Normal Physiology- Hypothalamus/Pituitary/Adrenal Axis
Normal neural stimulation of the hypothalamus produces corticotropin-releasing hormone (CRH). Corticotropin-releasing hormone
stimulates the release of adrenocorticotropic hormone (ACTH) from the anterior pituitary. ACTH exerts its effects on the adrenal
cortex and stimulates the zona fasiculata to release cortisol, the zona reticularis to release androgens and the zona glomerulosa
to release mineralocorticoids, but the primary effect of ACTH is on cortisol release. Cortisol provides a negative feedback
to ACTH and CRH. Glucocorticoids are involved in many normal physiologic responses in the body.
Mineral corticoid release from the zona glomerulosa is primarily mediated by the renin- angiotensin-aldosterone system and
only minimally by ACTH. Renin is released from the juxtaglomerular apparatus of the kidney into circulation as a result of
sympathetic stimulation, hypotension, hyponatremia and hypochloremia. Renin then converts circulating angiotensinogen to angiotensin
I. Angiotensin converting enzyme in the pulmonary vascular endothelium converts angiotensin I to angiotensin II. Angiotensin
II then stimulates aldosterone secretion from the zona glomerulosa. In the absence of ACTH, atrophy of the zona glomerulosa
can occur and mineralocorticoid deficiency result. Mineralocorticoids are primarily involved in water and electrolyte balance.
This is a disease that results from dysfunction or destruction of the majority of the adrenocortical tissue. Most cases arise
from primary adrenocortical failure resulting in signs of glucocorticoid and mineralocorticoid deficiency. The adrenal disease
is termed idiopathic but is suspected to be immune mediated in origin. Destruction of cells results in atrophy of the gland.
There is an atypical form of hypoadrenocorticism, that occurs when there is atrophy of the zona fasciculata alone, resulting
in hypocortisolism without the concurrent lack of aldosterone. This results in vague clinical signs and a disease that is
more challenging to diagnose.