What affects tsh levels?

The lowdown on thyroid slowdown

Updated: March 19, 2019Published: March, 2014

Hypothyroidism can cause a host of health problems. Fortunately, an underactive thyroid can be easily diagnosed and treated.

Midlife can bring subtle changes in our skin, hair, energy, weight, and even mental outlook. Before writing them off as products of aging, it’s a good idea to make sure they’re not the result of an underactive thyroid.

This tiny butterfly-shaped gland influences virtually every organ system in the body. The hormones it secretes into the bloodstream play a vital role in regulating metabolism — the rate at which our bodies convert food and oxygen to energy.

Low thyroid hormone production, or hypothyroidism, causes a range of symptoms, such as fatigue, constipation, dry skin and brittle nails, aches and pains, and feeling down. You might easily attribute hypothyroidism symptoms to other health problems.

Moreover, hypothyroidism is especially common in women. Between ages 35 and 65, about 13% of women will have an underactive thyroid, and the proportion rises to 20% among those over 65. Because the link between hypothyroidism symptoms and thyroid disease isn’t always obvious, especially in older people, many women won’t know they have an underactive thyroid — and won’t be treated for it.

Untreated hypothyroidism can increase your risk for high cholesterol, high blood pressure, and heart disease. That’s why it’s important to keep an eye out for hypothyroidism symptoms and have your thyroid function checked. Hypothyroidism can be diagnosed with a blood test and treated with a pill.

Hypothyroidism symptoms

Hypothyroidism symptoms can differ from person to person. In some women, the onset is so gradual that it’s hardly noticeable; in others, hypothyroidism symptoms come on abruptly over the course of a few weeks or months. An underactive thyroid is mild in some women and severe in others. In general, the lower thyroid hormone levels are, the more pronounced and severe the symptoms.

Characteristic signs of hypothyroidism include:

  • Fatigue. Low thyroid function can result in less energy.
  • Cold intolerance. Slowed-down cells burn less energy, so the body produces less heat. You may feel chilly even when others around you are comfortable.
  • Appetite loss, weight gain. With lower energy needs, you require fewer calories, so your appetite declines. Yet, you may gain a few pounds because your body converts fewer calories into energy, leaving more to be stored as fat.
  • Cardiovascular effects. Low levels of thyroid hormone can lead to high blood pressure and elevated levels of total and LDL cholesterol. The heart’s pumping ability may slow, reducing blood flow to the skin, kidneys, brain, and other vital tissues, and increasing the risk of heart failure, especially in older women.
  • Mental effects. Hypothyroidism and depression share many of the same symptoms, including difficulty in concentrating, memory problems, and loss of interest in things that are normally important to you. They call for different treatments, so proper diagnosis is important.
  • Other signs and symptoms. Slowed metabolism reduces sweating, the skin’s natural moisturizer, so the skin may become dry and flaky and nails brittle. Hair may thin or become coarse. Digestive processes slow, causing constipation. Speech and movement may also slow down. In younger women, periods may become heavier and more frequent, or they may stop; infertility is sometimes a problem. Muscle aches and pain around the joints, including carpal tunnel syndrome, are common. Older women may have balance problems.

Anatomy of thyroid function

The thyroid gland produces and stores hormones that regulate metabolism: Too much hormone production (hyperthyroidism) and the body goes into overdrive; too little (hypothyroidism) and it bogs down.

The two most important thyroid hormones, triiodothyronine (T3) and thyroxine (T4), are made from the iodine in foods such as salt, seafood, bread, and milk. (T4 is the main thyroid hormone in the blood.) Both hormones travel from the thyroid via the bloodstream to distant parts of the body, including the brain, heart, liver, kidneys, bones, and skin, where they activate genes that regulate body functions.

Normally, the thyroid gland releases T3 and T4 when the hypothalamus (a regulatory region of the brain) senses that their circulating levels have dropped. The hypothalamus signals the pituitary gland, which sends thyroid-stimulating hormone (TSH) to the thyroid to trigger the release of thyroid hormones. In hypothyroidism, the thyroid gland doesn’t respond fully to TSH, so not enough T3 and T4 reach the body’s organs, and functions begin to slow. The pituitary releases more and more TSH in an effort to stimulate thyroid hormone production. That’s why TSH levels in the blood are high when thyroid function is low.

