Clinical and biological parameters in 362 Klinefelter syndrome subjects: The KING experience

Klinefelter syndrome (KS) is a fascinating condition for clinicians and researchers due to the variety of open questions still waiting for an answer. KS is one of the most frequent chromosomal disorders, occurring in 1:500 to 1:1000 live male births. Although significant research has been conducted, KS remains frustratingly underdiagnosed with a remarkable portion of cases being unidentified, among which only 10% are in the prepubertal age while 25-50% in the adulthood. As a consequence, medical research results often become clouded due to the relatively small number of patients reported in scientific papers. To overcome this difficulty, the Italian Society of Andrology and Sexual Medicine (SIAMS) relayed to the expertise of Italian researchers and clinicians in this field to constitute an outstanding working group on KS. Thus, a network named KING (Klinefelter ItaliaN Group), aiming at sharing the know- how and collecting KS patients, to improve the knowledge of this syndrome, was created. KING is composed by fifteen high-specialized Endocrinology and Andrology units, either academic or institutes for treatment and research (IRCCS), located throughout Italy. Each unit has a principal investigator and a KING coordinator has been identified. Methods: A retrospective observational study of 362 KS patients among those regularly attending the units, after written informed consent has been obtained. Results: Up to now, three hundred and sixty two KS from 10 units have been registered. The mean age was 41.6±13.0 years (range:8–76years). Only seventeen KS were diagnosed before the age of 18 years. The mean testicolar volume was 2.9 ml in both testis(fig 1 A), BMI was 27.6±6 (fig 1 B) and 62 KS out of 265 meet the diagnostic criteria for metabolic syndrome (Mets). Total testostosterone plasma level was 386,3±202 ng/dl (Fig 2 panel A) with LH (Fig 2 panel A) and FSH mean levels of 16,65 ± 10 and 29,14±17 UI/L respectively. Conclusions: Our preliminary data showed a higher rate than expected of underdiagnosed KS compared to the Italian population that is made up of about 27.000.000 male subjects. This result, even if partial, raises the question of the true prevalence of KS, at least in Italy. Our patients presented with a wide spectrum of the classical Klinefelter symptoms. KS were overweight and, surprisingly, only 27% of them were diagnosed with Mets. In adulthood, two features were consistently present in every subject: small testes and high FSH and LH/testosterone ratio, despite normal testosterone levels. We confirm that such biochemical parameters combined with small testes should lead to a suspicion of KS.