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Familial Partial 17,20-Desmolase and 17α-Hydroxylase Deficiency Presenting as Infertility

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Abstract

Purpose : Females with 17α-hydroxylase/17,20-desmolase deficiency normally present with amenorrhea, sexual infantilism, hypertension, and hypokalemia. We report on a new clinical presentation of this combined enzymatic defect.

Methods : Four Jewish women from two unrelated families presented with primary infertility. All patients exhibited a normal phenotype, blood pressure, and serum potassium levels, with abnormally high follicular phase serum progesterone and low E2 levels. In order to characterize the underlying defect, the following steps were undertaken: 1) ovarian suppression by GnRH agonist, 2) adrenal suppression by dexamethasone, 3) ovarian stimulation by gonadotropins, 4) adrenal stimulation by ACTH, 5) hormonal assessment of follicular fluid aspirates, and 6) assessment of in vitro E2 production by luteinized granulosa cells.

Results : The clinical characteristics and endocrine testing results support the diagnosis of a partial deficiency in 17α-hydroxylase/17,20-desmolase activities, shared by the adrenal gland and the ovaries.

Conclusions : Female infertility can be the first and sole clinical manifestation of this enzymatic defect. Its exact nature and prevalence remain to be determined.

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REFERENCES

  1. Eldar-Geva T, Hurwitz A, Vecsei P, Palti Z, Milwidsky A, Rosler A: Secondary biosynthetic defects in women with late-onset congenital adrenal hyperplasia. N Engl J Med 1990;323:855–863

    Google Scholar 

  2. Bradshaw KD, Waterman MR, Couch RT, Simpson ER, Zuber MX: Characterization of complementary deoxyribonucleic acid for human adrenocortical 17 alpha-hydroxylase: A probe for analysis of 17 alpha-hydroxylase deficiency. Mol Endocrinol 1987;1:348–354

    Google Scholar 

  3. Doody KJ, Lorence MC, Mason JI, Simpson ER: Expression of messenger ribonucleic acid species encoding steroidogenic enzymes in human follicles and corpora lutea throughout the menstrual cycle. J Clin Endocrinol Metab 1990;70:1041–1045

    Google Scholar 

  4. Biglieri EG, Herron MA, Brust N: 17-hydroxylation deficiency in man. J Clin Invest 1966;45:1946–1954

    Google Scholar 

  5. de Lange WE, Doorenbos H: Incomplete virilization and subclinical mineralocorticoid excess in a boy with partial 17,20-desmolase/17 alpha-hydroxylase deficiency. Acta Endocrinol (Copenh) 1990;122:263–266

    Google Scholar 

  6. Jones HW, Jr., Lee PA, Rock JA, Archer DF, Migeon CJ: A genetic male patient with 17 alpha-hydroxylase deficiency. Obstet Gynecol 1982;59:254–259

    Google Scholar 

  7. New MI. Male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency. J Clin Invest 1970;49:1930–1941

    Google Scholar 

  8. Salti IS, Hajj H, Dhib-Jalbut S: Testicular in vitro conversion of progesterone to testosterone and androstenedione in 17 alpha-hydroxylase deficiency. J Steroid Biochem 1982;17:155–15

    Google Scholar 

  9. Biglieri EG, Kater CE. 17 alpha-hydroxylation deficiency. Endocrinol Metab Clin North Am 1991;20:257–268

    Google Scholar 

  10. Pellicer A, Miro F, Sampaio M, Gomez E, Bonilla-Musoles FM: In vitro fertilization as a diagnostic and therapeutic tool in a patient with partial 17,20-desmolase deficiency. Fertil Steril 1991;55:970–975

    Google Scholar 

  11. Yanase T, Kagimoto M, Suzuki S, Hashiba K, Simpson ER, Waterman MR: Deletion of a phenylalanine in the N-terminal region of human cytochrome P-450(17 alpha) results in partial combined 17 alpha-hydroxylase/17,20-lyase deficiency. J Biol Chem 1989;264:18076–18082

    Google Scholar 

  12. Barash A, Weissman A, Manor M, Milman D, Ben-Arie A, Shoham Z: Prospective evaluation of endometrial thickness as a predictor of pituitary down-regulation after gonadotropin-releasing hormone analogue administration in an in vitro fertilization program. Fertil Steril 1998;69:496–499

    Google Scholar 

  13. Schlaff WD: Dynamic testing in reproductive endocrinology. Fertil Steril 1986;45:589–606

    Google Scholar 

  14. Speckart PF, Nicoloff JT, Bethune JE: Screening for adrenocortical insufficiency with cosyntropin (synthetic ACTH). Arch Intern Med 1971;128:761–763

    Google Scholar 

  15. Pariente C, Rabinovici J, Lunenfeld B, Rudak E, Dor J, Mashiach S, Levran D, Blankstein J, Geier A: Steroid secretion by granulosa cells isolated from a woman with 17 alpha-hydroxylase deficiency. J Clin Endocrinol Metab 1990;71:984–987

