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A number of medications available either over the counter, or through a doctors prescription, may affect thyroid function and cause hyper or hypothyroidism. Medications or foods containing excess Iodine may cause either hypothyroidism or hyperthyroidism in susceptible individuals, and patients with thyroid disease who have not had their thyroid removed should generally avoid such medicines. Over the counter cough and cold remedies will often contain small amounts of iodine or stimulants (norepinephrine, neosynephrine, adrenaline etc) that may affect blood pressure and heart rate. Health food supplements containing kelp or seaweed extracts may contain substantial amounts of iodine which may also precipitate or exacerbate thyroid disease in susceptible persons. Many commonly used medications or supplements (iron, calcium, estrogen, proton pump inhibitors, statins) can cause alterations in thyroid hormone absorption or binding to plasma proteins, sometimes requiring dose adjustment of L-thyroxine Drugs that interact with levothyroxine: an observational study from the Thyroid Epidemiology, Audit and Research Study (TEARS) Clin Endocrinol (Oxf). 2014 Jul 17. doi: 10.1111/cen.12559

 

In many parts of the world including most of North America, iodine deficiency is no longer a problem, and individuals taking moderate or large amounts of iodine in the form of supplements may actually aggravate a pre-existing, or a latent predisposition to develop a thyroid condition. There continues to be enormous interest in the effects of supplements, nutrients and Vitamins on human health and thyroid function.

Medications that may cause Hypothyroidism

Lithium, Amiodarone, sulfonamides, Bexarotene, ethionamide, anticonvulsants, Iodine, Interferon, high dose Glucocorticoids ('steroids'), Oral cholecystographic agents for visualization of the gall bladder, Sunitinib and other tyrosine kinase inhibitors, Proton pump inhibitors, and angiogenesis inhibitors such as lenalidomide

Medications that may cause Hyperthyroidism

Amiodarone, Interferon, Iodine

Medications used to treat seizure disorders (epilepsy) may also affect thyroid function. Dilantin may displace thyroid hormone binding and produce abnormal thyroid blood tests, but thyroid function in Dilantin-treated patients is usually normal. Children taking medications for seizure control, such as valproic acid or carbamazepine may also be at increased risk for the development of hypothyroidism. Epilepsia 1999 Dec;40(12):1761-6 Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism.

Medications used for the Treatment of HYPOTHYROIDISM

L-thyroxine or Levothyroxine (Thyroid hormone, or T4)

The most common medicine prescribed for the treatment of hypothyroidism is L-thyroxine, commonly known as the principal thyroid hormone or T4 (levothyroxine). The thyroxine provided in tablet form is identical to the thyroxine made by your own thyroid. Hence once patients establish the correct dose of L-thyroxine replacement they need to return their thyroid function to normal, side effects are few to non-existent as our bodies cannot distinguish L-thyroxine secreted from our thyroids from L-thyroxine absorbed via tablet form. Allergies to thyroid hormone generally do not occur, and allergies to dye or other constituents present in the thyroid hormone tablet have been reported but are extremely rare. The 50 ug tablet has no color additives and hence is not usually a problem even for patients with dye allergies. As thyroxine has a long half life (5-7 days) and disappears slowly from your system, it needs to be taken only once a day. Hence, even if a patient forgets to take thyroxine on any given day, the circulating levels of thyroxine will generally be only very slightly perturbed.

Thyroxine therapy is usually initiated in a small dose, perhaps 25-50 ug once daily, and a repeat set of blood tests, commonly a TSH, is repeated after ~ 4 weeks to ascertain if the prescribed dose is correct. In young healthy patients without other co-existing illnesses, thyroxine treatment may be initiated at higher doses, with the ultimate expected replacement dose being ~1.6 ug/kg/day (1 kg = 2.2 lbs). It is important to remember that thyroxine (T4) is converted to T3, a more active short-acting form of thyroid hormone, in our bodies by an enzyme known as a deiodinase. Hence prescribing T4 allows the body to convert T4 to T3 as needed in a physiologically regulated manner. Whether prescribing both T4 and T3 confers added benefits over prescribing T4 alone is the subject of ongoing controversy and requires careful study in well designed randomized clinical trials. More information on this topic is found in Optimal Thyroid Hormone Replacement. Thyroxine ingested in the fasted state will produce slightly higher levels of circulating thyroid hormone and a lower TSH compared to thyroxine ingested before meals or at bed time as outlined in Timing of Levothyroxine Administration Affects Serum Thyrotropin Concentration. J Clin Endocrinol Metab. 2009 Jul 7. [Epub ahead of print]. In contrast, morning vs. evening ingestion of thyroid hormone was examined in 105 patients with hypothyroidism, who served as their own controls in a cross-over study. In this study, TSH levels were slightly lower, and thyroid hormone levels slightly higher, when thyroxine was ingested at bed time. Effects of evening vs morning levothyroxine intake: a randomized double-blind crossover trial Arch Intern Med. 2010 Dec 13;170(22): 1996-2003. Conflicting results were obtained in a separate study of 152 hypothyroid patients randomized to take thyroxine either in the morning or evening. There was no difference in thyroid hormone profiles or quality of life in the two groups. Can Levothyroxine Be Taken as Evening Dose? Comparative Evaluation of Morning versus Evening Dose of Levothyroxine in Treatment of Hypothyroidism J Thyroid Res. 2011;2011:505239. Hence, the available conflicting data suggest that it is not critical to take thyroxine at a specific time, as long as thyroid hormone levels are monitored and adjusted according to the specific goals established for each patient.

