17-Hydroxylase Deficiency Syndrome Differential Diagnoses

  • Author: J Paul Frindik, MD, FACE; Chief Editor: Stephen Kemp, MD, PhD   more...
 
Updated: May 10, 2012
 
 

Diagnostic Considerations

Impaired hepatic drug metabolism may be a problem in patients with P450 oxidoreductase (POR) deficiency[9] , but further study is necessary before specific recommendations can be made.

Differential Diagnoses

Proceed to Workup
 
 
Contributor Information and Disclosures
Author

J Paul Frindik, MD, FACE  Associate Professor, Department of Pediatrics, University of Arkansas for Medical Sciences

J Paul Frindik, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists

Disclosure: Nothing to disclose.

Specialty Editor Board

Erawati V Bawle, MD, FAAP, FACMG  Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry B Bercu, MD  Professor, Departments of Pediatrics, Molecular Pharmacology and Physiology, University of South Florida College of Medicine, All Children's Hospital

Barry B Bercu, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Federation for Clinical Research, American Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Pituitary Society, Society for Pediatric Research, Society for the Study of Reproduction, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Merrily P M Poth, MD  Professor, Department of Pediatrics and Neuroscience, Uniformed Services University of the Health Sciences

Merrily P M Poth, MD is a member of the following medical societies: American Academy of Pediatrics, Endocrine Society, and Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD  Professor, Department of Pediatrics, Section of Pediatric Endocrinology, University of Arkansas for Medical Sciences College of Medicine, Arkansas Children's Hospital

Stephen Kemp, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, American Pediatric Society, Endocrine Society, Phi Beta Kappa, Southern Medical Association, and Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

References

  1. Auchus RJ, Gupta MK. Towards a unifying mechanism for CYP17 mutations that cause isolated 17,20-lyasedeficiency. Endocr Res. Nov 2002;28(4):443-7. [Medline].

  2. Rosa S, Duff C, Meyer M, et al. P450c17 deficiency: clinical and molecular characterization of six patients. J Clin Endocrinol Metab. Mar 2007;92(3):1000-7. [Medline].

  3. Tian Q, Zhang Y, Lu Z. Partial 17alpha-hydroxylase/17,20-lyase deficiency-clinical report of five Chinese 46,XX cases. Gynecol Endocrinol. Jul 2008;24(7):362-7. [Medline].

  4. Bhangoo A, Aisenberg J, Chartoffe A, et al. Novel mutation in cytochrome P450c17 causes complete combined 17alpha-hydroxylase/17,20-lyase deficiency. J Pediatr Endocrinol Metab. Feb 2008;21(2):185-90. [Medline].

  5. Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. Apr 2009;23(2):181-92. [Medline].

  6. Bao X, Ding H, Xu Y, Cui G, He Y, Yu X, et al. Prevalence of common mutations in the CYP17A1 gene in Chinese Han population. Clin Chim Acta. Jun 11 2011;412(13-14):1240-3. [Medline].

  7. Tian Q, Yao F, Zhang Y, Tseng H, Lang J. Molecular study of five Chinese patients with 46XX partial 17a-hydroxylase/17,20-lyase deficiency. Gynecol Endocrinol. Mar 2012;28(3):234-8. [Medline].

  8. Costa-Santos M, Kater CE, Auchus RJ, Brazilian Congenital Adrenal Hyperplasia Multicenter Study Group. Two prevalent CYP17 mutations and genotype-phenotype correlations in 24 Brazilian patients with 17-hydroxylase deficiency. J Clin Endocrinol Metab. Jan 2004;89(1):49-60. [Medline]. [Full Text].

  9. Fluck CE, Pandey AV, Huang N, et al. P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia. Endocr Dev. 2008;13:67-81. [Medline].

  10. Scott RR, Miller WL. Genetic and clinical features of p450 oxidoreductase deficiency. Horm Res. 2008;69(5):266-75. [Medline].

  11. Arlt W. P450 oxidoreductase deficiency and Antley-Bixler syndrome. Rev Endocr Metab Disord. Dec 2007;8(4):301-7. [Medline].

  12. Fukami M, Horikawa R, Nagai T, Tanaka T, Naiki Y, Sato N, et al. Cytochrome P450 oxidoreductase gene mutations and Antley-Bixler syndrome with abnormal genitalia and/or impaired steroidogenesis: molecular and clinical studies in 10 patients. J Clin Endocrinol Metab. Jan 2005;90(1):414-26. [Medline].

