Changes

January 2025 — reviewed. A literature search was conducted in December 2024 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The recommendations have been updated in line with the National Institute for Health and Care Excellence (NICE) clinical guideline Thyroid disease: assessment and management (2023) and other current evidence in the literature.

Update

Goals

To support primary healthcare professionals to:

• Make a diagnosis of suspected hyperthyroidism or subclinical hyperthyroidism on the basis of symptoms and/or blood test results.
• Arrange referral to an endocrinologist for specialist assessment and management, the urgency depending on clinical judgement.
• Arrange referral to a thyroid eye disease specialist if Graves' orbitopathy is suspected, the urgency depending on clinical judgement.
• Offer information and advice about hyperthyroidism and subclinical hyperthyroidism.
• Arrange ongoing monitoring of a person with hyperthyroidism or subclinical hyperthyroidism, depending on specialist advice.

Outcome measures

Audit criteria

QOF indicators

QIPP - Options for local implementation

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

NICE quality standards

What is it?

• Hyperthyroidism is a biochemical diagnosis due to pathologically increased thyroid hormone production and secretion by the thyroid gland [Bathgate, 2018; Shahid, 2023].
• Thyrotoxicosis is the clinical manifestation of excess circulating thyroid hormones due to any cause, including hyperthyroidism [Bathgate, 2018; Mathew, 2023].
  • Thyroid hormones are essential for normal growth, development, and cellular metabolism.
  • Circulating thyroid hormone levels are normally controlled through the process of negative feedback on the hypothalamus and pituitary gland.
• Primary hyperthyroidism occurs when thyrotoxicosis is caused by an abnormality of the thyroid gland such as [Biondi, 2018; Mathew, 2023]:
  • Overt primary hyperthyroidism is diagnosed when thyroid-stimulating hormone (TSH) is suppressed below the normal reference range, and free thyroxine (FT4) and/or free triiodothyronine (FT3) concentrations are above the normal reference range.
  • Subclinical hyperthyroidism is diagnosed when TSH is suppressed below the normal reference range, but FT4 and FT3 concentrations are within the normal reference range.
• Thyrotoxicosis without hyperthyroidism describes thyrotoxicosis without thyroid gland overactivity such as thyroiditis, which is usually transient [Blick, 2023].

What are the risk factors?

Risk factors for developing hyperthyroidism include:

• Female sex — women are ten times more likely to develop hyperthyroidism than men [BTA, 2006; Mathew, 2023]. Women are more likely to develop Graves' disease [Lee, 2023; Pokhrel, 2023].
• Family history — Graves' disease occurs more commonly in patients with a positive family history. It is more common in monozygotic twins (concordance rate is 20% [BMJ Best Practice, 2024]) than in dizygotic twins [Pokhrel, 2023]. Family and twin studies demonstrate that Graves’ disease is not caused by a single gene defect but has a complex pattern of inheritance. A number of gene regions have been linked to Graves' hyperthyroidism, including the human leukocyte antigen (HLA)-DRB1*16:02 allele [BMJ Best Practice, 2024].
• Smoking — smoking is a dose‐dependent risk factor for Graves’ hyperthyroidism and Graves’ orbitopathy [Wiersinga, 2013].
  • Graves' disease
    • The risk is higher for women than men. In addition, smoking is related to a higher recurrence rate of Graves’ hyperthyroidism [Wiersinga, 2013].
  • Graves' orbitopathy
    • Observational studies show that current and previous tobacco use increases the risk of orbitopathy four- to eightfold. Among patients who have orbitopathy, the severe forms are more often observed in smokers and they are more likely to experience disease progression and poorer outcomes following treatment [Bartalena, 2021; BMJ Best Practice, 2024].
    • If a person has Graves' disease, the most significant modifiable risk factor for developing Graves' orbitopathy is smoking [Bartalena, 2021].
• Low iodine intake — this may cause a multinodular or single nodular goitre, and is likely to occur if iodine intake increases, either gradually through dietary changes, or suddenly with the use of iodine-containing drugs, such as amiodarone [Mathew, 2023].
• Autoimmune disease — co-existent autoimmune conditions are a risk factor for developing Graves' orbitopathy, hyperthyroidism, and postpartum thyroiditis [Alexander, 2017].
  • The prevalence of postpartum thyroiditis is 3–4 times higher in women with type 1 diabetes mellitus compared with unselected populations [Alexander, 2017].
• Graves’ disease is a common side effect of alemtuzumab, which is used to treat multiple sclerosis [BMJ Best Practice, 2024].