Drug interactions and absorption: Thyroxine therapy will enhance the response to anticoagulant therapy, hence patients taking oral anticoagulants should be monitored carefully. A number of hormones, steroids, anticonvulsants, or psychotropic medications may affect thyroxine binding to circulating proteins. Iron, often found in multivitamins, may interfere with absorption of thyroxine and should not be taken at the same time of day as the thyroid tablet. Nevertheless, patients with iron deficiency anemia who have mild hypothyroidism may gain important benefits after treatment of the hypothyroidism with thyroxine, with a significant rise in levels of iron and hemoglobin after correction of hypothyroidism Hematologic effects of levothyroxine in iron-deficient subclinical hypothyroid patients: a randomized, double-blind, controlled study J Clin Endocrinol Metab. 2009 Jan;94(1):151-6.

Calcium may also interfere with absorption of thyroid hormone. A study of 9 women and 11 men examined the effect of taking calcium supplements (1200 mg/day of calcium carbonate) on thyroid function tests in patients who were on long term thyroxine therapy. The results of the study show a small effect of calcium intake, resulting in a modest decrease in levels of thyroid hormones and a slight rise in levels of TSH. Although the magnitude of changes detected is small, patients who vary their intake of calcium may want to take their thyroid hormone tablet at a different time of day than their calcium supplement, to minimize any potential interaction between the two. Similar comments pertain to patients taking iron. To review the study, see The acute effect of calcium carbonate on the intestinal absorption of levothyroxine. Thyroid. 2001 Oct;11(10):967-71. Patients with gastrointestinal disorders may be particularly prone to reduced thyroxine absorption in the setting of calcium administration. See Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders. Ann Pharmacother. 2001 Dec;35(12):1578-83. To review the effects of different forms of calcium supplementation, see  Absorption of levothyroxine when coadministered with various calcium formulations Thyroid. 2011 May;21(5):483-6.

Grape fruit juice is known to change the absorption or metabolism of many different drugs. Although ingestion of grape fruit juice produces small changes in the absorption of thyroid hormone, it does not seem likely that regular ingestion of grapefruit juice will significantly affect the absorption or metabolism of thyroid hormone in patients taking L-thyroxine Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol. 2005 Sep;60(3):337-41

Coffee ingestion has also been shown to reduce the absorption of thyroxine in short term studies done in healthy study subjects as outlined in Altered Intestinal Absorption of L-Thyroxine Caused by Coffee Thyroid. 2008 Mar;18(3):293-301

Thyroid status is an important determinant of how our bodies handle and metabolize anticoagulants such as coumadin (warfarin). The hyperthyroid state may be associated with a reduced need for coumadin (dose may need to be decreased) whereas the hypothyroid state conversely may be associated with a need for an increased dose of coumadin. Patients on these types of anticoagulants who have changing thyroid function should ensure that their anticoagulant status is appropriately monitored. See Response to warfarin and other oral anticoagulants: effects of disease states. South Med J. 2000 May;93(5):448-54 and Complex Drug-Drug-Disease Interactions Between Amiodarone, Warfarin, and the Thyroid Gland. Medicine (Baltimore). 2004 Mar; 83(2): 107-113.

