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Laufgraben - 5/11/11
Terms in this set (30)
What is a glucocorticoid excess?
Cushing's syndrome: Cortisol excess
(too much sugar!)
General: what are the primary physical presentations of Cushing's?
central obesity (legs arms fairly normal)
round faces, red
striae - dark stretch marks
dorsocervical fat deposits (buffalo hump)
What are the causes of HTN in Cushings?
Increase sensitivity to catecholamines (NE/E) and angiotensin II in vascular smooth muscle
Decrease NO-mediated endothelial dilatation
Sodium retention from mineralocorticoid activity
General: what are the primary non-physical presentations of Cushing's?
hypokalemia (b/c excessive cortisol stimulates aldosterone)
* How does Cortisol act as a mineralcorticoid? what results?
Excessive Cortisol overwhlems 11B-HSD2 (converts Cortisol to Cortisone) --> cortisol stimulates mineralocorticoids --> salt rentention (HTN) & K+ secretion (**hypokalemic alkylosis)
Why do you see mood changes in Cushing's?
Brain is an important target tissue of GC
- Agitated depression and lethargy
- Memory and cognitive dysfunction
- Paranoia and pychosis
* What are the two general categories of underlying causes of Cushing's Syndrome?
ACTH-dependent (driven by high ACTH)
ACTH-independent (problem is in adrenal gland)
*What are the two ACTH-dependent sources of ACTH?
Ectopic ACTH or Ectopic CRH (non-pituitary neoplasm)
*What are the two ACTH-independent sources of Cortisol?
1. Adrenal Tumors (independent synthesis)
*2. Exogenous source
What is Cushing's Disease? (vs. syndrome)
ACTH-secreting Pituitary Adenoma
-Pituitary neoplasm that secretes ACTH
-Impairment of normal feedback suppression results in continued ACTH secretion despite high levels of cortisol
What are the most common ectopic ACTH tumors?
Small-cell lung carcinoma (#1)
Bronchial carcinoid tumors
What "type" of Cushing's would a cortisol secreting adrenal tumor fall under?
What is meant by ACTH-independent macronodular adrenal hyperplasia?
Cortisol secretion is stimulated by aberrant expression of receptors for hormones that are NOT suppressed by Cortisol (so, other hormones than ACTH are stimulating the adrenal gland to secrete)
What is the most common endogenous cause of Cushings syndrome?
Pituitary-dependent/ACTH-dependent (Cushing's disease)
* What are some "other" induced conditions that cause cortisol excess and Pseudo-Cushings?
* What are the three screening tests for Cushing's Syndrome?
overnight Dexamethasone suppression test
24 hour Urinary Free Cortisol (UFC)
Bedtime salivary cortisol
How does an overnight Dexamethasone suppression test work?
A low dose of dexamethasone (synthetic glucocorticoid) will suppress a normal HPA axis, but will not suppress cortisol production in patient's with Cushing's Syndrome
What are two common reasons for a false positive DMT?
1. elevated CBG (estrogens): bind cortisol, test measures free and bound
2. increased dexamehsone metabolism (antiseizure meds)
What is considered the most useful Cushings test? what is a "unique" advantage of this?
Urine free cortisol
-not affected by CBG (cortisol binding globulin (estrogens))
What is the bedtime salivary cortisol a "good" test?
midnight serum has high sensitivity and specificity for CS --> free serum cortisol is in equilibrium with salivary cortisol
[FYI] what is a general "guideline" in endocrine testing?
should be step-by-step: biochemical confirmation before radiology
* If ACTH levels are normal or elevated, what are you looking for in the diagnostic algorithm?
*ACTH-dependent (not suppressed!)
1) Pituitary adenoma
2) Ectopic ACTH (or ectopic CRH)
What is a diagnostic challenge with ACTH-dependent CS?
Imaging is NOT reliable
-Pituitary MRI is normal in up to 50% patients with ACTH-secreting pituitary adenoma
-10% of general population will have incidental pituitary tumor on MRI
--> need biochemical testing (high-dose dexamethasone test)
What test is needed to distinguish the causes of ACTH-dependent Cushing's Syndrome? why?
High-Dose Dexamethasone suppression test (HDDST)
- imaging not reliable
- low dose won't suppress
- high-dose will partially suppress pituitary adenoma, but NOT ectopic ACTH-secreting adenoma
What is a non-biochemical diagnostic test that can establish if pituitary is source of ACTH?
Inferior Petrosal Sinus Sampling
If an ectopic tumor is secreting ACTH, what will the ACTH levels be in the periphery as compared to the petrosal sinus?
--> pituitary suppressed, so all circulation is same level
What is the first line treatment of an ACTH-secreting pituitary adenoma (and ectopic)?
If not curative
* same treatment for ectopic ACTH tumors
What are anti adrenal agents used in the management of ACTH-secreting pituitary tumors?
Mitotane (used against adrenal carcinomas (cortisol secreting)) -- very serious
What is Nelson's disease? what causes it?
Enlarged pituitary: after bilateral adrenalectomy, lack of Cortisol feedback, further increases activity of ACTH by pituitary adenoma
What is the treatment of choice for adrenal caricinoma? what is a downside?
Mitotane "mighty mito-tane"
severe side effects (GI and neuro)
THIS SET IS OFTEN IN FOLDERS WITH...
Pathology of Pituitary and Adrenal Glands
Pharmaceutical Industry/ Drug Development Process
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