Graves' disease hyperthyroidism medical therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1],Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

Overview

Antithyroid drugs are the first line treatment in Europe but ablation therapy either by thyroidectomy or radioactive iodine is more accepted in North America.

Hyperthyroidism Therapy

Genreral aspects

In a small proportion of patients, spontaneous remission occurs.
Smoking cessation is one of the mainstay of treatment.
Antithyroid drugs are the first line treatment in Europe.
Ablation therapy either by thyroidectomy or radioactive iodine is more accepted in North America.
Each treatment approach has advantages and drawbacks. The patient’s preference after receiving adequate counseling, remains a critical factor in therapy decisions.

The following table summarizes the medical therapy and surgical option for treatment.

Treatment	Mechanism	Route of administration	Advantages	Disadvantages	Special considerations
Beta-blockers	Block β-adrenergic receptors; propranolol may block conversion of T4 to T3	Oral; may be administered intravenously in acute cases	Ameliorates sweating, anxiety, tremulousness, palpitations, and tachycardia	Does not influence course of disease Use cautiously in patients with asthma, CHF , bradyarrhythmias or Raynaud’s phenomenon	Use cardioselective beta-blockers, especially in patients with COPD Use calcium-channel blockers as alternative
Antithyroid drugs (methimazole, carbimazole, and propylthiouracil)	Methimazole, carbimazole, and propylthiouracil block thyroid peroxidase and thyroid hormone synthesis propylthiouracil also blocks conversion of thyroxine to triiodothyronine	Given as either a single, high fixed dose (e.g., 10–30 mg of methimazole or 200–600 mg of propylthiouracil daily) and adjusted as euthyroidism is achieved or combined with thyroxine to prevent hypothyroidism (“block–replace” regimen)	Outpatient therapy Low risk of hypothyroidism No radiation hazard or surgical risk Remission rate 40–50%	High recurrence rate Frequent testing required unless block-replacement therapy is used Minor side effects in ≤5% of patients (rash, urticaria, arthralgia, fever, nausea, abnormalities of taste and smell)	Major side effect usually within first 3 mo of therapy Agranulocytosis in <0.2% of patients Hepatotoxicity in ≤0.1% Cholestasis for the thionamides and hepatocellular necrosis for propylthiouracil Antineutrophil cytoplasmic antibody–associated vasculitis in ≤0.1% of patients
Radioactive iodine (iodine-131)	Irradiation causes thyroid cell damage and cell death	Oral; activity either fixed (e.g., 15 mCi [555 MBq]) or calculated on the basis of goiter size and uptake and turnover investigations	Normally outpatient procedure Definitive therapy Low cost Few side effects Effectively reduces goiter size	Potential radiation hazards Adherence to a country’s particular radiation regulations Radiation thyroiditis Decreasing efficacy with increasing goiter size Eventual hypothyroidism in most patients	Should not be used in patients with active thyroid ophthalmopathy Contraindicated in women who are pregnant or breast-feeding and for 6 wk after breast-feeding has stopped
Thyroidectomy	Most or all thyroid tissue is removed surgically	—–	Rapid euthyroidism Recurrence extremely rare No radiation hazard, Definitive histologic results Rapid relief of pressure symptoms	Most expensive therapy Hypothyroidism is the aim Risks associated with surgery and anesthesiology Minor complications in 1–2% of patients (bleeding, infection, scarring), Major complications in 1–4% (hypoparathyroidism, recurrent laryngeal-nerve damage)	Does not influence course of Graves’ ophthalmopathy during pregnancy Is best performed during the second trimester

Antithyroid Drugs

Methimazole, carbimazole and propylthiouracil are the available anti thyroid drugs.
Methimazole is preferred for initial therapy in both Europe and North America because of its favorable side-effect profile.^[1]^[2]
Durable remission occurs in 40 to 50% of patients which is defined as euthroidism for at least 12 months following 1-2 years of treatment.
Patients may be switched from one drug to another when necessitated by minor side effects.
Monitoring by means of liver-function tests and white-cell counts before and during antithyroid drug therapy is advocated by some experts but is not currently supported by consensus opinion.

Radioactive Iodine

Radioactive iodine therapy offers relief from symptoms of hyperthyroidism within weeks.
Radioiodine is not associated with an increased risk of cancer.^[3]
It can provoke or worsen ophthalmopathy.^[4]

References

↑ Burch HB, Burman KD, Cooper DS (2012). “A 2011 survey of clinical practice patterns in the management of Graves’ disease”. J. Clin. Endocrinol. Metab. 97 (12): 4549–58. doi:10.1210/jc.2012-2802. PMID 23043191.
↑ Bartalena L, Burch HB, Burman KD, Kahaly GJ (2016). “A 2013 European survey of clinical practice patterns in the management of Graves’ disease”. Clin. Endocrinol. (Oxf). 84 (1): 115–20. doi:10.1111/cen.12688. PMID 25581877.
↑ Ron E, Doody MM, Becker DV, Brill AB, Curtis RE, Goldman MB, Harris BS, Hoffman DA, McConahey WM, Maxon HR, Preston-Martin S, Warshauer ME, Wong FL, Boice JD (1998). “Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group”. JAMA. 280 (4): 347–55. PMID 9686552.
↑ Bartalena L, Tanda ML (2009). “Clinical practice. Graves’ ophthalmopathy”. N. Engl. J. Med. 360 (10): 994–1001. doi:10.1056/NEJMcp0806317. PMID 19264688.

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[pmid23043191-1] Burch HB, Burman KD, Cooper DS (2012). “A 2011 survey of clinical practice patterns in the management of Graves’ disease”. J. Clin. Endocrinol. Metab. 97 (12): 4549–58. doi:10.1210/jc.2012-2802. PMID 23043191.

[pmid25581877-2] Bartalena L, Burch HB, Burman KD, Kahaly GJ (2016). “A 2013 European survey of clinical practice patterns in the management of Graves’ disease”. Clin. Endocrinol. (Oxf). 84 (1): 115–20. doi:10.1111/cen.12688. PMID 25581877.

[pmid9686552-3] Ron E, Doody MM, Becker DV, Brill AB, Curtis RE, Goldman MB, Harris BS, Hoffman DA, McConahey WM, Maxon HR, Preston-Martin S, Warshauer ME, Wong FL, Boice JD (1998). “Cancer mortality following treatment for adult hyperthyroidism. Cooperative Thyrotoxicosis Therapy Follow-up Study Group”. JAMA. 280 (4): 347–55. PMID 9686552.

[pmid19264688-4] Bartalena L, Tanda ML (2009). “Clinical practice. Graves’ ophthalmopathy”. N. Engl. J. Med. 360 (10): 994–1001. doi:10.1056/NEJMcp0806317. PMID 19264688.

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