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37 Cards in this Set
- Front
- Back
How does cortisol
A. modulate vascular response to beta agonists B. effect GFR C. effect immune system D. maintain ionotropy of heart muscle |
Cortisol's effects:
A. modulate vascular response to beta agonists - increased expression of edrenergic receptors in smooth muscle, decreased inactivation of catecholamines B. effect GFR - increases it C. effect immune system - immunosuppressive and anti-inflammatory. This is why glucocorticoids are commonly used to treat inflammatory and autoimmune dz! D. maintain ionotropy of heart muscle - by induction of cardiac Na/K ATPase |
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Regarding RAA system: increased renin results in cleavage of __________ (secreted by the liver) to angiotensin I. Angiotensin I is cleaved to Angiotensin II by _________ in the lungs. Angiotensin II stimulates synthesis and secretion of _______ and also acts as a potent vasopressor. Result is increase in blood pressure due to both indirect and direct effects of AII.
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angiotensinogen,
angiotensin converting enzyme (ACE) indirect = sodium retention in kidney due to aldosterone action direct - vasopressor response |
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Regarding adrenal insufficiency, what is the primary and secondary classification?
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Primary means there is destruction of adrenal cortex itself resulting in both glucocorticoid as well as mineralocorticoid deficiency
Secondary insufficiency is defect at the pituitary or higher (hypthalamus) level leading to atrophy of the glutocorticoid producing cells due to loss of normal trophic stimulation by ACTH. Secondary adrenal insufficiency, therefore, results in primarily glucocorticoid and not mineralocorticoid deficiency. |
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True or False:
Secondary adrenal insufficiency results in primarily glucocorticoid and not mineralocorticoid deficiency. |
TRUE
Primary adrenal insufficiency results in glucocorticoid as well as mineralocorticoid deficiency |
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What are some etiologies of primary adrenal deficiency? What is most common in US? How about worldwide?
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Primary adrenal deficiency or when there is destruction of the adrenal cortex itself resulting in both glucocorticoid and mineralocorticoid deficiencies, is commonly caused by:
- in US: autoimmune. antibodies to 21-hydroxylase frequent - worldwide: TB or other infiltrative dz - other causes: hemorrhage, fungal infections, AIDs (though less than 5% will be symptomatic, since 80% of adrenal cortex needs to be destroyed to have clinical adrenal insufficiency), metastatic tumor (v. rare) |
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What drug, used to treat Cushings, can also result in primary adrenal insufficiency?
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Ketoconazole
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What two genetic conditions can cause primary adrenal insufficiency?
A. Adrenoleukodystrophy B. Congenital adrenal hyperplasia C. Turner's syndrome D. Klinefelter's syndrome E. Prader-Willi syndrome F. DiGeorge's syndrome |
A. Adrenoleukodystrophy: X-linked recessive disorder resulting in progressive demyelination of CNS.
B. Congenital adrenal hyperplasia: occurs as result of mutation in one of the enzymes required for cortisol and/or aldosterone biosynthesis. Usually 21-hydroxylase enzyme. B/c of the block in the biosynthesis, there is less deeback to pituitary , ,leading to increased ACTH production . Increased ACTH --> increased pregnenolone --> shunted to testosterone making pathway. Thus, female babies could present with virilization. see back of syllabus p.278 for diagram |
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Why does congenital adrenal hyperplasia cause female babies to present with virilization?
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CAH occurs due to a mutation in one of the enzymes required for cortisol and/or aldosterone biosynthesis. Most common is defect in 21-hydroxylase enzyme. Lack of negative feedback --> increased ACTH --> increased pregnenolone --> but since no cortisol or aldosterone is able to be made, shunted to testosterone pathway. Thus, high levels of testosterone present virilizes baby girl.
see back of syllabus p.278 for diagram |
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Secondary adrenal insufficiency can be caused by: hypothalamic dz (lymphocytic hypophysitis, neurosarcoidosis, any infiltrative dz interrupting the connection between the hypothalamus and pituitary), pituitary dz (tumors, hemorrhage, infarction, trauma), pituitary axis suppression by exogenous glucocorticoids, chronic opiate use.
Which is the most common cause? |
pituitary axis suppression by exogenous glucocorticoids
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What is the most common cause of secondary adrenal insufficiency?