Causes of permanent hypothyroidism

Permanent hypothyroidism can be successfully treated, though not cured. These are the main causes:

  • Hashimoto’s thyroiditis. This disease causes most hypothyroidism. The immune system makes antibodies that attack the thyroid gland, which may enlarge (producing a goiter) or shrink in response and lose its ability to produce adequate thyroid hormone. Hashimoto’s thyroiditis tends to run in families and is much more common in women than in men, particularly as they get older. The condition is also associated with other autoimmune diseases, including type 1 diabetes, Addison’s disease, rheumatoid arthritis, pernicious anemia, and even prematurely gray hair. In people with a genetic susceptibility, the onset of Hashimoto’s thyroiditis can be triggered by factors such as high iodine intake, pregnancy, or cigarette smoking.
  • Surgery. Surgical removal of all or part of the thyroid gland is sometimes necessary in treating thyroid cancer, nodules, goiter, or an overactive thyroid. But removing the entire gland causes permanent hypothyroidism, and thyroid hormone replacement is required. If the gland is partially removed, it may or may not be able to make sufficient thyroid hormone.
  • Radiation treatment or exposure. Radioactive iodine taken to treat an overactive thyroid gland can damage the gland, causing permanent hypothyroidism. Radiation treatment for Hodgkin’s disease, lymphoma, and cancers of the head and neck may have the same effect. Radiation (and surgery) can also damage the pituitary gland, a key player in the production of thyroid hormones.

Temporary hypothyroidism

Inflammation of the thyroid gland (thyroiditis) may occur after a viral infection, pregnancy (postpartum thyroiditis), or an autoimmune attack. Sometimes an episode of temporary thyroiditis will cause a bout of overactive thyroid (hyperthyroidism), as the inflamed gland releases too much thyroid hormone, followed by a period of hypothyroidism. In some people, the hypothyroidism becomes permanent.

Some medications can suppress thyroid hormone production. These include the heart arrhythmia drug amiodarone (Cordarone); the psychiatric medication lithium; interferon alpha, which is used to treat hepatitis C and certain types of leukemia and other cancers; and the cancer drug interleukin-2. Drugs taken to treat an overactive thyroid — methimazole (Tapazole, Thiamazole) and propylthiouracil (PTU) — may overcorrect the problem, converting an overactive thyroid into an underactive one.

Diagnosing hypothyroidism

If you have any low thyroid symptoms, see your clinician for a physical exam. You’ll be checked for signs of hypothyroidism, such as an enlarged thyroid gland, dry skin, hair loss, weight gain, and elevated cholesterol levels. Your clinician may test your blood for levels of thyroid-stimulating hormone (TSH) — the single best screening test for thyroid disease — as well as the thyroid hormone thyroxine (T4). You’ll most likely get one of the following results:

  • Normal. If your TSH is between 0.45 and 4.5 mU/L, you have normal thyroid function and do not need treatment.
  • Subclinical hypothyroidism. If your TSH is elevated (above 4.5 mU/L) and the amount of available (free) T4 is normal (0.8–2.0 ng/dL), you have subclinical hypothyroidism. There’s no agreed-upon approach to managing this condition. The symptoms may or may not be due to borderline thyroid function, and not everyone who does have subclinical disease will progress to full-fledged, or primary, hypothyroidism. Most physicians decide what to do based on a woman’s symptoms and family history. This may involve a trial of thyroid medication to see if you feel better.
  • Primary hypothyroidism. If your TSH is high and your T4 low, you have an underactive thyroid, which should be treated.

Treating low thyroid

Hypothyroidism is usually treated with a daily dose of synthetic T4 (levothyroxine sodium), in pill form. Levothyroxine works exactly like your own body’s thyroid hormone. It’s available in the generic form and under such brand names as Levothroid, Levoxyl, and Synthroid. Although all brands contain the same synthetic T4, their inactive ingredients can vary, possibly affecting absorption, so it’s best to stick with one brand. Also, if you’re prescribed a particular brand and the pharmacy switches to a generic version, let your physician know. If your hypothyroidism is permanent, you’ll need to take synthetic T4 for the rest of your life. Some patients also require a small dose of T3 (Cytomel).

The goal of drug treatment is to lower your TSH to about the midpoint of normal range and maintain it at that level. Typically, you’ll start with a relatively low dose and have your TSH checked six to eight weeks later. If necessary, your physician will adjust the dose, repeating this process until your TSH is in the normal range. Physicians must be careful not to give you too much because excessive doses can stress the heart and increase your risk for osteoporosis by accelerating bone turnover. Once the right dose is established, your TSH and possibly T4 levels will be checked every six months to a year.

Thyroid hormone is best absorbed on an empty stomach. Don’t take antacids or supplemental iron at the same time because they can interfere with thyroid hormone absorption. Although certain factors like pregnancy or other medications affect your need for thyroid hormone, the dose usually remains fairly stable over time.

Most people who take enough synthetic T4 to normalize TSH levels will find that their symptoms go away.

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Blood Tests

Click here for Frequently Asked Questions on Blood Tests.

Thyroid blood tests generally include determination of the levels of circulating thyroid hormones (Free T4 and Free T3 and thyroid stimulating hormone TSH). These tests, especially the TSH, are highly sensitive and reliable, and the levels of thyroid hormones or TSH do not fluctuate widely during the day, or from day to day. Hence it is highly unlikely that a significant disturbance of thyroid function (hypo or hyperthyroidism) is present if the TSH is normal, even if only a single TSH determination is carried out. The results of thyroid blood tests can be affected by other medications a patient may be taking, so be sure that this information is provided to your physician. Patients who are being treated for hyperthyroidism usually require more than just a TSH determination to assess their thyroid status, since the TSH level can remain low for a prolonged period of time, even as the hyperthyroidism is getting better and the levels of Free T4 and T3 are dropping.

