Partial androgen insensitivity: the Reifenstein syndrome revisited

Area of Science:

• Endocrinology
• Genetics
• Reproductive Medicine

Background:

• Reifenstein syndrome presents with undervirilization in 46,XY individuals.
• The exact hormonal basis and genetic underpinnings of Reifenstein syndrome require further elucidation.

Purpose of the Study:

• To investigate the hormonal basis of Reifenstein syndrome in eight patients.
• To determine if the condition stems from androgen synthesis defects or impaired androgen action.
• To explore potential genetic variants related to androgen receptor function.

Main Methods:

• Assessed plasma androgen concentrations, testosterone and dihydrotestosterone production rates.
• Measured serum luteinizing hormone levels.
• Evaluated 5alpha-reductase activity and dihydrotestosterone binding in skin fibroblasts.

Main Results:

• Patients exhibited normal/elevated plasma androgens and normal testosterone/dihydrotestosterone production rates.
• Elevated serum luteinizing hormone levels were observed, suggesting impaired negative feedback.
• Skin fibroblast studies revealed normal 5alpha-reductase activity, but dihydrotestosterone binding showed variations, including partial deficiency in one patient.
• Four patients had normal dihydrotestosterone binding, indicating an unknown cause for androgen insensitivity.

Conclusions:

• Reifenstein syndrome is characterized by defective androgen action, not diminished androgen synthesis.
• Partial androgen insensitivity syndrome is a more accurate descriptor.
• Genetic heterogeneity exists, with some cases linked to dihydrotestosterone binding defects and others having an unknown molecular basis.
• Testosterone treatment demonstrated potential for mild virilization and suppressed luteinizing hormone.