Shehab M A, Mahmood Tahseen, Hasanat M A, Fariduddin Md, Ahsan Nazmul, Hossain Mohammad Shahnoor, Hossain Md Shahdat, Jahan Sharmin
Department of Endocrinology, BSMMU, Dhaka, Bangladesh.
Department of Genetic Engineering & Biotechnology, University of Dhaka, Dhaka, Bangladesh.
Endocrinol Diabetes Metab Case Rep. 2018 Oct 13;2018(1):18-0108. doi: 10.1530/EDM-18-0108.
Congenital adrenal hyperplasia (CAH) due to the three-beta-hydroxysteroid-dehydrogenase (3β-HSD) enzyme deficiency is a rare autosomal recessive disorder presenting with sexual precocity in a phenotypic male. Klinefelter syndrome (KS) is the most common sex chromosome aneuploidy presenting with hypergonadotropic hypogonadism in a male. However, only a handful of cases of mosaic KS have been described in the literature. The co-existence of mosaic KS with CAH due to 3β-HSD enzyme deficiency portrays a unique diagnostic paradox where features of gonadal androgen deficiency are masked by simultaneous adrenal androgen excess. Here, we report a 7-year-old phenotypic male boy who, at birth presented with ambiguous genitalia, probably a microphallus with penoscrotal hypospadias. Later on, he developed accelerated growth with advanced bone age, premature pubarche, phallic enlargement and hyperpigmentation. Biochemically, the patient was proven to have CAH due to 3β-HSD deficiency. However, the co-existence of bilateral cryptorchidism made us to consider the possibility of hypogonadism as well, and it was further explained by concurrent existence of mosaic KS (47,XXY/46,XX). He was started on glucocorticoid and mineralocorticoid replacement and underwent right-sided orchidopexy on a later date. He showed significant clinical and biochemical improvement on subsequent follow-up. However, the declining value of serum testosterone was accompanied by rising level of FSH thereby unmasking hypergonadotropic hypogonadism due to mosaic KS. In future, we are planning to place him on androgen replacement as well. Learning points: •• Ambiguous genitalia with subsequent development of sexual precocity in a phenotypic male points towards some unusual varieties of CAH. •• High level of serum testosterone, adrenal androgen, plasma ACTH and low basal cortisol are proof of CAH, whereas elevated level of 17-OH pregnenolone is biochemical marker of 3β-HSD enzyme deficiency. •• Final diagnosis can be obtained with sequencing of HSD3B2 gene showing various mutations. •• Presence of bilateral cryptorchidism in such a patient may be due to underlying hypogonadism. •• Karyotyping in such patient may rarely show mosaic KS (47,XXY/46,XX) and there might be unmasking of hypergonadotropic hypogonadism resulting from adrenal androgen suppression from glucocorticoid treatment.
由于3β-羟基类固醇脱氢酶（3β-HSD）缺乏引起的先天性肾上腺增生（CAH）是一种罕见的常染色体隐性疾病，表现为表型男性性早熟。克氏综合征（KS）是最常见的性染色体非整倍体疾病，表现为男性高促性腺激素性性腺功能减退。然而，文献中仅描述了少数嵌合型KS病例。嵌合型KS与由于3β-HSD缺乏引起的CAH并存呈现出一种独特的诊断难题，即性腺雄激素缺乏的特征被同时存在的肾上腺雄激素过多所掩盖。在此，我们报告一名7岁表型男性患儿，出生时生殖器模糊，可能为小阴茎伴阴茎阴囊型尿道下裂。后来，他出现生长加速、骨龄提前、青春期早熟、阴茎增大和色素沉着。生化检查证实该患者因3β-HSD缺乏患有CAH。然而，双侧隐睾的存在使我们也考虑到性腺功能减退的可能性，而嵌合型KS（47,XXY/46,XX）的同时存在进一步解释了这一情况。他开始接受糖皮质激素和盐皮质激素替代治疗，并在之后接受了右侧睾丸固定术。在随后的随访中，他在临床和生化方面均有显著改善。然而，血清睾酮值下降的同时促卵泡生成素水平升高，从而揭示了嵌合型KS导致的高促性腺激素性性腺功能减退。未来，我们还计划给他进行雄激素替代治疗。学习要点：••表型男性生殖器模糊并随后出现性早熟提示某些不寻常类型的CAH。••血清睾酮、肾上腺雄激素、血浆促肾上腺皮质激素水平升高以及基础皮质醇水平降低是CAH的证据，而17-羟孕烯醇酮水平升高是3β-HSD缺乏的生化标志物。••通过对HSD3B2基因进行测序显示各种突变可获得最终诊断。••此类患者双侧隐睾的存在可能是由于潜在的性腺功能减退。••对此类患者进行核型分析很少会显示嵌合型KS（47,XXY/46,XX），并且可能会因糖皮质激素治疗抑制肾上腺雄激素而揭示高促性腺激素性性腺功能减退。