TSH is made by specialized cells in the pituitary called thyrotrophs. These cells are highly sensitive to the levels of circulating thyroid hormone in our body, and function like a sensitive thermostat. If the levels of thyroid hormone drop, the pituitary gland makes more TSH to stimulate the thyroid gland to work harder and make more thyroid hormone. Accordingly, an increased level of TSH strongly suggests the presence of hypothyroidism. Conversely, if thyroid hormone levels are too high, the pituitary gland shuts off production of TSH and the level of TSH will become low, or even undetectable, indicating a hyperthyroid state. The reliance on TSH as a key indicator of thyroid status depends on normal function of the hypothalamus and pituitary. Patients with a history of pituitary disease may not always be able to produce TSH normally, rendering the TSH less than 100% reliable in some patients with known pituitary problems.

Although the TSH test is currently considered the gold standard for the initial assessment of thyroid function, one must remember that the TSH tells us only what the pituitary thinks of the circulating levels of thyroid hormone. Although the TSH is the best indicator we have for knowing what our body thinks of the levels of thyroid hormones, it remains possible that there may be subtle differences in how our peripheral tissues (liver, muscles, heart etc) sense optimal levels of thyroid hormone. At present, it is not possible to sensitively or specifically assess how peripheral tissues perceive levels of thyroid hormone, so the TSH test remains our best surrogate marker of thyroid function. Although other parameters have been advocated as sensitive indicators of thyroid function, such as basal body temperature, these parameters are not specific indicators of thyroid status and may be influenced by other variables independent of thyroid function.

The optimal level of TSH to aim for may differ in various patients, depending on the precise diagnosis of thyroid disease present and what the clinical endpoints are. Moreover, there is some evidence that “normal” TSH levels may vary with age, as older individuals may have somewhat higher levels of TSH, yet still have no evidence of thyroid dysfunction, as outlined in and Age-Related Changes in Thyroid Function: A Longitudinal Study of a Community-Based Cohort J Clin Endocrinol Metab. 2012 Feb 16

Although newer TSH assays may indicate that many individuals have TSH levels that appear somewhat lower with the current generation of assays, there is no strong consensus among experts about whether the lower limit of normal for TSH determinations should be redefined, as outlined in The thyrotropin reference range should remain unchanged. J Clin Endocrinol Metab. 2005 Sep;90(9):5489-96 and in The evidence for a narrower thyrotropin reference range is compelling. J Clin Endocrinol Metab. 2005 Sep;90(9):5483-8. A brief discussion of this issue is also found in the section on osteoporosis.

Thyroid antibodies may be ordered to search for evidence of autoimmune thyroid diseases, such as Hashimoto’s or Grave’s disease. Thyroid antibodies may remain positive for years, and do not provide an indication of whether the person has normal or abnormal thyroid function. Furthermore, some patients with Hashimoto’s disease may have negative levels of circulating antibodies, and conversely, patients with positive levels of thyroid antibodies may never develop thyroid disease during their lifetime. It is generally not useful to repeatedly measure levels of thyroid antibodies in the blood. Although the presence of antibodies predicts a slightly higher rate of progression to hypothyroidism, some studies suggest that a slightly higher TSH in the mid upper normal range might convey the same prognostic information. See Serum thyrotropin is a better predictor of future thyroid dysfunction than thyroid autoantibody status in biochemically euthyroid patients with diabetes: implications for screening. Thyroid. 2004 Oct;14(10):853-7.

A Thyroglobulin level may be useful for monitoring patients with thyroid cancer, particularly after surgery and treatment with radioactive iodine. Many benign thyroid diseases can be associated with increased levels of thyroglobulin, hence an elevated thyroglobulin alone is not a specific indicators for the presence or absence of malignancy. At the Toronto General Hospital, normal values are:

0 – 34 ug/L for patients who still have their thyroid gland and

0 – 3 ug/L for patients following surgical removal and thyroid ablation

Thyroid stimulating immunoglobulins may be measured in patients with Grave’s disease, but are not required to make a clinical diagnosis. The presence or absence of these antibodies in a mother may also provide predictive information about whether a fetus or infant has an increased risk of developing transient hyperthyroidism.

A calcitonin blood test may be ordered if a diagnosis of medullary thyroid carcinoma (MTC) is suspected. Occasionally, a stimulation test may be carried out to examine the increase in levels of calcitonin in response to secretory agents such as calcium or pentagastrin.

A serum calcium may be done to assess parathyroid function, particularly in patients following thyroid surgery. For more information on regulation of blood calcium, see the parathyroid gland section.

FAQs

Do the levels of thyroid antibodies vary depending on the assay used?

