(707) The Impact of Metabolic SHBG Suppression on the Misdiagnosis of Hypogonadism in Obesity and Type 2 Diabetes

Introduction Total testosterone (TT) is the standard biochemical marker for diagnosing male hypogonadism (MH). However, in metabolic disorders such as obesity and T2DM, reduced sex hormone–binding globulin (SHBG) may lower TT despite preserved free testosterone (FT) levels, leading to false-positive diagnoses. Objective This study evaluated the prevalence and clinical profile of men presenting low TT but normal cFT due to metabolic SHBG suppression. Methods A retrospective study included patients with ED who had been screened for hypogonadism. Fasted early morning TT, SHBG, and albumin were measured to calculate cFT using Vermeulen formula. Low TT and low cFT were defined as < 345 ng/dL and < 6.5 ng/dL, respectively. The discordant phenotype of interest-low TT with normal cFT-was analyzed according to BMI and diabetes status. A linear model was used to identify metabolic and demographic predictors. Results Mean age was 59.4 ± 10.1 years and mean BMI was 28.4 ± 4.0 kg/m2. According to the WHO classification, 50 (22%) had normal weight, 106 (46.7%) overweight, 53 (23.3%) obesity type 1 and 18 (7.9%) obesity type 2. 33.5% had T2DM, 3.8% were on corticosteroids and 1.1% had hypothyroidism. Overall, 17 (6.4%) of men exhibited low TT but normal cFT. These men showed significantly lower SHBG (19.6 ± 6.3 nmol/L) compared with eugonadal controls and higher BMI (p < 0.001). Among men with T2DM and overweight/obesity, the prevalence of this phenotype reached 4.5% and 7.9%. Higher BMI and diabetes were independently associated with the false-positive phenotype (p = 0.002; p = 0.045). A multiple linear regression was conducted, and although the overall model was not statistically significant, corticosteroid use (p = 0.064) and hypothyroidism (p = 0.072) showed a non-significant trend. Low SHBG was associated with hypothyroidism (p < 0.001) as well as with obesity (p = 0.042). A marginal association was observed between low SHBG and diabetes (p = 0.052). Conclusions Metabolic suppression of SHBG in obesity and T2DM frequently results in low TT despite normal cFT, creating false-positive biochemical hypogonadism. Reliance on TT alone may therefore lead to unnecessary testosterone therapy in these patients. Routine SHBG measurement and cFT calculation should be incorporated into the diagnostic algorithm for men with metabolic disease to ensure accurate assessment of androgen status and avoid overtreatment. Disclosure No