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)
Only a small amount of T
3 in the blood comes from the thyroid. Most T
3 comes from cells all over the body, where it is made from T
4.
Thyroid-stimulating hormone (TSH), which is made by the pituitary gland
in the brain, regulates thyroid hormone production. When thyroid
hormone levels in the blood are low, the pituitary releases more TSH.
When thyroid hormone levels are high, the pituitary decreases TSH
production.
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.
More information about thyroid disorders is provided in the NIDDK health topics,
Hyperthyroidism and
Hypothyroidism.
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)
A blood test involves drawing blood at a health care provider’s
office or a commercial facility and sending the sample to a lab for
analysis. Blood tests assess thyroid function by measuring TSH and
thyroid hormone levels, and by detecting certain autoantibodies present
in autoimmune thyroid disease. Autoantibodies are molecules produced by
a person’s body that mistakenly attack the body’s own tissues.
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 T
4 and only a small amount of T
3. T
4 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
A high level of total T
4—bound and FT
4 together—or FT
4 suggests hyperthyroidism, and a low level of total T
4 or FT
4 suggests hypothyroidism.
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 T
4 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 T
4 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 FT
4 level, a T
3 test can be useful to confirm the condition. In some cases of hyperthyroidism, FT
4 is normal yet free T
3 (FT
3) is elevated, so measuring both T
4 and T
3 can be useful if a health care provider suspects hyperthyroidism. The T
3 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 |
Key: ↑ = Above Normal ↓ = Below Normal + = Positive − = Negative
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 |
↓ |
↓ |
- |
Key: ↑ = Above Normal ↓ = Below Normal + = Positive − = Negative
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.
Nuclear medicine tests. Nuclear medicine tests of
the thyroid include a thyroid scan and a radioactive iodine uptake
test. People often have to follow a low iodine diet prior to having the
tests. Read more about a low iodine diet from the American Thyroid
Association at
www.thyroid.org/faq-low-iodine-dietExternal Link Disclaimer.
- 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.
https://www.niddk.nih.gov/health-information/health-topics/diagnostic-tests/thyroid-tests/Pages/default.aspx
Hypothyroidism
Investigation and management
Michelle So
Richard J MacIsaac
Mathis Grossmann
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.
Hypothyroidism is one of the most common endocrine disorders, with a greater burden of disease in women and the elderly.1
A 20 year follow up survey in the United Kingdom found the annual
incidence of primary hypothyroidism to be 3.5 per 1000 in women and 0.6
per 1000 in men.2 A cross sectional Australian survey found the prevalence of overt hypothyroidism to be 5.4 per 1000.3
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.
5
The main causes of hypothyroidism and associated clinical features are shown in
Table 1.
Table 1. Causes of hypothyroidism and associated clinical features
| Cause | Clinical features to elicit |
|---|
Allied health referrals
- Hashimoto thyroiditis
- Atrophic thyroiditis
|
Personal or family history of autoimmune conditions
Evidence of specific autoimmune diseases such as vitiligo on examination |
Postablative therapy or surgery
- Radioiodine therapy
- Thyroidectomy
|
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
- Subacute thyroiditis
- Silent thyroiditis
- Postpartum thyroiditis
- Early postablative therapy
|
Preceding history of viral infection, pregnancy or radioiodine ablation
Evidence of an enlarged tender thyroid on examination (subacute thyroiditis) |
Iodine associated
- Iodine deficiency
- Iodine induced
|
Dietary intake history |
Drug induced
- Carbimazole
- Propylthiouracil
- Iodine
- Amiodarone
- Lithium
- Interferons
- Thalidomide
- Sunitinib
- Rifampicin
|
Medication history |
Infiltrative
- Riedel thyroiditis (fibrous thyroiditis)
- Scleroderma
- Amyloid disease
- Haemochromatosis
- Infection (eg. tuberculosis)
|
Personal history or other systemic features of an infiltrative disorder |
Neonatal/congenital
- Thyroid agenesis/ectopia
- Genetic disorders affecting thyroid hormone synthesis
- Transplacental passage of TSH receptor blocking antibody
|
Family history of thyroid disease/hypothyroidism
Maternal medication use during pregnancy |
Neonatal/congenital
- Thyroid agenesis/ectopia
- Genetic disorders affecting thyroid hormone synthesis
- Transplacental passage of TSH receptor blocking antibody
|
Family history of thyroid disease/hypothyroidism
Maternal medication use during pregnancy |
Rare
- Thyroid agenesis/ectopia
- Secondary (pituitary or hypothalamic disease)
- Thyroid hormone resistance syndrome
- Anomalous laboratory TSH results (eg. caused by heterophil antibodies)
|
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
Table 2. Symptoms, signs and additional investigation findings in hypothyroidism
| Organ system | Symptoms and signs |
|---|
| Appearance |
- Puffy and pale facies
- Dry, brittle hair
- Sparse eyebrows
- Dry, cool skin
- Thickened and brittle nails
- Myxoedema – fluid infiltration of tissues
|
| Energy and nutrient metabolism |
- Cold intolerance
- Weight gain
- Fatigue
|
| Nervous system |
- Headache
- Paraesthesias (including carpal tunnel syndrome)
- Cerebellar ataxia
- Delayed relaxation of deep tendon reflexes
|
| Cognitive/ psychiatric |
- Reduced attention span
- Memory deficits
- Depression
|
| Cardiovascular |
- Bradycardia
- Diastolic hypertension
- Pericardial effusion
- Decreased exercise tolerance
|
| Musculoskeletal |
|
| Gastrointestinal |
|
| Reproductive system |
- Irregular or heavy menses
- Infertility
|
| Additional investigations |
|---|
- Hypercholesterolaemia*
- Mild anaemia
- Hyponatraemia
- Raised creatinine kinase†
|
* 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 population
2,3,9
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.
2
A 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 results
Management
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.
10
Typically, 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
week
8
(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).
Table 3. AACE* guidelines for indications for referral to a specialist in cases of hypothyroidism7
- Patients aged 18 years or less
- Patients unresponsive to therapy
- Pregnant patients
- Cardiac patients
- Presence of goitre, nodule, or other structural changes in the thyroid gland
- Presence of other endocrine disease
|
| * 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.
14
Drug 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.
Patients should be instructed to take their thyroxine on an empty
stomach, at least half an hour before other drugs (this includes
espresso coffee).
16 Medicines that may increase thyroxine requirements include:
15
- 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.
15
Persistent 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.
11
Levothyroxine 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.
In general, involvement of a specialist is required for the
management of raised TSH levels with 4 weekly thyroid function
monitoring to 20 weeks gestation, with less frequent monitoring
thereafter.
24 The key features of managing hypothyroidism/raised TSH levels during pregnancy are summarised in
Table 4.
There is no clear evidence to recommend population screening with TSH
of pregnant women, or of women desiring pregnancy, in the absence of
suggestive symptoms or of risk factors for thyroid disease.
24
Table 4. Definition and management of a raised TSH/hypothyroidism during pregnancy
| | 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.
26
Subclinical 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 review
27
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.
28
Where 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.
.
