What is the thyroid?
The thyroid is a 2-inch-long, butterfly-shaped gland weighing less than 1 ounce. Located in the front of the neck below the larynx, or voice box, it has two lobes, one on either side of the windpipe.The thyroid is one of the glands that make up the endocrine system. The glands of the endocrine system produce and store hormones and release them into the bloodstream. The hormones then travel through the body and direct the activity of the body’s cells.
What is the role of thyroid hormones?
Thyroid hormones regulate metabolism—the way the body uses energy—and affect nearly every organ in the body. Thyroid hormones also affect brain development, breathing, heart and nervous system functions, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels.The thyroid makes two thyroid hormones:
- thyroxine (T4)
- triiodothyronine (T3)
Why do health care providers perform thyroid tests?
Health care providers perform thyroid tests to assess how well the thyroid is working. The tests are also used to diagnose and help find the cause of thyroid disorders such as hyperthyroidism and hypothyroidism:- Hyperthyroidism is a disorder caused by too much thyroid hormone in the bloodstream, which increases the speed of bodily functions and leads to weight loss, sweating, rapid heart rate, and high blood pressure, among other symptoms.
- Hypothyroidism is a disorder that occurs when the thyroid doesn’t make enough thyroid hormone for the body’s needs. Without enough thyroid hormone, many of the body’s functions slow down. People may have symptoms such as fatigue, weight gain, and cold intolerance.
What blood tests do health care providers use to check a person’s thyroid function?
A health care provider may order several blood tests to check thyroid function, including the following:- TSH test
- T4 tests
- T3 test
- thyroid-stimulating immunoglobulin (TSI) test
- antithyroid antibody test, also called the thyroid peroxidase antibody test (TPOab)
Many complex factors affect thyroid function and hormone levels. Health care providers take a patient’s full medical history into account when interpreting thyroid function tests.
TSH Test
A health care provider usually performs the TSH blood test first to check how well the thyroid is working. The TSH test measures the amount of TSH a person’s pituitary is secreting. The TSH test is the most accurate test for diagnosing both hyperthyroidism and hypothyroidism. Generally, a below-normal level of TSH suggests hyperthyroidism. An abnormally high TSH level suggests hypothyroidism.The TSH test detects even tiny amounts of TSH in the blood. Normally, the pituitary boosts TSH production when thyroid hormone levels in the blood are low. The thyroid responds by making more hormone. Then, when the body has enough thyroid hormone circulating in the blood, TSH output drops. The cycle repeats continuously to maintain a healthy level of thyroid hormone in the body. In people whose thyroid produces too much thyroid hormone, the pituitary shuts down TSH production, leading to low or even undetectable TSH levels in the blood.
In people whose thyroid is not functioning normally and produces too little thyroid hormone, the thyroid cannot respond normally to TSH by producing thyroid hormone. As a result, the pituitary keeps making TSH, trying to get the thyroid to respond.
If results of the TSH test are abnormal, a person will need one or more additional tests to help find the cause of the problem.
T4 Tests
The thyroid primarily secretes T4 and only a small amount of T3. T4 exists in two forms:- T4 that is bound to proteins in the blood and is kept in reserve until needed
- a small amount of unbound or “free” T4 (FT4), which is the active form of the hormone and is available to enter body tissues when needed
Both pregnancy and taking oral contraceptives increase levels of binding protein in the blood. In either of these cases, although a woman may have a high total T4 level, she may not have hyperthyroidism. Severe illness or the use of corticosteroids—a class of medications that treat asthma, arthritis, and skin conditions, among other health problems—can decrease binding protein levels. Therefore, in these cases, the total T4 level may be low, yet the person does not have hypothyroidism.
T3 Test
If a health care provider suspects hyperthyroidism in a person who has a normal FT4 level, a T3 test can be useful to confirm the condition. In some cases of hyperthyroidism, FT4 is normal yet free T3 (FT3) is elevated, so measuring both T4 and T3 can be useful if a health care provider suspects hyperthyroidism. The T3 test is not useful in diagnosing hypothyroidism because levels are not reduced until the hypothyroidism is severe.TSI Test
Thyroid-stimulating immunoglobulin is an autoantibody present in Graves’ disease. TSI mimics TSH by stimulating the thyroid cells, causing the thyroid to secrete extra hormone. The TSI test detects TSI circulating in the blood and is usually measured- in people with Graves’ disease when the diagnosis is obscure
- during pregnancy
- to find out if a person is in remission, or no longer has hyperthyroidism and its symptoms
Antithyroid Antibody Test
Antithyroid antibodies are markers in the blood that are extremely helpful in diagnosing Hashimoto’s disease. Two principal types of antithyroid antibodies are- anti-TG antibodies, which attack a protein in the thyroid called thyroglobulin
- anti-thyroperoxidase, or anti-TPO, antibodies, which attack an enzyme in thyroid cells called thyroperoxidase
What do thyroid test results tell health care providers?
