Clinical Information

Cortisol, the main glucocorticoid (representing 75%-90% of the plasma corticoids) plays a central role in glucose metabolism and in the body's response to stress.

Cortisol levels are regulated by adrenocorticotropic hormone (ACTH), which is synthesized by the pituitary gland in response to corticotropin-releasing hormone (CRH). CRH is released in a cyclic fashion by the hypothalamus, resulting in diurnal peaks (6 a.m.-8 a.m.) and troughs (11 p.m.) in plasma ACTH and cortisol levels.

The majority of cortisol circulates bound to cortisol-binding globulin (CBG-transcortin) and albumin. Normally, less than 5% of circulating cortisol is free (unbound). The free cortisol is the physiologically active form and is filterable by the renal glomerulus.

Although hypercortisolism is uncommon, the signs and symptoms are common (eg, obesity, high blood pressure, increased blood glucose concentration). The most common cause of increased plasma cortisol levels in women is a high circulating concentration of estrogen (eg, estrogen therapy, pregnancy) resulting in increased concentration of cortisol-binding globulin.

Spontaneous Cushing syndrome results from overproduction of glucocorticoids as a result of either primary adrenal disease (adenoma, carcinoma, or nodular hyperplasia) or an excess of ACTH (from a pituitary tumor or an ectopic source). ACTH-dependent Cushing syndrome due to a pituitary corticotroph adenoma is the most frequently diagnosed subtype; most commonly seen in women in the third through fifth decades of life. The onset is insidious and usually occurs 2 to 5 years before a clinical diagnosis is made.

Causes of hypocortisolism are:

-Addison disease-primary adrenal insufficiency

-Secondary adrenal insufficiency:

--Pituitary insufficiency

--Hypothalamic insufficiency

-Congenital adrenal hyperplasia-defects in enzymes involved in cortisol synthesis