Management of Primary Hypothyroidism: Statement by the British Thyroid Association Executive Committee

Statement by the British Thyroid Association Executive Committee

Onyebuchi Okosieme; Jackie Gilbert; Prakash Abraham; Kristien Boelaert; Colin Dayan; Mark Gurnell; Graham Leese; Christopher McCabe; Petros Perros; Vicki Smith; Graham Williams; Mark Vanderpump

Disclosures

Clin Endocrinol. 2016;84(6):799-808. 

In This Article

Background

Primary hypothyroidism is an insidious condition with a significant morbidity and often subtle and nonspecific symptoms and clinical signs.[1,2] The earliest biochemical abnormality is an increase in serum thyroid-stimulating hormone (thyrotrophin) (TSH) concentration associated with normal serum free thyroxine (T4) and triiodothyronine (T3) concentrations (subclinical hypothyroidism), followed by a decrease in serum free T4 concentration, at which stage, most patients have symptoms and benefit from treatment (overt hypothyroidism).[1–3] In the UK, the prevalence of spontaneous hypothyroidism is between 1% and 2%, and it is more common in older women and ten times more common in women than in men.[4,5] The cause is either chronic autoimmune disease [atrophic autoimmune thyroiditis or goitrous autoimmune thyroiditis (Hashimoto's thyroiditis)] or destructive treatment for hyperthyroidism with either radioiodine or surgery which may account for up to one-third of cases of hypothyroidism in the community.[6] Less frequent causes include surgery and radioiodine ablation for benign nodular thyroid disease and thyroid cancer, external beam irradiation of malignant tumours of the head and neck and drugs including lithium, amiodarone and interferon.[1] Congenital hypothyroidism affects about one newborn in 3500–4000 births.[7]

The term subclinical hypothyroidism describes the finding of a raised serum TSH but a normal free T4.[3,8,9] It represents a compensated state in which increased TSH output is required to maintain normal circulating thyroid hormone levels. An elevated serum TSH is a sensitive indicator of some degree of thyroid failure, and there is a clear inverse relationship with free T4 levels. The term implies that patients should be asymptomatic, although symptoms are difficult to assess, especially in patients in whom thyroid function tests have been checked because of nonspecific complaints such as tiredness. Subclinical hypothyroidism is common in studies of healthy people in the community and is found in 5–10% of the population, being more common in women and increasing with age.[9] It can progress to overt hypothyroidism, particularly if antithyroid antibody positive.[10] In the community, the most common aetiology is chronic autoimmune thyroiditis.[6]

There has been a growing controversy about the upper limit of the reference range for serum TSH.[11,12] Reference ranges are derived from a reference population that comprises a large group of subjects who do not have thyroid disease and are otherwise well. By convention, a reference range usually only comprises 95% of a reference population. Thus, 2·5% of 'normal' individuals will fall above the reference range and 2·5% will fall below the range. For serum TSH, the reference population shows a log normal distribution and has a diurnal variation with the reference range in thyroid disease free individuals typically cited as between 0·4 and 4·0 mU/l.[8] The reference range varies in different ethnic communities, pregnancy and by age.[13] It has been reported that serum TSH distribution progressively shifts towards higher concentration with age.[13] Studies addressing the relationship between symptoms suggestive of thyroid hormone deficiency and the biochemical finding of subclinical hypothyroidism have produced conflicting results.[3] It is recognized that up to one-quarter of the healthy normal population may have 'hypothyroid' symptoms such as lethargy and weight gain.[14] The evidence for benefit in randomized controlled trials of thyroid hormone treatment in subclinical hypothyroidism is inconsistent and further studies are needed.[3,15] Although epidemiological studies have shown an association between subclinical hypothyroidism and coronary heart disease in younger people (<65 years)[16] or those with high TSH (>10 mU/l),[17] recent evidence suggests that in older people, higher serum TSH and lower free T4 concentrations within the euthyroid range are associated with lower risk of multiple adverse events including mortality.[18] In neonates and children, pregnancy, or in women trying to conceive, a mildly increased serum TSH should always be treated as mild thyroid failure which is associated with adverse outcomes for both mother and foetus.[19]

In England, 3% of people are prescribed synthetic L-T4[20] with the goal of therapy being to restore patient well-being and normalize serum TSH levels.[21] Most patients respond satisfactorily, but a minority of treated individuals experience persistent symptoms despite adequate biochemical correction.[22] The care of such individuals is challenging and remains the subject of considerable public interest.[23] Although some nonmainstream practitioners advocate the use of alternative thyroid therapies including liothyronine (L-T3) and thyroid extracts, combination therapy with L-T4 and L-T3 is also prescribed by accredited specialists. In the United States, 3·6% of endocrinologists report that they would give L-T3 to patients with hypothyroidism with persistent symptoms and normal biochemical thyroid status.[24]

In 2008, the Royal College of Physicians (RCP) issued a position statement on the diagnosis and management of primary hypothyroidism endorsed by various professional bodies, namely the British Thyroid Association (BTA), the British Thyroid Foundation (BTF), the Association for Clinical Biochemistry and Laboratory Medicine (ACB), the British Society of Paediatric Endocrinology and Diabetes (BSPED), the Society for Endocrinology (SFE) and the Royal College of General Practitioners (RCGP).[25] This RCP statement, updated in 2011, did not support the use of thyroid extracts or L-T3 in the treatment of hypothyroidism and recommended that L-T3 'should be reserved for use by accredited endocrinologists in individual patients'.[25]

More recently, the European Thyroid Association (ETA) published guidelines on the use of L-T4/L-T3 combination therapy in primary hypothyroidism[26] and subsequently, the American Thyroid Association (ATA)[27] and the Latin America Thyroid Society (LATS)[28] have released their own separate hypothyroidism treatment guidelines. These international guidelines have generated further interest in the role of L-T3 in hypothyroidism and have been interpreted in some quarters as representing a departure from the earlier UK RCP position.[29]

It is recognized that clinicians must be committed to delivering individualized patient-centred care and shared decision-making in all patients with primary hypothyroidism. This report summarizes the key points in the ETA and ATA guidelines and contains a statement on the management of primary hypothyroidism written by the BTA and endorsed by the ACB, BTF, RCP and SFE based on the current evidence and international guidelines.

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