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Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency

Endocrine volume 55, pages 19–36 (2017)Cite this article

Abstract

Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency is a rare autosomal recessive genetic disorder. It is caused by reduced or absent activity of 11β-hydroxylase (CYP11B1) enzyme and the resultant defects in adrenal steroidogenesis. The most common clinical features of 11 beta-hydroxylase deficiency are ambiguous genitalia, accelerated skeletal maturation and resultant short stature, peripheral precocious puberty and hyporeninemic hypokalemic hypertension. The biochemical diagnosis is based on raised serum 11-deoxycortisol and 11-deoxycorticosterone levels together with increased adrenal androgens. More than 100 mutations in CYP11B1 gene have been reported to date. The level of in-vivo activity of CYP11B1 relates to the degree of severity of 11 beta-hydroxylase deficiency. Clinical management of 11 beta-hydroxylase deficiency can pose a challenge to maintain adequate glucocorticoid dosing to suppress adrenal androgen excess while avoiding glucocorticoid-induced side effects. The long-term outcomes of clinical and surgical management are not well studied. This review article aims to collate the current available data about 11 beta-hydroxylase deficiency and its management.

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References

  1. P.W. Speiser, R. Azziz, L.S. Baskin, L. Ghizzoni, T.W. Hensle, D.P. Merke, H.F. Meyer-Bahlburg, W.L. Miller, V.M. Montori, S.E. Oberfield, M. Ritzen, P.C. White, S. Endocrine, Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 95(9), 4133–4160 (2010). doi:10.1210/jc.2009-2631

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. H. Falhammar, M. Thoren, Clinical outcomes in the management of congenital adrenal hyperplasia. Endocrine. 41(3), 355–373 (2012). doi:10.1007/s12020-011-9591-x

    CAS  PubMed  Article  Google Scholar 

  3. L.d Crecchio, Sopra un caso di apparenzi virili in una donna. Morgagni 7, 154–188 (1865)

    Google Scholar 

  4. L. Wilkins, R.A. Lewis, R. Klein, E. Rosemberg, The suppression of androgen secretion by cortisone in a case of congenital adrenal hyperplasia. Bull. Johns. Hopkins. Hosp. 86(4), 249–252 (1950)

    CAS  PubMed  Google Scholar 

  5. T.H. Shepard, S.W. Clausen, Case of adrenogenital syndrome with hypertension treated with cortisone. Pediatrics. 8(6), 805–811 (1951)

    CAS  PubMed  Google Scholar 

  6. L. Wilkins, J.F. Crigler Jr., S.H. Silverman, L.I. Gardner, C.J. Migeon, Further studies on the treatment of congenital adrenal hyperplasia with cortisone. III. The control of hypertension with cortisone, with a discussion of variations in the type of congenital adrenal hyperplasia and report of a case with probable defect of carbohydrate-regulating hormones. J. Clin. Endocrinol. Metab. 12(8), 1015–1030 (1952). doi:10.1210/jcem-12-8-1015

    CAS  PubMed  Article  Google Scholar 

  7. A.M. Bongiovanni, W.R. Eberlein, Plasma and urinary corticosteroids in the hypertensive form of congenital adrenal hyperplasia. J. Biol. Chem. 223(1), 85–94 (1956)

    CAS  PubMed  Google Scholar 

  8. P.C. White, P.W. Speiser, Congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr. Rev. 21(3), 245–291 (2000). doi:10.1210/edrv.21.3.0398

    CAS  PubMed  Google Scholar 

  9. D.P. Merke, S.R. Bornstein, Congenital adrenal hyperplasia. Lancet. 365(9477), 2125–2136 (2005). doi:10.1016/S0140-6736(05)66736-0

    PubMed  Article  Google Scholar 

  10. M. Zachmann, D. Tassinari, A. Prader, Clinical and biochemical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. A study of 25 patients. J. Clin. Endocrinol. Metab. 56(2), 222–229 (1983). doi:10.1210/jcem-56-2-222

    CAS  PubMed  Article  Google Scholar 

  11. S. Nimkarn, M.I. New, Steroid 11beta- hydroxylase deficiency congenital adrenal hyperplasia. Trends. Endocrinol. Metab. 19(3), 96–99 (2008). doi:10.1016/j.tem.2008.01.002

    CAS  PubMed  Article  Google Scholar 

  12. W. Arlt, D.S. Willis, S.H. Wild, N. Krone, E.J. Doherty, S. Hahner, T.S. Han, P.V. Carroll, G.S. Conway, D.A. Rees, R.H. Stimson, B.R. Walker, J.M. Connell, R.J. Ross; United Kingdom Congenital Adrenal Hyperplasia Adult Study, E., Health status of adults with congenital adrenal hyperplasia: a cohort study of 203 patients. J. Clin. Endocrinol. Metab. 95(11), 5110–5121 (2010). doi:10.1210/jc.2010-0917

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  13. S. Gidlof, H. Falhammar, A. Thilen, U. von Dobeln, M. Ritzen, A. Wedell, A. Nordenstrom, One hundred years of congenital adrenal hyperplasia in Sweden: a retrospective, population-based cohort study. Lancet Diabetes Endocrinol. 1(1), 35–42 (2013). doi:10.1016/S2213-8587(13)70007-X

    PubMed  Article  Google Scholar 

  14. H. Falhammar, A. Nordenstrom, Nonclassic congenital adrenal hyperplasia due to 21-hydroxylase deficiency: clinical presentation, diagnosis, treatment, and outcome. Endocrine 50(1), 32–50 (2015). doi:10.1007/s12020-015-0656-0

    CAS  PubMed  Article  Google Scholar 

  15. A. Rosler, E. Leiberman, T. Cohen, High frequency of congenital adrenal hyperplasia (classic 11 beta-hydroxylase deficiency) among Jews from Morocco. Am. J. Med. Genet. 42(6), 827–834 (1992). doi:10.1002/ajmg.1320420617

    CAS  PubMed  Article  Google Scholar 

  16. P.C. White, Steroid 11 beta-hydroxylase deficiency and related disorders. Endocrinol. Metab. Clin. North. Am. 30(1), 61–79 (2001). vi

    CAS  PubMed  Article  Google Scholar 

  17. P.W. Speiser, P.C. White, Congenital adrenal hyperplasia. N. Engl. J. Med. 349(8), 776–788 (2003). doi:10.1056/NEJMra021561

    CAS  PubMed  Article  Google Scholar 

  18. M.I. New, M.P. Seaman, Secretion rates of cortisol and aldosterone precursors in various forms of congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 30(3), 361–371 (1970). doi:10.1210/jcem-30-3-361

    CAS  PubMed  Article  Google Scholar 

  19. N. Krone, W. Arlt, Genetics of congenital adrenal hyperplasia. Best. Pract. Res. Clin. Endocrinol. Metab. 23(2), 181–192 (2009). doi:10.1016/j.beem.2008.10.014

    CAS  PubMed  Article  Google Scholar 

  20. L. Schiffer, S. Anderko, F. Hannemann, A. Eiden-Plach, R. Bernhardt, The CYP11B subfamily. J. Steroid. Biochem. Mol. Biol. 151, 38–51 (2015). doi:10.1016/j.jsbmb.2014.10.011

    CAS  PubMed  Article  Google Scholar 

  21. H. Selye, H. Stone, Hormonally induced transformation of adrenal into myeloid tissue. Am. J. Pathol. 26(2), 211–233 (1950)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. S. Jaresch, E. Kornely, H.K. Kley, R. Schlaghecke, Adrenal incidentaloma and patients with homozygous or heterozygous congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 74(3), 685–689 (1992). doi:10.1210/jcem.74.3.1311000

    CAS  PubMed  Google Scholar 

  23. H. Falhammar, Non-functioning adrenal incidentalomas caused by 21-hydroxylase deficiency or carrier status? Endocrine. 47(1), 308–314 (2014). doi:10.1007/s12020-013-0162-1

    CAS  PubMed  Article  Google Scholar 

  24. E. Charmandari, G. Eisenhofer, S.L. Mehlinger, A. Carlson, R. Wesley, M.F. Keil, G.P. Chrousos, M.I. New, D.P. Merke, Adrenomedullary function may predict phenotype and genotype in classic 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 87(7), 3031–3037 (2002). doi:10.1210/jcem.87.7.8664

    CAS  PubMed  Article  Google Scholar 

  25. H. Falhammar, H. Filipsson Nystrom, A. Wedell, M. Thoren, Cardiovascular risk, metabolic profile, and body composition in adult males with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur. J. Endocrinol. 164(2), 285–293 (2011). doi:EJE-10-0877 [pii] 10.1530/EJE-10-0877

    CAS  PubMed  Article  Google Scholar 

  26. G.P. Finkielstain, M.S. Kim, N. Sinaii, M. Nishitani, C. Van Ryzin, S.C. Hill, J.C. Reynolds, R.M. Hanna, D.P. Merke, Clinical characteristics of a cohort of 244 patients with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 97(12), 4429–4438 (2012). doi:10.1210/jc.2012-2102

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  27. F. Tutunculer, N. Saka, S.C. Arkaya, S. Abbasoglu, F. Bas, Evaluation of adrenomedullary function in patients with congenital adrenal hyperplasia. Horm. Res. 72(6), 331–336 (2009). doi:10.1159/000249160

