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17-Hydroxylase Deficiency Syndrome Medication

  • Author: J Paul Frindik, MD, FACE; Chief Editor: Stephen Kemp, MD, PhD  more...
 
Updated: Dec 18, 2015
 

Medication Summary

Exogenous glucocorticoid therapy is the treatment of choice.

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Exogenous Glucocorticoids

Class Summary

Exogenous glucocorticoid therapy suppresses adrenocorticotropic hormone (ACTH) secretion, decreases 11-deoxycorticosterone (11-DOC) and corticosterone levels, and normalizes serum K levels and blood pressure. Patients tend to respond to smaller doses of glucocorticoids than those required in other forms of congenital adrenal hyperplasia, possibly due to the glucocorticoid activity of endogenous corticosterone. Dosages are somewhat empirical and must be individualized based on clinical findings, growth, skeletal maturation, and hormonal data, including monitoring of 11-DOC and corticosterone levels.

Hydrocortisone (Hydrocortone, A-Hydrocort)

 

Hydrocortisone is the drug of choice for infants and children. Longer-acting preparations (eg, prednisone, dexamethasone) are difficult to titrate and can lead to overtreatment and growth suppression.

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Contributor Information and Disclosures
Author

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

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

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 Medical Association, American Pediatric Society, Association of Clinical Scientists, Endocrine Society, Florida Medical Association, Pediatric Endocrine Society, Society for Pediatric Research, Southern Society for Pediatric Research, Society for the Study of Reproduction, American Federation for Clinical Research, Pituitary Society

Disclosure: Nothing to disclose.

Chief Editor

Stephen Kemp, MD, PhD Former 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, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

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 Genomics, American Society of Human Genetics

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. 2002 Nov. 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. 2007 Mar. 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. 2008 Jul. 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. 2008 Feb. 21(2):185-90. [Medline].

  5. Krone N, Arlt W. Genetics of congenital adrenal hyperplasia. Best Pract Res Clin Endocrinol Metab. 2009 Apr. 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. 2011 Jun 11. 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. 2012 Mar. 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. 2004 Jan. 89(1):49-60. [Medline]. [Full Text].

  9. Kim YM, Kang M, Choi JH, Lee BH, Kim GH, Ohn JH, et al. A review of the literature on common CYP17A1 mutations in adults with 17-hydroxylase/17,20-lyase deficiency, a case series of such mutations among Koreans and functional characteristics of a novel mutation. Metabolism. 2014 Jan. 63 (1):42-9. [Medline].

  10. Zhang M, Sun S, Liu Y, Zhang H, Jiao Y, Wang W, et al. New, recurrent, and prevalent mutations: Clinical and molecular characterization of 26 Chinese patients with 17alpha-hydroxylase/17,20-lyase deficiency. J Steroid Biochem Mol Biol. 2015 Jun. 150:11-6. [Medline].

  11. 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].

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

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

  14. 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. 2005 Jan. 90(1):414-26. [Medline].

  15. Auchus RJ. The classic and nonclassic concenital adrenal hyperplasias. Endocr Pract. 2015 Apr. 21 (4):383-9. [Medline].

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

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

  18. 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. 1997 Oct-Dec. 89(10-12):197-9. [Medline].

  19. 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. 2008 Sep. 93(9):3584-8. [Medline].

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

  21. 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].

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

  23. 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. 1992 Apr. 89(1):95-6. [Medline].

  24. Reisch N, Idkowiak J, Hughes BA, Ivison HE, Abdul-Rahman OA, Hendon LG, et al. Prenatal diagnosis of congenital adrenal hyperplasia caused by P450 oxidoreductase deficiency. J Clin Endocrinol Metab. 2013 Mar. 98(3):E528-36. [Medline]. [Full Text].

  25. Marsh CA, Auchus RJ. Fertility in patients with genetic deficiencies of cytochrome P450c17 (CYP17A1): combined 17-hydroxylase/17,20-lyase deficiency and isolated 17,20-lyase deficiency. Fertil Steril. 2014 Feb. 101 (2):317-22. [Medline].

  26. Achermann JC, Hughes LA. Disorders of Sex Development. Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa: Saunders; 2011. 868-935.

  27. Stewart PM, Krone NP. The Adrenal Cortex. Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa: Saunders; 2011. 479-545.

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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.
 
 
 
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