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PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Hyperthyroidism (Overactive Thyroid) written for patients

Synonym: thyrotoxicosis

See related separate articles Thyroid Eye Disease and Hyperthyroidism in Pregnancy.

Hyperthyroidism is overactivity of the thyroid gland, which results in a number of symptoms and signs. It can be primary or secondary:[1]

Primary hyperthyroidism is the term used when the pathology is within the thyroid gland.

Secondary hyperthyroidism is the term used when the thyroid gland is stimulated by excessive thyroid-stimulating hormone (TSH) in the circulation.

Anatomy and physiology of the thyroid gland:[2] 
  • The thyroid gland is situated in the neck and its hormones control the metabolic rate of tissues.
  • It is stimulated and controlled by TSH from the anterior pituitary.
  • TSH is released by thyrotropin-releasing hormone (TRH) from the hypothalamus.
  • The thyroid gland, in response to TSH, produces thyroxine (T4) and triiodothyronine (T3). Greater amounts of T4 are produced than T3.
  • T4 is inactive and needs to be converted to T3 - which occurs peripherally (such as in the liver and kidney).
  • Most T3 and T4 in the circulation are bound to protein (mostly thyroglobulin); it is only free thyroid hormone that is active.
  • Free thyroid hormones in the circulation act negatively on the hypothalamus and pituitary - thus reducing the release of TRH and TSH.


An American study reported a prevalence of about 400 per 100,000 persons, with a lifetime risk of 1% in men and up to 2% in women. 60-80% of cases are due to Graves' disease with a peak onset at 20-50 years; the remainder of cases are due largely to nodular thyroid disease that appears later in life. It affects females more than males (ratio 9:1).[3] 


A Scottish study found an incidence of 0.77/1,000 annually in women and 0.14/1,000 annually in men.[4] In England the incidence of Graves' disease has been reported as 0.5 per 1,000 per year.[5] 

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Risk factors

This includes family history, high iodine intake, smoking (particularly for thyroid-associated ophthalmopathy) trauma to the thyroid gland (including surgery),[6] toxic multinodular goitre (which is especially associated with an increased iodine intake, either from a change in diet or an acute dose from iodine-containing agents (eg, amiodarone, contrast agents)), childbirth, and highly active antiretroviral therapy (HAART).[3]

Graves' disease is associated with genetic susceptibility including CD40, CTLA-4, thyroglobulin, TSH receptor and PTPN22). There is a link with a specific HLA haplotype (HLA-B8). Specific gene loci have been identified which are different in different racial groups. An interaction between genetic predisposition and certain trigger factors are then thought to initiate the disease process (eg, organochlorines, pesticides).[7] It was thought that Yersinia enterocolitica infection raised the risk of developing Graves' disease but doubt has now been cast on this theory.[8]Other possible triggers include smoking, stress, pollutants, allergy, iatrogenic causes (percutaneous injection of ethanol, interferon therapy such as interferon beta-1b or interleukin-4 therapy) and selenium intake.

  • Weight loss despite an increased appetite.
  • Weight gain.
  • Increased or decreased appetite.
  • Irritability.
  • Weakness and fatigue.
  • Diarrhoea ± steatorrhoea.
  • Sweating.
  • Tremor.
  • Mental illness: may range from anxiety to psychosis.
  • Heat intolerance.
  • Loss of libido.
  • Oligomenorrhoea or amenorrhoea.
  • Palmar erythema.
  • Sweaty and warm palms.
  • Fine tremor.
  • Tachycardia - may be atrial fibrillation and/or heart failure (common in the elderly).
  • Hair thinning or diffuse alopecia.
  • Urticaria, pruritus.
  • Brisk reflexes.
  • Goitre.
  • Proximal myopathy (muscle weakness ± wasting).
  • Gynaecomastia.
  • Lid lag (may be present in any cause of hyperthyroidism).

