This Article Full Text 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 Jamieson, A. Articles by Connell, J. M. C. Search for Related Content PubMed PubMed Citation Articles by Jamieson, A. Articles by Connell, J. M. C.

Apparent Cortisone Reductase Deficiency: A Functional Defect in 11ß-Hydroxysteroid Dehydrogenase Type 1¹

Department of Medicine and Therapeutics (A.J.) and MRC Blood Pressure Group (R.F., P.C.W., J.M.C.C.), Western Infirmary, Glasgow G11 6NT; Department of Pathological Biochemistry (A.M.W.), Royal Infirmary, Glasgow G4 0SF; Department of Medical Sciences (B.R.W.), University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom; and University of Texas Southwestern Medical Center (B.S.N., P.C.W.), Dallas, Texas 75235-9063

Address correspondence and requests for reprints to: Dr. Robert Fraser, MRC Blood Pressure Group, Western Infirmary, Glasgow G11 6NT, Scotland; E-mail: rfraser{at}clinmed.gla.ac.uk

A 36-yr-old woman was referred to the endocrine clinic for investigation of oligomenorrhea, hirsutism, and acne. She was plethoric and overweight with central fat distribution. Plasma cortisol was normal, but her adrenal glands were enlarged (CT scan). Urinary tetrahydrocortisone excretion rate was consistently high, raising the possibility of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) deficiency. In addition, 5ß- reduction of cortisol and cortisone was markedly enhanced. The levels of all cortisol metabolites were suppressed normally with dexamethasone, but conversion of oral cortisone acetate to plasma cortisol was delayed and subnormal compared with that of healthy volunteers. This was accompanied by a larger than normal increase in plasma cortisone concentration. Thus, the defect appears to be in 11ß-HSD1 activity and not in 5ß-reductase activity. Three close relatives of the subject showed no comparable abnormalities, and analysis of the coding region and exon/intron boundaries of the 11ß-HSD1 gene of the case revealed no differences from the consensus sequence. The defect may lie outside the coding region. Alternatively, some other inherited or acquired defect may lead to inhibition of this enzyme system.

This article has been cited by other articles:

				G. G. Lavery, E. A. Walker, A. Tiganescu, J. P. Ride, C. H. L. Shackleton, J. W. Tomlinson, J. M. C. Connell, D. W. Ray, A. Biason-Lauber, E. M. Malunowicz, et al. Steroid Biomarkers and Genetic Studies Reveal Inactivating Mutations in Hexose-6-Phosphate Dehydrogenase in Patients with Cortisone Reductase Deficiency J. Clin. Endocrinol. Metab., October 1, 2008; 93(10): 3827 - 3832. [Abstract] [Full Text] [PDF]

				P. C. White Genotypes at 11{beta}-Hydroxysteroid Dehydrogenase Type 11B1 and Hexose-6-Phosphate Dehydrogenase Loci Are Not Risk Factors for Apparent Cortisone Reductase Deficiency in a Large Population-Based Sample J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5880 - 5883. [Abstract] [Full Text] [PDF]

				M. Quinkler, D. Zehnder, J. Lepenies, M. D Petrelli, J. S Moore, S. V Hughes, P. Cockwell, M. Hewison, and P. M Stewart Expression of renal 11{beta}-hydroxysteroid dehydrogenase type 2 is decreased in patients with impaired renal function Eur. J. Endocrinol., August 1, 2005; 153(2): 291 - 299. [Abstract] [Full Text] [PDF]

				N. Draper and P. M Stewart 11{beta}-Hydroxysteroid dehydrogenase and the pre-receptor regulation of corticosteroid hormone action J. Endocrinol., August 1, 2005; 186(2): 251 - 271. [Abstract] [Full Text] [PDF]

				I. J Bujalska, N. Draper, Z. Michailidou, J. W Tomlinson, P. C White, K. E Chapman, E. A Walker, and P. M Stewart Hexose-6-phosphate dehydrogenase confers oxo-reductase activity upon 11{beta}-hydroxysteroid dehydrogenase type 1 J. Mol. Endocrinol., June 1, 2005; 34(3): 675 - 684. [Abstract] [Full Text] [PDF]

