Severe hypothyroidism after thalidomide treatment

Abstract

A man aged 49 reported lethargy and back pain and was found to have multiple myeloma. The treatment began with radiotherapy to the spine and repeated courses of vincristine, doxorubicin and dexamethasone. Then, on reaching plateau phase, he underwent autologous stem-cell transplantation following high-dose melphalan. This led to complete remission of the myeloma. As a part of a clinical trial investigating thalidomide as maintenance therapy for multiple myeloma, he was randomized to receive this drug, initially at 50 mg/day. The dose was increased to 100 mg/day after two weeks and to 200 mg/day after eight weeks. Three months after starting thalidomide, he reported increasing lethargy, constipation and cold intolerance. He had slow-relaxing ankle jerks. There was no goitre. Thyroid function tests revealed gross biochemical hypothyroidism, with thyrotropin (TSH) 4100 mu/L (normal range 0.25–5.5) and free T4 (FT4) 1.8 pmol/L (9.7–25.7). Thyroid peroxidase (TPO) antibodies were present. Two days before starting thalidomide his thyroid function had been essentially normal (TSH 0.21 mu/L, FT4 23.4 pmol/L), and there was no family history of thyroid disease. After the diagnosis of hypothyroidism he was taken off thalidomide and started on thyroxine, with resolution of his symptoms. On thyroxine 125 mg daily he remained euthyroid and his multiple myeloma was still in remission eighteen months from diagnosis. The UK Committee on Safety of Medicines say that they received no other reports of thalidomide-induced hypothyroidism between 1966 and 2003.