We report the case of a 26 year old man who presented to his GP with infertility; biochemical investigations revealed elevated serum free thyroid hormones (FT4 41 pmol/l (1222); FT3 13.4 pmol/l (2.87.1); and a normal TSH (2 pmol/l (0.274.2). He was referred to the endocrine department.
On examination, he was found to be clinically well though thin (BMI 18), anxious and tremulous. His heart rate was 110 bpm and blood pressure was normal. The thyroid was smooth and firm. His testes were small (8 mls) and penis was adult sized.
Initial investigations supported a diagnosis of thyroid hormone resistance, which was confirmed by genotyping, showing he was heterozygous for the R438H mutation in THRb (CM910370). Other investigations revealed partial testicular failure with raised FSH and complete azoospermia whilst testosterone production remained unaffected at 23.3 nmol/l (9.927.8); LH was 6.6 u/l (0.86.0). He had a normal 46XY Karyotype. He was also found to have severe osteoporosis with a basal metabolic rate (BMR) of 125% of that expected for his age and weight.
Significant past medical history includes mumps as a child, but the testes were apparently unaffected.
His treatment consists of alendronic acid and propranolol, with plans to initiate triac. Previous control of his thyroid with carbimazole proved difficult, culminating in gross hypothyroidism (FT4 1.2; FT3 2.5; TSH> 100) and a massive goitre.
Questions arising from this case include how to control the FT3 and FT4 without inducing pituitary hyperstimulation, given its associated risks and, exploring the possibility of using BMR as a marker of tissue responsiveness to treatment, in particular his osteoporosis.
This case suggests sertoli cell function or development may have been compromised following chronic overexposure to thyroid hormones in utero and postnatally, though the possibility of a co-factor dysregulation cannot be ruled out.
06 - 07 Nov 2006
Society for Endocrinology