Sibship with 17-ketosteroid reductase (17-KSR) deficiency and hypothyroidism. Lack of linkage of histocompatibility leucocyte antigen and 17-KSR loci

A family with nine children, three with male pseudohermaphroditism due to testicular deficiency of 17-ketosteroid reductase activity (17-KSR) and four with congenital hypothyroidism is presented. The three subjects with 17-KSR deficiency were raised as females until puberty, at which time they assumed a male gender role. Only one developed gynecomastia. Laparotomy on one of the three patients revealed normal epididymi and vas deferens with absence of Mullerian structures. Testicular biopsy in all three showed Leydig cell hyperplasia, hyalinization of the tubular basement membrane, normal Sertoli cells and maturational arrest at the spermatogonial stage. The endocrine profile in peripheral blood revealed markedly increased plasma androstenedione concentrations but normal testosterone, dihydrotestosterone, progesterone, 17-hydroxyprogesterone, and dehydroepiandrosterone. The levels of estradiol and estrone and of LH and FSH were elevated. Genital skin fibroblasts from the three patients exhibited normal dihydrotestosterone-binding activity and 5α-reductase activity. Congenital hypothyroidism affected one of the three siblings with male pseudohermaphroditism. All four hypothyroid patients had thyroid enlargement and significant titers of circulating antithyroglobulin but not antithyroid microsomal antibodies. Neither the locus for the 17-KSR enzyme nor that for congenital hypothyroidism were linked to the histocompatibility leucocyte antigen complex in this sibship. Transmission of the trait for both congenital hypothyroidism and 17-KSR deficiency appeared to be autosomal recessive.