Endocrine Abstracts

Klinefelter syndrome (KS; 47,XXY) is the most common sex chromosome disorder in man, affecting approximately 1:660 men, and is a common cause of infertility.

Patients with KS are characterized by tall stature and progressive testicular failure. This results in azoospermia and androgen deficiency with an accompanying risk of developing several phenotypic characteristics in adulthood, e.g., osteopenia or even frank osteoporosis, and metabolic syndrome.

Recent studies on Klinefelter infants during the so-called minipuberty have indicated that serum testosterone (T) concentrations are low or low- normal. Many adults with Klinefelter syndrome have subnormal serum concentrations of total T and the majority of patients have T in the lower half of the normal range, as well as elevated LH. A bivariate LH-T comparison reveals an abnormal LH-T setpoint suggestive of abnormal Leydig cell function.

Sertoli cell function is not impaired in KS patients until puberty, as reflected by normal AMH and inhibin B concentrations in KS boys during infancy and childhood. However, in mid- to late puberty, Sertoli cell function deteriorates progressively, resulting in extremely low or undetectable AMH and inhibin B concentrations, very high FSH levels and small testicular volumes.

Accordingly, patients with Klinefelter syndrome are at increased risk of developing osteopenia or osteoporosis already in young adulthood, whereas normal bone mineralization during childhood and adolescence has been reported. Recent studies showed an increased incidence of an unfavourable change in body composition; with accumulation of body fat and decreased muscle mass already in prepubertal boys with KS. In addition, adult patients have an increased risk of diabetes with decreased insulin sensitivity. It is not known to which degree these symptoms are the result of additional copies of non-inactivated genes on the supernumerary X chromosomes, lifestyle factors, or whether they are partly (or completely) the result of an impaired pituitary-gonadal function.

Special efforts to detect this under-diagnosed chromosome disorder are necessary in order to initiate early androgen therapy, and to prevent the development of a deleterious body composition with the risk of metabolic syndrome.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.