Changes

November 2024 — reviewed. A literature search was conducted in November 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone minor restructuring. The recommendations have been updated in line with the National Institute for Health and Care Excellence (NICE) clinical guideline Thyroid disease: assessment and management and other current evidence.

Update

Goals

To support primary healthcare professionals to:

• Make a diagnosis of hypothyroidism.
• Offer appropriate initial and subsequent management in primary care.
• Offer information and advice about hypothyroidism and subclinical hypothyroidism.
• Arrange referral to secondary care for specialist assessment and management, when appropriate.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

No NICE quality standards were found during the review of this topic.

What is it?

• Hypothyroidism is a common condition of thyroid hormone (thyroxine [T4] and tri-iodothyronine [T3]) deficiency, which are essential for normal growth, development, and metabolism [Chaker, 2022; BMJ Best Practice, 2024].
  • The thyroid gland releases T3 and T4 when it is stimulated by thyrotrophin (also known as thyroid-stimulating hormone [TSH]) from the anterior pituitary. The pituitary gland releases TSH when it is stimulated by thyrotrophin-releasing hormone (TRH) from the hypothalamus. T4 is converted to the more biologically active T3 in peripheral tissues.
  • Circulating thyroid hormone levels are controlled through the process of negative feedback on the hypothalamus and pituitary.
• Primary hypothyroidism (95% of cases) occurs when there is thyroid hormone deficiency due to the thyroid gland being unable to produce thyroid hormones because of iodine deficiency or an abnormality within the gland itself  [Chaker, 2022; BMJ Best Practice, 2024]. It is categorised into:
  • Overt hypothyroidism (OH)
    • TSH levels are above the normal reference range (usually above 10 mU/L) and free thyroxine (FT4) is below the normal reference range [Wilson, 2021].
    • In pregnancy, maternal hypothyroidism is defined as TSH levels above the trimester-specific reference range, which may or may not be associated with a FT4 level below the trimester-specific reference range [Alexander, 2017; BTF, 2024].
  • Subclinical hypothyroidism (SCH)
    • TSH levels are above the normal reference range, but T3 and T4 levels are within the normal reference range [BMJ Best Practice, 2024].
    • SCH in pregnancy is defined as TSH above the normal pregnancy-related reference range with a normal T4 [Alexander, 2017] .
• Secondary (or central) hypothyroidism
  • Secondary hypothyroidism is the result of insufficient thyroid stimulation due to a pituitary or hypothalamic disorder [Chaker, 2022; BMJ Best Practice, 2023].
    • TSH levels may be inappropriately low or normal (or rarely raised), but FT4 is below the normal reference range [BMJ Best Practice, 2023].
• Myxoedema coma is a rare severe form of hypothyroidism with multi-organ failure [Wilson, 2021].

What causes it?

• Causes of primary hypothyroidism
  • Iodine deficiency (or relative excess) [Chaker, 2022].
    • Worldwide, dietary iodine deficiency is the most common cause of hypothyroidism [Wilson, 2021].
  • Autoimmune thyroiditis
    • In iodine-sufficient areas, such as the UK, hypothyroidism and subclinical hypothyroidism are most often caused by autoimmune thyroiditis. This may be associated with a goitre (Hashimoto's thyroiditis) or occur without a goitre (atrophic thyroiditis) [Pearce, 2013; Chaker, 2017; Biondi, 2019].
  • Post-ablative therapy or surgery
    • Thyroid damage can occur after thyroid or other neck surgery, radioiodine therapy (for example, Graves' disease or toxic nodular disease), or post-radiotherapy to the head or neck [Chaker, 2017; BMJ Best Practice, 2024].
  • Drugs
    • About 15% of people treated with anti-thyroid drugs for Graves’ disease (such as carbimazole and propylthiouracil) develop hypothyroidism 10–20 years later [Pearce, 2013].
    • Treatment with several other drugs, such as iodine (including kelp supplements), amiodarone, lithium, anti-epileptic drugs such as sodium valproate, interferon-alpha, thalidomide, and rifampicin can also cause hypothyroidism [Chaker, 2017].
  • Transient thyroiditis
    • Subacute (de Quervain's) thyroiditis — this typically causes a painful swelling of the thyroid gland, thought to be due to viral infection [Chaker, 2017].
    • Postpartum thyroiditis (PPT) — this is a painless inflammatory autoimmune condition which describes the development of transient thyrotoxicosis, hypothyroidism, or thyrotoxicosis followed by hypothyroidism, followed by a return to the euthyroid state within a year of giving birth, in women who were euthyroid prior to pregnancy [Alexander, 2017].
  • Thyroid infiltrative disorders
    • These include amyloidosis, sarcoidosis, and tuberculosis, and malignant infiltration due to thyroid malignancy, lymphoma, or metastasis [Chaker, 2017].
  • Congenital hypothyroidism
    • This is due to thyroid gland dysgenesis (80%), or the absence of enzymes required for thyroid hormone synthesis and iodide transfer [Bowden, 2023]. Iodine deficiency is still an important cause of CH worldwide, especially in iodine-poor regions.
• Causes of secondary (central) hypothyroidism
  • Pituitary or hypothalamic dysfunction, due to [BMJ Best Practice, 2023]:
    • Tumours — most commonly pituitary adenomas or gliomas.
    • Surgery, radiotherapy, or trauma.
    • Pituitary infarction.
    • Sheehan's syndrome — postpartum pituitary necrosis due to postpartum haemorrhage.
    • Infiltrative disorders — such as amyloidosis, sarcoidosis, haemachromatosis, and tuberculosis.
    • Isolated thyroid-stimulating hormone (TSH) deficiency or inactivity.
    • Idiopathic hypothalamic disease.
    • Drugs — such as cocaine, dopamine, glucocorticosteroids, and metformin.