    CAS  PubMed  Article  Google Scholar 

  28. A. Rosler, E. Leiberman, J. Sack, H. Landau, A. Benderly, S.W. Moses, T. Cohen, Clinical variability of congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Horm. Res. 16(3), 133–141 (1982)

    CAS  PubMed  Article  Google Scholar 

  29. N.A. al-Jurayyan, Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency in Saudi Arabia: clinical and biochemical characteristics. Acta. Paediatr. 84(6), 651–654 (1995)

    CAS  PubMed  Article  Google Scholar 

  30. C.P. Burren, J. Montalto, A.B. Yong, J.A. Batch, CYP11 beta 1 (11-beta-hydroxylase) deficiency in congenital adrenal hyperplasia. J. Paediatr. Child. Health. 32(5), 433–438 (1996)

    CAS  PubMed  Article  Google Scholar 

  31. S. Riedl, H.H. Nguyen, S. Clausmeyer, E. Schulze, F. Waldhauser, R. Bernhardt, A homozygous L299P mutation in the CYP11B1 gene leads to complete virilization in 46,XX individuals with 11-beta-hydroxylase deficiency. Horm. Res. 70(3), 145–149 (2008). doi:10.1159/000137659

    CAS  PubMed  Article  Google Scholar 

  32. S. Parajes, L. Loidi, N. Reisch, V. Dhir, I.T. Rose, R. Hampel, M. Quinkler, G.S. Conway, L. Castro-Feijoo, D. Araujo-Vilar, M. Pombo, F. Dominguez, E.L. Williams, T.R. Cole, J.M. Kirk, E. Kaminsky, G. Rumsby, W. Arlt, N. Krone, Functional consequences of seven novel mutations in the CYP11B1 gene: four mutations associated with nonclassic and three mutations causing classic 11{beta}-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 95(2), 779–788 (2010). doi:10.1210/jc.2009-0651

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  33. A. Nordenskjold, G. Holmdahl, L. Frisen, H. Falhammar, H. Filipsson, M. Thoren, P.O. Janson, K. Hagenfeldt, Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 93(2), 380–386 (2008). doi:jc.2007-0556 [pii] 10.1210/jc.2007-0556

    PubMed  Article  CAS  Google Scholar 

  34. A.S. Oberman, E. Flatau, R. Luboshitzky, Bilateral testicular adrenal rests in a patient with 11-hydroxylase deficient congenital adrenal hyperplasia. J. Urol. 149(2), 350–352 (1993)

    CAS  PubMed  Google Scholar 

  35. P.C. White, K.M. Curnow, L. Pascoe, Disorders of steroid 11 beta-hydroxylase isozymes. Endocr. Rev. 15(4), 421–438 (1994). doi:10.1210/edrv-15-4-421

    CAS  PubMed  Google Scholar 

  36. V. Harde, M. Muller, W.G. Sippell, T. Schwarz, R. Folster-Holst, [Acne infantum as presenting symptom of congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency]. J. Dtsch. Dermatol. Ges. 4(8), 654–657 (2006). doi:10.1111/j.1610-0387.2006.06016.x

    PubMed  Article  Google Scholar 

  37. Z. Hochberg, J. Schechter, A. Benderly, E. Leiberman, A. Rosler, Growth and pubertal development in patients with congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Am. J. Dis. Child. 139(8), 771–776 (1985)

    CAS  PubMed  Google Scholar 

  38. N. Reisch, W. Hogler, S. Parajes, I.T. Rose, V. Dhir, J. Gotzinger, W. Arlt, N. Krone, A diagnosis not to be missed: nonclassic steroid 11beta-hydroxylase deficiency presenting with premature adrenarche and hirsutism. J. Clin. Endocrinol. Metab. 98(10), E1620–1625 (2013). doi:10.1210/jc.2013-1306

    CAS  PubMed  Article  Google Scholar 

  39. M. Mimouni, H. Kaufman, A. Roitman, C. Morag, N. Sadan, Hypertension in a neonate with 11 beta-hydroxylase deficiency. Eur. J. Pediatr. 143(3), 231–233 (1985)

    CAS  PubMed  Article  Google Scholar 

  40. M. John, S.K. Menon, N.S. Shah, P.S. Menon, Congenital adrenal hyperplasia 11beta-hydroxylase deficiency: two cases managed with bilateral adrenalectomy. Singapore Med. J. 50(2), e68–70 (2009)

    CAS  PubMed  Google Scholar 

  41. A. Sathya, R. Ganesan, A. Kumar, Congenital adrenal hyperplasia masquerading as periodic paralysis in an adolescent girl. Singapore Med. J. 53(7), e148–149 (2012)

    PubMed  Google Scholar 

  42. H. Falhammar, M. Thoren, J. Calissendorff, Thyrotoxic periodic paralysis: clinical and molecular aspects. Endocrine 43(2), 274–284 (2013). doi:10.1007/s12020-012-9777-x

    CAS  PubMed  Google Scholar 

  43. Z. Zadik, L. Kahana, H. Kaufman, A. Benderli, Z. Hochberg, Salt loss in hypertensive form of congenital adrenal hyperplasia (11-beta-hydroxylase deficiency). J. Clin. Endocrinol. Metab. 58(2), 384–387 (1984). doi:10.1210/jcem-58-2-384

    CAS  PubMed  Article  Google Scholar 

  44. Z. Hochberg, A. Benderly, Z. Zadik, Salt loss in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Arch. Dis. Child. 59(11), 1092–1094 (1984)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  45. Y. Liel, Acute adrenal crisis complicating hypertensive congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Clin. Genet. 43(2), 92–93 (1993)

    CAS  PubMed  Article  Google Scholar 

  46. B. Ezquieta, C. Luzuriaga, Neonatal salt-wasting and 11 beta-hydroxylase deficiency in a child carrying a homozygous deletion hybrid CYP11B2 (aldosterone synthase)-CYP11B1 (11 beta-hydroxylase). Clin. Genet. 66(3), 229–235 (2004). doi:10.1111/j.1399-0004.2004.00291.x

    CAS  PubMed  Article  Google Scholar 

  47. H. Falhammar, M. Thoren, K. Hagenfeldt, A 31-year-old woman with infertility and polycystic ovaries diagnosed with non-classic congenital adrenal hyperplasia due to a novel CYP21 mutation. J. Endocrinol. Invest. 31(2), 176–180 (2008). doi:10.1007/BF03345586

    CAS  PubMed  Article  Google Scholar 

  48. M. Pall, R. Azziz, J. Beires, D. Pignatelli, The phenotype of hirsute women: a comparison of polycystic ovary syndrome and 21-hydroxylase-deficient nonclassic adrenal hyperplasia. Fertil. Steril. 94(2), 684–689 (2010). doi:10.1016/j.fertnstert.2009.06.025

    CAS  PubMed  Article  Google Scholar 

  49. R. Azziz, E. Carmina, D. Dewailly, E. Diamanti-Kandarakis, H.F. Escobar-Morreale, W. Futterweit, O.E. Janssen, R.S. Legro, R.J. Norman, A.E. Taylor, S.F. Witchel, Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen, E., Society, P., The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil. Steril. 91(2), 456–488 (2009). doi:10.1016/j.fertnstert.2008.06.035

    PubMed  Article  Google Scholar 

  50. M.I. New, F. Lorenzen, A.J. Lerner, B. Kohn, S.E. Oberfield, M.S. Pollack, B. Dupont, E. Stoner, D.J. Levy, S. Pang, L.S. Levine, Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J. Clin. Endocrinol. Metab. 57(2), 320–326 (1983). doi:10.1210/jcem-57-2-320

    CAS  PubMed  Article  Google Scholar 

  51. I.A. Hughes, O. Arisaka, L.A. Perry, J.W. Honour, Early diagnosis of 11 beta-hydroxylase deficiency in two siblings confirmed by analysis of a novel steroid metabolite in newborn urine. Acta. Endocrinol. 111(3), 349–354 (1986)

    CAS  PubMed  Google Scholar 

  52. K. Lange-Kubini, M. Zachmann, B. Kempken, T. Torresani, 15 beta-hydroxylated steroids may be diagnostically misleading in confirming congenital adrenal hyperplasia suspected by a newborn screening programme. Eur. J. Pediatr. 155(11), 928–931 (1996)

    CAS  PubMed  Article  Google Scholar 

  53. F. Mantero, G. Opocher, D. Armanini, S. Filipponi, 11 Beta-hydroxylase deficiency. J. Endocrinol. Invest. 18(7), 545–549 (1995)

    CAS  PubMed  Article  Google Scholar 

  54. R. Azziz, L.R. Boots, C.R. Parker Jr., E. Bradley Jr., H.A. Zacur, 11 beta-hydroxylase deficiency in hyperandrogenism. Fertil. Steril. 55(4), 733–741 (1991)

    CAS  PubMed  Article  Google Scholar 

  55. F. Kelestimur, Y. Sahin, D. Ayata, A. Tutus, The prevalence of non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency among hirsute women in a Turkish population. Clin. Endocrinol. 45(4), 381–384 (1996)