Yes, the various test kits can give different results, which may influence the interpretation of thyroglobulin levels. See Comparison of some different methods for analysis of thyroid autoantibodies: importance of thyroglobulin autoantibodies. Thyroid. 2001 Mar;11(3):265-9.

My levels of Free T4 and T3 are normal, yet my TSH is abnormal, how can this be?

The levels of circulating thyroid hormones that are “normal” for any given individual may vary tremendously. For example, one subject may have a normal level of Free T4 at the upper end of the normal range, and a slight decrease in this Free T4 may cause an increase in TSH, despite still “high normal” levels of Free T4. Conversely, another individual may have a “normal” Free T4 at the lower end of the range, and even a slight increase in this persons level of circulating thyroid hormones may be associated with mild hyperthyroidism and a suppressed TSH. Hence, one needs to individualize each persons range of normal circulating thyroid hormones, and look at the laboratory limits of what is normal for a large population in this context. See Narrow individual variations in serum t(4) and t(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab. 2002 Mar;87(3):1068-72.

Why do my levels of thyroglobulin (Tg) fluctuate?

There are several possibilities, including the presence or absence of antibodies against thyroglobulin, and the use of different assays to measure thyroglobulin, as outlined in Discordant serum thyroglobulin results generated by two classes of assay in patients with thyroid carcinoma: correlation with clinical outcome after 3 years of follow-up. Cancer. 2003 Jul 1;98(1):41-7. Indeed, the newer more sensitive thyroglobulin assays which do not use radioactive tracers are more widely used, but are more prone to interference from circulating antithyroglobulin antibodies which can greatly compromise the accuracy of the thyroglobulin test. Hence, measurement of thyroid antibodies should always be done at the same time the thyroglobulin is measured. Some experts have advocated that the use of the newer highly sensitive Tg assays may one day supplant the need for a TSH-stimulated thyroglobulin in many patients. For an excellent overview of this area, see Measuring thyroglobulin and thyroglobulin autoantibody in patients with differentiated thyroid cancer Nat Clin Pract Endocrinol Metab. 2008 Apr;4(4):223-33

I have heard that measurement of the levels of thyroglobulin (Tg) RNA in a blood test may be a more sensitive way to look for recurrent tumors-is this test useful?

Although theoretically measurement of very low levels of Tg RNA in the circulation might provide a more sensitive test than the currently utilized blood test which measures the level of the circulating protein, ongoing evaluation of the clinical utility of such a test has shown inappropriately low utility, with suboptimal specificity in follow-up of patients with thyroid cancer. See Low specificity of blood thyroglobulin messenger ribonucleic acid assay prevents its use in the follow-up of differentiated thyroid cancer patients. J Clin Endocrinol Metab. 2004 Jan; 89(1): 33-9.

Does age affect levels of thyroid hormones?

Although levels of T4 and T3 do not change much in older individuals, the TSH response to hypothyroidism is age-dependent, with older subjects demonstrating a less robust TSH elevation in response to declining thyroid hormone levels

Are you sure the thyroid function tests are influenced by medications/drugs?

Drug-induced thyroid dysfunction should be considered when thyroid function test results are inconsistent with the clinical scenario or when a patient is taking a medication known to commonly disrupt thyroid function. Pseudo-abnormalities in thyroid function tests should be differentiated from true thyroid dysfunction. Certain drugs or agents can cause either or both of these abnormalities and understanding their potential thyroidal effects will help the clinician to appropriately manage the patient.

The use of certain drugs or agents have the potential to interfere with various steps of thyroid hormone metabolism which results in hypothyroidism or hyperthyroidism:

  • thyroid hormone absorption (in patients already taking levothyroxine therapy)

  • hypothalamic and pituitary regulation of thyroid hormone production

  • thyroid hormone synthesis and production

  • binding of T4 and T3 (triiodothyronine) to serum carrier proteins, mainly thyroxine binding globulin (TBG)

  • thyroid hormone pharmacokinetics

  • thyroid hormone pharmacodynamics (e.g. interference with the conversion of T4 to T3 in peripheral target organs)

Thyroid dysfunction can be transient or permanent, depending on the specific drug or agent, status of iodine nutrition, and presence of absence of any pre-existing autonomous thyroid nodules, subclinical thyroid dysfunction, and thyroid autoantibodies.

Because primary hypothyroidism (e.g. Hashimoto’s disease) or hyperthyroidism (e.g. Graves’ disease, toxic multinodular goiter, silent thyroiditis) are common, the distinction between drug-induced and primary thyroid dysfunction cannot always be easily made. Clinical judgment should dictate whether the suspected drug should be withdrawn and how the thyroid dysfunction should be further investigated and treated.

