Male pseudohermaphroditism consistent with 17,20-desmolase deficiency

Area of Science:

• Endocrinology
• Genetics
• Reproductive Biology

Background:

• Male pseudohermaphroditism is a rare disorder of sex development where an individual with a Y chromosome has ambiguous or female-appearing genitalia.
• This case presents an unusual, nonfamilial form of the condition in a phenotypic female with an XY genotype.

Observation:

• A 16-year-old XY individual, raised as female, presented with absent pubertal development, primary amenorrhea, and underdeveloped secondary sexual characteristics.
• Physical examination revealed scant pubic hair, absent axillary hair, lack of breast development, and a blind-ending vagina without palpable uterus or adnexa.
• Hormonal analysis showed barely detectable testosterone and estradiol, with castrate levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH).

Findings:

• Testicular biopsy revealed atrophic seminiferous tubules and Leydig cells without hyperplasia, indicating impaired steroidogenesis.
• Exclusion of other steroidogenic enzyme deficiencies (20,22-desmolase, 3beta-HSD, 17-hydroxylase, 17beta-HSD) was established through extensive hormonal assays.
• Low levels of dehydroepiandrosterone sulfate (DHEA-S) and androstenedione (delta4 A), along with diminished excretion of dehydroepiandrosterone (DHEA), strongly indicate a 17,20-desmolase deficiency.

Implications:

• The findings highlight 17,20-desmolase deficiency as a potential cause of severe disorders of sex development in XY individuals.
• This case underscores the complexity of diagnosing steroidogenic enzyme defects, often requiring a combination of clinical, biochemical, and histological data.
• Further in vitro studies of testicular steroidogenesis are needed for definitive confirmation of the enzymatic defect.