Endocrine Abstracts

Introduction: The term syndrome of ‘inappropriate secretion of TSH’ was originally coined to indicate two forms of central hyperthyroidism-resistance to thyroid hormone (RTH) and thyrotropin (TSH)-secreting pituitary adenomas (TSHomas). We present such a case that poses a diagnostic challenge.

Case: A 44-year-old female presented with fatigue post COVID infection four months ago. Thyroid function tests (TFT) revealed high thyroid-stimulating hormone (TSH) 6.1 mU/l (range:0.3-4.2) with raised free thyroxine (fT4) 25.1 pmol/l (range:11-22) and free triiodothyronine (fT3) 7.1 pmol/l (range:3.1-6.8). She denied palpitations, weight loss, bowel changes, or menstrual irregularities. She was not on any regular or over the counter medications. She has 2 children and no family history of thyroid disorders. On examination, BMI 1 kg/m², pulse 70beats/min, regular, clinically euthyroid, no palpable goitre, visual fields normal. She had normal TSH at 1.1 mU/l and 3.1 mU/l, checked 14years and 4years back. Blood investigations showed normal anterior pituitary profile including short synacthen test. Repeat TFT’s revealed a similar pattern and assay interference was ruled out by DELFIA for TSH, Atellica for fT3 and radioligand binding assay for familial dysalbuminaemic hyperthyroxinemia (FDH) negative in two referral laboratories. Serum glycoprotein alpha subunit (α-GSU) was 0.37IU/l (range:<3.0). Pituitary MRI scan showed a 1 mm anterior pituitary microadenoma. Thyroid pertechnetate scan suggested increased thyroid uptake. TRH (thyrotropin-releasing hormone) stimulation test showed less than 1.5-fold rise in TSH at 20minutes from baseline. T3 suppression test showed partial suppression of TSH at day 10. She is awaiting results of genetic testing for thyroid hormone receptor β (TRβ) gene mutation and somatostatin analogue suppression test.

Discussion: Assay interference should be first excluded with high fT4, fT3 and TSH prior considering other causes. RTH and TSHoma are rare and differentiating the two could be challenging. RTH is inherited as autosomal dominant in 80% of cases, with mutation in TRβ in majority. TSHoma accounts for 1% of all pituitary tumours, with prevalence of one per million, 80% being macroadenomas. Alpha-subunit is raised in TSHoma in 70% cases. TRH stimulation test with more than fivefold increase in TSH is suggestive of RTH while in TSHoma there is an attenuated (no greater than 1.5-fold increase) response in TSH. In T3 suppression test, TSH suppression occurs in RTH while absent in TSHoma. Response to Octreotide LAR, but not short acting single octreotide injection, is seen in TSHoma, but not RTH.

Conclusion: A panel of clinical, biochemical, radiological, dynamic testing, and genetic analysis, help to differentiate between RTH and TSHoma.