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Managing Thyroid Disease in General Practice

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Managing Thyroid Disease in General Practice Narrative review Managing thyroid disease in general practice John P Walsh1,2 hyroid disease can be broadly categorised as thyroid Summary dysfunction (hypothyroidism, hyperthyroidism) and Serum thyroid-stimulating hormone (TSH) testing is the best T structural disease (goitre, nodules and cancer). Manage- screening tool for thyroid dysfunction. When TSH levels are in ment is often straightforward, but there are pitfalls that may lead to the reference range, additional tests such as free thyroxine, misdiagnosis, overdiagnosis and inappropriate treatment. This free triiodothyronine or thyroid antibodies rarely add value, article reviews the approach to common thyroid problems in except in patients with pituitary disease, when TSH is general practice. unreliable. Overt hypothyroidism and subclinical hypothyroidism with Epidemiology TSH levels > 10 mU/L can be treated without further investi- gation. The health impact of subclinical hypothyroidism with mildly elevated levels of TSH (4e10 mU/L) remains uncertain, Worldwide, iodine deficiency is the most common cause of thyroid fi particularly in older people; treatment or observation are disease. Iodine de ciency has long been known in Tasmania, and a reasonable options. fi survey published in 2006 found evidence of iodine de ciency in Thyroxine remains standard treatment for hypothyroidism, 1 mainland Australia, particularly New South Wales and Victoria. with optimal dosage determined by clinical response and In 2009, use of iodised salt in bread became mandatory in serum TSH. Australia and New Zealand (following a Tasmanian program Hyperthyroidism is commonly caused by Graves’ disease, 2 started in 2001), and Australia is now considered iodine sufficient. thyroiditis or toxic nodular goitre. The cause should be established before offering treatment. Radionuclide scanning Autoimmune thyroid disease is the commonest cause of thyroid is the imaging modality of choice. Positive TSH-receptor an- dysfunction in Australia, with prevalence as shown in Box 1. Some tibodies indicate Graves’ disease. e 10 15% of the population have positive thyroid antibodies, most Thyroid ultrasound is indicated for assessment of palpable commonly to thyroid peroxidase (TPOAb), with a higher preva- goitre and thyroid nodules. It is not part of routine assessment 3 lence in women than men. Patients who are euthyroid with pos- of hyperthyroidism or hypothyroidism. Overzealous use of ul- itive thyroid antibodies do not require treatment, but are at trasound identifies clinically unimportant thyroid nodules and increased risk of thyroid dysfunction (particularly hypothyroid- can lead to overdiagnosis of thyroid cancer. ism),4,5 and should be followed with annual measurement of For thyroid nodules, the key investigation is ultrasound-guided serum thyroid-stimulating hormone (TSH). fine needle aspiration biopsy, depending on size and sono- graphic appearance. Biopsy should not be performed routinely TSH testing is the most sensitive means of detecting thyroid on small nodules < 1 cm. dysfunction. Debate surrounding the laboratory reference interval It remains controversial whether pregnant women should be for TSH has largely resolved, and a range of about 0.4e4.0 mU/L is screened for thyroid disease. Reference intervals for thyroid generally accepted.6,7 TSH concentrations increase with age,7,8 and function tests during pregnancy are not well established, and it some laboratories have adopted age-related reference intervals, is uncertain whether thyroxine treatment for pregnant women with upper limits of up to 7 mU/L in older patients. with serum TSH levels between 2.5 and 4.0 mU/L is beneficial. Iodine supplementation is recommended during pregnancy. Hypothyroidism elevated TSH (up to 10 mU/L), TSH normalises without treatment Diagnosis in over 50% of cases,10 so treatment need not be offered immedi- Classic symptoms of hypothyroidism include fatigue, weight gain, ately. Instead, serum TSH testing should be repeated 6e8 weeks cold intolerance, arthralgia, constipation, menorrhagia, and dry later, together with free T4 and TPOAb, and treatment offered if the skin and hair. Physical signs include pallor, coarse skin and hair, abnormality persists. Thyroid imaging (including ultrasound) is bradycardia and goitre, but may be absent in mild hypothyroid- not indicated in the investigation of hypothyroidism.11 ism. These symptoms and signs are non-specific and common in people without thyroid disease,9 so laboratory diagnosis is The importance of detecting and treating subclinical hypothy- 12,13 required. Serum TSH should be measured; if this is in the reference roidism remains uncertain. Randomised controlled trials of range, then