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Pituitary axis suppression by exogenous glucocorticoids
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What are the clinical manifestations of chronic primary adrenal insufficiency? (signs and symptoms and lab findings)
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SYMPTOMS: WEAKNESS AND FATIGUE AND ANOREXIA, nausea/abdominal pain, vomiting
SIGNS: WEIGHT LOSS, HYPERPIGMENTATION, HYPOTENSION, vitiligo LAB FINDINGS: hyponatremia, hyperkalemia, anemia |
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Signs and symptoms between primary and secondary adrenal insufficiency are similar except what differences with regards to the following:
A. hyperpigmentation - howso? why? B. hyperkalemia - howso and why? C. Hyponatremia - howso and why? |
A. primary has hyperpigmentation because of the increased ACTH, but secondary does NOT exhibit increased ACTH so ergo no hyperpigmentation
B. present has hyperkalemia due to lack of aldosterone, but secondary does not since aldosterone is present C. hyponatremia present in both since increased ADH levels in response to hypotension |
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An individual presenting with nausea vomiting, abdominal pain, shock not responsive to IV fluids or pressor agents, hypoglycemia, hyponatremia, hyperkalemia and increased BUN is suffering from:
A. primary adrenal insufficiency B. secondary adrenal insufficiency C. acute adrenal insufficiency (primary or secondary) |
C. acute adrenal insufficiency (primary or secondary)
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How does one determine whether a patient has adrenal insufficiency?
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1) Does adrenal insufficiency exist?
2) If yes, then primary or secondary? Random plasma cortisol drawn at any time of the day is only suggestive if value is low in the face of stress (when it should be high). Note that normal diurnal variation occurs with cortisol. Morning cortisol level is only helpful if normal because then you don't need to do further testing. A low response would proceed to do ACTH stimulation test. Rapid high dose ACTH stimulation test is a the test of choice to adrenal insufficiency (will be abnormal result). To determine whether primary or secondary, do insulin induce hypoglycemia test. |
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How does one do the ACTH stimulation test?
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Give ACTH. Then measure cortisol 60 minutes following intravenous or intramuscular injection. Normal response is measured cortisol > 20 micrograms/dL.
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What is the gold standard test for secondary adrenal insufficiency?
A. ACTH stimulation test B. insulin-induced hypoglycemia C. morning cortisol test D. plasma ACTH level |
B. insulin-induced hypoglycemia
this is also useful to test the whole hypothal-pituit-adrenal axis |
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What is the treatment for each:
A. Chronic primary adrenal insufficiency B. Chronic secondary adrenal insufficiency C. Acute adrenal insufficiency |
A. Chronic primary adrenal insufficiency - maintenance glucocorticoids (hydrocortisone or cortisone acetate) and oral mineralocorticoid (fludrocortisone) if patientsremains hypotensive or hyperkalemic on glucocorticoids alone
B. same as primary but no mineralocorticoid C. infuse saline and glucose, draw blood to assess plasma cortisol, ACTH, electrolytes and glucose (but do not wait for results), give high dose hydrocortisone. At these high doses, hydrocortisone has both glucocorticoid as well as mineralocorticoid effects so you do not need to give fludrocortisone. |
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MEN or multiple endocrine neoplasia syndromes, are characterized by ... (think v. general).
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Tumors that occur in endocrine organs. Tumors may be multifocal within one organ or across many organs in an individual or family.
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MEN1 is associated with the three P's. What are they and what are the clinical syndromes?
What is the genetics behind it? |
Parathyroid - hyperparathyroidism (elevated Ca2+, elevated PTH)
Pancreas - gastrinoma, insulinoma, gluconoma, non-secretory islet cell tumor Pituitary - prolactinoma, acromegaly, Cushing's dz, non-secretory tumor GENETICS: MEN1 gene, a tumor suppressor gene. Loss of function. |
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MEN2 is associated with what type of cancer in all MEN2 classes?
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medullary thyroid cancer (MTC)
In MEN2A: medullary thyroid cancer, pheochromocytoma, hyperparathyroidism, cutaneous lichen amyloidosis In MEN2B: medullary thyroid cancer, mucosal ganglioneuromas, pheochromocytoma In FMTC: MTC in 10 or more familyi members, no pheo, HPT |
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Discern which is part of MEN2A, MEN2B, and/or Familial medullary thyroid cancer.
A. cutaneous lichen amyloidosis B. hyperparatyroidism C. medullary thyroid cancer D. mucosal ganglioneuromas E. no pheochromocytoma F. no hyperparathyroidism G. no ganglioneuromas H. pheochromocytoma |
In MEN2A: medullary thyroid cancer, pheochromocytoma, hyperparathyroidism, cutaneous lichen amyloidosis
In MEN2B: medullary thyroid cancer, mucosal ganglioneuromas, pheochromocytoma In FMTC: MTC in 10 or more familyi members, no pheo, HPT MEN2 involves the RET gene and encodes the RET protein which is a receptor tyrosine kinase. gain of function. |
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True or False:
For MEN2, presymptomatic diagnosis does not affect morbidity/mortality. |
FALSE.
