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CamillaSchalin-Jäntti

Hyperthyroidism

Essentials

  • In a hyperthyroid patient, TSH concentration is below reference range (often unmeasurable), and free T4 and/or free T3 concentrations are increased.
  • As a general rule, patients with hyperthyroidism are referred to a specialist in internal medicine or an endocrinologist for assessment.
  • Start a beta-blocker and also antithyroid medication already at referral to a specialist when the diagnosis of hyperthyroidism is clear. Remember to inform the patient concerning the risk of agranulocytosis associated with antithyroid medication.
  • Patients with thyroid eye disease (in Basedow's [Grave's] disease only Graves' Ophthalmopathy) or with pregnancy-induced hyperthyroidism are promptly referred to a specialist.
  • Hyperthyroidism is always treated. In uncertain cases, begin with a beta-blocker only.
  • Depletion of hormone storages that is associated with an inflammatory state is not treated with antithyroid drugs (e.g subacute thyroiditis Subacute Thyroiditis).
  • The thyroid gland is palpated in order to estimate its size, whereasultrasonography has no place in the diagnostics of hyperthyroidism.

Causes

  • Basedow's disease (Graves' disease)
    • The most common cause; concentration of TSH receptor antibodies increased
    • Age at onset most commonly 30-40 years. The majority of patients are women.
    • Overactivity of the thyroid gland is often substantial.
  • Overactive (toxic) multinodular goitre
  • Overactive adenoma
  • Other causes

Transient thyrotoxicosis

Symptoms

  • General symptoms
    • Hypersensitivity to heat and sweating
    • Fatigue, muscular weakness, deterioration of general condition
    • Palpitations, hand tremor
    • Weight loss, increased bowel motility
    • Thirst, polyuria
    • Disturbances in menstrual cycle
  • Thyroid gland is often enlarged.
  • Skin symptoms
    • Warm and moist skin
  • Psychological symptoms
    • Lability, nervousness, irritability, sleeplessness
  • Cardiac symptoms
    • Tachycardia and arrhythmias, particularly atrial fibrillation
  • GI symptoms
    • Increased bowel function, diarrhoea, weight loss even if the appetite is good
  • Ophthalmopathy in Basedow's disease only
    • Other types of ocular symptoms occur in many other patients with hyperthyroidism.
  • Symptoms vary between patients. The elderly are often monosymptomatic (e.g. atrial fibrillation, fatigue, weight loss, worsening of angina pectoris, exertional dyspnoea alone) or their symptoms are masked (those already on beta-blocker treatment).

Diagnosis

  • The patient has symptoms compatible with hyperthyroidism.
  • The thyroid gland is palpated.
  • TSH below and free T4 (FT4) above reference range http://www.dynamed.com/condition/hyperthyroidism-and-other-causes-of-thyrotoxicosis-37#THYROID_FUNCTION_TESTS.
  • Increased TSH receptor antibody concentration confirms the underlying Basedow's disease http://www.dynamed.com/condition/hyperthyroidism-and-other-causes-of-thyrotoxicosis-37#THYROID_ANTIBODIES.
  • If TSH is < 0.1 and FT4 is normal, FT3 is tested to identify T3 hyperthyroidism.
  • If TSH is below reference range but both FT4 and FT3 are normal, the patient has subclinical hyperthyroidism. The thyroid parameters are checked after e.g. 3 months. If TSH concentration is only slightly decreased (0.1-0.4 mU/l) and the patient is symptomless, monitoring is sufficient. Principles for referring the patient to specialized care for assessment:
    • Repeated measurement of TSH is always necessary. A single measurement of TSH level of < 0.1 mU/l is not sufficient.
    • If TSH is persistently < 0.1 mU/l and the patient is over 60 years of age, refer him/her for assessment even if he/she would be asymptomatic.
    • If TSH is persistently < 0.1 mU/l or repeatedly mildly decreased (0.1-0.4) and the patient has goitre, symptoms of hyperthyroidism, atrial fibrillation or some other cardiac disease or osteoporosis, refer him/her for assessment.
    • Advanced age speaks for the need of assessment.

Treatment principles

  • All patients are treated to euthyroid state with antithyroid medication (may be started in primary health care).
  • The actual treatment strategy is decided in specialized care and may consist of
  • The choosing of treatment approach is influenced by the size of the thyroid gland, possible earlier thyroid surgery, possible eye symptoms, pregnancy and breast-feeding, patient's age and possible other severe diseases.
  • Long-term antithyroid medication and radioiodine treatment are good alternatives when the thyroid gland is small.
  • A very large thyroid gland is operated on.
  • Radioiodine treatment may worsen thyroid eye disease.
  • In overactive (toxic) multinodular goitre, permanent treatment results cannot be expected with antithyroid medication.
  • Patients with mild hyperthyroidism and good general condition may be started immediately on radioiodine with beta-blocker cover alone; other patients should first be made euthyroid with a short course of antithyroid medication.

