Endocrine Abstracts

Thyroid Orbitopathy is rarely associated with de novo Primary Hypothyroidism; this phenomenon is incompletely understood. Here we present the case of a 51-year-old female presenting with Primary Hypothyroidism, Thyroid Orbitopathy, and high titres of Anti-TSH Receptor Antibodies (TRAb), and discuss the potential underlying pathogenesis. Our patient first presented to Regional Hospital Mullingar with an unrelated, and ultimately self-limiting, complaint. The Endocrinology service consulted for abnormal Thyroid Function Tests (TFTs); TSH - 42.46 mIU/l (0.33 – 4.8), Free T4 - 9.1 pmol/l (9.8 – 20). Thyroid Orbitopathy, with proptosis and mild periorbital oedema, was noted on examination. Levothyroxine was commenced and TFTs normalised within 12 weeks of presentation; TSH - 1.3mIU/l, Free T4 - 15.9 pmol/l. TRAb was grossly elevated at 68.4IU/l (<1.8). CT and MRI of the Orbits demonstrated bilateral proptosis, prominence of the inferior medial and superior rectus muscles, and increased retro-ocular fat sparing the anterior tendon, consistent with Thyroid Orbitopathy. A functional bioassay using a Chinese Hamster Ovary (CHO) cell line, expressing a TSH holoreceptor and utilising a luciferase-based homogenous cAMP biosensor demonstrated both TSH Receptor stimulating activity (+632%, ref < 140%) and TSH Receptor blocking activity (-62%, ref > -34%) of the patients serum. The patient remained biochemically euthyroid (TSH - 3.22mIU/l) but Thyroid Orbitopathy progressed; Clinical Activity Score (CAS) increased necessitating high dose, pulsed intravenous glucocorticoid therapy (Methylprednisolone) to ameliorate worsening Thyroid Orbitopathy. It seems unlikely, given the well maintained TSH levels, that endogenous TSH contributed to the progression of Thyroid Orbitopathy. We therefore hypothesise that this patient is producing TRAb that has both TSH Receptor stimulating activity and TSH Receptor blocking activity, and that these antibodies are antagonising TSH at the Thyroidal TSH receptor, but providing a stimulus to orbital fibroblasts. Functional TSH Receptor bioassay analysis of similar patients may help to better characterise this rare phenomenon.