Case Study

A thirty-year-old gentleman presented with primary infertility after inability to conceive for fifteen months. Medical history was significant for obesity with body mass index of 40kg/m². He was on no regular medications. On physical examination, he has well-virilised with testicular volumes of 15ml bilaterally. Serial investigations revealed progressive oligospermia (Table 1), whilst total testosterone concentrations were unexpectedly unrecordably high (>52nmol/L) and accompanied by marked elevation in serum hormone binding globulin (SHBG) concentrations (Table 2). Despite normal liver function tests (LFTs), liver imaging demonstrated cirrhosis. Hepatitic screen identified a reduced serum ceruloplasmin level and an elevated 24-hour urinary copper excretion. Our patient was diagnosed with Wilson’s disease and was commenced on penicillamine.

Discussion

Total testosterone (TTe) concentrations reflect both free and protein-bound testosterone proportions¹. Approximately 50% of protein-bound testosterone is bound to SHBG with high affinity¹. TTe can therefore be inaccurate where SHBG concentrations are altered². The role of measuring calculated free testosterone levels when TTe levels are unreliable remains debated given no consensus regarding a standardised formula³.

Elevated serum total testosterone levels in conjunction with elevated SHBG concentrations should prompt investigation into the underlying aetiology¹. Causes of increased SHBG concentrations include hyperthyroidism, elevated oestrogen states such as chronic liver disease and pregnancy, and medications including the oral contraceptive pill¹. Our case highlights the need to exclude cirrhosis despite normal LFTs.