Malfunctions of the paired adrenal glands. The adrenal glands each consist of two morphologically and functionally distinct components, the cortex and medulla. These secrete different types of hormones: the cortex secretes steroids and the medulla secretes amines. The cortex is controlled by hormones from the anterior pituitary and the kidney; the medulla is directly controlled by the nervous system. Although the cortex and medulla are functionally separate, they both contribute to the mammalian body's response to outside stimuli, especially stress. See also Pituitary gland; Steroid.
The adrenal glands can have congenital defects and can be damaged by infections and destructive tumors. Anencephaly, that is, gross underdevelopment of the brain in fetal life, leads to hypoplasia of the adrenal cortex. The cortex is also, although rarely, invaded by acute bacterial diseases, for example, septicemia due to the colon bacillus or meningococcus, which can result in failure of the adrenal cortex followed by shock and death (Waterhouse-Friderichsen syndrome). Chronic infection of the cortex by the tubercle bacillus or a fungal infection such as histoplasmosis can cause primary adrenal deficiency. Cancer may spread to the adrenal glands, and there are uncommon primary tumors of the adrenal that do not secrete hormones. The most important disorders of the adrenal cortex and medulla are those characterized by abnormal hormone secretion.
Adrenal cortex
There are a number of disorders of the adrenal cortex. Primary adrenal cortical insufficiency, or Addison's disease, is rare, but if it is not treated it always results in death. The disease is usually caused by autoimmune destruction of the adrenals, by tuberculosis, or less often by chronic fungal diseases. Symptoms include lassitude, muscular weakness, weight loss, prostration during minor illnesses, low blood pressure, and brown pigmentation of the skin. The water and electrolyte loss associated with this condition results from deficiency of the adrenal hormone, aldosterone. Maintenance therapy with small daily doses of hydrocortisone and synthetic, salt-retaining steroids permits a normal life. See also Aldosterone; Tuberculosis.
Secondary adrenal cortical insufficiency sometimes accompanies pituitary failure due to tumors, vascular accidents, chronic infectious diseases, or granulomas. The clinical picture differs from Addison's disease: weak, listless, and intolerant of minor illness, individuals also are pale and usually show neurologic signs related to the pituitary lesion. Treatment consists of cortisol, thyroid hormone, and sex steroids. A more common form of secondary adrenal failure follows long-term administration of high doses of semisynthetic steroids for treatment of such diseases as rheumatoid arthritis, asthma, and acute lymphoblastic leukemia.
Manifestations of adrenal cortical hyperfunction, or hyperadrenocorticism, can result from excessive secretion of steroid hormones normally secreted by the adrenal cortex. The four classes of adrenal cortical hormones include mineralocorticoids, such as aldosterone, which regulate salt retention; glucocorticoids, such as cortisol, that affect carbohydrate and protein metabolism, muscle function, and blood pressure; androgens, such as dehydroepiandrosterone; and estrogens, such as estradiol. See also Androgen; Estrogen.
Excess secretion of aldosterone produces hyperaldosteronism. The classic primary form arises from a small unilateral tumor known as an adenoma of the adrenal cortex, from bilateral nodular overgrowth of the cortex, or sometimes from overfunction of the kidney's renin-angiotensin system which stimulates the cortex to secrete too much aldosterone (Bartter's syndrome). The affected individuals have high blood pressure, muscle weakness, and decreased levels of potassium in the blood. The tumors can be removed surgically. In cases where there is no tumor, the individual can be treated with diuretics that act by physiologically opposing the action of aldosterone on the kidney. Secondary hyperaldosteronism occurs in very severe hypertension and in advanced liver disease (cirrhosis), kidney disease (nephrotic syndrome), and heart failure when the body retains excess salt and water with swelling.
Excessive secretion of cortisol produces hypercortisolism, or Cushing's syndrome. Clinical manifestations include obesity of the trunk with thin arms and legs, round red face, thin skin, brittle bones, high blood pressure, diabetes mellitus, and, in women, virilism (masculinity). If not treated, Cushing's syndrome is fatal within five years because of complications of hypertension or infections. The most common cause of Cushing's syndrome is overactivity of the pituitary gland, often due to a small tumor that secretes excess adrenocorticotropic hormone. The disease is difficult to treat; methods include surgical removal of the pituitary tumor, x-ray or proton-beam treatment of the pituitary region, chemotherapy, or surgical removal of both adrenals. If the excess cortisol secretion is controlled, the individual can lead a normal life, although sometimes requiring hormone replacement. See also Cancer (medicine).
Adrenal medulla
There is no recognized hormone deficiency of the adrenal medulla in humans. Excess secretion of norepinephrine and epinephrine accompanies pheochromocytoma, a rare adrenal medullary tumor that may be single or multiple, benign or malignant. Sometimes the tumor occurs in multiple endocrine adenomatosis, type II (Sipple's syndrome), characterized clinically by pheochromocytoma, tumors of the parathyroid glands with high blood calcium, and carcinoma of the thyroid. Treatment is difficult, and consists of careful surgical removal of the tumor. Neuroblastoma (in children), ganglioneuroblastoma, and ganglioneuroma are malignant tumors of the adrenal medulla or sympathetic ganglia; they may secrete amines that have only a minor effect on blood pressure. The clinical importance of these tumors arises from their extreme malignancy, but some are known to regress spontaneously. See also Epinephrine.