Extra features in Graves' disease[9] 

  • The pathophysiology of Graves' disease can have a variable effect on thyroid function and patients may remain euthyroid or become hypothyroid.
  • There may be a personal or family history of autoimmune disease.
  • Eye changes - exophthalmos, ophthalmoplegia, conjunctival oedema, papilloedema and keratopathy. May be severe enough to cause visual loss.
  • Pretibial myxoedema - due to accumulation of glycosaminoglycans. This is but one form of dermopathy and occurs in about 40% of patients with Graves' disease. It causes non-pitting pink/purple plaques of oedema just above the lateral malleolus. Thyroid dermopathy can occur anywhere, particularly in sites of trauma. <5% have pretibial myxoedema called thyroid dermopathy (as can occur anywhere, particularly following trauma). This is usually associated with moderate to severe ophthalmopathy. Thyroid dermopathy usually appears as non-pitting plaques with pink/purple colour. There are also nodular and generalised forms.
  • Thyroid acropachy is a type of dermopathy affecting the hands and causes clubbing with painful swelling of digits.
  • Diffuse moderate enlargement of the thyroid gland which feels firm on palpation.
  • Thyroid bruit.
  • There may also be lymphoid hyperplasia including splenomegaly and an enlarged thymus.
  • Associated with other autoimmune conditions - eg, pernicious anaemia, type 1 diabetes mellitus.
  • Thyrotoxic periodic paralysis has been traditionally described in Southeast Asian patients. This rare entity is now increasingly being described in patients of other ethnic backgrounds, particularly Arabs. A genetic susceptibility has been identified.[10]

See separate article Hyperthyroid Crisis (Thyrotoxic Storm).

  • Occasionally, patients may present with thyrotoxic crisis or storm in either previously undiagnosed or ineffectively treated cases.[11]
  • Infections, poor compliance and radio-iodine therapy are all precipitants.
  • It presents with fever >38.5°C, tachycardia, delirium or coma, seizures, vomiting, diarrhoea and jaundice. It is a clinical diagnosis.[11]
  • Treatment involves correcting the thyroid hormones, using high doses of propylthiouracil, fluid resuscitation and treating any precipitating causes.
  • It is also important to look for the presence of Addison's disease in these patients.
  • It has 20-30% mortality due to arrhythmias and hypothermia.
  • Graves' disease:[9]
    • This is the most common cause of hyperthyroidism and has an autoimmune basis. It is mediated by B and T lymphocytes, characterised also by the presence of thyroid-stimulating immunoglobulins (TSIs). These are directed at four different thyroid antigens:
      • Thyroglobulin.
      • Thyroid peroxidase (or antimicrosomal antibodies).
      • Sodium-iodide symporter.
      • TSH receptor.
    • The condition is characterised by a small to moderate diffuse, firm goitre with 50% of these showing ophthalmopathy.
    • There may be a personal or family history of autoimmune disease.
    • <5% have pretibial myxoedema called thyroid dermopathy (as can occur anywhere, particularly following trauma). This is usually associated with moderate to severe ophthalmopathy. 10-20% have clubbing (thyroid acropathy). Thyroid dermopathy usually appears as non-pitting plaques with pink/purple colour. There are also nodular and generalised forms.
    • There may also be lymphoid hyperplasia including splenomegaly and an enlarged thymus.
    • Associated with other autoimmune conditions - eg, pernicious anaemia, type 1 diabetes mellitus.
    • Although anti-thyroid peroxidase antibodies appear to play little role in the aetiology of thyrotoxicosis in Graves' disease, they are a reflection of autoimmune activity and patients who have these antibodies as well as TSI may become hypothyroid in time (about 5%). Some patients produce antibodies which block rather than stimulate the TSH receptors and this produces hypothyroidism. Hence, Graves' disease can produce a spectrum from hyperthyroidism to hypothyroidism (some patients are euthyroid).
    • There is a genetic component that may predispose individuals (susceptibility genes include CD40, CTLA-4, thyroglobulin, TSH receptor and PTPN22) and there is a link with a specific HLA haplotype (HLA-B8). Specific gene loci have been identified which are different in different racial groups.
    • Toxic nodular goitre: the presence of a multinodular goitre without the above symptoms (ie specific features of Graves' disease) suggests toxic nodular goitre (common in the elderly).
  • Solitary thyroid nodule: palpable, toxic adenoma.
  • De Quervain's thyroiditis:
    • Transient hyperthyroidism which probably results from a viral infection.
    • Presents with features of hyperthyroidism with pyrexia and pain in the neck.
  • Self-medication: eg, over-the-counter iodine supplements, 'energy boosting' preparations containing thyroid hormones.
  • Follicular carcinoma of the thyroid gland: associated with metastatic disease.
  • Drugs: eg, amiodarone, lithium, exogenous iodine.
  • Ovarian teratomas.