    CAS  Article  Google Scholar 

  56. Y. Sahin, F. Kelestimur, The frequency of late-onset 21-hydroxylase and 11 beta-hydroxylase deficiency in women with polycystic ovary syndrome. Eur. J. Endocrinol. 137(6), 670–674 (1997)

    CAS  PubMed  Article  Google Scholar 

  57. M. Peter, W.G. Sippell, Evidence for endocrinological abnormalities in heterozygotes for adrenal 11 beta-hydroxylase deficiency of a family with the R448H mutation in the CYP11B1 gene. J. Clin. Endocrinol. Metab. 82(10), 3506–3508 (1997). doi:10.1210/jcem.82.10.4051

    CAS  PubMed  Google Scholar 

  58. S. Pang, L.S. Levine, F. Lorenzen, D. Chow, M. Pollack, B. Dupont, M. Genel, M.I. New, Hormonal studies in obligate heterozygotes and siblings of patients with 11 beta-hydroxylase deficiency congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 50(3), 586–589 (1980). doi:10.1210/jcem-50-3-586

    CAS  PubMed  Article  Google Scholar 

  59. A. Rosler, H. Cohen, Absence of steroid biosynthetic defects in heterozygote individuals for classic 11 beta-hydroxylase deficiency due to a R448H mutation in the CYP11B1 gene. J. Clin. Endocrinol. Metab. 80(12), 3771–3773 (1995). doi:10.1210/jcem.80.12.8530633

    CAS  PubMed  Google Scholar 

  60. E. Mornet, J. Dupont, A. Vitek, P.C. White, Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta. J. Biol. Chem. 264(35), 20961–20967 (1989)

    CAS  PubMed  Google Scholar 

  61. K.M. Curnow, L. Slutsker, J. Vitek, T. Cole, P.W. Speiser, M.I. New, P.C. White, L. Pascoe, Mutations in the CYP11B1 gene causing congenital adrenal hyperplasia and hypertension cluster in exons 6, 7, and 8. Proc. Natl. Acad. Sci. U. S. A. 90(10), 4552–4556 (1993)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  62. N. Kandemir, D.Y. Yilmaz, E.N. Gonc, A. Ozon, A. Alikasifoglu, A. Dursun, R.K. Ozgul, Novel and prevalent CYP11B1 gene mutations in Turkish patients with 11-beta hydroxylase deficiency. J. Steroid. Biochem. Mol. Biol. (2016). 10.1016/j.jsbmb.2016.03.006

  63. A. Wedell, A. Thilen, E.M. Ritzen, B. Stengler, H. Luthman, Mutational spectrum of the steroid 21-hydroxylase gene in Sweden: implications for genetic diagnosis and association with disease manifestation. J. Clin. Endocrinol. Metab. 78(5), 1145–1152 (1994). doi:10.1210/jcem.78.5.8175971

    CAS  PubMed  Google Scholar 

  64. J. Jaaskelainen, A. Levo, R. Voutilainen, J. Partanen, Population-wide evaluation of disease manifestation in relation to molecular genotype in steroid 21-hydroxylase (CYP21) deficiency: good correlation in a well defined population. J. Clin. Endocrinol. Metab. 82(10), 3293–3297 (1997). doi:10.1210/jcem.82.10.4271

    CAS  PubMed  Google Scholar 

  65. H. Falhammar, A. Wedell, A. Nordenstrom, Biochemical and genetic diagnosis of 21-hydroxylase deficiency. Endocrine. 50(2), 306–314 (2015). doi:10.1007/s12020-015-0731-6

    CAS  PubMed  Article  Google Scholar 

  66. R. Marino, P. Ramirez, J. Galeano, N. Perez Garrido, C. Rocco, M. Ciaccio, D.M. Warman, G. Guercio, E. Chaler, M. Maceiras, I. Bergada, M. Gryngarten, V. Balbi, E. Pardes, M.A. Rivarola, A. Belgorosky, Steroid 21-hydroxylase gene mutational spectrum in 454 Argentinean patients: genotype-phenotype correlation in a large cohort of patients with congenital adrenal hyperplasia. Clin. Endocrinol. 75(4), 427–435 (2011). doi:10.1111/j.1365-2265.2011.04123.x

    CAS  Article  Google Scholar 

  67. M.I. New, M. Abraham, B. Gonzalez, M. Dumic, M. Razzaghy-Azar, D. Chitayat, L. Sun, M. Zaidi, R.C. Wilson, T. Yuen, Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency. Proc. Natl. Acad. Sci. U. S. A. 110(7), 2611–2616 (2013). doi:10.1073/pnas.1300057110

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  68. H. Falhammar, H. Filipsson, G. Holmdahl, P.O. Janson, A. Nordenskjold, K. Hagenfeldt, M. Thoren, Fractures and bone mineral density in adult women with 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 92(12), 4643–4649 (2007). doi:jc.2007-0744 [pii] 10.1210/jc.2007-0744

    CAS  PubMed  Article  Google Scholar 

  69. K. Hagenfeldt, P.O. Janson, G. Holmdahl, H. Falhammar, H. Filipsson, L. Frisen, M. Thoren, A. Nordenskjold, Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Hum. Reprod. 23(7), 1607–1613 (2008). doi:den118 [pii] 10.1093/humrep/den118

    CAS  PubMed  Article  Google Scholar 

  70. H. Falhammar, H. Filipsson, G. Holmdahl, P.O. Janson, A. Nordenskjold, K. Hagenfeldt, M. Thoren, Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Endocr. J. 56(4), 601–608 (2009)

    CAS  PubMed  Article  Google Scholar 

  71. L. Frisen, A. Nordenstrom, H. Falhammar, H. Filipsson, G. Holmdahl, P.O. Janson, M. Thoren, K. Hagenfeldt, A. Moller, A. Nordenskjold, Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency. J. Clin. Endocrinol. Metab. 94(9), 3432–3439 (2009). doi:10.1210/jc.2009-0636

    CAS  PubMed  Article  Google Scholar 

  72. A. Nordenstrom, L. Frisen, H. Falhammar, H. Filipsson, G. Holmdahl, P.O. Janson, M. Thoren, K. Hagenfeldt, A. Nordenskjold, Sexual function and surgical outcome in women with congenital adrenal hyperplasia due to CYP21A2 deficiency: clinical perspective and the patients’ perception. J. Clin. Endocrinol. Metab. 95(8), 3633–3640 (2010). doi:jc.2009-2639 [pii] 10.1210/jc.2009-2639

    PubMed  Article  CAS  Google Scholar 

  73. H. Falhammar, H.F. Nystrom, U. Ekstrom, S. Granberg, A. Wedell, M. Thoren, Fertility, sexuality and testicular adrenal rest tumors in adult males with congenital adrenal hyperplasia. Eur. J. Endocrinol. 166(3), 441–449 (2012). doi:10.1530/EJE-11-0828

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  74. H. Falhammar, H. Filipsson Nystrom, A. Wedell, K. Brismar, M. Thoren, Bone mineral density, bone markers, and fractures in adult males with congenital adrenal hyperplasia. Eur. J. Endocrinol. 168(3), 331–341 (2013). doi:10.1530/EJE-12-0865

    CAS  PubMed  Article  Google Scholar 

  75. U. Nygren, H.F. Nystrom, H. Falhammar, K. Hagenfeldt, A. Nordenskjold, M. Sodersten, Voice problems due to virilization in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin. Endocrinol. 79(6), 859–866 (2013). doi:10.1111/cen.12226

    CAS  Article  Google Scholar 

  76. A. Strandqvist, H. Falhammar, P. Lichtenstein, A.L. Hirschberg, A. Wedell, C. Norrby, A. Nordenskjold, L. Frisen, A. Nordenstrom, Suboptimal psychosocial outcomes in patients with congenital adrenal hyperplasia: epidemiological studies in a nonbiased national cohort in Sweden. J. Clin. Endocrinol. Metab. 99(4), 1425–1432 (2014). doi:10.1210/jc.2013-3326

    CAS  PubMed  Article  Google Scholar 

  77. H. Falhammar, A. Butwicka, M. Landen, P. Lichtenstein, A. Nordenskjold, A. Nordenstrom, L. Frisen, Increased psychiatric morbidity in men with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 99(3), E554–560 (2014). doi:10.1210/jc.2013-3707

    CAS  PubMed  Article  Google Scholar 

  78. H. Falhammar, H.F. Nystrom, M. Thoren, Quality of life, social situation, and sexual satisfaction, in adult males with congenital adrenal hyperplasia. Endocrine. 47(1), 299–307 (2014). doi:10.1007/s12020-013-0161-2

    CAS  PubMed  Article  Google Scholar 

  79. H. Engberg, A. Butwicka, A. Nordenstrom, A.L. Hirschberg, H. Falhammar, P. Lichtenstein, A. Nordenskjold, L. Frisen, M. Landen, Congenital adrenal hyperplasia and risk for psychiatric disorders in girls and women born between 1915 and 2010: a total population study. Psychoneuroendocrinology. 60, 195–205 (2015). doi:10.1016/j.psyneuen.2015.06.017

    PubMed  Article  Google Scholar 

  80. H. Falhammar, L. Frisen, A.L. Hirschberg, C. Norrby, C. Almqvist, A. Nordenskjold, A. Nordenstrom, Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency: a Swedish population-based national cohort study. J. Clin. Endocrinol. Metab. 100(9), 3520–3528 (2015). doi:10.1210/JC.2015-2093

