Endocrine Pathology

Front 1

In what zones of the adrenal cortex are glucocorticoids made?

Back 1

zona fasiculata

zona reticularis

Front 2

In what zone of the adrenal cortex are mineralocorticoids made?

Back 2

zona glomerulosa

Front 3

What are the effects of aldosterone of the kidney?

Back 3

↑ tubular reabsorption of Na+

↑ tubular excretion of K+

Front 4

What are the effects of cortisol?

Back 4

antagonism of insulin: promote gluconeogenesis & glycogenesis, ↓ glucose uptake by insulin-sensitive tissues

↑ lipolysis

suppress wound healing, inflammation, & immune response

Front 5

What zone of the adrenal cortex secretes sex hormones?

Back 5

zona reticularis

Front 6

What is the most common lesion associated w/ hypoadrenocorticism in dogs?

Back 6

lymphocytic adrenalitis: destroys all 3 zones

Front 7

What are causes of primary hypoadrenocorticism?

Back 7

lymphocytic adrenalitis
-no regeneration of adrenal cortex --> require life-long therapy
-all 3 zones destroyed --> glucocorticoid & mineralocorticoid deficiency, electrolyte disturbances
-may be immune mediated
-end stage: “idiopathic
adrenal cortical atrophy”

necrosis +/- hemorrhage that destroys glands
-endotoxemia, DIC = adrenal cortical necrosis
-bacterial septicemia: Actinobacillosis (foals), Salmonella (horses)
-Waterhouse-Frederichsen: massive hemorrhage & necrosis of adrenal cortex (calves)
-viruses (fetuses, neonates): Herpes (IBR: cow, pseudorabies: pigs, equine rhinotracheitis)

granulomatous: rare

Front 8

What are causes of secondary hypoadrenocorticism?

Back 8

pituitary tumor that destroys ACTH producing cells --> secondary atrophy of ZF

rapid withdrawal of exogenous steroids: exogenous administration of steroids --> negative feedback to ACTH

overdose of Lysodren when treating Cushings --> massive adrenal cortical necrosis (ZG destroyed)

↓ ACTH --> atrophy of ZF & ZR --> glucocorticoid deficiency
ZG spared: only 10% dependent on ACTH for stimulation --> no mineralocorticoid deficiency or electrolyte disturbances

reversible: adrenal cortex will regenerate if causative agent removed

Front 9

What is the most common lesion assoc. w/ hyperadrenocorticism in dogs?

Back 9

functional pituitary tumor --> bilateral adrenal hypertrophy

Front 10

What is the cause of primary hyperadrenocorticism?

Back 10

functional adrenal tumor --> 1 big adrenal & contralateral atrophy

10-15% of dogs w/ Cushings

autonomous production of cortisol from functional adrenal cortical tumor (50% benign, 50% malignant)

Front 11

What are causes of secondary hyperadrenocorticism?

Back 11

functional pituitary tumor --> bilateral adrenal hypertrophy
-80-85% of dogs w/ Cushings
-80-90% of these are pituitary microadenomas --> ↑ ACTH production
-only 10-20% are pituitary carcinomas (if large enough, can produce CNS signs, ex. blidness)
-pituitary tumor is NOT responsive or only partially responsive to neg. feedback inhibition of ↑ cortisol --> continues to secrete ACTH

100% of horses w/ Cushings (tumor in pars intermedia)

most cats w/ Cushings: large pituitary tumor

iatrogenic: long term administration of steroids (may be #1 cause of Cushings in vet med)

idiopathic bilateral adrenal cortical hyperplasia: poodles, toys, minis, etc. (< 10% of all cases)

Front 12

What causes the PU/PD in hyperadrenocorticism?

Back 12

glucocorticoids antagonize ADH function on tubules (biochemical nephrogenic DI)

↑ GFR --> dilute urine

destruction of pituitary by tumor --> ↓ production of ADH

Front 13

What is the pathway of thyroid hormone production?

Back 13

thyrotropic releasing hormone (TRH) from hypothalamus stimulates thyroid stimulating hormone (TSH) from pituitary, which stimulates thyroid follicular cells to hypertrophy & undergo hyperplasia & produce more T3 & T4

Front 14

calcitonin

a. produced by what cells?
b. secreted d/t...
c. function

Back 14

a. C cells of thyroid
b. increased serum Ca, gut hormones
c. decrease serum Ca conc.

Front 15

What are lesions assoc. w/ hypothyroidism in dogs?

Back 15

lymphocytic thyroiditis: 90% of cases in dogs
-end stage: “idiopathic follicular collapse”
-gland destroyed w/ no regeneration: requires life-long tx

functional thyroid tumor: RARE
-thyroid tumors that cause NO functional problems are common in older horses & dogs

secondary: pituitary lesion --> ↓ TSH (uncommon)

Front 16

What is the most common lesion of hyperthyroidism in cats?

Back 16

thyroid adenoma: COMMON in cats

rarely metastasizes

Front 17

thyroid tumors in dogs

a. prevalence
b. biologic behavior
c. functional effects

Back 17

a. common
b. 80% of thyroid tumors in dogs are carcinomas (larger tumors more likely to be malignant; mets: invade lungs before lymph nodes)
c. ↑ T4 likely d/t hypothyroidism w/ presence of Abs to thyroid Ags that cross react w/ assay rather than thyroid tumor

Front 18

How is total serum calcium distributed in the body?

Back 18

ionized: ~45% (biologically active fraction)
protein-bound: ~50% (most bound to albumin)
complexed: ~5%

Front 19

What are ddx for hypocalcemia w/ hyperphosphatemia?

