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Diagnosis

In its early stages, adrenal insufficiency can be difficult to diagnose. A review of a patient's medical history based on the symptoms, especially the dark tanning of the skin, will lead a doctor to suspect Addison's disease.
A diagnosis of Addison's disease is made by biochemical laboratory tests. The aim of these tests is first to determine whether there are insufficient levels of cortisol and then to establish the cause. X-ray exams of the adrenal and pituitary glands also are useful in helping to establish the cause.

ACTH Stimulation Test This is the most specific test for diagnosing Addison's disease. In this test, blood and/or urine cortisol levels are measured before and after a synthetic form of ACTH is given by injection. In the so called short, or rapid, ACTH test, cortisol measurement in blood is repeated 30 to 60 minutes after an intravenous ACTH injection. The normal response after an injection of ACTH is a rise in blood and urine cortisol levels. Patients with either form of adrenal insufficiency respond poorly or do not respond at all.
When the response to the short ACTH test is abnormal, a "long" ACTH stimulation test is required to determine the cause of adrenal insufficiency. In this test, synthetic ACTH is injected either intravenously or intramuscularly over a 48- to 72-hour period, and blood and/or urine cortisol are measured the day before and during the 2 to 3 days of the injection. Patients with primary adrenal insufficiency do not produce cortisol during the 48- to 72-hour period; however, patients with secondary adrenal insufficiency have adequate responses to the test on the second or third day.

In patients suspected of having an addisonian crisis, the doctor must begin treatment with injections of salt, fluids, and glucocorticoid hormones immediately. Although a reliable diagnosis is not possible while the patient is being treated, measurement of blood ACTH and cortisol during the crisis and before glucocorticoids are given is sufficient to make the diagnosis. Once the crisis is controlled and medication has been stopped, the doctor will delay further testing for up to 1 month to obtain an accurate diagnosis.

Insulin-Induced Hypoglycemia Test A reliable test to determine how the hypothalamus and pituitary and adrenal glands respond to stress is the insulin-induced hypoglycemia test. In this test, blood is drawn to measure the blood glucose and cortisol levels, followed by an injection of fast-acting insulin. Blood glucose and cortisol levels are measured again at 30, 45, and 90 minutes after the insulin injection. The normal response is for blood glucose levels to fall and cortisol levels to rise.

Other Tests Once a diagnosis of primary adrenal insufficiency has been made, x-ray exams of the abdomen may be taken to see if the adrenals have any signs of calcium deposits. Calcium deposits may indicate TB. A tuberculin skin test also may be used.
If secondary adrenal insufficiency is the cause, doctors may use different imaging tools to reveal the size and shape of the pituitary gland. The most common is the CT scan, which produces a series of x-ray pictures giving a cross-sectional image of a body part. The function of the pituitary and its ability to produce other hormones also are tested.

Treatment of Addison's disease involves replacing, or substituting, the hormones that the adrenal glands are not making. Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid, taken once or twice a day. If aldosterone is also deficient, it is replaced with oral doses of a mineralocorticoid, called fludrocortisone acetate (Florinef)), which is taken once a day. Patients receiving aldosterone replacement therapy are usually advised by a doctor to increase their salt intake. Because patients with secondary adrenal insufficiency normally maintain aldosterone production, they do not require aldosterone replacement therapy. The doses of each of these medications are adjusted to meet the needs of individual patients.
During an addisonian crisis, low blood pressure, low blood sugar, and high levels of potassium can be life threatening. Standard therapy involves intravenous injections of hydrocortisone, saline (salt water), and dextrose (sugar). This treatment usually brings rapid improvement. When the patient can take fluids and medications by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.

This e-pub was written by Eileen K. Corrigan of NIDDK's Office of Health Research Reports. The draft was reviewed by Dr. George P Chrousos, National Institute of Child Health and Human Development, Dr. Judith Fradkin, National Institute of Diabetes and Digestive and Kidney Diseases, and by Dr. Richard Horton, University of Southern California Medical Center.

NIH Publication No. 90-3054

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