Document Detail

A novel form of human mendelian hypertension featuring nonglucocorticoid-remediable aldosteronism.
MedLine Citation:
PMID:  18505761     Owner:  NLM     Status:  MEDLINE    
CONTEXT: Primary aldosteronism is a leading cause of secondary hypertension (HTN), but the mechanisms underlying the characteristic renin-independent secretion of aldosterone remain unknown in most patients.
OBJECTIVES: We report a new familial form of aldosteronism in a father and two daughters. All were diagnosed with severe HTN refractory to medical treatment by age 7 yr. We performed a variety of clinical, biochemical, and genetic studies to attempt to clarify the underlying molecular defect.
RESULTS: Biochemical studies revealed hyporeninemia, hyperaldosteronism, and very high levels of 18-oxocortisol and 18-hydroxycortisol, steroids that reflect oxidation by both steroid 17-alpha hydroxylase and aldosterone synthase. These enzymes are normally compartmentalized in the adrenal fasciculata and glomerulosa, respectively. Administration of dexamethasone failed to suppress either aldosterone or cortisol secretion; these findings distinguish this clinical syndrome from glucocorticoid-remediable aldosteronism, another autosomal dominant form of HTN, and suggest a global defect in the regulation of adrenal steroid production. Genetic studies excluded mutation at the aldosterone synthase locus, further distinguishing this disorder from glucocorticoid-remediable aldosteronism. Because of unrelenting HTN, all three subjects underwent bilateral adrenalectomy, which in each case corrected the HTN. Adrenal glands showed dramatic enlargement, with paired adrenal weights as high as 82 g. Histology revealed massive hyperplasia and cellular hypertrophy of a single cortical compartment that had features of adrenal fasciculata or a transitional zone, with an atrophic glomerulosa.
CONCLUSION: These findings define a new inherited form of aldosteronism and suggest that identification of the underlying defect will provide insight into normal mechanisms regulating adrenal steroid biosynthesis.
David S Geller; Junhui Zhang; Max V Wisgerhof; Cedric Shackleton; Michael Kashgarian; Richard P Lifton
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-05-27
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  93     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2008 Aug 
Date Detail:
Created Date:  2008-08-07     Completed Date:  2008-09-08     Revised Date:  2013-03-27    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3117-23     Citation Subset:  AIM; IM    
Section of Nephrology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, Connecticut 06520-8029, USA.
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MeSH Terms
Adrenal Glands / pathology
Aldosterone Synthase / genetics
Child, Preschool
Glucocorticoids / therapeutic use
Hydrocortisone / biosynthesis
Hyperaldosteronism / complications*,  genetics,  metabolism
Hypertension / etiology*,  genetics
Renin / blood
Steroid 11-beta-Hydroxylase / genetics
Grant Support
//Howard Hughes Medical Institute
Reg. No./Substance:
0/Glucocorticoids; 50-23-7/Hydrocortisone; EC Synthase; EC 11-beta-Hydroxylase; EC
Comment In:
J Clin Endocrinol Metab. 2008 Aug;93(8):2972-4   [PMID:  18685118 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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