Endocrine Abstracts

Section 1: Case history: A 19-year-old British-Asian man presented with a two-year history of gynaecomastia. He had no other symptoms of hypogonadism. He had an unremarkable past medical history, did not take any regular medications and denied the use of any illicit drugs. There was a family history of consanguinity, with his parents being first cousins. On examination, his BMI was 28 kg/m² and he had post-pubertal-sized testes (20 ml) with normal secondary sexual characteristics.

Section 2: Investigations: Hypogonadism was confirmed by two morning fasting total testosterone levels of 4.7 and 5.2 (RR 9.2–31.6 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 1.2–7.8 iU/l), FSH 2.1 (RR 2.0–5.0 iU/l) consistent with hypogonadotrophic hypogonadism. Other pituitary hormone levels and MRI pituitary were normal. In view of his unequivocal biochemical hypogonadism, he was started on testosterone replacement therapy. A DEXA scan following six years of testosterone replacement showed slightly low bone density for chronological age in the spine only (spine Z −2.1, hip Z −1.3). Seminal fluid analysis was normal on several occasions and he had fathered a child.

Section 3: Results and treatment: He was re-evaluated following 7 years 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 15–55 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 father was also found to have a low fasting morning testosterone of 4.3 nmol/l and low SHBG of 4 nmol/l (father’s BMI 24 kg/m²), suggestive of a rare inherited SHBG mutation (analysis pending). Blood samples from the patient and his father have also been sent for direct measurement of salivary testosterone and free testosterone (results pending).

Conclusion and points for discussion: 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 misdiagnosis of gonadal function even in patients with very low (ie non-borderline) testosterone levels, if SHBG is not evaluated. Minimal end-organ pathology and/or kisspeptin challenge may provide a clue in these cases.