Incomplete androgen insensitivity: asymmetry in morphology and steroid profile and metabolism of the gonads. An analysis of a case

Abstract

A patient with clinical manifestations of the incomplete androgen insensitivity syndrome was studied with respect to peripheral blood levels of steroids and steroid sulphates before, during and after gonadectomy. Steroid and steroid sulphate concentrations were also analyzed in spermatic venous blood and gonadal tissue collected during surgery. The metabolic capacity of gonadal tissue was also studied in vitro using progesterone, dehydroepiandrosterone sulphate and oestrone sulphate as substrates.Profound differences between the two gonads were noted with respect to both steroid content and release into pampiniform veins and to in vitro conversion of progesterone and oestrone sulphate. Histological examination revealed the presence of seminiferous tubules with carcinoma in situ in both gonads. It is suggested that the differences between the gonads may be due to an autonomous steroid production in the right gonad in spite of adequate or even elevated gonadotrophic stimulation resulting in a steroidogenic situation resembling the complete androgen insenstitivity syndrome, while the conditions found in the left gonad more resembles the incomplete form of the disease.The syndrome of testicular feminization is con¬ sidered to be due to androgen receptor deficiency. Therefore, gonadotrophic stimulation and steroidogenesis would be expected to be enhanced. How¬ ever, sometimes selected enzymatic steps involved in testosterone production may be deficient (Bell 1975). A case is here presented with fundamental differences between the two gonads with respect to both morphology, steroid content and steroid metabolism. Case Description and MethodsA 35-year old Arabian woman sought advice because of primary amenorrhoea and infertility. She had experi¬ enced pubertal development at the age of 13 to 14 years and had always been healthy. On examination ordinary female sex characteristics were apparent, breasts were well developed and pubic hair growth was present. No uterus could be found and the vagina ended blindly. In the right groin a plum-sized tumour was found, later identified as the gonad. The left gonad was not accessible to examination. Chromosome analysis of short-term cul¬ tured lymphocytes revealed the karyotype 46,XY (Q-and G-banding). The clinical diagnosis of incomplete testicu¬ lar feminization was based on these findings together with the histologie picture of the gonads, in accordance with the definition given by Rosenfield et al. (1971).