What are the causes?

Causes of thyrotoxicosis with hyperthyroidism (increased thyroid hormone synthesis)

• Thyroidal origin
  • Graves' disease
    • This is the most common cause of hyperthyroidism in iodine-sufficient areas, accounting for about 80% of cases. It is a systemic autoimmune disorder mediated by thyroid-stimulating hormone (TSH)-receptor antibodies (TRAbs) that stimulate the TSH receptor, leading to thyroid hyperplasia and unregulated excessive production and secretion of thyroid hormone [Bathgate, 2018; Kahaly, 2018; Lee, 2023; Mathew, 2023].
    • Peak incidence is at 30–50 years of age, and it is 10 times more common in women than men [Bathgate, 2018].
    • Typical eye signs of Graves' orbitopathy occur in about 25% of cases [BMJ Best Practice, 2024].
    • People with a personal or family history of autoimmune disorders, such as type 1 diabetes mellitus, are at increased risk [BMJ Best Practice, 2024].
  • Toxic multinodular goitre
    • This is the second most common cause of hyperthyroidism in the UK, and is more common in older adults [Bathgate, 2018; Mathew, 2023].
    • It occurs in a thyroid gland with at least two autonomously functioning thyroid nodules that secrete excess thyroid hormone [Franklyn, 2012]. Histologically the nodules are benign follicular adenomas [Vaidya, 2014].
    • People over 60 years of age, and people living in iodine-deficient areas are at increased risk, as thyroid autonomy develops after a long period of low iodine intake [Samuels, 2021; Blick, 2023; BMJ Best Practice, 2024].
  • Toxic thyroid nodule (adenoma)
    • This accounts for around 2% of cases of hyperthyroidism, and is more common in older adults [Samuels, 2021]. The nodule produces enough hormone to suppress secretion of TSH from the pituitary, with consequent suppression of the contralateral thyroid lobe [Bathgate, 2018]. Histologically the nodule is a benign follicular adenoma [Samuels, 2021].
  • TSH-secreting pituitary adenoma
    • This is a rare tumour secreting large quantities of TSH, leading to inappropriately normal or elevated TSH levels, with elevated free thyroxine (FT4), and total triiodothyronine (T3) levels. The pituitary does not respond to normal T4 and T3 feedback mechanisms [Bathgate, 2018].
  • Pituitary thyroid hormone resistance syndrome
    • This is a rare condition caused by genetic mutations in the thyroid hormone receptor-beta gene. A positive family history supports the diagnosis. Usually the person is euthyroid, but thyrotoxic symptoms may occur [Bathgate, 2018].
  • High concentrations of human chorionic gonadotrophin (hCG) can stimulate TSH receptors and suppress TSH [Alexander, 2017; Blick, 2023].
    • Gestational thyrotoxicosis — this is a benign and transient disorder typically seen in the first trimester of pregnancy, caused by the stimulatory action of placental beta-hCG. There is an absence of thyroid autoimmunity, and it does not require any specialist treatment.
    • Hyperemesis gravidarum — defined as 5% weight loss of pre-pregnancy weight, dehydration, and ketonuria. See the CKS topic on Nausea/vomiting in pregnancy for more information.
    • Chorionic gonadotrophin-secreting tumours, such as choriocarcinoma or hydatidiform mole (rare). Tumour produces beta-hCG, which stimulates thyroid TSH receptors.
  • Iodine
    • Iodine may suppress TSH levels and is found in over-the-counter preparations, such as kelp supplements [Bathgate, 2018].
    • Amiodarone-induced thyrotoxicosis (AIT type 1) — if a person with underlying thyroid disease is exposed to the high iodine content of amiodarone, this may lead to excess thyroid hormone synthesis and release [Anfinsen, 2021]. The long half-life of amiodarone may cause hyperthyroidism for up to one year after it is discontinued [BTA, 2006].
    • Iodinated radiographic contrast agents may suppress TSH levels [Bathgate, 2018].
• Extrathyroidal origin
  • Struma ovarii
    • This describes ectopic thyroid hormone secretion from thyroid tissue located in an ovarian teratoma [Bathgate, 2018].
  • Functional thyroid cancer metastases
    • These can result in extrathyroidal foci of thyroid hormone production [Blick, 2023].