Phaeochromocytoma and any cause of weight loss.

  • Thyroid function tests (TFTs): serum TSH can exclude primary thyrotoxicosis. Confirm the diagnosis with free T4 levels. If TSH is suppressed but free T4 levels are normal, then if not previously supplied, free T3 level is needed (T3 toxicosis occurs in 5% of patients).
  • Autoantibodies - these are most commonly seen in Graves' disease:
    • Antimicrosomal antibodies - against thyroid peroxidase.
    • Antithyroglobulin antibodies.
    • TSH-receptor antibodies which are commonly present in Graves' disease but are not routinely measured.
    • TSI if elevated helps to establish a diagnosis of Graves' disease.
  • Imaging:
    • Thyroid ultrasound scan.
    • Thyroid uptake scans: to locate hot (overactivity) and cold (no activity) spots.

Refer to a specialist for treatment. Beta-blockers can be used for rapid symptom control whilst waiting for thyroid function to normalise. Calcium-channel blockers may be used if patients are intolerant of beta-blockers.

There are three kinds of definitive treatment:[1][12]

  • Antithyroid drugs: carbimazole (methimazole) or propylthiouracil (Class: thionamides):
    • These drugs act very quickly and inhibit the production of thyroid hormones. Full benefit may take 2-3 weeks to become apparent.
    • Recent reports from America about liver damage with propylthiouracil are currently being evaluated. Until these reports can be further evaluated propylthiouracil should be reserved for specific situations in which it is considered first-line (eg, pregnancy).[13]
    • The aim is to avoid drug-induced hypothyroidism which occurs in 40-60% cases.
    • There are two potential methods of treating hyperthyroid patients: 'block and replace' - where antithyroid drugs are given with thyroxine replacement, and 'dose titration' - where only antithyroid drugs are used and doses are adjusted to achieve normalisation of thyroid hormone production.
    • A systematic review and meta-analysis suggest that both types of methods are equally effective. Furthermore, the dose titration method was associated with a lower rate of side-effects.[14]
    • Carbimazole is most commonly used to begin with, in a dose of 10 mg twice or three times daily initially (depending on the weight of the patient), adjusting or stepping down according to response and TFT results. TFTs usually normalise in a few weeks to months.
    • TFTs are repeated every month and the dose altered according to the T4 level. TSH may remain suppressed for months despite the T4 coming into the normal range and is, thus, unreliable. Once the patient is euthyroid the dose of carbimazole is reduced until the patient is on the lowest amount necessary to maintain the T4 and T3 within the normal range.
    • Remission is usually achieved at 18-24 months, after which attempts may be made to stop antithyroid drugs. But monitoring for recurrence is needed. One study recommends that block and replace therapy should be continued in patients with Graves' orbitopathy until the orbitopathy has resolved.[15]
    • Minor side-effects include: nausea and a bitter taste after taking medication. Warn patients to come for FBC if they develop a sore throat, etc (as anti-thyroid drugs can cause bone marrow suppression). This is seen in less than 0.5% of patients.
  • Radio-iodine - is increasingly the first-line treatment in teenagers:[16]
    • Radioactive iodine is given to the patient as a drink and is taken up by the thyroid gland, leading to destruction of the gland. It is given as 200-600 MBq and some may need a second treatment. It can take 3-4 months to take effect.
    • Radio-iodine has the advantages that it is relatively inexpensive and a definitive method of treating hyperthyroidism.
    • It cannot be given to pregnant or breast-feeding females and females must be advised not to get pregnant for at least four months.
    • Radioactive iodine may also worsen eye disease in Graves' thyrotoxicosis: this is more marked in smokers.
    • The patient does have to be informed that the radioactive iodine is cleared via the urine and thus can be passed on.
    • They are usually advised to avoid close contact with children and pregnant women. It also requires patients to sleep alone for a week.
    • Hypothyroidism is also a potential and common complication. Estimates suggest that between 50% to 80% of patients can develop hypothyroidism.[17] Therefore, there is a need for long-term follow-up of the TFTs.
    • Radio-iodine is the treatment of choice for toxic adenoma.[18]
    • Toxic multinodular goitre is usually treated by radio-iodine; anti-thyroid drugs will work but relapse always occurs when the drugs are discontinued.
  • Surgical:
    • Subtotal or near total thyroidectomy achieves a 98% cure rate. It is indicated if there is suboptimal response to anti-thyroid medication or radio-iodine, especially in patients who are pregnant or who have Graves' orbitopathy. Complications include: haemorrhage, hypoparathyroidism and vocal cord paralysis. Patients who undergo surgery will need to be followed up over a number of years, as they may develop hypothyroidism.
    • Toxic adenoma or toxic multinodular goitre which is resistant to conservative treatment or causing compression symptoms is best treated with surgical excision.[18]

