Phenotypic Variation of 46,XX Late Identified Congenital Adrenal Hyperplasia among Indonesians
Keywords:
CAH, late-identified, phenotype, virilizationAbstract
Objective. To describe the phenotype variation in Indonesian 46,XX late-identified congenital adrenal hyperplasia (CAH) and the correlation between 17-hydroxyprogesterone (17-OHP) and genital virilization.
Methodology.Retrospective study of 39 cases with five salt-wasting (SW) and 34 simple virilizing (SV) types.
Results. The median age of the patients was 9.83 years (range, 0.58 to 44 years) with Prader score 2 to 5. Clitoromegaly (100%) and skin hyperpigmentation (87%) were the most common features. Lack of breast development (Tanner 1 to 2) and menstrual disorders occurred in 9 patients (teenagers and adults). Short stature (n=6), low voice (14), prominent Adam’s apple (9) and hirsutism (4) were found only in SV types. Rapid growth (n=7) and precocious puberty (8) were identified in children. Male gender on admission was found in 13 patients. The mean of 17-OHP level was 304.23 nmol/L [standard deviation (SD) 125.03 nmol/L]. There was no correlation between 17-OHP levels and virilization (r=0.19, p>0.05).
Conclusion. Late-identified CAH showed severe virilization and irreversible sequelae, with clitoromegaly and skin hyperpigmentation as the most commonly seen features. Masculinization of CAH females created uncertainty with regard to sex assignment at birth, resulting in female, male and undecided genders. There is no significant correlation between 17-OHP levels with the degree of virilization in CAH females.
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Ekenze SO, Nwangwu EI, Amah CC, Agugua-Obianyo NE, Onuh AC, Ajuzieogu OV. Disorders of sex development in a developing country: Perspectives and outcome of surgical management of 39 cases. Pediatr Surg Int. 2015;31(1):93-9. PMID: 25326123. https://doi.org/1007/s00383-014-3628-1.
Speiser PW, White PC. Congenital adrenal hyperplasia. N Engl J Med. 2003;349(8):776-88. PMID: 12930931. https://doi.org/10.1056/NEJMra021561.
Mooij CF, van Herwaarden AE, Claahsen-van der Grinten HL. Disorders of adrenal steroidogenesis: Impact on gonadal function and sex development. Pediatr Endocrinol Rev. 2016;14(2):109-28. PMID: 28508605. https://10.17458/PER.2016.MEC.DisordersofAdrenal.
Auchus RJ. The classic and nonclassic congenital adrenal hyperplasias. Endocr Pract. 2015;21(4):383-9. PMID: 25536973. https://doi.org/10.4158/EP14474.RA.
Sugiyama Y, Mizuno H, Hayashi Y, et al. Severity of virilization of external genitalia in Japanese patients with salt-wasting 21-hydroxylase deficiency. Tohoku J Exp Med. 2008;215(4):341-8. PMID: 18679008.
van der Kamp HJ, Wit JM. Neonatal screening for congenital adrenal hyperplasia. Eur J Endocrinol. 2004;151(Suppl 3):U71-5. PMID: 15554889.
Trapp CM, Oberfield SE. Recommendations for treatment of nonclassic congenital adrenal hyperplasia (NCCAH): An update. Steroids. 2012;77(4):342-6. PMID: 22186144. PMCID: PMC3638754. NIHMSID: NIHMS461777.
Juniarto AZ, van der Zwan YG, Santosa A, et al. Application of the new classification on patients with a disorder of sex development in Indonesia. Int J Endocrinol. 2012;2012:237084. PMID: 22253624. PMCID: PMC3255103. https://doi.org/10.1155/2012/237084.
Ediati A, Faradz SM, Juniarto AZ, van der Ende J, Drop SL, Dessens AB. Emotional and behavioral problems in late-¬identified Indonesian patients with disorders of sex development. J Psychosom Res. 2015;79(1):76-84. PMID: 25563666. https://doi.org/10.1016/j.jpsychores.2014.12.007.
Chang KSF, Lee MMC, Low WD. Standards of height and weight of Southern Chinese Children. Far East Med J. 1965;1:101-9.
Juniarto AZ, van der Zwan YG, Santosa A, et al. Hormonal evaluation in relation to phenotype and genotype in 286 patients with a disorder of sex development from Indonesia. Clin Endocrinol (Oxf). 2016;85(2):247-57. PMID: 26935236. https://doi.org/10.1111/cen.13051.
Dörr HG, Odenwald B, Nennstiel-Ratzel U. Early diagnosis of children with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency by newborn screening. Int J Neonatal Screen. 2015;1:36-44. https://doi.org/10.3390/ijns1010036.
Knowles RL, Khalid JM, Oerton JM, Hindmarsh PC, Kelnar CJ, Dezateux C. Late clinical presentation of congenital adrenal hyperplasia in older children: Findings from national paediatric surveillance. Arch Dis Child. 2014;99(1):30-4. PMID: 24043550. PMCID: PMC3888619. https://doi.org/10.1136/archdischild-2012-303070.
Ambroziak U, Bednarczuk T, Ginalska-Malinowska M, et al. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency - management in adults. Endokrynol Pol. 2010;61(1):142-55. PMID: 20205117.
Kulshreshtha B, Eunice M, Ammini AC. Pubertal development among girls with classical congenital adrenal hyperplasia initiated on treatment at different ages. Indian J Endocrinol Metab. 2012;16(4):599-603. PMID: 22837923. PMCID: PMC3401763. https://doi.org/10.4103/2230-8210.98018.
Sahakitrungruang T. Clinical and molecular review of atypical congenital adrenal hyperplasia. Ann Pediatr Endocrinol Metab. 2015;20(1):1-7. PMID: 25883920. PMCID: PMC4397267. https://doi.org.10.6065/apem.2015.20.1.1.
Moshiri M, Chapman T, Fechner PY, et al. Evaluation and management of disorders of sex development: Multidisciplinary approach to a complex diagnosis. Radiographics. 2012;32(6):1599-618. PMID: 23065160. https://doi.org/10.1148/rg.326125507.
Bonfig W, Schwarz HP. Growth pattern of untreated boys with simple virilizing congenital adrenal hyperplasia indicates relative androgen insensitivity during the first six months of life. Horm Res Paediatr. 2011:75(4):264-8. PMID: 21196707. https://doi.org/10.1159/000322580.
Hargitai B, Solyom J, Battelino T, et al. Growth patterns and final height in congenital adrenal hyperplasia due to classical 21-hydroxylase deficiency. Results of a multicenter Study. Horm Res. 2001;55(4):161-71. PMID: 11598369. https://doi.org/10.1159/000049990.
Rocha RO, Billerbeck AE, Pinto EM, et al. The degree of external genitalia virilization in girls with 21-hydroxylase deficiency appears to be influenced by the CAG repeats in the androgen receptor gene. Clin Endocrinol (Oxf). 2008;68(2):226-32. PMID: 17803691. https://doi.org/10.1111/j.1365-2265.2007.03023.x.
Warne GL, Raza J. Disorders of sex development (DSDs), their presentation and management in different cultures. Rev Endocr Metab Disord. 2008;9(3):227-36. PMID: 18633712. https://doi.org/10.1007/s11154-008-9084-2.
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