First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy

Pasquali D; Chiodini P; Simeon V; Ferlin A; Vignozzi L; Corona G; Lanfranco F; Rochira V; Calogero AE; Bonomi M; Pivonello R; Balercia G; Pizzocaro A; Giagulli VA; Salacone P; Aversa A; Accardo G; Maggi M; Lenzi A; Isidori A; Foresta C; Jannini EA; Garolla A; KING; Klinefelter ItaliaN Group

doi:10.1007/s40618-022-01816-4

Genetics and Immunology · Reproductive Genetics

First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy

Pasquali D, Chiodini P, Simeon V, Ferlin A, Vignozzi L, Corona G, Lanfranco F, Rochira V, Calogero AE, Bonomi M, Pivonello R, Balercia G, Pizzocaro A, Giagulli VA, Salacone P, Aversa A, Accardo G, Maggi M, Lenzi A, Isidori A, Foresta C, Jannini EA, Garolla A, KING, Klinefelter ItaliaN Group

Published September 2022 Journal of endocrinological investigation

DOI 10.1007/s40618-022-01816-4 PMID 35608733 PMC PMC9360143

RRM Academy Synopsis

Klinefelter syndrome was diagnosed at a mean age of 37.4 in Italy

Klinefelter syndrome was diagnosed at a mean age of 37.4 years in a multicenter cohort of 609 men seen at Italian national network centers from 2014 to 2018. The men had small testes and raised LH and FSH. Metabolic syndrome affected 25.5% of the cohort, fewer than earlier reports.

Key Findings

The 609 men had a mean age at diagnosis of 37.4 ± 13.4 years. Age at diagnosis did not change from 2014 to 2018.
Only 46 men in the cohort were diagnosed before 18 years of age.
Mean age at diagnosis was 33.3 ± 13 years in Southern Italy, 40.2 ± 12.5 in Central Italy and 39.2 ± 13.3 in Northern Italy (p < 0.0001).
Metabolic syndrome was present in 25.5% of the cohort, against 44% and 34.3% in two earlier reports. Mean BMI was 26.6 ± 5.8 kg/m2.
Each testis averaged 3 ml in size. LH and FSH were raised, and median total testosterone was in the low-normal range.

Interpretation

The KING study is an observational cohort run across many centers. Investigators enrolled 609 men in the order they appeared, each with a confirmed 47,XXY karyotype. Data came from the time of diagnosis, and the study collected no follow-up measurements. The network centers are responsible mainly for the care of adult men. The authors say the results support the view that the syndrome is under-diagnosed in Italy, since the network saw only a small fraction of the men expected from population prevalence. They call the reason for the lower metabolic syndrome share unclear and name diet as one possible factor.

RRM Context

Klinefelter syndrome is the most common chromosomal disorder linked to male infertility. The authors note that many men first learn the diagnosis during couple infertility counseling. They give low awareness among health professionals and missed genital exams in adult men as reasons for late diagnosis. Restorative reproductive medicine treats the couple as the patient. It looks for causes in both partners from the outset, so a male cause such as Klinefelter syndrome enters the first workup.

Our editorial summary of this paper, not the article's abstract.

Abstract

Background

Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.

Objective

We describe KS clinical presentation in a large Italian cohort.

Design

This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution.

Methods

We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients.

Results

Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m2, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis.

Conclusions

These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.

Topics

Genetics and Immunology Reproductive Genetics Chromosomal Abnormalities

Genetics and Immunology › Reproductive Genetics › Chromosomal Abnormalities

PMID 35608733 35608733 DOI 10.1007/s40618-022-01816-4 10.1007/s40618-022-01816-4 Pasquali et al. 2022, Pasquali 2022

First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy

Klinefelter syndrome was diagnosed at a mean age of 37.4 in Italy

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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