Health care providers look at thyroid test results in people with hyperthyroidism or hypothyroidism to find the underlying cause of their thyroid disorder. The following tables illustrate what test results may show based on the type of thyroid problem.
Table 1. Typical thyroid function test results:
Hyperthyroidism
Cause
|
Test
| |||
|---|---|---|---|---|
| TSH | T3/T4 | TSI | Radioactive Iodine Uptake Test | |
| Graves' disease | ↓ | ↑ | + | ↑ |
| Thyroiditis (with hyperthyroidism) | ↓ | ↑ | - | ↓ |
| Thyroid nodules (hot, or toxic) | ↓ | ↑ | - | ↑ or Normal |
Table 2. Typical thyroid function test results:
Hypothyroidism
Cause
|
Test
| ||
|---|---|---|---|
| TSH | T3/T4 | Antithyroid Antibody | |
| Hashimoto’s disease (thyroiditis, early stage) | ↑ | ↓ or Normal | + |
| Hashimoto’s disease (thyroiditis, later stage) | ↑ | ↓ | + |
| Pituitary abnormality | ↓ | ↓ | - |
What imaging tests do health care providers use to diagnose and find the cause of thyroid disorders?
A health care provider may use one or a combination of imaging tests, such as an ultrasound of the thyroid, a computerized tomography (CT) scan, or nuclear medicine tests, to diagnose and find the cause of thyroid disorders.- Ultrasound. Ultrasound uses a device, called a transducer, that bounces safe, painless sound waves off organs to create an image of their structure. A specially trained technician performs the procedure in a health care provider’s office, an outpatient center, or a hospital, and a radiologist—a doctor who specializes in medical imaging—interprets the images; a patient does not need anesthesia. The images can show the size and texture of the thyroid, as well as a pattern of typical autoimmune inflammation. The images can also show nodules or growths within the gland that suggest a malignant tumor.
- CT scan. CT scans use a combination of x rays and computer technology to create images. For a CT scan, a health care provider may give the patient a solution to drink and an injection of a special dye, called contrast medium. CT scans require the patient to lie on a table that slides into a tunnel-shaped device where the x rays are taken. An x-ray technician performs the procedure in an outpatient center or a hospital, and a radiologist interprets the images. The patient does not need anesthesia. CT scans are usually not needed to diagnose thyroid disease; however, health care providers will use them to view a large goiter. Also, a CT scan will often show a thyroid nodule when a person is having the scan for other health problems.
- Thyroid scan. A thyroid scan is a type of nuclear medicine imaging. Nuclear medicine uses small amounts of radioactive material to create a picture of an organ and give information about the organ’s structure and function. A thyroid scan is used to look at the size, shape, and position of the gland. This test can help find the cause of hyperthyroidism and check for thyroid nodules. The scan also can help a health care provider evaluate thyroid nodules; however, it does not confirm whether the nodules are cancerous or benign.
- A specially trained technician performs the procedure in an outpatient center or a hospital, and a radiologist interprets the images; a patient does not need anesthesia. For the scan, radioactive iodine or radioactive technetium is injected into the patient’s vein or swallowed in liquid or capsule form. The scan takes place 30 minutes after an injection or 6 to 24 hours after the radioactive substance is swallowed. The patient lies on an exam table for the scan, which takes about 30 minutes.
- A device called a gamma camera is suspended over the table or may be located within a large, tunnel-shaped device that resembles a CT scanner. The gamma camera detects the radioactive material and sends images to a computer that show how and where the radioactive substance has been distributed in the thyroid. Nodules that produce too much thyroid hormone—called “hot,” or toxic, nodules—show up clearly because they absorb more radioactive material than normal thyroid tissue. Graves’ disease shows up as a spread-out, overall increase in radioactivity rather than an increase in a localized spot.
