Endocrine-Exam-Ii-Ldp-2010

Front 1

hyperparathyroidism treatments

Back 1

Thiazide diuretics should be avoided
because they increase calcium reabsorption.

Front 2

Loops Mm

Back 2

Increases excretion of water and calcium.
Increases urinary calcium excretion, thus, used to treat hypercalcemia.
Interferes with chloride-binding cotransport system by inhibiting the reabsorption of sodium and chloride in the:

Front 3

Loops alert

Back 3

CLINICAL ALERT
Hyperhydration and Furosemide

Electrolyte abnormalities, Hypokalemia

Front 4

Loop diuretics
Furosemide (Lasix) – Adverse Effects

Back 4

ototoxicity ....
Na/K/Cl symport
this same symporter is in inner ear

Weakness
Lethargy
Dizziness
Leg cramps
Vomiting
Possibly mental confusion

Front 5

loops - adverse ... with K

Back 5

Furosemide (Lasix) – Adverse Effects
Excessive potassium loss impairs proper functioning of the:
Heart
Skeletal muscle
Kidneys
Orthostatic hypotension is a common reaction because of large fluid losses.

Front 6

interactions , loops

Back 6

Metformin decreases concentrations of furosemide.

Other oral hypoglycemic drugs:
Increased potential for hyperglycemia.
Auditory toxicity appears to be increased with coadministration of aminoglycosides or cisplatin:
Hearing loss of varying degrees may occur.

Front 7

warfarin and loops

Back 7

loops displaces warfarrin from bound albumin

free drug = warfarrin

Front 8

Lithium and salicylates with loops

Back 8

Decreased elimination; thus lithium or salicylate toxicity.

Front 9

loops precautions

Back 9

Observe for blood dyscrasias and liver or kidney damage.

Perform frequent serum electrolyte, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter.

Front 10

Hormonal Therapy
Indicated in postmenopausal females.

Back 10

Estrogen (Premarin)
Reduces bone re-absorption resulting from hyperparathyroidism.

Front 11

estrogen C/I

Back 11

Known or suspected pregnancy
Breast cancer
Undiagnosed abnormal genital bleeding
Active thrombophlebitis, or thromboembolic disorders
History of thrombophlebitis, thrombosis, or thromboembolic disorders associated with previous estrogen use (except when used in treatment of breast malignancy)

Front 12

estrogen interactions

Back 12

May reduce hypoprothrombinemic effect of anticoagulants.
Coadministration of barbiturates, rifampin, (induce hepatic microsomal enzymes) may reduce estrogen levels.

Front 13

other estrogen interactions

Back 13

Toxicologic effects of corticosteroids may occur as a result of estrogen-induced inactivation of hepatic cytochrome P-450 enzyme.

Front 14

Calcimimetic agents (eg., Cinacalcet)

Back 14

tricks cells into thinking too much calcium around ....

so parthyroid will not respond

Front 15

chief cell receptors

Back 15

Cinacalcet

Increases the affinity of the calcium-sensing
receptor (CaSR) on the surface of the chief
cell of the parathyroid gland to extracellular
calcium.

This leads to an increase in intracelluler calcium,
thereby decreasing the secretion pf PTH.

In turn, this results in lower serum calcium levels.

Front 16

flecanide

Back 16

1 c antiarrythmic

Front 17

Bisphosonates

Back 17

C-P bond ---instead of C-O

cannot be destroyed by osteoclasts

Front 18

Bisphosphonates Mm

Back 18

Bisphosphonates are stable pyrophosphate analog that bind to hydroxyapatide in bone and act as potent inhibitors of PTH-mediated osteoclastic bone resorption.

Front 19

cortisol is an antagonist of ..

Back 19

insulin ..
different Mm , different recptor

Front 20

synthetic glucocortocoids

Back 20

fludrocortisone, dexamethasone, betamethasone etc

Front 21

Clinical Uses of Glucocorticoid

Back 21

A) Congenital Adrenal Hyperplasia is caused by poor production of cortisol (the most common cause). An infant with this disease initially has similar symptoms to those of acute adrenal insufficiency and should initially be treated similarly (i.e. an i.v. administration of hydrocortisone accompanied by correction of fluid & electrolyte imbalance)

Front 22

Clinical Uses of Glucocorticoid

Back 22

B) Cushing Syndrome is a consequence of bilateral adrenal hyperplasia some times caused by an ACTH-secreting pituitary adenoma (Cushing’s disease)

Symptoms include a rounded plethoric face, muscle wasting and trunk obesity. Appearance of purple striae, osteoporosis, poor wound heeling and easily bruising skin. Mental disorders, hypertension and diabetes are other serious disorders associated with Cushing syndrome

Front 23

cushings tx

Back 23

include surgical removal of ACTH-producing pituitary tumor, irradiation of pituitary tumor, or removal of one or both adrenal glands
Large doses of cortisol (300mg) are required initially, the dose is tapered down. Long term HRP is required if adrenal gland are removed.

