Further Evidence of the Clinical, Hormonal, and Genetic Heterogeneity of Klinefelter Syndrome: A Study of 216 Infertile Egyptian Patients

Abstract

This study aims to provide further insight into the phenotypic heterogeneity of Klinefelter syndrome (KS) by presenting clinical, hormonal, and genetic data from a large series of Egyptian infertile patients with KS. A retrospective case series of KS patients was studied over a period from January 2003 to April 2010. All patients underwent a complete history and physical examination; color duplex examination; semen analysis; measurement of total testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL); and chromosomal typing. Mosaic KS diagnosis was confirmed by fluorescence in situ hybridization. The series included 216 KS patients (198 nonmosaic, 16 mosaic, and 2 KS variants). Typical clinical signs of hypoandrogenism were observed in 86% of patients. Gynecomastia affected 20.8% of the patients. Eunuchoidal body proportions, with arm span exceeding height and lower segment length exceeding upper segment length, were detected in 43.9% and 64.4% of the patients, respectively. In all patients, a reduction in testicular size and azoospermia were detected. Normal levels of T, FSH, LH, E2, and PRL were detected in 44.5%, 3.7%, 3.3%, 93.5%, and 91.2% of patients, respectively. Differences were not significant between patients with classic KS and those with mosaic KS in terms of the frequency of clinical signs of hypoandrogenism, gynecomastia, low T concentrations, or high concentrations of FSH, LH, E2, and PRL (all P . .05). The results of the current study emphasize the heterogeneous clinical, hormonal, and genetic phenotype of infertile KS patients. Our findings support the usefulness of cytogenetic studies in infertile patients showing small testicular size and azoospermia, regardless of the presence of other clinical or endocrine findings.

Obesity and Hyperglycemia in Korean Men with Klinefelter Syndrome: The Korean Endocrine Society Registry

“…The median total testosterone level in the current study was in the lower-to-normal range, whereas LH and FSH levels were increased, consistent with previous studies [1891925]. This suggests that hypogonadism in KS is relative rather than absolute [4].…”

“…This suggests that hypogonadism in KS is relative rather than absolute [4]. Among patients with KS, 45.1% to 56.5% have low total testosterone levels [1925]. …”

Endogenous sex hormones and risk of venous thromboembolism in women and men

“…A similar risk has been observed in randomized clinical intervention trials of estrogen treatment of men, and studies have been discontinued due to an excess of cardiovascular events, including thromboembolisms . Also, patients with Klinefelter′s syndrome (47, XXY), who have low endogenous testosterone and high estradiol concentrations, have a prevalence of DVT and PE 5–20 times higher than in the general population . The present finding that high endogenous estrogen concentrations in both women and men were not associated with the risk of VTE is therefore a reassuring finding.…”

TRANSITION IN ENDOCRINOLOGY: Management of Klinefelter syndrome during transition

“…Insufficient awareness of the presenting symptoms of KS, as well as the wide spectrum of symptoms, disables an early diagnosis: only a minority (about 10%) of patients with KS are currently diagnosed before puberty (3,20). Cryptorchidism, behavioral problems, and learning disabilities as well as tall stature may suggest the diagnosis before puberty.…”

“…Routine karyotyping is therefore advocated in all adolescents and young men with small testes, hypergonadotropic hypogonadism, and eventually diagnosed non-obstructive azoospermia (20).…”