- Even though the amount of radiation used in this test is small, women who are pregnant or breastfeeding should not have this test because of the risks of exposing the fetus or the baby to radiation.
- Radioactive iodine uptake test. The radioactive iodine uptake test, also known as a thyroid uptake, is a nuclear medicine test used to evaluate the function of the thyroid and find the cause of a patient’s hyperthyroidism. A whole-body thyroid scan is used for people who have had thyroid cancer. The test measures the amount of iodine the thyroid collects from the bloodstream in a given time period. The thyroid uptake is not used to assess hypothyroidism.
- A specially trained technician performs the test in an outpatient center or a hospital, and a radiologist interprets the images; a patient does not need anesthesia. For this test, the patient swallows a small amount of radioactive iodine in liquid or capsule form. After 4 to 6 hours and again at 24 hours, the patient returns to the testing center, where the technician measures the amount of radioactive iodine taken up by the thyroid. The measurement is taken with a small device called a gamma probe, which resembles a microphone. The gamma probe is positioned near the patient’s neck over the thyroid. Measurement takes only a few minutes and is painless.
- In the diagnosis of hyperthyroidism, a high thyroid uptake reading usually indicates an overactive thyroid that produces too much thyroid hormone, as seen in Graves’ disease or a condition called toxic nodular goiter, an enlargement of the thyroid. A low thyroid uptake reading suggests the thyroid is not overactive.
- Several thyroid disorders that cause inflammation of the thyroid, or thyroiditis, may cause leakage of thyroid hormone and iodine out of the thyroid into the bloodstream, which can lead to high T4 levels. When the thyroid is inflamed, it does not take up the radioactive iodine given as part of the thyroid uptake test. For example, hyperthyroidism seen in Graves’ disease would be marked by high blood T4 and a high thyroid uptake reading. In thyroiditis, temporary hyperthyroidism may exist because of the release of T4 into the blood; however, the thyroid uptake reading is low because of the inflammation. Temporary hyperthyroidism in thyroiditis is often followed by a period of hypothyroidism before the thyroid heals.
- Even though the amount of radiation used in this test is small, women who are pregnant or breastfeeding should not have this test because of the risks of exposing the fetus or infant to radiation.
What tests do health care providers use if a thyroid nodule is found?
If a health care provider feels a nodule in a patient’s neck during a physical exam or detects one during imaging tests of the thyroid, a fine needle aspiration biopsy may be done to confirm whether the nodule is cancerous or benign.A fine needle aspiration biopsy of the thyroid involves taking cells from the thyroid for examination with a microscope. The health care provider with experience in needle aspirations performs the biopsy in his or her office, an outpatient center, or a hospital; he or she may use medication to numb the area. The patient may feel mild discomfort during the test and the biopsy site may be tender for 1 to 2 days.
For this test, the patient lies back with support under the shoulders so the neck can be extended and bent back slightly. The health care provider inserts a small, thin needle attached to a syringe into the thyroid nodule and uses ultrasound to guide its insertion. Samples of the cells in the nodule are drawn through the needle and sent to a lab to be examined by a pathologist—a doctor who specializes in diagnosing diseases. The health care provider may need to take several samples. Once the biopsy is complete, a bandage is placed on the area to lower the chance of bleeding.
Points to Remember of Thyroid diseaseases
- The thyroid is one of the glands that make up the endocrine system. Thyroid hormones affect metabolism, brain development, breathing, heart and nervous system functions, body temperature, muscle strength, skin dryness, menstrual cycles, weight, and cholesterol levels.
- The TSH test is the most accurate test for diagnosing both hyperthyroidism and hypothyroidism.
- Health care providers perform thyroid function tests to assess how well the thyroid is working. The tests also are used to diagnose and help find the cause of thyroid disorders.
- Hyperthyroidism is caused by too much thyroid hormone in the bloodstream, which increases the speed of bodily functions and leads to weight loss, sweating, rapid heart rate, and high blood pressure, among other symptoms.
- Hypothyroidism is a disorder that occurs when the thyroid doesn’t make enough thyroid hormone for the body’s needs. Without enough thyroid hormone, many of the body’s functions slow down. People may have symptoms such as fatigue, weight gain, and cold intolerance.
- A health care provider may order several blood tests to check thyroid function.
- A health care provider may use one or a combination of imaging tests, such as an ultrasound of the thyroid, a thyroid scan, or a radioactive iodine uptake test, to diagnose and find the cause of thyroid disorders.
