Partial Androgen Insensitivity: The Reifenstein Syndrome Revisited

We investigated eight patients with the Reifenstein syndrome to define the hormonal basis for this condition. The patients had normal or elevated concentrations of plasma androgens, normal production rates of testosterone and dihydrotestosterone, elevated serum levels of luteinizing hormone and normal 5α-reductase activity in skin fibroblasts. These findings indicate that the syndrome results from defective androgen action rather than from decreased androgen synthesis. The term “partial androgen insensitivity syndrome” describes this condition more accurately than a term based on clinical phenotype. Dihydrotestosterone binding studies in skin fibroblasts demonstrated two genetic variants similar to those reported in complete androgen insensitivity syndrome. One patient had a partial deficiency of cytoplasmic dihydrotestosterone binding, and four others had normal binding activity. The cause of the androgen insensitivity in the last four cases is unknown. Treatment with testosterone suppressed serum luteinizing hormone levels and promoted mild virilizing effects. (N Engl J Med 297:350–356, 1977) Reifenstein originally described a clinical phenotype of hereditary male pseudohermaphroditism consisting of hypospadias, gynecomastia with incomplete virilization at puberty and infertility.¹ In 1965 Bowen et al.² evaluated three families with this syndrome, including the original family of Reifenstein, and found decreased urinary testosterone glucuronide excretion in three affected members of two of the families, suggesting that the syndrome was due to inadequate testosterone production. However, Wilson et al.³ recently restudied one of the three families reported by Bowen and provided evidence that the abnormality in this family is diminished end-organ sensitivity to androgen rather than decreased androgen production. In the.