				R. Andrew, J. Westerbacka, J. Wahren, H. Yki-Jarvinen, and B. R. Walker The Contribution of Visceral Adipose Tissue to Splanchnic Cortisol Production in Healthy Humans Diabetes, May 1, 2005; 54(5): 1364 - 1370. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, E. A. Walker, I. J. Bujalska, N. Draper, G. G. Lavery, M. S. Cooper, M. Hewison, and P. M. Stewart 11{beta}-Hydroxysteroid Dehydrogenase Type 1: A Tissue-Specific Regulator of Glucocorticoid Response Endocr. Rev., October 1, 2004; 25(5): 831 - 866. [Abstract] [Full Text] [PDF]

				G. Banhegyi, A. Benedetti, R. Fulceri, and S. Senesi Cooperativity between 11{beta}-Hydroxysteroid Dehydrogenase Type 1 and Hexose-6-phosphate Dehydrogenase in the Lumen of the Endoplasmic Reticulum J. Biol. Chem., June 25, 2004; 279(26): 27017 - 27021. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, J. S. Moore, P. M. S. Clark, G. Holder, L. Shakespeare, and P. M. Stewart Weight Loss Increases 11{beta}-Hydroxysteroid Dehydrogenase Type 1 Expression in Human Adipose Tissue J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2711 - 2716. [Abstract] [Full Text] [PDF]

				G. P. Chrousos Is 11{beta}-hydroxysteroid dehydrogenase type 1 a good therapeutic target for blockade of glucocorticoid actions? PNAS, April 27, 2004; 101(17): 6329 - 6330. [Full Text] [PDF]

				J. R. Seckl, N. M. Morton, K. E. Chapman, and B. R. Walker Glucocorticoids and 11beta-Hydroxysteroid Dehydrogenase in Adipose Tissue Recent Prog. Horm. Res., January 1, 2004; 59(1): 359 - 393. [Abstract] [Full Text]

				M. N. Kerstens, G. Navis, and R. P. F. Dullaart Does a reduced 11{beta}HSD type 2 activity contribute to sodium retention in the nephrotic syndrome? Nephrol. Dial. Transplant., March 1, 2003; 18(3): 620 - 620. [Full Text] [PDF]

				T. Dimitriou, C. Maser-Gluth, and T. Remer Adrenocortical activity in healthy children is associated with fat mass Am. J. Clinical Nutrition, March 1, 2003; 77(3): 731 - 736. [Abstract] [Full Text] [PDF]

				B. Vogt, B. M. Frey, and F. J. Frey Reply Nephrol. Dial. Transplant., March 1, 2003; 18(3): 620 - 621. [Full Text] [PDF]

				J. W. Tomlinson, B. Sinha, I. Bujalska, M. Hewison, and P. M. Stewart Expression of 11{beta}-Hydroxysteroid Dehydrogenase Type 1 in Adipose Tissue Is Not Increased in Human Obesity J. Clin. Endocrinol. Metab., December 1, 2002; 87(12): 5630 - 5635. [Abstract] [Full Text] [PDF]

				J. W. Tomlinson, N. Draper, J. Mackie, A. P. Johnson, G. Holder, P. Wood, and P. M. Stewart Absence of Cushingoid Phenotype in a Patient with Cushing's Disease due to Defective Cortisone to Cortisol Conversion J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 57 - 62. [Abstract] [Full Text] [PDF]

				R. Andrew, K. Smith, G. C. Jones, and B. R. Walker Distinguishing the Activities of 11{beta}-Hydroxysteroid Dehydrogenases in Vivo Using Isotopically Labeled Cortisol J. Clin. Endocrinol. Metab., January 1, 2002; 87(1): 277 - 285. [Abstract] [Full Text] [PDF]

				A. Johansson, R. Andrew, H. Forsberg, K. Cederquist, B. R. Walker, and T. Olsson Glucocorticoid Metabolism and Adrenocortical Reactivity to ACTH in Myotonic Dystrophy J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4276 - 4283. [Abstract] [Full Text] [PDF]

				J. R. Seckl and B. R. Walker Minireview: 11{beta}-Hydroxysteroid Dehydrogenase Type 1-- A Tissue-Specific Amplifier of Glucocorticoid Action Endocrinology, April 1, 2001; 142(4): 1371 - 1376. [Abstract] [Full Text]

				A. Nordenstrom, C. Marcus, M. Axelson, A. Wedell, and M. Ritzén Defective 11{beta}-HSD Reductase Activity in a Patient with Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 1426 - 1427. [Full Text]