Pharmacotherapy

Starting preventive treatment

  • An antithyroid drug (generally carbimazole 15-20-30 mg divided into two daily doses) should be given alone or preferably combined with a beta-blocker.
  • It is important to instruct the patient for the possibility of agranulocytosis: to seek medical advice if there is fever or a sore throat, in which case the leucocyte count is controlled.
  • Basic blood count with platelet count and thyroid parameters are controlled after 1 month if the patient is not already admitted to specialized care.

Long-term antithyroid treatment Antithyroid Drug Regimen for Treating Graves' Hyperthyroidism

  • Initiated if the underlying disease is hyperthyroidism caused by Basedow disease and the patient has a small thyroid gland, eye symptoms, or both, and it is the first hyperthyroid phase http://www.dynamed.com/condition/hyperthyroidism-and-other-causes-of-thyrotoxicosis-37#GRAVES_DISEASE. The duration in adults is 12(-18) months.
  • Long-term antithyroid treatment does not lead to permanent hypothyroidism (cf radioiodine treatment and surgery).
  • Follow-up: basic blood count with platelet count, TSH, FT4 (and FT3 if necessary) initially every 4 to 6 weeks and later in a stable phase every 2 to 3 months. TSH receptor antibody concentration should be measured, at least, at the diagnostic phase and before discontinuing the antithyroid treatment.
  • After euthyroidism has been achieved, beta-blocker medication is discontinued.
  • The antithyroid drug (carbimazole 5-20 mg/24 h) is sometimes combined with thyroxine if euthyroidism is otherwise difficult to achieve.
  • In euthyroidism, FT4 and FT3 are normal; for TSH, it often takes a longer time to be reversed back into the reference range.
  • When the projected treatment time (12-18 months) is over, the treatment is discontinued and the thyroid parameters are controlled after 1-3 months.
  • When the treatment is stopped, a recurrence is seen in half of the patients with Basedow's disease and in all patients with toxic nodular goitre. A large thyroid gland, a large dose of antithyroid drug and an increased concentration of TSH receptor antibodies are predictors of recurrence. In a patient with recurrence, antithyroid treatment is restarted, and the actual treatment strategy, either radioiodine treatment http://www.dynamed.com/condition/hyperthyroidism-and-other-causes-of-thyrotoxicosis-37#TOXIC_MULTINODULAR_GOITER or surgery, is decided in specialized care.
  • In somewhat older patients, life-long antithyroid medication is sometimes justified, if euthyroidism can be maintained with a small dose of antithyroid drug.

Notes on different treatment modes

Antithyroid medication

  • Risk of agranulocytosis (induced by all antithyroid drugs; see Leucopenia)
    • Fever and sore throat are the first signs.
    • Develops in 0.5% of patients.
    • Refer to hospital on an emergency basis (blood cultures, treatment for septicaemia)
    • Interrupt the antithyroid medication.
  • Hypersensitivity reactions (itching, urticaria, erythema) and an increase in liver parameters
  • Complete remission is not achieved in multinodular goitre.

Radioiodine treatment

  • Whether the patient is euthyroid, hypothyroid or hyperthyroid after the treatment is not revealed until follow-up laboratory tests are performed.
  • If hyperthyroidism persists, antithyroid treatment is restarted and the treatment strategy is planned anew (if necessary, repeated radioiodine treatment after 4 to 6 months, surgery).
  • Hypothyroidism as such is easy to manage with thyroxine.
  • Eye symptoms may worsen.
  • After the treatment, instructions concerning radiation safety are to be followed according to the received dose (see locally available patient information materials).
  • Radioiodine treatment is used especially in the treatment of the elderly. The most important indications are overactive multinodular goitre and recurring hyperthyroidism after long antithyroid treatment.

Surgery

  • Requires an 8-10 week initial treatment with an antithyroid drug. Surgery is usually performed in the euthyroid state. Antithyroid treatment should be followed up with laboratory tests until the patient is admitted to surgery.
  • Requires life-long thyroxine medication. Thyroxine medication is started immediately in the morning on the first postoperative day so that hypothyroidism cannot develop.
  • The risk of recurrent nerve paresis and hypoparathyroidism is about 2-4%. Therefore, thyroid surgery should be concentrated in specialized units.
  • Surgery is used especially to treat a large, overactive, thyroid gland that responds poorly to pharmacotherapy.

Evidence Summaries