Table I lists the drugs and agents most frequently associated with thyroid dysfunction:

Table In

General considerations regarding drug-induced hypothyroidism

The clinical presentation of drug-induced hypothyroidism is indistinguishable from other causes of hypothyroidism. The types of drug-induced hypothyroidism are:

  • Impaired levothyroxine absorption arising from use of calcium, iron, bile acid sequestrants, coffee, sulcralfate, aluminum hydroxide, and sevelamer (to minimize this, patients should be encouraged to take their levothyroxine in the morning on an empty stomach to reduce the risk of interaction)

  • Transient hypothyroidism, similar to the hypothyroid phase of painless thyroiditis (silent lymphocytic thyroiditis), which normalizes after withdrawal of the drug or agent

  • Permanent hypothyroidism (with or without detectable thyroid autoantibodies)

General considerations regarding drug-induced hyperthyroidism

Similarly, symptoms and signs resulting from drug-induced hyperthyroidism are indistinguishable from causes of spontaneous hyperthyroidism. The types of drug-induced hyperthyroidism are:

  • Transient hyperthyroidism, similar to the hyperthyroid phase of painless thyroiditis (silent lymphocytic thyroiditis)

  • Hyperthyroidism due to Graves’ disease (with or without positive TSH receptor antibodies)

  • Hyperthyroidism arising from an iodine load in a patient with thyroid nodules

Which drugs can modify thyroid hormone metabolism?

Use of certain drugs may result in altered thyroid hormone metabolism and require higher doses of replacement LT4 to achieve a normal TSH.

  • Increased hepatic enzymes from certain antiepileptic medications (phenobarbital, carbamazepine or phenytoin) and the antibiotic, rifampicin, may reduce the half-lives of T4 and T3

  • Imatinib (a tyrosine kinase inhibitor used to treat certain cancers) is thought to increase the hepatic metabolism of thyroid hormone

  • Drugs that increase thyroxine binding globulin (TBG) levels (e.g. estrogens) will reduce the availability of FT4

  • Amiodarone impairs the peripheral de-iodination of T4, and therefore, the conversion of T4 to T3

  • Glucocorticoids and some beta blockers at high doses can also inhibit T4 toT3 de-iodination, although these changes are not usually clinically relevant

What else could the patient have?

Some drugs or agents can directly lower TSH secretion without altering thyroid gland function (i.e. TT4 and FT4 remain normal). This effect is transient and has been reported primarily with high doses of glucocorticoids and intravenous dopamine or dobutamine. However, a sustained decrease in TSH production leading to a decrease of FT4 (central hypothyroidism) has rarely been reported during prolonged use of somatostatin analogs.

In subclinical hyperthyroidism, the TSH is low and FT4 is normal. A small increase in FT4 (even within the normal range) is usually detected by the hypothalamus and the pituitary to result in decreased TSH secretion. One may suspect subclinical hyperthyroidism if the FT4 is in the upper part of the normal range.

In patients with acute illness, including infection, heart failure, or respiratory failure, non-thyroidal illness may be associated with thyroid dysfunction. In these scenarios, serum TSH and T3 levels may be initially decreased and followed by a later decrease of the serum FT4 level. Clinical judgement and repeat thyroid function tests should be carried out after the illness is resolved.

Key laboratory and imaging tests

TSH is the most sensitive test to detect thyroid dysfunction. A low TSH is most frequently diagnostic of spontaneous hyperthyroidism. In addition to some types of drug-induced thyroid dysfunction, the differential diagnoses for a low TSH are:

  • Graves’ disease

  • Toxic multinodular goiter

  • Toxic adenoma

  • Thyroiditis (silent, painful, de Quervain)

  • Exogenous sources of thyroid hormone ingestion

  • Non-thyroidal illness (euthyroid sick syndrome)

  • Central hypothyroidism

  • Recovery phase after treatment for hyperthyroidism

  • Laboratory artifact (analytical interference)

  • Rare genetic conditions

When the TSH is abnormal, the next test in the evaluation of thyroid dysfunction is the measurement of TT4 and FT4 and/or TT3. While alterations in serum T4 and T3 levels are parallel to each other, there are some conditions associated with discrepancies in these tests, including non-thyroidal illness, amiodarone therapy, T3-toxicosis, hypothyroidism, and some rare conditions of impaired de-iodination.

Thyroid autoantibodies may be of some use in the evaluation of hypothyroidism, although they are not particularly specific and sensitive. For example, transient hypothyroidism after painless thyroiditis is not easily differentiated from permanent Hashimoto’s hypothyroidism because autoantibodies are present in both conditions. Furthermore, up to 20% of the general euthyroid population may have positive thyroid antibodies (anti-thyroglobulin or/and anti-TPO antibodies), although these individuals may progress over many years to hypothyroidism.

However, in suspected spontaneous hyperthyroidism, the measurement of TSH-receptor antibodies can prove useful because they are highly specific to Graves’ disease, although they can be absent in 10-20% of individuals. In patients with preexisting thyroid autoantibodies, there is a higher risk of developing thyroid dysfunction during treatment with interferon. In summary, the occurrence of drug-induced thyroid dysfunction cannot be accurately predicted, but pretreatment autoantibody screening may be helpful.

Which drugs can lower TSH without inducing true thyroid dysfunction?