How common is it?

The prevalence of hypothyroidism in the literature varies according to the definition used, the population characteristics, and the geographical area studied.

• Primary hypothyroidism
  • In areas where dietary iodine is adequate, such as the UK, the prevalence of spontaneous hypothyroidism is 1–2%. It is up to 10 times more common in women than in men and increases with age [Mendes, 2019; Gottwald-Hostalek, 2022].
  • A meta-analysis of 17 European studies of thyroid dysfunction found that [Madariaga, 2014]:
    • The total prevalence (diagnosed and undiagnosed) of hypothyroidism was 3%.
    • The prevalence of undiagnosed hypothyroidism was 4.9% (6.4% in females and 3.4% in males). Of these, the prevalence of overt hypothyroidism was 0.8% in females and 0.3% in males, and the prevalence of subclinical hypothyroidism was 5.9% in females and 3.4% in males.
    • The incidence rate of hypothyroidism was 226.2 per 100,000 people per year; 370 per 100,000 per year in women and 72.5 per 100,000 per year in men.
  • A review article notes that the prevalence of overt hypothyroidism in Europe varies between 0.2–5.3%, depending on the definition of hypothyroidism used [BMJ Best Practice, 2024].
  • A retrospective analysis of General Practice data in the North East of England (n = 66,843) found the overall single-point prevalence of treated hypothyroidism was 4.5% in 2016 [Ingoe, 2017].
    • The prevalence increased with increasing age.
  • A review of UK national databases found the prevalence of treated hypothyroidism increased from 2.3% (1.4 million) to 3.5% (2.2 million) of the total UK population between 2005 and 2014 [Razvi, 2019].
    • There was large geographical variation of treated hypothyroidism across the UK, with London having the lowest (1.4%) and the Western Isles of Scotland having the highest (6.3%) prevalence.
    • The prevalence of treated hypothyroidism was positively associated with female sex, White ethnicity, and obesity.
  • A meta-analysis of 20 European studies found the estimated prevalence of undiagnosed overt hypothyroidism was 0.65% and undiagnosed subclinical hypothyroidism was 4.11% [Mendes, 2019].
    • The authors noted, however, high heterogeneity between studies regarding study design, populations studied, sample size, diagnostic tests, and reference ranges used.
  • The British Thyroid Association (BTA) advises that subclinical hypothyroidism affects 5–10% of the population [Okosieme, 2015].
    • The prevalence increases in women and with increasing age [Biondi, 2019].
    • In a 2020 UK primary care-based study 2870 individuals aged over 65 years were screened: 2703 (94%) were categorised as euthyroid (normal), 29 (1%) subclinically hyperthyroid, and 138 (5%) subclinically hypothyroid.
      • Symptoms were common in all groups, but no significant differences in the prevalence of individual symptoms were observed between the euthyroid and subclinically hypothyroid groups nor in comparison with the subclinically hyperthyroid group.
      • Multivariate logistic regression analysis failed to reveal an association between individual or multiple symptoms and subclinical status.
  • The true prevalence of subclinical hypothyroidism may have been overestimated in older people (over the age of 70 years, for example), due to the physiological increase in TSH levels with increasing age, which may be misinterpreted as thyroid disease [Chaker, 2017; Biondi, 2019].
• Secondary hypothyroidism
  • Secondary hypothyroidism is rare. The prevalence ranges from 1 in 16,000 to about 1 in 100,000 in the general adult or neonatal populations.
  • Variability in worldwide prevalence data can mostly be attributed to differences in screening programmes. [BMJ Best Practice, 2023].
• Pregnancy
  • The European Thyroid Association (ETA) guidelines state that the prevalence is as follows: [Lazarus, 2014]:
    • Overt hypothyroidism in pregnancy is 0.2–0.5%.
    • Subclinical hypothyroidism in pregnancy is 2–2.5%.
• Congenital hypothyroidism [Bowden, 2023] 
  • This has an estimated prevalence of 1 in 500–3000 newborns, depending on ethnicity.
  • The prevalence is higher in Hispanic (1 in 1600) and Asian (1 in 2380) infants and lower in black (1:11,000) infants.
  • Is 1.5-2 times more common in female infants.
• Postpartum thyroiditis (PPT)
  • The Endocrine Society states the prevalence of PPT in iodine-sufficient areas is about 7% [De Groot, 2012].
  • The American Thyroid Association (ATA) guideline states that the prevalence of PPT is about 5%, although it notes that estimates vary [Alexander, 2017].

