This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Charmandari, E. Articles by Chrousos, G. P. Search for Related Content PubMed PubMed Citation Articles by Charmandari, E. Articles by Chrousos, G. P.

Endocrinologic and Psychologic Evaluation of 21-Hydroxylase Deficiency Carriers and Matched Normal Subjects: Evidence for Physical and/or Psychologic Vulnerability to Stress

Pediatric and Reproductive Endocrinology Branch (E.C., D.P.M., M.F.K., G.P.C.), National Institute of Child Health and Human Development, The Warren Grant Magnuson Clinical Center (D.P.M.), and Clinical Neuroendocrinology Branch (P.J.N., P.E.M., A.H., P.W.G.), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Evangelia Charmandari, Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, 10 Center Drive, Building 10, Room 9D42, Bethesda, Maryland 20892-1583.

Carriers of congenital adrenal hyperplasia due to 21-hydroxylase (21-OH) deficiency demonstrate increased secretion of cortisol precursors after ACTH stimulation, suggestive of impaired cortisol production and compensatory increases in hypothalamic CRH secretion. Because both cortisol and CRH have behavioral effects, and hypothalamic CRH hypersecretion has been associated with chronic states of anxiety and depression, we performed endocrine and psychologic studies in consecutively admitted parents of patients with classic congenital adrenal hyperplasia due to 21-OH deficiency and parents of children with other chronic endocrine disorders. The number of excluded carriers because of pathologic reasons was higher than that of controls (P = 0.05). Carriers of 21-OH deficiency had a lower mean 24-h urinary free cortisol excretion (26.4 ± 3.4 vs. 42.7 ± 6.4 µg/d, P = 0.03) and higher peak ACTH (75.7 ± 8.1 vs. 54.2 ± 5.9 pg/ml, P = 0.04) and 17-hydroxyprogesterone (224.2 ± 28.1 vs. 107.1 ± 12.5 ng/dl, P < 0.001) concentrations post CRH stimulation than control subjects. Cortisol and androstenedione responses were similar in the two groups. Psychometric assessment performed by administering the State-Anxiety Inventory, Beck Depression Inventory, Profile of Mood States, Symptom Checklist-90R, and Temperament and Character Inventory revealed no differences between the two subject groups. Interestingly, a stepwise multiple linear regression model analysis in each population sample revealed that in carriers of 21-OH deficiency but not in the control subjects, a lower mean 24-h urinary free cortisol excretion and a higher ACTH response to ovine CRH stimulation predicted predisposition to obsessive-compulsive behavior, novelty seeking, reward dependence, and harm avoidance. We conclude that carriers of 21-OH deficiency appear to have mild hypocortisolism and compensatory changes of CRH secretion secondary to lower cortisol concentrations. These changes might predict mild predisposition of these subjects to physical and psychologic pathology, suggesting that larger studies are necessary.

D.P.M. is a Commissioned Officer in the U.S. Public Health Service.

Abbreviations: AUC, Total area under the plasma concentration curve of a given hormone vs. time; CAH, congenital adrenal hyperplasia; CBG, cortisol binding globulin; CNS, central nervous system; CV, coefficient of variation; LC, locus ceruleus; NE, norepinephrine; o, ovine; 21-OH, 21-hydroxylase; 17-OHP, 17-hydroxyprogesterone; POMS, Profile of Mood States; STAI, State-Anxiety Inventory; UFC, urinary free cortisol.

This article has been cited by other articles:

				A. M. Rasmusson, M. R. Picciotto, and S. Krishnan-Sarin Smoking as a complex but critical covariate in neurobiological studies of posttraumatic stress disorders: a review J Psychopharmacol, September 1, 2006; 20(5): 693 - 707. [Abstract] [PDF]

				E. Charmandari, A. Raji, T. Kino, T. Ichijo, A. Tiulpakov, K. Zachman, and G. P. Chrousos A Novel Point Mutation in the Ligand-Binding Domain (LBD) of the Human Glucocorticoid Receptor (hGR) Causing Generalized Glucocorticoid Resistance: The Importance of the C Terminus of hGR LBD in Conferring Transactivational Activity J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3696 - 3705. [Abstract] [Full Text] [PDF]