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 [00BB]gonadal dysplasia[00AB] had primitive genital streaks differing from those of typical gonadal aplasia (Turner's Syndrome) only in the presence of masses of Leydig-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 [00BB]asymmetricalgonadal differentiation[00AB]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

Predictive Value of Anatomical Findings and Karyotype Analysis in the Diagnosis of Patients with Disorders of Sexual Development

“…It is now well established, for example, that patients with asymmetric gonadal differentiation frequently have a 45,X/46,XY mosaicism [Bergadá and Cleveland, 1962;Josso et al, 1966] or that the presence of a 46,XX cell line and ovotestes are the most frequent findings in ovotesticular DSD [Verkauskas et al, 2007]. However, in his usual practice the physician is confronted with a patient in whom he finds signs or symptoms, from which he has to draw conclusions in order to approach a diagnosis and take an action.…”

“…A vast majority of these patients (86%) had asymmetric gonadal differentia-tion -also known as mixed gonadal dysgenesis and included in the sex chromosome DSD of the recently proposed nomenclature -but the mosaicism was also found in patients with 2 dysgenetic testes. Asymmetric gonadal differentiation was first described in patients with a 45,X/46,XY mosaicism [Bergadá and Cleveland, 1962], and it was believed for years that the sole existence of this abnormal karyotype would be associated with abnormal gonadal differentiation. However, the increasing practice of prenatal karyotyping has shown that a 45,X/46,XY mosaicism can be an accidental finding in a boy with normal genitalia [Telvi et al, 1999].…”

“…3 nmol/l) and/or extremely low number of Leydig cells in a biopsy after hCG stimulation (500-1000 U i.m. injections every other day for 1-2 weeks), or to steroidogenic protein defects, as diagnosed by low serum testosterone after hCG stimulation and/or abnormal steroid ratios and/ or a steroidogenic enzyme mutation; (b) partial androgen insensitivity syndrome, as diagnosed by normal or high serum testosterone after hCG stimulation and/or an androgen receptor mutation or a familial history of androgen insensitivity; and (c) 5 ␣ -reductase defects, as diagnosed by normal or high serum testosterone and low serum DHT/T ratio after hCG stimulation; (3) dysgenetic MPH or Y chromosme bearing testicular DSD: 46,XY karyotype or mosaicisms containing at least one 46,XY cell line with signs of testicular dysgenesis in the biopsy and/or low serum AMH [Rey et al, 1999], including asymmetric gonadal differentiation or mixed gonadal dysgenesis defined by the presence of one male gonad and a contralateral streak by histological studies [Bergadá and Cleveland, 1962]; and (4) true hermaphroditism or ovotesticular DSD: various karyotypes and existence of testicular and ovarian tissue as defined by the presence of at least one ovarian follicle in the histological study.…”

Mixed Gonadal Dysgenesis

“…According to Sohval [3] the condition is classified as mixed gonadal dysgenesis, corresponding to the term asym m etrical gonadal differentiation, as named by Bergada et al [1]. Both term s indicate th a t these patients form a transient group from pure gonadal dysgenesis to male pseudohermaphoroditism with bi lateral testicular developm ent.…”

Mixed Gonodal Dysgenesis with 46/XY Karyotype

“…[10] and Greenblatt [9]. 8 cases were reported by Bergada et al [2]. Recently Sohval in his excellent reviews [19,20] delineated such cases as a special type of intersexuality and proposed the name of " mixed" gonadal dys genesis.…”