Hypothyroidism and Hyperthyroidism are relatively common endocrine disorders. Most patients taking T3 and T4 (triiodothyronine and thyroxine) are also on other medicines for other diseases. Some of these medicines have significant drug-drug interactions. Drugs that affect the efficacy of thyroxine may be affecting its production, transport, metabolism or iodination. This results in overt thyroidal dysfunction with clinical manifestations or may not be significant but commonly misinterpreted by physicians.
Drugs that affect TSH secretion:
- Drugs that inhibit TSH secretion:
- More than 20 mg of steroids
- Dopamine of more than 1 mcg/kg/min
- Dobutamine
- Octreotide 100 mcg/day
- Bexarotene
These drugs inhibit TSH secretion but usually do not have effects on T4. Therefore, patients on these drugs should have t4 levels done along with TSH to avoid misinterpretations of the results.
Drugs that cause hyperthyroidism:
Iodine and drugs that contain more than 50% of iodine by weight can cause hyperthyroidism. Amiodarone and radiocontrast agents are notorious in causing hyperthyroidism weeks after the administration of these agents. Lithium usually causes hypothyroidism but can also cause hyperthyroidism. Interferon-alpha and interleukin-2 can cause graves disease and painless thyroiditis.
Drugs that cause hypothyroidism:
High doses of iodine can cause hypothyroidism. Oxidation of iodide and thyroid hormone synthesis decreases after thyroid follicles are exposed to high doses of iodide (the Wolff-chaikoff effect). This effect may also be seen in patients using amiodarone. Lithium can also lead to hypothyroidism. It may result in thyroid enlargement in half of the patients. In addition, some patients may have positive antithyroid antibodies. However, patients who develop hypothyroidism with the use of lithium, treatment with thyroxine should be initiated instead of discontinuing lithium. Tyrosine kinase inhibitors like sunitinib, sorafenib, imatinib, and motesanib can cause hypothyroidism by mechanisms not properly understood. However, ischemia, thyroid destruction, reduced iodine uptake, and reduced thyroid peroxidase activity can cause hypothyroidism. Other drugs include aminoglutethimide for the treatment of Cushing's syndrome, Bexarotene (causing central hypothyroidism) and thalidomide can all cause hypothyroidism.
Drugs that interfere with T3 and T4 transport and metabolism:
Drugs influencing Thyroid hormone binding to proteins:
Estrogens and selective estrogen receptor modulators raise thyroid hormone-binding globulin. This necessitates an adjustment in the thyroxine dose.
Androgens and anabolic steroids decrease TBG (thyroid hormone binding globulin).
Salicylates and mefenamic acid reduce the binding of T3 and T4 to TBG.
Heparin can cause an increase in the fatty acid generation which displaces Free T3 and T4 from binding to TBG, increasing its serum concentration.
Drugs influencing Thyroid hormone absorption from the GastroIntestinal tract:
Calcium carbonate, proton-pump inhibitors, and bile acid-binding resins like cholestyramine inhibit T3 and T4 absorption from the gastrointestinal tract. These drugs should be taken at least 2 to 3 hours after thyroxine.
Other drugs affecting T3 and T4 absorption include ciprofloxacin, raloxifene, sucralfate, aluminium hydroxide, sevelamer, lanthanum carbonate, and chromium.
Drugs affecting T3 and T4 metabolism:
Phenobarbital, rifampin, phenytoin and carbamazepine increase the metabolism of Thyroid hormones.
Phenytoin and carbamazepine augment the rate of thyroid hormone metabolism and displace T3 and T4 from binding proteins. The net effect is a reduction in T4, minimal reduction in T3 and a normal TSH levels.
Oxcarbazepine has minimal effect on cytochrome P-450, however, it still reduces T4 concentration but TSH levels remain the same.
Drugs affecting T3 production:
Amiodarone, high doses of steroids, Beta-Blockers, propyl-thiouracil, and iodinated contrast agents inhibit the peripheral conversion of T4 to T3.
In conclusion:
Patients with hypothyroidism or hyperthyroidism are usually using Medicines for other conditions as well. The drug-drug interactions should be kept in mind before changing T3 and T4 or antithyroid drug dosages.