Causes of thyrotoxicosis without hyperthyroidism (increased availability of preformed thyroid hormone)

• Thyroidal origin
  • Thyroiditis causes a usually transient release of pre-formed thyroid hormones into the circulation due to inflammatory destruction of the thyroid follicles, and includes [Bathgate, 2018]:
    • Postpartum thyroiditis (PPT) — this is a painless, inflammatory autoimmune condition which typically occurs within 2–6 months after delivery or miscarriage. It is defined as the development of thyrotoxicosis, hypothyroidism, or thyrotoxicosis followed by hypothyroidism within a year of giving birth, in women who were euthyroid prior to pregnancy. Most women become euthyroid within 12 months of delivery, but there is a 30% risk of permanent hypothyroidism. If thyroid peroxidase autoantibodies (TPOAbs) are positive in early pregnancy, there is a 40–60% chance of PPT developing [Alexander, 2017]. See the CKS topic on Hypothyroidism for more information.
    • Subacute (de Quervain's) thyroiditis — typically presents with thyroid pain and fever, and is thought to be due to a viral infection or a postviral inflammatory process [Ross, 2016].
    • Drug-induced — amiodarone-induced thyrotoxicosis (AIT type 2) describes a destructive thyroiditis caused by the direct toxic effect of amiodarone on thyroid cells (usually self-limiting); lithium rarely causes hyperthyroidism, and this may present more than one year after starting the drug; anti-retrovirals and cancer immunotherapy drugs such as interferon-alpha can precipitate thyroiditis [Bathgate, 2018].
• Extrathyroidal origin
  • Exogenous thyroid hormone
    • Excess intake of levothyroxine (LT4) — in the UK, the most common cause of a serum TSH level less than 0.1 mU/L is excess use of LT4 medication which may be intentional (factitious) or unintentional (iatrogenic) [Bathgate, 2018]. Thyroid hormone may also be a constituent of over-the-counter weight loss supplements [Bathgate, 2018; Biondi, 2018]. See the CKS topic on Hypothyroidism for more information on prescribing and monitoring LT4 therapy.

How common is it?

Overt and subclinical hyperthyroidism

• In areas where there is sufficient iodine available the prevalence of overt hyperthyroidism is 0.2% to 1.3%  [Taylor, 2018; BMJ Best Practice, 2024]. The prevalence of overt hyperthyroidism is roughly similar in Europe and the United States (0.7% versus 0.5%) [Taylor, 2018].
• A meta-analysis of 17 European studies of thyroid dysfunction found that [Madariaga, 2014]:
  • The total prevalence (diagnosed and undiagnosed) of hyperthyroidism was 0.75%.
  • The prevalence of undiagnosed hyperthyroidism was 1.72% (1.71% in females and 1.81% in males); and the prevalence of undiagnosed subclinical hyperthyroidism was 0.42% in females and 0.27% in males.
  • The incidence rate of hyperthyroidism was 51.04 per 100,000 people per year; 82.47 per 100,000 women per year and 16.24 per 100,000 men per year.
• The prevalence of hyperthyroidism increases with age [Taylor, 2018].
• In 1977, the UK Whickham study reported that the incidence of hyperthyroidism was estimated at between 100 and 200 cases per 100,000 per year with a prevalence of 2.7% in women and 0.23% in men [Tunbridge, 1977]. A UK follow-up community survey of thyroid disease found the prevalence of hyperthyroidism in women was 0.5–2%, and it was ten times more common in women than in men [Vanderpump, 1995].
• The prevalence of subclinical hyperthyroidism is approximately 0.7–1.4% [Lee, 2023]. It increases with age and is higher in iodine-deficient areas compared with iodine-sufficient areas [Cooper, 2012].
  • In England, the prevalence of subclinical hyperthyroidism was found to be 2.1% in a cross-sectional screening survey of 5950 adults aged over 65 years [Franklyn, 2012].

