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Nonclassic adrenal hyperplasia
Nonclassic adrenal hyperplasia Carlos Moran, M.D., M.Sc. Health Research Council, Mexican Institute of Social Security (IMSS), Mexico City, Mexico
Among 297 women with nonclassic adrenal hyperplasia (NCAH), premature pubarche was the most common complaint in girls (87%), and the frequency of hirsutism increased progressively with age from adolescence (50%) to adulthood (70%). The frequency of spontaneous miscarriages was high in NCAH patients (20%), but it decreased significantly after treatment. (Fertil Steril威 2006;86(Suppl 1):S3. ©2006 by American Society for Reproductive Medicine.) Key Words: Nonclassic adrenal hyperplasia, hyperandrogensim, autosomal recessive diseases
Congenital adrenal hyperplasia is an autosomal recessive genetic disorder. Mutations of gene CYP21 result in 21hydroxylase (21-OH) deficiency. This disease ranges from the classic adrenal hyperplasia (CAH), with clinical features since prenatal life, to the milder nonclassic adrenal hyperplasia (NCAH), without apparent signs at birth (1). Nonclassic adrenal hyperplasia affects approximately 0.05%– 0.1% of the general population, and 1%–10% of hyperandrogenic women, with higher frequencies in some ethnic groups (2). Some patients with NCAH develop symptoms since childhood, whereas others do so during adolescence or adulthood. The symptoms of NCAH are premature pubarche, primary amenorrhea, menstrual dysfunction, hirsutism, acne, alopecia, and infertility; however, some patients are asymptomatic (3). The phenotypes of NCAH and polycystic ovary syndrome (PCOS) are similar, making it difficult to distinguish them by their clinical features (2). The endocrine diagnosis of 21-OH– deficient NCAH is based on high basal or ACTHstimulated 17-hydroxyprogesterone levels (⬎10 ng/mL) (2). The diagnosis can be confirmed by genotyping (4). Some affected patients with NCAH are homozygous, and others have different mutations in each allele of CYP21 (compound heterozygotes). We have undertaken an international multicenter study on NCAH (3) to characterize the relationship between clinical Received January 13, 2006; revised and accepted March 9, 2006. Supported in part by research grants 38371-M from Consejo Nacional de Ciencia y Tecnología (CONACYT) and FP-2003/166 from the Mexican Institute of Social Security (IMSS). Presented in part at the 85th Annual Meeting of The Endocrine Society, Philadelphia, PA, June 19 –22, 2003. Reprint requests: Carlos Moran, M.D., 413 Interamerica Blvd. WH1, PMB 67-139, Laredo, Texas (FAX: 52-55-5653-1903; E-mail: cemoranv@ hotmail.com).
0015-0282/06/$32.00 doi:10.1016/j.fertnstert.2006.03.004
manifestations and age at the time of appearance, and to evaluate general outcome of pregnancies in NCAH patients. At present, 297 NCAH patients have been recruited, whose age distribution is as follows: ⬍10 yrs (n ⫽ 31), 10 –19 yrs (n ⫽ 80), 20 –29 yrs (n ⫽ 116), 30 –39 yrs (n ⫽ 44), and 40 – 49 yrs (n ⫽ 26). Premature pubarche was the most common complaint in children (87%). The frequency of hirsutism increased progressively with age from approximately 50% in adolescence to 70% in women 40 – 49 yrs old (3). To date, 107 NCAH women who had 206 pregnancies have been gathered, of which 71% were singleton term live births. These preliminary data show that the frequency of miscarriages decreases significantly (from 20% to 5%) after diagnosis of NCAH and treatment, as previously reported (5). The results of this ongoing study will assist in counseling women with NCAH regarding their reproductive outcome. Acknowledgments: To all members of the Nonclassic Adrenal Hyperplasia Multicenter Study Group who are participating in this ongoing project.
REFERENCES 1. New MI. An update of congenital adrenal hyperplasia. Ann N Y Acad Sci 2004;1038:14 – 43. 2. Moran C, Knochenhauer ES, Azziz R. Non-classic adrenal hyperplasia in hyperandrogenism: a reappraisal. J Endocrinol Invest 1998;21:707–20. 3. Moran C, Azziz R, Carmina E, Dewailly D, Fruzzetti F, Ibañez L, et al. 21-Hydroxylase– deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol 2000; 183:1468 –74. 4. Speiser PW, Knochenhauer ES, Dewailly D, Fruzzetti F, Marcondes JAM, Azziz R. A multicenter study of women with nonclassical congenital adrenal hyperplasia: relationship between genotype and phenotype. Mol Genet Metab 2000;71:527–34. 5. Feldman S, Billaud L, Thalabard JC, Raux-Demay MC, Mowszowicz I, Kuttenn F, et al. Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 1992;74:635–9.
Fertility and Sterility姞 Vol. 86, Suppl 1, July 2006 Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc.
