Thyroid disease

Practice nurses and health care assistants will frequently be asked to perform thyroid function tests: but what are they intended to reveal?

The thyroid gland weighs about 20 grams and is composed of two lobes joined by an isthmus, making it look a bit like a butterfly. It sits beneath the skin at the front of the neck, just under the 'Adam's apple', and is not normally obvious unless it is swollen for some reason.

The main function of the thyroid in adults is to control the body's metabolic rate. In children it also controls growth and maturation. The thyroid works mainly through the production of thyroxine (also called T4). In its turn, the thyroid gland is controlled by thyroid stimulating hormone (TSH) secreted by the pituitary gland. T4 and TSH work in a negative feedback loop to retain balance, so that if T4 is too high then TSH reduces, and vice versa. Both T4 and TSH can be measured in blood (the Thyroid Function Tests [TFTs]), and their levels play an important part in the diagnosis and management of thyroid disease.

Thyroid disease is seen in general practice in three forms: underactivity (hypothyroidism or myxoedema); overactivity (hyperthyroidism); and swellings of the thyroid, which may also be associated with abnormal function of the gland.

The Whickham survey¹ looked at the prevalence, incidence and natural history of thyroid disease in a sample of 2779 adults in the north east of England. Twenty years later, the survey was repeated.²

Hypothyroidism

• Annual incidence of new cases in women is about 0.5% and the prevalence in women is about 2%
• It is 20 times more common in women than in men
• Peak incidence of new cases is in those aged 70, and it is rare under age 30. Prevalence is also greater with age — it is not curable so prevalence rises steadily with age.

Hyperthyroidism

• In women the annual incidence is 0.08% and the prevalence 2%.
• It is ten times more common in women than in men
• The incidence of new cases is spread over all age groups

Thyroid swelling

• Prevalence of diffuse goitre is greatest in pre-menopausal women (around 25%), then declines with age.
• It is four times more common in women than men.
• Thyroid nodules and multinodular goitre are more likely with increasing age, so that 3% of elderly women and 1% of elderly men are affected.
• Around 5% of solitary thyroid nodules are malignant.³

HYPOTHYROIDISM

In years gone by, iodine deficiency was a major cause of hypothyroidism. Most people in the UK now get enough iodine in their diet so now the most common causes of primary hypothyroidism are chronic autoimmune thyroiditis (Hashimoto's thyroiditis or atrophic thyroiditis) or destructive treatments for hyperthyroidism.⁴ Drugs such as lithium and amiodarone can also cause the thyroid to fail. Secondary hypothyroidism due to pituitary failure is very much rarer, and is usually associated with the failure of other pituitary hormones as well as TSH.

Suspected hypothyroidism should be biochemically confirmed.⁶ An elevated TSH of over 10mU/L confirms primary hypothyroidism.⁷ Low levels of both T4 and TSH confirm secondary hypothyroidism.

It is not uncommon in general practice to be approached by a patient with low-grade anxiety or depression, or someone who has been dieting unsuccessfully to lose weight, with a specific request to see if there might be thyroid underactivity. The clinical features of hypothyroidism are shown in Box 1.

• Many of the symptoms of hypothyroidism are vague and common in people who do not have a thyroid problem — especially lack of energy, weight-gain, and stiff and aching muscles.
• Taking a daily thyroid supplement is a relatively simple and tempting way of solving what might otherwise be a much more difficult problem.
• People with a TSH at the upper limit of the normal range or higher, feel better in a non-specific way, if started on levothyroxine.⁸
• Once a hypothyroid state has been diagnosed, then all prescriptions (including those not related to thyroid replacement) are free.

As with any blood test, it is important to know what you are going to do with the result, so if you are uncertain, have a word with your GP before going ahead. It is also important that other reasons for the symptoms are not neglected.

Treatment with levothyroxine

Levothyroxine is the treatment of choice for hypothyroidism.⁶ It is usual to start with 100mcg as a single daily dose before breakfast (25mcg in the over 50s). After 8—12 weeks TSH can be checked again: if it is still elevated add 25mcg or 50mcg a day (25mcg in the elderly). Symptoms should improve within 3 weeks of starting treatment,9 but changes in TSH take a little longer.