What are the complications?

• Cardiovascular
  • Coronary heart disease (CHD) and stroke.
    
    • Epidemiological studies have shown an association between subclinical hypothyroidism and CHD in people younger than 65 years of age, and in those with TSH levels higher than 10 mU/L [Okosieme, 2015; Bekkering, 2019; Bauer, 2022].
      • A 2020 cohort study found that CVD mediated the associations of subclinical hypothyroidism and high-normal TSH concentrations with higher all-cause mortality in the US general population [Inoue, 2020].
    • A large meta-analysis of 55 cohort studies (n = 1,898,314) found that people with hypothyroidism, compared with euthyroid controls, had higher risks of ischaemic heart disease (relative risk [RR] 1.13), myocardial infarction (RR 1.15), cardiac mortality (RR 1.96), and all-cause mortality (RR 1.25). A diagnosis of SCH was also associated with an increased risk of ischaemic heart disease and all-cause mortality. It found no significant association between hypothyroidism and risk of stroke, heart failure, or atrial fibrillation [Ning, 2017].
    • A retrospective cohort study of general practice patients with a diagnosis of hypothyroidism (n = 160,439) with a median follow-up of six years, found an increased risk of ischaemic heart disease and heart failure in people with high TSH concentrations (greater than 10 mU/L), with a hazard ratio of 1.18 and 1.42 respectively. In addition, increased all-cause mortality was observed with a hazard ratio of 2.21 [Thayakaran, 2019].
  • Metabolic syndrome
    