Back 19

renal dz (common)

primary hypoparathyroidism (rare)

Front 20

What are ddx for hypocalcemia w/ normo- to hypo-phosphatemia?

Back 20

hypoalbuminemia (#1), renal failure (incl. EG toxicity), 1º hypoparathyroidism, milk fever (cow), eclampsia (bitch), pancreatitis, blister beetle poisoning (horse), nutritional 2º hyperparathyroidism, endurance racing (horse), hypomagnesemia

Front 21

How does renal dz cause hypocalcemia?

Back 21

↓ reabsorption of Ca from tubules d/t loss of tubular cells
↓ conc. of vitamin D d/t destruction of renal cells that produce vitamin D
↑ conc. of P that reciprocally --> ↓ Ca
soft tissue deposition of Ca x P (mineralization)
hypoalbuminemia d/t ↓ GFR
if cause of renal failure is EG toxicity --> Ca complexed w/ oxalate --> often SEVERE hypocalcemia

Front 22

primary hypoparathyroidism

a. most common lesion
b. results

Back 22

a. lymphocytic parathyroiditis (RARE): occurs in dogs only
b. immune mediated stimulus --> infiltration of lymphocytes & plasma cells --> destruction of PT gland
eventually, all PT glands will be destroyed --> conc. of PTH in serum will be undetectable --> cannot maintain serum Ca w/in RR

Front 23

What are ddx for hypercalcemia w/ hypophosphatemia?

Back 23

hypercalcemia of malignancy, 1º hyperparathyroidism, renal failure (HORSES only)

Front 24

What are ddx for hypercalcemia w/ normo- to hyper-phosphatemia?

Back 24

1º hyperparathyroidism, hypercalcemia of malignancy, vitamin D toxicosis, hypoadrenocorticism, renal disease, blastomycosis, young animals (esp. large breed dogs), idiopathic (cats), bone lesion (rare)

Front 25

primary hyperparathyroidism

a. lesions
b. results

Back 25

a. PT adenoma (seen in dogs, rare in cats), 1º PT hyperplasia may be more common than adenoma in cats
b. inc. PTH --> inc. serum Ca

Front 26

hypercalcemia of malignancy

a. cause
b. associated tumors

Back 26

a. tumor cells produce a protein very similar to native PTH (PTH-rp) that stimulates essentially the same biological functions: hypercalcemia & hypophosphatemia via stimulation of receptors on renal epi, osteoblasts, MPs
b. LSA, apocrine gland adenocarcinoma of anal sac, multiple myeloma in dogs, gastric SCC in horses

Front 27

What causes renal secondary hyperparathyroidism?

Back 27

↓ in serum Ca --> stimulation of PT glands

Front 28

What causes nutritional secondary hyperparathyroidism?

Back 28

d/t insufficient Ca or too much phosphorous in diet (ex. all meat diets for carnivores, excessive grain diets in horses)

Front 29

What are ddx for hypoglycemia?

Back 29

β-cell neoplasm, insulin overdose, sepsis, neonatal, starvation, small dog, hunting dog, endurance horses, Addison’s, ketosis, artifact (failure to separate serum), pregnancy toxemia

Front 30

B cell tumors (insulinomas)

a. species most commonly affected
b. biologic behavior
c. results

Back 30

a. dogs, ferrets, sometimes cats
b. tumors are invariably malignant in dogs & mets 1st go to regional ln’s & liver (despite benign cytologic & histologic appearance)
patient’s glucose conc. can be managed relatively well w/ diet & prednisone & may extend dog’s life for several years (it’s the hypocalcemia, not the tumor, that kills)
c. secrete excessive quantities of insulin --> life-threatening hypoglycemia

Front 31

What are ddx for hyperglycemia?

Back 31

diabetes mellitus
↑ blood catecholamine (epi) conc.
↑ blood glucocorticoid conc.
postprandial hyperglycemia
EG toxicosis (~50%)
cattle: epi & glucocorticoid induced hyperglycemia is common!
lipemia often interferes w/ glucose measurement (often present in patients w/ DM)

Front 32

Type I DM

a. cause
b. % of dogs & cats w/ DM
c. most common lesions in dogs
d. most common lesion in cats
e. other possible lesions

Back 32

a. absolute insulin deficiency
b. ~100% of dogs, 50-70% of cats w/ DM
c. recurrent pancreatitis (#1), immune mediated destruction of islets
d. islet amyloidosis
e. vacuolation of islets, lymphocytic inflammation of islets, islet cell aplasia

Front 33

Type II DM

a. cause
b. % of dogs & cats w/ DM

Back 33

a. insulin is present but does not produce its functional effect
insulin secretion in response to hyperglycemia is sluggish: inappropriately slow
peripheral tissues respond to insulin slowly (insulin resistance)
b. rare in dogs, 30-50% of cats w/ DM (many of these cats CAN be tx w/ insulin)

Front 34

Type III DM

a. cause

Back 34

insulin is present but does not produce its functional effect b/c of insulin antagonists in circulation
antagonists include glucocorticoids (#1), growth hormone, progesterones, glucagons
dogs may have this type, esp. w/ Cushing’s or in diestrus
cats w/ islet amyloidosis: amylin is co-secreted w/ insulin & is a competitive inhibitor of insulin

Type III probably precedes Types I & II
β-cell hypertrophy in an attempt to ↓ serum glucose conc. --> degeneration of β cells --> vacuolation & necrosis of islet cells from “exhaustion” --> Type I