Graves' and Graves' orbitopathy

• The incidence of Graves’ disease is between 20 to 50 cases per 100,000 person per year. It is around 6 times more common in women than in men and individuals of any age can be affected, but the incidence peaks between 30 and 50 years of age [BMJ Best Practice, 2024].
• The overall incidence of Graves' disease in children and adolescents is around 4.58 per 100,000 person per year, but before age 15 years incidence is lower (1 to 2.91 per 100,000 per year)[Mooij, 2022]. Graves' disease is 3.4 times more common in girls than boys before age 5 years, and the prevalence is about ten times lower [Mooij, 2022].
• Around 25% of all those with Graves disease have Graves' orbitopathy. The estimated incidence is 0.54–0.9 cases per 100,000 men per year, and 2.67–3.3 cases per 100,000 women per year [Bartalena, 2021]. Mild and non-progressive cases are more common and moderate-to-severe cases comprising only 5–6% of cases [Bartalena, 2021]. The prevalence of Graves' orbitopathy has decreased in recent years, possibly due to earlier diagnosis and treatment of Graves' disease [Bartalena, 2021].
  • More than 90% of cases occur in people presenting with hyperthyroidism due to Graves' disease [Ross, 2016], but it may also present up to a year before the onset of hyperthyroidism, or up to 5 years after a diagnosis of hyperthyroidism [Lazarus, 2012].
• A large prospective Danish population-based study which analyzed approximately 8.9 million person-years of observational data, found the incidence of new cases of moderate-to-severe Graves' orbitopathy was 0.161 per 10,000 people per year [Laurberg, 2012].
• The European Group on Graves’ Orbitopathy (EUGOGO) position statement states that cross-sectional studies from secondary or tertiary centres have found 2% of cases of Graves' orbitopathy were sight-threatening [Perros, 2017].

Pregnancy and postpartum

• Hyperthyroidism affects 1 in 500 pregnancies but the majority are diagnosed before conception [Oriaifo, 2024].
• The risk of developing hyperthyroidism in pregnancy varies depending on the stage of pregnancy. A Danish population-based cohort study (n = 403,958) reported that overall, 0.9% of women developed hyperthyroidism in and around the time of pregnancy, with an incidence rate of 65 per 100,000 women per year. It found [Andersen, 2015]:
  • A high incidence rate during the first trimester (relative risk [RR 1.5]).
  • A low incidence rate during the third trimester (RR 0.26).
  • The highest incidence rate was in the 7–9 months postpartum (RR 3.8).
• The American Thyroid Association (ATA) guideline notes that hyperthyroidism due to Graves' disease occurs in 0.5–1.0% of women in the reproductive age range, and 0.1–0.2% of these women are treated with antithyroid drugs during pregnancy [Ross, 2016].
• Postpartum thyroiditis is the most common cause of thyrotoxicosis post pregnancy. The prevalence is 4.1% as compared to 0.2% for Graves’ disease [Yap, 2023].

What are the complications?

Complications of untreated or undertreated hyperthyroidism include:

