Male pseudohermaphroditism due to 17-beta-hydroxysteroid dehydrogenase deficiency

Male pseudohermaphroditism due to 17-beta-hydroxysteroid dehydrogenase deficiency is a rare endocrine disorder characterized by a deficiency in the enzyme 17-beta-hydroxysteroid dehydrogenase (17β-HSD), which is crucial in the biosynthesis of androgens, including testosterone. This condition is a form of pseudohermaphroditism where individuals have male genotypes (typically 46,XY) but develop female or ambiguous external genitalia due to the inability to adequately produce testosterone during fetal development.

Etiology

The deficiency in 17β-HSD is caused by mutations in the HSD17B3 gene, which encodes the enzyme responsible for the conversion of androstenedione (a weak androgen) to testosterone, the potent androgen necessary for the masculinization of male genitalia in utero. The lack of this enzyme leads to insufficient testosterone levels, resulting in incomplete virilization of the external genitalia.

Clinical Presentation

Individuals with this condition often present at birth with ambiguous genitalia, which may lead to initial misassignment of gender. The phenotype can vary widely, from predominantly female external genitalia with a blind-ending vaginal pouch, to mildly undervirilized males. Internal reproductive structures (testes) are typically present but may be undescended (cryptorchidism). At puberty, affected individuals may experience virilization, including increased muscle mass, deepening of the voice, and growth of facial hair, due to the partial activity of other enzymes that can produce testosterone.

Diagnosis

Diagnosis is based on clinical examination, hormonal assays showing low testosterone and high androstenedione levels, and genetic testing confirming mutations in the HSD17B3 gene. Imaging studies, such as ultrasound, may be used to evaluate the presence and location of testicular tissue.

Treatment

Treatment is tailored to the individual's phenotype and gender identity. It may include hormone replacement therapy to promote development of secondary sexual characteristics consistent with the individual's gender identity. Surgical correction of genital anomalies may also be considered. Psychological support is crucial to address issues of gender identity, social integration, and fertility.

Prognosis

With appropriate medical and psychological support, individuals with male pseudohermaphroditism due to 17-beta-hydroxysteroid dehydrogenase deficiency can lead healthy and fulfilling lives. Fertility may be affected, and assisted reproductive technologies may be required for those wishing to have biological children.