GONADAL HISTOLOGY IN PATIENTS WITH MALE PSEUDOHERMAPHRODITISM AND ATYPICAL GONADAL DYSGENESIS: RELATION TO THEORIES OF SEX DIFFERENTIATION

Abstract

The anatomic findings and gonadal histology of 41 patients who had atypical forms of gonadal dysgenesis or of male pseudohermaphroditism are described. Fourteen of these cases were classified as atypical gonadal dysgenesis because there were gross evidences of abnormal gonadal development, differing from those of classical Turner''s syndrome. In this group there was no incidence of familial inheritance but there were evidences of chromosomal aberrations. Two patients diagnosed as "gonadal dysplasia" had primitive genital streaks differing from those of typical gonadal aplasia (Turner''s Syndrome) only in the presence of masses of Ley dig-like cells. That this condition is a variant of gonadal aplasia is suggested by the association of short stature in one case and by the demonstration in the other case of chromosomal mosaicism of XO/XX pattern, with the XO cell type predominant as in chromatin-negative Turner''s Syndrome. Ten patients had "asymmetrical gonadal differentiation" with a testis on one side and on the other side either no gonad (2 cases), a primitive genital streak (6 cases) or an undifferentiated gonad (2 cases). Among these mosaicism of XO/XY type was demonstrated in one case and it is suspected that more intensive chromosomal studies in the future may show a high incidence of mosaicism or other chromosomal aberration in this group. In addition 2 cases of true hermaphroditism are described. There were 27 male pseudohermaphrodites who had two testes with no histological evidences of dysgenesis. Eight of these patients had female external genitalia and 19 had genitalia which were ambiguous or resembled the male. In 4 patients of the latter group there were completely developed uterus and Fallopian tubes. Since the testes of all the male hermaphrodites showed good development of the medullary components believed to be responsible for male differentiation, it must be assumed that there was a defect in the biosynthesis of the "male organizing substances" of the foetal testes. Normal male XY chromosomal patterns were found in all of our cases which were studied and have been reported by other workers. The high familial incidence of this disorder suggests that an enzyme defect is transmitted by a mutant gene. In the "syndrome of feminizing testes" the demonstration of oestrogenic manifestations after puberty is further evidence of an abnormality of synthesis of testicular hormones. The correlation of gonadal pathology and the sex differentiation of gonaducts and external genitalia is compatible with the theory of Jost that normal masculinization is dependant upon the production of adequate amounts of masculinizing substances by the foetal testes. Discordances between the degree of masculinization (or feminization) of the gonaducts and the external genitalia can be explained only by postulating that there are at least two substances concerned: one causing masculinization of the Wolffian ducts and external genitalia and the other causing disappearance of the Mullerian ducts.