Women taking estrogen may need to have their levels of thyroid hormones tested and dose of thyroid hormone replacement adjusted within several months of initiation of the estrogen therapy. Those woman specifically at risk for a potential change in thyroid hormone dose are patients who have thyroid gland failure and hypothyroidism, or patients who have hypothyroidism as a result of thyroid surgery or ablation with radioactive iodine for benign or malignant tumors of the thyroid. Such patients should simply have a repeat TSH test between 10-12 weeks after initiation of estrogen therapy. In contrast, patients with otherwise normal thyroid function taking thyroid hormone for "suppressive therapy" to prevent growth of nodules or goiters are not likely to need a change in thyroxine dose. See Increased need for thyroxine in women with hypothyroidism during estrogen therapy. N Engl J Med. 2001 Jun 7;344(23):1743-9. Similarly, womentaking transdermal estrogen are much less likely to require a change in their dose of thyroxine. See Interaction of estrogen therapy and thyroid hormone replacement in postmenopausal women. Thyroid. 2004 Mar;14 Suppl 1:27-34.

Patients with a specific type of coexisting stomach inflammation (atrophic gastritis) who have reduced gastric acid secretion may exhibit modest impairment in the absorption of thyroid hormone, resulting in increase requirements for thyroxine. Conversely, treatment of H. Pylori in some patients may improve thyroxine absorption, leading to increased levels of circulating t4 and potentially a need for reduction in the dose of thyroxine. These findings imply that a certain level of gastric acid production is required for optimal absorption of thyroid hormone. Furthermore, institution of therapy for gastritis with proton pump inhibitors is frequently associated with a rise in levels of TSH-see Effect of proton pump inhibitors on serum thyroid-stimulating hormone level in euthyroid patients treated with levothyroxine for hypothyroidism. Endocr Pract. 2007 Jul-Aug;13(4):345-9

Thyroxine does not cross the placenta nor into breast milk in significant amounts, hence the effect of excess thyroxine treatment in the pregnant or lactating mother on the baby is not clinically significant. Nevertheless, it is important to maintain normal levels of thyroid hormone during pregnancy in the mother. For more information, see Pregnancy.

For a detailed overview of the safety of specific drugs and agents during pregnancy, see http://www.motherisk.org.

Precautions: Patients with known or suspected heart disease, particularly angina or cardiac arrhythmias, should only start L-thyroxine under the supervision of an experienced physician, and at low initial doses. For more information, see Thyroid disease and the heart.

It is very uncommon for patients to exhibit problems with gastrointestinal absorption of thyroid hormone. Rarely, patients with intestinal disease may exhibit increasing requirements for thyroxine if the GI tract is not working optimally, as described in Gluten-Induced Enteropathy (Coeliac Disease) Revealed by Resistance to Treatment with Levothyroxine and Alfacalcidol in a Sixty-Eight-Year-Old Patient: A Case Report. Thyroid. 2002 Jul;12(7):633-636.

More detailed information on thyroxine replacement may be obtained from your pharmacist or from various pharmaceutical company product information sheets. For one example of this type of information, see www.synthroid.com.

Triiodothyronine or T3

T3 is derived from T4 by enzymatic conversion in the blood and peripheral tissues. T3 is the more active form of thyroid hormone, and binds to nuclear thyroid hormone receptors in different cells and tissues. In contrast to T4 which has a long half-life of several days, T3 has a short half life (hours), and disappears more rapidly from our blood after a single dose. Furthermore, T3 is much more potent, and if taken in excessive dosages, T3 may rapidly cause problems such as fast heart beats and palpitations, increased sweating or anxiety, increased blood pressure, and in some patients, even chest pain (angina). T3 is often used for a brief period of time following thyroid surgery for thyroid cancer, following which the T3 is discontinued prior to administration of radioactive iodine. There are some reports suggesting that patients with hypothyroidism treated with T3 alone, or T3 in combination with T4 feel better and may experience less depression than patients treated with thyroxine alone. Only a few small studies have been carried out to examine this issue, and more information and larger studies are clearly warranted to examine the risks and benefits of T3 administration, as reviewed in Optimal Thyroid Hormone Replacement.

Side effects

Since T3 is far more potent than T4, there is a greater risk of side effects with T3, principally from conditions where excess T3 has been ingested. Many of these 'side effects' resemble the symptoms of severe hyperthyroidism, as T3 excess will produce a form of iatrogenic or medication-induced hyperthyroidism. Particular caution should be observed in patients with heart disease or high blood pressure, as T3 excess may precipitate angina or an arrhythmia, or may complicate control of blood pressure in patients with hypertension. For further information on T3, see the home page of  one manufacturer of T3, Cytomel.

For information on drugs such as methimazole and propylthiouracil (PTU) that are used to treat hyperthyroidism, see the section on Medications used to treat hyperthyroidism.