Both surgery and radioiodine require the patient to be euthyroid.

  • Make the diagnosis:
    • Note presence of signs and symptoms.
    • TFTs: await results before initiating therapy if possible.
  • Does the patent need urgent admission or can they be managed on an outpatient basis?

    Consider referral for urgent admission if any of the following are present:
    • Unwell or unable to manage at home.
    • Presence of atrial fibrillation or cardiac failure.
    • Dehydrated - eg, from severe diarrhoea.
    • Psychosis.
  • If the patient can be managed in the community:
    • Educate them on the nature of the illness and the management plan.
    • Start carbimazole - eg, 10 mg three times a day, after specialised advice is sought.
    • Warn the patient of the importance of seeking urgent help if they develop a sore throat or a rash.
    • Consider starting a beta-blocker or calcium-channel blocker to control symptoms driven by the sympathetic nervous system - eg, atenolol or verapamil. Again, discuss this initially with specialists.
  • Monitor TFTs monthly.
  • Refer immediately to a thyroid surgeon for patients with symptoms of tracheal compression due to a thyroid swelling.
  • Refer ugently to a thyroid surgeon for hyperthyroid patients with a thyroid swelling associated with:
    • A solitary enlarging nodule.
    • Previous neck irradiation.
    • Family history of endocrine tumour.
    • Hoarseness or voice changes without other obvious cause.
    • Neck glands.
    • Young age (before puberty).
    • Older age (65 or more).
  • Refer routinely to outpatient endocrinology for patients without the above features but who have thyrotoxicosis confirmed by TFTs. It is helpful to include the thyroid peroxidase result in the referral letter.

Secondary hyperthyroidism is rare. The pathology is at the level of the pituitary. TSH, T3 and T4 are all very high. TRH stimulation tests are used in the diagnosis and result in a flat response curve.
Causes include:

  • TSH-secreting pituitary adenoma.
  • Thyroid hormone-resistance syndrome.
  • HCG-secreting tumour.
  • Gestational thyrotoxicosis.
  • This is confirmed when T4 and T3 are within the normal range but TSH is less than 0.4 mIU/L (check with a local laboratory for the reference range that applies to your area).
  • Look for secondary causes of low TSH with normal thyroid hormone levels - eg, concomitant illness or medications such as glucocorticoids, dopaminergic drugs or amiodarone.
  • Recheck TFTs in two months - if no change in levels and no development of new symptoms or signs then check every 3-6 months based on clinical judgement.
  • If abnormal results persist for more than six months, refer to endocrinologists.
  • Subclinical hyperthyroidism is associated with increased risks of coronary heart disease (CHD) mortality and incident atrial fibrillation, with highest risks of CHD mortality and atrial fibrillation when thyrotropin level is lower than 0.10 mIU/L.[19]

This condition occurs rarely and is principally seen in newborn babies of mothers who have Graves' disease. Occasionally it is seen in neonates of euthyroid mothers. Maternal TSH-receptor antibody levels may be high. Clinical features vary but may include tachycardia, pulmonary hypertension and cardiopulmonary failure. Neonates commonly develop tachycardia and are treated with carbimazole and beta-blockers once the diagnosis is confirmed.

