Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography–tandem mass spectrometry

Belli, Serena; Santi, Daniele; Leoni, E; Dall'Olio, Enrico; Fanelli, Flaminia; Mezzullo, Marco; Pelusi, Carla; Rovedatti, L.; Tagliavini, Silvia; Trenti, Tommaso; Granata, Antonio R. M.; Pagotto, Uberto; Pasquali, Renato; Rochira, Vincenzo; Carani, Cesare; Simoni, Manuela

doi:10.1530/eje-15-1224

Cited by 26 publications

(22 citation statements)

References 40 publications

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“…Consistently, when adult men are acutely deprived of testosterone, CCL2 levels increase. These data suggest that a proinflammatory status in KS may also account for some dysfunction of Leydig cells [47,48] and that macrophage infiltration into an expanded adipose tissue might be involved in the development of MS in KS [49].…”

Section: Insulin-resistance and Metabolic Syndrome In Klinefelter Synmentioning

confidence: 89%

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

et al. 2018

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Section: Insulin-resistance and Metabolic Syndrome In Klinefelter Synmentioning

confidence: 89%

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

et al. 2018

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“…Progesterone, 17‐hydroxyprogesterone (17‐OHP), androstenedione, dehydroepiandrosterone (DHEA), and T were determined by liquid chromatography‐tandem mass spectrometry (LC–MS/MS) at the laboratory of the Centre for Applied Biomedical Research of the S. Orsola‐Malpighi Hospital, Alma Mater Studiorum, University of Bologna, Bologna, Italy, as previously reported 9 …”

Section: Methodsmentioning

confidence: 99%

Effects of acute hCG stimulation on serum INSL3 and 25‐OH vitamin D in Klinefelter syndrome

et al. 2020

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Background It has recently been suggested that the hypergonadotropic hypogonadism characterizing Klinefelter syndrome (KS) might not be due to a steroidogenic dysfunction per se, but mainly to an altered testosterone (T) secretion into the bloodstream. However, the Leydig cell functionality remains incompletely studied in KS, and new markers should be considered. Previous data indicated that chronic hCG stimulation influences the production of both insulin‐like peptide 3 (INSL3) and 25‐hydroxy‐vitamin D (25‐VD) in eugonadal men. Aim of the study To evaluate INSL3 and 25‐VD serum levels, as markers of Leydig cell functionality, in association with sex steroids, after an acute hCG test in a group of KS patients and healthy volunteers. Methods A retrospective analysis of a prospective case‐control clinical trial was carried out. KS patients (n = 11) and age‐matched healthy controls (n = 11) provided a basal blood sample (V0) immediately followed by a single intramuscular injection of hCG 5000 IU. Blood samples were taken in the following five days (V1‐V5). Results At baseline, INSL3 was lower in KS patients compared with controls (P = .007). When adjusted for INSL3 levels, the production of steroids was similar between KS patients and controls. 25‐VD was in the insufficient range both in KS patients and in controls and was not different (P = .064). Acute hCG stimulation increased neither INSL3 nor 25‐VD in both KS patients and controls. In controls, an inverse correlation was detected between INSL3 levels and body mass index (P = .020) and waist circumference (P = .020). Conclusions INSL3 secretion is independent from steroidogenesis, and its production is mostly not influenced by acute hCG stimulation both in KS men and in controls. INSL3 serum levels should be considered as a marker of Leydig cell differentiation and numbers rather than steroidogenesis. 25‐VD serum levels are also not increased by a single acute hCG administration, which was not able to restore the normal concentrations of 25‐VD.

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“…We aimed to optimize pre‐operative serum testosterone levels as follows: All patients with serum testosterone levels below 7.5 nmol/L were treated by subcutaneous human chorionic gonadotropin (hCG) injections 1500 IU twice weekly for 3 (−5) months prior to mTESE. The use of this protocol was based on the finding that KS men with low T levels—despite high levels of serum gonadotropins—may respond to hCG stimulation with subsequent elevation of serum T levels (Belli et al ., ). HCG was applied to optimize the intratesticular environment for spermatogenesis by increasing intratesticular testosterone levels during at least one spermatogenic cycle, without suppressing gonadotropin stimulation of the gonads, to improve chances for sperm retrieval (Ramasamy et al ., ).…”

Section: Methodsmentioning

confidence: 97%

A history of undescended testes in young men with Klinefelter syndrome does not reduce the chances for successful microsurgical testicular sperm extraction

et al. 2018

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Klinefelter syndrome (KS) and undescended testes (UDT) are known etiologies for non-obstructive azoospermia (NOA), and coexistence of both etiologies is not uncommon. Patients with both KS and a history of UDT are therefore considered to have extremely reduced chances for paternity. We aimed to analyze the impact of previous surgically corrected unilateral or bilateral UDT on sperm retrieval rates (SRRs) by microsurgical testicular sperm extraction (mTESE) in azoospermic men with KS. Age, testicular volumes, and hypothalamo-pituitary-gonadal axis function were investigated in relation to SRRs in 29 non-mosaic KS patients (47,XXY) with a history of UDT (group 1) who underwent mTESE between 2008 and 2016 in our center and compared to the data of age- and serum testosterone-matched non-mosaic KS controls with eutopic testes at birth (group 2), and to those of 51 men with NOA and a normal male karyotype (46,XY), but previous UDT (group 3). SRRs in KS patients with surgically corrected UDT during childhood were comparable to SRRs of KS patients with eutopic testes at birth: 31% (35% in unilateral and 22% in bilateral UDT) vs. 38% (p = 0.581). SRRs and Leydig cell function in group 1 were negatively correlated with age. Significantly higher SRRs (66%) were found in euploid azoospermic men with surgically corrected UDT (p < 0.001). A history of UDT does not preclude chances for future fatherhood in young azoospermic males with KS. In one of three men with previous unilateral UDT and in one of 4-5 in those with previous bilateral UDT, spermatozoa can be harvested by mTESE during late adolescence or young adulthood for immediate or future use in assisted reproduction.

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Human chorionic gonadotropin stimulation gives evidence of differences in testicular steroidogenesis in Klinefelter syndrome, as assessed by liquid chromatography–tandem mass spectrometry

Cited by 26 publications

References 40 publications

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Effects of acute hCG stimulation on serum INSL3 and 25‐OH vitamin D in Klinefelter syndrome

A history of undescended testes in young men with Klinefelter syndrome does not reduce the chances for successful microsurgical testicular sperm extraction

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