S3
Among 297 women with nonclassic adrenal hyperplasia (NCAH), premature pubarche was the most common complaint in girls (87%), and the frequency of hirsutism increased progressively with age from adolescence (50%) to adulthood (70%). The frequency of spontaneous miscarriages was high in NCAH patients (20%), but it decreased significantly after treatment. (Fertil Steril威 2006;86(Suppl 1):S3. ©2006 by American Society for Reproductive Medicine.) Key Words: Nonclassic adrenal hyperplasia, hyperandrogensim, autosomal recessive diseases
Congenital adrenal hyperplasia is an autosomal recessive genetic disorder. Mutations of gene CYP21 result in 21hydroxylase (21-OH) deficiency. This disease ranges from the classic adrenal hyperplasia (CAH), with clinical features since prenatal life, to the milder nonclassic adrenal hyperplasia (NCAH), without apparent signs at birth (1). Nonclassic adrenal hyperplasia affects approximately 0.05%– 0.1% of the general population, and 1%–10% of hyperandrogenic women, with higher frequencies in some ethnic groups (2). Some patients with NCAH develop symptoms since childhood, whereas others do so during adolescence or adulthood. The symptoms of NCAH are premature pubarche, primary amenorrhea, menstrual dysfunction, hirsutism, acne, alopecia, and infertility; however, some patients are asymptomatic (3). The phenotypes of NCAH and polycystic ovary syndrome (PCOS) are similar, making it difficult to distinguish them by their clinical features (2). The endocrine diagnosis of 21-OH– deficient NCAH is based on high basal or ACTHstimulated 17-hydroxyprogesterone levels (⬎10 ng/mL) (2). The diagnosis can be confirmed by genotyping (4). Some affected patients with NCAH are homozygous, and others have different mutations in each allele of CYP21 (compound heterozygotes). We have undertaken an international multicenter study on NCAH (3) to characterize the relationship between clinical Received January 13, 2006; revised and accepted March 9, 2006. Supported in part by research grants 38371-M from Consejo Nacional de Ciencia y Tecnología (CONACYT) and FP-2003/166 from the Mexican Institute of Social Security (IMSS). Presented in part at the 85th Annual Meeting of The Endocrine Society, Philadelphia, PA, June 19 –22, 2003. Reprint requests: Carlos Moran, M.D., 413 Interamerica Blvd. WH1, PMB 67-139, Laredo, Texas (FAX: 52-55-5653-1903; E-mail: cemoranv@ hotmail.com).
0015-0282/06/$32.00 doi:10.1016/j.fertnstert.2006.03.004
manifestations and age at the time of appearance, and to evaluate general outcome of pregnancies in NCAH patients. At present, 297 NCAH patients have been recruited, whose age distribution is as follows: ⬍10 yrs (n ⫽ 31), 10 –19 yrs (n ⫽ 80), 20 –29 yrs (n ⫽ 116), 30 –39 yrs (n ⫽ 44), and 40 – 49 yrs (n ⫽ 26). Premature pubarche was the most common complaint in children (87%). The frequency of hirsutism increased progressively with age from approximately 50% in adolescence to 70% in women 40 – 49 yrs old (3). To date, 107 NCAH women who had 206 pregnancies have been gathered, of which 71% were singleton term live births. These preliminary data show that the frequency of miscarriages decreases significantly (from 20% to 5%) after diagnosis of NCAH and treatment, as previously reported (5). The results of this ongoing study will assist in counseling women with NCAH regarding their reproductive outcome. Acknowledgments: To all members of the Nonclassic Adrenal Hyperplasia Multicenter Study Group who are participating in this ongoing project.
REFERENCES 1. New MI. An update of congenital adrenal hyperplasia. Ann N Y Acad Sci 2004;1038:14 – 43. 2. Moran C, Knochenhauer ES, Azziz R. Non-classic adrenal hyperplasia in hyperandrogenism: a reappraisal. J Endocrinol Invest 1998;21:707–20. 3. Moran C, Azziz R, Carmina E, Dewailly D, Fruzzetti F, Ibañez L, et al. 21-Hydroxylase– deficient nonclassic adrenal hyperplasia is a progressive disorder: a multicenter study. Am J Obstet Gynecol 2000; 183:1468 –74. 4. Speiser PW, Knochenhauer ES, Dewailly D, Fruzzetti F, Marcondes JAM, Azziz R. A multicenter study of women with nonclassical congenital adrenal hyperplasia: relationship between genotype and phenotype. Mol Genet Metab 2000;71:527–34. 5. Feldman S, Billaud L, Thalabard JC, Raux-Demay MC, Mowszowicz I, Kuttenn F, et al. Fertility in women with late-onset adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Endocrinol Metab 1992;74:635–9.
Fertility and Sterility姞 Vol. 86, Suppl 1, July 2006 Copyright ©2006 American Society for Reproductive Medicine, Published by Elsevier Inc.
S3