What does the thyroid gland do?
The thyroid produces the hormones thyroxine (T4) and triiodothyronine (T3). T3 and, to a lesser extent, T4 control protein, carbohydrate and fat metabolism in many tissues of the body. Although T4 is relatively inactive compared with T3, it can be converted and acts as a reservoir.
How is hypothyroidism diagnosed?
A rise in serum TSH associated with normal serum T4 and T3 levels is known as subclinical hypothyroidism. Diagnosis cannot be made from a single test showing a raised TSH level; an initial finding must be confirmed three to six months later. Overt hypothyroidism is diagnosed on the basis of characteristic clinical features, together with TSH greater than 10mU/l and free T4 below 9.0Ð25pmol/l.
What is thyroid storm?
Thyroid storm is a medical emergency involving severe hyperthyroidism. It is usually caused by Graves’ disease or by nodules in a goitre, and produces a variety of symptoms.
The thyroid has a fundamental role in the functioning of our bodies. It produces hormones that set the rate at which energy is released from our bodily stores. Problems caused by patients having too much or too little thyroid hormone represent an important but neglected group of conditions, which have seen few new treatments developed for several decades.
Perhaps this can be put down to a widespread perception that the treatment of thyroid problems has been solved: patients with hypothyroid problems simply need to be given thyroxine, and those with hyperthyroid problems can have their thyroid hormone levels lowered by surgical or chemical means.
But this perception is only partly accurate. The treatments used in thyroid disease only deal with its effects: there are still no drug treatments aimed at the autoimmune conditions underlying most thyroid disease, or making sure patients get the dietary iodine they require.
Thyroid disease is very common, but because its presentation is varied, under-diagnosis and wrong diagnosis may occur. Patients with thyroid problems may be told they have some other condition, while other patients whose symptoms are not related to their thyroid may receive thyroid treatments.
Another big issue is that thyroid disease is an area where deep disagreements often exist between some patients and clinicians, who may be opposed to treatments they believe are not supported by evidence, may be unsafe, or both.
One example is the issue of whether patients with underactive thyroid who do not feel better when treated with levothyroxine treatment, which is designed to raise thyroxine (T4) levels, should also be offered the active hormone triiodothyronine (T3). Some patients, it is argued, need T3 as well as T4. However, studies suggest adding T3 to T4 is not of benefit and practical experience shows that at least some patients on this combined treatment run into serious problems, including cardiac arrhythmias.
Similarly, it has been argued some patients require natural thyroid hormones extracted from pig thyroids rather than levothyroxine. However, in 2008 the Royal College of Physicians stated over-whelming evidence supports the use of T4 alone.
In addition, it stated pig thyroid extract is inconsistent with normal physiology, has not been scientifically proven to be of any benefit to patients and may be harmful.1
The thyroid is made up of two lobes, lying just below the Adam’s apple at the front of the neck. It concentrates iodides in food and water, which are then converted to organic iodine and combined with tyrosine to form T4 and T3.2
These are excreted from the thyroidÕs follicular cells, and combine with receptors in cell nuclei to influence the functioning of many tissues in the human body, in which T3 and, to a much lesser extent T4, control protein, carbohydrate and fat metabolism. Although relatively inactive compared with T3, T4 is converted to T3 in body tissues and so serves as a reservoir.3
Thyroid hormone production is triggered by thyroid stimulating hormone (TSH), produced by the pituitary gland, which is in turn controlled by thyrotropin-releasing hormone (TRH), synthesised by the hypothalamus in response to low levels of T3 and T4.2 T3 and T4 production is therefore controlled by a negative feedback control loop: high levels of free T4 and T3 inhibit TRH and TSH synthesis and secretion, while falling levels of T4 and T3 cause the pituitary and hypothalamus to produce more TRH and TSH, which in turn stimulate the thyroid to produce more T3 and T4.
The thyroid includes another group of cells that secrete calcitonin, a hormone that lowers body calcium levels whenever they become high. Calcitonin supplements derived from salmon are therefore used in the treatment of osteoporosis and related conditions such as Paget’s disease.4
The most common thyroid-related conditions cause either hypothyroidism or hyperthyroidism. Ten million requests for thyroid function tests are made each year in the UK, assessing thyroid stimulating hormone (TSH), free T4 and free T3 levels. A range of other tests is used to determine the specific causes of thyroid disease.
The vast majority of T3 and T4 in the bloodstream is bound to proteins and is therefore inactive Ð only 0.3 per cent of serum T3 and 0.03 per cent of serum T4 are free and available to act on body tissues. Lab results usually report only free T4 and T3.