  • One study in the UK and Ireland reported an incidence in children under the age of 15 of acquired hyperthyroidism of 0.9 per 100,000.
  • 96% of cases were due to autoimmune disease.
  • Girls had a mucher higher incidence than boys in the group aged 10-14 years.
  • Weight loss, tiredness, change in behaviour and heat intolerance were the most common symptoms. Goitre and tremor were the most common signs.
  • There were no reported cases of thyroid storm.
  • Paediatric patients are treated in a similar fashion to adults: antithyroid medication, radio-iodine (for adolescents) and surgery.
  • Amiodarone is a heavily iodinated drug used commonly in several forms of arrhythmias.
  • Patients should have their thyroid function tested prior to starting amiodarone.
  • Amiodarone can cause hyperthyroidism and hypothyroidism.
  • Amiodarone-induced thyrotoxicosis (AIT) is divided into two types: AIT I - thyrotoxicosis in a patient who has underlying thyroid dysfunction, and AIT II - which is thyrotoxicosis resulting from destructive thyroiditis.
  • In both forms of thyrotoxicosis the amiodarone should be stopped (bearing in mind the potential risk of developing the original arrhythmia). Type I is treated as per Graves' hyperthyroidism - ie antithyroid medication and radio-iodine or surgery to prevent recurrence. Type 2 is treated with antithyroid medication to control symptoms and more definitively with steroids.
  • Hyperthyroidism is characterised by relapses and remittances.
  • Surgical treatment and radioactive iodine can both lead to hypothyroidism and thus close follow-up with TFTs is required.
  • Spontaneous remission is seen in <10% and may not persist.
  • There is a 3 x increased risk of death from osteoporotic fracture and 1.3 x increased risk of death from cardiovascular disease and stroke in untreated hyperthyroidism. The risk of cerebrovascular disease is also significant in younger adults.[23]
  • Long-term follow-up studies have shown increased mortality from cardiovascular and cerebrovascular disease in those with a past history of treatment with radio-iodine for overt hyperthyroidism.[24]

Robert James Graves (1796-1853) was an outstanding Irish physician and teacher. He was a prolific medical author and his paper 'Newly observed affection of the thyroid gland in females' was published in the London Medical and Surgical Journal in 1853.

