This Article Full Text (PDF) Submit a related Letter to the Editor 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 LAMBERTS, S. W.J. Articles by DE JONG, F. H. Search for Related Content PubMed PubMed Citation Articles by LAMBERTS, S. W.J. Articles by DE JONG, F. H.

Familial Cortisol Resistance: Differential Diagnostic and Therapeutic Aspects

Department of Medicine, Erasmus University, Rotterdam, The Netherlands Rotterdam, The Netherlands

Address all correspondence and requests for reprints to:Steven W.J. Lamberts, M.D., Department of Medicine, University Hospital Dijkzigt, 40 Dr. Molewaterplein, 3015 GD Rotterdam, The Netherlands.

A 26-yr-old woman presented with hirsutism,male pattern scalp baldness ("geheimratsecken"), and menstrualirregularities. She had no hypertension or other signs and symptomsof Cushings syndrome. Plasma cortisol levels were greatlyelevated and did not suppress normally in response to dexamethasone.Cortisol binding to transcortin was normal. Plasmaandrostenedione and testosterone levels were also increased, but17-hyroxyprogesterone and aldosterone levels were normal. Furtherstudies revealed an increased cortisol production rate, increased24-h urinary cortisol excretion, increased plasma ACTHlevels, a normal diurnal rhythm of cortisol at an elevated level,and normal increments of plasma ACTH, cortisol, GH, and PRLin response to insulin-induced hypoglycemia. The father andtwo brothers also had increased plasma cortisol levels, which didnot suppress normally in response to dexamethasone.

Chronic therapy with dexamethasone (at first 1 and later 0.5mg, three times daily) for more than 30 weeks resulted indecreased hirsutism, normalization of scalp hair and menstrualcyclicity, and normal plasma testosterone and androstenedionelevels. No signs or symptoms of Cushing’s syndrome developed,and the central regulation of secretion of ACTH, cortisol, GH,and PRL (insulin test, diurnal rhythm) remained qualitatively normal at a lower set-point.

We conclude that this patient had autosomal dominantlyinherited hereditary (partial) cortisol insensitivity, which hadresulted in increased adrenocortical cortisol and androgen secretion.The latter had not resulted in clinical symptoms in thethree afflicted male members of the family, but had in thepropositus. The results also indicate the potential usefulness ofthe insulin test in distinguishing this disorder from Cushing’s disease.

Received March 24, 1986.

This article has been cited by other articles:

				J. Zhang, R. Ge, C. Matte-Martone, J. Goodwin, W. D. Shlomchik, M. J. Mamula, A. Kooshkabadi, M. P. Hardy, and D. Geller Characterization of a Novel Gain of Function Glucocorticoid Receptor Knock-in Mouse J. Biol. Chem., March 6, 2009; 284(10): 6249 - 6259. [Abstract] [Full Text] [PDF]

				B. B. Mendonca, M. V. Leite, M. de Castro, T. Kino, L. L. K. Elias, T. A. S. Bachega, I. J. P. Arnhold, G. P. Chrousos, and A. C. Latronico Female Pseudohermaphroditism Caused by a Novel Homozygous Missense Mutation of the GR Gene J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1805 - 1809. [Abstract] [Full Text] [PDF]

				T. Kino, R. H. Stauber, J. H. Resau, G. N. Pavlakis, and G. P. Chrousos Pathologic Human GR Mutant Has a Transdominant Negative Effect on the Wild-Type GR by Inhibiting Its Translocation into the Nucleus: Importance of the Ligand-Binding Domain for Intracellular GR Trafficking J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5600 - 5608. [Abstract] [Full Text] [PDF]

				N. A. T. M. Huizenga, P. de Lange, J. W. Koper, W. W. de Herder, R. Abs, J. H. L. M. v. Kasteren, F. H. de Jong, and S. W. J. Lamberts Five Patients with Biochemical and/or Clinical Generalized Glucocorticoid Resistance without Alterations in the Glucocorticoid Receptor Gene J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 2076 - 2081. [Abstract] [Full Text]

				P. de Lange, J. W. Koper, N. A. T. M. Huizenga, A. O. Brinkmann, F. H. de Jong, M. Karl, G. P. Chrousos, and S. W. J. Lamberts Differential Hormone-Dependent Transcriptional Activation and -Repression by Naturally Occurring Human Glucocorticoid Receptor Variants Mol. Endocrinol., July 1, 1997; 11(8): 1156 - 1164. [Abstract] [Full Text]