  • Glucocorticoids in high doses during initial treatment; in contrast, prolonged exposure to glucocorticoid therapy or endogenous hypercortisolism (Cushing’s syndrome) do not result in thyroid dysfunction

  • Dopamine or dobutamine

  • Octreotide

These drugs do not generally cause clinically significant central hypothyroidism, and their suppressant effect on TSH production is transient. An exception is bexarotene, in which the associated central hypothyroidism that is occasionally seen normalizes after the discontinuation of the medication.

Which drugs can cause thyroid dysfunction and should this be treated?

Amiodarone

Amiodarone can cause transient alterations of thyroid function tests, as well as overt hypothyroidism or hyperthyroidism. The incidence of amiodarone-induced thyroid dysfunction varies with iodine nutrition. In iodine-sufficient populations, hypothyroidism is more common, whereas in iodine-deficient populations, hyperthyroidism is more common. In most cases of hyperthyroidism, amiodarone should be withdrawn if agreed upon by the cardiologist. Amiodarone impairs the peripheral de-iodination of T4 to generate T3.

Following amiodarone administration, TSH levels transiently increase with a subsequent increase of T4. A new steady state is achieved, and TSH returns to normal. In euthyroid amiodarone-treated patients, the T4 and FT4 concentrations are high normal or slightly increased and the T3 and FT3 concentrations are in the lower range of normal. The half-life of amiodarone is extremely long, and elimination from adipose tissue may take several months.

In iodine-sufficient areas, the occurrence of amiodarone-induced hypothyroidism is approximately 5-15%. Hypothyroidism continues as long as amiodarone is given. The mechanism is thought to be the failure to escape from the acute Wolff-Chaikoff phenomenon. Permanent hypothyroidism may result, especially in individuals with pre-existing thyroid autoimmunity. Treatment for amiodarone-induced hypothyroidism is LT4. The dose of LT4 required to achieve euthyroidism may be higher than usual because of the decrease in T4 de-iodination to T3.

Amiodarone-induced thyrotoxicosis (AIT) is categorized as type 1 (iodine-induced thyroid autonomy) versus type 2 (thyroiditis) AIT. In type 1 AIT, thionamides are the treatment of choice, whereas type 2 AIT will improve with high-dose glucocorticoids given approximately for 3-6 months. Use of amiodarone is associated with a large iodine load (200 mg contains approximately 70 mg of iodide, of which 10% is bioavailable; this is almost 50 times the daily recommended intake of 0.150 mg). This iodine load is the presumed mechanism of type 1 AIT, which is most commonly seen in patients with an underlying nodular goiter. Type 2 AIT is a painless thyroiditis due to amiodarone-induced inflammatory changes in the thyroid, which is also seen in other tissues.

Color-flow Doppler thyroid ultrasound may demonstrate increased blood flow in an enlarged, frequently nodular goiter (type 1 AIT) or decreased blood flow in a normal or small-sized thyroid (type 2 AIT). Treatment of type 1 AIT with large doses of methimazole and beta-blockers is recommended, and if a poor response is seen, the addition of 200 mg perchlorate (a competitive inhibitor of the sodium/iodide symporter on the basolateral surface of the thyroid epithelial cell) every 8 hours.

Corticosteroids are extremely efficacious in type 2 AIT. Some patients have a combination of the two types of AIT and require both methimazole and corticosteroids. Thyroidectomy is reserved for refractory cases. Regular monitoring (every 6 months) of TSH is recommended for patients on amiodarone therapy, since the incidence of hyperthyroidism is reported in 2-10% of patients, with higher incidences seen with longer durations of treatment. Baseline thyroid function tests prior to amiodarone administration are recommended.

Lithium

Hypothyroidism is the most common thyroid complication of lithium therapy and may be confused with the depressive phase in bipolar patients. Lithium-induced hypothyroidism most commonly occurs in patients with positive thyroid peroxidase (TPO) antibodies. Replacement LT4 is indicated if the hypothyroidism is permanent.

Lithium-induced hyperthyroidism is transient and similar to silent thyroiditis. As lithium is primarily used in the treatment of bipolar disorder, hyperthyroidism should be considered in the differential diagnosis during manic or anxious episodes. The hyperthyroidism is usually self-limited. Only symptomatic treatment with beta blockers may be required, although cases of lithium-associated Graves’ disease have been reported. Thionamides (e.g. methimazole) are not indicated, as the underlying mechanism is not increased thyroid hormone synthesis, but rather the release of thyroid hormones arising from a destructive thyroiditis. Unless an alternative psychiatric medication is available, withdrawal of lithium is not required.

Lithium therapy has also been used as an adjunctive treatment for hyperthyroidism with 131I since it enhances the retention of 131I in the thyroid, a factor which also supports its use in the treatment of thyroid cancer with 131I. Among other endocrine abnormalities, lithium may induce primary hyperparathyroidism and diabetes insipidus by decreasing the action of antidiuretic hormone (ADH) on the kidney tubules; hence, regular monitoring of TSH, calcium, and fluid intake is recommended during lithium use.