Front 24

CLINICAL USES OF GLUCOCORTOCOIDS

Back 24

C) Aldosteronism (primary): adrenal adenoma, adrenal hyperplasia may all result in excessive aldosterone production leading to hypertension, weakness, tetany, hypokalemia, alkalosis and  plasma [Na+]

Excessive production of adrenal corticosteroids like deoxycorticosterone, corticosterone, 18-hydroxycorticosterone all with intrinsic salt retaining activity can also produce this syndrome

Front 25

Low plasma renin and angiotensin 2

Back 25

is a characteristic of primary unlike secondary aldosteronism
Spironolactone is used both for diagnosis and treatment of aldosteronism

Front 26

Dexamethasone suppression test

Back 26

use for diagnosing Cushing syndrome and also in the differential diagnosis of psychiatric state.

Front 27

Distinguishing between pseudo-Cushing’s syndrome and bona fide Cushing’s syndrome.

Back 27

A combine test of dexamethasone and CRH is required. A small dose of dexamethasone is administered every 6hrs for two days, followed with a standard CRH test.

A plasma cortisol concentration  1.4mg/dl measured 15minutes after cortisol administration distinguished Cushing’s syndrome

Front 28

Distinguish between Cushing’s disease and steroid-producing tumors of the adrenal gland or an ectopic ACTH syndrome

Back 28

. 0.5mg oral dexamethasone is administered every 6hrs for two days followed by oral 2mg every 6hrs for two days. A 50%  in urine cortisol levels distinguishes Cushing’s disease

Front 29

Clinical Uses of Glucocorticoids

Back 29

Stimulation of Lung maturation in fetus
Lung maturation is stimulated by fetal cortisol. Prior to premature deliver a maternal dose of an intramuscular betamethasone is administered to avert fetal respiratory distress syndrome

Front 30

Betamethasone

Back 30

is a better choice than cortisol because of less maternal protein binding and placental metabolism. This makes it more available to the fetus across the placenta

Front 31

glucocortocid toxicity

Back 31

Osteoporosis
Impaired wound healing
Peptic ulcers, psycosis (with large doses), salt retention and its complications(cortisone, hydrocortisone)

Redistribution of fat from periphery to trunk
Protein break down

Front 32

glucocortocoid C/I and cautions

Back 32

should be taken to watch for Hyperglycemia, glycosuria, sodium retention with edema and / or hypertension, hypokalemia, peptic ulcer, osteoporosis and hidden infection

May be contraindicated or use great caution in peptic ulcer, hypertension with heart failure, tuberculosis, psychosis, osteoporosis, or glaucoma

Front 33

mineralocorticoids

Back 33

Aldosterone, Deoxycorticosterone and Fludrocortisone

Front 34

mineralocortocoids , specifics..

Back 34

udrocortisone is a synthetic glucocorticoid and has a reputation as the most commonly prescribe salt-retaining hormone

Deoxycorticosterone has similar pharmacology as aldosterone but less important pharmacologically

Aldosterone is the most important mineralocorticoid in humans. It is regulated by at least two pathways: ACTH and the renin-angiotensin pathways.

Front 35

Physiologic and Pharmacologic Effects

mineralocortocoids

Back 35

aldosterone promotes , mechanism
Na+/K+ ATPase

Front 36

Deoxycorticosterone

Back 36

(DOC) is an endogenous precursor of aldosterone and is normally secreted in far lower amounts than aldosterone.
Unlike aldosterone, the release of DOC is controlled mainly by ACTH

Front 37

Fludrocortisone

Back 37

is a potent synthetic steroid with both glucocorticoid and mineralocorticoid activity
As low as 0.1mg dose seven times per week are very effective in treating adrenocortical insufficiency associated with mineralocorticoid defficiency

Front 38

extracellular calcium effect on Na channels

Back 38

high calcium gets in the way, inhibits excitable Na channels

symptoms : cramping and tetany
Weakness
Mental slugishness
Constipation, gastoparesis

Front 39

hypocalcemia
symptoms

Back 39

Na free to tickle receptors

 excitability:
Spasms: hands/wrists & feet/ankles first, diaphragm last
Excitability, aggression, nervousness, etc.
Diarrhea & other GI issues