Spontaneous hypothyroidism has a prevalence of 1-2 per cent of the population in the UK. It is more common in older women, and 10 times more common in women than in men. Hyperthyroidism is found in 0.5-2 per cent of the population and, again, is seen 10 times more commonly in women than men.5
Thyroid disease is a very important issue in pregnancy; some 5-9 per cent of all pregnancies are complicated by thyroid problems. In the growing foetus and babies, T4 and T3 are essential for normal brain and body development Ð if they are not available, either during pregnancy or following birth, the baby will become what’s technically known as a cretin, although healthcare workers have avoided the term for many years.
The most common cause of hypothyroidism worldwide is iodine deficiency. As the thyroid runs out of iodine, production of T3 and T4 falls and the pituitary produces increasing amounts of TSH, causing the thyroid to enlarge and to become a goitre. In areas where dietary iodine is in short supply, babies and young children are at risk of cretinism. While extreme iodine deficiency is not common in the UK, hypothyroidism due to other causes is frequent; as many as 10 per cent of patients over 60 have subclinical hypothyroidism.
In the UK, the most common causes of hypothyroidism are either destructive treatment for hyperthyroidism, or one of two chronic autoimmune diseases: Hashimoto’s thyroiditis and atrophic autoimmune thyroiditis.6
Signs of possible hypothyroidism include weight gain, depression, increased hair growth, heavy or abnormal periods, constipation, feeling cold, dry skin and tiredness.2
Heart disease, a susceptibility to infections, infertility and miscarriage can also be the result of falling thyroid hormone levels. Patients with untreated hypothyroidism are known to be at increased risk of birth defects, heart disease due to raised low density lipids (LDL) and heart failure. Hypothyroidism can cause coma, although this is rare.3
Despite these clues, hypothyroidism can be subtle and difficult to spot; its symptoms and signs are frequently mistaken for other illnesses, particularly in postpartum women and older patients. Many patients with milder forms of the disease exhibit few clinical features and some will show none. In addition, many of the signs and symptoms associated with hypothyroidism are found in many patients with normal thyroid hormone levels.5
The first biochemical indicator suggestive of thyroid disease is a rise in serum TSH associated with normal serum T4 and T3 levels, which is known as subclinical hypothyroidism. This may then be followed by a fall in T4 concentration, at which point patients have overt hypothyroidism, and will develop symptoms that will benefit from thyroid hormone treatment.5
A diagnosis of subclinical hypothyroidism cannot be made from a single test showing a raised TSH level; in order to exclude transient causes, an initial finding must be confirmed three to six months later.
Measurements of thyroid antibodies indicating autoimmune disease are used in calculating the patients’ chances of progressing to overt hypothyroidism. Overt hypothyroidism is diagnosed on the basis of characteristic clinical features, together with TSH greater than 10mU/l and free T4 below 9.0-25pmol/l.7,2
Patients with hyperthyroidism exhibit a range of well-known symptoms, including palpitations; shortness of breath; emotional changes or irritability, nervousness, anxiety or depression; difficulty sleeping; diarrhoea; feeling hot; exercise intolerance, weakness or fatigue; weight loss despite feeling hungry; polyuria, thirst and generalised itch; tremor; hair loss; gynaecomastia and reduced libido in men; light or absent periods in women.3,7
There is also the risk of thyroid eye disease (TED). Patients with thyroid disease exhibit eye signs including stare, eyelid lag, eyelid retraction and redness of the conjunctiva. These usually return to normal with treatment, but infiltrative ophthalmopathy, which is associated with Graves’ disease, is a much more serious development. In this situation the patient is likely to have pain and a bulging swelling in the orbit of the eye, with tears and irritation, photophobia, increased retro-orbital tissue and an ocular muscle weakness that may cause the patient to see double.3
In patients with diabetes, hyperthyroidism may result in a deterioration in diabetic control and recurrent hypoglycaemic attacks.
In the elderly the predominant feature is ‘apathetic’ hyperthyroidism, which includes weight loss and depression. Cardiovascular problems are common, especially atrial fibrillation and deterioration of pre-existing heart disease.2
Hyperthyroidism can have many different causes. The most common cause is Graves’ disease, or toxic diffuse goitre. This is an autoimmune disease in which the immune system makes the antibody thyroid stimulating immunoglobulin (TSI), which mimics TSH and causes the thyroid to over-produce thyroid hormones. Other causes of hyperthyroidism include thyroid nodules, inflammation of the thyroid gland, ingesting too much iodine and taking too much synthetic thyroid hormone treatment, which is commonly used to treat underactive thyroid.
