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Endocrine Physiology > TBL > Flashcards

TBL Flashcards

1
Q

What are the various ranges of hypertension?

A

Normal160>100

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2
Q

What is the incidence of hypertension?

A

15-20% of Americans, 40% adult African-Americans, 50% Americans over the age of 60

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3
Q

What are the common cuases of hypertension and the rates of occurrence?

A

Primary or Essential HTN - 92-94%, Secondary to renal disease, 2-5%, Secondary to other reversible causes - 2

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4
Q

What is a tip off to a reversible cause of HTN?

A

Onset at age < 30 or > 50, Increased resistance to drug therapy, Worsening of HTN

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5
Q

Renin is an enzyme secreted by the juxtaglomerular apparatus of the kidney in response to what?

A

Decreased intravascular volume, Decreased serum [Na+], Increased serum [K+], Decreased blood pressure, Prostaglandins, Beta-adrenergic stimulation

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6
Q

Increased renin results in what?

A

cleavage of Angiotensin I (AI) from angiotensinogen which is secreted by the liver

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7
Q

Angiotensin I is converted to Angiotensin II by what?

A

angiotensin converting enzyme (ACE)

which resides in the vascular endothelium

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8
Q

Angiotensin II stimulates what?

A

synthesis and secretion of aldosterone by the zona glomerulosa of the adrenal gland and is also potent vasoconstrictor. The result is an increase in blood
pressure due to both indirect (sodium retention by the kidney due to aldosterone action) and direct (vasopressor response) effects of AII

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9
Q

Aldosterone acts to do what?

A

promote Na+ reabsorption in exchange for K+ and H+ in the distal tubules and collecting ducts. Increased Na+ reabsorption results in increased water reabsorption, thus increasing extracellular fluid volume. Because water follows sodium,
the patients generally do not develop hypernatremia. Due to the loss of K+ in exchange for the Na+ the patient becomes hypokalemic

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10
Q

Primary hyperaldosteronism should be suspected in any patient with what?

A

HTN associated with hypokalemia it is also seen in patients with hypertension and normal potassium levels, manifests during the 3rd to 4th
decade, clues include the presence of a metabolic alkalosis since both K+ and H+ are lost in
the urine, effect of high aldosterone results in expanded plasma volume leading to increased
blood pressure and suppressed renin secretion

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11
Q

How is the HTN of primary hyperaldosteronism managed?

A

usual medications and the patient requires large doses of potassium supplements

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12
Q

What is the etiology of primary hyperaldosteronism?

A

solitary, unilateral adrenal adenomas (70%), Bilateral adrenal hyperplasia ~30%, Aldosterone producing carcinomas <1% (familial condition, suppress aldosterone by glucocorticoids)

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13
Q

What is the syndrome of apparent mineralocorticoid excess?

A

hypokalemia and HTN but low aldosterone levels, occurs due to an inactive mutation of the type 2 11beta-hyrdoxy steroid dehydrogenase (11b-HSD) enzyme, which is co-localized with the mineralocorticoid receptor, Cortisol can bind and activate the mineralocorticoid receptor and mimic the aldosterone effect in producing
HTN and hypokalemia

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14
Q

Type 2 11-betahyrdoxy steroid dehydrogenase does what?

A

converts cortisol to inactive cortisone in mineralocorticoid target tissues.

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15
Q

What else can cause the syndrome of apparent mineralocorticoid excess?

A

ingestion of glycyrrhizin or glycyrrhetinic acid can produce Apparent Mineralocorticoid Excess syndrome because its metabolite (3b-D-
(monglucuronyl) 18β-glycyrrhetinic acid) inactivates type 2 11b-HSD and allows cortisol to activate the mineralocorticoid receptor, thus producing HTN and
hypokalemia.

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16
Q

How is syndrome of apparent mineralocorticoid excess diagnosed?

A

24-hour urine potassium showing excessive renal losses despite hypokalemia is consistent with hyperaldosteronism, if low look for GI, Randomly elevated aldosterone and low renin with an aldosterone to renin ratio > 25-30 are suspicious for primary aldosteronism, Elevated aldosterone that does not suppress with volume expansion (salt loading or saline infusion) confirms the diagnosis, Abdominal CT or MRI will demonstrate 80% of adenomas.

