In the second part of our endocrinology series, H S Randeva and P M G Bouloux explain a complicated multisystem disorder
Cushing's syndrome is a multisystem disorder resulting from chronic exposure to in appropriately elevated concentrations of free circulating glucocorticoids.
Cortisol secretion from the zona fasciculata of the adrenal cortex is regulated by pituitary adrenocorticotrophic hormone (ACTH). ACTH - and therefore cortisol - has a diurnal rhythm, with peak secretion at 7-9 am and a nadir at midnight. Its secretion is regulated by hypothalamic corticotrophin releasing hormone (CRH) and arginine vasopressin (AVP). There is synergism between CRH and AVP in ACTH release.
A number of physical and psychological factors (box 1) increase secretion of both ACTH and cortisol. Inhibition of CRH and AVP synthesis and release in the hypothalamus is a classic example of regulation of negative feedback by hormones. Cortisol is largely bound to cortisol-binding globulin (CBG) in the circulation; only 20% is free. CBG concentrations are regulated by oestrogen (for example, the oral contraceptive pill, pregnancy).
The most common