4 levels are not affected as much

Front 464

Causes of Euthyroid Sick dogs

Back 464

-Hyperadrenocorticism (Cushing’s disease)
-Diabetes mellitus
-Starvation
-Any concurrent disease or systemic diseases
-Pyoderma

Front 465

Euthyroid Sick Treatment

Back 465

-NOT helpful to treat with thyroid supplementation!
-Treat underlying disease

Front 466

Other factors affecting Thyroid Hormone measurement

Back 466

-Drugs:
--glucocorticoids
--phenobarbitol

Front 467

Phenobarbital and Thyroid Hormone

Back 467

-May cause decreased T4, Free T4
-Increases TSH
-Makes diagnosis of hypothyroidism difficuly

Front 468

Suggested approach for diagnosing Hypothyroidism

Back 468

-Clinical index of suspicion
-Measure T4: if in upper part of reference range, hypothyroidism is low
-Measure Total T4, TSH, and free T4
-Measure auto-antibodies
-Elevated TSH, Low T4 and free T4: diagnose!
-Trial treatment with levothyroxine, monitor response to therapy

Front 469

Hypothyroid Treatment

Back 469

-Simple treatment, give thyroid hormone!
-Sodium levothyroxine is treatment of choice
--L-thyroxine
-Use good generic or brand name
--some compounding pharmacies will change concentration or mis-label
--if need to change companies, monitor for changes in illness
-Start at lower dose for dogs with cardiac illness, severely debilitated dogs, or geriatric patients
-If emergency (myxedema stupor or coma) give IV L-thyroxine and supportive care

Front 470

Monitoring for Hypothyroid treatment

Back 470

-Measure T4 4-8 hours after administration
--check at peak function
-T4 or free T4 should be in upper range of normal or slightly higher than normal
-Adjust dose if necessary
-Check pre-pill if dosing once per day
-Monitor for signs of hyperthyroidism
--will lead to renal and heart issues
-Few side effects

Front 471

Prognosis for Hypothyroidism

Back 471

-Good if treatment is appropriate

Front 472

Feline Hypothyroidism

Back 472

-Rare!
-Severe lethargy, inappetence, obesity, seborrhea sicca
-Constipation
-Diagnose by measuring T4 and free T4
-Treatment is similar to dogs

Front 473

Hyperthyroidism and Hypothyroid take home message

Back 473

-Hyperthyroidism:
--easy to diagnose, T4 is elevated
--finding appropriate treatment is based on renal and cardiac issues
-Hypothyroidism:
--easy to treat
--need to make sure you have the right diagnosis!

Front 474

Calcium in the Body

Back 474

-More than 99% of calcium is in the bone
-Plasma calcium is present in 3 forms
--bound to protein (40%)
--Complexed to citrate and phosphate (10%)
--Diffusable and ionized (50%)
-Diffusable and ionized calcium is physiologically active and regulated form
-50% of 1% is the calcium that is available and has physiologic effect

Front 475

Serum calcium

Back 475

-Measures total calcium
-Bound, complexed, and ionized

Front 476

Ionized Calcium measurement

Back 476

-Most accurate way to determine calcium status
-Best measured anaerobically

Front 477

pH and Calcium

Back 477

-pH of plasma affects ratio of protein bound Ca to ionized Ca
-if pH is high, ionized Ca will be lower
--more plasma protein anions to bind Ca, more Ca is bound
--free Ca decreases
-Decreased plasma pH (academia) results in fewer plasma protein anions
--free Ca is increased
-When exposed to air, serum pH usually increases and free Ca decreases

Front 478

Acidemia and Ca

Back 478

-Acidemia results in increase in free Ca

Front 479

Biological roles of Ca in the body

Back 479

-Muscle contraction
-Nerve function
-Blood coagulation
-Enzyme activity
-Cell secretion
-Skeletal structure

Front 480

Endocrine regulation of Ca homeostasis

Back 480

-Very common that patients have Ca problems

Front 481

Vitamin D in Intestine

Back 481

-Increases plasma Ca and phosphorous concentrations
-Intestine is the main target organ
-Works on absorption of Ca and P from intestine
-Formation of calcium-binding protein in the intestinal epithelial cells that actively transport Ca into the cell
-Increases P absorption by unknown mechanism

Front 482

Vitamin D in Bone

Back 482

-Works with parathyroid hormone
-Mobilizes Ca and P from the bone
-Appears to be less important than parathyroid hormone PTH