Front 40

Magnesium in Premature labor

Back 40

Mg2+ is used to delay labor by inhibiting smooth muscle

Front 41

Acidosis

Back 41

 excitability due to both H+ & K+

Front 42

Alkalosis

Back 42

 Free Ca2+ may account for high lethality (COD **** )

Front 43

Hyperventilation

Back 43

acute respiratory alkalosis, →  free Ca++ levels.

numbness & tingling associated with hyperventilation

Front 44

levy--hypercalcemia S and S

Back 44

Polyuria
Nausea, vomiting, constipation
Confusion, coma, death

so levy , hypercalemia COD
McCabe -hypocalcemia

Front 45

levy - SS hypocalc

Back 45

tetany , prolonged QT

Front 46

PTH

Back 46

preprohormone
less than 2 hours stored amount
calcium levels regulate degredation

Front 47

actions of PTH

Back 47

Increases bone resorption of Ca++
Increases renal reabsorption of Ca++
Increases intestinal absorption of Ca++ (via Vitamin D3)

PTH prevents hypocalcemia due to dietary insufficiency by release of Ca++ from bone (largest supply)

Front 48

actions of PTH part II

Back 48

PTH increases both Ca++ & phosphate release from bone
PTH increases renal phosphate clearance . . .
prevents the formation of calcium-phosphate precipitates

Front 49

biochem -mechanics of PTH ****

Back 49

binds to receptors in kidney & bone
Receptor linked to two G-proteins:
Gs + Gq- activate protein kinases

Front 50

regulation of PTH secretion

Back 50

Low plasma levels of Ca++ stimulate PTH secretion via . . .
G-protein - Ca++ receptor on the parathyroid membrane senses low Ca++
The G-protein  adenyl cyclase & ↑ cAMP production  release of PTH

Front 51

clearance of PTH

Back 51

T½ 2-4 minutes
parathyroidectomy complication

Front 52

D2 (ergocalciferol-diet)
+ D3 (cholecalciferol- skin)

Back 52

gives u Vitamin D )not really a vitamin but a sterol hormone

Front 53

synthesis of vitamin D

Back 53

requires sunlight to convert 7-dehydrocholesterol to vitamin D3- nonenzymatic

2 hydroxylations occur- 1st in liver, 2nd in kidneys

Front 54

liver rxn LO 6

Back 54

1st hydroxylation- 25-hydroxylase converts vitamin D3 to 25(OH)D3.

Front 55

kidney rxn LO6

Back 55

2nd hydroxylation, **1-alpha-hydoxylase , to form 1,25-(OH)2D3

Front 56

Vitamin D-binding protein

Back 56

Transports Vitamin D3 to the liver
Transports 25(OH)D3 to the kidney

Front 57

Regulation of Vit D Metabolism & Synthesis

Back 57

1a-hydoxylase- the key to Vit D synthesis

Regulators of 1a-hydroxylase
PTH (stimulates)
1,25(OH)2D3 (inhibits)
Glucocorticoids (inhibits)

Front 58

pathophys of hypercalcemia and hypercalciuria

Back 58

thought to be due to an increased conversion of
1-OH vitamin D3 to the active 1,25(OH)2 vitamin D3 by macrophages and epithelioid cells from granulomas.

Front 59

Mode of Action of Vitamin D3

Back 59

Typical steroid hormone
Intracellular receptor (like steroids, thyroid hormone)
Hormone-receptor complex (HRC) binds to DNA- hormone response element (promoter region)
The HRC modulates transcription- RNA polymerase II

Front 60

genetic affect of the steroid hormone vitamin D

Back 60

Induces transcription of Ca++ binding protein, ***calbindin, in the brush border

Intestine primary target of vitamin D
Increases Ca++ absorption

Front 61

actions of vitamin D -- LO 4 *******

Back 61

Constant remodeling
Primary target cell- osteoblast,
Vit D builds strong bones by stimulating transcription, producing ****osteocalcin, collagen type I, and alkaline phosphatase.

Indirectly stimulates osteoclast- increases release of Ca++ & PO4 into blood

so affects both

Front 62

other issues with Vitamin D

Back 62

Maturation of hair follicles (lack of vit D receptors- life long alopecia totalis)

Inhibits epidermal kerotinocytes- treatment of psoriasis

Front 63

nutrition of vit D

Back 63

D2- milk and dairy
D3 - fish and eggs

Front 64

symptoms of hypercalcemia levy II

Back 64

Nausea, vomiting, constipation
Polyuria, polydipsia
nephrogenic DI
Malaise, weakness
Myopathy

Front 65

signs of hypercalcemia
objective

Back 65

Hypertension
Nephrolithiasis
MS changes- memory loss, confusion
Hyporeflexia
Coma
Short QT interval****

Front 66

Causes of Hypercalcemia****

Back 66

Multiple Myeloma
Bony mets
Sarcoidosis
Thiazides
Vitamin A and D intoxication
Adrenal insufficiency
Pheo

Front 67

hyperparathyroidism

Back 67

Usually adenoma (primary hyper PTH)
Asymptomatic
Hypercalcemia
inc PTH
dec PO4

Front 68

hyperpara in renal disease ?

distinguishing factor

Back 68

PO4 will be high ****

PTH up *****

Front 69

surgery is indicated for hyperparathyroid when ?

