Physical exam findings include truncal obesity and fat accumulation around the head (moon facies) and neck (buffalo hump). Proximal muscle wasting can make it difficult for patients to stand from a seated position or climb stairs. The skin thins out, resulting in purple striae on the abdomen and extremities, easy bruising, and a reddish coloration of the face (plethora). Women may present with amenorrhea and hirsutism. Patients often have associated metabolic conditions, i.e., obesity, type 2 diabetes mellitus, elevated cholesterol or lipid levels, and hypertension. Hypercortisolism is also associated with osteoporosis, poor wound healing, and psychiatric symptoms.

Most hypercortisolism is iatrogenic or exogenous. Pharmacologic glucocorticoids are administered for a spectrum of inflammatory conditions and for as immunosuppression following organ transplantation. Cushing’s syndrome describes the cluster of clinical findings (signs and symptoms) associated with glucocorticoid excess (described above), regardless of the underlying cause. In other words, patients with Cushing’s syndrome may be receiving exogenous glucocorticoids, or they may have a cortisol-producing adrenal tumor, or they may have a tumor producing adrenocorticotropic hormone (ACTH). The latter two circumstances represent endogenous causes of hypercortisolism. The majority of endogenous cases arise from ACTH hypersecretion, which is almost always caused by a pituitary tumor (Cushing’s disease = hypercortisolism due to an ACTH-producing pituitary adenoma). A second, much rarer cause of ACTH-dependent Cushing’s syndrome is an ectopic source of ACTH production (e.g., non-small cell lung cancer and bronchial carcinoids). Up to 25 % of patients with endogenous hypercortisolism have a primary adrenal cause, most commonly a single adrenal adenoma (80 % of cases). A minority of patients have bilateral adrenal hyperplasia or multiple adrenal nodules.

The hallmark of hyperaldosteronism is hypertension with hypokalemia. Patients with hyperaldosteronism often have refractory hypertension requiring management with three or more antihypertensive agents. Many of them show an excellent response to spironolactone, an aldosterone antagonist. Hypokalemia, a sign of biochemically severe disease, is less prevalent among patients with hyperaldosteronism today than reported historically, due to earlier detection of the disease. Currently the proportion of hypokalemic patients is less than 50 %. Hypokalemia may present with muscle cramping, muscle weakness, or rarely paralysis.

Patients with pheochromocytoma most often present with sustained or episodic hypertension. Though only a minority present with the classic triad of headache, flushing, and palpitations, more than 90 % complain of at least one of these symptoms.

Adrenocortical carcinomas are highly lethal malignancies (5-year survival <25 %) which often present at an advanced stage after having grown in a quiescent fashion. Approximately 60 % are functional. The most common hormone hypersecretion associated with adrenocortical carcinoma is Cushing’s syndrome, with virilization being a distant second and feminization a very distant third. Patients with nonfunctional tumors may present with an abdominal mass, abdominal pain, nausea, anorexia, early satiety, or weight loss. Approximately 75 % of adrenocortical carcinomas are >6 cm at the time of presentation (Figs. 8.1 and 8.2).

An incidentaloma is an incidentally discovered mass seen on imaging performed for an unrelated reason. Approximately 5 % of patients who undergo an abdominal CT scan will have an incidentally discovered adrenal mass. The incidence increases with patient age, with up to 10 % of patients having adrenal nodules on autopsy studies (Fig. 8.3).

The most common adrenal mass is a nonfunctional benign adrenocortical adenoma. Only 15 % of adrenal adenomas are associated with hormone hypersecretion. The most common functional lesion discovered incidentally is an adenoma associated with cortisol hypersecretion.

Each adrenal gland has an outer cortex and an inner medulla. The cortex is composed of three zones (from outer to inner): glomerulosa, fasciculata, and reticularis. The outer zona glomerulosa is the site of mineralocorticoid (aldosterone) production. The middle zona fasciculata is the site of glucocorticoid (cortisol) production. The inner zona reticularis is the site of adrenal androgen (dehydroxyepiandrosterone, dehydroxyepiandrosterone-sulfate, and androstenedione) synthesis. The adrenal medulla is the location for catecholamine synthesis.