Case report reveals azoospermia in a male with congenital adrenal hypoplasia, suggesting the need for genetic testing.
X-linked congenital adrenal hypoplasia (X-linked AHC) is a rare endocrine disorder causing primary adrenal insufficiency (PAI) and often associated with hypogonadotropic hypogonadism (HH). We report a 23-year-old male with early-onset PAI, normal puberty, and azoospermia despite normal testosterone levels. Whole-exome sequencing revealed a novel NR0B1 pathogenic variant (c.625C>T; p.Gln209). NR0B1, also known as DAX1, is critical for adrenal and gonadal development, and animal models suggest that Sertoli cell dysfunction is a key mechanism of infertility, occurring independently of gonadotropin or androgen deficiencies. Taken together, this case expands the clinical spectrum of NR0B1-related disease and underscores the importance of early genetic testing and consideration of this diagnosis even in patients with X-linked AHC and atypical presentations.
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Meireles et al. (2026) studied this question.
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