adrenals gone bad

let's do a review of some endocrine pathologies, shall we?

starting with my most favourite: Cushing's syndrome.

what is it? an increase of cortisol due to various reasons, which can be divided into:

• exogenous: steroid intake (iatrogenic)

• endogenous:
  
  1. cushing's disease (70%). a pituitary adenoma secreting excess ACTH, which in turn increases secretion of cortisol from the adrenals. serum shows an increase in both ACTH and cortisol.
  2. ectopic ACTH, made by non pituitary tissues (small cell lung cancer, bronchial carcinoids). serum will show an increase in both ACTH and cortisol.
  3. adrenal adenoma, carcinoma, nodular hyperplasia. ACTH levels would be LOW.

how do we test for it and differentiate between the three?

Dexamethasone suppression test  

• in healthy individuals, cortisol levels drop after a low dose of dexamethasone (the increase in cortisol, inhibits secretion of ACTH, which means there's no stimulation for the adrenals to produce cortisol)
  
• in an ACTH producing pituitary tumor (1), the cortisol levels increase after a low dose, but decrease after a high dose.
  
  now, you have a tissues producing excess ACTH, with almost no negative feedback from cortisol. that's why a low dose of exogenous steroid (dexamethasone) fails to inhibits further ACTH secretion and therefore the levels of cortisol still appear high. when a bigger dose of dexamethasone is administered, the negative feedback system is triggered to decrease the cortisol level.
  
  so, low dose dexamethasone, cortisol levels high. high dose dexamethasone, cortisol levels drop.
  
• ectopic ACTH producing tissues (2) and adrenal adenomas (3) differ in the sense that they are not influenced by the hypothalamus-pituitary-adrenal axis, and therefor not subjected to the negative feedback system.
  
  so, both a low and high dose of dexamethasone will result in high cortisol levels.

now onto HYPERALDOSTERONISM. two types exist:

1. primary (Conn's syndrome): aldosterone secreting tumor (uni/bilatera) that results in hypertension, hypoK+, metabolic alkalosis, low plasma renin.
   
   
2. secondary: kidney perceives low intravascular volume (due to renal artery stenosis, CHF, CRF, cirrhosis, nephrotic syndrome) and this results in an overactive renin-angiotensin-aldosteron activation. key point here is: PLASMA RENIN WOULD BE HIGH.

treatment? spironolactone, an aldosterone antagonist (its MOA as a K+ sparring diuretic).

next up: ADDISON'S.

• chronic adrenal insufficiency due to adrenal hypoplasia (primary = problem at adrenal) . results in total absence of hormones from all three layers of the adrenal cortex (primary deficiency of cortisol and aldosterone = hypotension).
  
  skin pigmentation occurs due to increase MSH, a by product of ACTH, which is increased because the pituitary tries stimulating the non responding adrenals.
  
  so increased ACTH, low adrenal hormones (salt, sugar, sex), high MSH = hyperpigmentation (bronze).
  
• secondary adrenal insufficiency = problem at pituitary. so ACTH would be LOW, no skin hyperpigmentation and no hyperkalemia.

that's all for today folks. stay tuned =)