CO CHARACTERISTICS GEOGRAPHICAL DISTRIBUTION AND AGE AT DIAGNOSIS OF PATIENTS WITH KLINEFELTER SYNDROME IN ITALY A COHORT STUDY FROM THE KLINEFELTER ITALIAN GROUP KING

PATIENTS WITH KLINEFELTER SYNDROME IN ITALY A COHORT STUDY FROM THE KLINEFELTER ITALIAN GROUP KING D Pa a i A Ga a G Acca d P Chi di i V Si e A Fe i M Maggi L Vig i G C a F La f a c V R chi a A Ca ge V Giag i M B i R Pi e G Ba e cia A Pi ca P Sa ac e A A e a Di a i e di Scie e Mediche e Chi giche A a a e Na i U i e i à di Pad a Pad a Di a i e di Sa e Me a e e Fi ica E edici a P e e i a Na i U i e i à di B e cia B g a U i e i à di Fi e e Fi e e AUSL di B g a B g a Di a i e di Scie e Mediche di T i T i U i e i à di M de a e Reggi E i ia M de a U i e i à di Ca a ai Ca a ia ASL di Ba i Ba i U i e i à di Mi a e IRCCS I i A gic Mi a U i e i à di Medici a C i ica e Chi gica Na i U i e i à di A c a e de e Ma che A c a IRCCS I i C i ic H a i a R a Mi a Mi a Sa a Ma ia G e i H i a La i a U i e i à di Ca a a Ca a a I d c


D Pa a i A Ga a G Acca d P Chi di i V Si e A Fe i M Maggi L Vig i G C a F La f a c V R chi a A Ca ge V Giag i M B i R Pi e G Ba e cia A Pi ca P Sa ac e A A e a Di a i e di Scie e Mediche e Chi giche A a a e Na i U i e i à di Pad a Pad a
Klinefelter syndrome (KS) is the most frequent chromosomal disorders, occurring in : to : live male births, associated to male infertility. Although significant research has been conducted, KS remains frustratingly underdiagnosed with a remarkable portion of cases being unidentified, among which only are in the prepubertal age while -in the adulthood. Under diagnosis may be due to men's hesitancy about seeking medical attention, low awareness of KS among health professionals, and failure by health professionals to perform routine genital examinations in adult men.
A Our purpose was to describe the phenotypic characteristics and the hormonal patterns of a large cohort of patients currently attending a national network of academic or general hospitals of the Klinefelter Italian Group (KING). Moreover, we focused our interest on the geographical distribution, and age at diagnosis of KS patients in Italy.

Me d
A multicenter, observational study of KS was performed among the patients regularly attending the KING centers, after written informed consent has been obtained.

Re
Five hundred and ninety four KS from units have been registered. The mean age was .
. years (median IQR -) The mean testicular volume was ml in both testis (fig A), BMI was .

(fig
of KS meet the diagnostic criteria for metabolic syndrome (Mets). Mean total testosterone was . ng/dl, and LH and FSH mean levels were , (median IQR . -. ) and . (median IQR ( . -), respectively. A descriptive analysis performed in KS, showed that KS were referred to KING centers of Northern Italy, and KS patients to KING facilities in Central and Southern Italy, respectively. Analysis of variance showed significant statistical differences (p ) between the ages at diagnosis of the KS of the three geographical groups. In particular the age of KS patients was significantly lower in Southern Italy ( . SD) compared to Central and Northern Italy ( .
. SD and .

C c
Our preliminary data showed that KS is highly underdiagnosed in Italy, raising the question of the true prevalence of KS. Our patients presented with a wide spectrum of the classical Klinefelter symptoms. KS were overweight and, surprisingly, only , of them were diagnosed with Mets. This figure is very close to the Mets prevalence in the Italian general population quoted around . In adulthood, two features were consistently present in every subject: small testes and high FSH and LH/testosterone ratio, despite normal testosterone levels. The differences of KS age between geographical groups highlight the need for increased awareness leading to timely detection.