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17
Q

Why are biochemical tests necessary for diagnoses instead of just CT or MRI chowing a mass?

A

Nonfunctional adrenal adenomas are seen in up to 10% of the population

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18
Q

What therapy is used to treat primary hyperaldosteronism caused by an adenoma?

A

unilateral adrenalectomy is curative in 50-70% patients. The remainder of patients will remain hypertensive but require less potassium supplements.

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19
Q

What therapy is used to treat primary hyperaldosteronism caused by bilateral hyperplasia?

A

spironolactone (mineralocorticoid receptor antagonist) to control serum potassium and HTN. Other potassium sparing diuretics and anti-hypertensives may be required as well

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20
Q

What causes secondary hyperaldosteronism due to decreased renal perfusion?

A

Associated with any cause of decreased renal perfusion such as dehydration, blood loss, or hypotension. Edematous states (CHF, nephrotic syndrome, and liver failure) have decreased effective renal perfusion resulting in increased renin and aldosterone despite edematous state.
Renal artery stenosis produces decreased renal perfusion leading to increased renin and aldosterone

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21
Q

What are the characteristics of a pheochromocytoma?

A

Catecholamine producing tumors of the adrenal medulla, Most produce mainly norepinephrine with some epinephrine, Most patients have either sustained or episodic hypertension: 50% sustained HTN, 30% episodic HTN, and 20% normotensive, Elevated catecholamines results in a “fight or flight” response, Rare (1/1000 with HTN),

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22
Q

What other familial diseases are associated with pheochromocytoma?

A

Multiple endocrine neoplasia (MEN) IIa and Iib, Neurofibromatosis, Von Hippel-Lindau syndrome

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23
Q

What effects of the fight or flight response are produced in a pheochromocytoma?

A

Alpha-adrenergic effects: vasoconstriction to the abdominal viscera, decreased GI motility, pallor, diaphoresis, Beta-adrenergic effects: vasodilatation to skeletal muscles and increased muscle contractility, increased heart rate and contractility, bronchodilatation, increased renin, increased ADH release

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24
Q

What is the clinical presentation of pheochromocytoma?

A

Triad of headache, palpitations, and diaphoresis has > 90% specificity and sensitivity for pheochromocytoma usually paroxysmal, Dizziness and orthostatic hypotension, Intravascular volume depletion Weight loss, Glucose intolerance, Pallor, Cardiac arrhythmias

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25
Q

What causes the cardiac arrhythmias in pheochromocytoma?

A

due to beta-adrenergic effects

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26
Q

What causes the pallor in pheochromocytoma?

A

due to vasoconstriction

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27
Q

What causes the glucose intolerance in pheochromocytoma?

A

may develop due to increased gluconeogenesis, glycogenolysis, and lipolysis

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28
Q

What causes the weight loss in pheochromocytoma?

A

may occur due to the hypermetabolic state

29
Q

What causes the dizziness and orthostatic hypotension in pheochromocytoma?

A

from intravascular volume depletion

30
Q

What causes the intravascular volume depletion in pheochromocytoma?

A

occurs due to chronic vasoconstriction associated with high levels of circulating catecholamines. The vasoconstriction and elevated blood pressure overrides the direct beta-adrenergic effects on renin secretion and leads to decreased renin and aldosterone secretion resulting in less sodium and water retention and decreased intravascular volume

31
Q

What is the etiology of pathology that arise from adrenal medullary chromaffin (neuroendocrine) cells?

A

50% extra-adrenal, 10% multiple, 10% familial, and 10% malignant

32
Q

How are phoechromocytomas diagnosed?

A

paroxysmal symptoms, labile HTN, family history or an adrenal mass, or very difficult to control HTN; Plasma metanephrine or Urinary (24 hour) metanephrines and/or catecholamines, Single plasma catecholamine value is seldom helpful, Urinary vanillylmandelic acids (VMA) is less helpful; Clonidine suppression test often very helpful

33
Q

Why is plasma metanephrine very helpful in diagnosing pheochromocytoma?

