hyperthyroidism
HYPERTHYROIDISM
Hyperthyroidism is the overactivity of the thyroid gland resulting in excessive production of thyroid hormones.
Symptoms are of gradual onset.
Earliest signs may be emotional lability and motor hyperactivity; decline in school performance may also be noted.
Causes are autoimmune (Grave's disease), inappropriate stimulation by trophic factors, passive release of preformed thyroid hormone stores in response to infections, trauma, or other offensive factors inside the body, and extra-thyroidal sources.

Pharmacotherapy

Antithyroid Agents

  • Carbimazole & Methimazole are considered 1st-line treatment
  • 2 methods in treating hyperthyroid patients
    • Dose titration: Dose is reduced & titrated against thyroid function tests to achieve a euthyroid state
    • Block & replace regimen: Combination therapy with thyroid preparation (eg Levothyroxine) may be considered in patients inadequately controlled by single-dose Carbimazole or Methimazole therapy, or in noncompliant patients 
  • Effects: About 25% of patients remain euthyroid ≥5 years after antithyroid treatment
    • Remission is most likely to occur in patients with a small thyroid gland (<2.5x normal size for age), children & adolescents >13 years old, non-Caucasian, serum TRAb levels less than normal or low T4 levels during therapy
    • Relapse usually appears within 3-6 months after stopping the therapy
  • Usually takes 3-6 weeks for clinical response to be noticeable
    • 3-4 months to have adequate control
    • May use beta-blockers to control symptoms during this period, but not always needed

Carbimazole

  • Inhibit thyroid hormone biosynthesis by decreasing iodide oxidation & iodination of tyrosine
  • Recommended as first-line antithyroid treatment in pediatric patients
  • Fewer tablets are needed for initial treatment compared w/ Propylthiouracil (PTU)

Methimazole

  • Methimazole is preferred over PTU because of less adverse effects 
    • 10-fold more potent on wt basis than PTU
  • Recommended as first-line antithyroid treatment in pediatric patients

Propylthiouracil (PTU)

  • Blocks the conversion of T4 to T3 in thyroid gland & peripheral tissues, also inhibits thyroid hormone biosynthesis by decreasing iodide oxidation & iodination of tyrosine
  • May be considered in patients with minimal response to Carbimazole or Methimazole therapy & opposed to surgical or radioactive iodine treatment, or patients with thyroid storm
  • Patients/caregivers should be informed of the potential to develop irreversible hepatic dysfunction with long-term
  • PTU therapy
    • Obtaining a written consent prior to initiation of PTU therapy is advised

Symptomatic Management
Beta-Blockers

  • Eg Propanolol, Atenolol, Metoprolol, Nadolol
  • Recommended for symptomatic treatment of hyperthyroidism especially in children with a heart rate (HR) of >100 bpm
  • Contraindicated in hyperthyroidism patients w/ bronchospastic asthma
    • Nadolol may be given to asthmatic hyperthyroidism patients w/ mild chronic obstructive pulmonary disease (COPD), symptomatic Raynaud’s phenomenon, or those whom HR control is essential
  • Atenolol is the most used beta-blocker because of its cardioselective property, thus less risk for bronchospasm
  • Esmolol is preferred over other beta-blockers for older intensive care unit (ICU) patients w/ thyroid storm/severe thyrotoxicosis

Surgical Intervention

  • Patients may undergo near-total or total thyroidectomy
  • Effects: Up to 97% cure rate when performed by experienced surgeons
  • Indications:
    • Sufficient cooperation for medical therapy is not possible
    • Adequate trial of antithyroid agents has failed to cause permanent remission
    • Intolerance to severe side effects of antithyroid drugs
    • Large thyroid gland size (>80 g)
    • Need for immediate disease control
    • <5 years of age
    • For very young patients intolerant to radioactive iodine therapy
  • Potential complications: Hypoparathyroidism, recurrent laryngeal nerve paralysis, hemorrhage, hypocalcemia
  • Iodine therapy rather than surgery is more advisable for patients with thyroid enlargement of >80 g

Prior to Surgery

  • Restoration of euthyroidism
    • Antithyroid drug treatment over 1-2 months prior to surgery
    • Iodide (eg saturated solution of potassium iodide) is added in the regimen x 10 days prior to surgery; given to decrease the vascularity of the thyroid gland

Permanent Hypothyroidism

  • If patient becomes hypothyroid, T4 replacement may be considered

Radiotherapy

  • Effective & relatively safe in patients >10 years
    • May be considered in patients 5-10 years old but caution during duration of therapy is recommended
  • Main goal is to induce hypothyroidism; may be considered in patients who relapse after medical therapy
  • A single therapeutic dose of RAI 200-300 μCi/g of thyroid tissue is recommended
  • Consider pretreatment with β-adrenergic blockade & antithyroid agents in asymptomatic patients with Graves’disease at increased risk for complications caused by exacerbation or worsening of hyperthyroidism
  • Patients may expect long-term thyroid replacement with thyroxine (T4)
  • Frequency of radioactive iodine therapy is reduced due to theoretical risk of malignancy or genetic damage
  • Instructions on radiation safety precautions immediately following treatment
    • Close & prolonged physical contact with other people should be avoided for 3 days
    • Caregiver is advised to have the patient take a break from daycare or school for 2 weeks

Ophthalmopathy

  • Usually resolves gradually & independently of hyperthyroidism
    • May resolve when patient becomes euthyroid
  • Some symptoms may not resolve especially if the symptoms are caused by autoimmune reaction against fibroblasts or muscles of the orbit
  • May be treated w/ high-dose Prednisone
  • Surgical decompression of orbits or orbital radiotherapy may also be done
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