What are the treatment options for thyroid dysfunction, including Graves disease (hyperthyroidism) and Hashimoto thyroiditis (hypothyroidism)?

Treatment of Thyroid Dysfunction: Graves Disease to Hashimoto's Thyroiditis

Hypothyroidism (Hashimoto's Thyroiditis)

Levothyroxine monotherapy is the standard treatment for hypothyroidism, administered as a single daily dose on an empty stomach, one-half to one hour before breakfast 1.

Initial Treatment Decision Algorithm

For TSH >10 mIU/L (regardless of free T4):

• Initiate levothyroxine therapy immediately, regardless of symptoms 1
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
• Treatment may improve symptoms and lower LDL cholesterol 1

For TSH 4.5-10 mIU/L with normal free T4 (subclinical hypothyroidism):

• Routine levothyroxine treatment is NOT recommended for asymptomatic patients 1
• Monitor thyroid function tests every 6-12 months 1
• Consider treatment in specific situations:
  • Symptomatic patients (fatigue, weight gain, cold intolerance, constipation) 1
  • Pregnant women or those planning pregnancy 1
  • Positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk) 1, 2
  • Patients with goiter or infertility 1

For overt hypothyroidism (elevated TSH AND low free T4):

• Start levothyroxine without delay to prevent cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration 1

Levothyroxine Dosing Strategy

For patients <70 years without cardiac disease:

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1
• More aggressive titration is appropriate using 25 mcg increments 1

For patients >70 years OR with cardiac disease/multiple comorbidities:

• Start with lower dose of 25-50 mcg/day 1
• Titrate gradually using smaller increments (12.5 mcg) to avoid cardiac complications 1
• Elderly patients with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic doses 1

Critical Safety Considerations

Before initiating levothyroxine, rule out concurrent adrenal insufficiency 1:

• Starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1
• In suspected central hypothyroidism or hypophysitis, always start physiologic dose steroids 1 week prior to thyroid hormone replacement 1
• Obtain morning (≈8 AM) serum cortisol and ACTH measurement before starting levothyroxine 1

Monitoring Protocol

During dose titration:

• Monitor TSH every 6-8 weeks while adjusting hormone replacement 1
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1
• Adjust dose by 12.5-25 mcg increments based on patient's current dose and clinical characteristics 1

Once adequately treated:

• Repeat testing every 6-12 months or if symptoms change 1
• Target TSH within reference range (0.5-4.5 mIU/L) with normal free T4 levels 1

Special Population: Pregnancy

For women planning pregnancy or currently pregnant:

• Treat any TSH elevation immediately, targeting TSH <2.5 mIU/L in first trimester 1
• Levothyroxine requirements typically increase by 25-50% during pregnancy 1
• Check TSH and free T4 every 4 weeks until stable, then at minimum once per trimester 1
• Untreated maternal hypothyroidism increases risk of preeclampsia, low birth weight, and permanent neurodevelopmental deficits in the child 1

Common Pitfalls to Avoid

• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1
• Do not treat based on a single elevated TSH value, as 30-60% normalize on repeat testing 1
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1
• Overtreatment occurs in 14-21% of treated patients and increases risk for serious complications 1

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Hyperthyroidism (Graves Disease)

Three main treatment options exist for Graves disease: antithyroid drugs (ATD), radioactive iodine (RAI), and surgery 3, 4, 5.

Antithyroid Drug Therapy

First-line pharmacologic options:

• Methimazole (MMI) is preferred over propylthiouracil (PTU) for most patients 3, 5
• MMI has longer half-life allowing once-daily dosing, improving adherence 3
• Propylthiouracil is indicated 6:
  • In patients intolerant of methimazole 6
  • For whom surgery or radioactive iodine is not appropriate 6
  • To ameliorate symptoms in preparation for thyroidectomy or RAI in methimazole-intolerant patients 6
  • Historically preferred for pregnant and breast-feeding women due to limited placental and breast milk transfer 3

Treatment duration and outcomes:

• A 12- to 18-month course of antithyroid drugs may lead to remission in approximately 50% of patients 5
• Fewer than 50% of patients treated with ATD remain in long-term remission 7
• Adverse reactions typically occur within the first 90 days of therapy, including agranulocytosis and hepatotoxicity 5

Radioactive Iodine (RAI) Therapy

RAI has become the preferred treatment for adults with Graves disease in the US 3, 5:

• Easy to administer, safe, effective, and more affordable than long-term ATD treatment 3
• Well tolerated with only long-term sequela being risk of radioiodine-induced hypothyroidism 4
• Can be used in all age groups except children 4

Contraindications and precautions:

• Contraindicated in pregnancy (can damage fetal thyroid causing fetal hypothyroidism) 3, 4
• Should be avoided during lactation 4
• Pregnancy should be avoided for 4 months following administration 4
• May cause deterioration in Graves' ophthalmopathy in approximately 15-20% of patients 4, 5
• Corticosteroid cover may reduce risk of ophthalmopathy worsening 4

RAI is the treatment of choice for toxic nodular goiter hyperthyroidism 4.

Surgical Management

Surgery (bilateral subtotal or near-total thyroidectomy) has limited but specific roles 3, 4, 5:

• Patients with concomitant suspicious or malignant thyroid nodules 5
• Coexisting hyperparathyroidism 5
• Large goiters causing compressive symptoms in the neck 4, 5
• Moderate to severe thyroid eye disease in patients who cannot be treated with ATD 5
• Patients who refuse radioiodine 4

Potential complications:

• Laryngeal nerve damage 3
• Hypoparathyroidism 3, 5
• Hypothyroidism 3
• Vocal cord paralysis 5

Adjunctive Therapies

Beta-blockers:

• Used to decrease symptoms of hyperthyroidism 3
• Do not treat underlying disease but provide symptomatic relief 3

Inorganic iodide:

• Primarily used to prepare patients for thyroid surgery 3
• Decreases vascularity of the thyroid gland 3

Lithium:

• Acts in manner similar to iodine 3
• Not routinely used due to transient effect and risk of potentially serious adverse effects 3

Treatment Selection Algorithm

The optimal approach depends on 5:

• Patient preference 5
• Age 5
• History of arrhythmia or ischemic heart disease 5
• Size of goiter 5
• Severity of thyrotoxicosis 5
• Geography 5

Surgery is favored when:

• Concomitant suspicious/malignant thyroid nodules present 5
• Coexisting hyperparathyroidism 5
• Large goiters or moderate to severe thyroid eye disease in patients who cannot receive ATD 5

RAI is increasingly used as first-line therapy 3, 7:

• Growing use as first-line therapy for hyperthyroidism 4
• Preferred in US for adults with Graves disease 3

ATD may be preferred when:

• Patient desires to avoid radiation exposure 7
• Patient wants to avoid invasive procedures 8
• Goal is to normalize thyroid function quickly without causing hypothyroidism 8
• Desire to ameliorate immune disorder 8

Important Considerations

• No single treatment method offers an absolute cure 3, 4
• ATD will not 'cure' hyperthyroidism associated with toxic nodular goiter 4
• Treating Graves disease with RAI and surgery results in gland destruction or removal, necessitating life-long levothyroxine replacement 5
• In pregnancy, antithyroid drugs are the primary therapy, but some women opt for definitive therapy with RAI or surgery prior to becoming pregnant to avoid potential teratogenic effects of ATD during pregnancy 5