- If a health care provider feels a nodule in a patient’s neck during a physical exam or detects one during imaging tests of the thyroid, a fine needle aspiration biopsy may be done to confirm whether the nodule is cancerous or benign.
Background
Hypothyroidism is a common endocrine disorder that mainly affects women and the elderly.Objective
This article outlines the aetiology, clinical features, investigation and management of hypothyroidism.Discussion
In the Western world, hypothyroidism is most commonly caused by autoimmune chronic lymphocytic thyroiditis. The initial screening for suspected hypothyroidism is thyroid stimulating hormone (TSH). A thyroid peroxidase antibody assay is the only test required to confirm the diagnosis of autoimmune thyroiditis. Thyroid ultrasonography is only indicated if there is a concern regarding structural thyroid abnormalities. Thyroid radionucleotide scanning has no role in the work-up for hypothyroidism. Treatment is with thyroxine replacement (1.6 μg/kg lean body weight daily). Poor response to treatment may indicate poor compliance, drug interactions or impaired absorption. The significance of elevated TSH associated with thyroid hormones within normal range is controversial; thyroxine replacement may be beneficial in some cases. Unless contraindicated, iodine supplementation should be prescribed routinely in women planning a pregnancy. Where raised TSH levels are detected periconceptually or during pregnancy, specialist involvement should be sought.Aetiology
Iodine deficiency remains the most common cause of hypothyroidism worldwide.4 However, in Australia and other iodine replete countries, autoimmune chronic lymphocytic thyroiditis is the most common aetiology.5The main causes of hypothyroidism and associated clinical features are shown in Table 1.
| Cause | Clinical features to elicit |
|---|---|
Allied health referrals
|
Personal or family history of autoimmune conditions Evidence of specific autoimmune diseases such as vitiligo on examination |
Postablative therapy or surgery
|
History of previous radioiodine therapy or thyroid surgery Evidence of a surgical scar or skin changes suggestive of previous external neck irradiation on examination |
Transient
|
Preceding history of viral infection, pregnancy or radioiodine ablation Evidence of an enlarged tender thyroid on examination (subacute thyroiditis) |
Iodine associated
|
Dietary intake history |
Drug induced
|
Medication history |
Infiltrative
|
Personal history or other systemic features of an infiltrative disorder |
Neonatal/congenital
|
Family history of thyroid disease/hypothyroidism Maternal medication use during pregnancy |
Neonatal/congenital
|
Family history of thyroid disease/hypothyroidism Maternal medication use during pregnancy |
Rare
|
Other clinical features of pituitary deficiency |
When to suspect hypothyroidism
Symptoms are influenced by the severity of the hypothyroidism, as well as its rapidity of onset. Slow failure of thyroid function caused by autoimmune thyroiditis typically presents insidiously over years.6 Where the diagnosis is suspected, a neck examination should be performed looking for the presence or absence of a goitre or thyroid nodules, as well as a systematic examination considering both aetiology (eg. thyroidectomy scar, skin changes suggestive of previous external neck irradiation, specific autoimmune diseases such as vitiligo), and signs of hypothyroidism (Table 2). The spectrum of clinical presentations range from clinically unapparent disease to myxoedema coma, a rare endocrine emergency.7 Given the poor specificity of the symptoms of hypothyroidism, patients may manifest clinical features that are suggestive of the diagnosis without any abnormality of thyroid function. Thyroid hormone supplementation in such a situation has shown no clear response and is not justified.8| Organ system | Symptoms and signs |
|---|---|
| Appearance |
|
| Energy and nutrient metabolism |
|
| Nervous system |
|
| Cognitive/ psychiatric |
|
| Cardiovascular |
|
| Musculoskeletal |
|
| Gastrointestinal |
|
| Reproductive system |
|
| Additional investigations | |
|
|
| * Patients with unexplained hypercholesterolaemia may have undiagnosed hypothyroidism † Statin therapy in hypothyroid patients increases the risk of rhabdomyolysis and should be avoided Adapted from www.thyroidmanager.org |
|
Investigations
