The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry

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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“…The steroid profiles after hCG stimulation in KS patients and controls have been previously published 9,27 …”

Section: Resultsmentioning

confidence: 99%

“…The steroid profiles after hCG stimulation in KS patients and controls have been previously published. 9,27 On average, baseline INSL3 levels (V0) were lower in KS patients (444 ± 350 pg/mL) than in controls (780 ± 190 pg/mL) (P = .007) (Table 1).…”

Section: Baseline Leydig Cell Functionalitymentioning

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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“…The need of partitioning the IGF‐1 RI by age requires a larger number of subjects in each age range, so as to fulfill the recommendations of the CLSI standard. Moreover, we recently demonstrated that immunoenzymatic methods constitutively overestimate T detection, compared with mass spectrometry, although in a different clinical setting . Thus, this result should be better evaluated using different assays.…”

Section: Discussionmentioning

confidence: 98%

“…Moreover, we recently demonstrated that immunoenzymatic methods constitutively overestimate T detection, compared with mass spectrometry, although in a different clinical setting. 34 Thus, this result should be better evaluated using different assays. Moreover, many variables, both related to female physiology and to lifestyle, can influence T circulating levels in female subjects and can underlie the difference we found.…”

Section: Hormonal Trend During Regular Seasonmentioning

confidence: 99%

Testosterone, cortisol,hGH, andIGF‐1 levels in anItalianfemale elite volleyball team

Rovedatti

Vincentis

Rocchi

et al. 2018

Health Science Reports

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PurposeTo assess the transferability of the reference intervals (RI) of testosterone (T), cortisol (C), human growth hormone (hGH), and insulin‐like growth factor (IGF)‐1, calculated on a normal healthy population, to a population of female elite volleyball players. Secondary aim of this study is the evaluation of the T/C ratio as predictive tool of overtraining during the annual regular season.MethodsA retrospective, longitudinal, observational study was performed, enrolling 58 professional female volleyball players periodically evaluated during the regular sportive season, which lasts from September to May.ResultsStatistically significant differences between the volleyball players and reference populations for T (P = .010), C (P < .001), and IGF‐1 (P < .001) were found. Three different statistical approaches to calculate the RI in the athlete group showed a high degree of concordance and pointed out a shift upwards of both lower and upper reference limits. The T/C ratio significantly changed among visits (P = .009). In particular, an overall decrease of about 30% was observed for this ratio during the season, suggesting a state of overtraining.ConclusionT, C, hGH, and IGF‐1 reference values calculated on elite volleyball female players are higher than those of the reference population used in normal clinical practice, suggesting that the health status of highly trained subjects needs the definition of tailored RI for these variables. Moreover, the utility of T/C ratio in the evaluation of overtraining is confirmed.

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“…Some studies comparing limits, advantages and disadvantages of steroid levels using IA and LC-MS/MS methods are available in the literature [1,4,19,20] but none of them have compared the performance of such methods to assess androgen secretion under hCG stimulus conditions in children.…”

Section: Introductionmentioning

confidence: 99%

Androgens by immunoassay and mass spectrometry in children with 46,XY disorder of sex development

Oliveira

Longui

Guaragna-Filho

et al. 2020

Endocrine Connections

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Objective: Steroid measurement is a challenge in pediatric endocrinology. Currently, liquid chromatography with tandem mass spectrometry (LC-MS/MS) is considered a gold standard for this purpose. The aim of this study was to compare both LC-MS/MS and immunoassay (IA) for androgens before and after human recombinant chorionic gonadotropin (r-hCG) stimulus in children with 46,XY Disorders of Sex Development (DSD). Methods: Nineteen patients with 46,XY DSD were evaluated; all of them were prepubertal and non gonadectomized. Testosterone, dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA) and androstenedione were measured by IA and LC-MS/MS before and 7 days after rhCG injection. The correlation between IA and LC-MS/MS was analysed by the intraclass correlation coefficient (ICC) and Spearman's rank correlation coefficient (SCC). For concordance analysis the Passing and Bablok (PB) regression and the Bland and Altman (BA) method were used. Results: Testosterone showed excellent correlation (ICC = 0.960 and SCC = 0.964); DHT showed insignificant and moderate correlations as indicated by ICC (0.222) and SCC (0.631), respectively; DHEA showed moderate correlation (ICC = 0.585 and SCC = 0.716); and androstenedione had poor and moderate correlations in ICC (0.363) and SCC (0.735), respectively. Using the PB method, all hormones showed a linear correlation, but proportional and systematic concordance errors were detected for androstenedione, systematic errors for testosterone and no errors for DHEA and DHT. By the BA method, there was a trend of IA to overestimate testosterone and androstenedione and underestimate DHEA and DHT when compared to LC-MS/MS. Conclusion: Traditional IA should be replaced by LC-MS/MS for the androgens measurement in prepubertal children whenever is possible.

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The steroid response to human chorionic gonadotropin (hCG) stimulation in men with Klinefelter syndrome does not change using immunoassay or mass spectrometry

Cited by 8 publications

References 31 publications

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

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

Testosterone, cortisol,hGH, andIGF‐1 levels in anItalianfemale elite volleyball team

Androgens by immunoassay and mass spectrometry in children with 46,XY disorder of sex development

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