Back 69

Renal insuff

***Kidney stones- recurrent

**Bone disease (osteitis fibrosa cystica)

Watch for post op ???

Front 70

causes of hypocalcemia

Back 70

Acute pancreatitis
Hyperventilation
Post op PTH
CRF
Hypomagnesemia
Blood tx

Front 71

hypo

Back 71

alkylo

Front 72

rickets

Back 72

Rickets occurs when vitamin D production and intake are, together, inadequate for needs. Levels were very high at one time but fell greatly after milk was supplemented with vitamin D. There has been a resurgence with less outdoor activity and less milk consumption in children.


Rickets is characterized by hypocalcemia bones and periodic carpal or pedal tetany. Increased bone flexibility with slow mineralization causes the bones to bend under the weight of the body.

Front 73

osteomalacia (soft bones)

Back 73

Osteomalacia is a deficiency of vitamin D in mid-late teens or adults.

Causes include:
Steatorrhea, sometimes with symptoms of vitamin A (night blindness), E or K (bleeding) deficiency (treat with vitamin D)
Liver failure (treat with 25-OH vitamin D)
Renal disease (treat with 1, 25-OH vitamin D – far more difficult to manage)

Front 74

osteoporosis primary cause

Back 74

Primary cause is likely reduced bone stress due to reduced exercise in modern society.

Front 75

Pagets

Back 75

Paget’s disease is an inappropriate activation of osteoclasts followed by activation of osteoblasts so bone turnover is greatly increased.

Front 76

Radiologic and Ultrasound Quantification of Bone Loss

DEXA

Back 76

(dual energy X-ray absorptiometry): standard for measuring hip & spine BMD (2 major fracture sites)
- Used for osteoporosis diagnosis and monitoring

Front 77

SXA

Back 77

Single energy x-ray absorptiometry (SXA): measure peripheral sites (wrist, heel)
- Do not use for diagnosis and management

Front 78

OsteoporosisMedication Risk Factors

Back 78

prednisone **
Thyroid supplements
Chronic lithium therapy
Heparin
Chemotherapy
Methotrexate
Anticonvulsants (ex: phenytoin, phenobarbital)
Drugs alter Ca absorption: tetracycline, Al antacids
Drugs alter Ca elimination: loop diuretics
Immunosuppressants
Parental nutrition
Medroxyprogesterone acetate (black box warning on insert)
Cyclosporine
Tacrolimus

Front 79

diet

Back 79

most adults need 800 to 1000mg of Ca daily
* 400IU of vitamin D daily

Front 80

calcium goal

Back 80

1200 mg of calcium / day

Front 81

***drug interactions with Calcium supplements

Back 81

Tetracyclines and quinolones (Ca decreases absorption of these drugs)

Front 82

Adverse effects of Ca2+ supplements

Back 82

Abdominal cramps, bloating, flatulence an diarrhea
* Caffeine  calcium excretion
* Hypercalcemia and urinary stones

Front 83

Bisphosphnates
Mm ?

Back 83

inhibit osteoclast activity

reduce resorption and formation of hydroxypatite crystals

* inhibit osteoclast activity
* long half lives
* poor GI absorption

Front 84

uses
Alandronate, & Risedronate

Back 84

prevention & treatement of postmenuposal and glucocorticoid-induced osteoporosis

Front 85

Ibandronate

Back 85

treatment and prevention of postmenuposasl osteoporosis

Front 86

bisphosphonates adverse****

Back 86

caution in pregnancy
* esophageal ulcer, esophageal stricture, dyspepsia, dysphagia, acid regurgitation, abdominal pain, nausea, diarrhea musculoskeletal pain
* osteomalacia ( more with long term therapy of etidronate)

Front 87

bisphosphonates adverse**** recall

Back 87

bone pain in patients with Pagets
osteomalacia
N/D
esophagitis .

Front 88

bisphosphonates C/I

Back 88

hypocalcaemia (other bone & mineral metabolism disturbances)
* severe renal impairment

esophageal abnormalities
* precaution with gastric ulcers
* precaution with dysphagia, esophagitis

Front 89

calcintonin also used for osteoporosis
adverse ?