A

becoming the standard screening test,not as much fluctuation as seen with urinary metanephrines. Metanephrines are metabolites of catecholamines and will be elevated in the setting of chronically high catecholamines. However there are a significant number of false positives.

34
Q

Why is urinary metanephrine or catecholamines very helpful in diagnosing pheochromocytoma?

A

an alternative screening test but more difficult to obtain. If plasma metanephrines are elevated then 24 hour urine is done as confirmatory test.

35
Q

Why is single plasma catecholamine value seldom helpful in diagnosing pheochromocytoma?

A

can be acutely affected by the stress of the blood draw.

36
Q

Why is Urinary vanillylmandelic acids value seldom helpful in diagnosing pheochromocytoma?

A

yields false negatives and positives and is a less helpful screening test

37
Q

Why is Clonidine suppression test often very helpful in diagnosing pheochromocytoma?

A

clonidine is a centrally acting alpha adrenergic agonist that normally decreases catecholamine levels. Failure of catecholamine levels to suppress after clonidine administration is consistent with pheochromocytoma, Plasma catecholamine level are drawn before and after clonidine, Essential HTN may have mildly elevated catecholamines which suppresses after clonidine, Catecholamine levels in patients with pheochromocytoma will be elevated and will not be suppressed by clonidine

38
Q

When and how should localization of a pheochromocytoma be done?

A

after biochemical confirmation, Abdominal CT or abdominal MRI will detect most pheochromocytomas, ifnegative do pelvic and chest CT to look for extra-adrenal lesion, Nuclear medicine scans (MIBG or octreotide) for those with negative CT

39
Q

What are the treatment options for pheochromocytoma?

A

surgical removal, Preoperative alpha -adrenergic blockade (phenoxybenzamine) as well as volume expansion is required to prevent hypertensive crisis and arrhythmia intraop and hypotension after removal, Beta-blockers for arrhythmias should only be added after alpha-blockade. Use of beta-blockers without prior alpha-blockade may worsen hypertension. Beta-adrenergic stimulation causes vasodilation. If the vasodilatory beta-adrenergic effect is blocked by treatment with a beta-blocker there will be unopposed alpha-adrenergic activation causing further vasoconstriction and potential further elevation of blood pressure

40
Q

What are the metabolic consequences of excessive glucocorticoid activity in Cushing’s syndrome?

A

Impaired glucose tolerance to frank diabetes mellitus - due to effects of cortisol on gluconeogenesis. Also causes insulin resistance, Adiposity - glucocorticoids cause preferential deposition of fat centrally leading to central obesity, round face, and increased dorsal and supraclavicular fat pads, Protein wasting due to increased catabolism and decreased protein synthesis, Psychological disturbances, Immunosuppression with increased susceptibility to infections

41
Q

Protein wasting due to increased catabolism and decreased protein synthesis of pheochromocytoma is manifested by what?

A

Muscle atrophy and weakness due to muscle breakdown, Thin skin due to decreased collagen production leads toviolaceous striae, easy bruisability, and poor wound healing, Osteoporosis due to increased bone resorption and decreased bone formation, Growth retardation

42
Q

What are the consequences of excessive mineralocorticoid-like activity - due to high levels of cortisol acting on mineralocorticoid receptor to produce effects similar to aldosterone?

A

hypertension, edema, and hypokalemic alkalosis

43
Q

What are the consequences of excessive androgenic activity - due to adrenal androgens secreted in conjunction with cortisol? When is it most commonly seen?

A

hirsuitism, acne, menstrual disturbances- Cortisol also directly inhibits gonadotropin secretion which contributes to the menstrual disorder; adrenal carcinoma

44
Q

What are the etiologies of pheochromocytoma?

A

iatrogenic, ACTH dependent, ACTH independent and Pseudocushings syndrome

45
Q

What are the features of iatrogenic pheochromocytoma?

A

exogenous glucocorticoids used in supraphysiologic doses. By far the most common etiology

46
Q

What are the features of ACTH dependent pheochromocytoma?

