Disorders of the adrenal glands result in classic endocrine syndromes such as Cushing's syndrome, hyperaldosteronism, and catechol excess from pheochromocytoma (Figure 31–1). The diagnosis of these disorders requires careful endocrine evaluation and imaging with computed tomography (CT) or magnetic resonance imaging (MRI).
The hypothalamic–pituitary–adrenocortical relationships in various adrenocortical syndromes.
In addition, many adrenal lesions are discovered on cross-sectional imaging performed for other reasons. These “incidentalomas” require metabolic evaluation and assessment to determine their need for treatment.
Cushing's syndrome is the clinical disorder caused by overproduction of cortisol. Most cases (80%) are due to bilateral adrenocortical hyperplasia stimulated by overproduction of pituitary adrenocorticotropic hormone (ACTH, corticotropin), known as Cushing's disease. About 10% of cases are due to the ectopic production of ACTH from nonpituitary tumors. Ectopic ACTH production occurs most frequently in small-cell lung carcinoma; other tumors producing ACTH include carcinoids (lung, thymic, gastrointestinal tract), islet cell tumors of the pancreas, medullary thyroid carcinoma, pheochromocytoma, and small-cell carcinoma of the prostate. Adrenal adenoma is the cause in 5% of cases and carcinoma in 5%. In children, adrenocortical carcinoma is the most common cause of Cushing's syndrome.
Overproduction of cortisol by adrenocortical tissue leads to a catabolic state. This causes liberation from muscle tissue of amino acids, which are transformed into glucose and glycogen in the liver by gluconeogenesis. The resulting weakened protein structures (muscle and elastic tissue) cause a protuberant abdomen and poor wound healing, generalized muscle weakness, and marked osteoporosis, which is made worse by excessive loss of calcium in the urine.
In addition, glucose is transformed largely into fat and appears in characteristic sites such as the abdomen, supraclavicular fat pads, and cheeks. There is a tendency to diabetes, with an elevated fasting plasma glucose level in 20% of cases and abnormal glucose tolerance in 80% of patients.
The cortisol excess also suppresses the immune mechanisms, making patients susceptible to infection. Inhibition of fibroblast function by excess cortisol further interferes with wound healing.
Hypertension is present in 90% of cases. Although the aldosterone level is not usually elevated, cortisol itself exerts a hypertensive effect when present in excessive amounts, as does 11-deoxycorticosterone. The hypertension may be accompanied by manifestation of mineralocorticoid excess (hypokalemia and alkalosis), especially in patients with ectopic ACTH syndrome or adrenocortical carcinoma.
The cells in adrenal hyperplasia resemble those of the zona fasciculata of the normal adrenal cortex. Frank adenocarcinoma reveals pleomorphism and invasion of the capsule, the vascular system, or both (Figure 31–2). Local invasion may occur, and metastases are common to the liver, lungs, bone, or brain. Histologic differentiation between adenoma and adenocarcinoma is frequently difficult.