FAQs

My doctor or pharmacist switched my brand of thyroxine-should I be concerned?

This is an area that has engendered quite a bit of discussion amongst thyroid specialists, manufacturers and regulatory authorities responsible for drug approval. Scrutiny of the standards for manufacturing of L-thyroxine has revealed that in some instances there is potential for clinically significant variability in thyroid hormone levels when patients are switched from one brand to another. The Endocrine Society has prepared a position statement in June 2008 on Bioequivalence of Sodium Levothyroxine. A prudent course of action is to simply recheck levels of TSH and Free T4 4-8 weeks after switching brands of thyroxine.

Should I always take my thyroxine on an empty stomach? 

Although this is generally recommended, it is likely not 100% critical. For instance, in studies of older subjects in a nursing home, no significant changes in levels of TSH were detected if the thyroxine tablets were given on an empty stomach at midnight, versus after breakfast. The important lesson is to try and take your tablet at ~ the same time each day to minimize potential variability in absorption of the thyroid hormone. See Effect of levothyroxine administration time on serum TSH in elderly patients. Ann Pharmacother. 2001 May;35(5):529-32.

I take sucralfate and thyroxine together; is this a problem?

Some patients taking sucralfate may have decreased absorption of thyroxine, leading to a need for an increased strength of the thyroxine tablet. See Sucralfate causes malabsorption of L-thyroxine. Am J Med. 1994 Jun;96(6):531-5.

Can anti-seizure (epilepsy) medications affect thyroid function?

Patients taking medications for the treatment of seizure disorders may exhibit mild to moderate changes in levels of thyroid hormones, but the majority of patients do not seem to have a major problem. It may be difficult to ascertain in some patients whether the drugs are causing actual hypothyroidism, or simply decreasing the levels of free thyroid hormone. See Thyroid hormones in epileptic children receiving carbamazepine and valproic acid. Pediatr Neurol. 2001 Jul;25(1):43-6. and Thyroid function with antiepileptic drugs. Epilepsia. 1992 Jan-Feb;33(1):142-8 and Thyroid function tests in patients on long-term treatment with various anticonvulsant drugs. Clin Endocrinol (Oxf). 1978 Mar;8(3):185-91 and Thyroid Function in Men Taking Carbamazepine, Oxcarbazepine, or Valproate for Epilepsy. Epilepsia. 2001 Jul;42(7):930-4  and Risk factors for development of subclinical hypothyroidism during valproic acid therapy. J Pediatr. 2007 Aug;151(2):178-81. Epub 2007 Jun 22

I am taking raloxifene (Fosamax) for oesteoporosis-is there any problem taking thyroid hormone at the same time?

Although most patients have not taking the same medications together, rae observations suggest that in some instances, raloxifene may interfere with the absorption of thyroid hormone, as outlined in Increased thyroid-stimulating hormone levels associated with concomitant administration of levothyroxine and raloxifene. Pharmacotherapy. 2006 Jun;26(6):881-5

I am taking heparin and my thyroid hormone levels are abnormal. Is there a connection?

It appears that some forms of heparin may displace thyroid hormone binding sites resulting in elevated levels of free thyroid hormones. The mechanism for this interaction remains incompletely understood. See Abnormal serum free thyroid hormone levels due to heparin administration. QJM. 2001 Sep;94(9):471-3.

I take an anti-inflammatory medicine for arthritis. Will this affect my thyroid? 

In most cases, there should be no problem, however very rare case reports have described misleading thyroid blood tests in patients taking one specific anti-inflammatory medicine. See Cross-reactive mechanism for the false elevation of free triiodothyronine in the patients treated with diclofenac. Endocr J. 2001 Dec;48(6):717-22.

I am being treated with Bexarotene and my thyroid stopped working. What is going on?

Bexarotene is a synthetic retinoid X receptor (RXR)-selective retinoid used in the treatment of cutaneous T-cell lymphoma.  Bexarotene causes hypothyroidism by reducing levels of both thyroid-stimulating hormone (TSH) and thyroxine, and treatment may require relatively high levels of thyroxine. See Etiology, diagnosis, and treatment recommendations for central hypothyroidism associated with bexarotene therapy for cutaneous T-cell lymphoma. Clin Lymphoma. 2003 Mar;3(4):249-52.

I have been prescribed metformin for my diabetes and now my TSH is abnormal-any connection?