Further reading & references

  • Hendriks LE, Looij BJ; Hyperthyroidism caused by excessive consumption of sausages. Neth J Med. 2010 Mar;68(3):135-7.
  • Gesing A, Lewi Ski A, Karbownik-Lewi Ska MG; The thyroid gland and the process of aging; what is new? Thyroid Res. 2012 Nov 24;5(1):16.
  • Leger J, Carel JC; Hyperthyroidism In Childhood: Causes, When and How To Treat. J Clin Res Pediatr Endocrinol. 2012 Nov 15. doi: 10.4274/jcrpe.854.
  • Selmer C, Olesen JB, Hansen ML, et al; The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ. 2012 Nov 27;345:e7895. doi: 10.1136/bmj.e7895.
  1. Hyperthyroidism, Prodigy (March 2008)
  2. Pernick N; Clinical Chemistry,, 2012
  3. Kasper D et al; Hyperthyroidism (Graves' Disease), Harrison's Practice, 2012
  4. Flynn RW, MacDonald TM, Morris AD, et al; The thyroid epidemiology, audit, and research study: thyroid dysfunction in the general population. J Clin Endocrinol Metab. 2004 Aug;89(8):3879-84.
  5. Epocrates Online, Graves' Disease, 2012.
  6. Saranac L, Zivanovic S, Bjelakovic B, et al; Why is the thyroid so prone to autoimmune disease? Horm Res Paediatr. 2011;75(3):157-65. Epub 2011 Feb 22.
  7. Duntas LH; Environmental factors and thyroid autoimmunity. Ann Endocrinol (Paris). 2011 Apr;72(2):108-13. Epub 2011 Apr 20.
  8. Effraimidis G, Tijssen JG, Strieder TG, et al; No causal relationship between Yersinia enterocolitica infection and autoimmune thyroid disease: evidence from a prospective study. Clin Exp Immunol. 2011 Jul;165(1):38-43. doi: 10.1111/j.1365-2249.2011.04399.x. Epub 2011 Apr 13.
  9. Yeung S-CJ et al; Grave's Disease, Medscape, Sep 2011
  10. Aldasouqi S, Bokhari SA, Khan PM, et al; Thyrotoxic periodic paralysis in a Saudi patient complicated by life-threatening arrhythmia. Saudi Med J. 2009 Apr;30(4):564-8.
  11. Migneco A, Ojetti V, Testa A, et al; Management of thyrotoxic crisis. Eur Rev Med Pharmacol Sci. 2005 Jan-Feb;9(1):69-74.
  12. Lawrence D; Thyroid problems in primary care, InnovAiT, Volume 1, Issue 12Pp. 788-79, 2008.
  13. Glinoer D, Cooper DS; The propylthiouracil dilemma. Curr Opin Endocrinol Diabetes Obes. 2012 Oct;19(5):402-7. doi: 10.1097/MED.0b013e3283565b49.
  14. Abraham P, Avenell A, McGeoch SC, et al; Antithyroid drug regimen for treating Graves' hyperthyroidism. Cochrane Database Syst Rev. 2010 Jan 20;(1):CD003420.
  15. Elbers L, Mourits M, Wiersinga W; Outcome of very long-term treatment with antithyroid drugs in Graves' hyperthyroidism associated with Graves' orbitopathy. Thyroid. 2011 Mar;21(3):279-83. Epub 2010 Dec 29.
  16. Turner N, Driver I, Salotti JA, et al; Increasing use of radioiodine in young people with thyrotoxicosis in Great Britain. Eur J Endocrinol. 2012 Nov;167(5):715-8. doi: 10.1530/EJE-12-0542. Epub 2012 Sep 6.
  17. Reid JR, Wheeler SF; Hyperthyroidism: diagnosis and treatment. Am Fam Physician. 2005 Aug 15;72(4):623-30.
  18. Yano Y, Sugino K, Akaishi J, et al; Treatment of autonomously functioning thyroid nodules at a single institution: radioiodine therapy, surgery, and ethanol injection therapy. Ann Nucl Med. 2011 Dec;25(10):749-54. Epub 2011 Oct 5.
  19. Collet TH, Gussekloo J, Bauer DC, et al; Subclinical hyperthyroidism and the risk of coronary heart disease and mortality. Arch Intern Med. 2012 May 28;172(10):799-809.
  20. Obeid R, Kalra VK, Arora P, et al; Neonatal thyrotoxicosis presenting as persistent pulmonary hypertension. BMJ Case Rep. 2012 May 30;2012. pii: bcr0220125939. doi: 10.1136/bcr.02.2012.5939.
  21. Williamson S, Greene SA; Incidence of thyrotoxicosis in childhood: a national population based study in the UK and Ireland. Clin Endocrinol (Oxf). 2010 Mar;72(3):358-63. Epub 2009 Sep 21.
  22. Bogazzi F, Tomisti L, Bartalena L, et al; Amiodarone and the thyroid: a 2012 update. J Endocrinol Invest. 2012 Mar;35(3):340-8. Epub 2012 Mar 19.
  23. Sheu JJ, Kang JH, Lin HC, et al; Hyperthyroidism and risk of ischemic stroke in young adults: a 5-year follow-up Stroke. 2010 May;41(5):961-6. Epub 2010 Apr 1.
  24. Metso S, Jaatinen P, Huhtala H, et al; Increased cardiovascular and cancer mortality after radioiodine treatment for hyperthyroidism. J Clin Endocrinol Metab. 2007 Jun;92(6):2190-6. Epub 2007 Mar 20.
  25. Biography - Robert James Graves; Mayo Clinic Libraries, 2012

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Gurvinder Rull
Current Version:
Peer Reviewer:
Prof Cathy Jackson
Document ID:
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