Interferons (IFN)

IFN-α, used in the treatment of hepatitis C, can cause both hypothyroidism and hyperthyroidism, with hypothyroidism being far more common. Symptoms of IFN-induced hypothyroidism or hyperthyroidism may be difficult to distinguish from the side-effects of IFN therapy. Regular monitoring of TSH is recommended during IFN use.

The incidence of IFN-induced hypothyroidism is increased with combined ribavirine treatment and in subjects with preexisting thyroid autoantibodies. Furthermore, hepatitis C virus has been directly linked to an increased risk of thyroid dysfunction in the absence of IFN treatment. Hypothyroidism has also been reported with interferon-β treatment for multiple sclerosis, but the thyroid dysfunction is usually subclinical and transient, with LT4 replacement usually not required.

IFN-α-induced hyperthyroidism can occur as typical Graves’ disease (sometimes with ophthalmopathy) or transiently as the hyperthyroid phase of thyroiditis. Both interferon-α or pegylated interferon-α can induce thyroid dysfunction. The incidence is approximately 10-20%. A thyroid nuclear study may be helpful and demonstrates decreased uptake in IFN-induced hyperthyroidism. Monitoring of thyroid function will allow the clinician to assess whether the hyperthyroidism is transient or more permanent.

Tyrosine Kinase Inhibitors (TKIs)

TKIs have been associated with both hypothyroidism and hyperthyroidism. Sunitinib has been shown to be associated with hypothyroidism in 30-50% of patients taking this medication. In some cases, thyroid gland atrophy is seen. There have been some reports of a correlation between cancer response to sunitinib and the occurrence of hypothyroidism. Hypothyroidism has also been reported with sorafenib and imatinib treatments. Similar to other causes of hypothyroidism, LT4 replacement may be indicated. Transient hyperthyroidism associated with a destructive thyroiditis and possible subsequent hypothyroidism (transient or permanent) has been described.

Alemtuzumab

Alemtuzumab, used in the treatment of multiple sclerosis, has been associated with new-onset Graves’ disease that is confirmed with positive serum TSH-receptor antibodies.

Iodine-containing medications and agents

Exogenous iodine administration (from topical disinfectants, radiologic contrast agents, amiodarone, and other sources) can induce hyperthyroidism or hypothyroidism. In certain individuals (including those with Hashimoto’s thyroiditis), hypothyroidism may develop due to a failure to escape from the acute Wolff-Chaikoff phenomenon following an iodine load. In iodine-deficient areas, iodine supplementation (used to prevent endemic goiter) has been associated with an increase in the incidence of hyperthyroidism. This is more likely in susceptible individuals (those with euthyroid nodular goiter, toxic thyroid nodules, or euthyroid Graves’ disease), in which iodine administration may unmask latent hyperthyroidism.

Although screening for thyroid dysfunction before administration of radiologic contrast agents is not routinely recommended, if previous thyroid function tests suggest a borderline low serum TSH, prophylactic treatment with methimazole or 200 mg potassium perchlorate every 8 hours (not available in the U.S., but can be compounded using reagent grade sodium or potassium perchlorate) may help block thyroidal iodine uptake and prevent hyperthyroidism.

What’s the Evidence?/References

Surks, MI, Ross, DS. “Drug interactions with thyroid hormones”. 2011. (An authoritative review.)

Surks, MI, Sievert, R. “Drugs and thyroid function”. N Engl J Med.. vol. 333. 1995. pp. 1688-94. (An authoritative review.)

Barbesino, G. “Drugs affecting thyroid function”. Thyroid. vol. 20. 2010. pp. 763-70. (Excellent review with recent evidence.)

Sarne, D, De Groot, LJ. “Chapter 5a. Effects of the environment, chemicals and drugs on thyroid function”. thyroid disease manager . 2010. (Extensive review with more than 400 references.)

Basaria, S, Cooper, DS. “Amiodarone and the thyroid”. Am J Med. vol. 118. 2005. pp. 706-14. (Excellent concise review.)

Singh, N, Hershman, J. “Interference with the absorption of levothyroxine”. Curr Opin Endocrinol Diabetes. vol. 10. 2003. pp. 347-352. (Review of medications which affect levothyroxine absorption.)

What to know about the TSH test

A TSH test helps doctors determine how well the thyroid gland is functioning. People may require TSH testing for several different reasons, which we explore in more detail below.

Symptoms of a thyroid problem

Share on PinterestSymptoms of a thyroid problem can include fatigue and irritability.

The TSH test helps doctors diagnose common thyroid disorders, such as hyperthyroidism and hypothyroidism.

