Endocrine Abstracts

Introduction: Consumptive hypothyroidism is a rare condition characterized by the aberrant expression and increased activity of thyroid hormone deiodinase type 3 (DIO3) in neoplastic tissue. This leads to an augmented conversion of thyroxine (T4) to the inactive reverse triiodothyronine (rT3). So far, most cases of consumptive hypothyroidism have been described in infants with hemangiomas.

Case presentation: We report the case of a 64-year-old woman with metastatic melanoma of the choroid that first presented with immunotherapy-induced thyroiditis (ipilimumab/nivolumab). Due to progression to hypothyroidism, she was started on L-thyroxine. Because of metastatic tumor progression, the patient received multiple local and systemic treatments including trametinib (MEK inhibitor), olaparib (PARP inhibitor), pembrolizumab (anti-PD-1), lenvatinib (multikinase inhibitor), binimetinib (MEK inhibitor), and finally autologous Tumor-Infiltrating Lymphocytes enriched for tumor antigen specificity (NeoTIL). After 2 years of L-thyroxine treatment, TSH values started to rise, and despite high doses of L-thyroxine (up to 6.1 mg/kg/jour) thyroid function never normalized. Low T3 levels and persistent hypothyroidism despite high doses of L-thyroxine and adequate compliance arose the suspicion of consumptive hypothyroidism. While the biochemical characterization remained incomplete due to the passing of the patient, analysis of metastatic tumor tissue demonstrated very abundant overexpression of DIO3 by immunohistochemistry.

Conclusion: Consumptive hypothyroidism is a rare entity that must be considered in oncologic patients with hypothyroidism requiring high doses of L-thyroxine. Recent observations, including this case report, show that certain epithelial malignancies can also overexpress DIO3 and, hence, lead to consumptive hypothyroidism. Treatment consists of high doses of L-thyroxine, sometimes in association with liothyronine (LT3). The role of new forms of immunotherapy on DIO3 overexpression and the development of consumptive hypothyroidism needs to be further investigated.