Thyroid nodules, or adenomas, are lumps in the thyroid. They are common Ð as many as half the population has a nodule somewhere in the thyroid by age 50. The overwhelming majority of these nodules are harmless and not cancerous, but may become overactive and produce too much hormone; multiple nodules producing a large amount of excess thyroid hormone are often found in older adults.
Thyroid storm is a rare medical emergency in which the patient has severe hyperthyroidism.
It is usually caused by Graves’ disease or by nodules in a goitre, and produces a variety of symptoms including fever, weakness, restlessness, emotional swings, confusion and psychosis, vomiting, diarrhoea and cardiovascular collapse. Thyroid storm may be brought on by various factors including infection, trauma, embolism, diabetic ketoacidosis or pre-eclampsia.3
Gavin Atkin is former clinical and CPD editor of Chemist+Druggist and editor of The Practitioner
1. Royal College of Physicians (2008)The Diagnosis and Management of Primary Hypothyroidism [online] www.rcplondon.ac.uk/specialties/Endocrinology-Diabetes/Documents/Hypothyroidism.pdf
2. Lab Tests Online (2010) Thyroid Diseases [online] www.labtestsonline.org.uk/understanding/conditions/thyroid.html
3. Merck (2008) The Merck Manual of Diagnosis and Therapy ‘Thyroid disorders’ [online] www.merck.com/mmpe/sec12/ch152/ch152a.html
4. Electronic Medicines Compendium (2010) SPC: Miacalcic 200 IU Nasal Spray [online] www.medicines.org.uk/EMC/medicine/7877/SPC/MIACALCIC+200+IU+Nasal+Spray/
5. Association of Clinical Biochemistry, the British Thyroid Association, the British Thyroid Foundation (2006) Thyroid Function Tests 2006: UK Guidelines for the use of Thyroid Function Tests [online] www.btf-thyroid.org/index.php?option=com_content&view=article&id=154&Itemid=218
6. Medline Plus (2010) Hypothyroidism [online] www.nlm.nih.gov/medlineplus/ency/article/000353.htm
7. Clinical Knowledge Summaries (2008) Hyperthyroidism [online] available from: www.cks.nhs.uk/hyperthyroidism
Aside from Graves’ disease, there are several types of thyroiditis capable of resulting in hyperthyroidism by causing stored thyroid hormone to leak out of the inflamed gland and raise hormone levels in the blood.
– Subacute thyroiditis The cause of subacute thyroiditis isn’t known, but it usually clears up after a few months. Some patients with the condition briefly develop hypothyroidism while the thyroid gland heals.
– Postpartum thyroiditis Due to an autoimmune effect, as many as 8 per cent of women develop postpartum thyroiditis within months of giving birth. The resulting hyperthyroidism usually lasts for up to two months, and is likely to recur following future pregnancies. As with subacute thyroiditis, some women develop hypothyroidism on their way to recovery; in some, however, the gland does not heal and hormone levels remain low.
– Silent thyroiditis This is a painless thyroiditis. The thyroid may be enlarged, and is probably caused by an autoimmune condition. In some cases, it develops into permanent hypothyroidism.
– Iodine ingestion The quantity of iodine a patient consumes can influence the amount of thyroid hormone their thyroid produces Ð iodine is present in some medicines and in food supplements containing seaweed.
– Pituitary adenoma Occasionally, hyperthyroidism may be caused by a
pituitary adenoma, in which case the hyperthyroidism is due to the gland producing high levels of TSH, which in turn stimulates the thyroid.
How is the production of thyroid hormones controlled by the body? What is subclinical hypothyroidism and how is it diagnosed? What are the symptoms of thyroid eye disease?
This article discusses the causes, testing and diagnosis of thyroid disease. It includes information about the function of the thyroid gland and the causes and symptoms of hypo and hyperthyroidism. Thyroid eye disease, thyroid nodules and thyroid storm are also described.
– Find out more about thyroid testing and also how some drugs can affect the results from the Patient UK website at http://tinyurl.com/thyroid01.
– Read more about hypothyroidism on the Patient UK website at http://tinyurl.com/thyroid02.
– Read more about hyperthyroidism on the Patient UK website at http://tinyurl.com/thyroid03.
– Revise your knowledge of thyroid eye disease from the Royal National Institute of Blind People website at http://tinyurl.com/thyroid04.