The signs and symptoms of hyperthyroidism, in which the thyroid overproduces hormones, include:

  • anxiety or irritability
  • bulging eyes
  • fatigue
  • increased appetite
  • increased sensitivity to heat
  • menstrual changes
  • muscle weakness
  • rapid or irregular heart rate
  • sleep problems
  • increased sweating
  • thinning skin or hair
  • tremors
  • weight loss with no apparent cause
  • goiter, which is an abnormally enlarged thyroid gland

People with hypothyroidism, where the thyroid does not produce enough hormones, may experience signs and symptoms that include:

  • aches and pains
  • constipation
  • depression and memory problems
  • dry skin
  • fatigue
  • goiter
  • high cholesterol
  • hoarseness
  • low heart rate
  • menstrual changes
  • muscle weakness
  • sensitivity to cold temperatures
  • thinning hair
  • weight gain

A TSH test may also help indicate other types of thyroid problem, such as:

  • Graves’ disease, which causes greater activity of the thyroid
  • Hashimoto’s disease, an autoimmune condition where the body attacks the thyroid
  • thyroid nodules, which are lumps on the thyroid that contribute to an overactive thyroid
  • inflammation of the thyroid gland, called thyroiditis
  • postpartum thyroiditis, which is temporary thyroiditis following pregnancy

Already have a thyroid disorder diagnosis

People who have a known thyroid disorder may have regular TSH testing to monitor their condition and the effectiveness of their treatment.

Pregnancy

Some doctors will recommend that pregnant women have TSH tests to check their thyroid hormone levels.

According to the ATA, many experts support testing for thyroid disease in women who are pregnant or thinking of becoming pregnant.

Newborn babies in the United States will also often get a routine TSH test for congenital hypothyroidism as part of their screening program.

Thyroiditis May Be to Blame for Switching Between Hypo- and Hyperthyroidism

June 3, 2011

Dear Mayo Clinic:

What could be causing me to swing back and forth between hypo- and hyperthyroidism?

Answer:
You may be switching between these two disorders for several reasons. Before exploring possible causes, though, it’s important that you get a definitive diagnosis of hypothyroidism or hyperthyroidism, if you haven’t done so already.

The thyroid, a small gland at the base of the front of the neck, produces hormones that help control body temperature, influence the heart rate, regulate the production of protein and maintain the rate at which the body uses fats and carbohydrates.

An underactive thyroid (hypothyroidism) doesn’t produce enough hormone. An overactive thyroid (hyperthyroidism) produces too much hormone. Symptoms may include unintentional weight gain or loss, persistent fatigue, palpitations, and sensitivity to hot or cold temperatures. But because other health problems cause similar symptoms, diagnosing hypothyroidism or hyperthyroidism based on symptoms alone is not possible. Instead, a blood test that measures your level of thyroid hormone is required. If a blood test confirms hypo- or hyperthyroidism and verifies that you have switched between them, there could be several possible explanations.

If you don’t have a history of thyroid problems, the most common reason for a change in thyroid function is inflammation of the thyroid gland (thyroiditis). Initially, thyroiditis leads to overactive thyroid function because when the thyroid first becomes inflamed, it releases all its stored hormones. After that, the thyroid slowly begins to return to normal, but it doesn’t maintain its usual hormone production. So once the hormone stores are depleted, hypothyroidism develops. Its outcome depends on the type of thyroiditis, as follows.

Two main types of thyroiditis exist. The first, subacute thyroiditis, involves pain that begins at the front of the neck and shoots toward the ears. Subacute thyroiditis is caused by a virus and often resolves on its own, without lasting problems.

The second type, silent thyroiditis, is painless and appears to be an autoimmune disorder, in which the immune system attacks thyroid tissue. Silent thyroiditis is most likely to occur in women during the months following pregnancy. For many people with silent thyroiditis, thyroid function returns to normal after the first episode. This type of thyroiditis can recur, though. If it does, over time people with silent thyroiditis may develop long-term hypothyroidism.

If you’re already being treated for a thyroid problem, and your thyroid function begins to shift between underactive and overactive, thyroiditis probably isn’t the source of the problem. More likely, your medication is to blame.

People diagnosed with hyperthyroidism usually take the medication methimazole to prevent the thyroid from producing excess hormones. This medication sometimes can initially decrease hormone production too much, and hypothyroidism results. The dose of methimazole then needs to be adjusted and the condition is monitored closely over time.

In people being treated for hypothyroidism, the medication prescribed is often a generic form of the drug levothyroxine. The generic form isn’t a problem as long as the same manufacturer’s product is used consistently. If the manufacturer changes, the new pill could have a variation of 10 to 15 percent in its active component compared with the prior tablet. That can significantly affect your body, possibly leading to either hyperthyroidism or hypothyroidism. If your pharmacy can’t ensure that the generic medication will come from the same manufacturer when you need prescription refills, consider a brand-name drug instead.

Finally, remember that thyroid medication must be taken consistently to ensure your body absorbs it properly. When and how you take thyroid medications, as well as other medications you may take, can impact how effective thyroid medication will be. Follow medication directions carefully, and whenever a new medication is prescribed, discuss with your doctor the impact it may have on your thyroid treatment.

— Marius Stan, M.D., Endocrinology, Mayo Clinic, Rochester, Minn.

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