    • A 2024 systematic review and meta-analysis showed that metabolic syndrome (MetS) is associated with an elevated risk of developing subclinical hypothyroidism (SCH) (OR 2.56, 95% CI 1.44–4.55)[Zhong, 2024]. However, the five individual components of MetS (obesity, hyperglycaemia, hypertension, low levels of HDL cholesterol and high serum triglycerides) were not associated with the risk of SCH. Subgroup analysis revealed that different definitions of MetS had varying effects on SCH.
  • Heart failure
    • Untreated overt hypothyroidism has been associated with an increased risk of diastolic heart failure [Chaker, 2017].
    • Subclinical hypothyroidism may be an independent risk factor for the development of heart failure and for progression of existing heart failure [Chaker, 2017; Bauer, 2022].
• Reproductive
  • Overt hypothyroidism is associated with:
    • An increased risk of infertility and subfertility [Alexander, 2017; Chaker, 2022].
  • Untreated overt hypothyroidism in pregnancy is associated with:
    • An increased risk of miscarriage, anaemia, pre-eclampsia, placental abruption, postpartum haemorrhage, and stillbirth [Alexander, 2017; Chaker, 2022].
    • Adverse neonatal outcomes including preterm delivery, low birthweight, neonatal respiratory distress, congenital abnormalities, congenital hypothyroidism, and impaired fetal neurocognitive development [Lazarus, 2014; Alexander, 2017].
  • Untreated SCH and thyroid autoimmunity in pregnancy may be associated with:
    • An increased risk of miscarriage, pregnancy loss, preterm delivery, low birthweight, gestational diabetes, gestational hypertension, and pre-eclampsia [Maraka, 2016; Alexander, 2017; Peeters, 2017].
    • Evidence is currently absent to support improved outcomes with treatment of SCH [Chaker, 2022].
• Impaired quality of life due to symptoms such as fatigue and comorbidities [Wouters, 2023].
• Neurological and cognitive
  • Overt hypothyroidism is associated with:
    • Decreased taste, vision, or hearing [Chaker, 2017].
    • Impaired attention, concentration, memory, language, executive function, and psychomotor speed [Chaker, 2017].
  • Data on the association between subclinical hypothyroidism and cognitive impairment are inconsistent [Biondi, 2019].
    • One systematic review and meta-analysis of 15 studies (n = 19,944) found no evidence of an association between subclinical hypothyroidism and cognitive impairment in adults over 60 years of age [Akintola, 2015].
    • A meta-analysis of 15 studies on the association between subclinical hypothyroidism and depression (n = 12,315) found that people with subclinical hypothyroidism had a higher risk of depression than euthyroid controls (relative risk 2.35), and this was particularly marked in the older population cohort [Loh, 2019].
• Myxoedema coma
  • This is a rare, life-threatening (25% to 60% mortality rate) medical emergency due to untreated severe hypothyroidism, that may present with lethargy, bradycardia, hypothermia, seizures and/or coma [Chaker, 2017; Wilson, 2021].
  • Affected people are typically older and have previously undiagnosed hypothyroidism. The precipitant is usually onset of another condition such as heart failure, sepsis, or stroke [BMJ Best Practice, 2024].

What is the prognosis?

• Primary hypothyroidism
  • This usually has a good prognosis, and most people will recover full physical and psychological wellbeing following adequate thyroid hormone replacement with levothyroxine (LT4), which is usually needed for life [BMJ Best Practice, 2024]. 
  • About 5–10% of people have persistent symptoms (such as impaired wellbeing and cognitive disturbance) after 6 months of thyroid hormone treatment, even when thyroid function tests have normalised [Hughes, 2021].
• Subclinical hypothyroidism (SCH)
  • The European Thyroid Association (ETA) guideline states that thyroid function may normalize in 6–35% of people with untreated subclinical hypothyroidism, depending on initial thyroid-stimulating hormone (TSH) levels, thyroid autoantibody status, and length and frequency of follow-up [Pearce, 2013].
    • A large retrospective, observational study (n = 346,549) found that 62.1% of people with TSH levels between 5.5 and 10 mU/L had normal TSH levels on repeat testing without treatment within five years [Meyerovitch, 2007].
  • The risk of progression to overt hypothyroidism is around 5% a year [Hughes, 2021].
    • Higher serum TSH levels (especially greater than 10 mU/L), positive thyroid autoantibodies, and female sex increase the risk of disease progression [Okosieme, 2015].
• Postpartum thyroiditis (PPT)
  • The clinical course of PPT varies, with about 25% of women presenting with the classical form (transient thyrotoxicosis followed by transient hypothyroidism followed by a return to the euthyroid state); 25% have isolated thyrotoxicosis; and about 50% present with isolated hypothyroidism [Alexander, 2017].
  • PPT usually resolves spontaneously within one year of giving birth [Alexander, 2017].
  • Women with a history of PPT have a markedly increased risk of developing permanent primary hypothyroidism in the 5–10 year period after the episode of PPT [De Groot, 2012].
  • A minority of women do not recover from the initial hypothyroid phase of PPT, and 10–50% of women where the initial hypothyroid phase has resolved will go on to develop permanent hypothyroidism [Alexander, 2017].
  • Women who fully recover from PPT have a 70% chance of developing PPT in each subsequent pregnancy [Alexander, 2017].

When should I suspect a diagnosis of hypothyroidism?