Front 483

Vitamin D in the kidneys

Back 483

-Promotes Ca and P reabsorption from the urine in the kidney
-NOT the major player
-May work with PTH

Front 484

Regulation of Vitamin D secretion

Back 484

-Formation of calciferol in the kidney by 1-alpha hydroxylase
-Elevated plasma Ca has a direct effect
--primarily works through decreasing PTH
-Responsible for day-to-day control of Ca
--not minute to minute, does not respond to changes quickly
--long-term regulation of Ca

Front 485

Parathyroid Hormone PTH

Back 485

-Synthesized and secreted by the Chief cells in the parathyroid glands
-Synthesized as part of a larger molecule
--pre-pro-PTH

Front 486

Actions of PTH

Back 486

-Bone: increases bone resorption and Ca mobilization
-Kidney:
--decreases P reabsorption, increases P secretion in proximal tubules
--enhances P excretion in urine
--increases Ca reabsorption in distal tubules and collecting ducts
--Increases formation of 1,25 dihydroxycholecalciferol

Front 487

Regulation of PTH secretion

Back 487

-Decreased plasma Ca increases PTH secretion
-Elevated plasma Ca inhibits PTH secretion
-1,25-dihydroxycholecalciferol decreases PTH synthesis
--negative feedback, PTH causes vitamin D3 to be formed
--too much vitamin D3 decreases PTH which decreases Vitamin D 3 production
-Mg is required for normal PTH secretion and target organ responses

Front 488

Calcium Regulation

Back 488

-PTH up, Ca is up and P is down
-Vitamin D up, Ca up and P up

Front 489

Vitamin D vs. PTH

Back 489

-Vitamin D is a steroid, acts in intracellular receptors
--Long-acting, produces proteins
--acts on GI Tract
--Increases phosphorous
-PTH is a polypeptide
--much shorter acting
--acts on bone and kidney
--decreases Phosphorous

Front 490

Calcitonin

Back 490

-Synthesized by parafollicular cells in thyroid
--C-cells produce
-Small peptide, 35 KDa and 32 amino acids
-Lowers circulating Ca and P levels
-Inhibits bone resorption via direct effect on osteoclasts
--osteoclasts are inhibited, less bone resorption
-IN kidney increases Ca excretion

Front 491

Factors affecting Plasma Ca

Back 491

-Intestinal absorption via vitamin D (IN)
-Bone resorption via PTH and vitalin D (IN)
-Urinary Excretion via calcitonin, PTH and vitamin D (OUT)
-Bone formation via calcitonin (OUT)

Front 492

Ca and the Kidney

Back 492

-Ca inhibits action of ADH on collecting ducts
--no ADH action, PU/PD
-Hypercalcemia may induce renal injury
-Total Ca increases in renal failure
-Renal secondary hyperthyroidism

Front 493

Clinical sins of Hypercalcemia

Back 493

-PU/PD
-Muscle weakness/atrophy
-Depression, coma
-Anorexia, vomiting, constipation
-Bone pain, pathological fractures
-Signs related to specific tumors (enlarged peripheral lymph nodes
-Cardiac arrhythmias (prolonged P-R and shortened Q-T intervals

Front 494

PU/PD due to hypercalcemia

Back 494

-Ca interferes with ADH receptors in collecting duct
-Ca uroliths can cause problems
-usually the first sign that is noticed by the owner
--sometimes the only sign

Front 495

Primary Hyperparathyroidism

Back 495

-Parathyroid gland is overactive, secretes too much PTH
-Relatively uncommon in dogs
-Rare in cats
-Can be due to Adenoma, carcinoma, hyperplasia, ectopic parathyroid tissue

Front 496

Clinical signs of Hyperparathyroid disease

Back 496

-Signs are often absent in mild forms of the disease
-Signs associated with hyperclacemia
--PU/PD
--anorexia
--depression
-As hypercalcemia progresses, severe illness and organ failure may occur
-Usually will not result in renal failure because P is decreased

Front 497

Physical exam for patient with hyperparathyroidism

Back 497

-Often normal PE
-Non-specific abnormalities
-Rare that you can feel an enlarged parathyroid
-Ca uroliths may be present
-Ca will be high
-PTH will be normal to elevated
-measure PTH and Ca at the same time
--if Ca and PTH are both increased, know there is an issue
-P will be normal to low, relative “protective” effect on the kidneys

Front 498

Hypercalcemia of Malignancy

Back 498

-Most common and important cause of hypercalcemia in dogs
-Caused by release of a factor by a tumor
--PTH-related hormone (PTHrP)
--causes up-regulation of osteoclast activity in bone
-Leads to bone resorption
-Lymphoma, anal sac carcinoma

