1Sapienza University of Rome; [email protected]; 2Department of Experimental Medicine, Sapienza University of Rome; 3Department of Pediatrics, Sapienza University of Rome
Background: Experimental studies on Klinefelter syndrome (KS) reported increased intratesticular testosterone (T) levels coexisting with reduced circulating levels. Abnormalities in testicular microcirculation have been claimed; however, no studies investigated in vivo testicular blood flow dynamics in humans with KS.
Objective: To analyze the testicular microcirculation in KS by contrast-enhanced ultrasonography (CEUS) and correlate vascular parameters with endocrine function.
Methods: We conducted 51 testicular scans in 17 testes from 10 T-naïve subjects with KS and in 34 testes from age-matched eugonadal men (CNT), who underwent CEUS for incidental nonpalpable testicular lesions. SonoVue contrast was employed, and QLAB software was used for perfusion analyses. CEUS kinetic parameters represented the main outcome measures.
Results: CEUS revealed slower testicular perfusion kinetics in subjects with KS than in age-matched CNT. Specifically, the wash-in time (Tin, 9.36 [7.54-12.73] vs. 7.42 [5.458.82] seconds, P=0.008), mean transit time (MTT, 11.8 [10.6617.53] vs. 10.46 [8.2112.75] seconds, P=0.008), time to peak (TTP, 42.3[37.8550.47] vs. 35 [26.838.54] seconds, p<0.001), and washout time (Tout 50%, 31.51 [21.9338.76] vs. 23.41 [16.9229.95] seconds, P=0.008) were all prolonged. Faster testicular blood flow was associated with higher total T levels (rS -0.52 , p<0.001). Principal component analysis and multiple linear regression analyses confirmed the findings and supported a role for reduced venous blood flow as independent predictor of total T levels (b=-2.467 [-4.757, -0.1], P=0.04).
Conclusions: In our study we confirm an altered testicular microcirculation in men with KS, with slower venous blood flow compared to age-matched eugonadal CNT, independently predicting peripheral T release. Further studies are required to expand our findings and to establish whether CEUS may be useful in predicting the testicular catastrophe of KS.