The aim of treatment is to relieve symptoms. In addition, a TSH in the normal range (0.4 to 4.5mU/l) should be aimed for: however, if symptoms remain a problem then a target of 0.4 to 2.5mU/l can be used.⁵ Patients feel best when their TSH is normal or a bit low.⁶ Overtreatment runs the risk of osteoporosis and atrial fibrillation.⁷

In patients with ischaemic heart disease, starting levothyroxine may cause worsening angina, myocardial infarction or even sudden death. Start with low doses and increase slowly.

Levothyroxine treatment usually has to carry on for life, with thyroid function being checked every 12 months. In postpartum thyroiditis and after treatment for hyperthyroidism, however, the hypothyroid state may not be permanent: in such cases, treat for 6 months and then stop for a month before checking thyroid function.⁹

Most cases of hypothyroidism are managed entirely in general practice. Until April 2014 there were QOF points available for the treatment of hypothyroidism, but these have now all been 'retired'. Nevertheless it is good practice to treat the condition properly so the relevant templates and clinics may well have been retained.

Subclinical Hypothyroidism

Subclinical hypothyroidism is detected by a TSH of between 5mU/l and 10mU/l7. This can be found in up to 10% of women aged 55 to 60, and is more common after iodine-131 (radioiodine) or surgery for hyperthyroidism.⁸

If a TSH is found in the subclinical range in a patient who has symptoms, then a trail of levothyroxine for 3-6 months is recommended. If symptoms are improved, then treatment is for life.⁷

Hyperthyroidism

It may feel as if thyroid over-activity is much less common than thyroid under-activity, even though the published prevalence rates are similar. Possible reasons for this are:

• Hyperthyroidism may present at any age, and the incidence of new cases is not bunched in one age group as it is with hypothyroidism.
• Virtually all cases of hyperthyroidism are successfully treated, but as a result most patients are left hypothyroid.
• Hyperthyroidism is usually transient, but hypothyroidism is usually permanent.

The clinical features of hyperthyroidism are shown in Box 2. The diagnosis is confirmed by the finding of an elevated T4 and a below-normal TSH.

Graves' disease is one cause of hyperthyroidism. It is an auto-immune disease caused by the presence of antibodies to TSH receptors on the thyroid follicular cells. It usually affects women in the third to fifth decades of life.¹¹ In a third of cases it causes eye problems: pain, tearing, problems looking up and down. If eye problems occur then the sufferer probably needs admission to hospital.¹⁰

REFERRAL AND TREATMENTS

All patients with confirmed hyperthyroidism will benefit from referral to a specialist.⁶ Nevertheless you may find patients who will turn to you for advice about available treatments.

Carbimazole is often used, at least at first, and after a few months, this treatment will usually have caused hypothyroidism needing levothyroxine replacement — the 'block-replace' regime. (The 'titration' regime works just as well and causes fewer side effects, but takes longer). Pruritis and rash are common, but usually pass with time. Agranulocytosis is more serious and usually occurs within 3 months of starting treatment. The drug must be stopped and an urgent blood count arranged if there is sore throat or another infection.⁶

Iodine 131, radioiodine, damages thyroids and so is a definitive treatment for hyperthyroidism. Treatment takes 3 months to work, and by 2 years 20% of patients need levothyroxine replacement. Patients given radiation treatment will be informed at the time about precautions to take afterwards. For example, coming into regular close contact with children is not a good idea for a time, depending on the radiation dose. Also avoid public transport for 2 weeks, and if flying take the radiation certificate along as the iodine 131 can trigger airport detectors.¹²

Surgery is the other definitive treatment for hyperthyroidism: some or all of the thyroid is removed.

