Endocrine Abstracts

Background: Thyrotropinomas (TSHomas) are traditionally considered a rare albeit important cause of thyrotoxicosis, accounting for ∼1% of all pituitary adenomas. Although early case series reported a preponderance of macroadenomas, emerging evidence suggests microadenomas are being increasingly diagnosed. In addition, the clinical/biochemical phenotype appears to be more variable than previously suspected. We therefore examined the clinical, metabolic, biochemical and radiological features of patients referred to our centre with a diagnosis of TSHoma over a 24-month period.

Methods: 20 patients with hyperthyroxinaemia and non-suppressed TSH were identified, in whom laboratory assay artefact, confounding intercurrent illness/drug therapy and THRB mutations were excluded. Further investigations included: hyperthyroid symptom score, measurement of resting energy expenditure (REE), sleeping heart rate (SHR), bone mineral density (BMD), sex hormone-binding globulin (SHBG), α-subunit (ASU):TSH molar ratio, TRH test, OGTT, octreotide suppression test and volume MRI. 14 patients proceeded to a formal trial of somatostatin receptor ligand (SRL) therapy.

Results: Clinical/metabolic features varied markedly, ranging from euthyroid to overtly hyperthyroid, and were not clearly correlated with the degree of hyperthyroxinaemia; ∼70% had evidence of cardiac (arrhythmias) and/or bone (osteopenia/osteoporosis) complications. Basal TSH levels were normal in 14 (70%) patients, and most exhibited a blunted response to TRH stimulation, but the fold-rise varied from 1.1 to 8. In one third of patients, SHBG levels were not raised (associated with evidence of co-existing GH hypersecretion in two (33%) cases). Similarly, the ASU:TSH molar ratio was not uniformly elevated. In ∼40% of cases, volume MRI revealed a microadenoma; no demonstrable lesion was seen in two patients. SRL therapy normalised TFTs in 85% of patients, typically within 1 week of starting treatment. To date, eight patients have proceeded to surgery with histological confirmation of the diagnosis of thyrotropinoma.

Conclusion: The clinical, biochemical and radiological phenotype of thyrotropinomas is highly variable, with many cases exhibiting one or more atypical features often leading to diagnostic confusion.

Declaration of funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.