Back 89

rhitinitis, nasal irritation, nasal dryness
* pain, arthralgia
* headache

Front 90

estrogen and HRT

Back 90

-- stabilizes bone remodeling - stim osteoblasts
promotes calcintonin syn
inc vit D recptors ..
dec LDL
INc HDL
relieves hot flashes

Front 91

Teriparatide

Back 91

Biologically active human PTH
* Stimulates new bone formation
* uses: postmenopausal osteoporosis

Front 92

definitions

Back 92

Osteoporosis: Reduced bone mass- matrix (collagen and mineral)
BMD > 2.5 SD below mean

Front 93

def

Back 93

Osteopenia: less severe osteoporosis
BMD 1-2.5 SD below mean

Front 94

def

Back 94

Osteomalacia: abnormal bone mineralization (rickets in kids)

Front 95

blue sclera

Back 95

Osteogenesis imperfecta: abnormal collagen

Front 96

normal distribution

Back 96

mean, median , and mode are all the same number **

Front 97

BMD standard dev - osteoporosis

Back 97

outside of 2.5 SD below the mean

Front 98

osteopenia stats

Back 98

BMD 1-2.5 SD below mean

Front 99

normal sodium 135-145

Back 99

stat defined , 2 standard dev above and below the mean ********
but 2.5 % outside of range ---can still be normal
dont be bent out of shape over every lab abnormality - some normal people .. outside range

Front 100

exception for SD
cardiology....

Back 100

cholesterol
normal range , but unhealthy **

Front 101

secondary osteoporosis

Back 101

hypercortisolism
thyrotoxicosis ..
immobilization
space travel

long term heparin (should bbe a short term heparin )
why would u put someone on long term heparin ---- preggers (b/c not warfarin)

Front 102

bone mineral density test

Back 102

DEXA

Front 103

diagnosis
T scores

Back 103

T score (not aged matched)
> 2.5

this person has this standard deviation

normal girls in front -- T scores will be zero

60 years later -- their T scores

dont worry about Z scores

Front 104

Z score ?

Back 104

also a standard deviation
and it's the standard eviation of an age matched population

Front 105

you want ...

Back 105

non-aged matched dependant

Front 106

Mm of calcitonin

Back 106

inhibits osteoclasts

Front 107

Estrogen- a double edged sword

Back 107

Conserves bone mass
Protects against fractures
Effective for menopausal symptoms

Front 108

estrogen - side effect ********

Back 108

Higher incidence of MI, CVA, PTE, and breast CA

JAMA, July 17, 2002, vol. 288, no. 3, pp321-333

Front 109

rule for estrogen ...
give what with it ?

Back 109

progesteone

Estrogen –builds up the uterine lining …
Causes cell growth and cell division
Builds up uterus for a preggers

Cell growth … can develop uterine cancer…
How to minimize.. Combo ---- progesterone –causes shedding of that lining

Front 110

if had a historectomy

Back 110

can give unopposed estrogen

Front 111

Bisphosphonates

Back 111

All anti-resorptive – inhibit osteoclasts *********

dosed weekly or monthly .. after fosamax

Front 112

Bisphosphonates
common side effect...
so how to take ?

Back 112

dont go back in lye down
take in the morning with water..

impt instructions *** early in the morning, empty stomach, dont lye down

Common side effect
Gastritis/esophagitis

Front 113

SERMS

Back 113

do different things at liver receptors***

Agonist at bone inc BMD
Agonist at liver dec LDL cholesterol
Inert at uterus
Antagonist at breast***

Front 114

Calcitonin

Back 114

Inhibits osteoclasts
Nasal spray
Modestly effective

not a first line agent

Front 115

no longer used...

Back 115

fluoride.... inc bone mineral density ..

what are we really trying to do ?
inc bone mineral dens ?
no, just .. keep them from
breaking bone

Front 116

physiological vs clinical end point ****

Back 116

flouride works well in inc bone density.. but , kept breaking bones *******

corticol vs trabelcular bone .. can inc both.... fluoride inc trabeccular part of the bone ...
** have to inc density the right way **********

you think a drug is gooing to be good , b/c good science behind it.. but it has to change clinical end ppoints...
will it reduce fracture rates.......

