Endocrine Abstracts

Introduction: Graves’ disease (GD) is caused by TSH receptor antibodies (TRAbs) which stimulate thyroid activity. Initial treatment usually relies on antithyroid drugs (ATDs), mainly methimazole, carbimazole or propylthiouracil (PTU). These drugs inhibit the enzyme thyroperoxidase, blocking the synthesis of T3 and T4. Definitive therapeutic options include radioactive iodine and total thyroidectomy which are usually reserved for patients who do not tolerate or respond to ATDs, or for those who relapse or do not achieve remission after a course of ATDs. Here, we present a GD patient who suffered from remarkable resistance to ATDs requiring an early definitive therapy in order to solve her thyrotoxicosis.

Clinical case: A 57-year-old female presented with a 1-year history of palpitations, increased sweating, anxiety, insomnia and weight loss. Laboratory work-up confirmed hyperthyroidism: TSH<0.01 mIU/l, FT4 2.33 ng/dl (0.7-1.9). The titration of TRAbs was 8.55 IU/l (< 2.13) confirming the diagnosis of GD. Methimazole was commenced and progressively titrated up to 70 mg/day (i.e. fourteen 5 mg-tablets), which the patient has reassured us to be fully compliant with. Nevertheless, she remained in hyperthyroidism, and under methimazole 70 mg/day her thyroid function tests were: TSH <0.005 mIU/l, FT4 2.56 ng/dl and FT3 9.76 pg/ml (2.0-4.4). This prompted us to consider an early definitive therapy, and the patient was then proposed for total thyroidectomy. Lugol’s solution was added to her ATD therapy, and her thyroid function has improved over the following two weeks, with FT4 and FT3 serum levels dropping from 2.00 and 9.76 down to 1.57 and 4.39 ng/dl, respectively. After controlling her thyrotoxicosis, she underwent an uneventful total thyroidectomy.

Discussion: This case highlights the uncommon, but possible, scenario of resistance to high-dose ATD therapy in patients with GD. In these cases, poor compliance to therapy should always be suspect, but other possible explanations include: i) decreased intestinal absorption; ii) impaired thyroid uptake; iii) greater metabolism and excretion of ATDs. High dietary intake of iodine can also impair the action of ATDs, and may further contribute to resistance to high-dose ATDs. Lugol’s solution inhibits thyroperoxidase through Wolff-Chaikoff effect, thus blocking the synthesis and release of T4 and T3, as well as it reduces the vascularization of the thyroid gland. Hence, Lugol’s solution must be used in GD patients prior to thyroidectomy, particularly in patients unresponsive to ATDs, as illustrated here.