• Graves orbitopathy
  • This is an autoimmune disorder, and in about 90% of cases it occurs in people with a current or past history of Graves' disease [Ross, 2016; Bathgate, 2018]. About 25% of people with Graves' disease have Graves' orbitopathy [BMJ Best Practice, 2024].
  • Sight-threatening complications include dysthyroid optic neuropathy, severe corneal exposure and ulceration, or corneal breakdown leading to frank perforation [Bartalena, 2021].
  • It can affect a person's quality of life and psychosocial wellbeing due to possible distressing changes in facial appearance [Bathgate, 2018; Bartalena, 2021].
• Thyrotoxic crisis (thyroid storm)
  • This is a rare and potentially life-threatening complication, which may occur after a trigger such as acute infection, trauma, pregnancy, surgery including thyroidectomy, or stroke [Pokhrel, 2022].
  • It may occur in people with previously undiagnosed hyperthyroidism or those who have abruptly stopped antithyroid medication [Bathgate, 2018].
  • Clinical features reflect systemic decompensation and include fever, tachycardia, agitation, hyperthermia, hypertension, atrial fibrillation, heart failure, jaundice, delirium, and coma [Ross, 2016; Bathgate, 2018].
  • The mortality rate is estimated at about 10% due to hyperthermia, cardiac arrhythmias, multi-organ failure, and sepsis [Kahaly, 2018].
• Compression symptoms
  • A large goitre may cause dysphagia or breathlessness due to oesophageal or tracheal compression [Lee, 2023].
• Musculoskeletal
  • Thyrotoxic periodic paralysis —  this is a rare complication characterized by muscle paralysis and hypokalaemia, which is more prevalent in Asian people with hyperthyroidism [De Leo, 2016].
• Cardiovascular
  • Atrial fibrillation 
    • Recent studies estimated that AF occurs in 5–15% of the hyperthyroid patients, depending on the study population, compared with the 1–3% in the general population [Kostopoulos, 2024].
    • A 2019 study from the UK demonstrated that 5.7% of the 4189 Graves’ disease patients, developed AF during a long-term follow-up. The study also suggests that Graves’ disease patients have over twice the risk of incident AF compared with population controls [Okosieme, 2019].
    • A meta-analysis of individual-level data from five prospective cohort studies (n = 7901 euthyroid cases and 810 cases with subclinical hyperthyroidism) analysed the risk of incident atrial fibrillation. During a mean follow-up of 8.8 years, the overall hazard ratio for incident atrial fibrillation was higher in people with subclinical hyperthyroidism than in those who were euthyroid, and the attributable risk for atrial fibrillation was 41.5% in people with subclinical hyperthyroidism. After age- and sex-adjusted analysis, incident atrial fibrillation was found to be more common in people with more severe subclinical hyperthyroidism [Collet, 2012].
  • Heart failure  [Bathgate, 2018; Biondi, 2018].
    • Atrial fibrillation is an independent predictor of the development of heart failure in people with hyperthyroidism [De Leo, 2016].
    • Premature atrial and ventricular beats and heart failure with preserved ejection fraction may be associated with severe subclinical hyperthyroidism [Biondi, 2018]. The American Thyroid Association (ATA) guidelines on hyperthyroidism note that the risk of atrial fibrillation is increased in people with subclinical hyperthyroidism who are older and have lower TSH levels [Ross, 2016]. 
• Reduced bone mineral density and osteoporosis
  • Overt hyperthyroidism is associated with an increased risk of osteoporosis and fracture [Bathgate, 2018; Biondi, 2018; Lee, 2023].
  • In a prospective cohort study with case-cohort sampling of 686 women aged 65 years and older with subclinical hyperthyroidism, there was a four-fold increased risk for vertebral fracture and a three-fold increased risk for hip fracture, compared with women with normal thyroid function [Bauer, 2001].
• Increased mortality
  • There is an increased risk of death from all causes in people with hyperthyroidism and subclinical hyperthyroidism, including due to coronary heart disease [Biondi, 2018].
  • A meta-analysis of individual-level data from 10 prospective cohort studies (n = 52,674) found that subclinical hyperthyroidism was associated with a 24% increased risk of all-cause mortality and 29% increased risk of coronary heart disease mortality. The cardiovascular mortality risk was greater in people with more severe subclinical hyperthyroidism [Collet, 2012].
• Mood disorders
  • A 2022 meta-analysis found a statistically significant association of hyperthyroidism and depression[Bode, 2022].
  • Psychosis (rare) has been noted to complicate some cases of severe hyperthyroidism [Bathgate, 2018].
• Pregnancy
  • There is an increased risk of miscarriage, pregnancy-induced hypertension, maternal heart failure, preterm delivery, intrauterine growth restriction, low birthweight, and fetal death, if maternal hyperthyroidism is inadequately controlled during pregnancy [Alexander, 2017; Oriaifo, 2024].
  • Fetal complications of maternal hyperthyroidism include intrauterine growth restriction, fetal goitre, fetal hydrops and heart failure, fetal or neonatal thyrotoxicosis [Oriaifo, 2024].
    • Fetal or neonatal thyrotoxicosis may occur as a result of thyroid-stimulating hormone receptor antibodies (TRAbs) crossing the placenta in women with Graves' disease, and stimulating the fetal thyroid [Oriaifo, 2024].
    • The incidence of fetal and neonatal hyperthyroidism is between 1–5% in all women with active or a past history of Graves’ hyperthyroidism, and it is associated with an increased risk of fetal or neonatal morbidity and mortality if it is unrecognized and untreated [Alexander, 2017].

