Diagnosing a Rare but Potentially Deadly Disease of the Adrenal Glands

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The summary below is from the full report titled "Paradoxical Response to Dexamethasone in the Diagnosis of Primary Pigmented Nodular Adrenocortical Disease." It is in the 19 October 1999 issue of Annals of Internal Medicine (volume 131, pages 585-591). The authors are C.A. Stratakis, N. Sarlis, L.S. Kirschner, J.A. Carney, J.L. Doppman, L.K. Nieman, G.P. Chrousos, and D.A. Papanicolaou.

What is the problem and what is known about it so far?

Primary pigmented nodular adrenocortical disease (PPNAD) is a rare disease of the adrenal glands. The adrenal glands are small glands located above each kidney. The adrenals make hormones. Hormones are chemical substances formed in one organ or part of the body that travel in the blood to other body parts where they influence how that body part works. Cortisol is one of the hormones made by the adrenals. Cortisol influences body metabolism (how the body converts small molecules to large and vice versa) and can decrease inflammation. People with PPNAD have adrenal glands that make too much cortisol or make it at inappropriate times (when the body does not need it).

The Cushing syndrome is a condition that results from too much cortisol in the body. People with the Cushing syndrome accumulate fat in their bodies and faces while their legs and arms remain thin. Other symptoms seen in the Cushing syndrome include abnormal facial hair, menstrual irregularities, high blood pressure, weak muscles, stretch marks on the skin, acne, back pain, bruising, psychological problems, and thinning of the bones. In addition to PPNAD, many other medical conditions can cause the Cushing syndrome. PPNAD is one of the rarest causes of the Cushing syndrome, but it can be associated with a potentially fatal condition known as the Carney complex. People with PPNAD who have the Carney complex develop unusual types of tumors that can be deadly, so you don't want to miss the diagnosis of PPNAD. Unfortunately, the diagnosis is very difficult to make.

The Liddle test is a test that doctors can use to help determine whether persons with the Cushing syndrome have it because there is something wrong with their adrenal glands or because there is a problem elsewhere in the body that is causing the adrenal glands to make extra cortisol. For this test, the patient takes low and high doses of a drug called dexamethasone and the doctor measures the amount of cortisol in the patient's urine over a period of days. This test has not usually been used to help sort out which of a patient's adrenal problems is the cause of the Cushing syndrome.

Why did the researchers do this particular study?

The researchers wanted to find out if the Liddle test could help determine whether patients have PPNAD or another problem with their adrenal glands.

Who was studied?

21 patients with PPNAD and 24 patients with other problems with their adrenal glands. All patients were patients seen at the National Institutes of Health.

How was the study done?

The researchers performed the Liddle test, hormone measurements, and CAT scans of the adrenal glands. They also examined the patients and their medical records.

What did the researchers find?

The CAT scans and baseline hormone measurements were not very useful in separating the patients with PPNAD from the other patients, but the Liddle test was. Patients with PPNAD had unexpectedly high increases in the amount of cortisol in their urine on the sixth day of the test.

What were the limitations of the study?

The researchers studied a small number of patients, but PPNAD is a rare genetic disorder.

What are the implications of the study?

The Liddle test may be useful in helping to make a diagnosis of PPNAD. Early diagnosis of PPNAD would allow earlier diagnosis of the Carney complex, a potentially deadly disorder that can occur with PPNAD.