lenvatinib and Hyperthyroidism

Hyperthyroidism after total thyroidectomy is extremely rare. No studies have investigated hyperthyroidism during multiple kinase inhibitor treatment for advanced thyroid carcinoma.. A 57-year-old man with a history of radioactive iodine refracted thyroid follicular carcinoma presented to our hospital with back pain. Computed tomography (CT) showed a huge tumor at the left ilium and multiple metastases in the lung, liver, and bone. His serum thyroglobulin was 322,000 ng/mL and bone biopsy revealed thyroid carcinoma metastasis. After left iliac tumor decompression surgery, lenvatinib and denosumab treatment were initiated. Serum thyroglobulin decreased to 88,600 ng/mL, and no progression was observed on CT. Although thyrotropin (TSH) was suppressed at 125 µg of levothyroxine sodium, serum free T3 started to increase at 70 weeks after lenvatinib initiation. Levothyroxine sodium was gradually reduced to 25 µg. At 83 weeks after initiation, the patient was hospitalized due to nausea, diarrhea, and anorexia. Serum free T3 increased to 13.98 pg/mL, whereas CT showed progression of lung and liver metastasis. Given the patient's positivity for anti-thyrotropin receptor antibody (TRAb), levothyroxine sodium and lenvatinib were discontinued and methimazole was administered at the dose of 15 mg/day. Lenvatinib was restarted after 2 weeks withdrawal. Methimazole was gradually reduced to 5 mg/day as thyroid function normalized. However, CT showed pleural effusion and enlargement of the lung, liver, and adrenal metastases. The patient died at 100 weeks after lenvatinib initiation due to disease progression.. The patient developed Graves' disease after lenvatinib treatment for radioactive iodine refracted thyroid follicular carcinoma. Persistent TSH stimulation caused by TRAb can be involved in tumor growth and thyroid hormone secretion from metastases.

Topics: Carcinoma; Humans; Hyperthyroidism; Iodine Radioisotopes; Male; Methimazole; Middle Aged; Thyroglobulin; Thyroid Neoplasms; Thyrotropin; Thyroxine

Hypothyroidism is a frequently occurring complication in patients on lenvatinib treatment. However, little is known about lenvatinib-induced thyrotoxicosis and destructive thyroiditis. We herein report the cases of three patients who developed hyperthyroidism during the course of lenvatinib treatment. All patients had multiple hepatocellular carcinoma of Child-Pugh class A. Two patients required beta blockers for the management of palpitations. One patient developed hyperthyroidism only one week after the initiation of lenvatinib treatment. Thus, the possibility of hyperthyroidism developing within one week after the first administration should be kept in mind, and periodic surveillance of the thyroid function should be performed during the early period of lenvatinib therapy (within the first two weeks or so after the initial administration).

Topics: Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Humans; Hyperthyroidism; Liver Neoplasms; Male; Phenylurea Compounds; Quinolines; Thyroiditis