Front 499

Lymphoma and hypercalcemia

Back 499

-Commonly produces hypercalcemia in dogs
-Cats are usually FeLV negative
-PTHrP is isolated from dogs and cats with lymphosarcoma

Front 500

Multiple myeloma and hypercalcemia

Back 500

-Malignant plasma cells
-can be in bone marrow
-Osteoclast-activating factor
-Causes bone changes
-Seen in cats and dogs

Front 501

Apocrine cell Adenocarcinoma of the Anal Sac

Back 501

-Hypercalcemia due to humoral factors
-80-90% of dogs have hypercalcemia
-Older females are predisposed, can see in either sex

Front 502

Common tumors causing Hypercalcemia

Back 502

-Lymphosarcoma (top 9 cancer causes of hypercalcemia)
-Multiple myeloma
-Anal sac adenocarcinoma
-mammary gland carcinoma
-Lymphocytic leukemia
-Carcinomas of lung and thyroid
-Testicular interstitial cell tumors
-Metastatic squamous cell carcinoma in cats

Front 503

Renal disease and hpercalcemia

Back 503

-Most patients with chronic or renal disease are normocalcemic
-May see increased complexed Ca due to retention of ligands
-Some patients may have true ionized hypercalcemia
--maybe related to acidosis?

Front 504

Hypoadrenocorticism and hypercalcemia

Back 504

-Increased Ca caused by glucocorticoid deficiency, hyperproteinemia, increased renal Ca reabsorption
-May also cause hypocalcemia
-uncommon cause, but can happen

Front 505

Other causes of Hypercalcemia

Back 505

-Hypervitaminosis D
--rodenticides
--skin creams
-Granulomatous disease
--fungal infections

Front 506

Feline Idiopathic Hypercalcemia

Back 506

-Most common cause of hypercalcemia in cats
-Syndrome of young to middle-aged cats
-Mild to moderate hypercalcemia for months to years
-Can cause vomiting and weight loss
-Dietary factors? Increased dietary fiber? Mg limited diets? Dietary acidification?

Front 507

HARD-IONS

Back 507

-Hyperparathyroidism
-Addison’s Disease (hyperadrenocorticism)
-Renal disease
-Vitamin D toxicosis
-Idiopathic
-Osteolytic
-Neoplasia
-Spurious (lipemia)

Front 508

Hypercalcemia

Back 508

-Elevated ionized Ca
-False elevations can be caused by many factors
--elevated total protein, especially albumin
--serum lipemia
--renal failure due to increase in complexed Ca

Front 509

Diagnostics for Hypercalcemia

Back 509

-CBC
-Chemistry: check albumin levels and renal function
-Urinalysis: look for UTI
-Ionized Ca: confirm hypercalcemia
-ACTH stimulation test to rule out Addison’s disease
-Aspirate lymph nodes, even if they feel normal
--Lymphoma is so common it is worth doing
-Radiographs
-Ultrasound
-Bone marrow exam
-Check PTH levels

Front 510

Radiographs for hypercalcemia diagnosis

Back 510

-Chest, abdominal, skeletal radiographs
-Look for metastatic disease
-Look for bony lesions on skeleton

Front 511

Ultrasound for Hypercalcemia diagnosis

Back 511

-Abdomen: look for neoplasia
-Neck: assess parathyroid glands

Front 512

Bone marrow analysis for hypercalcemia diagnosis

Back 512

-Look for hematologic cancer
-Sometimes is the only tissue that can provide a diagnosis

Front 513

PTH levels for Hypercalcemia

Back 513

-Need ionized Ca levels at the same time
-Elevated PTH levels with hypercalcemia strongly suggests hyperparathyroidism
-PTH can also be normal with hyperparathyroidism
-Also elevated in renal failure

Front 514

PTHrP levels for hylercalcemia

Back 514

-Elevated concentrations of PTHrP are associated with tumors
--Lymphoma
--anal sac adenocarcinoma
-If levels are normal, does not rule out neoplasia

Front 515

Vitamin D levels for Hypercalcemia diagnosis

Back 515

-Can be useful if hyperphosphatemia is also present
-Indicates rodenticide poisoning, vitamin D over-supplementation, or granulomatous disease

Front 516

Treatment for Hypercalcemia

Back 516

-Treat underlying condition
-Surgical removal of parathyroid mass
-Ethanol injection or heat ablation of parathyroid tumors
-Chemotherapy for neoplasia