What is the prognosis?

• Overt hyperthyroidism
  • Compared to euthyroidism, overt hyperthyroidism is associated with a 35-400% increase in all-cause mortality, varying according to the acuity and severity of hyperthyroidism [Lee, 2023].
  • The American Thyroid Association (ATA) guidelines cite US studies that found Graves' disease may go into remission in 20–30% of people after 12–18 months of antithyroid drug treatment [Ross, 2016].
  • Relapse is most likely in people with Graves' disease within the first 6–12 months after antithyroid drug withdrawal, but may occur years later [Kahaly, 2018].
    • A Cochrane systematic review of 26 randomized controlled trials (n = 3388) found the risk of recurrence in people with Graves' disease was 51–54%, depending on what antithyroid drug regimen was used [Abraham, 2010].
  • People at higher risk of recurrence of hyperthyroidism have [De Leo, 2016; Kahaly, 2018]:
    • Severe hyperthyroidism.
    • Large goitre.
    • Persistently suppressed thyroid-stimulating hormone (TSH) level.
    • A high baseline concentration of TSH-receptor antibodies (TRAbs) and persistently high concentrations thereafter.
    • Presence of orbitopathy in Graves' disease.
• Subclinical hyperthyroidism
  • People with subclinical hyperthyroidism may have stable thyroid function, may progress to overt hyperthyroidism, or may become euthyroid over time, depending on the degree of TSH suppression [Ross, 2016].
    • Prospective studies have found that more than 50% of people with subclinical hyperthyroidism (especially those with a TSH level of 0.1–0.4 mU/L) have only a transient abnormality and subsequently thyroid function tests normalize [Biondi, 2018].
  • Subclinical hyperthyroidism may resolve spontaneously and progress to overt hyperthyroidism in approximately 8% of patients at 1 year, and 26% by 5-year follow-up [Lee, 2023]. Progression to overt hyperthyroidism is more common in people with undetectable serum TSH at baseline and in those with toxic multinodular goitre.
    
    • The European Thyroid Association guideline on Graves' hyperthyroidism reports that in the presence of TRAb indicating subclinical Graves' disease, the rate of progression to overt hyperthyroidism is up to 30% in the subsequent 3 years [Kahaly, 2018].
• Graves' orbitopathy
  • Mild Graves' orbitopathy is self-limiting in the majority of cases [Bartalena, 2021]. If untreated, it tends to gradually deteriorate over 6–12 months, and then slowly improve over 2–3 years.
  • The prognosis is worse in smokers and those with high TRAb concentrations [Kahaly, 2018].
• Postpartum thyroiditis (PPT)
  • Postpartum thyroiditis usually resolves spontaneously within one year postpartum [Yap, 2023]. Many cases are mild and of short duration, and spontaneously revert to euthyroidism [Alexander, 2017].
  • The natural history of PPT typically involves transient thyrotoxicosis followed by transient hypothyroidism, with a return to the euthyroid state by 1 year postpartum. All episodes of thyrotoxicosis resolve spontaneously [Alexander, 2017].
    • The clinical course of PPT can vary, however, with about 25% of women presenting with the typical natural history, 25% with isolated thyrotoxicosis, and 50% with isolated hypothyroidism [Alexander, 2017]. See the CKS topic on Hypothyroidism for more information.
    • The initial thyrotoxic phase usually occurs between 1–6 months postpartum, and lasts 1–2 months [Yap, 2023].
  • A retrospective study of postpartum women (n = 54) found that those who recovered fully from PPT had a 70% chance of developing the condition again in each subsequent pregnancy [Lazarus, 1997].