    Google Scholar 

  16. Kater CE, Biglieri EG: Disorders of steroid 17 alpha-hydroxylase deficiency. Endocrinol Metab Clin North Am 1994;23:341–357

    Google Scholar 

  17. Adachi M, Tachibana K, Asakura Y, Suwa S, Nishimura G: A male patient presenting with major clinical symptoms of glucocorticoid deficiency and skeletal dysplasia, showing a steroid pattern compatible with 17alpha-hydroxylase/17,20-lyase deficiency, but without obvious CYP17 gene mutations. Endocr J 1999;46:285–292

    Google Scholar 

  18. Auchus RJ, Worthy K, Geller DH, Miller WL: Probing structural and functional domains of human P450c17. Endocr Res 2000;26:695–703

    Google Scholar 

  19. Miller WL, Geller DH, Auchus RJ: The molecular basis of isolated 17,20 lyase deficiency. Endocr Res 1998;24:817–825

    Google Scholar 

  20. Geller DH, Auchus RJ, Mendonca BB, Miller WL: The genetic and functional basis of isolated 17,20-lyase deficiency. Nat Genet 1997;17:201–205

    Google Scholar 

  21. Takeda Y, Yoneda T, Demura M, Furukawa K, Koshida H, Miyamori I, Mabuchi H: Genetic analysis of the cytochrome P-450c17alpha (CYP17) and aldosterone synthase (CYP11B2) in Japanese patients with 17alpha-hydroxylase deficiency. Clin Endocrinol (Oxf) 2001;54:751–758

    Google Scholar 

  22. Yamaguchi H, Nakazato M, Miyazato M, Kangawa K, Matsukura S: A 5'-splice site mutation in the cytochrome P450 steroid 17alpha-hydroxylase gene in 17alpha hydroxylase deficiency. J Clin Endocrinol Metab 1997;82:1934–1938

    Google Scholar 

  23. Yamaguchi H, Nakazato M, Miyazato M, Toshimori H, Oki S, Shimizu K, Suiko M, Kangawa K, Matsukura S: Identification of a novel splicing mutation and 1-bp deletion in the 17alpha-hydroxylase gene of Japanese patients with 17alpha-hydroxylase deficiency. Hum Genet 1998;102:635–63

    Google Scholar 

  24. Speroff L, Glass RH, Kase NG: Clinical Gynecologic Endocrinology and Infertility, 6th edn. Philadelphia, Lippincott Williams & Wilkins, 1999

    Google Scholar 

  25. Yanase T, Sanders D, Shibata A, Matsui N, Simpson ER, Waterman MR: Combined 17 alpha-hydroxylase/17,20-lyase deficiency due to a 7-basepair duplication in the N-terminal region of the cytochrome P45017 alpha (CYP17) gene. J Clin Endocrinol Metab 1990;70:1325–1329

    Google Scholar 

  26. Araki S, Chikazawa K, Sekiguchi I, Yamauchi H, Motoyama M, Tamada T: Arrest of follicular development in a patient with 17 alpha-hydroxylase deficiency: Folliculogenesis in association with a lack of estrogen synthesis in the ovaries. Fertil Sreril 1987;47:169–172

    Google Scholar 

  27. Rabinovici J, Blankstein J, Goldman B, Rudak E, Dor Y, Pariente C, Geier A, Lunenfeld B, Mashiach S: In vitro fertilization and primary embryonic cleavage are possible in 17 alpha-hydroxylase deficiency despite extremely low intrafollicular 17 beta-estradiol. J Clin Endocrinol Metab 1989;68:693–697

    Google Scholar 

  28. Levran D, Dor J, Rudak E, Nebel L, Ben-Shlomo I, Ben-Rafael Z, Mashiach S: Pregnancy potential of human oocytes—The effect of cryopreservation. N Engl J Med 1990;323:1153–1156

    Google Scholar 

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Authors and Affiliations

  1. In Vitro Fertilization Unit, Edith Wolfson Medical Center, Holon, 58100, Israel

    David Levran & Ariel Weissman

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    David Levran, Izhar Ben-Shlomo, Clara Pariente, Jehoshua Dor, Shlomo Mashiach & Ariel Weissman

  3. Department of Obstetrics and Gynecology, Sheba Medical Center, Tel Hashomer, Israel

    Izhar Ben-Shlomo, Clara Pariente, Jehoshua Dor & Shlomo Mashiach

Authors
  1. David Levran
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  2. Izhar Ben-Shlomo
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  3. Clara Pariente
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  4. Jehoshua Dor
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  5. Shlomo Mashiach
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  6. Ariel Weissman
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Levran, D., Ben-Shlomo, I., Pariente, C. et al. Familial Partial 17,20-Desmolase and 17α-Hydroxylase Deficiency Presenting as Infertility. J Assist Reprod Genet 20, 21–28 (2003). https://doi.org/10.1023/A:1021206704958

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