The symptoms and signs of hypothyroidism may be mild and non-specific, especially in the elderly. Suspect a diagnosis of hypothyroidism if there are more than one of the following clinical features:

• Primary hypothyroidism
  • Fatigue/lethargy, cold intolerance, weight gain, constipation.
  • Non-specific weakness, arthralgia, and myalgia.
  • Menstrual irregularities; infertility or subfertility.
  • Depression, impaired concentration and memory, 'brain fog'.
  • Dry skin and hair loss (such as loss of lateral eyebrows).
  • Thyroid pain, for example, in subacute thyroiditis.
  • Changes to appearance such as coarse dry hair and skin, and hair loss.
  • Oedema, including swelling of the eyelids.
  • Hoarseness or deepening of the voice; goitre.
  • Bradycardia and diastolic hypertension; pericardial effusion.
  • Delayed relaxation of deep tendon reflexes.
  • Paraesthesia (due to carpal tunnel syndrome) or peripheral neuropathy.
  • A diagnosis of other autoimmune disease.
• Secondary hypothyroidism
  • There may be clinical features of primary hypothyroidism together with clinical features of possible hypothalamic-pituitary disease such as recurrent headache, diplopia, and/or visual field defects.
  • In addition, abnormal pituitary hormone production may cause skin depigmentation, atrophic breasts, galactorrhoea, amenorrhoea, erectile dysfunction, loss of body hair, Cushing’s syndrome, or acromegaly.
• Subclinical hypothyroidism
  • Clinical features of hypothyroidism are usually absent but, if present, are related to the degree of thyroid-stimulating hormone (TSH) elevation.
• Postpartum thyroiditis (PPT)
  • The hypothyroid phase of PPT usually occurs between 3–8 months (most often at 6 months) postpartum and typically lasts 4–6 months.

How should I assess a person with suspected hypothyroidism?

If a diagnosis of hypothyroidism is suspected, assess the person and arrange investigations in primary care.

• Ask about:
  • Typical symptoms of hypothyroidism.
  • Current or recent pregnancy. See the sections on Scenario: Preconception or pregnant and Scenario: Postpartum for more information.
  • Any current or recent non-thyroidal illness.
    • If suspected, do not check thyroid function tests (TFTs) during acute illness unless it is felt that symptoms may be due to thyroid dysfunction, as acute non-thyroidal illness is likely to affect thyroid function test (TFT) results.
  • Any drug treatment such as amiodarone, lithium, or over-the-counter supplements such as biotin that may affect TFTs.
  • Any other risk factors associated with hypothyroidism, such as:
    • Family history of thyroid or autoimmune disease; personal or family history of hypothalamic-pituitary disease.
    • Personal history of autoimmune disorders, such as Addison’s disease, alopecia areata, pernicious anaemia, coeliac disease, type 1 diabetes mellitus, and vitiligo. See the CKS topics on Addison's disease, Alopecia areata, Anaemia - B12 and folate deficiency, coeliac disease, Diabetes - type 1, and Vitiligo for more information.
    • History of Turner or Down's syndrome.
    • Previous radiotherapy to the head and neck, radioiodine treatment, or thyroid or neck surgery.
    • History of iodine deficiency.
  • Any possible causes of secondary hypothyroidism, such as history of brain or metastatic cancer; infiltrative disease; head trauma; surgery, radiotherapy or disease affecting the pituitary gland or hypothalamus.
• Examine the person for:
  • Possible signs or complications of hypothyroidism.
  • Thyroid enlargement (a goitre) and/or thyroid nodules.
    • A hard and irregular goitre or nodule may indicate malignancy. See the CKS topic on Head and neck cancers - recognition and referral for more information on urgent management.
    • Thyroid pain may indicate subacute thyroiditis.
  • Signs of other autoimmune disease such as Addison’s disease, alopecia areata, pernicious anaemia, coeliac disease, type 1 diabetes mellitus, and vitiligo. See the CKS topics on Addison's disease, Alopecia areata, Anaemia - B12 and folate deficiency, coeliac disease, Diabetes - type 1, and Vitiligo for more information.
• Check the serum thyroid-stimulating hormone (TSH) level, using clinical judgement to interpret thyroid function test (TFT) results, especially if TFTs do not match the clinical presentation.
  • Consider arranging repeat TFTs depending on clinical judgement, if indicated.
  • If symptoms worsen or new symptoms develop, consider rechecking TFTs at least six weeks after the last sample.
• If the TSH level is above the normal reference range, the free thyroxine (FT4) level should be measured in the same sample.
  • Suspect a diagnosis of primary hypothyroidism if TSH levels are above the normal reference range (usually above 10 mU/L) and FT4 is below the normal reference range.
  • Suspect a diagnosis of subclinical hypothyroidism if TSH levels are above the normal reference range and FT4 is within the normal reference range.
    • In non-pregnant people, repeat TFTs 3–6 months after the initial result to exclude other causes of a transiently raised TSH and to confirm the diagnosis.
  • Suspect hypothyroidism in pregnancy if TSH levels are elevated (using trimester-specific reference ranges), which may or may not be associated with a FT4 level below the trimester-specific reference range.
  • Suspect the hypothyroid phase of postpartum thyroiditis (PPT) if TSH is raised within a year of giving birth.
  • Suspect a diagnosis of secondary hypothyroidism if clinical features are suggestive and TSH levels are inappropriately low (may be normal), but FT4 is below the normal reference range. Note: check both TSH and FT4 levels in these cases when arranging initial tests.
  • Suspect an alternative diagnosis if TFTs are within the normal euthyroid range.
  • Note: do not routinely measure total tri-iodothyronine (T3), total thyroxine (T4), or free tri-iodothyronine (FT3) levels in primary care.
• Consider checking additional blood tests if primary hypothyroidism is suspected:
  • Full blood count (FBC) and serum B12 level — to assess for possible associated pernicious anaemia. See the CKS topic on Anaemia - B12 and folate deficiency for more information.
  • Glycated haemoglobin (HbA1c) — to assess for associated type 1 diabetes mellitus. See the CKS topic on Diabetes - type 1 for more information.
  • Coeliac serology — to assess for coeliac disease if a diagnosis of autoimmune thyroid disease is suspected. See the CKS topic on Coeliac disease for more information.
  • Serum lipids — to assess for associated dyslipidaemia. See the CKS topics on CVD risk assessment and management and Lipid modification - CVD prevention for more information.
• Consider checking serum thyroid peroxidase antibodies (TPOAb) if:
  • Autoimmune thyroid disease is suspected — raised levels may suggest autoimmune primary hypothyroidism.
    • Do not arrange repeat testing of TPOAb.
  • A diagnosis of subclinical hypothyroidism is suspected — positive TPOAb can predict progression to overt hypothyroidism.
    • Do not arrange repeat testing of TPOAb.
  • The person is pregnant — be aware that after the first trimester, thyroid autoantibodies may be negative due to immune suppression in pregnancy.
• Arrange an ultrasound of the neck to image palpable thyroid enlargement or focal nodularity in adults with normal thyroid function if malignancy is suspected. See the CKS topic on Neck lump for more information.

