Paradoxical Response to Dexamethasone in the Diagnosis of Primary Pigmented Nodular Adrenocortical Disease

Paradoxical Response to Dexamethasone in the Diagnosis of Primary Pigmented Nodular Adrenocortical Disease

From the National Institutes of Health, Bethesda, Maryland; and the Mayo Clinic, Rochester, Minnesota.

Abstract

Background: Primary pigmented nodular adrenocortical disease causes the Cushing syndrome in children and young adults and is most frequently associated with the Carney complex.

Objective: To evaluate diagnostic tests for primary pigmented nodular adrenocortical disease.

Design: Retrospective cohort study.

Setting: Tertiary care center.

Patients: 21 patients with primary pigmented nodular adrenocortical disease. The control groups consisted of 9 patients with macronodular adrenocortical disease and 15 patients with primary unilateral adrenocortical disease (single adenomas).

Measurements: Clinical characteristics, radiologic imaging, and a 6-day Liddle test with determination of urinary free cortisol and 17-hydroxycorticosteroid excretion.

Results: Adrenal imaging and other tests were of limited value for the diagnosis of primary pigmented nodular adrenocortical disease. The Liddle test, however, distinguished patients with this disorder from those with other primary adrenocortical lesions. An increase of 50% or more in urinary free cortisol levels on day 6 of the Liddle test identified 9 of 13 patients (69.2% [95% CI, 46.6% to 91.8%]) with primary pigmented nodular adrenocortical disease, excluded all patients with macronodular adrenocortical disease, and was present in only 3 of the 15 patients with single adrenocortical adenomas (20% [CI, 0% to 40.2%]). An increase in urinary free cortisol excretion of 100% or more on day 6 of the Liddle test identified only patients with primary pigmented nodular adrenocortical disease.

Conclusions: Patients with primary pigmented nodular adrenocortical disease responded to dexamethasone with a paradoxical increase in glucocorticoid excretion during the Liddle test. This feature distinguishes such patients from those who have the Cushing syndrome caused by other primary adrenal disorders and may lead to timely detection of the Carney complex (a potentially fatal disorder) in asymptomatic patients.

Article and Author Information

Acknowledgments: The authors thank the nursing staff of the 8W and 9W wards of the NIH clinical center for their help and expert technical assistance in completing patient tests. They especially thank Barbara Filmore, who supervised performance of all hormonal assays, and the patients who participated in our clinical research protocol. They also thank Dr. David E. Schteingart of the University of Michigan for useful discussions of dexamethasone-related paradoxical response of urinary glucocorticoids and for a critical review of this work.
Grant Support: By intramural funds of the National Institute of Child Health and Human Development for clinical research protocol 95-CH-059 (Dr. Stratakis, principal investigator).
Requests for Reprints: Constantine A. Stratakis, MD, DSc, National Institutes of Health, Building 10, Room 10N262, 10 Center Drive, MSC 1862, Bethesda, MD 20892-1862; e-mail, stratakc{at}cc1.nichd.nih.gov. For reprint orders in quantities exceeding 100, please contact the Reprints Coordinator; phone, 215-351-2657; e-mail, reprints{at}mail.acponline.org.
Current Author Addresses: Drs. Stratakis, Sarlis, Kirschner, Nieman, Chrousos, and Papanicolaou: National Institutes of Health, Building 10, Room 10N262, 10 Center Drive, MSC 1862, Bethesda, MD 20892-1862.
Dr. Carney: Plummer N-10, Mayo Clinic, One South Drive, Rochester, MN 55905.
Dr. Doppman: Diagnostic Radiology Department, Warren Grant-Magnuson Clinical Center, 10 Center Drive, MSC 1182, Bethesda, MD 20892-1182.