Journal of Clinical Endocrinology & Metabolism, Vol 71, 1151-1157, Copyright © 1990 by Endocrine Society

ARTICLES

Defective fasciculata zone function as the mechanism of glucocorticoid- remediable aldosteronism

S Ulick, CK Chan, JR Gill Jr, M Gutkin, L Letcher, F Mantero and MI New
Veterans Affairs Hospital, Bronx, New York 10468.

Glucocorticoid-remediable aldosteronism is characterized by unusual sensitivity of aldosterone secretion to ACTH. Suppressibility by glucocorticoid and continued stimulability by exogenous ACTH has provided the basis for diagnosis and treatment of the disorder. A qualitative biochemical abnormality consisting of marked overproduction of the products of the cortisol C-18 oxidation pathway, 18- hydroxycortisol and 18-oxocortisol, has been examined in 10 patients with the disorder and compared to the normal C-18 oxidation products of corticosterone, aldosterone, and 18-hydroxycorticosterone. The technique, based on stable isotope dilution mass fragmentography, measured the tetrahydro urinary metabolites of aldosterone, 18- hydroxycorticosterone, and 18-oxocortisol and unmetabolized 18- hydroxycortisol. All 4 C-18 oxygenated corticosteroids were markedly elevated in the untreated state and showed rapid parallel suppression with low doses of glucocorticoid. The proportional changes in C-18 oxygenated cortisols together with aldosterone and 18- hydroxycorticosterone suggested the mechanism of a common catalytic site of a cytochrome P450 methyl oxidase serving both cortisol and corticosterone substrates. The ACTH-dependent secretion of the C-18 oxidation products of both corticosterone and cortisol in the disorder is attributed to the acquisition of methyl oxidase activity by the fasciculata zone, where there are abundant pools of these precursors.

This article has been cited by other articles:

				P. Mulatero, S. M. di Cella, T. A. Williams, A. Milan, G. Mengozzi, L. Chiandussi, C. E. Gomez-Sanchez, and F. Veglio Glucocorticoid Remediable Aldosteronism: Low Morbidity and Mortality in a Four-Generation Italian Pedigree J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3187 - 3191. [Abstract] [Full Text] [PDF]

				C. E. Fardella, M. Pinto, L. Mosso, C. Gomez-Sanchez, J. Jalil, and J. Montero Genetic Study of Patients with Dexamethasone-Suppressible Aldosteronism without the Chimeric CYP11B1/CYP11B2 Gene J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4805 - 4807. [Abstract] [Full Text] [PDF]

				A. Fisher, E. C. Friel, R. Bernhardt, C. Gomez-Sanchez, J. M. C. Connell, R. Fraser, and E. Davies Effects of 18-Hydroxylated Steroids on Corticosteroid Production by Human Aldosterone Synthase and 11{beta}-Hydroxylase J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4326 - 4329. [Abstract] [Full Text] [PDF]

				M. Stowasser, A. W. Bachmann, P. R. Huggard, T. R. Rossetti, and R. D. Gordon Treatment of Familial Hyperaldosteronism Type I: Only Partial Suppression of Adrenocorticotropin Required to Correct Hypertension J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3313 - 3318. [Abstract] [Full Text]

				M. Stowasser, A. W. Bachmann, P. R. Huggard, T. R. Rossetti, and R. D. Gordon Severity of Hypertension in Familial Hyperaldosteronism Type I: Relationship to Gender and Degree of Biochemical Disturbance J. Clin. Endocrinol. Metab., June 1, 2000; 85(6): 2160 - 2166. [Abstract] [Full Text]

				C. E. Fardella, L. Mosso, C. Gómez-Sánchez, P. Cortés, J. Soto, L. Gómez, M. Pinto, A. Huete, E. Oestreicher, A. Foradori, et al. Primary Hyperaldosteronism in Essential Hypertensives: Prevalence, Biochemical Profile, and Molecular Biology J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1863 - 1867. [Abstract] [Full Text]

				Glucocorticoid-Remediable Aldosteronism J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4341 - 4344. [Full Text]

				M. Stowasser, P. R. Huggard, T. R. Rossetti, A. W. Bachmann, and R. D. Gordon Biochemical Evidence of Aldosterone Overproduction and Abnormal Regulation in Normotensive Individuals with Familial Hyperaldosteronism Type I J. Clin. Endocrinol. Metab., November 1, 1999; 84(11): 4031 - 4036. [Abstract] [Full Text]

				P. Mulatero, K. M. Curnow, B. Aupetit-Faisant, M. Foekling, C. Gomez-Sanchez, F. Veglio, X. Jeunemaitre, P. Corvol, and L. Pascoe Recombinant CYP11B Genes Encode Enzymes that Can Catalyze Conversion of 11-Deoxycortisol to Cortisol, 18-Hydroxycortisol, and 18-Oxocortisol J. Clin. Endocrinol. Metab., November 1, 1998; 83(11): 3996 - 4001. [Abstract] [Full Text]

				S. H.M. van Uum, A. R.M.M. Hermus, P. Smits, T. Thien, and J. W.M. Lenders The role of 11{beta}-hydroxysteroid dehydrogenase in the pathogenesis of hypertension Cardiovasc Res, April 1, 1998; 38(1): 16 - 24. [Abstract] [Full Text] [PDF]

				W. R. Litchfield, M. I. New, C. Coolidge, R. P. Lifton, and R. G. Dluhy Evaluation of the Dexamethasone Suppression Test for the Diagnosis of Glucocorticoid-Remediable Aldosteronism J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3570 - 3573. [Abstract] [Full Text] [PDF]

				M. Stowasser, M. G. Gartside, W. L. Taylor, T. J. Tunny, and R. D. Gordon In Familial Hyperaldosteronism Type I, Hybrid Gene-Induced Aldosterone Production Dominates That Induced by Wild-Type Genes J. Clin. Endocrinol. Metab., November 1, 1997; 82(11): 3670 - 3676. [Abstract] [Full Text] [PDF]

				P. C. White Inherited Forms of Mineralocorticoid Hypertension Hypertension, December 1, 1996; 28(6): 927 - 936. [Abstract] [Full Text]

				P. C. White Disorders of Aldosterone Biosynthesis and Action N. Engl. J. Med., July 28, 1994; 331(4): 250 - 258. [Full Text]