Adrenal Gland Disorders

A. Adrenal Cortex. 1. Steroid-Deficiency Syndromes. Steroid-deficiency syndromes are due to either a primary disorder of the adrenal glands or a secondary or tertiary disorder caused by dysfunctions of the pituitary or hypothalamus, respectively. The most common causes of primary adrenal disorders are a congenital enzymatic block or destruction of the adrenal glands (Addison’s Disease) due to autoimmunity, infection, hemorrhage, tumor, drugs, surgery, or radiotherapy.

Signs and symptoms of these disease states vary with the pattern of steroid pathways affected and the degree to which they are altered. The most common form of congenital adrenal enzymatic block is 21-hydroxylase deficiency (see Fig. 4), in which the lack of synthesis of cortisol and mineralocorticoids causes hypoglycemia and electrolyte imbalance.

The overproduction of adrenal androgens causes masculinization of a female fetus with resultant ambiguous genitalia at birth, and the lack of cortisol feedback on ACTH secretion causes hypersecretion of ACTH and enlargement of both adrenal glands, which gives the syndrome the name congenital adrenal hyperplasia (CAH). Other forms of CAH result from decreased activity of other adrenal enzymes. Primary steroid-deficiency syndromes are verified by measurement of appropriate steroid hormones in the blood or urine before and after ACTH stimulation. Many synthetic steroid hormones are now available, which make lifesaving replacement therapy possible.

Secondary and tertiary forms of adrenal insufficiency are caused by the therapeutic usage of glucocorticoids for conditions such as obstructive and asthmatic lung disease, or arthritis, and by pituitary or hypothalamic tumors, surgery, or radiotherapy.

The use of high dosages of glucocorticoids for long periods of time results in atrophy of pituitary and adrenal cells which produce ACTH and cortisol, respectively. In ACTH deficiency, there is usually minimal electrolyte abnormality, because the renin-angiotensin system is still operative and the zona glomerulosa is spared. The opposite situation occurs in some patients with kidney disease and renin deficiency, who have decreased aldosterone but normal cortisol secretion.

2. Steroid-Excess Syndromes.States of circulating adrenocortical steroid excess are caused by taking glucocorticoids or by either primary disease of the adrenal gland or excessive pituitary or hypothalamic secretion. If there is an excess of glucocorticoids in the circulation, the problem is known as Cushing’s syndrome.

Primary Cushing’s syndrome results from adrenocortical adenomas and carcinomas. These can cause hyperglycemia (high blood sugar), muscle- wasting, and osteoporosis, due to overproduction of cortisol, and masculinization in women, due to adrenal androgen overproduction. If pituitary secretion of ACTH is excessive, this is called Cushing’s disease, which in some cases may be due to excessive hypothalamic CRH. Some tumors, such as lung tumors, regain their previously suppressed genetic ability to secrete peptide hormones, and if ACTH is secreted this is known as ectopic ACTH syndrome.

Cushing’s syndrome is verified by measurement of cortisol before and after attempted suppression of ACTH secretion with the synthetic glucocorticoid dexamethasone. Treatment depends on the source of steroid excess. For example, an adrenal tumor is treated by surgical removal of the affected adrenal gland, and pituitary oversecretion of ACTH is often treated by pituitary surgery.

Increased secretion of aldosterone can be caused by hyperplasia (enlargement) or tumor formation of the zona glomerulosa. Because cortisol secretion is normal, signs and symptoms are due to electrolyte imbalance. The most common problems associated with increased mineralocorticoid secretion are sodium retention and increased blood pressure, and renal potassium hypersecretion, with resultant serum potassium deficiency.

Potassium deficiency causes muscular weakness and, if severe or prolonged, decreased kidney function and life-threatening cardiac rhythm disorders. An excess of aldosterone secretion from both adrenals is usually treated with the aldosterone antagonist spironolactone, while a unilateral tumor of the zona glomerulosa, called an aldosteronoma, may be surgically removed.

B. Adrenal Medulla.Adrenalectomized patients are deficient in epinephrine, but if the rest of the sympathetic nervous system is normal, symptoms of autonomic insufficiency do not develop. If, however, peripheral sympathetic nervous system secretion of norepinephrine is deficient, low blood pressure may result. Symptoms of catecholamine excess occur in the presence of hypersecretion by chromaffin cells. Tumors of chromaffin cells may occur in association with sympathetic ganglia, anywhere in the body from the neck to the pelvis, but most often occur as tumors of the adrenal medulla, which are called pheochromocytomas. Tumor cells contain catecholamine storage granules. Although most are benign, they cause disease due to their oversecretion of catecholamines.

Pheochromocytomas cause signs and symptoms primarily due to episodic hypertension (high blood pressure). They increase blood pressure through excessive catecholamine secretion, mediated by alpha and beta stimulation, which results in increased peripheral vasoconstriction (blood vessel narrowing) and cardiac output. These tumors therefore cause episodic nonspecific symptoms such as headaches, palpitations, and sweating, which can be mistaken for thyroid, hormone oversecretion, or severe anxiety.

The hypertension caused by pheochromocytomas is usually too severe for treatment with the usual high blood pressure medications, and this fact may serve as a diagnostic clue. If blood pressure elevation persists, it may cause the usual hypertension-related complications of heart attack, heart failure, and stroke. Stimulation of glycogenolysis by catecholamines may result in hyperglycemia and prompt a mistaken diagnosis of primary diabetes.

In some cases, pheochromocytomas occur as part of the autosomal dominant syndrome of multiple endocrine neoplasia type II, which also includes calcitonin-secreting tumors of the C cells of the thyroid gland and parathyroid hormone-secreting tumors of the parathyroid gland.

The diagnosis of pheochromocytoma is verified by blood or urine catecholamine measurements. Drug treatment is usually begun with alpha and beta blockers such as phenoxybenzamine and propranolol employed together. Removal of the tumor after blood volume expansion, and during alpha and beta blockade, under careful cardiovascular monitoring, is often performed.