Endocrine Abstracts

JOINT265

Introduction: Hypothyroidism is a common endocrine disorder characterized by a wide range of etiologies, predominantly autoimmune causes in adults. While the etiological diagnosis is often straightforward, it can occasionally pose a challenge, particularly in cases of multiple or complex etiologies. We report the case of a patient presenting with peripheral hypothyroidism associated with pazopanib treatment.

Case Report: A 55-year-old woman, followed for 4 years for renal carcinoma with pulmonary metastases, treated with pazopanib (800 mg/day) for 13 months, presented with fatigue, hoarseness, and memory disturbances. Hormonal evaluation revealed a TSH level of 22 mIU/l and an FT4 level of 4 pmol/l, confirming peripheral hypothyroidism. Physical examination showed no goiter, and thyroid ultrasound revealed an atrophic thyroid gland. Anti-thyroperoxidase antibodies (anti-TPO) were strongly positive. The etiology was debated between atrophic Hashimoto’s thyroiditis, a side effect of pazopanib, or a combination of both. Hormone replacement therapy led to clinical and biological improvement.

Discussion and conclusion: Pazopanib, a tyrosine kinase inhibitor targeting tumor growth and pathological angiogenesis, is associated with hypothyroidism in approximately 12% of cases. Proposed mechanisms include thyroid atrophy due to vascular inhibition, drug-induced thyroiditis, interference with iodine uptake, or anti-TPO activity. Paradoxically, cases of pazopanib-induced hyperthyroidism have also been reported, challenging these hypotheses. In this patient, thyroid atrophy and the presence of anti-TPO antibodies, rarely described with pazopanib, suggested Hashimoto’s thyroiditis. For other tyrosine kinase inhibitors, such as sunitinib, hypothyroidism has been attributed to drug-induced anti-TPO activity. Regardless of the etiological diagnosis in our patient, the therapeutic approach remains unchanged, given the safety and efficacy of hormone replacement therapy.