A

Cushing’s Disease - partially autonomous ACTH- secreting pituitary adenoma. Accounts for 60% of cases of Cushing’s syndrome (non-iatrogenic) or Ectopic ACTH Syndrome - autonomous secretion of ACTH by a tumor, no suppression even with high dose dexamethasone (synthetic glucocorticoid).Accounts for 15% of cases of Cushing’s syndrome

47
Q

What are the features of Cushings disease?

A

Partially autonomous - i.e., suppressible but at higher set-point, requires higher levels of glucocorticoids (supraphysiologic) to inhibit ACTH secretion, Most often leads to uniform bilateral hyperplasia of adrenal glands due to tonic stimulation by ACTH, Rarely macronodular hyperplasia of adrenal glands can be seen

48
Q

What are the features of ectopic ACTH syndrome?

A

Undifferentiated Tumors - primarily oat cell (small cell) carcinoma of lung, Differentiated tumors- Carcinoid tumors - these are often small and difficult to locate, Pancreatic islet cell tumors, Medullary thyroid cancer

49
Q

What are the causes of ACTH independent pheochromocytoma?

A

primary adrenal disease, ectopic CRH (extremely rare), and GIP-dependent nodular hyperplasia (extremely rare)

50
Q

what are the features of ACTH independent pheochromocytoma caused by primary adrenal disease?

A

characterized by autonomous adrenocorticoid secretion independent of ACTH regulation - 25% of case, Adrenal adenoma- most common, benign tumor, Adrenal carcinoma- very poor prognosis, usually large adrenal tumors, and Micronodular disease

51
Q

What are the features of pseudo-cushings syndrome pheochromocytoma?

A

patients look Cushinoid but cortisol can be suppressed with specialized testing. They may have elevated cortisol but the elevation resolves with treatment of the underlying disease such as depression or alcoholism; depression, alcoholism, anorexia nervosa

52
Q

What features need to be determined when diagnosing a pheochromocytoma?

A

confirm hypercortisolism, confirm etiology, ACTH dependent, ACTH independent

53
Q

How do you confirm hypercortisolism?

A

document inappropriate levels of cortisol or failure to suppress cortisol normally; Overnight dexamethasone suppression, 24-hour urine free cortisol, Midnight salivary cortisol – this is obtained to document loss of diurnal variationof cortisol levels, and Dexamethasone - CRH test

54
Q

What is normal for overnight dexamethasone suppression test? What should you watch out for?

A

plasma cortisol < 2 μg/dl, Many false positives (e.g., depression) but very helpful if suppression isnormal (few false negatives), If positive (no suppression) then you need a confirmatory test

55
Q

What is 24-hour urine free cortisol measuring? What do the results mean?

A

Index of plasma free cortisol - Cortisol binding globulin nearly saturated at normal levels of plasma cortisol. If cortisol levels are high the unbound cortisol will be excreted in the urine., Normal in obesity - cortisol production increased in obesity but so is degradation, Elevated in Cushing’s, Stress, and Depression

56
Q

How is Midnight salivary cortisol found? What do the results indicate?

A

obtained to document loss of diurnal variation of cortisol levels, Normally there is a marked difference in Cortisol levels drawn at 8 am versus midnight, Now there is the capability to measure salivary cortisol at midnight –patient is sent a kit to obtain a salivary sample at midnight. If salivary cortisol is elevated this is another test that confirms the presence of hypercortisolism.

57
Q

How does the Dexamethasone - CRH test work? What do the results mean?

A

can be used in suspected cases of Pseudo-Cushing’s or if results of overnight dexamethasone suppression test or 24 hour urine cortisol are equivacol. The concept is that you first give high doses of glucocorticoid(dexamethasone) to suppress CRH and ACTH secretion. Then give exogenous CRH to see if you can overcome the suppression. In Pseudo-Cushings cortisol levels and ACTH will be suppressed and they do not respond to CRH; i.e. there is no increase in cortisol after CRH. In true Cushing’s syndrome you will see an exaggerated increase in ACTH and Cortisol levels after injection of CRH.

