14 CHEMIST+DRUGGIST 26.10.2013

CPD Zone Update

This module covers:

● Thyroid gland function and regulation

● Causes and symptoms of hypothyroidism and hyperthyroidism

● Management of hypothyroidism and hyperthyroidism

● Precautions to take after radioiodine treatment

UPDATEModule 1677

OCTOBER» Endocrine system

● Steroids Oct 5

● Type 1 diabetes Oct 12

● Diabetic complications Oct 19

● Thyroid disease Oct 26

chemistanddruggist.co.uk/update

Aedin Moore

The thyroid is a small endocrine gland at the front of the neck that consists of two lobes. Its main function is to convert dietary iodine into the thyroid hormones thyroxine (T4) and triiodothyronine (T3), which it stores and releases. T4 is converted to T3 in the cells and tissues of the body.

It is the T3, derived from T4 or secreted directly from the thyroid, which is biologically active and influences the activity of all the cells and tissues of the body.1

Thyroid hormones increase oxygen consumption and heat production, leading to an increase in basal metabolic rate and an increase in metabolism of carbohydrates, fats and proteins. They are essential for growth development, the maturation of the central nervous system and skeletal development.

Around 20 per cent of circulating T3 is derived from direct thyroid secretion, therefore T4 can be thought of as a pro-hormone that is converted to T3 in the peripheral tissues. The hormones are metabolised in the periphery (kidneys, liver and heart) by de-iodination.

More than 99 per cent of the thyroid hormone in the blood is bound to proteins and is not available to cells. So it is more useful to measure the amount of unbound T4 and T3 in the blood than the total amount of these hormones, ie free T4 (FT4) and free T3 (FT3).2

Thyroid function is modulated by the hypothalamus and the pituitary. When levels of T3 and T4 are low, or the body’s metabolic rate is low, the hypothalamus releases thyrotropin-releasing hormone (TRH), which stimulates the anterior pituitary to produce thyroid-stimulating hormone (TSH). TSH increases the production and release of T4 and T3 from the thyroid. Higher blood levels of circulating T3 and T4, in turn, exert a negative feedback on TSH production.

PREMIUM CPD CONTENT FOR £1 PER WEEK Buy UPDATEPLUS for £52+VATVisit chemistanddruggist.co.uk/update-plus for full details

HypothyroidismPrimary hypothyroidism is caused by the failure of the thyroid gland to produce thyroid hormones. This can be the result of an autoimmune disorder, dietary deficiency of iodine, antithyroid medication, thyroidectomy or adverse drug reactions. A low FT4 and high TSH indicate primary hypothyroidism.

Secondary hypothyroidism is caused by pituitary or hypothalamic dysfunction, which results in inadequate release of TRH and TSH. In turn, this reduces the stimulation of the thyroid gland to produce thyroid hormones. Levels of TSH and FT4 are low in this type of hypothyroidism.

Several other disorders are associated with primary hypothyroidism, including Addison’s disease, pernicious anaemia and diabetes mellitus. It is important to note that hypothyroidism can also be due to iodine

deficiency, rare associations such as cystic fibrosis or drug-induced.

Typically, the patient experiences non-specific symptoms, some of which are listed in Box 1, below right.

Management of hypothyroidismLevothyroxine is the mainstay in the treatment of hypothyroidism. Dosage usually depends on weight, age and sex and is started low, around 50 to 100mcg daily, then gradually increased to raise the metabolic rate slowly. The dose is usually adjusted in steps of 25 to 50mcg every three to four weeks according to response. A typical maintenance dosage is 100 to 200mcg once daily. For patients with cardiac disease or severe hypothyroidism, and those over 50 years old, the initial dosage is 25mcg once daily, adjusted in steps of 25mcg every four weeks according to response.3

Serum TSH levels are measured four to six weeks after starting treatment or changing the dose. If the dose is too high, a low TSH level will be seen, as the pituitary gland reduces TSH secretion. A dose that is too low will exhibit a high TSH level. Once established, patients normally have their thyroid function monitored annually.