  13. Aydin Z, Ozturk S, Gursu M, Uzun S, Karadag S, Kazancioglu R. Male pseudohermaphroditism as a cause of secondary hypertension: a case report. Endocrine. Aug 2010;38(1):100-3. [Medline].

  14. Kandemir N, Yordam N. Congenital adrenal hyperplasia in Turkey: a review of 273 patients. Acta Paediatr. Jan 1997;86(1):22-5. [Medline].

  15. Rosado A, Alegre M, Colon G. [Male pseudohermaphroditism caused by enzymatic deficiency of 17-alpha- hydroxylase. 1st case reported in Puerto Rico]. Bol Asoc Med P R. Oct-Dec 1997;89(10-12):197-9. [Medline].

  16. Hershkovitz E, Parvari R, Wudy SA, et al. Homozygous Mutation G539R in the Gene for P450 Oxidoreductase in a Family Previously Diagnosed as Having 17,20-Lyase Deficiency. J Clin Endocrinol Metab. Sep 2008;93(9):3584-8. [Medline].

  17. Monig H, Sippell W. Congenital adrenal hyperplasia in adulthood: do men need to continue treatment?. Horm Res. 2005;64 Suppl 2:71-3. [Medline].

  18. Ross RJ, Rostami-Hodjegan A. Timing and type of glucocorticoid replacement in adult congenital adrenal hyperplasia. Horm Res. 2005;64 Suppl 2:67-70. [Medline].

  19. Philip J, Anjali N, Thomas S, et al. 17-Alpha hydroxylase deficiency: an unusual cause of secondary amenorrhoea. Aust N Z J Obstet Gynaecol. Oct 2004;44(5):477-8. [Medline].

  20. Imai T, Yanase T, Waterman MR, et al. Canadian Mennonites and individuals residing in the Friesland region of The Netherlands share the same molecular basis of 17 alpha-hydroxylase deficiency. Hum Genet. Apr 1992;89(1):95-6. [Medline].

  21. Biglieri EG, Herron MA, Brust N. 17-hydroxylation deficiency in man. J Clin Invest. Dec 1966;45(12):1946-54. [Medline]. [Full Text].

  22. Ducharme JR, Forest MG. Normal pubertal development. In: Pediatric Endocrinology: Physiology, Pathophysiology & Clinical Aspects. 2nd ed. 1993:372-86.

  23. Forest MG, Lecornu M, de Peretti E. Familial male pseudohermaphroditism due to 17-20-desmolase deficiency. I. In vivo endocrine studies. J Clin Endocrinol Metab. May 1980;50(5):826-33. [Medline].

  24. Grumbach MM, Conte FA. Disorders of sex differentiation. In: Williams Textbook of Endocrinology. 8th ed. 1992:853-951.

  25. Kater CE, Biglieri EG. Disorders of steroid 17 alpha-hydroxylase deficiency. Endocrinol Metab Clin North Am. Jun 1994;23(2):341-57. [Medline].

  26. Orth DN, Kovacs WJ, Debold CR. The adrenal cortex. In: Williams Textbook of Endocrinology. 8th ed. 1992:489-619.

 
Previous
Next
 
Normal adrenal steroid biosynthesis results in 3 products: mineralocorticoids (aldosterone), glucocorticoids (cortisol), and androgens (androstenedione). Cortisol production is regulated by feedback with adrenocorticotropic hormone (ACTH). ACTH stimulates the enzyme P-450scc (20,22 desmolase), with subsequently increased production of all adrenal steroids.
Representation of typical congenital adrenal hyperplasia (CAH). This example shows a deficiency in both the mineralocorticoid and glucocorticoid pathways. Decreased serum cortisol levels stimulate adrenocorticotropic hormone (ACTH) release via negative feedback. Increased ACTH secretion causes overproduction of adrenal steroids preceding the missing enzyme as well as those not requiring the missing enzyme. The example depicts a deficiency of 21-hydroxylase, resulting in deficient mineralocorticoid and glucocorticoid production and excessive androgen production.
C-17α-hydroxylase is necessary to convert pregnenolone to 17-hydroxypregnenolone (17-OH Preg) and progesterone to 17-hydroxyprogesterone (17-OH Prog). Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production. Low levels of cortisol result in increased adrenocorticotropic hormone (ACTH) stimulation of steroids prior to the 17-hydroxylase step, resulting in increased accumulation and secretion of 17-deoxysteroids by the zona fasciculata, including pregnenolone, progesterone, deoxycorticosterone (DOC), and corticosterone.
Graphic illustration of deficiency. Absence of C-17α-hydroxylase impairs all sex steroid and cortisol production.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.