Initial screening is by measuring the thyroid stimulating hormone (TSH) level. If this is elevated, the TSH should be repeated within 2–8 weeks with a free T4 level to confirm the diagnosis. A free T4 level should be ordered if there is a convincing clinical picture for hypothyroidism, despite the absence of TSH elevation, to exclude the (much less common) possibility of central hypothyroidism due to pituitary or hypothalamic pathology (Figure 1). Thyroid autoantibodies (antithyroid peroxidase and antithyroglobulin antibodies) are positive in 95% of patients with autoimmune thyroiditis. The thyroid peroxidase (TPO) antibody assay is sufficiently sensitive and specific to make this the only test now needed to confirm a diagnosis of autoimmune thyroiditis.5 Antithyroglobulin antibodies are nonspecific and the use of this test is now confined to thyroid cancer follow up. Thyroid peroxidase antibody positivity is seen in 10–15% of the general population2,3,9 and is not an indication for treatment where there is no biochemical abnormality of thyroid function. Annual thyroid function testing is recommended in euthyroid patients who have positive antithyroid antibodies, as progression to hypothyroidism is more common in this patient group.2A diagnosis of hypothyroidism in itself is not an indication for thyroid imaging. Thyroid ultrasonography is only indicated to evaluate suspicious structural thyroid abnormalities (ie. palpable thyroid nodules). While thyroid radionucleotide scanning may be useful in elucidating the aetiology of hyperthyroidism, it has no role in the work-up for hypothyroidism. There is an association between chronic thyroiditis and thyroid nodules, but whether this association is related to an increased risk of thyroid cancer is controversial.7
A low serum T4 without the expected increase in serum TSH raises the possibility of central hypothyroidism due to pituitary or hypothalamic pathology (Figure 1). However, as this pattern is also seen transiently during recovery from severe illness, it should be confirmed on a repeat test when the patient is well. Clinical clues for central hypothyroidism include other features of pituitary failure (eg. amenorrhoea, hypotension, fine wrinkling of the skin, abnormal pallor, hyponatraemia or hypoglycaemia) or features suggestive of a pituitary mass lesion (eg. visual impairment or headache).8 If central hypothyroidism is suspected, the function of the hypothalamic-pituitary-adrenal axis should be tested and a magnetic resonance imaging (MRI) scan of the pituitary gland obtained.10 Importantly, if there is associated secondary adrenal failure, thyroid hormone supplementation should only be commenced after glucocorticoid replacement, otherwise an adrenal crisis may be precipitated.11
Figure 1. Interpretation of hypothyroid function test resultsManagement
Thyoxine replacement therapy is the mainstay of treatment for hypothyroidism and is usually lifelong. However, it is important to recognise when the cause of the hypothyroidism is transient or drug induced because this may require no treatment or only short term thyroxine supplementation (Table 1).Dosing
The average daily dose of thyroxine is 1.6 µg per kilogram body weight. However, lower initial doses should be considered in patients who are elderly, frail or who have symptomatic angina, as thyroid hormone increases myocardial oxygen demand with the risk of inducing angina or a myocardial infarction. An initial dose of 50 µg/day is appropriate for healthy elderly patients and 25 µg/day or 12.5 µg/day for the very frail and those with symptomatic angina.10Typically, thyroxine is administered on a daily basis. However, due to its half life of approximately 1 week, weekly administration is occasionally an option where compliance is an issue. Its long half life also means dosing should be adjusted at an interval of no less than 6–8 weeks to allow a steady state to be achieved.12 An appropriate initial target is the relief of symptoms (if present) and a serum TSH within the laboratory range. In patients with persistent symptoms of ill health, then further titration of thyroxine dosage aiming for a TSH level in the lower reference range (eg. 0.4–2.5 mIU/L) is reasonable. A TSH level in the upper half of the reference range is usually acceptable in older persons. Lower TSH targets may be adopted in pregnancy, and in patients with thyroid cancer, and specialist advice should be sought in these cases (Table 3). In secondary hypothyroidism, TSH is unreliable, and thyroxine dose is adjusted according to free T4 levels, which should be in the mid to normal range.5
The thyroxine dose should be increased by 12.5–25 µg/day if the TSH remains above target. In Australia, levothyroxine (LT4) tablets are available in 50, 75, 100 and 200 µg preparations. A practical approach to adjusting thyroxine dosages without cutting tablets would be to use alternate day dosing or to vary the dose depending on the day of the week8 (eg. Monday to Friday 100 µg with 200 µg on weekends). Once the TSH has normalised, the frequency of review can be reduced to 6 months and then annually thereafter, unless there are situations that may alter thyroxine requirements (eg. significant weight change, commencement of a proton pump inhibitor or the oral contraceptive pill, or plans for pregnancy).