58
Q

How do you confirm the etiology of the pheochromocytoma?

A

Plasma ACTH level. An ACTH will differentiate between ACTH dependent and ACTH independent causes of cortisol excess. Since ACTH may be appropriately elevated in the morning, best discrimination is achieved by obtaining a late afternoon or evening ACTH as well as a plasma cortisol

59
Q

Once determined the pheochromocytoma is ACTH dependent how do you sort whether it is primary or ectopic?

A

most pituitary tumors retain ability to suppress to high doses of glucocorticoids. Ectopic sources usually do not respond to suppression by high dose glucocorticoids; High-dose dexamethasone suppression test, CRH test, Pituitary imaging, Inferior petrosal sinus sampling,Non-pituitary imaging

60
Q

What tests is used for high dose dexamethasone suppression? What does the test results mean?

A

Overnight high-dose (8mg) Dexamethasone suppression test. 10 times the normal physiologic dose- Suppression of cortisol level to less than 68% of baseline cortisol = pituitary disease. Suppression of cortisol levels after high dose dexamethasone suggests a pituitary tumor. This is the “classic” response. failure to suppress can be seen with both pituitary tumors and ectopic ACTH.

61
Q

What is the CRH test? What do the results mean?

A

inject recombinant CRH to assess for change in ACTH and cortisol levels. With pituitary disease there will be an exaggerated response with increase in ACTH and cortisol. With ectopic ACTH secretion, there would be little or no change in already elevated levels of ACTH and cortisol after CRH injection since the ectopic production is independent of CRH stimulation.

62
Q

What does the pituitary imaging show?

A

CT or MRI 6 mm AND evidence of suppression of ACTH secretion with high dose dexamethasone testing as consistent with Cushing’s disease (pituitary disease), The lack of a tumor seen on pituitary MRI does not exclude a pituitary source of ACTH excess excretion

63
Q

What does inferior petrosal sinus sampling test for? What do the results mean?

A

Venous sampling of pituitary venous drainage to obtain ACTH levels. If ACTH levels from pituitary are markedly elevated compared to the periphery then this confirms a pituitary source for the ACTH. This is done if the biochemical work up suggests pituitary disease but no tumor is seen on MRI or high dose dexamethasone testing is inconclusive

64
Q

What is the non pituitary imaging looking for?

A

CT/MRI chest - to look for ectopic source of ACTH such as bronchial carcinoids or oat cell carcinoma, Octreotide imaging - if unable to find tumor by MRI or CT scan, neuroendocrine cells (including ACTH-producing cells) have cell surface receptors for somatostatin. This test may be useful to detect bronchial carcinoids (up to 86% have been detected with this test). However, false positives may occur due to inflammatory diseases

65
Q

What are the diagnostic pitfalls of pheochromocytoma?

A

Periodic hormonogenesis – may miss diagnosis if test is not done at the correct time. Often need to repeat tests multiple times if index of suspicion is high, Pseudo-Cushing’s can cause false positives, Drugs that accelerate dexamethasone metabolism such as anti-convulsants including phenytoin and phenobarbital. These drugs accelerate the metabolism of dexamethasone which may lead to false positive suppression tests (failure to suppress)

66
Q

What are the treatments of a pheochromocytoma?

A

Surgical removal tumor (primary modality), medical therapy- drugs which inhibit production of glucocorticoids. Used incases where surgery was not curative or if patient is not a surgical candidate, and pituitary irradiation

67
Q

When is surgery utilized for pheochromocytoma?

A

Transphenoidal pituitary resection for Cushing’s Disease, Adrenalectomy for adrenal tumors, and removal of tumor producing ectopic ACTH

68
Q

What medical therapies are used for pheochromocytomas?

A

Ketoconazole – high doses (much higher doses are used than used for treatment of fungal disease), Metyrapone, Aminoglutethimide, Mitotane, RU486

69
Q

When is pituitary irradiation used for pheochromocytomas? Over what time? side effects?

A

cushings disease; slow response to radiation occurs over up to 5 yrs, side effects of hypopituitarism in many patients

Endocrine Physiology (9 decks)

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