Levothyroxine should be taken on an empty stomach, 30 minutes before food, preferably in the morning. Side e�ects, usually at excessive dosage, include diarrhoea, vomiting, anginal pain, arrhythmias, palpitations, tachycardia, tremor, restlessness, insomnia and headache.3

Some patients with long-standing hypothyroidism may complain of angina at presentation or develop it following treatment with levothyroxine. Exacerbation of myocardial ischaemia and myocardial infarction are well recognised complications of levothyroxine therapy. Patients who complain of ankle swelling or shortness of breath after starting therapy should be referred.

The risk of developing atrial fibrillation and osteoporosis increases with long periods

Thyroid disorders

The thyroid, an endocrine gland at the front of the

neck, converts dietary iodine into thyroid hormones

CPD Zone Update

of over-treatment with thyroid hormone, as shown by TSH levels below the reference range.2

Hyperthyroidism6

The two principal causes of hyperthyroidism in the UK are autoimmune disease and benign tumours. In autoimmune thyroid overactivity, an abnormal antibody that targets the TSH-receptor stimulates excess thyroid hormone production. This also causes thyroid cells to grow and can lead to thyroid enlargement, known as goitre.

Goitre is a highly recognisable symptom of thyroid dysfunction, characterised by swelling of the thyroid or the formation of one or more nodules. It can be associated with hypothyroidism and hyperthyroidism. In some cases, the patient may even be euthyroid (have normal thyroid gland function).

This form of autoimmune thyroid disease is often called Graves’ disease, named after the Irish doctor Robert James Graves, who described the condition in the 19th century. Graves’ disease is almost always accompanied by TSH-receptor auto-antibodies in the blood and frequently by thyroid peroxidase (TPO) auto-antibodies, both of which may be useful for diagnosis. Around one in three people with Graves’ disease develop eye problems, including a staring appearance, grittiness and soreness, exophthalmos (protruding eyeballs) and, more rarely, double vision or sight problems.

The thyroid can develop one or more benign tumours (often referred to as nodules). These tumours secrete excess thyroid hormone, which is unregulated. Depending on how many nodules there are, this nodular hyperthyroidism is known as solitary toxic nodule or toxic multinodular goitre. It is seen more commonly in older people.

Together, these two types of hyperthyroidism (usually classified as primary) account for more than 90 per cent of all cases. Rarer causes include inflammatory conditions (thyroiditis), which sometimes result from pregnancy, viral infection or drugs such as amiodarone, lithium or interferon.

Secondary thyroid overactivity can be

caused by the pituitary gland producing excess TSH, which leads to thyroid overactivity with normal or high blood TSH, but this is rare. Taking too much thyroid hormone, such as levothyroxine, is a more common secondary cause and is associated with test results resembling primary thyroid overactivity.

Symptoms of hyperthyroidism are shown in Box 1 below.

Management of hyperthyroidism6

The aim is to relieve symptoms and manage the underlying condition. Antithyroid medications – carbimazole and propylthiouracil – reduce the synthesis of thyroid hormones. Propylthiouracil also inhibits the conversion of T4 to T3.

Antithyroid drugs reduce thyroid hormone production for most people with hyperthyroidism. Treatment for between six months and two years can achieve a long-term remission in around 50 per cent of people with Graves’ disease after the drug is stopped.

Side e�ects include nausea, gastrointestinal disturbances, taste disturbance, headache, fever, malaise, rash, pruritis and joint pain. Rashes and pruritis are common side e�ects, but they can be treated with antihistamines without discontinuing treatment. Agranulocytosis (a serious reduction in circulating white blood cells) or hepatic dysfunction may – relatively rarely – happen during treatment, so patients need to be told what symptoms to look out for and to go to their doctor immediately if they experience them.3

Symptoms indicative of agranulocytosis include sore throat, mouth ulcers, bruising, bleeding, fever and malaise. Patients should be told to report any symptoms or signs of infection, including non-specific illness, as soon as they experience them.3 Hepatic dysfunction can cause general pruritus, jaundice, dark urine, pain in the upper abdomen, nausea or vomiting and anorexia.