    CAS  PubMed  Article  Google Scholar 

  81. P.C. White, J. Dupont, M.I. New, E. Leiberman, Z. Hochberg, A. Rosler, A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin. J. Clin. Invest. 87(5), 1664–1667 (1991). doi:10.1172/JCI115182

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  82. K. Matsubara, N. Kataoka, S. Ogita, S. Sano, T. Ogata, M. Fukami, N. Katsumata, Uniparental disomy of chromosome 8 leading to homozygosity of a CYP11B1 mutation in a patient with congenital adrenal hyperplasia: implication for a rare etiology of an autosomal recessive disorder. Endocr. J. 61(6), 629–633 (2014)

    CAS  PubMed  Article  Google Scholar 

  83. K. Joehrer, S. Geley, E.M. Strasser-Wozak, R. Azziz, H.A. Wollmann, K. Schmitt, R. Kofler, P.C. White, CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Hum. Mol. Genet. 6(11), 1829–1834 (1997)

    CAS  PubMed  Article  Google Scholar 

  84. S. Menabo, S. Polat, L. Baldazzi, A.E. Kulle, P.M. Holterhus, J. Grotzinger, F. Fanelli, A. Balsamo, F.G. Riepe, Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency: functional consequences of four CYP11B1 mutations. Eur. J. Hum. Genet. 22(5), 610–616 (2014). doi:10.1038/ejhg.2013.197

    CAS  PubMed  Article  Google Scholar 

  85. S. Polat, A. Kulle, Z. Karaca, I. Akkurt, S. Kurtoglu, F. Kelestimur, J. Grotzinger, P.M. Holterhus, F.G. Riepe, Characterisation of three novel CYP11B1 mutations in classic and non-classic 11beta-hydroxylase deficiency. Eur. J. Endocrinol. 170(5), 697–706 (2014). doi:10.1530/EJE-13-0737

    CAS  PubMed  Article  Google Scholar 

  86. C. Brautbar, A. Rosler, H. Landau, I. Cohen, D. Nelken, T. Cohen, C. Levine, J. Sack, A. Benderli, S. Moses, E. Lieberman, B. Dupont, L.S. Levine, M.I. New, No linkage between HLA and congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. N. Engl. J. Med. 300(4), 205–206 (1979)

    CAS  PubMed  Google Scholar 

  87. F. Mantero, C. Scaroni, P. Masarotto, C.V. Pasini, HLA and hormonal data for identification of heterozygotes in 11 beta- and 17 alpha-hydroxylase deficiency syndromes. Clin. Exp. Pharmacol. Physiol. 9(3), 265–269 (1982)

    CAS  PubMed  Article  Google Scholar 

  88. V. Tonetto-Fernandes, S.H. Lemos-Marini, H. Kuperman, L.M. Ribeiro-Neto, I.T. Verreschi, C.E. Kater, Serum 21-Deoxycortisol, 17-Hydroxyprogesterone, and 11-deoxycortisol in classic congenital adrenal hyperplasia: clinical and hormonal correlations and identification of patients with 11beta-hydroxylase deficiency among a large group with alleged 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 91(6), 2179–2184 (2006). doi:10.1210/jc.2005-1890

    CAS  PubMed  Article  Google Scholar 

  89. N. Kandemir, N. Yordam, Congenital adrenal hyperplasia in Turkey: a review of 273 patients. Acta. Paediatr. 86(1), 22–25 (1997)

    CAS  PubMed  Article  Google Scholar 

  90. E. Carmina, G. Malizia, M. Pagano, A. Janni, Prevalence of late-onset 11 beta-hydroxylase deficiency in hirsute patients. J. Endocrinol. Invest. 11(8), 595–598 (1988)

    CAS  PubMed  Article  Google Scholar 

  91. T. Eldar-Geva, A. Hurwitz, P. Vecsei, Z. Palti, A. Milwidsky, A. Rosler, Secondary biosynthetic defects in women with late-onset congenital adrenal hyperplasia. N. Engl. J. Med. 323(13), 855–863 (1990). doi:10.1056/NEJM199009273231302

    CAS  PubMed  Article  Google Scholar 

  92. R.D. Brown, R. Gaunt, E. Gisoldi, N. Smith, The role of deoxycorticosterone in adrenal regeneration hypertension. Endocrinology 91(4), 921–924 (1972). doi:10.1210/endo-91-4-921

    CAS  PubMed  Article  Google Scholar 

  93. G.P. Vinson, The mislabelling of deoxycorticosterone: making sense of corticosteroid structure and function. J. Endocrinol. 211(1), 3–16 (2011). doi:10.1530/JOE-11-0178

    CAS  PubMed  Article  Google Scholar 

  94. A. Glenthoj, M.D. Nielsen, J. Starup, Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency: final diagnosis in adult age in three patients. Acta. Endocrinol. 93(1), 94–99 (1980)

    CAS  PubMed  Google Scholar 

  95. W.M. Hague, J.W. Honour, Malignant hypertension in congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. Clin. Endocrinol. 18(5), 505–510 (1983)

    CAS  Article  Google Scholar 

  96. O. Chabre, S. Portrat-Doyen, P. Chaffanjon, J. Vivier, P. Liakos, F. Labat-Moleur, E. Chambaz, Y. Morel, G. Defaye, Bilateral laparoscopic adrenalectomy for congenital adrenal hyperplasia with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1. J. Clin. Endocrinol. Metab. 85(11), 4060–4068 (2000). doi:10.1210/jcem.85.11.6897

    CAS  PubMed  Article  Google Scholar 

  97. E. Melcescu, J. Phillips, G. Moll, J.S. Subauste, C.A. Koch, 11Beta-hydroxylase deficiency and other syndromes of mineralocorticoid excess as a rare cause of endocrine hypertension. Horm. Metab. Res. 44(12), 867–878 (2012). doi:10.1055/s-0032-1321851

    CAS  PubMed  Article  Google Scholar 

  98. R.M. Williams, A. Deeb, K.K. Ong, W. Bich, P.R. Murgatroyd, I.A. Hughes, C.L. Acerini, Insulin sensitivity and body composition in children with classical and nonclassical congenital adrenal hyperplasia. Clin. Endocrinol. 72(2), 155–160 (2010). doi:10.1111/j.1365-2265.2009.03587.x

    CAS  Article  Google Scholar 

  99. C.F. Mooij, J.M. Kroese, F.C. Sweep, A.R. Hermus, C.J. Tack, Adult patients with congenital adrenal hyperplasia have elevated blood pressure but otherwise a normal cardiovascular risk profile. PLoS. One. 6(9), e24204 (2011). doi:10.1371/journal.pone.0024204

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  100. H. Falhammar, H. Filipsson, G. Holmdahl, P.O. Janson, A. Nordenskjold, K. Hagenfeldt, M. Thoren, Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 92(1), 110–116 (2007). doi:jc.2006-1350 [pii] 10.1210/jc.2006-1350

    CAS  PubMed  Article  Google Scholar 

  101. P. Sartorato, E. Zulian, S. Benedini, B. Mariniello, F. Schiavi, F. Bilora, G. Pozzan, N. Greggio, A. Pagnan, F. Mantero, C. Scaroni, Cardiovascular risk factors and ultrasound evaluation of intima-media thickness at common carotids, carotid bulbs, and femoral and abdominal aorta arteries in patients with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 92(3), 1015–1018 (2007). doi:10.1210/jc.2006-1711

    CAS  PubMed  Article  Google Scholar 

  102. C. Bouvattier, L. Esterle, P. Renoult-Pierre, A.B. de la Perriere, F. Illouz, V. Kerlan, V. Pascal-Vigneron, D. Drui, S. Christin-Maitre, F. Galland, T. Brue, Y. Reznik, F. Schillo, D. Pinsard, X. Piguel, G. Chabrier, B. Decoudier, P. Emy, I. Tauveron, M.L. Raffin-Sanson, J. Bertherat, J.M. Kuhn, P. Caron, M. Cartigny, O. Chabre, D. Dewailly, Y. Morel, P. Touraine, V. Tardy-Guidollet, J. Young, Clinical outcome, hormonal status, gonadotrope axis, and testicular function in 219 adult men born with classic 21-hydroxylase deficiency. A French national Survey. J. Clin. Endocrinol. Metab. 100(6), 2303–2313 (2015). doi:10.1210/jc.2014-4124

    CAS  PubMed  Article  Google Scholar 

  103. G. Jermendy, I. Szabolcs, G. Szilagyi, L. Domotor, P. Karpati, Diabetes mellitus associated with late onset congenital adrenal hyperplasia: coincidence or causality? Diabet. Med. 8(5), 489–491 (1991)

    CAS  PubMed  Article  Google Scholar 

  104. J. Helleday, B. Siwers, E.M. Ritzen, K. Carlstrom, Subnormal androgen and elevated progesterone levels in women treated for congenital virilizing 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 76(4), 933–936 (1993). doi:10.1210/jcem.76.4.8473408

    CAS  PubMed  Google Scholar 

  105. R.E. Cornean, P.C. Hindmarsh, C.G. Brook, Obesity in 21-hydroxylase deficient patients. Arch. Dis. Child. 78(3), 261–263 (1998)