Front 117

**blood supply to adrenals **

Back 117

1. superior suprarenal artery that comes off of phrenic artery (332 netter)

2. right middle suprarenal artery - off of aorta

3. inferior suprarenal artery (from renal artery)

Front 118

innervation of adrenals

Back 118

**Sympathetic fibers directly innervate the cells of medulla
Equivalent to postsynaptic neurons

Front 119

central adrenomedulllary vein is special

Back 119

as it has tunica media containing smooth muscle

Front 120

layers of the cortex

Back 120

Zona glomerulosa – globular clusters, small pyramidal cells, rich capillary network
Zona fasciculata – straight cords of large and polyhedral cells - glucocorticoids
Zona Reticularis – small cells in anastomosing cords: glucocorticoids and androgens

Front 121

glomereulosa layer

Back 121

thin , in globule clusters
rich in capillary network
MINERALCORTOCOIDS

Each cluster is associated with a capillary
Cells have abundant SER
Secrete mineralocorticoids (aldosterone)
Activated by angiotensin II

***Conn’ syndrome:
Hypertension
Hypokalaemia
Metabolic alkalosis

Front 122

Zona fasciculata

Back 122

cells are arranged in fasciles (cords and bundles)
straight cords , GLUCOCORTOCOIDS

Relatively large, lightly staining cells
Each cluster is associated with a capillary
Cells have abundant SER, Golgi, mitochondria with tubular cristae and many lipid droplets
Secrete glucocorticoids (cortisol) and corticosterone
Activated by hypothalamus and hypophysis

Front 123

Zona Reticularis

Back 123

means network
glucocorticoids and androgens
Cells are large (but smaller than those of the ZF), tightly packed and stain darkly
Each cluster is associated with a capillary
Cells have abundant SER and many lipid droplets

Front 124

Cushings syndrome vs. cushings disease ...

Back 124

syndrome : central obesity

Front 125

addison's disease

Back 125

Hypotension
Hyperkalemia
Hair loss in women
Vs Addisons (ACTH↓)

Front 126

what's in the adrenal medulla ?

Back 126

chromafinn cells
vessicles with norepi and epi

chrome salt staining :
cells with NorEpi are oxidized to a darker color ****

norepi is also found in larger vessicles

Front 127

adrenal medulla ganglion cells are contacted by preganglionic sympathetic fibers

Back 127

are contacted by preganglionic sympathetic fibers

Front 128

blood supply to the medulla of adrenal

Back 128

The medulla has a dual blood supply:
Arterial blood from the medullary arterioles
Venous blood for the cortical sinusoids

Front 129

hydroxyl at the 17 position =

Back 129

glucocortocoid

Front 130

biochem of zona glomerulosa

Back 130

makes aldosterone
***lacks cytoc P450 (17-alpha hydroxylase) and cant make cortisol or androgens

Front 131

Zona fasciculata and zona reticularis
function, biochem

Back 131

***lacks the 18

function as a unit
produce cortisol and androgens

lack the enzyme cytochrome P450C18 (18β-hydroxylase) and thus cannot produce aldosterone

Front 132

steroids in adrenal gland
from cholestrol and LDL
stimulation ?

Back 132

results in:
hydrolysis of stored cholesterol esters to free cholesterol
increased uptake of cholesterol from plasma lipoproteins
synthesis of cholesterol within the adrenal cells

Front 133

cum path question

Back 133

Follicular adenoma goes outside of capsule ….. And causes carcinoma

Front 134

Osteitis fibrosa cystica*********

Back 134

Cortex is grossly thinned
Marrow has increased amounts of fibrous tissue
Foci of hemorrhage and cyst formation

Brown tumors
Aggregates of osteoclasts, reactive giant cells, and hemorrhagic debris

Front 135

Painful bones, renal stones, abdominal groans, and psychic moans

Back 135

Primary hyperparathyroidism

Front 136

Calciphylaxis

Back 136

Vascular calcification associated with secondary hyperparathyroidism
Significant ischemic damage to skin and other organs

Front 137

DiGeorge syndrome

Back 137

Thymic defects + absence of parathyroid glands

Front 138

tetany

Back 138

low plasma calcium

Front 139

Pseudohypoparathyroidism

Back 139

End-organ resistance to actions of PTH
Serum PTH levels are normal or elevated
PTH resistance
Most obvious clinical manifestation
Hypocalcemia
Hyperphosphatemia
Elevated circulating PTH

Front 140

cushing disease ***
vs syndrome

Back 140

in the pitutitary is cushing disease *******
ACTH-secreting pituitary microadenomas

Front 141

small cell tumors secrete ?