Front 517

Surgical removal of parathyroid masses

Back 517

-Closely monitor post-surgery, animals often become hypocalcemic
--other glands will have atrophied, takes time for them to become functional
-Rarely the disease may recur, may need further surgery
-Ultrasound-guided ethanol injection or heat ablation or Parathyroid tumors

Front 518

Neoplasia treatment for Hypercalcemia

Back 518

-Chemotherapy or surgical intervention of underlying neoplasia
-Often resolves hypercalcemia

Front 519

Emergency treatment for Hypercalcemia

Back 519

-Indicated when there are severe clinical signs
-Cardiac arrhythmias
-Renal failure
-Ca x P is more than 60 mg/dl
-Give IV fluids, 0.9% NaCL
--natriuresis promotes calciuresis
-Furosemide promotes natriuresis and calciuresis

Front 520

Bisphosphanates as treatment for Hypercalcemia

Back 520

-Inhibit osteoclast activity
-Decrease Ca and P
-Long-acting, can be used to manage patient until specific diagnosis is reached
-Useful in vitamin D toxicity
-May be useful in feline idiopathic hypercalcemia
-Pamidronate, clodronate, alendronate

Front 521

Calcitonin as treatment for Hypercalcemia

Back 521

-Increases secretion of Ca in kidneys
-Salmon calcitonin is most often used, more potent than human or dog calcitonin
-Commercially available
-Very expensive
-Can be given IV or SQ

Front 522

Corticosteroids as treatment for Hypercalcemia

Back 522

-Glucocorticoids promote calciuresis, gets rid of Ca
-Should not be used until Lymphoma has been ruled out!
--steroids are lymphotoxic, may induce multiple drug resistance
-Interfere with testing for hypoadrenocorticism (Addison’s Disease)

Front 523

Primary Hypoparathyroidism

Back 523

-Failure of PTH action
-Iatrogenic
-Idiopathic
-Pancreatitis
-Intestinal malabsorption
-Phosphate enemas
-MUCH less common than hypercalcemia

Front 524

Idiopathic primary hypocalcemia

Back 524

-Lymphocytic parathyroiditis, immune system attachs parathyroid
-Lack of circulating PTH levels
-Occurs in young, or mature dogs

Front 525

Iatrogenic Primary Hypocalcemia

Back 525

-Parathyroid glands are injured or removed during thyroid surgery

Front 526

Eclampsia

Back 526

-Occurs during first 4 weeks of lactation
-Clinical signs develop rapidly
-Often concurrent with hyperthermia and hypoglycemia
-Due to poor nutrition?
-Excess Ca supplementation?

Front 527

Intestinal malabsorption leading to hypocalcemia

Back 527

-Lymphamgectasia
-May be concurrently hypomagnesemic

Front 528

Clinical signs of Hypocalcemia

Back 528

-Caused by excitatory effects of hypocalcemia on nerve and muscle cells
-Muscle twitching, cramps, tremors, tetany
-Lethargy, restlessness, seizures
-Cataracts are common in hypocalcemic people, rarely seen in dogs

Front 529

Diagnostics for Hypocalcemia

Back 529

-CBC, Chem, urinalysis
-Measure ionized Ca
-Serum magnesium
--important for management of the patient
--hypomagnesemia can cause hypocalcemia on its own
-Check PTH levels

Front 530

PTH and hypocalcemia

Back 530

-Low normal or decreased PTH with hypocalcemia indicates primary hypoparathyroidism
--should increase when Ca decreases
-Check ionized Ca on same blood sample for comparison
-PTH level means nothing on its own

Front 531

Treatment for Hypocalcemia

Back 531

-10% Calcium gluconate
-Give slowly, IV over 15-30 minutes
-Monitor ECG
-Can give as CRI or intermittent SQ injection

Front 532

Treatment of Acute hypocalcemic patient

Back 532

-Vitamin D and oral Ca supplementation
--begin as soon as oral medication can be tolerated
-After 1-2 days of normocalcemia with oral Ca and vitamin D, can discontinue parenteral Ca

Front 533

Vitamin D therapy

Back 533

-Vitamin D2 is the active form
--inexpensive, fat soluble, takes longer to raise serum Ca and takes longer to go away
--hard to regulate
-Dihydrotachysterol: works more quickly
--more expensive, easier to regulate
-Vitamin D3 (Calcitriol)

Front 534

Vitamin D3 Calcitriol

Back 534

-More rapid onset
-Biologically active compound
--can use physiological doses
-Goes away quickly
-more expensive
-May have to reformulate capsules since doses are usually too large for dogs and cats