When should I suspect a diagnosis of hyperthyroidism?

The symptoms and signs of hyperthyroidism may be mild and non-specific, especially in the elderly. The clinical presentation can also vary depending on the person's co-morbidities and the underlying cause of hyperthyroidism.

• Suspect a diagnosis of hyperthyroidism if there are one or more symptoms of:
  • Rapid-onset malaise, fever, and thyroid pain (may suggest subacute thyroiditis).
  • Compression symptoms of breathlessness, hoarse voice, dysphagia, and neck pressure (may be caused by a toxic multinodular goitre).
  • Agitation, emotional lability, insomnia, irritability, anxiety, and palpitations.
  • Exercise intolerance, fatigue, and muscle weakness.
  • Heat intolerance and increased sweating.
  • Increased appetite with unintentional weight loss and diarrhoea.
  • Subfertility, oligomenorrhoea, and amenorrhoea.
  • Polyuria, thirst, and generalized itch.
  • Reduced libido and gynaecomastia in men.
  • Deterioration in blood glucose control and hyperglycaemia in people with diabetes mellitus. See the CKS topic on Diabetes - type 1 for more information.
  • Deterioration of co-morbid heart disease, for example, in the elderly. See the CKS topics on Angina for more information.
• Suspect a diagnosis of hyperthyroidism if there are one or more signs of:
  • Agitation, fine tremor, warm moist skin, and palmar erythema.
  • Sinus tachycardia, atrial fibrillation, heart failure, and peripheral oedema.
  • Thyroid enlargement (a goitre).
    • In Graves' disease, the thyroid gland is usually diffusely symmetrically enlarged without nodules, and there may be a bruit.
    • A toxic multinodular goitre typically presents with non-tender thyroid nodules.
    • A toxic adenoma typically presents with a unilateral, non-tender thyroid mass.
    • Subacute thyroiditis typically presents with a tender, firm, irregular, diffusely enlarged thyroid gland which may be asymmetrical.
    • In amiodarone-induced thyroiditis, a small goitre is usually present.
  • Pruritus, urticaria, vitiligo, and diffuse alopecia.
  • Muscle wasting, proximal myopathy, and hyper-reflexia.
  • Splenomegaly and lymphadenopathy.
  • Gynaecomastia in men.
  • Extrathyroid manifestations of Graves' disease (rare):
    • Thyroid acropachy (clubbing and swelling of the distal fingers and toes).
    • Thyroid dermopathy (slightly pigmented thickened skin and swelling of both legs, usually in the pretibial area).
• Suspect a diagnosis of Graves' orbitopathy if there are clinical features of:
  • Eye irritation, photophobia, or excessive watering of the eyes.
  • Redness of the eyes or eyelids and/or lid swelling.
  • Change in the appearance of the eye or eyelids:
    • Eyelid retraction (sclera is visible above the superior corneal limbus).
    • Lid lag (delay in moving the eyelid as the eye moves downward).
    • Proptosis (exophthalmos, eyeball protrusion, an inability to fully close the eyes as the upper and lower lids do not fully appose).
  • Persistent double vision in any direction of gaze (typically when looking upwards and outwards).
  • Unexplained deterioration in visual acuity; change in the intensity or quality of colour vision in one or both eyes; orbital aching or restricted eye movements — suggests dysthyroid optic neuropathy.
  • History of globe subluxation — one or both eyes suddenly 'popping out'; typically lasts more than a few seconds, is painful, and the lids could not be closed.
  • Note: be aware that Graves' orbitopathy is often asymmetrical, and is unilateral in 15% of people. It may occur in the context of hyperthyroidism, hypothyroidism, or euthyroidism.
• Be aware that clinical symptoms and signs are typically absent, mild, or non-specific in subclinical hyperthyroidism.
  • If clinical features are present, they are more likely in younger people.
• Suspect the thyroxtoxic phase of postpartum thyroiditis (PPT):
  • Typically between 1–6 months postpartum, which usually lasts only 1–2 months.
  • Note: be aware that other conditions such as Graves' disease can also present postpartum. See the section on Managing women postpartum in the section on Scenario: Pre-conception, pregnancy, and postpartum for more information.