|
| * American Association of Clinical Endocrinologists |
Side effects
Treatment side effects are rare when the correct dose is given. Fatigue, increased appetite, diarrhoea, nervousness, palpitations, insomnia and tremors are indicative of overtreatment.13 These symptoms should prompt a repeat TSH level and if suppressed, a reduction in dose of thyroxine. A true allergic reaction to the active ingredient of standard levothyroxine tablets is rare and specialist advice should be sought where alternative therapy (ie. triiodothyronine) is being considered.Addressing poor response to treatment
There are a few factors to be considered where biochemical or symptomatic correction is not achieved despite adequate thyroxine dosing. These include compliance, drug interactions and absorption.Compliance
Poor compliance is one of the most common reasons for failure to achieve euthyroidism, despite the prescription of otherwise adequate doses of thyroxine.14 Occasionally, where a patient has been noncompliant for a period of time and takes a large dose of thyroxine before their blood test it results in a pattern of TSH elevation with high to normal or elevated free T4.10 In these cases it is important to review the frequency of missed tablets with the patient and discuss the importance of treatment compliance.14Drug interactions
There are a number of drugs that increase thyroxine requirements either by reducing absorption or increasing metabolism. Drugs that have been shown to reduce absorption include:15- calcium carbonate
- ferrous sulphate
- multivitamins
- cholestyramine
- phosphate binders
- proton pump inhibitors.
- the oral contraceptive pill
- anti-epileptic medication (eg. carbamazepine, phenytoin)
- some antibiotics (eg. rifampicin)
- the new tyrosine kinase inhibitors (eg. imatinib).
Absorption
Much of the variability in replacement thyroxine doses between individuals, after adjustment for body weight, is derived from differences in efficiency of gastrointestinal absorption. Malabsorptive conditions may affect the percentage of the ingested thyroxine dose absorbed and thus increase the required dose. These conditions include small bowel bypass, inflammatory bowel disease, coeliac disease and lactose intolerance. In addition, Helicobacter pylori infection and associated chronic gastritis has been found to impair thyroxine absorption. This may improve with treatment of the H. pylori infection with combination therapy.15Persistent symptoms
Symptoms compatible with hypothyroidism may occasionally persist with a TSH level within normal range. In some cases, further dose adjustment to achieve a TSH level in the lower reference range (around 1 mIU/L) may provide symptom resolution.17,18 However, in a controlled Western Australian trial of escalating doses of thyroxine therapy, there were no differences in measures of wellbeing or quality of life between patients who achieved a TSH target of 0.3, 1.0 or 2.8 mIU/L, respectively.19 In addition, TSH levels of <0.4 mIU/L have been associated with osteoporosis and atrial fibrillation in people over 60 years of age.20 Persistent symptoms with low normal TSH levels should prompt a search for other causes such as sleep apnoea, pernicious anaemia or depression. If there is a clear worsening with commencing or increasing thyroxine, co-existing Addison disease should be considered.11Levothyroxine is the preferred way to replace thyroid hormone, and a meta-analysis of 11 randomised studies with more than 1000 patients has shown no obvious benefit of combined levothyroxine and triiodothyronine (T3) therapy.21 Desiccated thyroid or thyroid hormone extracts, marketed as 'bioidentical hormones' are not a pure product, not approved by the Therapeutic Goods Administration, and have limited quality control. A recent Endocrine Society of Australia position statement has therefore concluded that, 'in general, desiccated thyroid hormone or thyroid extract, combinations of thyroid hormones or triiodothyronine should not be used as thyroid replacement therapy'.22
Pregnancy and hypothyroidism
Unless contraindicated, iodine supplementation should be prescribed routinely in women planning a pregnancy. The National Health and Medical Research Council recommends an iodine supplement of 150 µg each day.23 Maternal thyroid function during pregnancy changes in response to the increased metabolic requirements and the presence of the fetus. In addition, thyrotropic activity of β-hCG results in a decrease in TSH in the first trimester.24 To reflect this adaptation, trimester specific reference intervals for thyroid function tests are recommended.25 If laboratory reference ranges are not available, the following ranges have been provided by the American Thyroid Association:24- first trimester 0.1–2.5 mIU/L
- second trimester 0.2–3.0 mIU/L
- third trimester 0.3–3.0 mIU/L.