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  106. K. Hagenfeldt, E. Martin Ritzen, H. Ringertz, J. Helleday, K. Carlstrom, Bone mass and body composition of adult women with congenital virilizing 21-hydroxylase deficiency after glucocorticoid treatment since infancy. Eur. J. Endocrinol. 143(5), 667–671 (2000)

    CAS  PubMed  Article  Google Scholar 

  107. C. Paganini, G. Radetti, C. Livieri, V. Braga, D. Migliavacca, S. Adami, Height, bone mineral density and bone markers in congenital adrenal hyperplasia. Horm. Res. 54(4), 164–168 (2000). doi:53253

    CAS  PubMed  Google Scholar 

  108. N.M. Stikkelbroeck, W.J. Oyen, G.J. van der Wilt, A.R. Hermus, B.J. Otten, Normal bone mineral density and lean body mass, but increased fat mass, in young adult patients with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 88(3), 1036–1042 (2003). doi:10.1210/jc.2002-021074

    CAS  PubMed  Article  Google Scholar 

  109. J.A. King, A.B. Wisniewski, B.J. Bankowski, K.A. Carson, H.A. Zacur, C.J. Migeon, Long-term corticosteroid replacement and bone mineral density in adult women with classical congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 91(3), 865–869 (2006). doi:10.1210/jc.2005-0745

    CAS  PubMed  Article  Google Scholar 

  110. T.M. Volkl, D. Simm, C. Beier, H.G. Dorr, Obesity among children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Pediatrics. 117(1), e98–105 (2006). doi:10.1542/peds.2005-1005

    PubMed  Article  Google Scholar 

  111. A. Bachelot, G. Plu-Bureau, E. Thibaud, K. Laborde, G. Pinto, D. Samara, C. Nihoul-Fekete, F. Kuttenn, M. Polak, P. Touraine, Long-term outcome of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Horm. Res. 67(6), 268–276 (2007). doi:10.1159/000098017

    CAS  PubMed  Google Scholar 

  112. T.M. Volkl, D. Simm, A. Korner, W. Rascher, W. Kiess, J. Kratzsch, H.G. Dorr, Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency? Eur. J. Endocrinol. 160(2), 239–247 (2009). doi:10.1530/EJE-08-0770

    PubMed  Article  CAS  Google Scholar 

  113. H.J. Zhang, J. Yang, M.N. Zhang, C.Q. Liu, M. Xu, X.J. Li, S.Y. Yang, X.Y. Li, Metabolic disorders in newly diagnosed young adult female patients with simple virilizing 21-hydroxylase deficiency. Endocrine. 38(2), 260–265 (2010). doi:10.1007/s12020-010-9382-9

    CAS  PubMed  Article  Google Scholar 

  114. S. Bjornsdottir, M. Saaf, S. Bensing, O. Kampe, K. Michaelsson, J.F. Ludvigsson, Risk of hip fracture in Addison’s disease: a population-based cohort study. J. Intern. Med. 270(2), 187–195 (2011). doi:10.1111/j.1365-2796.2011.02352.x

    CAS  PubMed  Article  Google Scholar 

  115. F.J. Cameron, B. Kaymakci, E.A. Byrt, P.R. Ebeling, G.L. Warne, J.D. Wark, Bone mineral density and body composition in congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 80(7), 2238–2243 (1995). doi:10.1210/jcem.80.7.7608286

    CAS  PubMed  Google Scholar 

  116. M. Gussinye, A. Carrascosa, N. Potau, M. Enrubia, E. Vicens-Calvet, L. Ibanez, D. Yeste, Bone mineral density in prepubertal and in adolescent and young adult patients with the salt-wasting form of congenital adrenal hyperplasia. Pediatrics. 100(4), 671–674 (1997)

    CAS  PubMed  Article  Google Scholar 

  117. H. Falhammar, L. Frisen, C. Norrby, A.L. Hirschberg, C. Almqvist, A. Nordenskjold, A. Nordenstrom, Increased mortality in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 99(12), E2715–2721 (2014). doi:10.1210/jc.2014-2957

    CAS  PubMed  Article  Google Scholar 

  118. R.L. Rushworth, H. Falhammar, C.F. Munns, A.M. Maguire, D.J. Torpy, Hospital admission patterns in children with CAH: admission rates and adrenal crises decline with age. Int. J. Endocrinol. 2016, 5748264 (2016). doi:10.1155/2016/5748264

    PubMed  PubMed Central  Article  Google Scholar 

  119. K. Muthusamy, M.B. Elamin, G. Smushkin, M.H. Murad, J.F. Lampropulos, K.B. Elamin, N.O. Abu Elnour, J.F. Gallegos-Orozco, M.M. Fatourechi, N. Agrwal, M.A. Lane, F.N. Albuquerque, P.J. Erwin, V.M. Montori, Clinical review: adult height in patients with congenital adrenal hyperplasia: a systematic review and metaanalysis. J. Clin. Endocrinol. Metab. 95(9), 4161–4172 (2010). doi:10.1210/jc.2009-2616

    CAS  PubMed  Article  Google Scholar 

  120. E.A. Eugster, L.A. Dimeglio, J.C. Wright, G.R. Freidenberg, R. Seshadri, O.H. Pescovitz, Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. J. Pediatr. 138(1), 26–32 (2001). doi:10.1067/mpd.2001.110527

    CAS  PubMed  Article  Google Scholar 

  121. C.G. Bergstrand, Growth in congenital adrenal hyperplasia. Acta. Paediatr. Scand. 55(5), 463–472 (1966)

    CAS  PubMed  Article  Google Scholar 

  122. R.T. Kirkland, B.S. Keenan, J.H. Holcombe, J.L. Kirkland, G.W. Clayton, The effect of therapy on mature height in congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 47(6), 1320–1324 (1978). doi:10.1210/jcem-47-6-1320

    CAS  PubMed  Article  Google Scholar 

  123. M.D. Urban, P.A. Lee, C.J. Migeon, Adult height and fertility in men with congenital virilizing adrenal hyperplasia. N. Engl. J. Med. 299(25), 1392–1396 (1978). doi:10.1056/NEJM197812212992505

    CAS  PubMed  Article  Google Scholar 

  124. J. DiMartino-Nardi, E. Stoner, A. O’Connell, M.I. New, The effect of treatment of final height in classical congenital adrenal hyperplasia (CAH). Acta. Endocrinol. Suppl. 279, 305–314 (1986)

    CAS  Google Scholar 

  125. A. Balsamo, A. Cicognani, L. Baldazzi, M. Barbaro, F. Baronio, M. Gennari, M. Bal, A. Cassio, K. Kontaxaki, E. Cacciari, CYP21 genotype, adult height, and pubertal development in 55 patients treated for 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 88(12), 5680–5688 (2003). doi:10.1210/jc.2003-030123

    CAS  PubMed  Article  Google Scholar 

  126. J. Jaaskelainen, R. Voutilainen, Bone mineral density in relation to glucocorticoid substitution therapy in adult patients with 21-hydroxylase deficiency. Clin. Endocrinol. 45(6), 707–713 (1996)

    CAS  Article  Google Scholar 

  127. Z. Chakhtoura, A. Bachelot, D. Samara-Boustani, J.C. Ruiz, B. Donadille, J. Dulon, S. Christin-Maitre, C. Bouvattier, M.C. Raux-Demay, P. Bouchard, J.C. Carel, J. Leger, F. Kuttenn, M. Polak, P. Touraine, Centre des Maladies Endocriniennes Rares de la, C., Association, S., Impact of total cumulative glucocorticoid dose on bone mineral density in patients with 21-hydroxylase deficiency. Eur. J. Endocrinol. 158(6), 879–887 (2008). doi:10.1530/EJE-07-0887

    CAS  PubMed  Article  Google Scholar 

  128. D. El-Maouche, S. Collier, M. Prasad, J.C. Reynolds, D.P. Merke, Cortical bone mineral density in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Clin. Endocrinol. (Oxf). 82(3), 330–337 (2015). doi:10.1111/cen.12507

    CAS  PubMed  Article  Google Scholar 

  129. H.L. Claahsen-van der Grinten, B.J. Otten, M.M. Stikkelbroeck, F.C. Sweep, A.R. Hermus, Testicular adrenal rest tumours in congenital adrenal hyperplasia. Best. Pract. Res. Clin. Endocrinol. Metab. 23(2), 209–220 (2009). doi:10.1016/j.beem.2008.09.007

    CAS  PubMed  Article  Google Scholar 

  130. M.A. Rich, M.A. Keating, Leydig cell tumors and tumors associated with congenital adrenal hyperplasia. Urol. Clin. North. Am. 27(3), 519–528 (2000). x

    CAS  PubMed  Article  Google Scholar 

  131. H.L. Claahsen-van der Grinten, B.J. Otten, A.R. Hermus, F.C. Sweep, C.A. Hulsbergen-van de Kaa, Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia can cause severe testicular damage. Fertil. Steril. 89(3), 597–601 (2008). doi:10.1016/j.fertnstert.2007.03.051

