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Glucocorticoid-remediable Aldosteronism in a Large Kindred: Clinical Spectrum and Diagnosis Using a Characteristic Biochemical Phenotype

Glenn M. Rich, MD; Stanley Ulick, MD; Sandra Cook, RN; Jennifer Z. Wang, MA; Richard P. Lifton, MD, PhD; and Robert G. Dluhy, MD
[+] Article, Author, and Disclosure Information

Grant Support: In part by grants RO1-HL45321 and HL-18323 from the National Institutes of Health, Bethesda, Maryland; and grants from the following General Clinical Research Centers: grant 5MO1-RR-02635 from Brigham and Women's Hospital, Boston, Massachusetts; grant MO1-RR109 from Medical Center Hospital of Vermont, Burlington, Vermont; and grant MO1-RR43 from the University of Southern California, Los Angeles, California. The study was also supported by the Department of Veterans Affairs. Data storage and statistical analysis were done using a CLINFO facility supported by the same grants. Dr. Rich is on a National Institutes of Health training grant (T32-DK07529). Dr. Lifton is a clinician-scientist of the American Heart Association.

Requests for Reprints: Robert G. Dluhy, MD, Endocrinology-Hypertension Division, 221 Longwood Avenue, Brigham and Women's Hospital, Boston, MA 02115.

Current Author Addresses: Drs. Rich and Dluhy and Ms. Cook: Endocrine-Hypertension Division, Brigham and Women's Hospital, 221 Longwood Avenue, Boston, MA 02115.

Dr. Ulick and Ms. Wang: Veterans Affairs Hospital, 130 West Kingbridge Road, Bronx, NY 10468.

Dr. Lifton: Howard Hughes Medical Institute and Department of Human Genetics, University of Utah Medical School, Salt Lake City, UT 84132.

Ann Intern Med. 1992;116(10):813-820. doi:10.7326/0003-4819-116-10-813
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Objective: To define the clinical spectrum of glucocorticoid-remediable aldosteronism (GRA) in a large kindred.

Design: Screening all at-risk relatives of a proband for GRA using a specific biochemical phenotype and collecting of medical histories of kindred members from five generations.

Setting: Outpatient General Clinical Research Centers and patients' homes.

Measurements: Screening was done while patients were on a self-selected diet and included blood pressure determinations; serum potassium and plasma renin activity and aldosterone measurements; and 24-hour urinary tetrahydroaldosterone, 18-oxotetrahydrocortisol, and 18-hydroxycortisol measurements.

Results: Diagnosis of GRA was established on the basis of a previously described specific biochemical abnormality, overproduction of the cortisol C-18 oxidation products (18-oxotetrahydrocortisol and 18-hydroxycortisol) in urine and their ratio relative to tetrahydroaldosterone. Glucocorticoid-remediable aldosteronism was diagnosed in 11 additional patients spanning three generations; this group included the youngest patient (3 months old) ever diagnosed with GRA. Complete penetrance of the biochemical abnormality is likely, with 11 of 18 at-risk patients displaying the phenotype. All patients with GRA had elevated blood pressure. Affected adult patients had been diagnosed as hypertensive before reaching 21 years of age (n = 7 mean, 16.1 ± 3.4 years). All affected patients were normokalemic (4.3 ± 0.3 mmol/L).

Conclusion: Hypertension is a characteristic feature of GRA. Elevated blood pressure in this kindred developed at an early age and often was severe. Because a normal potassium level does not exclude the diagnosis of GRA, the disorder may be underdiagnosed. The value of a specific cortisol C-18 oxidation phenotype in the diagnosis of GRA has been confirmed.





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