What else might it be?

Conditions which may present similarly to hypothyroidism include:

• Non-thyroidal illness ('sick euthyroid syndrome') — a wide range of acute or chronic non-thyroidal conditions, starvation, and trauma can lead to abnormal thyroid function tests (TFTs) which are not due to true dysfunction of the hypothalamic-pituitary-thyroid (HPT) axis.
  • Thyroid-stimulating hormone (TSH) can be normal or low, then becomes high during recovery from acute illness. Free thyroxine (FT4) can be normal, low, or high. Free tri-iodothyronine (FT3) is usually low due to reduced conversion of thyroxine (T4) to tri-iodothyronine (T3).
• Endocrine/autoimmune conditions such as type 1 diabetes mellitus, Addison's disease, coeliac disease, atrophic gastritis with pernicious anaemia, hypopituitarism, or rheumatoid arthritis. See the CKS topics on Diabetes - type 1, Addison's disease, Coeliac disease, Anaemia - B12 and folate deficiency, and Rheumatoid arthritis for more information.
• Haematological conditions such as anaemia and multiple myeloma. See the CKS topics on Anaemia - iron deficiency and Multiple myeloma for more information.
• End-organ damage such as chronic kidney disease, chronic liver disease, and heart failure. See the CKS topics on Chronic kidney disease, Jaundice in adults, and Heart failure - chronic for more information.
• Metabolic abnormalities such as hypercalcaemia. See the CKS topic on Hypercalcaemia for more information.
• Vitamin and mineral deficiencies such as vitamin B1 deficiency, folate deficiency, iron deficiency, and vitamin D deficiency. See the CKS topics on Anaemia - B12 and folate deficiency, Anaemia - iron deficiency, and Vitamin D deficiency in adults - treatment and prevention for more information.
• Stress, poor sleep, alcohol misuse, anxiety, and depression. See the CKS topics on Generalized anxiety disorder, Insomnia, Alcohol - problem drinking, and Depression for more information.
• Dementia — in older people symptoms of dementia may be difficult to distinguish from hypothyroidism. See the CKS topic on Dementia for more information.
• Post-viral syndromes and chronic fatigue syndrome. See the CKS topic on Tiredness/fatigue in adults for more information.
• Polymyalgia rheumatica and fibromyalgia. See the CKS topic on Polymyalgia rheumatica for more information.
• Obesity and obstructive sleep apnoea. See the CKS topics on Obesity and Obstructive sleep apnoea syndrome for more information.
• Menopause — be aware that in menopausal women symptoms of thyroid dysfunction may be mistaken for menopause. See the CKS topic on Menopause for more information.
• Carbon monoxide poisoning. See the CKS topic on Carbon monoxide poisoning for more information.

