We present, a 72-year-old lady, ex-smoker, with Graves’ Disease (GD) and severe extrathyroidal manifestations of Graves’ ophthalmopathy (GO), thyroid acropachy and elephantiasic form of pretibial myxoedema (PTM). At diagnosis, aged 58, she had mild GO with a TRAb of 6.4IU/L (< 1.8IU/L). Initial unsuccessful therapy with carbimazole was followed by radioactive iodine (RAI) ablation with subsequent hypothyroidism requiring thyroxine replacement. Post RAI therapy, her GO and dermopathy worsened significantly, with persistent massively elevated TRAb titres. Currently she is clinically euthyroid, but with inactive GO, marked thyroid acropachy in hands, wrists and feet and severe bilateral lower limb elephantiasic PTM, with a TRAb level of 883IU/L. Indocyanine green fluorescence lymphography, which has not previously been applied to this condition, confirmed dermopathy with normal lymphatic drainage.
Worsening of GO is well-reported following RAI and is thought to be a consequence of release of thyroid antigenic material and activation of autoimmune reaction directed to orbital tissues, from radiation induced thyrocyte injury1. Overexpression of IGF-1 receptors in orbital fibroblasts, which synergistically enhance actions of thyrotropin, has also been postulated. Post RAI worsening of GO has been associated with several risk factors including smoking, pre-existing GO, high TRAb titres and high serum free T31, the first three of which were identified in our patient. The severe elephantiasic form of PTM, has been postulated to be secondary to stimulation of fibroblasts, increasing glycosaminoglycans and hyaluronic acid deposition in the dermis, as a result of TRAb immunoreactivity2. The finding of autoantibodies that activate IGF-1R signalling in GD, has led to development and trial of teprotumumab, a monoclonal antibody to block the IGF-1 receptor in GO, that has shown superiority to placebo3. Although not used in Australia, this severe case warrants consideration, as to whether this targeted therapy might prove beneficial for other severe extrathyroidal manifestations of GD.