This statement is true for MEN1. But for MEN2, mortality has been impacted favorably by early thyroidectomy and by pheocromocytoma identification and management. |
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Which autoimmune polyglandular syndrome is
A. more common B. an autosomal recessive disorder C. of childhood onset D. of 20-40 y/o onset E. can be sutosomal dominant, recessive or polygenic F. involves the AIRE gene on chromosome21 |
A. more common - APS II
B. an autosomal recessive disorder - APS I C. of childhood onset - APS I D. of 20-40 y/o onset - APS II E. can be autosomal dominant, recessive or polygenic - APS II F. involves the AIRE gene on chromosome 21 - APS I |
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Which clinical features belong to APS I and/or which to APS II?
A. Autoimmune thyroid dz B. Hypoparathyroidism C. Mucocutaneous candidiases D. Myasthenia gravis E. Primary adrenal insufficiency F. Primary hypogonadism G. Type I DM |
A. Autoimmune thyroid dz - APS II
B. Hypoparathyroidism - BOTH C. Mucocutaneous candidiases - APS I D. Myasthenia gravis- APS II E. Primary adrenal insufficiency - APSI F. Primary hypogonadism - BOTH G. Type I DM - BOTH |
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What are the three main clinical features of APS I?
A. Autoimmune thyroid dz B. Hypoparathyroidism C. Mucocutaneous candidiases D. Myasthenia gravis E. Primary adrenal insufficiency F. Primary hypogonadism G. Type I DM |
B. Hypoparathyroidism
C. Mucocutaneous candidiases E. Primary adrenal insufficiency |
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What gene is responsible for APSI? APSII?
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APSI: AIRE gene on chromosome 21. It encodes nuclear protein involved in transcriptional processes.
APSII: no identified gene, only 50% of cases are familial |
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What is the difference between Cushing's Syndrome and Cushing's Disease?
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Cushing's Syndrome = glucocorticoid excess of any etiology
Cushing's Disease = pituitary ACTH excess leading to adrenal stimulation and chronically elevated glucocorticoids |
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Why does HTN, edema, hypokalemic alkalosis occur in Cushing's syndrome?
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Those are all conesquences of excessive mineralocorticoid-like activity that occurs due to high levels of cortisol acting on meralocorticoid receptors producing effects similar to aldosterone.
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Why does hrsutism, acne and menstrual disturbances in females, occur in Cushing's syndrome?
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These are consequences of excessive androgenic activity - due to adrenal androgens secreted in conjunction with cortisol. Cortisol also directly inhibits gonadotropin secretion at the level of the pituitary caushing amenorrhea.
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Why does amenorrhea occur with high cortisol levels?
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Cortisol directly inhibits gonadotropin secretion at the level of the pituitary causing amenorrhea.
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What is the most common cause of Cushing's syndrome?
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Exogenous glucocorticoids used in supraphysiologic doses to treat another disease such as asthma or inflammatory bowel disease.
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What are some ACTH independent causes of Cushing's syndrome? (3)
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Primary adrenal disease - autonomous adrenocorticoid secretion independent of ACTH regulation
Extopic CRH- extremely rare though Pseudo-Cushing's Syndrome : looks like Cushing's except is resolved by treating underlying disease- usually depression, alcoholism, anorexia nervosa |
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What is the diagnosis/testing algorithm for Cushing's ?
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patient must NOT be stressed. 2 different screening tests must be positive in order to make the diagnosis of hypercortisolism. (Overnight low dose dexamethasone suppression, 24 hour urine free cortisol, midnight salivary cortisol). Then, you confirm etiology (ACTH dependent or ACTH independent). Once the presence of hypercortisolism is established biochemically, the source of excess cortisol needs to be determined- do plasma ACTH level. see p.297of syllabus for whole algorithm
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If you suspect a pituitary tumor as a reason for hypercortisolism, what test can be done?
A. low dose dexamethasone suppression test B. ACTH suppression test C. high dose dexamethasone suppression test D. 24 hour urine free cortisol E. Dexamethasone-CRH test |
C. high dose dexamethasone suppression test
an overnight high dose 8mg Dexamethasone suppression test involves dexamethasone that is 10x the normal physiologic dose. if cortisol measured at next day shows inadequate suppression of cortisol- it can be due to a pituitary tumor OR ectopic ACTH. If levels are indeed suppressed adequately, then it suggests a pituitary tumor. |
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Inferior petrosal sinus sampling involves venous sampling of pituitary to obtain ACTH levels. If ACTH levels from pituitary are markedly elevated in comparison to the periphery then...
A . this confirms pituitary source for ACTH B. you can assume the patient has either a pituitary tumor or an ectopic ACTH producing source |
A . this confirms pituitary source for ACTH
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What drugs affect dexamethasone metabolism and thus can serve as diagnostic confounders for Cushing's?
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anti-convulsants like phenytoin and phenobarbital. These accelerate the metabolism of dexamethasone which can lead to false positive suppression tests. (failure to suppress)
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What are possible treatment options for hypercortisolism?
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Surgical removal of tumor
Medical therapy with drugs like ketoconazole and metyrapone pituitary irradiation for Cushing's dz |