How should I assess a person with suspected hyperthyroidism?

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

• Ask about:
  • Typical symptoms of hyperthyroidism and their severity and duration, including the presence of any compression symptoms.
  • Current or recent pregnancy. See the section on Scenario: Pre-conception, pregnancy, and postpartum in the section on Management for more information.
  • Any current or recent non-thyroidal illness or other possible causes of a transiently suppressed thyroid-stimulating hormone (TSH) level. See the section on Interpreting thyroid function tests for more information.
    • 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 TFT results.
  • Any drug treatment that may affect TFTs, including levothyroxine medication or recent exposure to radioactive iodine contrast media.
  • Any risk factors associated with hyperthyroidism, such as:
    • Smoking history.
    • Personal history of autoimmune disorders, such as type 1 diabetes mellitus or vitiligo. See the CKS topics on Diabetes - type 1 and Vitiligo for more information.
    • Family history of thyroid disease; personal or family history of hypothalamic-pituitary disease.
  • Any possible features of pituitary disease, such as history of brain or metastatic cancer; headache or visual field defects.
• Examine the person for:
  • Possible signs or complications of hyperthyroidism, including assessment of pulse, blood pressure, temperature, weight, signs of fluid overload or heart failure.
  • Thyroid enlargement (a goitre) and/or thyroid nodules, tenderness, and symmetry.
    • 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.
  • Signs of Graves' disease, including orbitopathy.
  • Signs of other autoimmune disease such as type 1 diabetes mellitus and vitiligo. See the CKS topics on Diabetes - type 1 and Vitiligo for more information.
• Check the serum TSH level, using clinical judgement to interpret TFT results, especially if TFTs do not match the clinical presentation.
  • If the TSH is within the reference range, further investigations are not usually needed, as hyperthyroidism is very unlikely.
    • If symptoms worsen or new symptoms develop, consider rechecking TFTs at least 6 weeks after the last sample.
• If the TSH level is below the normal reference range, the free thyroxine (FT4) and free triiodothyronine (FT3) levels should be measured in the same sample.
  • Suspect a diagnosis of overt hyperthyroidism if the TSH level is low and FT4 and/or FT3 levels are raised above the normal reference ranges.
  • Suspect a diagnosis of subclinical hyperthyroidism if the TSH level is below the normal reference range and FT3 and FT4 levels are within the normal reference range.
    • Repeat TFTs 3 months after the initial result to exclude other causes of a transiently suppressed TSH and to confirm the diagnosis.
    • If on repeat testing there is a persistently low TSH level with normal FT4 and FT3 levels, the diagnosis is confirmed.
• Consider checking additional blood tests, depending on clinical judgement, such as:
  • TSH-receptor antibodies (TRAbs) if a diagnosis of Graves' disease is suspected or the person is pregnant.
  • Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) if a diagnosis of thyroiditis is suspected.
  • Thyroid peroxidase antibodies (TPOAbs) if a woman is postpartum and a diagnosis of postpartum thyroiditis is suspected. See the CKS topic on Hypothyroidism for more information.
  • Baseline full blood count (FBC) and liver function tests (LFTs) if antithyroid drugs are to be started. See the section on Management for more information.
• 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.

Scenario: Management

From age 18 years onwards.

Scenario: Pre-conception, pregnancy, and postpartum

From age 18 years onwards (Female).

Propylthiouracil

• Propylthiouracil should only be initiated on specialist advice and should have ongoing specialist monitoring. The following is provided for reference purposes only.

Carbimazole

• Carbimazole should only be initiated on specialist advice and should have ongoing specialist monitoring. The following is provided for reference purposes only.

Beta-blockers

Search strategy

Scope of search

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

Search dates

November 2019 - December 2024

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 26th November 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. 

S5    S1 OR S2 OR S3 OR S4 
S4    AB ( grave* N2 (disease* or ophthalm* or orbitopath*) ) OR TI ( grave* N2 (disease* or ophthalm* or orbitopath*) ) 
S3    AB "overactive thyroid" OR TI "overactive thyroid" 
S2    AB hyperthyroidism OR TI hyperthyroidism 
S1    (MH "Hyperthyroidism+") 

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.