Endocrine Abstracts

Introduction: Moderate to severe thyroid eye disease (TED) has a significant impact on quality of life. In some cases, TED is resistant to systemic glucocorticoids, the mainstay of treatment since the 1950s, requiring alternative therapies. We describe here a patient with active severe TED who is refractory to various treatments.

Case presentation: A 48-year-old non-smoker male, with a long history of psoriasis, vitiligo and atrophic gastritis, presented in May 2019 with Graves’ thyrotoxicosis and was treated with methimazole. In July 2020, following 14 months of euthyroidism, he started experiencing eye pain, proptosis, and diplopia, with a clinical activity score (CAS) of 6/7. TSI (thyroid stimulated immunoglobulin) levels were 16.2 IU/l (normal range < 1.75 IU/l). He was treated with oral methylprednisolone for 3 months, showing a small response in eyelid swelling, but developed a 15 kg weight gain, proximal myopathy, peripheral edema, restlessness, and insomnia. In November 2020, he underwent total thyroidectomy. After a brief period of hypothyroidism, which was corrected with levothyroxine, he had TED improvement (CAS 4/7) and TSI normalization. In March 2021, a few weeks after COVID vaccination, his TED deteriorated significantly (CAS 6/7), while TSI rose to 4.45 IU/l. Administration of a total dose of 4.5 gr methylprednisolone in 12 weekly intravenous infusions resulted in slight reduction of eyelid swelling, some pain relief, and TSI normalization. Throughout this period, he received artificial tears and oral selenium, while he remained euthyroid. However, he gradually developed worsening diplopia and several side effects, including a 7 kg weight gain, irritability, and insomnia. Tocilizumab, a monoclonal antibody against interleukin-6 (IL-6) receptor, was started intravenously (8 mg/kg). After three monthly infusions, there was significant improvement in eyelid swelling and pain, but no effect on proptosis and diplopia (CAS 5/7). Severe arthralgias and intractable pruritus necessitated discontinuation of treatment.

Conclusion: This case illustrates the therapeutic challenges around severe refractory active TED. Glucocorticoids and tocilizumab improved soft-tissue inflammation, but had minimal impact on proptosis and diplopia. There is an unmet clinical need in Europe for therapies with efficacy against proptosis and diplopia, such as teprotumumab, a monoclonal antibody against the insulin-like growth factor-I receptor. Teprotumumab, approved in 2020 by the US Food and Drug Administration for TED, is still not routinely available in Europe. In a rapidly evolving treatment landscape of TED, it is essential to ensure patient access to therapeutic advances targeting the underlying pathogenetic mechanisms in order to improve patient outcomes.