    PubMed  Article  Google Scholar 

  132. R.V. Clark, B.D. Albertson, A. Munabi, F. Cassorla, G. Aguilera, D.W. Warren, R.J. Sherins, D.L. Loriaux, Steroidogenic enzyme activities, morphology, and receptor studies of a testicular adrenal rest in a patient with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 70(5), 1408–1413 (1990). doi:10.1210/jcem-70-5-1408

    CAS  PubMed  Article  Google Scholar 

  133. J. Blumberg-Tick, P. Boudou, K. Nahoul, G. Schaison, Testicular tumors in congenital adrenal hyperplasia: steroid measurements from adrenal and spermatic veins. J. Clin. Endocrinol. Metab. 73(5), 1129–1133 (1991). doi:10.1210/jcem-73-5-1129

    CAS  PubMed  Article  Google Scholar 

  134. M.E. Combes-Moukhovsky, M.L. Kottler, P. Valensi, P. Boudou, M. Sibony, J.R. Attali, Gonadal and adrenal catheterization during adrenal suppression and gonadal stimulation in a patient with bilateral testicular tumors and congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 79(5), 1390–1394 (1994). doi:10.1210/jcem.79.5.7962333

    CAS  PubMed  Google Scholar 

  135. J.P. Bercovici, J. Fiet, L. Gibault, A. Volant, J.H. Abalain, H.H. Floch, E. Sonnet, G. Fournier, Testicular adrenal rest tumours in salt wasting congenital adrenal hyperplasia (in vivo and in vitro studies). J. Steroid. Biochem. Mol. Biol. 93(1), 67–72 (2005). doi:10.1016/j.jsbmb.2004.10.023

    CAS  PubMed  Article  Google Scholar 

  136. H.L. Claahsen-van der Grinten, B.J. Otten, F.C. Sweep, P.N. Span, H.A. Ross, E.J. Meuleman, A.R. Hermus, Testicular tumors in patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency show functional features of adrenocortical tissue. J. Clin. Endocrinol. Metab. 92(9), 3674–3680 (2007). doi:10.1210/jc.2007-0337

    CAS  PubMed  Article  Google Scholar 

  137. G.J. Hamwi, G. Gwinup, J.H. Mostow, P.K. Besch, Activation of testicular adrenal rest tissue by prolonged excessive acth production. J. Clin. Endocrinol. Metab. 23, 861–869 (1963). doi:10.1210/jcem-23-9-861

    CAS  PubMed  Article  Google Scholar 

  138. A.C. Bonaccorsi, I. Adler, J.G. Figueiredo, Male infertility due to congenital adrenal hyperplasia: testicular biopsy findings, hormonal evaluation, and therapeutic results in three patients. Fertil. Steril. 47(4), 664–670 (1987)

    CAS  PubMed  Article  Google Scholar 

  139. N.M. Stikkelbroeck, A.R. Hermus, H.M. Suliman, G.J. Jager, B.J. Otten, Asymptomatic testicular adrenal rest tumours in adolescent and adult males with congenital adrenal hyperplasia: basal and follow-up investigation after 2.6 years. J. Pediatr. Endocrinol. Metab. 17(4), 645–653 (2004)

    PubMed  Article  Google Scholar 

  140. N. Reisch, M. Scherr, L. Flade, M. Bidlingmaier, H.P. Schwarz, U. Muller-Lisse, M. Reincke, M. Quinkler, F. Beuschlein, Total adrenal volume but not testicular adrenal rest tumor volume is associated with hormonal control in patients with 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 95(5), 2065–2072 (2010). doi:10.1210/jc.2009-1929

    CAS  PubMed  Article  Google Scholar 

  141. N.M. Stikkelbroeck, B.J. Otten, A. Pasic, G.J. Jager, C.G. Sweep, K. Noordam, A.R. Hermus, High prevalence of testicular adrenal rest tumors, impaired spermatogenesis, and Leydig cell failure in adolescent and adult males with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 86(12), 5721–5728 (2001). doi:10.1210/jcem.86.12.8090

    CAS  PubMed  Article  Google Scholar 

  142. H.L. Claahsen-van der Grinten, F.C. Sweep, J.G. Blickman, A.R. Hermus, B.J. Otten, Prevalence of testicular adrenal rest tumours in male children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Eur. J. Endocrinol. 157(3), 339–344 (2007). doi:10.1530/EJE-07-0201

    CAS  PubMed  Article  Google Scholar 

  143. A. Martinez-Aguayo, A. Rocha, N. Rojas, C. Garcia, R. Parra, M. Lagos, L. Valdivia, H. Poggi, A. Cattani, Chilean Collaborative Testicular Adrenal Rest Tumor Study, G., Testicular adrenal rest tumors and Leydig and Sertoli cell function in boys with classical congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 92(12), 4583–4589 (2007). doi:10.1210/jc.2007-0383

    CAS  PubMed  Article  Google Scholar 

  144. U. Willi, M. Atares, A. Prader, M. Zachmann, Testicular adrenal-like tissue (TALT) in congenital adrenal hyperplasia: detection by ultrasonography. Pediatr. Radiol. 21(4), 284–287 (1991)

    CAS  PubMed  Article  Google Scholar 

  145. Z. Aycan, V.N. Bas, S. Cetinkaya, S. Yilmaz Agladioglu, T. Tiryaki, Prevalence and long-term follow-up outcomes of testicular adrenal rest tumours in children and adolescent males with congenital adrenal hyperplasia. Clin. Endocrinol. 78(5), 667–672 (2013). doi:10.1111/cen.12033

    Article  Google Scholar 

  146. M. Kaynar, M.G. Sonmez, Y. Unlu, T. Karatag, E. Tekinarslan, A. Sumer, Testicular adrenal rest tumor in 11-Beta-hydroxylase deficiency driven congenital adrenal hyperplasia. Korean J. Urol. 55(4), 292–294 (2014). doi:10.4111/kju.2014.55.4.292

    PubMed  PubMed Central  Article  Google Scholar 

  147. I. Karnak, M.E. Senocak, S. Gogus, N. Buyukpamukcu, A. Hicsonmez, Testicular enlargement in patients with 11-hydroxylase deficiency. J. Pediatr. Surg. 32(5), 756–758 (1997)

    CAS  PubMed  Article  Google Scholar 

  148. G.I. Bayhan, S. Cetinkaya, H.G. Cinar, Z. Aycan, Testicular adrenal rest tumor in a patient with 11beta-hydroxylase deficient congenital adrenal hyperplasia. J. Pediatr. Endocrinol. Metab. 23(7), 729–732 (2010)

    PubMed  Google Scholar 

  149. T. Unuvar, K. Demir, A. Abaci, A. Atas, H. Cakmakci, E. Bober, A 2-year-old boy with a testicular mass. Diagnosis: testicular tumor of adrenogenital syndrome due to 11-beta-hydroxylase deficiency. Pediatr. Ann. 39(8), 471–474 (2010). doi:10.3928/00904481-20100726-04

    PubMed  Article  Google Scholar 

  150. B.R. Walker, S.J. Skoog, B.H. Winslow, D.A. Canning, E.S. Tank, Testis sparing surgery for steroid unresponsive testicular tumors of the adrenogenital syndrome. J. Urol. 157(4), 1460–1463 (1997)

    CAS  PubMed  Article  Google Scholar 

  151. T. Tiryaki, Z. Aycan, S. Hucumenoglu, H. Atayurt, Testis sparing surgery for steroid unresponsive testicular tumors of the congenital adrenal hyperplasia. Pediatr. Surg. Int. 21(10), 853–855 (2005). doi:10.1007/s00383-005-1547-x

    PubMed  Article  Google Scholar 

  152. I. Nermoen, J. Rorvik, S.H. Holmedal, D.L. Hykkerud, K.J. Fougner, J. Svartberg, E.S. Husebye, K. Lovas, High frequency of adrenal myelolipomas and testicular adrenal rest tumours in adult Norwegian patients with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency. Clin. Endocrinol. 75(6), 753–759 (2011). doi:10.1111/j.1365-2265.2011.04151.x

    CAS  Article  Google Scholar 

  153. H. Falhammar, D.J. Torpy, Congenital adrenal hyperplasia due to 21-hydroxylase deficiency presenting as adrenal incidentaloma: a systematic review and meta-analysis. Endocr. Pract. 22(6), 736–752 (2016). doi:10.4158/EP151085.RA

    PubMed  Article  Google Scholar 

  154. S.M. Baumgartner-Parzer, S. Pauschenwein, W. Waldhausl, K. Polzler, P. Nowotny, H. Vierhapper, Increased prevalence of heterozygous 21-OH germline mutations in patients with adrenal incidentalomas. Clin. Endocrinol. (Oxf). 56(6), 811–816 (2002)

    CAS  PubMed  Article  Google Scholar 

  155. H. Falhammar, M. Thoren, An 88-year-old woman diagnosed with adrenal tumor and congenital adrenal hyperplasia: connection or coincidence? J. Endocrinol. Invest. 28(5), 449–453 (2005)

    CAS  PubMed  Article  Google Scholar 

  156. J. Patrova, I. Jarocka, H. Wahrenberg, H. Falhammar, Clinical outcomes in adrenal incidentaloma: experience from one center. Endocr. Pract. 21(8), 870–877 (2015). doi:10.4158/EP15618.OR

