Hypogonadism with Normal Serum Testosterone

A 69-year-old man was referred to the endocrine clinic with a 3-year history of erectile dysfunction, reduced libido, and lack of nocturnal tumescence with no response to phosphodiesterase type 5 inhibitors (sildenafil and tadalafil). The symptoms troubled him to such an extent that he asked his general practitioner to be referred to a specialist clinic. The patient had been through a normal puberty. Although he fathered no children, he was unconcerned about this and never sought fertility investigation or treatment. His past medical history was clinically significant for newly diagnosed interstitial lung disease owing to hypersensitivity pneumonitis, osteoarthritis, and gastroesophageal reflux; his only medications were ibuprofen gel and lansoprazole. He was never prescribed steroids, ketoconazole, or spironolactone. He had not undergone ionizing radiation and denied using over-the-counter or recreational drugs. He was an ex-smoker who drank 8 units of alcohol weekly. He did not recall a prior history of mumps or testicular trauma. He was unaware of any family members who had an autoimmune disorder or fertility issues. On examination he was 178 cm tall and obese [body mass index (BMI) 37.3 kg/m2]. His arm-span-to-height ratio was <1.05 and his cardiovascular examination did not reveal heart murmurs. He had a normal hair pattern and no gynecomastia. Testicular volume was reduced bilaterally at 12–15 mL (reference interval ≥15 mL). Testosterone, measured by a 1-step chemiluminescent immunoassay (Abbott Architect, second generation testosterone assay) was 16.0 nmol/L (reference interval 4.9–32 nmol/L); his sex hormone–binding globulin (SHBG)3 was increased at 153 nmol/L (13.5–71.4 nmol/L) as were luteinizing hormone (LH) and follicle-stimulating hormone (FSH) at 33.4 IU/L (0.6–12.0 IU/L) and 54.7 IU/L (1.0–11.9 IU/L), respectively (Table 1). These results, which indicated hypergonadotropic hypogonadism, were confirmed on repeated testing 3 weeks later. At that time, testosterone was also measured by LC-MS/MS and the …