Back 141

ectopic ACTH

Front 142

Waterhouse-Friderichsen Syndrome

Back 142

Overwhelming bacterial infection (Neisseria meningitidis septicemia)
Rapidly progressive hypotension leading to shock
DIC associated with widespread purpura
Rapidly developing adrenocortical insufficiency
Massive bilateral adrenal hemorrhage

Front 143

Li-Fraumeni syndrome

Back 143

Germline p53 mutations

Front 144

rule of 10s

Back 144

10% of pheochromocytomas are extra-adrenal
10% of sporadic adrenal pheochromocytomas are bilateral
10% of adrenal pheochromocytomas are biologically malignant
10% of adrenal pheochromocytomas are not associated with hypertension

Front 145

cholestrerol to pregenolone

Back 145

Desmolase

Front 146

pregnelone to 17 alpha-OH preg

Back 146

17 alpha-hydroxylase

can make cortisol if def in

Front 147

17

Back 147

no androgens

Front 148

18

Back 148

takes you to aldosterone

Front 149

symptoms for cushings

Back 149

central obesity
facial plethora
depression/anxiety
abdominal striae
dorsal fat pad
hypertension
glucose intolerance
hirsutism
Acne*****
amenorrhea

Front 150

Aminoglutethamide

Back 150

inhibits conversion of cholesterol to pregnenolone)

cushings tx

Front 151

key with aldosterone as far as ddx

Back 151

under the control of two systems

under the control of 18

two loops for an 8 (two pathways )

Front 152

types of steroids

Back 152

catabolic - cortisol****

(some are anabolic-- such as androgens )

Front 153

cushings syndrome vs cushingsdisease..again !!!

Back 153

cushings diseaseis from a pituitary adenoma

cushings syndrome -- from an adrenal adenoma, exogenous steroids

oat celllung CA
adrenal cancer

Front 154

ACTH dependency...

Back 154

an adrenal adenoma that secretes cortisol is ACTH independent

pituitart adenoma, oat cell, are ACTH dependent

Front 155

treatment for cushings

Back 155

dexamethasone ?

Front 156

dx cushings..

Back 156

24 hour urine collection -- will see free cortisol

do a CT , brain, belly, chest

Front 157

Overnight dexamethasone suppression test (DST-screening test)

Back 157

normally if you give someone a steroid , you will stop making cortisol .. neg feedback type

low dose doesn't work , but high dose does ? the problem is at the pituitary

Front 158

dx of cuhsings...more

Back 158

can also look at ACTH
if high ... then at pituitary

if low, then at adrenal

can also sample inferior petrosal sinus ****sure sign me up

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more on cushings tx ***********

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Aminoglutethamide (inhibits conversion of cholesterol to pregnenolone)

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I have hyperaldosteronism , but normal cortisol production

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cortisol not made in glomerula

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embryology of adrenal medulla

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neural crest migrate
medulla-more like nervous tissue then endocrine because.. the chomaffin cells receive pre-synaptic inneration****

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what is made in adrenal medulla ?

Back 162

mostly epi
norepi made in brain (locus cerrulus ?)

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COMT enzymne

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catecol-O-methyl transferase-
breaks down norepi into normatenephrine

this is inhibited by Entacapone, used to treat parkinsons... backs up whole system ..

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tumors in adrenal medulla

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Pheo

DDx: hyperthyroidism, anxiety, cocaine abuse, hypoglycemia

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super-important
tx of Pheos *************
(order)

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alpha blockers then beta blockers..

if u give beta blockers first .. then alpha actions are unopposed in vessel... already htn , will clmap down even more!!!!!!!!!1

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Incidental-oma "

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over 5 cm a problem

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adrenal insuff
types...

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primary -- addison's --auto-antibodies..
will see lymphocitic infiltrate

secondary= pituitary problem

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addison has ?

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lacks gfr ?

hypotnesion , hyponatremia , hypeerkalemia , hypoglycemia

hyperpigmentation

ACTH would be up , so hyperpigmentation ***********

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patient on steroids

Back 169

Normally ACTH inject, cortisol should go up
In primary adrenal failure= no response
Wont have inc in cortisol like supposed to

Flud– synthetic mineralocortociod
****** take exogenous steroids---- will atrophy .. Adrenals -- will suppress adrenals…
Wont respond to stress ***

Have to give more steroids..
Not being on, but having been on..

Asthma- I get stoids…
Wont respond to stress if you have been on steroids – this effect can last a year ***************************
Have to give them steroids------------ to get them through …. How long do you have to be on for, for this to happen ?
One week

******have to give steroids… in order to make cortisol ….

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ACTH

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ACTH is synthesized in the anterior pituitary.
ACTH secretion is stimulated by CRH and inhibited by cortisol

ACTH stimulates the secretion of adrenocortical steroids from the adrenal cortex

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details of ACTH and cortisol syn

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G protein mediated

ACTH stimulates cholesterol release by a lipase and transport across the mitochondrial membrane by StAR (steroidogenic acute response protein)

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steps in syn of cortisol

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CYP450scc
3β-hydroxysteroid dehydrogenase
CYP17A
CYP21A
CYP11


4 of 5 are cytochromes

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***reductive biosynthesis

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Hydroxylation reactions in steroid biosynthesis are catalyzed by Cytochrome P450-containing enzymes

Cytochrome P-450 enzymes are required for the hydroxylation of steroids to yield adrenocortical hormones.