    PubMed  Article  Google Scholar 

  157. H. Falhammar, D.J. Torpy, A 42-year-old man presented with adrenal incidentaloma due to non-classic congenital adrenal hyperplasia with a novel CYP21A2 mutation. Intern. Med. J. 46(9), 1115–1116 (2016). doi:10.1111/imj.13177

    CAS  PubMed  Article  Google Scholar 

  158. H.G. Doerr, W.G. Sippell, S.L. Drop, F. Bidlingmaier, D. Knorr, Evidence of 11 beta-hydroxylase deficiency in childhood adrenocortical tumors. The plasma corticosterone/11-deoxycorticosterone ratio as a possible marker for malignancy. Cancer 60(7), 1625–1629 (1987)

    CAS  PubMed  Article  Google Scholar 

  159. E.A. Werder, R. Voutilainen, M. Zachmann, Virilizing adrenal tumour mimicking congenital adrenal hyperplasia with P450c11 (11 beta-hydroxylase) deficiency. Eur. J. Pediatr. 153(6), 411–415 (1994)

    CAS  PubMed  Google Scholar 

  160. M. Reincke, M. Peter, W.G. Sippell, B. Allolio, Impairment of 11 beta-hydroxylase but not 21-hydroxylase in adrenal ‘incidentalomas’. Eur. J. Endocrinol. 136(2), 196–200 (1997)

    CAS  PubMed  Article  Google Scholar 

  161. C. Dall’Asta, L. Barbetta, R. Libe, E. Passini, B. Ambrosi, Coexistence of 21-hydroxylase and 11 beta-hydroxylase deficiency in adrenal incidentalomas and in subclinical Cushing’s syndrome. Horm. Res. 57(5–6), 192–196 (2002). doi:58381

    PubMed  Google Scholar 

  162. M. Kacem, M. Said, L. Achour, F. Hadj Youssef, S. Ben Kacem, S. Mahjoub, M. Elmay, Large bilateral adrenal incidentalomas complicating untreated 11B hydroxylase deficiency in the third decade of life. A case report. Ann. Endocrinol. 61(5), 418–421 (2000)

    CAS  Google Scholar 

  163. Y. Touitou, P. Lecomte, A. Auzeby, A. Bogdan, Y. Besnier, Evidence of 11 beta-hydroxylase deficiency in a patient with cortical adrenal adenoma. Horm. Metab. Res. 21(5), 272–274 (1989). doi:10.1055/s-2007-1009210

    CAS  PubMed  Article  Google Scholar 

  164. N. Reisch, L. Flade, M. Scherr, M. Rottenkolber, F. Pedrosa Gil, M. Bidlingmaier, H. Wolff, H.P. Schwarz, M. Quinkler, F. Beuschlein, M. Reincke, High prevalence of reduced fecundity in men with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 94(5), 1665–1670 (2009). doi:10.1210/jc.2008-1414

    CAS  PubMed  Article  Google Scholar 

  165. P.J. Simm, M.R. Zacharin, Successful pregnancy in a patient with severe 11-beta-hydroxylase deficiency and novel mutations in CYP11B1 gene. Horm. Res. 68(6), 294–297 (2007). doi:10.1159/000107651

    CAS  PubMed  Google Scholar 

  166. M.E. Toaff, R. Toaff, R. Chayen, Congenital adrenal hyperplasia caused by 11 beta-hydroxylase deficiency with onset of symptoms after one spontaneous pregnancy. Am. J. Obstet. Gynecol. 121(2), 202–204 (1975)

    CAS  PubMed  Article  Google Scholar 

  167. R.M. Mulaikal, C.J. Migeon, J.A. Rock, Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. N. Engl. J. Med. 316(4), 178–182 (1987). doi:10.1056/NEJM198701223160402

    CAS  PubMed  Article  Google Scholar 

  168. J. Jaaskelainen, M. Hippelainen, O. Kiekara, R. Voutilainen, Child rate, pregnancy outcome and ovarian function in females with classical 21-hydroxylase deficiency. Acta. Obstet. Gynecol. Scand. 79(8), 687–692 (2000)

    CAS  PubMed  Google Scholar 

  169. N. Krone, I. Wachter, M. Stefanidou, A.A. Roscher, H.P. Schwarz, Mothers with congenital adrenal hyperplasia and their children: outcome of pregnancy, birth and childhood. Clin. Endocrinol. 55(4), 523–529 (2001)

    CAS  Article  Google Scholar 

  170. B.J. Otten, M.M. Stikkelbroeck, H.L. Claahsen-van der Grinten, A.R. Hermus, Puberty and fertility in congenital adrenal hyperplasia. Endocr. Dev. 8, 54–66 (2005). doi:10.1159/000084093

    CAS  PubMed  Google Scholar 

  171. F. Gastaud, C. Bouvattier, L. Duranteau, R. Brauner, E. Thibaud, F. Kutten, P. Bougneres, Impaired sexual and reproductive outcomes in women with classical forms of congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 92(4), 1391–1396 (2007). doi:10.1210/jc.2006-1757

    CAS  PubMed  Article  Google Scholar 

  172. J.C. Lo, M.M. Grumbach, Pregnancy outcomes in women with congenital virilizing adrenal hyperplasia. Endocrinol. Metab. Clin. North. Am. 30(1), 207–229 (2001)

    CAS  PubMed  Article  Google Scholar 

  173. A. Casteras, P. De Silva, G. Rumsby, G.S. Conway, Reassessing fecundity in women with classical congenital adrenal hyperplasia (CAH): normal pregnancy rate but reduced fertility rate. Clin. Endocrinol. 70(6), 833–837 (2009). doi:10.1111/j.1365-2265.2009.03563.x

    Article  Google Scholar 

  174. M. Bouchard, M.G. Forest, M. David, H. Dechaud, J.G. Juif, [Familial congenital adrenal hyperplasia caused by 11 beta-hydroxylase. Failure of prevention of sexual ambiguity and prenatal diagnosis]. Pediatrie. 44(8), 637–640 (1989)

    CAS  PubMed  Google Scholar 

  175. S. Geley, K. Kapelari, K. Johrer, M. Peter, J. Glatzl, H. Vierhapper, S. Schwarz, A. Helmberg, W.G. Sippell, P.C. White, R. Kofler, CYP11B1 mutations causing congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 81(8), 2896–2901 (1996). doi:10.1210/jcem.81.8.8768848

    CAS  PubMed  Google Scholar 

  176. B.I. Cerame, R.S. Newfield, R.C. Wilson, M.I. New, Prenatal diagnosis and treatment of 11beta-hydroxylase deficiency congenital adrenal hyperplasia. Diagnosis and treatment of unborn child, ed. by M.I. New (Idelson-Gnocchi Ltd., Reddick, FL, 1999), pp. 175–178

    Google Scholar 

  177. N.K. Maclaren, C.J. Migeon, S. Raiti, Gynecomastia with congenital virilizing adrenal hyperplasia (11-beta-hydroxylase deficiency). J. Pediatr. 86(4), 579–581 (1975)

    CAS  PubMed  Article  Google Scholar 

  178. M. Zachmann, A. Prader, Letter: Gynecomastia with congenital virilizing adrenal hyperplasia (11beta-hydroxylase deficiency). J. Pediatr. 87(5), 839–840 (1975)

    CAS  PubMed  Article  Google Scholar 

  179. Z. Zadik, A. Pertzelan, H. Kaufman, S. Levin, Z. Laron, Gynaecomastia in two prepubertal boys with congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Helv. Paediatr. Acta. 34(2), 185–187 (1979)

    CAS  PubMed  Google Scholar 

  180. Z. Hochberg, L. Even, Z. Zadik, Mineralocorticoids in the mechanism of gynecomastia in adrenal hyperplasia caused by 11 beta-hydroxylase deficiency. J. Pediatr. 118(2), 258–260 (1991)

    CAS  PubMed  Article  Google Scholar 

  181. K.M. Ajlouni, M.A. Arnaout, Y. Qoussous, Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency with skeletal abnormalities. J. Endocrinol. Invest. 19(5), 316–319 (1996)

    CAS  PubMed  Article  Google Scholar 

  182. H. Haibach, M.J. Rosenholtz, Prepubertal gynecomastia with lobules and acini: a case report and review of the literature. Am. J. Clin. Pathol. 80(2), 252–255 (1983)

    CAS  PubMed  Article  Google Scholar 

  183. A. Rosler, E. Leiberman, Enzymatic defects in steroidogenesis: 11beta hydroxylase deficiency CAH in Pediatric and adolescent endocrinology, ed. by M.I. New, L.S. Levine (Karger, Basel, 1984), pp. 47–64

    Google Scholar 

  184. E. Khorasani, R. Vakili, Congenital Adrenal Hyperplasia and Schmid Metaphyseal Chondrodysplasia in a Child. Iran J. Med. Sci. 41(1), 64–66 (2016)

    PubMed  Google Scholar 

  185. M. Peter, Congenital adrenal hyperplasia:11b-hydroxylase deficiency. Semin. Reprod. Med. 20(3), 249–254 (2002)

    CAS  PubMed  Article  Google Scholar 

  186. D.P. Merke, Approach to the adult with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J. Clin. Endocrinol. Metab. 93(3), 653–660 (2008). doi:10.1210/jc.2007-2417

