Serum insulin-like factor 3 quantification by LC-MS/MS in male patients with hypogonadotropic hypogonadism and
Trine Holm Johannsen1,2, Marie Lindhardt Ljubicic3,4, Jacques Young5
1Dept. of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. trine.holm.johannsen@regionh.dk.
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.
