Case: A 19-year-old British-Asian man presented with a two-year history of gynaecomastia. He had no other symptoms of hypogonadism. On examination, BMI was 28 kg/m2 and he had post-pubertal-sized testes (20 ml) with normal secondary sexual characteristics. Hypogonadism was confirmed by two morning fasting total testosterone levels of 4.7 and 5.2 (RR 9.231.6 nmol/l). Haemoglobin was normal (152 g/l) and serum oestradiol was <100 pmol/l. He had inappropriately normal serum gonadotrophin levels: LH 1.2 (RR 1.27.8 iU/l), FSH 2.1 (RR 2.05.0 iU/l) consistent with hypogonadotrophic hypogonadism. Other pituitary hormone levels and MRI pituitary were normal. In view of his biochemical hypogonadism, he was started on testosterone replacement therapy. A DEXA scan following six years of testosterone replacement showed Z scores of −2.1 in the spine and −1.3 in the hips. Seminal fluid analysis was normal on several occasions and he had fathered a child. He was re-evaluated following 7yrs of testosterone therapy. Both pituitary-function tested with a 100 mcg GnRH test, and hypothalamic-function tested with a kisspeptin-54 challenge test, were consistent with responses of healthy men. His sex hormone binding globulin (SHBG) was found to be consistently low at 6 (RR 1555 nmol/l). His calculated free testosterone level by the Vermeulen equation was found to be borderline at 0.251 (RR >0.225 nmol/l). His fathers SHBG was also found to be very low at 4 nmol/l (fathers BMI 24 kg/m2) consistent with a rare inherited SHBG mutation (analysis pending).
Conclusion: The interpretation of serum gonadotrophins relies on the initial determination that testosterone levels are consistent with hypogonadism. Endocrine Society guidance suggests that SHBG does not need to be measured unless the testosterone level is borderline, or conditions that could affect the SHBG level exist. This case highlights the potential for misclassification of gonadal function if unexpectedly low SHBG levels are not considered when evaluating patients presenting with possible hypogonadism.