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  187. K. Liivak, V. Tillmann, 24-hour blood pressure profiles in children with congenital adrenal hyperplasia on two different hydrocortisone treatment regimens. J. Pediatr. Endocrinol. Metab. 22(6), 511–517 (2009)

    CAS  PubMed  Article  Google Scholar 

  188. A. Nordenstrom, C. Marcus, M. Axelson, A. Wedell, E.M. Ritzen, Failure of cortisone acetate treatment in congenital adrenal hyperplasia because of defective 11beta-hydroxysteroid dehydrogenase reductase activity. J. Clin. Endocrinol. Metab. 84(4), 1210–1213 (1999). doi:10.1210/jcem.84.4.5584

    CAS  PubMed  Google Scholar 

  189. M. Quinkler, R. Miodini Nilsen, K. Zopf, M. Ventz, M. Oksnes, Modified-release hydrocortisone decreases BMI and HbA1c in patients with primary and secondary adrenal insufficiency. Eur. J. Endocrinol. 172(5), 619–626 (2015). doi:10.1530/EJE-14-1114

    CAS  PubMed  Article  Google Scholar 

  190. A. Bajpai, M. Kabra, P.S. Menon, Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency. J. Pediatr. Endocrinol. Metab. 19(6), 855–857 (2006)

    PubMed  Article  Google Scholar 

  191. L.J. Chalmers, L. Casas, M.I. New, P.R. Blackett, Prolongation of growth by treatment of 11-hydroxylase deficiency with depot-leuprolide, growth hormone, and hydrocortisone. J. Pediatr. Endocrinol. Metab. 19(10), 1251–1255 (2006)

    CAS  PubMed  Article  Google Scholar 

  192. M. Orio Hernandez, J. Yebra Yebra, C. Bezanilla Lopez, R. Gracia Bouthelier, [11beta-hydroxylase deficiency: improvement of final height with growth hormone and gonadotropin-releasing hormone analog]. An. Pediatr. 67(2), 153–156 (2007)

    CAS  Google Scholar 

  193. M.A. Nour, D. Pacaud, Height augmentation in 11beta-hydroxylase deficiency congenital adrenal hyperplasia. Int. J. Pediatr. Endocrinol. 2015(1), 12 (2015). doi:10.1186/s13633-015-0008-0

    PubMed  PubMed Central  Article  Google Scholar 

  194. D.I. Shulman, G.L. Francis, M.R. Palmert, E.A. Eugster, Lawson Wilkins Pediatric Endocrine Society, D., Therapeutics, C., Use of aromatase inhibitors in children and adolescents with disorders of growth and adolescent development. Pediatrics. 121(4), e975–983 (2008). doi:10.1542/peds.2007-2081

    PubMed  Article  Google Scholar 

  195. L. Laue, D.P. Merke, J.V. Jones, K.M. Barnes, S. Hill, G.B. Cutler Jr., A preliminary study of flutamide, testolactone, and reduced hydrocortisone dose in the treatment of congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 81(10), 3535–3539 (1996). doi:10.1210/jcem.81.10.8855797

    CAS  PubMed  Google Scholar 

  196. D.P. Merke, M.F. Keil, J.V. Jones, J. Fields, S. Hill, G.B. Cutler Jr., Flutamide, testolactone, and reduced hydrocortisone dose maintain normal growth velocity and bone maturation despite elevated androgen levels in children with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 85(3), 1114–1120 (2000). doi:10.1210/jcem.85.3.6462

    CAS  PubMed  Article  Google Scholar 

  197. K. Lin-Su, M.G. Vogiatzi, I. Marshall, M.D. Harbison, M.C. Macapagal, B. Betensky, S. Tansil, M.I. New, Treatment with growth hormone and luteinizing hormone releasing hormone analog improves final adult height in children with congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 90(6), 3318–3325 (2005). doi:10.1210/jc.2004-2128

    CAS  PubMed  Article  Google Scholar 

  198. J.J. Van Wyk, D.F. Gunther, E.M. Ritzen, A. Wedell, G.B. Cutler Jr., C.J. Migeon, M.I. New, The use of adrenalectomy as a treatment for congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 81(9), 3180–3190 (1996). doi:10.1210/jcem.81.9.8784066

    PubMed  Google Scholar 

  199. R.L. Meyers, J.R. Grua, Bilateral laparoscopic adrenalectomy: a new treatment for difficult cases of congenital adrenal hyperplasia. J. Pediatr. Surg. 35(11), 1586–1590 (2000). doi:10.1053/jpsu.2000.18321

    CAS  PubMed  Article  Google Scholar 

  200. S.A. Warinner, D. Zimmerman, G.B. Thompson, C.S. Grant, Study of three patients with congenital adrenal hyperplasia treated by bilateral adrenalectomy. World. J. Surg. 24(11), 1347–1352 (2000)

    CAS  PubMed  Article  Google Scholar 

  201. P.E. Clayton, W.L. Miller, E.M. Ritzen, S. Oberfield, W.G. Sippell, P.W. Speiser, Consensus statement on 21-hydroxylase deficiency from the Lawson Wilkins Pediatric endocrine society and the European society for Paediatric endocrinology. J. Clin. Endocrinol. Metab. 87(9), 4048–4053 (2002). doi:10.1210/jc.2002-020611. JOINT LWPES/ESPE CAH WORKING GROUP

    CAS  Article  Google Scholar 

  202. D.P. Merke, S.R. Bornstein, N.A. Avila, G.P. Chrousos, NIH conference. Future directions in the study and management of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Ann. Intern. Med. 136(4), 320–334 (2002)

    CAS  PubMed  Article  Google Scholar 

  203. J.J. Van Wyk, E.M. Ritzen, The role of bilateral adrenalectomy in the treatment of congenital adrenal hyperplasia. J. Clin. Endocrinol. Metab. 88(7), 2993–2998 (2003). doi:10.1210/jc.2002-022026

    PubMed  Article  CAS  Google Scholar 

  204. C.M. Ogilvie, G. Rumsby, T. Kurzawinski, G.S. Conway, Outcome of bilateral adrenalectomy in congenital adrenal hyperplasia: one unit’s experience. Eur. J. Endocrinol. 154(3), 405–408 (2006). doi:10.1530/eje.1.02096

    CAS  PubMed  Article  Google Scholar 

  205. J. Nasir, C. Royston, C. Walton, M.C. White, 11 beta-hydroxylase deficiency: management of a difficult case by laparoscopic bilateral adrenalectomy. Clin. Endocrinol. 45(2), 225–228 (1996)

    CAS  Article  Google Scholar 

  206. M. Kacem, A. Moussa, I. Khochtali, R. Nabouli, Y. Morel, A. Zakhama, Bilateral adrenalectomy for severe hypertension in congenital adrenal hyperplasia due to 11beta-hydroxylase deficiency: long term follow-up. Ann. Endocrinol. 70(2), 113–118 (2009). doi:10.1016/j.ando.2008.12.005

    CAS  Article  Google Scholar 

  207. J. Solyom, K. Racz, F. Peter, J. Homoki, W.G. Sippell, M. Peter, Clinical, hormonal and molecular genetic characterization of Hungarian patients with 11-hydroxylase deficiency. Int. J. Disabil. Hum. Dev 2, 37–44 (2001)

    CAS  Article  Google Scholar 

  208. M. Zhang, Y. Liu, S. Sun, H. Zhang, W. Wang, G. Ning, X. Li, A prevalent and three novel mutations in CYP11B1 gene identified in Chinese patients with 11-beta hydroxylase deficiency. J. Steroid. Biochem. Mol. Biol. 133, 25–29 (2013). doi:10.1016/j.jsbmb.2012.08.011

    CAS  PubMed  Article  Google Scholar 

  209. M. Kharrat, S. Trabelsi, M. Chaabouni, F. Maazoul, L. Kraoua, L. Ben Jemaa, N. Gandoura, S. Barsaoui, Y. Morel, R. M’Rad, H. Chaabouni, Only two mutations detected in 15 Tunisian patients with 11beta-hydroxylase deficiency: the p.Q356X and the novel p.G379V. Clin. Genet. 78(4), 398–401 (2010). doi:10.1111/j.1399-0004.2010.01403.x

    CAS  PubMed  Article  Google Scholar 

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Funding

Dr Krupali Bulsari has not received funding or research grant for this study. Associate Prof Henrik Falhammar has received support from the Magnus Bergvall Foundation, Karolinska Institutet and the Stockholm County Council.

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Authors and Affiliations

  1. Department of Endocrinology, Royal Darwin Hospital, Darwin, NT, Australia

    Krupali Bulsari & Henrik Falhammar

  2. Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden

    Henrik Falhammar

  3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Henrik Falhammar

  4. Menzies School of Health Research, Darwin, NT, Australia

    Henrik Falhammar

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  1. Krupali Bulsari
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Correspondence to Krupali Bulsari.

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Bulsari, K., Falhammar, H. Clinical perspectives in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency. Endocrine 55, 19–36 (2017). https://doi.org/10.1007/s12020-016-1189-x

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Keywords

  • CYP11B1
  • Diagnosis
  • Management
  • Complications