Endocrine Abstracts

JOINT2958

Background: Individuals with 46,XX testicular DSD (T-DSD) and 47,XXY Klinefelter syndrome (KS) have a male phenotype, but sex chromosome aneuploidy with a supernumerary X chromosome. In contrast to KS, T-DSD males lack a major part of the Y chromosome. In both conditions, testicular dysgenesis leads to hypogonadism with infertility. While biological paternity can be achieved in a subset of KS men using assisted reproductive technology, this is impossible in men with T-DSD, where spermatogenesis cannot take place due to the absence of the Y chromosomal AZF region.

Aim of the study: To gain insight into the effects of X-linked supernumerary genes with and without additional Y-chromosomal gene deficiency on human body proportions, hypothalamic-pituitary-gonadal (HPG) axis function, testicular morphology and the risk of gonadal malignancy.

Patients and Methods: Retrospective and cross-sectional data from (n = 50) males with T-DSD aged 14-67 years and (n = 91) males with KS were evaluated, including medical history data, anthropometric and hormonal data, testicular ultrasound imaging and histological images of testicular biopsies.

Results: Men with T-DSD had a shorter stature than predicted from parental target height (TH). In contrast, final height of the KS men exceeded their TH. Both males with T-DSD and KS had significantly reduced testicular volumes and ultrasound imaging of their testes showed reduced echogenicity of the gonadal parenchyma, with multiple hypoechogenic areas in older men. Biopsies from these areas within the testes evidenced benign Leydig cell hyperplasia. There were no cases of testicular malignancies observed in either cohort. Hypergonadotropic hypogonadism developed during adolescence in both conditions, with decompensation of testicular endocrine function occurring at different times in life. LH serum concentrations were inadequately low for serum testosterone concentrations mainly in older men with T-DSD. The vast majority of T-DSD males had Inhibin B concentrations below the detection limit at any age, in contrast, Inhibin B was measurable in some young KS males.

Conclusions: Final height in males with T-DSD and KS does not result from hypogonadism, which occurs similarly in both conditions, but rather from the absence or presence of Y chromosomal genes. In both KS and T-DSD, decompensation of endocrine testicular function occurs at variable times in the course of life, but a relative central HPG axis deficiency contributes to this only in T-DSD. Focal areas of reduced echogenicity within the testes of men with KS and TDSD on ultrasound are not indicative of malignancy but correspond to clusters of hyperplastic Leydig cells.