additional tests such as free thyroxine (T4), free triio- thyroxine have shown inconsistent results on symptoms and MJA 205 (4) dothyronine (T3) or thyroid antibodies are rarely helpful. Tests quality of life, particularly in older patients and when TSH levels such as basal metabolic rate and reverse free T3 have no diagnostic are mildly elevated (up to 10 mU/L). Untreated subclinical hypo- value. thyroidism with TSH levels above 10 mU/L is associated with 14,15 increased risks of cardiovascular disease. The benefits of j Overt hypothyroidism (high TSH, low free T4) is usually symp- treating subclinical hypothyroidism are probably greater in 15 August 2016 tomatic, readily diagnosed and can be treated without further younger and middle-aged patients than in older people.13,16 investigation. A more common presentation in general practice is an elevated level of serum TSH with normal free T4. This may indicate subclinical hypothyroidism caused by autoimmune thy- Treatment roid disease, but can arise from non-thyroidal, systemic illness, Thyroid hormone replacement is indicated for overt hypothy- particularly in the recovery phase. In patients with a mildly roidism and for subclinical hypothyroidism with TSH levels above 179 1 2 Sir Charles Gairdner Hospital, Perth, WA. University of Western Australia, Perth, WA. [email protected] j doi: 10.5694/mja16.00545 Narrative review adherence, and it is probably more important that daily 1 Prevalence of thyroid disease in Australia dosing is consistent with regard to time of day and 18 Condition Definition Prevalence relationship to meals. The long half-life of thyroxine Thyroid Positive TPOAb or TgAb 12% means that if a dose has been missed, a catch-up dose autoimmunity can be taken later in the day or the following day. Subclinical Increased TSH, normal free T4 5% When treating hypothyroidism, the targets are relief of hypothyroidism symptoms and return of TSH to within the reference Overt Increased TSH, low free T4 0.5% interval. In thyroxine-treated patients, serum free T4 hypothyroidism may be within the reference range or elevated; the latter Subclinical Decreased TSH, normal free T4 0.3% is not an indication to reduce dosage if TSH is within the hyperthyroidism and free T3 reference interval. Measurement of free T3 is unhelpful 11,18 Overt Decreased TSH, elevated free 0.3% in monitoring thyroxine replacement. In some pa- hyperthyroidism T4 and/or free T3 tients, TSH levels remain elevated despite apparently Palpable thyroid About 5% adequate thyroxine dosage. The most common cause is nodules non-adherence; other causes and ways to address these Thyroid nodules at Increases with age, up to are shown in Box 2. ultrasound 70% of the elderly Three thyroxine preparations are available in Australia. ¼ ¼ ¼ ¼ T3 triiodothyronine. T4 thyroxine. TgAb thyroglobulin antibodies. TPOAb thyroid peroxidase Two of these (Eutroxsig and Oroxine, Aspen Pharma) antibodies. TSH ¼ thyroid-stimulating hormone. u are identical and interchangeable. A third preparation, Eltroxin (Aspen Pharma), has recently been marketed. It has a different formulation, a wider range of tablet 10 mU/L. Patients with persistent mild subclinical hypothyroid- strengths and (unlike Eutroxsig/Oroxine) does not require refrig- e ism (TSH, 4 10 mU/L) and minimal or no symptoms can be eration, so may be more convenient. Eltroxin product information offered a choice between thyroxine treatment or observation with states that it is not bioequivalent to Oroxine/Eutroxsig, but this is annual follow-up testing to detect progressive hypothyroidism. based on a study using single, large doses of thyroxine in healthy 4 Progression is more likely in TPOAb-positive patients. Women volunteers, which may not predict clinically relevant differences with subclinical hypothyroidism who are planning pregnancy during clinical use.18 Because of this uncertainty, patients should should be treated (see below). When it is uncertain whether non- not be switched between Eltroxin and Eutroxsig/Oroxine (or vice fi speci c symptoms are caused by, or merely coexist with, mild versa), except where explicitly intended by the prescribing doctor. subclinical hypothyroidism, a 3-month trial of thyroxine is Patients who do switch brands should have their serum TSH fi reasonable to assess symptomatic bene t. Thyroid replacement checked 6 weeks later, and dosage adjusted if necessary. therapy is not indicated for individuals with symptoms suggestive 17 of hypothyroidism if TSH levels are within the reference interval. Dissatisfaction with thyroxine replacement Thyroxine is the standard treatment for hypothyroidism.18 The In some patients, symptoms of ill health persist despite adherence usual approach is an initial dose of 50e100 mg/day with subse- to treatment and normalisation of TSH.18,19 There are three likely quent
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