There are two antithyroid drug regimens: ● A titrated dose regimen that keeps the thyroid hormone levels in the normal range by adjusting the dose every six to eight weeks according to blood test results. ▶

Box 1. Symptoms associated with hypothyroidism and hyperthyroidism

Hypothyroidism● Dry, pale skin● Coarse, brittle hair; hair loss● Depression; slow speech; poor memory● Hearing loss● Delayed deep-tendon reflexes● Muscle pain and weakness● Weight gain● Constipation● Bradycardia

Hyperthyroidism● Exophthalmos (protruding eyeballs)● Hunger and thirst● Sweating; heat intolerance● Weight loss● Tremor● Agitation● Anorexia● Muscle weakness● Diarrhoea● Tachycardia● Atrial fibrillation

REGAINE® for Men Extra Strength Scalp Foam 5% w/w Cutaneous Foam (minoxidil) for treatment of alopecia androgenetica in men. Legal cat: Triple pack: P; Single pack: GSL. MA Holder: McNeil Products Ltd, Foundation Park, Maidenhead, Berks, SL6 3UG. Information about this product, including adverse reactions, precautions, contra-indications, and method of use can be found at http://www.medicines.org.uk/emc/

A CASE FOR A QUIETCONVERSATION

THE CONVERSATION: Most men feel uncomfortable talking about hair loss, so offering to take him to a consulting room or quiet area is a good starting point. Ask questions and check it is hereditary hair loss. If it is, REGAINE® Foam can be a good recommendation as it is scienti�cally proven to help stop and even reverse hair loss,1 and results show that 9 out of 10 men said it helped them keep or re-grow hair.2 Furthermore, REGAINE® works best on men who are just starting to lose their hair.3

References: 1. REGAINE® for Men Extra Strength Scalp Foam 5% w/w Cutaneous

Foam SmPC. 2. Olsen EA et al. J Am Acad Dermatol 2007; 57: 767–74. 3. Khandpur S et al. J Dermatol 2002; 29: 489–98.

Date of preparation: February 2013ID: UK/RE/13-1312

THE CASE: A man in his mid 20’s comes to the counter and asks for a word in private. He says he’s concerned as he’s recently noticed that he’s starting to lose his hair.

Con�dence begins with a conversation

REGAINE® for Men Extra Strength Scalp Foam 5% w/w cutaneous foam

5% MinoxidilFOAM

10775_ocdreg_pharma_ad_270x60_C+D_Bookend_fa1.indd 110/21/13 6:00 PM

16 CHEMIST+DRUGGIST 26.10.2013

CPD Zone Update DID YOU KNOW? UPDATE users can upgrade to UPDATEPLUS for only £20+VATVisit chemistanddruggist.co.uk/update-plus for full details

Association website (british-thyroid-association.org/info-for-patients) and patient support groups such as the British Thyroid Foundation (btf-thyroid.org).

References1. www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/thyroid_disorders/overview_of_thyroid_function.html (accessed October 2013).2. www.british-thyroid-association.org/info-for patients/Docs/bta_patient_hypothyroidism.pdf (accessed October 2013).3. Joint Formulary Committee. British National Formulary. 66 ed. London: BMJ Group and Pharmaceutical Press; 2013. 4. www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/thyroid_disorders/hypothyroidism.html (accessed October 2013).5. www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/thyroid_disorders/hyperthyroidism.html (accessed October 2013).6. www.british-thyroid-association.org/info-for-patients/Docs/bta_patient_hyperthyroidism.pdf (accessed October 2013).7. www.nhs.uk/Conditions/Thyroid-over-active/Pages/Treatment.aspx (accessed October 2013).8. Reid JR, Wheeler SF; Hyperthyroidism: diagnosis and treatment. Am Fam Physician 2005;72(4):623-30.9. www.cancerresearchuk.org/cancer-help/type/thyroid-cancer/treatment/radiotherapy/radioactive-iodine-treatment-for-thyroid-cancer (accessed October 2013).10. Lloyd J, Yerbury P, Ruszala V. Thyroid disorders – management. Clinical Pharmacist 2011;3:330-7.

