Our case involves a 62 year-old man with severe, debilitating extra-thyroidal manifestations of Graves’ Disease, that have been refractory to standard therapies. Although Graves’ disease is a common endocrinopathy, its extra-thyroidal manifestations are less prevalent. Our case explores the incompletely understood pathogenesis of extrathyroidal manifestations of Graves’ disease and contrasts this with clinical features that are attributable to thyrotoxicosis. Extra-thyroidal manifestations of Graves’ may take a distinct course, and deteriorate even despite achieving a euthyroid state, as our patient demonstrates.
Our patient initially presented with fluid overload, clinical features of thyrotoxicosis and mild orbitopathy and dermopathy. Investigations showed biochemical thyrotoxicosis, neutropenia and highly elevated TSH-receptor antibodies (TRAB). Neutrophils reached a nadir of 0.60 x 109/L and TRABS have decreased, but still remain positive.
The neutropenia made extended thionamide therapy undesirable, therefore within weeks our patient proceeded to total thyroidectomy and now remaines euthyroid on thyroxine therapy.
Notwithstanding the attainment of a euthyroid state, our patient’s clinical activity index for Graves’ orbitopathy worsened. Treatment with pulsed intravenous methylprednisolone and retro-orbital radiotherapy resulted in little clinical improvement. In consultation with his immunologist Rituximab was administered, also with no benefit. Our patient continues to receive regular intravenous immunoglobulin infusions. Our patient then underwent bilateral orbital decompressive surgery. His orbitopathy remains clinically active and further treatment is being considered, including insulin-like growth factor 1 receptor (IGF1R) inhibitor therapy. Despite the above systemic therapy, pretibial myxoedema also remains problematic.
Graves’ disease impacts multiple organs with implications far beyond thyroid function. The systemic ramifications of thyrotoxicosis are wide-ranging, and even influence haematopoiesis – the well-described phenomenon of thyrotoxicosis-induced neutropenia. Although seemingly disparate, these consequences generally resolve with restoration of euthyroidism. In contrast, orbitopathy, dermopathy and acropachy, the traditionally recognised localised extra-thyroidal manifestations of Graves’ disease, are independent of thyrotoxicosis, suggesting a discrete pathogenesis, requiring targeted treatments.