Nonthionamide Drugs for the Treatment of Hyperthyroidism: From Present to Future

Abstract

Hyperthyroidism is a common endocrine disease. Although thionamide antithyroid drugs are the cornerstone of hyperthyroidism treatment, some patients cannot tolerate this drug class because of its serious side effects including agranulocytosis, hepatotoxicity, and vasculitis. Therefore, nonthionamide antithyroid drugs (NTADs) still have an important role in controlling hyperthyroidism in clinical practice. Furthermore, some situations such as thyroid storm or preoperative preparation require a rapid decrease in thyroid hormone by combination treatment with multiple classes of antithyroid drugs. NTADs include iodine-containing compounds, lithium carbonate, perchlorate, glucocorticoid, and cholestyramine. In this narrative review, we summarize the mechanisms of action, indications, dosages, and side effects of currently used NTADs for the treatment of hyperthyroidism. In addition, we also describe the state-of-the-art in future drugs under development including rituximab, small-molecule ligands (SMLs), and monoclonal antibodies with a thyroid-stimulating hormone receptor (TSHR) antagonist effect.

A comparison of thyroidal protection by stable iodine or perchlorate in the case of acute or prolonged radioiodine exposure

“…Historically, Plummer used 80–320 mg daily for 10 days (Plummer 1924 ). A review of the literature indicates a low frequency or mild thyroidal and extrathyroidal adverse effects (Calissendorf et al 2017 ; Suwansaksri et al 2018 ). In patients treated with amiodarone, the incidence of the occurrence of thyroidal dysfunction (hyperthyroidism or hypothyroidism) is given with 2–12% (Trip et al 1991 ).…”

Perioperative considerations of hyperthyroidism in a patient with liver failure: case report

“…Also, the effects of radioactive iodine takes weeks to assess so it is not fit for use in emergency situations [3,5,6]. Glucocorticoid was also considered due to its effects of reducing the conversion of thyroxine to triiodothyronine within 24 hours of usage, however it is only effective when used concomitantly with other therapies [7,12,16].…”

Prevention and Treatment of Iodine-Induced Thyrotoxicosis

“…Perchlorate reduces thyroid iodine uptake by sodium/iodide symporter inhibiting action and discharge iodine from the thyroid, but toxic effects are limiting its use. To minimize the nephro-and medullotoxicity of the drug, doses not exceeding 4 × 250 mg/day and a shorter period than 4-6 weeks were used [40,87,91]. Thyroid function should be assessed after 4 weeks by measurement of serum TSH, free T4, and T3.…”

“…Many patients with underlying autonomous nodular thyroid disease are able to taper and discontinue thiamazole within 6-12 months. In case of thioamide allergy, lithium is used to control the hyperthyroidism temporarily [91,92], but it has a narrow therapeutic range, produces nephrotoxicity, and its efficacy is not well documented. Therefore, it is not recommended by ETA for the type 1 AIT treatment [40].…”

“…In addition, it must be noted that i.v. administration of glucocorticoids (hydrocortisone, dexamethasone) has crucial benefits (inhibiting T4 transformation to T3) in thyroid storm and preoperative management of any type of thyrotoxicosis [91]. It was reported that glucocorticoid therapy (oral prednisone) restored the normal thyroid function and shrink goiter, preventing surgery, in a patient diagnosed with iodine containing supplement-induced hyperthyroidism [95].…”