Aedin Moore is a clinical pharmacist at University College London Hospitals NHS Foundation Trust

●A blocking-replacement regimen in which a fixed, higher dose is given and levothyroxine replacement added to maintain normal thyroid hormone levels.

Some of the symptoms of hyperthyroidism, including palpitations and tremor, can be improved by beta-blockers, such as propranolol. They do not a�ect thyroid overactivity, but many patients report that they feel better for taking them.

In nodular hyperthyroidism, antithyroid drugs do not result in cure, just a temporary reduction in thyroid hormone levels. A more permanent solution – a so-called definitive treatment – is often sought.

Radioiodine is a radioactive isotope of iodine (I131) that the thyroid gland selectively concentrates. A small dose of radioactivity delivered by treatment with the isotope is enough in most patients to destroy thyroid tissue gradually over six weeks to six months. If a follow-up dose is needed, it is usually given six to 12 months later.7

Around 50 to 80 per cent of patients with Graves’ disease are left with permanent thyroid underactivity after radioiodine treatment.8 In contrast, thyroid function tends to be better preserved in patients with nodular thyroid overactivity; around 50 per cent become underactive. Patients are monitored for underactivity and those who develop it are treated.

Thyroid underactivity seems to be acceptable as part of radioiodine therapy because replacement treatment with levothyroxine is relatively straightforward and associated with few, if any, side e�ects when given at the correct dose. Hyperthyroidism, on the other hand, has serious consequences.

Radioiodine treatment is well tolerated. However, women should be advised to avoid pregnancy for at least six months after treatment. Men should not father children for at least four months after treatment.

Patients with ophthalmopathy (thyroid eye disease) should be carefully evaluated, since radioiodine may worsen the condition, although a short course of steroid can prevent it.

After a standard dose of radioiodine, patients need to take some straightforward precautions to minimise other people’s exposure to radiation (see Box 2, left). Security alarms at airports may detect radiation from radioiodine treatment for up to 12 weeks following a dose, so a letter about the treatment should be provided for patients to carry with them on any flights they may make during this time.9

Surgical removal of most or all of the thyroid gland (known as subtotal or total thyroidectomy) is straightforward and carries a low risk of complications. However, lifelong levothyroxine replacement will be needed for the hypothyroidism that follows the operation.

Box 2. General precautions to take after receiving a dose of radioiodine

For four days after radioiodine treatment (or longer if there is likely to be contact with children and/or pregnant women, or a person’s job involves using equipment likely to be a�ected by small amounts of radiation), patients should take precautions to avoid exposing other people to the small amount of radiation emitted. These are detailed on a card given to patients. The general advice is:

● Try to stay more than an arm’s length away from other people, in particular children, pregnant women or women who may be pregnant

● Avoid public places where there is close contact with others, such as shops, cinemas and public transport, and do not go to work

● Sleep alone, if possible, and avoid sexual contact and kissing

● Do not share towels or face cloths

● Rinse your own dishes and cutlery before they are washed with other people’s

● Wash your clothes separately if any bodily fluids are spilt on them

● Flush the toilet twice after use. Wash your hands thoroughly and rinse the basin thoroughly.

Source: tinyurl.com/radioiodine1

People with a large goitre or those with thyroid eye disease may benefit from thyroidectomy. Thyroid overactivity needs to be controlled before surgery to reduce the risk of a dangerous hyperthyroid crisis (thyrotoxic storm), which can be associated with anaesthesia. This is usually achieved with antithyroid medicines.