Subclinical hyperthyroidism is defined as a persisting low TSH level with normal T4 and triiodothyronine levels 6(triiodothyronine [T3] is the active metabolite of thyroxine). About 3% of people have a TSH below the normal range, and in 1% it is so low as to be biochemically undetectable.⁴ Patients with subclinical hyperthyroidism are at higher risk of atrial fibrillation in their 7th decade, and are more prone to osteoporosis, but not more likely to have an osteoporotic fracture.⁶ In the absence of symptoms, treatment is not recommended.⁶

THYROID SWELLINGS

Generalised thyroid swelling is relatively common, though not as common as it used to be when iodine deficiency was more widespread. These swellings need a diagnosis but are much less likely to be of significance than the more localised nodules that can occur.

In some cases swelling is so severe that it causes difficulty in breathing. Like any other cause of breathing obstruction, this is an emergency.³

Thyroid cancer is relatively rare, accounting for about 1,000 new cases each year in England and Wales. Nodules which develop in men over the age of 70 are particularly worrying. Features of thyroid cancer include:13,14

• A goitre developing under age 20 or over age 60
• History of neck irradiation
• Rapid tumour growth
• Family history of thyroid cancer
• Male patient.

Most thyroid cancers have a good prognosis if treated promptly.

THYROID DISEASE IN PRIMARY CARE

Lack of energy or a perception of excessive tiredness or fatigue are symptoms associated with a lot of health problems. With the exception of mania, tiredness is a possible feature of all ill health presented to a practice nurse or GP. Thyroid underactivity is more likely to be on a patient's mind than over-activity. Testing thyroid function should be a routine part of the assessment of patients whose symptoms suggest thyroid disease (see boxes for typical symptoms). In addition, thyroid function testing may also be useful in the assessment of dementia, depression and anxiety, even where the clinical picture is not entirely convincing for thyroid disease.

Should thyroid tests be available on patient request? The symptoms of hypothyroidism, and particularly the individual symptoms, are very much more common than hypothyroidism itself. Patients will often present having already suspected the diagnosis, and it would be very difficult in such circumstances to deny them testing. If a normal result is obtained, that should be the end of things unless symptoms change. There is no justification for a therapeutic trial of levothyroxine if TSH is normal. This is not a view universally shared, especially by private endocrine clinics and Internet sites.

REFERENCES

1. Tunbridge WMG, Evered DC, Hall R, et al. The spectrum of thyroid disease in a community: the Whickham survey. Clin Epidemiol 1977;7:481-93.

2. Vanderpump MPJ, et al. The incidence of thyroid disorders in the community: a 20-year follow-up of the Whickham survey. Clin Endocrinol 1995;43:55-68.

3. Mehanna HM, Jain A, Morton RP, Watkinson J & Shaha A. Investigating the thyroid nodule. BMJ 2009;338:705-9.

4. Tan T and Vanderpump M. Thyroid disease. General Practitioner 12 May 2000:54-5.

5. NICE CKS Hypothyroidism http://cks.nice.org.uk/hypothyroidism

6. Vanderpump MPJ, Ahlquist JAO, Franklyn JA and Clayton RN on behalf of a working group of the Research Unit of the Royal College of Physicians of London, the Endocrinology and Diabetes Committee of the Royal College of Physicians of London, and the Society for Endocrinology. Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism. BMJ 1996;313:539-44.

7. Viadya B, Pearce SHS. Management of hypothyroidism in adults. BMJ 2008;337:284-9.

8. (No author stated) Managing subclinical hypothyroidism. Drug and Therapeutics Bulletin 1998;36(1):1-3.

9. Franklyn J. Prescribing thyroid hormones. Prescribers' Journal 1996;36(1):9-13.

10. NICE CKS hyperthyroidism http://cks.nice.org.uk/hyperthyroidism

11. Franklyn J. Thyroid disease. General Practitioner November 3 1995:53-6.

12. Cuthbertson DJ & Davidson J. What to tell patients about radioiodine therapy. BMJ 2006;333:271-2

13. Nygaard B. Primary hypothyroidism. Clinical Evidence Concise No 11 (June 2004).

14. Jones M K. Management of thyroid nodular disease. BMJ 2001;323:293-4.