Endocrine Abstracts

A 74 years old man was referred to endocrine clinic with abnormal TFTs with raised free T4 (39.7 pmol/l; NR: 7.0–17 pmol/l), raised FT3 (7.3 pmol/l; NR: 3.5–6.5 pmol/l) and normal TSH (1.9 mU/ml; NR: 0.35–5.5 mU/ml) which were done on routine testing by his GP. PMH included COPD and B12 deficiency. He had no symptoms suggestive of thyrotoxicosis and was clinically euthyroid. Investigations were arranged to exclude the three possibilities of assay interference, Resistance to Thyroid Hormone and TSHoma. Assay interference was excluded with negative anti-heterophil antibodies and the similar TFT results using several different assays. Further investigations showed elevated SHBG (84 nmol/l, NR: 12–78) and alpha-subunit (3.72 IU/l, NR: <1.00) which favoured TSHoma. CT pituitary surprisingly showed an empty sella. The rest of the pituitary profile including prolactin, LH, FSH, IGF-1 and testosterone were normal. Specialist centre at Cambridge agreed with possible diagnosis of TSHoma. On their advice a TRH stimulation test and an octreotide suppression test was performed. On the TRH stimulation the TSH risen from 1.86 mU/l at baseline to 8.20 mU/l at 20 min and 7.58 mU/l at 60 min. This was a brisk response but still within the fold rise for TSHoma The octreotide suppression test showed a reduction of TSH, FT4 and FT3 from 3.12 mU/l, 45.5 pmol/l and 6.5 pmol/l at baseline to 0.93 mU/l, 36.3 pmol/l and 5.1 mU/l at 300 min respectively. He was commenced on Lanreotide 90 mg monthly. After two injections there was no biochemical improvement in his TSH or FT4 and he developed side-effects. At this stage genetic testing was considered and this confirmed THR beta-gene mutation consistent with RTH.

Both RTH and TSHoma are rare conditions which can be completely asymptomatic. None of the biochemical tests are entirely pathognomonic but a combination of tests can be suggestive of either. A high SHBG and alpha-subunits favours TSHoma together with blunted TSH response to TRH and good response to octreotide. This case was unusual in that RTH behaved biochemically as a TSHoma. Genetic testing for RTH is not always positive with 10–15% of cases having no demonstrable mutation on the TR beta-gene. Therefore, physicians need to be cautious in the interpretation and be aware of the limitations of these tests in differentiating between RTH and TSHoma.