When should I screen for hypothyroidism?

• In pregnant women or women planning a pregnancy, if the woman:
  • Is older than 30 years of age — screen at the earliest opportunity.
  • Has a goitre — screen at the earliest opportunity and at 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).
  • Has come from an area with moderate to severe iodine deficiency (such as the Himalayas, Andes, parts of Africa such as Burkina Faso, Egypt, Niger, Morocco, and Senegal; Eastern and Southern Europe) — screen at the earliest opportunity.
  • Has a previous history or current thyroid condition such as hyperthyroidism, hypothyroidism, or autoimmune thyroid disease — screen at the earliest opportunity.
    • If there is a history of postpartum thyroiditis — screen also at 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).
  • Has a family history of thyroid disease — screen at the earliest opportunity.
  • Has type 1 diabetes mellitus or another autoimmune condition:
    • Screen at the earliest opportunity — measure TSH, free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb) before conception, at booking when pregnant, and at 6–8 weeks postpartum (or after miscarriage or termination of pregnancy).
  • Is known to be thyroid autoantibody positive — screen at the earliest opportunity, during pregnancy at 6–8 weeks, and 6 months postpartum (or after miscarriage or termination of pregnancy).
  • Has had a previous miscarriage, pregnancy loss, preterm delivery, or history of infertility — screen at the earliest opportunity.
  • Is morbidly obese (body mass index [BMI] greater than 40) — screen at the earliest opportunity.
• In other adults, if the person:
  • Has a goitre — screen at initial presentation. See the CKS topic on Neck lump for more information.
  • Has type 1 diabetes or other autoimmune disease — screen at initial presentation, then annually. See the CKS topic on Diabetes - type 1 for more information.
  • Has new onset atrial fibrillation. See the CKS topic on Atrial fibrillation for more information.
  • Has dyslipidaemia — screen at initial presentation. See the CKS topics on Hypercholesterolaemia - familial and Lipid modification - CVD prevention for more information.
  • Has suspected dementia — consider screen at initial presentation.
  • Has had radioiodine or surgery for hyperthyroidism — screen at 4–8 weeks post-treatment, then every 3 months for up to 1 year, and annually thereafter. See the CKS topic on Hyperthyroidism for more information.
  • Has had previous neck radiotherapy or surgery involving the thyroid gland for head and neck cancer, including lymphoma — screen annually.
  • Has other autoimmune disorders — screen at baseline and annually in Addison's disease. Have a low threshold for testing in other autoimmune disorders. See the CKS topic on Addison's disease for more information.
  • Has Turner or Down's syndrome — screen annually.
  • Has a history of postpartum thyroiditis — screen annually. See the CKS topic on Hyperthyroidism for more information.
  • Has a history of subfertility, abnormal menstrual cycle, or miscarriage — screen at initial presentation. See the CKS topics on Infertility and Miscarriage for more information.
  • Has a personal history of preterm birth or recurrent miscarriage — consider measuring TPOAbs in addition to TSH and FT4.
  • Is taking drug treatment such as amiodarone or lithium — screen at baseline and every 6 months. If amiodarone is stopped, monitoring should continue for a further 12 months.
  • Has postnatal depression — screen at presentation. See the CKS topic on Depression - antenatal and postnatal for more information.

Scenario: Overt hypothyroidism (non-pregnant)

From age 18 years onwards.

Scenario: Subclinical hypothyroidism (non-pregnant)

From age 18 years onwards.

Scenario: Preconception or pregnant

From age 18 years onwards (Female).

Scenario: Postpartum

From age 18 years onwards (Female).

