SUN-LB87 De-Novo Graves Ophthalmopathy After Total Thyroidectomy With Exacerbation Following Rifampicin Therapy for Latent Tuberculosis: A Call for Attention to Disease Modifying Interventions

Introduction Factors influencing development and course of ophthalmopathy, the most common extrathyroidal manifestation of Graves’ disease, remain poorly defined. Clinical Case A 46 year old healthy, non-smoking, medical secretary, presented with Graves’ disease. Laboratory investigation showed thyrotoxicosis with high thyroid stimulation immunoglobulin (TSI) levels (1608 %, normal <140%). At presentation there was no evidence of thyroid eye disease on clinical exam and orbital MRI. Treatment with Methimazol and PTU induced severe pruritus and she underwent total thyroidectomy. One month after surgery she presented with retroorbital pain, eyelid edema and chemosis, as well as bilateral limitation in abduction; a clinical activity score (CAS) of 3/7. She received IV pulse methylprednisolone 4.5 gr with minor improvement. MRI showed bilateral thickening of all rectus muscles with orbital fat infiltration. TSI increased concomitantly to 3600%. Three months later, she underwent standard retrobulbar radiotherapy (20 Gy), again with only minor improvement. She continued treatment with oral prednisone 20mg with small fluctuations in disease activity in the following months during which TSI remained high (3145%) and latent tuberculosis was detected (elevated interferon-gamma release assay). Therefore, rifampicin 600mg/d was started. A month later the ophthalmopathy worsened (a CAS score of 5/7 without optic neuropathy). Laboratory tests showed new perturbation in thyroid function tests (TSH increased from 5 to 15 mIU/l, normal: 0.5-5; FT4 decreased from 16 to 11 pmol/l, normal: 10-20) and TSI increased to 3879%. Euthyrox dose was increased by 50% from 800 to 1200 microgram/week. It was postulated that prednisone was also being rapidly metabolized by rifampicin mediated induction of the CYP450, and therefore the dose was increased from 20 to 40 mg/d. Six weeks later, normalization of thyroid function tests was followed by improvement in the ophthalmopathy (CAS-3). Conclusion (Clinical lesson) A) De-novo severe Graves’ ophthalmopathy after thyroidectomy requiring multiple forms of treatment is rare but close surveillance is advisable, perhaps particularly in the presence of high TSI. A plausible mechanism may be transient increase in antigenic exposure/dissemination during surgery. B) Rifampicin, through induction of cytochrome P450-mediated metabolism of levothyroxine, steroids and mycophenolate (the latter not used in our patient) can lead to disease flare-up. Tight clinical and laboratory monitoring of thyroid function tests with individualized dose escalation might be needed. In the future, pharmacogenomics may serve to personalize treatment protocols.