An unusual case of resistance to thyroid hormone behaving as TSH-secreting pituitary adenoma (TSHoma)

Abstract

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.

Full text

Poster
presented at:
BES2016
An unusual case of Resistance to Thyroid Hormone
behaving as TSH-secreting pituitary adenoma
S Ahmad ST5, A Dixon Consultant Endocrinologist
Dept. of Diabetes and Endocrine, Wrexham Maelor Hospital, Wrexham
Case Report:
A 74 years old man was referred to endocrine clinic with abnormal TFTs with raised free T4,FT3 but
normal TSH which were done on routine testing by his GP. His past medical history included COPD and
B12 deficiency and he was on inhalers, omeprazole and vitamin B12. He had no symptoms suggestive
of thyrotoxicosis and was clinically euthyroid.
Assay interference was excluded with negative anti-heterophil antibodies and the similar TFT results
using several different assays. Further investigations showed elevated SHBG and alpha-subunit which
are usually raised in TSHoma. Subsequent CT pituitary gland surprisingly showed an empty Sella. The
rest of the pituitary profile including prolactin, LH, FSH, IGF-1 and testosterone were normal. TRH
stimulation showed a reasonably robust response which can be seen in some TSHomas. The octreotide
suppression test showed a reduction of TSH, FT3 and FT4. Considering the possible underlying
diagnosis to be TSHoma he was commenced on Lanreotide 90mg monthly but after two doses there
was no biochemical improvement in his TSH or FT4. At this stage genetic testing was considered and
this confirmed THR beta-gene mutation consistent with Thyroid Hormone resistance.
Discussion:
Both RTH and TSHoma are rare conditions and both
can be completely asymptomatic. None of the
biochemical tests are entirely pathognomonic but a
combination of tests can be suggestive of either of
these two conditions. 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.
TRH stimulation test
Octreotide suppression test
Response to Lanreotide 90mg monthly
104--EP
sajjad ahmad DOI: 10.3252/pso.eu.BES2016.2016
Thyroid