Endocrine Abstracts

Introduction: Thyrotropinomas comprise <1% of all pituitary tumours, but detection is increasing with more widespread use of ultrasensitive TSH assays. Although distinct, the classical biochemical signature – hyperthyroxinaemia with non-suppressed TSH – is not specific to thyrotropinoma, as drug effects, non-thyroidal illness, and assay interference can all yield similar patterns of thyroid function tests. Even when these more common confounders have been excluded, and genuine inappropriate secretion of TSH (IST) confirmed, the task remains to distinguish thyrotropinoma from the genetic syndrome of resistance to thyroid hormone (RTH). Measurement of alpha-subunit:TSH molar ratio, sex hormone-binding globulin (SHBG), TSH response to thyrotropin-releasing hormone (TRH), T₃ suppressability, screening of other family members, pituitary MRI (dynamic) imaging, and thyroid hormone beta receptor gene screening may help to distinguish the two conditions.

Case: A 50-year-old female was incidentally discovered to have elevated freeT₄ (44 pmol/l, RR 9.0–20.0) and freeT₃ (21.5 pmol/l, RR 3.0–7.5) levels, but a non-suppressed TSH (8.8 mU/l, RR 0.4–4.0). She was clinically euthyroid and eupituitary. Confirmation of the biochemical findings on several assay platforms, and a linear hormone response to dilution excluded artefactual results. Further investigations demonstrated normal anterior pituitary function tests aside from a mildly elevated IGF-1 (39.1 nmol/l, RR 7.5–30). Growth hormone suppressed to 1.3 mU/l during OGTT. SHBG was normal (55 nmol/l, RR18–114), but alpha-subunit was mildly raised (2.25 IU/l, RR 0–1). TSH response to TRH was blunted (0 min 7.7 mU/l, 20 min 8.5 mU/l). Pituitary MRI and CT revealed a heterogeneous 2.4×2.2×1.7 cm sella mass with marked central calcification. Following transsphenoidal surgery, histology confirmed a mixed somatotroph/thyrotroph adenoma.

Discussion: Although the combination of elevated FT₄/FT₃ and non-suppressed TSH with a sella-based mass were strongly suggestive of a thyrotropinoma, the absence of clinical symptoms, the normal SHBG level and the unusual radiological appearances complicated establishment of a definitive pre-operative diagnosis. We discuss the complexities involved and describe a diagnostic algorithm.