Several patients have noted a reduction in levels of TSH after starting metformin therapy. The mechanism linking metformin to control of TSH levels is not known. An association between metformin and lower TSH levels has also been detected in large cohort studies. See Thyrotropin Suppression by Metformin. J Clin Endocrinol Metab. 2005 Oct 11; [Epub ahead of print] and Metformin reduces thyrotropin levels in obese, diabetic women with primary hypothyroidism on thyroxine replacement therapy Endocrine. 2007 Aug; 32(1):79-82. Epub 2007 Oct 2 and TSH-LOWERING EFFECT OF METFORMIN IN TYPE 2 DIABETIC PATIENTS: DIFFERENCES BETWEEN EUTHYROID, UNTREATED HYPOTHYROID AND EUTHYROID ON L-T4 THERAPY PATIENTS Diabetes Care. 2009 Jun 5. [Epub ahead of print] and Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome Clin Endocrinol (Oxf). 2011 Mar 10. doi: 10.1111/j.1365-2265.2011.04042.x. [Epub ahead of print] and Metformin and low levels of thyroid-stimulating hormone in patients with type 2 diabetes mellitus CMAJ. 2014 Oct 21;186(15):1138-45.

I am taking imatinib( Gleevac) and sunitinib (Sutent) and other drugs for cancer treatment-any side effects on my thyroid replacement and dose of thyroxine?

A few reports have documented an association between imatinib therapy and hypothyroidism with an increased requirement for thyroxine-See Imatinib induces hypothyroidism in patients receiving levothyroxine. Clin Pharmacol Ther. 2005 Oct;78(4):433-8. Sunitinib has also been associated with the development of hypothyroidism Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors. Ann Intern Med. 2006 Nov 7;145(9):660-4. and Hypothyroidism in patients with metastatic renal cell carcinoma treated with sunitinib. J Natl Cancer Inst. 2007 Jan 3;99(1):81-3. Similarly, hypothyroidism has been reported in patients receiving sorafenib, a VEGF receptor inhibitor as described in  Thyroid function test abnormalities in patients with metastatic renal cell carcinoma treated with sorafenib Ann Oncol. 2007 Oct 24; [Epub ahead of print]. For an overview of how a class of drugs used to treat cancer, specifically the tyrosine kinase inhibitors, may often cause hypothyroidism, see Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy Nat Rev Clin Oncol. 2009 Apr;6(4):219-28. The anti-angiogenesis inhibitor lenalidomide has also been associated with the development of hypothyroidism in just less than 10% of treated subjects Thyroid abnormalities in patients treated with lenalidomide for hematological malignancies: Results of a retrospective case review Am J Hematol. 2011 Jun;86(6):467-70.

I am taking the diuretic furosemide (Lasix) and my thyroid tests are now abnormal-is there a connection?

Some assays that measure free thyroid hormone levels may give abnormal results due to an interaction between the drug and thyroid binding proteins, leading to a spurious increase in levels of Free T4 and Free T3, as outlined in Effect of oral frusemide on diagnostic indices of thyroid function Clin Endocrinol (Oxf). 1987 Apr;26(4):423-31 and Interaction of furosemide with serum thyroxine-binding sites: in vivo and in vitro studies and comparison with other inhibitors J Clin Endocrinol Metab. 1985 May;60(5):1025-31

What about selenium?

Patients with mild Graves eye disease of less than 18 months duration were given either selenium (100 mg twice daily) or the anti-inflammatory agent pentoxifylline (600 mg twice daily) for 6 months, then followed after discontinuation of therapy for another 6 months. The majority of patients studied had proptosis, but most did not have double vision. Patients treated with selenium had a decrease in their disease activity scores. Selenium was well tolerated with few adverse events. There were only modest changes in visual acuity or level of propotosis, however eyelid aperture was reduced and appearance and quality of life improved. Selenium and the Course of Mild Graves' Orbitopathy N Engl J Med 2011; 364:1920-1931

I am taking metformin for diabetes-any concerns about thyroid interactions?

Although metformin is not known to produce major effects on the thyroid, a few patients have been described who developed a low TSH while taking metformin Thyrotropin Suppression by Metformin. J Clin Endocrinol Metab. 2005 Oct 11;. However, a much larger retrospective analysis of thyroid function and TSL levels in 250 euthyroid metformin-treated subjects with type 2 diabetes, there was no consistent significant relationship between metformin use and changes in thyroid hormone levels

Relationship between serum thyrotropin concentrations and metformin therapy in euthyroid patients with type 2 diabetes Clin Endocrinol (Oxf). 2012 Jun 12. doi: 10.1111/j.1365-2265.2012.04468.x.