Levothyroxine

Search strategy

Scope of search

A literature search was conducted for guidelines and systematic reviews on primary care management of hypothyroidism.

Search dates

December 2019 - November 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 2nd December 2019). These were combined with filters to identify guidelines, systematic reviews and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

S6    S1 OR S2 OR S3 OR S4 OR S5 
S5    AB ( (post-partum or postpartum) N2 thyroiditis ) OR TI ( (post-partum or postpartum) N2 thyroiditis ) 
S4    (MH "Postpartum Thyroiditis") 
S3    AB underactive thyroid OR TI underactive thyroid 
S2    AB hypothyroidism OR TI hypothyroidism 
S1    (MH "Hypothyroidism+") 

Sources of guidelines

• National Institute for Health and Care Excellence (NICE)
• Scottish Intercollegiate Guidelines Network (SIGN)
• Royal College of Physicians
• Royal College of General Practitioners
• Royal College of Nursing
• NICE Evidence
• World Health Organization
• Guidelines International Network
• TRIP database
• Agency for Healthcare Research and Quality
• Institute for Clinical Systems Improvement
• National Health and Medical Research Council (Australia)
• Royal Australian College of General Practitioners
• British Columbia Medical Association
• Canadian Medical Association
• Alberta Medical Association
• Michigan Quality Improvement Consortium
• Singapore Ministry of Health
• National Resource for Infection Control
• RefHELP NHS Lothian Referral Guidelines
• Medline (with guideline filter)
• Driver and Vehicle Licensing Agency
• NHS Health at Work (occupational health practice)

Sources of systematic reviews and meta-analyses

• The Cochrane Library:
  • Systematic reviews
  • Protocols
  • Database of Abstracts of Reviews of Effects
• Medline (with systematic review filter)
• EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

• NIHR Health Technology Assessment programme
• The Cochrane Library:
  • NHS Economic Evaluations
  • Health Technology Assessments
• Canadian Agency for Drugs and Technologies in Health
• International Network of Agencies for Health Technology Assessment

Sources of randomized controlled trials

• The Cochrane Library:
  • Central Register of Controlled Trials
• Medline (with randomized controlled trial filter)
• EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

• Bandolier
• Drug and Therapeutics Bulletin
• TRIP database
• Central Services Agency COMPASS Therapeutic Notes

Sources of national policy

• Department of Health
• Health Management Information Consortium (HMIC)

Patient experiences

• Healthtalk
• BMJ - Patient Journeys

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

• British National Formulary (BNF)
• electronic Medicines Compendium (eMC)
• European Medicines Agency (EMEA)
• LactMed
• Medicines and Healthcare products Regulatory Agency (MHRA)
• REPROTOX
• Scottish Medicines Consortium
• Stockley's Drug Interactions
• TERIS
• TOXBASE
• Micromedex
• UK Medicines Information

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

• Clinical accuracy.
• Consistency with other providers of clinical knowledge for primary care.
• Accuracy of implementation of national guidance (in particular NICE guidelines).
• Usability.

Principles of the consultation process

• The process is inclusive and any individual may participate.
• To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
• Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
• Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
• External reviewers are not paid for commenting on the draft topics.
• Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
• All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
• All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

• Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
• Stakeholders identified from the following groups are invited to review draft topics:
  • Experts in the topic area.
  • Professional organizations and societies (for example, Royal Colleges).
  • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
  • Guideline development groups where the topic is an implementation of a guideline.
  • The British National Formulary team.
  • The editorial team that develop MeReC Publications.
• Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

• Topic selection
• Scoping of topic
• Selection of clinical scenarios
• First draft internal review
• Second draft internal review
• External review
• Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

• Animal studies
• Original research is not written in English

Possible exclusions for reviewed literature:

• Sample size too small or study underpowered
• Bias evident or promotional literature
• Population not relevant
• Intervention/treatment not relevant
• Outcomes not relevant
• Outcomes have no clear evidence of clinical effectiveness
• Setting not relevant
• Not relevant to UK
• Incorrect study type
• Review article
• Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

• Feasibility
  • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
• Organizational and Financial Impact Analysis
• Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
  • Eligible population
  • Current interventions
  • Likely uptake of new intervention or recommendation
  • Cost of the current or new intervention mix
  • Impact on other costs
  • Condition-related costs
  • In-direct costs and service impacts
  • Time dependencies
• Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

• Personal financial interests
• Personal family interest
• Personal non-financial interest
• Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.