Role of the pharmacist10 Pharmacists can provide patients with thyroid disorders with valuable information, support and advice in relation to their treatment and ongoing care, including:● the importance of taking medicines and advice about when to take them● the need for follow-up blood tests● how to recognise side e�ects of medicines and how to report signs of agranulocytosis or hepatic dysfunction in particular to their doctor straight away● precautions to take to minimise other people’s exposure to the small amount of radiation present following radioiodine treatment (see Box 2, above)● signposting useful information such as the patient guides on the British Thyroid

CPD Zone Update

1. The thyroid gland converts dietary iodine into thyroxine (T4) and triiodothyronine (T3). True or false?2. Triiodothyronine is converted to thyroxine in the cells and tissues of the body.True or false?3. Thyroid function is modulated by the hypothalamus and the pituitary. True or false?4. Primary hypothyroidism is caused by pituitary or hypothalamic dysfunction. True or false?5. Patients with secondary hypothyroidism have low levels of free T4 and high levels of thyroid-stimulating hormone. True or false?6. For patients over 50 years old, the starting dose of levothyroxine is 25mcg, taken once a day. True or false?7. Levothyroxine therapy can cause

exacerbation of myocardial ischaemia and myocardial infarction. True or false?8. About three quarters of people with Graves’ disease develop thyroid eye disease. True or false?9. Antithyroid medications carbimazole and propylthiouracil act by reducing the synthesis of thyroid hormones. True or false?10. Common side e�ects of carbimazole and propylthiouracil include rashes and pruritis. True or false?

SIGN UP TO UPDATEPLUS Sign up for Update Plus, C+D’s premium CPD package for pharmacists and pharmacy technicians. Go to chemistanddruggist.co.uk/update-plus and sign up for £52+VAT today – that’s just £1+VAT a week

Take the 5 Minute Test

■ Sign up to take the 5 Minute Test and get your answers marked online: chemistanddruggist.co.uk/update

5 minute test

Reflect How is the function of the thyroid gland regulated? What are the symptoms of hypothyroidism and hyperthyroidism? What precautions should be taken in patients having radioiodine treatment?

Plan This article contains information for pharmacists about thyroid disorders. It discusses thyroid gland function and the causes and symptoms of hypothyroidism and hyperthyroidism, as well as the treatments available.

Act Read the Update article and the suggested reading (below), then take the 5 Minute Test (above). Update and Update Plus subscribers can then access their answers and a pre-filled CPD logsheet at www.chemistanddruggist.co.uk/mycpd.

Read more about hypothyroidism and hyperthyroidism on the NHS Choices website, nhs.uk tinyurl.com/thyroid11tinyurl.com/thyroid12

Find out more about goitre from the patient.co.uk websitetinyurl.com/thyroid13

ASK THE EXPERTOctober is endocrine system month and our expert is on hand to answer your queries. From diabetes to thyroid disease submit your questions by email: steve.titmarsh@ubm.com

Find out more about thyroid eye disease from the patient.co.uk websitetinyurl.com/thyroid14

Revise your knowledge of the treatment of thyroid disorders from BNF Section 6.2, Thyroid and antithyroid drugs

Read the MUR tips for thyroid disorders on the C+D website. Identify any patients who might benefit from an MUR or more advice about their conditiontinyurl.com/thyroid15

Evaluate Are you now confident in your knowledge of thyroid disorders and their causes and symptoms? Could you give advice to your patients about the side e�ects of thyroid and antithyroid medications?

Tips for your CPD entry on thyroid disorders

Looking for tips to get the most out of your MURs? Try C+D’s popular MUR Zone

»chemistanddruggist.co.uk/mur-zone

ChooseUpdate ToolkitsUpdate Toolkits allow you to top up your CPD while on the move using your tablet or mobile device

● Easy-to-read ebooks of three or four modules

● 5 minute online assessments

● Library of di� erent topics to choose from

For more details and to buy Update Toolkits go to

chemistanddruggist.co.uk/update-toolkit

Choose

ONLY£10+VATEACH

Update plus-toolkit side ads-v2.indd 2 16/07/2013 12:59