Endocrine Abstracts

JOINT2117

Background: KS is a genetic condition characterized by an extra X chromosome in male individuals associated with an increased risk of primary hypogonadism, which requires testosterone replacement therapy (TRT) when suggestive signs, symptoms and low serum Testosterone (T) are present. While IA remains the standard method for T measurement in the clinic, LC-MS/MS is increasingly being utilized also in clinical laboratory settings.

Aim: The aim of this study is to analyze the accuracy of IA compared to the gold standard LC-MS/MS for the diagnosis and monitoring of hypogonadism in patients with KS.

Materials and Methods: A total of 67 measurements (33 untreated and 34 under TRT) in KS patients were accrued: serum total T (TT) was assessed by both LC-MS/MS and IA, together with SHBG for calculated free testosterone (cfT). Hypogonadism was defined according to the Italian Society of Andrology and Sexual Medicine (SIAMS) threshold: serum TT ≤ 3.5 ng/mL and/or cfT < 6.5 ng/dl. TT was quantified using CMIA DxI800 Beckman Coulter (IA)and Chrosystems MassChrom® Steroids in Serum/Plasma kit on Sciex CitrineTM (LC-MS/MS); cfT was calculated with the Vermeulen formula.

Results: The overall cohort and the subgroup not under TRT showed similar results, with only some minor differences. Serum TT measured by IA showed a strong positive correlation with LC-MS/MS measurements (respectively R²=0.891, P < 0.001 and R²=0.849, P < 0.001) similarly to cfT (respectively R²=0.853, P < 0.001 and R²=0.638, P < 0.001). However, a higher prevalence of biochemical hypogonadism was observed with IA compared to LC-MS/MS for TT both in all (41.17% vs 23.53%, OR 1.94, P = 0.059) and in untreated KS (75.75% vs 60.61%, OR 2.03, P = 0.190). A similar but significant result was found for cfT in all (54.69% vs 34.38%, OR 2.16, P = 0.033) and in untreated KS (75.75% vs 45.46%, OR 3.75, P = 0.014). Finally, in the subgroup of patients not under TRT a higher concordance between the two methods, LC-MS/MS and IA, (R²=0.950, P < 0.001) was observed for total testosterone levels > 3.5 than ≤ 3.5 ng/ml, highlighting some challenges in discriminating hypogonadal subjects.

Discussion: In accordance with what discovered in the overall population at risk for hypogonadism, even in KS patients IA seems to overestimate significantly both the prevalence of hypotestosteronemia and TRT compensation for TT and cfT when compared to LC-MS/MS. Hence, LC-MS/MS and SHBG assessments in every day clinical practice are probably crucial to detect and to correctly address to treatment KS patients, as well as for monitoring TRT.