Exp Clin Endocrinol Diabetes 2004; 112(5): 236-240
DOI: 10.1055/s-2004-817969
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Applicability of the SHBG Androgen Sensitivity Test in the Differential Diagnosis of 46,XY Gonadal Dysgenesis, True Hermaphroditism, and Androgen Insensitivity Syndrome

A. Krause1 , G. H. G. Sinnecker2 , O. Hiort3 , B. Thamm4 , W. Hoepffner1
  • 1Children's Hospital of the University of Leipzig, Leipzig, Germany
  • 2Department of Paediatric and Adolescent Medicine, Klinikum der Stadt Wolfsburg, Wolfsburg, Germany
  • 3Children's Hospital of the University of Lübeck, Lübeck, Germany
  • 4Institute of Human Genetics of the University of Leipzig, Leipzig, Germany
Further Information

Publication History

Received: March 20, 2003 First decision: July 8, 2003

Accepted: October 30, 2003

Publication Date:
14 May 2004 (online)

Abstract

The sex hormone-binding globulin (SHBG) androgen sensitivity test has been used as a simple method to assess androgen receptor function in vivo. After a short term oral administration of the anabolic-androgenic steroid stanozolol the mean nadir serum concentration of SHBG is used as a measure of androgen response. We performed this test in order to evaluate its applicability in 16 patients with intersexual genital status: eleven with 46,XY gonadal dysgenesis and three with true hermaphroditism (group I), and in two patients with androgen insensitivity syndrome (AIS, group II). Ten healthy adult volunteers served as controls. In the two patients with AIS (group II) we found a diminished decrease of serum SHBG to 80.1 % and 80.7 %, respectively, indicating slight residual androgen responsiveness. In eleven patients of group I who were not on hormone replacement therapy, a mean nadir level of 51.7 ± 8.7 % was found. In the controls the mean nadir serum SHBG level was significantly higher (62.7 ± 5.2 %), probably due to interference of endogenous androgens and contraceptive medication with the stanozolol-induced SHBG decrease. In three gonadectomised patients who were on hormone replacement therapy the initial SHBG concentration was increased (513.5 ± 239.1 nmol/l); the mean nadir SHBG concentration of 45.6 ± 9.8 % of the initial level indicates an increased sensitivity of the test in patients in whom the counteracting ovarian androgens are absent. Our findings confirm that under standard test conditions the SHBG androgen sensitivity test is a simple diagnostic tool for the detection of androgen receptor malfunction.

References

  • 1 Belgorosky A, Rivarola M A. Sex hormone binding globulin response to testosterone. An androgen sensitivity test.  Acta Endocrinol (Copenh). 1985;  109 130-138
  • 2 Hampl R, Starka L, Kalvachova B, Lachman M, Snajderova M, Lisa L, Zapletalova J, Hill M. Evaluation of SHBG test for disclosure of insensitivity to androgens.  Endocr Regul. 1193;  27 65-70
  • 3 Hiort O, Holterhus P M, Sinnecker G HG, Kruse K. Androgenresistenzsyndrome - Klinische und molekulare Grundlagen.  Dt Ärztebl. 1999;  96 686-692
  • 4 Hiort O, Huang Q, Sinnecker G HG, Sadeghi-Nejad A, Kruse K, Wolfe H J, Yandell D W. Single strand conformation polymorphism analysis of androgen receptor gene mutations in patients with androgen insensitivity syndromes: Application for diagnosis, genetic counseling, and therapy.  J Clin Endocrinol Metab. 1993;  77 262-266
  • 5 Holterhus P M, Brüggenwirth H T, Hiort O. et al . Mosaicism due to a somatic mutation of the androgen receptor gene determines phenotype in androgen insensitivity syndrome.  J Clin Endocrinol Metab. 1997;  82 3584-3589
  • 6 Jäger R J, Anvret M, Hall K, Scherer G. A human XY female with a frame shift mutation in the candidate testis-determining gene SRY.  Nature. 1990;  348 452-454
  • 7 Jung-Hoffmann C, Kuhl H. Divergent effects of two low-dose oral contraceptives on sex hormone-binding globulin and free testosterone.  Am J Obstet Gynecol. 1987;  156 199-203
  • 8 Kuhl H, Jung-Hoffmann C, Heidt F. Alterations in the serum levels of gestodene and SHBG during 12 cycles of treatment with 30 µg ethinylestradiol and 75 µg gestodene.  Contraception. 1988;  38 477-486
  • 9 Limpongsanurak S, Jenkins N, Fortherby K. Effect of contraceptive steroids on serum levels of sex hormone binding globulin and caeruloplasmin.  Curr Med Res Opin. 1981;  7 185-191
  • 10 Prader A. Der Genitalbefund beim Pseudohermaphroditismus femininus des kongenitalen adrenogenitalen Syndroms.  Helv Paediatr Acta. 1954;  9 231-248
  • 11 Rodien P, Mebarki F, Mowszowicz I. Different phenotypes in a family with androgen insensitivity caused by the same M780I point mutation in the androgen receptor gene.  J Clin Endocrinol Metab. 1996;  81 2994-2998
  • 12 Sinnecker G HG, Hiort O, Nitsche E M, Holterhus P M, Kruse K. Functional assessment and clinical classification of androgen sensitivity in patients with mutations of the androgen receptor gene.  Eur J Pediatr. 1997;  156 7-14
  • 13 Sinnecker G HG, Köhler S. Sex hormone-binding globulin response to the anabolic steroid stanozolol: Evidence for its suitability as a biological androgen sensitivity test.  J Clin Endocrinol Metab. 1989;  68 1195-1200
  • 14 Sinnecker G HG, Lork S, Willig R P. Gonadal and adrenal steroids and their binding globulins SHBG and CBG in patients treated with ethinylestradiol and testosterone oenanthate.  Acta Endocrinol (Copenh). 1986;  111 18-20
  • 15 Thamm B. Direct non-isotopic sequencing of OCR products or standards. Köhler T, Lassner D, Rost AK, Thamm B, Pustoweit B, Remke D Quantification of mRNA by Polymerase Chain Reaction. Berlin, Heidelberg, New York; Springer 1995: 39-51

M. D. Wolfgang Hoepffner

University of Leipzig
Children's Hospital

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04317 Leipzig

Germany

Phone: + 493419726222

Fax: + 49 34 19 72 62 29

Email: ruth.gausche@medizin.uni-leipzig.de

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