RSS Feeds
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
Abstract
▪ 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.
Article and Author Information
-
From Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Veterans Affairs Hospital, Bronx, New York; New York Hospital and Cornell University Medical College, New York, New York; and University of Utah Medical School, Salt Lake City, Utah. For current author addresses, see end of text.
-
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.
Related Clinical Content
