Cushing syndrome exams informations1 @ Cho-Cho & Sophia

Adrenocorticotropic hormone (ACTH) #1
also known as 'corticotropin', 'Adrenocorticotrophic hormone',
is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland.
It is an important component of the hypothalamic-pituitary-adrenal axis and
is often produced in response to biological stress (along with corticotropin-releasing hormone from the hypothalamus).
Its principal effects are increased production and release of corticosteroids and, as its name suggests, cortisol from the adrenal cortex.

The ACTH stimulation test #2
(also called the cosyntropin test, tetracosactide test or Synacthen test) is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response
by measuring the adrenal response to adrenocorticotropic hormone (ACTH).
ACTH is a hormone produced in the pituitary gland that stimulates the adrenal glands to release cortisol.

During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone, the adrenals produce in response is measured.
This test may cause mild to moderate side effects in some individuals.
This test is used to diagnose or exclude primary and secondary adrenal insufficiency, Addison's disease and related conditions.

Corticotropin-releasing hormone (CRH) #3
originally named corticotropin-releasing factor (CRF),
and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response.
It belongs to corticotropin-releasing factor family.

Its main function is the stimulation of the pituitary synthesis of ACTH.
CRH is secreted by the paraventricular nucleus (PVN) of the hypothalamus in response to stress.

CRH is produced by parvocellular neuroendocrine cells (which are contained within the paraventricular nucleus(PVN)) of the hypothalamus
and is released at the median eminence from neurosecretory terminals of these neurons into the primary capillary plexus of the hypothalamo-hypophyseal portal system.
The portal system carries the CRH to the anterior lobe of the pituitary, where it stimulates corticotropes to secrete adrenocorticotrophic hormone (ACTH) and other biologically-active substances β-endorphin).
ACTH stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids and DHEA;
therefore high CRF levels are very common in individuals with Cushing's syndrome.

Corticotropin-releasing factor family
Corticotropin-releasing hormone(CRH) is a hormone found mainly in the paraventricular nucleus of the mammalian hypothalamus that regulates the release of corticotropin (ACTH) from the pituitary gland.
From here, CRF is transported to the anterior pituitary, stimulating adrenocorticotropic hormone (ACTH) release via CRF type 1 receptors,
thereby activating the hypothalamic–pituitary–adrenal axis (HPA) and thus glucocorticoid release.

Dexamethasone suppression test #4
The dexamethasone suppression test is designed to diagnose and differentiate among the various types of Cushing's syndrome and other hypercortisol states.

Dexamethasone is an exogenous steroid that provides negative feedback to the pituitary to suppress the secretion of ACTH.
This steroid is unable to pass the blood brain barrier which allows this test to assess a specific part of the hypothalamic-pituitary-adrenal axis.
Specifically, dexamethasone binds to glucocorticoid receptors in the pituitary gland, which lies outside the blood brain barrier, resulting in regulatory modulation.

Low-dose
A normal result is decrease in cortisol levels upon administration of low-dose dexamethasone.
Results indicative of Cushing's disease involve no change in cortisol on low-dose dexamethasone, but inhibition of cortisol on high-dose dexamethasone.
If the cortisol levels are unchanged by low- and high-dose dexamethasone then other causes of Cushing's syndrome must be considered with further work-up necessary.

High-dose
After the high-dose dexamethasone, it may be possible to make further interpretations.

ACTH	Cortisol	Interpretation
undetectable or low	is not suppressed by high or low doses.	Primary Adrenal Cushing syndrome is likely.
normal to elevated	is not suppressed by low or high doses	Ectopic ACTH syndromeis likely.
elevated	is not suppressed by low doses, but is suppressed by high doses	Cushing's disease should be considered.