Front 535

Calcium supplementation

Back 535

-Start at 25mg/kg/day during initial vitamin D therapy
-Gradually wean
-May not need long-term Ca supplementation
-Main issue with hypoparathyroid treatment is hypercalcemia!
-Serum Ca of animal should be checked during initial stages

Front 536

Pet Obesity

Back 536

-40-50% of pet population is over-weight or obese
-Especially in middle-aged dogs, 5-11 years old

Front 537

Health Risks associated with Pet Obesity

Back 537

-Glucose intolerance
-Abnormal insulin secretion
-Skin problems
-lameness
-FLUTD (cats)
-Idiopathic hepatic lipidosis

Front 538

Orthopedic disease and Obesity

Back 538

-Dogs with more weight have vastly increased orthopedic problems
-Earlier onset of osteoarthritis and greater proportion of animals
-Not obese dogs, just dogs that are “carrying around a few extra pounds”

Front 539

Factors promoting Weight gain in Animals

Back 539

-Animal factors
-Environmental factors
-Human companion factors

Front 540

Animal factors contributing to weight gain

Back 540

-Instinct to gorge
--unenriched, bored animals
-Feline metabolism
-Neutering

Front 541

Effect of Neutering

Back 541

-Neutered cats are 3.4 times more likely to be overweight than intact cats
-Increased food intake
-Decreased energy expenditure

Front 542

Environmental factors contributing to weight gain

Back 542

-Indoor confinement
-Palatable, energy dense foods
-Free choice feeding
-Multi-pet households

Front 543

Human factors contributing to weight gain

Back 543

-Perception of body condition
-Human-animal bond and sharing food/treats

Front 544

Energy Balance for pets

Back 544

-Energy intake vs. energy expenditure
-Want energy intake = energy expenditure
-Energy expenditure is based on lean tissue energy expenditure, NOT fat
--lean tissue, organ tissue, brain, heart, kidney, liver
-Resting energy requirement is the same whether the animal is overweight or not

Front 545

Weight loss program for Pets

Back 545

-Physical exam
-Medical history and emphasis on dietary information
-Estimate of lean body weight
-Estimate of current energy intake
-Formulate the treatment plan
-Monitor and adjust ongoing treatment program

Front 546

Diet History

Back 546

-Specific varieties and amounts of commercial foods fed
-Client may need to go home and check labels
-Need to know can size!
-Need to know how dry food is measured (if it is measured)
-May need to keep a food diary
-Who lives in the household
-Other pets in the household and feeding strategy
-Method of feeding
-Treats
--dental treats, rawhides, etc.
-Table foods
-Food to give pills
-Hunting or scavenging
-Activity level

Front 547

Identify problem areas based on diet history

Back 547

-Over-indulgence
-Begging
-Multi-pet household
-Sedentary lifestyle

Front 548

Estimating optimal weight of a patient

Back 548

-Breed standards
-Taking specific measurements to estimate percent body fat
-Check medical records
-Use body condition score
--10% for each level over optimal

Front 549

Best weight loss program

Back 549

-Caloric intake
-Exercise
-Behavior modification
-60-70% of current intake, feed 60-70% of estimated maintenance energy requirement

Front 550

Targeting rate of weight loss

Back 550

-1-3% of total body weight per week
--Safe weight loss without rebound
-No published studies in cats
-One published study in dogs

Front 551

Poteintial problems

Back 551

-Animal is “starving”
--feed multiple small meals per day
--Add non-starchy vegetables
--food puzzles
-Other people in the household
-Multi-pet households

Front 552

Carbohydrates

Back 552

-Not the carbohydrate in diet that makes the difference
-Calorid density is the big deal
-Macronutrient profile
-Fiber and water dilutes calories
--canned food is less calorically dense

Front 553

Therapeutic weight loss diets

Back 553

-Valuable for weight loss programs
-Low calorie density
-Fortified with essential nutrients
-High protein, preserves lean body mass
-Greater satiety?

Front 554

Important points of Obesity in pets

Back 554

-Obesity in companion animals is prevalent and has health consequences
-Teach people how to recognize optional body condition in their pets
-Get detailed history before formulating weight reduction plan
-Base estimates of energy requirements on an accurate account of intake OR MER calculated with optimal body weight
-Design a comprehensive weight loss plan that is tailored to the patient and its caregivers
-Mandate follow-up weigh-ins to monitor progress and adjust program