ECE2015 Guided Posters Pituitary – Hypopituitarism (9 abstracts)
1University of Cambridge, Cambridge, UK; 2Addenbrookes hospital, Cambridge, UK.
Background: Thyrotropinomas (TSHomas) are traditionally considered a rare, albeit important cause of thyrotoxicosis. Although early case series reported a predominance of invasive macroadenomas, emerging evidence suggests microadenomas are being increasingly diagnosed, and the clinical/biochemical phenotype appears to be more variable than previously suspected. We therefore performed detailed phenotyping of patients referred to our centre with a diagnosis of TSHoma over a 4-year period.
Methods: 35 patients with hyperthyroxinaemia and non-suppressed TSH were studied prospectively. Laboratory assay artefact, confounding intercurrent illness/drug therapy and THRB mutations were excluded in all cases. Further investigations included: hyperthyroid symptom score, measurement of resting energy expenditure, sleeping heart rate, bone mineral density, sex hormone-binding globulin (SHBG), alpha-subunit (ASU):TSH molar ratio, TRH test, OGTT, octreotide (100 mcg) suppression test (OST), volumetric MRI (vMRI) and 11C-methionine PET-CT. Patients then proceeded to a formal trial of depot somatostatin analogue (SSA) therapy.
Results: Clinical/metabolic features varied markedly, ranging from euthyroid to overtly hyperthyroid, and were not clearly correlated with the degree of hyperthyroxinaemia. Similarly, SHBG and ASU:TSH did not reliably identify many cases (both raised in <50%), especially microadenomas. In contrast, a blunted TSH response to TRH (<4.5-fold rise), combined with normalization of thyroid function during a 3 month trial of SSA therapy, was observed in 90% of cases. Interestingly, TSH and FT3 responses in the OST did not predict efficacy of depot SSA. 50% of patients had microadenomas, with several not reliably visualised using conventional MRI. In these patients, vMRI combined with PET/CT identified the site of the microadenoma. All 35 patients received SSA as a bridge to surgery or as long-term treatment where pituitary surgery was deemed inappropriate.
Conclusions: Modern diagnostic algorithms for TSHomas should place greater emphasis on the TRH test and response to depot SSA therapy. vMRI and functional imaging may aid visualisation/confirm the site of a suspected microadenoma and thereby guide surgical resection.