Adrenal Hypofunction

What is Adrenal Hypofunction?

Adrenal hypofunction (also called adrenal insufficiency) has primary and secondary forms. Primary adrenal hypofunction (Addison's disease) originates within the adrenal gland and is characterized by decreased mineralocorticoid, glucocorticoid, and androgen secretion. Addison's disease is a relatively uncommon disorder that occurs in people of all ages and both sexes.

Adrenal hypofunction can also occur secondary to a disorder outside the gland (such as pituitary tumor with corticotropin deficiency), but aldosterone secretion may continue intact. With early diagnosis and adequate replacement therapy, the prognosis for both primary and secondary adrenal hypofunction is good.

Adrenal crisis - also called addisonian crisis - is a critical deficiency of mineralocorticoids and glucocorticoids. Adrenal crisis is a medical emergency that necessitates immediate, vigorous treatment.

Causes of Adrenal Hypofunction

Addison's disease occurs when more than 90% of the adrenal gland is destroyed. Such massive destruction usually results from an autoimmune process in whicr circulating antibodies react specifically against the adrenal tissue.

Other causes include tuberculosis, bilateral adrenalectomy, hemorrhage into the adrenal gland, neoplasms, and infections, such as human immunodeficiency virus, histoplasmosis, meningococcal pneumonia, and cytomegalovirus. Rarely, a familial tendency toward autoimmune disease predisposes a patient to Addison's disease and to other endocrinopathies.

Secondary adrenal hypofunction that results in glucocorticoid deficiency can stem from hypopituitarism, which can cause decreased corticotropin secretion. It also can stem from abrupt withdrawal of long-term corticosteroid therapy, as when long-term exogenous corticosteroid stimulation suppresses pituitary corticotropin secretion and causes adrenal gland atrophy. In addition, it can result from removal of a nonendocrine, corticotropin-secreting tumor.

Adrenal crisis occurs in a patient with adrenal hypofunction when trauma, surgery, or other severe physiologic stress completely exhausts the body's stores of glucocorticoids.

Signs & Symptoms of Adrenal Hypofunction

Weakness, fatigue, and orthostatic hypotension are early symptoms. The following symptoms are listed from the most common to the least common:

• Unintentional weight loss, Nausea, Vomiting.
• Changes in the blood pressure or heart rate.
• Common are black freckles over the forehead, face, neck, and shoulders; areas of vitiligo; and bluish black discolorations of the areolae and of the mucous membranes of the lips, mouth, rectum, and vagina. Anorexia, nausea, vomiting, and diarrhea often occur.
• The gradual onset and nonspecific nature of early symptoms often lead to an incorrect initial diagnosis of neurosis. Weight loss, dehydration, hypotension, and small heart size are characteristic of the later stages of Addison's disease.

Diagnostic tests

Diagnosis of this disorder requires demonstration of decreased corticosteroid concentrations in plasma and an accurate classification of adrenal hypofunction as primary or secondary. Plasma cortisol levels and the corticotropin stimulation test are used to diagnose adrenal hypofunction.

Plasma cortisol levels confirm adrenal insufficiency. If secondary adrenal hypofunction is suspected, metyrapone is given I.V. or orally to stimulate the release of corticotropin. In Addison's disease, the hypothalamic-pituitary system responds normally and plasma reveals high levels of corticotropin. However, because adrenal glands are destroyed, plasma levels of cortisol precursor and urinary concentrations of 17-hydroxycorticosteroids don't increase. If either primary or secondary adrenal hypofunction is suspected, a corticotropin stimulation test is indicated.

• Corticotropin stimulation test demonstrates plasma cortisol response to corticotropin. After obtaining plasma cortisol samples and 24-hour urine cortisol levels, an I.V. infusion of corticotropin is administered over 6 to 8 hours. In Addison's disease, plasma and urine cortisol levels fail to increase normally in response to corticotropin. In secondary hypofunction repeated doses of corticotropin over successive days produce a gradual increase in cortisol levels until normal levels are reached.

In a patient with typical symptoms of Addison's disease, the following laboratory findings strongly suggest acute adrenal insufficiency:

• Plasma cortisol levels are decreased (less than 10 µl/dl in the morning, with lower levels in the evening). This test is time-consuming; crisis therapy shouldn't be delayed by waiting for results.
• Serum sodium levels are reduced.
• Serum potassium, serum calcium, and blood urea nitrogen levels are increased.
• Hematocrit, lymphocyte, and eosinophil counts are elevated.
• In addition, X-rays may show a small heart and adrenal calcification.

Treatment

Lifelong corticosteroid replacement is the main treatment for all patients with primary or secondary adrenal hypofunction. In general, cortisone or hydrocortisone (which have a mineralocorticoid effect) are given. Patients with Addison' disease may also need fludrocortisone, a synthetic drug that acts as a mineralocorticoid, to prevent dangerous dehydration and hypotension. Women with Addison's disease who have muscle weakness and decreased libido may benefit from testosterone injections but risk unfortunate masculinizing effects.

Treatment for a patient in adrenal crisis is prompt I.V. bolus administration of 100 mg of hydrocortisone, followed by 50 to 100 mg dose I.M. or diluted with dextrose in normal saline solution and given I.V. until the patient's condition stabilizes. Up to 300 mg/day of hydrocortisone and 3 to 5 L of I.V. normal saline solution may be required during the acute stage. With proper treatment, the crisis usually subsides quickly, with blood pressure stabilizing and water and sodium levels returning to normal. After the crisis, maintenance doses of hydrocortisone preserve physiologic stability.

Prevention Tips

There are no guidelines for preventing Addison's disease. If you think you are at risk for Addison's disease, talk to your doctor about how to diagnose and manage your symptoms.