Introduction to the Adrenals

Anatomy, Embryology , and Physiology

The adrenal (suprarenal) glands lie in the perirenal space, usually cephalic to the kidneys. The right adrenal gland lies above the kidney, lateral to the crus of the diaphragm, medial to the liver, and touches the posterior aspect of the inferior vena cava. The left adrenal gland usually lies anterior to the upper pole of the left kidney, posterior to the splenic vein and pancreas. The splenic vein is a useful landmark in identifying the source of left upper quadrant masses that may be of uncertain origin. Adrenal masses generally displace the splenic vein forward, while pancreatic or gastric masses displace it posteriorly.

The adrenal cortex and medulla are essentially different organs that lie within the same structure. The cortex is an endocrine gland, secreting primarily cortisol, aldosterone, and androgenic steroids, all of which are derived from cholesterol esters. This contributes to the high lipid content that is characteristic of most adrenal cortical adenomas.

The medulla is derived from the neural crest and secretes epinephrine and norepinephrine.

Adrenal physiology is controlled by an elaborate interaction between the hypothalamus, pituitary, and adrenals. Stress results in the release of epinephrine and cytokines, which cause the pituitary to secrete adrenocorticotrophic hormone (ACTH), which in turn stimulates the adrenals to secrete cortisol. Cortisol and epinephrine are often regarded as the "stress hormones." Elevated serum cortisol has a suppressing effect on the hypothalamus and pituitary, reducing further release of ACTH.

Cushing syndrome, due to excess cortisol, is characterized by truncal obesity, hirsutism, amenorrhea, hypertension, weakness, and abdominal striae. It is usually caused by adrenal hyperplasia (75-80% of cases) but may also result from an adrenal adenoma (20-25%), adrenal carcinoma (< 5%), or exogenous corticosteroid medication.

Conn syndrome is the eponym sometimes used for excess aldosterone and is characterized by hypertension, hypokalemia, alkalosis, muscle weakness, and cardiac dysfunction. Unlike Cushing syndrome, Conn syndrome is usually caused by an adrenal adenoma (65-70%). Adrenal hyperplasia accounts for most of the remaining (25-30%) cases, while adrenal carcinoma is a rare cause.

Because patients with Cushing syndrome are symptomatic, the diagnosis of either pituitary or adrenal-induced cortisol excess is typically made biochemically, prior to imaging. Imaging (either MR or CT) performed after diagnosis usually easily localizes the pituitary or adrenal adenoma responsible for Cushing syndrome, thus obviating catheter angiography or other invasive tests. Conn adenomas, however, may be quite small, and traditional imaging may be problematic in the setting of elevated aldosterone.

Addison syndrome or disease refers to adrenal insufficiency and is characterized by hypotension, weight loss, and altered pigmentation. Among the causes of "slow-onset" adrenal insufficiency are autoimmune disease, which is the most common cause in developed countries. Tuberculosis and other infections remain common causes of Addison syndrome in the developing world, while metastatic disease and AIDS are encountered in all populations.

The most common cause of abrupt onset adrenal insufficiency is adrenal hemorrhage, which may result from sepsis, shock, anticoagulation, or vasculitis. Abrupt withdrawal of corticosteroid medication and postpartum pituitary necrosis, known as Sheehan syndrome, also result in acute adrenal insufficiency. Prompt recognition and treatment of these conditions is critical.