TY - JOUR

T1 - Serum insulin-like factor 3 quantification by LC-MS/MS in male patients with hypogonadotropic hypogonadism and Klinefelter syndrome

AU - Johannsen, Trine Holm

AU - Ljubicic, Marie Lindhardt

AU - Young, Jacques

AU - Trabado, Severine

AU - Petersen, Jørgen Holm

AU - Linneberg, Allan

AU - Albrethsen, Jakob

AU - Juul, Anders

PY - 2021

Y1 - 2021

N2 - Purpose Insulin-like factor 3 (INSL3) is an emerging testicular marker, yet larger studies elucidating the clinical role of INSL3 in patients with hypogonadism are lacking. The aim was to describe serum INSL3 concentrations analyzed by LC-MS/MS methodology in males with hypogonadotropic hypogonadism (HH) and Klinefelter syndrome (KS).Methods This was a combined study from two tertiary centers in Denmark and France analyzing INSL3 concentrations by LC-MS/MS. In total, 103 patients with HH and 82 patients with KS were grouped into treated (HH: n = 96; KS: n = 71) or untreated (HH: n = 7; KS: n = 11). Treatment modalities included testosterone and hCG. Serum concentrations and standard deviation (SD) scores of INSL3, total testosterone, and LH according to age and treatment were evaluated.Results In both HH and KS, INSL3 concentrations were low. In HH, INSL3 was low regardless of treatment, except for some hCG-treated patients with normal concentrations. In untreated HH, testosterone was low, while normal to high in most testosterone- and hCG-treated patients. In untreated KS, INSL3 and testosterone concentrations were low to normal, while in testosterone-treated KS, serum INSL3 was low in most patients. INSL3 SD scores were significantly lower in untreated HH than in untreated KS (p = 0.01).Conclusions The dichotomy between lower INSL3 and higher testosterone concentrations, particularly observed in hCG-treated patients with HH, confirms that INSL3 is a different marker of Leydig cell function than testosterone. However, the clinical application of INSL3 in males with hypogonadism remains unclear.

AB - Purpose Insulin-like factor 3 (INSL3) is an emerging testicular marker, yet larger studies elucidating the clinical role of INSL3 in patients with hypogonadism are lacking. The aim was to describe serum INSL3 concentrations analyzed by LC-MS/MS methodology in males with hypogonadotropic hypogonadism (HH) and Klinefelter syndrome (KS).Methods This was a combined study from two tertiary centers in Denmark and France analyzing INSL3 concentrations by LC-MS/MS. In total, 103 patients with HH and 82 patients with KS were grouped into treated (HH: n = 96; KS: n = 71) or untreated (HH: n = 7; KS: n = 11). Treatment modalities included testosterone and hCG. Serum concentrations and standard deviation (SD) scores of INSL3, total testosterone, and LH according to age and treatment were evaluated.Results In both HH and KS, INSL3 concentrations were low. In HH, INSL3 was low regardless of treatment, except for some hCG-treated patients with normal concentrations. In untreated HH, testosterone was low, while normal to high in most testosterone- and hCG-treated patients. In untreated KS, INSL3 and testosterone concentrations were low to normal, while in testosterone-treated KS, serum INSL3 was low in most patients. INSL3 SD scores were significantly lower in untreated HH than in untreated KS (p = 0.01).Conclusions The dichotomy between lower INSL3 and higher testosterone concentrations, particularly observed in hCG-treated patients with HH, confirms that INSL3 is a different marker of Leydig cell function than testosterone. However, the clinical application of INSL3 in males with hypogonadism remains unclear.

KW - INSL3

KW - Hypogonadotropic hypogonadism

KW - Klinefelter syndrome

KW - LC-MS/MS

U2 - 10.1007/s12020-021-02609-0

DO - 10.1007/s12020-021-02609-0

M3 - Journal article

C2 - 33483888

VL - 71

SP - 578

EP - 585

JO - Endocrine

JF - Endocrine

SN - 1355-008X

ER -