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vitamins involved with reductive biosynthesis

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B2 and B3

riboflavin and niacin

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cytochromes in steroid metabolism

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CYP2, 11,17,19,21

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going from tyrosine to dopamine there is an intermediate .. to get ot this intermediate there is a cofactor....

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tetrahydrobioterin

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blood supply to anterior pituitary

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Anterior pituitary receives no direct arterial blood supply!

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anterior pituitary embryo

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rathke's poutch

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Gonadotropes (FSH and LH cells) – Basophils

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10% of the anterior lobe
Small cells, eccentric round nuclei, basophilic and PAS stain
Most of the cells produce both FSH and LH
FSH and LH release is regulated by hypothalamic gonadotropin-releasing hormone,
GnRH (=luteinizing hormone-releasing hormone, LHRH)

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Thyrotropes (TSH cells) – Basophils

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5% of the anterior lobe
Large cells, eccentric round nuclei, basophilic and PAS stain
TSH release is regulated by hypothalamic thyrotropic-releasing hormone (TRH)

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Somatotropes (GH cells) – Acidophils

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***50% of the anterior lobe
Medium sized cells, central round nuclei, eosinophilic granules
GH release is regulated by hypothalamic GHRH and somatostatin
Overproduction of GH results in gigantism and acromegaly

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Lactotropes (PRL cells, mammotrophes) – Acidophils, Chromophobes

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15-20 % of the anterior lobe
Large cells, oval nuclei, eosinophilic granules (granules released -> chromophobes)
PRL release is regulated by hypothalamic TRH, VIP(stim.) and dopamine (inh.)
During pregnancy and lactation these cells undergo hypertrophy -> larger pituitary

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Corticotropes (ACTH cells) – Basophils

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15-20 % of the anterior lobe
Medium sized cells, eccentric round nuclei, basophilic and PAS stain
Regulated by hypothalamic corticotropin-releasing hormone (CRH)
Produce proopiomelanocortin (POMC) that is cleaved into
ACTH
β-lipotrophic hormone (β-LPH)
Melanocyte stimulating hormone (MSH)
Endogenous opiates (β-endorphin, enkephalin)

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posterior lobe

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an extendion of the brain

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post pituitary hormones
signaling
oxytocin

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G protein , Calcium , PIP2

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vasopressin signaling
V1 or V3

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calcium , diacyl glycerol

v2-- uses dofferent path********* adenylate cyclase...

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oxytocin Mm

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protein kinase C -- calcium release
calmodulin rleated

labor, lactation, digestion

calcium binding to calmodulin is issue with calcium related systems

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V2 receptors and oxytocin ..

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Increases water resorption in the kidney by increasing the water permeability of aquaporin-2 water channels in renal luminal membranes

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dopamine and somatostatin
unique b/c ?

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are inhibitory in hypothalmus
somato --- dec growth hormone

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IGF-1 stim

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stimulates proliferation of chondrocytes (cartilage cells), resulting in bone growth

IGF-I also appears to be the key player in muscle growth stimulating differentiation and proliferation of myoblasts

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GH effects

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breakdown of fats

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conivaptam

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SIADH tx
caldwell

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3 sites of action where TSH works

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1. uptake of iodine into thyroid
2. oganified TG is endocytosed
3. hydrolysis

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where is ACTH derived

Back 194

from POMC cells
proopiomelanocortin

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action of ACTH

Back 195

stimulates the secretion of adrenocortical steroids from the adrenal cortex

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effects of LH

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men-stim testosterone production from leydig cells

women- stim estrogen and prgesterone from ovary
surge of LH is responsible for ovulation

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FSH

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men - stim testicular growth and angrogen binding to sertoli cells

women - development of ovarian follicle

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FSH

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makes follicles !
frustose -- spermatogeniss

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Levi-Lorain Syndrome

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inability to form IGF 1.

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Giantism

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excessive juvenile GH secretion, either form the pituitary or a GH secreting tumor. For giantism to occur the epiphysial plates of bones ****must not have closed.

Giants have hyperglycemia which ultimately results in diabetes.

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bone plates in acromegaly

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closed and bones become thicker

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post pituitary nerve endings ?

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SO and PV nuclei