| Definition | Concern | Recommended action24 | |
|---|---|---|---|
| Overt hypothyroidism (OH) (Prevalence 0.3–0.5%) |
TSH >2.5 with low T4 or TSH >10 irrespective of T4 level | Consistent evidence that OH is associated with adverse pregnancy outcomes29,30 and impaired fetal neurocognitive development31 | Treatment of OH with levothyroxine is recommended. The goal is to normalise maternal serum TSH values within the trimester specific pregnancy reference range. Commencement of thyroxine while awaiting specialist review is generally appropriate (eg. 50–100 µg/day) |
| Subclinical hypothyroidism (SCH) (Prevalence 2–2.5%) |
TSH between 2.5–10 with normal T4 levels | Evidence is variable as to the effect of SCH on pregnancy and the fetus At this stage, the associated risk of obstetric complications has been more clearly demonstrated than the risk of neurocognitive deficits in the fetus. In addition, TPO Ab positivity may in itself be associated with fetal miscarriage and levothyroxone intervention in TPO antibody positive women with SCH may be beneficial32 |
Options include treatment with levothyroxine to normalise maternal serum TSH or 4 weekly monitoring of TSH Obtain TPO Ab levels while awaiting specialist review |
| Known history of hypothyroidism | History of hypothyroidism on thyroxine before pregnancy | Normal self regulatory increase in endogenous T4, especially throughout the first trimester, is not achieved by the dysfunctional thyroid gland33 | Levothyroxine adjustment should be made as soon as pregnancy is confirmed Aim to normalise TSH levels (ie. TSH <2.5) by increasing levothyroxine by two additional tablets weekly or by 25–30% and monitor thyroid function test 4 weekly This adjustment can also be made preconception in women planning pregnancy |
Subclinical hypothyroidism in nonpregnant adults
Subclinical hypothyroidism is defined as a persistently elevated serum TSH with thyroid hormone levels within the reference range. This pattern of thyroid function tests has raised considerable controversy regarding clinical significance and optimum mode of management.26Subclinical hypothyroidism is detected in 4–8% of the general population and in up to 15–18% of women aged more than 60 years.27 Approximately 4–18% of patients will progress to overt hypothyroidism each year with an increased risk with the following factors:10
- presence of antithyroid antibodies (twofold increase in risk)
- presence of a goitre
- more pronounced TSH elevation
- history of radioiodine ablation therapy, external radiation therapy and chronic lithium therapy.
The controversy
The significance and hence the benefits of treating subclinical hypothyroidism remains controversial. Potential risks of not treating subclinical hypothyroidism include progression to overt hypothyroidism, cardiovascular effects, dyslipidaemia and neuropsychiatric effects.7,8,27 A recent Cochrane review27 found that thyroxine versus no treatment for subclinical hypothyroidism did not improve overall survival, cardiovascular morbidity, health related quality of life or symptoms ascribed to subclinical hypothyroidism. However, there was some evidence to suggest that thyroxine replacement improved surrogate markers for cardiovascular disease such as lipid profile, vascular compliance and left ventricular function.Recommended management
Levothyroxine therapy is usually recommended where the serum TSH is greater than 10 mIU/L.7 Where the TSH is consistently between 5–10 mIU/L and the patient is symptomatic, a 3–6 month trial of levothyroxine replacement is appropriate. Treatment can be continued where there is symptomatic benefit.28Where the TSH is between 5–10 mIU/L and there is the presence of anti-TPO antibodies, or a goitre, an alternative option to thyroxine therapy would be annual thyroid function tests for early detection of progression to frank hypothyroidism. In contrast, where the patient is antithyroid antibody negative, 3 yearly thyroid function tests are considered sufficient.28 An algorithm for the management of subclinical hypothyroidism in the nonpregnant adult is shown in Figure 2.
Where treatment is commenced, an initial dose of levothyroxine of 25–50 µg/day can be used with a target TSH level between 1.0 and 3.0 mIU/L. The TSH level should be measured in 6–8 weeks after commencement of therapy, and annual reviews once the TSH level is stable.6
Figure 2. Algorithm for management of subclinical hypothyroidism in
the nonpregnant adult Adapted from Vaidya B, Pearce SHS. Management of
hypothyroidism in adults. BMJ 2008;337:284–9.