How do I treat a patient with a thyroid disorder?

Treatment of Thyroid Disorders

Initial Diagnostic Approach

Measure TSH as the first-line test, followed by free T4 to distinguish between subclinical and overt thyroid dysfunction. 1

• TSH has a sensitivity above 98% and specificity greater than 92% for detecting thyroid dysfunction 1
• If TSH is elevated with low free T4, this indicates overt hypothyroidism requiring immediate treatment 1
• If TSH is elevated with normal free T4, this indicates subclinical hypothyroidism requiring risk stratification 1, 2
• If TSH is suppressed with elevated free T4, this indicates overt hyperthyroidism requiring treatment 3, 4
• If TSH is suppressed with normal free T4, this indicates subclinical hyperthyroidism requiring monitoring 1

Always confirm abnormal TSH with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously. 1, 2

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Treatment of Hypothyroidism

Overt Hypothyroidism (Elevated TSH + Low Free T4)

Initiate levothyroxine immediately for all patients with overt hypothyroidism. 1, 5

Critical Safety Precaution

Before starting levothyroxine, rule out concurrent adrenal insufficiency by checking morning cortisol and ACTH, especially in suspected central hypothyroidism or hypophysitis, as thyroid hormone can precipitate life-threatening adrenal crisis. 1

• If adrenal insufficiency is present, start hydrocortisone 20 mg in the morning and 10 mg in the afternoon for at least one week before initiating levothyroxine 1

Dosing Strategy

For patients <70 years without cardiac disease:

• Start with full replacement dose of approximately 1.6 mcg/kg/day based on ideal body weight 1, 2
• This rapidly normalizes thyroid function and prevents complications 1

For patients >70 years OR with cardiac disease:

• Start with 25-50 mcg/day 1, 2
• Increase by 12.5-25 mcg every 6-8 weeks based on TSH response 1
• Rapid normalization can unmask or worsen cardiac ischemia in patients with coronary artery disease 1

Administration:

• Take as a single daily dose on an empty stomach, 30-60 minutes before breakfast with a full glass of water 6
• Separate from iron, calcium supplements, and antacids by at least 4 hours 1, 6

Monitoring

Recheck TSH and free T4 every 6-8 weeks during dose titration until TSH reaches target range of 0.5-4.5 mIU/L. 1

• Once stable, monitor TSH every 6-12 months or sooner if symptoms change 1
• Free T4 helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

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Subclinical Hypothyroidism (Elevated TSH + Normal Free T4)

TSH >10 mIU/L

Initiate levothyroxine therapy regardless of symptoms for all patients with confirmed TSH >10 mIU/L. 1, 2, 5

• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1, 2
• Treatment may improve symptoms and lower LDL cholesterol 1
• Evidence quality is rated as "fair" by expert panels 1

Dosing follows the same strategy as overt hypothyroidism based on age and cardiac status. 1, 2

TSH 4.5-10 mIU/L

Routine levothyroxine treatment is NOT recommended for asymptomatic patients with TSH 4.5-10 mIU/L, as randomized controlled trials show no symptomatic benefit. 1, 2

Instead, monitor TSH and free T4 every 6-12 months. 1, 2

Consider treatment in these specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation: offer a 3-4 month trial of levothyroxine with clear evaluation of benefit 1, 2
• Pregnant women or those planning pregnancy: treat any TSH elevation, targeting TSH <2.5 mIU/L in the first trimester 1, 2
• Positive anti-TPO antibodies: these patients have 4.3% annual progression risk versus 2.6% in antibody-negative individuals 1, 2
• Patients with goiter or infertility: treatment may be beneficial 5

Special Populations

Elderly patients >85 years:

• Treatment of subclinical hypothyroidism with TSH up to 10 mIU/L should probably be avoided 5
• The normal TSH reference range shifts upward with age, reaching 7.5 mIU/L in patients over 80 1

Patients on immune checkpoint inhibitors:

• Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy 1
• Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms are present 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1

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Treatment of Hyperthyroidism

Overt Hyperthyroidism (Suppressed TSH + Elevated Free T4/T3)

Three treatment modalities are available: antithyroid drugs, radioiodine, and surgery. 7, 4

Graves' Disease (70% of hyperthyroidism cases)

First-line treatment is antithyroid drugs (methimazole or propylthiouracil) for 12-18 months. 7, 4

• Recurrence occurs in approximately 50% of patients after stopping antithyroid drugs 4
• Risk factors for recurrence include: age <40 years, FT4 ≥40 pmol/L, TSH-binding inhibitory immunoglobulins >6 U/L, and goiter size ≥WHO grade 2 4
• Long-term treatment (5-10 years) is associated with fewer recurrences (15%) than short-term treatment (12-18 months) 4

Radioiodine (¹³¹I) is preferred after failure of antithyroid drugs or when surgery is contraindicated. 3, 7

• The goal is to induce hypothyroidism, which is readily treatable with levothyroxine 3
• Avoid in pregnancy, lactation, and for 4 months before planned pregnancy 7
• May worsen Graves' ophthalmopathy; corticosteroid cover may reduce this risk 7

Surgery (subtotal or near-total thyroidectomy) has limited roles:

• Large goiter causing compressive symptoms 7
• Radioiodine refused or contraindicated 7

Toxic Nodular Goiter (16% of hyperthyroidism cases)

Radioiodine is the treatment of choice. 3, 7, 4

• The goal is to achieve euthyroid status 3
• Antithyroid drugs will not cure toxic nodular goiter 7
• Surgery is an alternative if radioiodine is contraindicated 4

Destructive Thyroiditis (3% of cases)

Usually mild and transient, requiring steroids only in severe cases. 4

• Includes subacute granulomatous thyroiditis and drug-induced thyroiditis 4
• Treatment is typically not recommended when thyroiditis is the cause 8

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Management of Iatrogenic Thyroid Dysfunction

Overtreatment with Levothyroxine (TSH <0.1 mIU/L)

Reduce levothyroxine dose by 25-50 mcg immediately if TSH <0.1 mIU/L. 1

Risks of prolonged TSH suppression include:

• Atrial fibrillation (3-5 fold increased risk, especially in patients >60 years) 1
• Osteoporosis and fractures (particularly in postmenopausal women) 1
• Increased cardiovascular mortality 1
• Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 1

For TSH 0.1-0.45 mIU/L:

• Reduce dose by 12.5-25 mcg, particularly in elderly or cardiac patients 1

Exception: Thyroid cancer patients may require intentional TSH suppression:

• Low-risk patients with excellent response: target TSH 0.5-2 mIU/L 1
• Intermediate-to-high risk patients with biochemical incomplete response: target TSH 0.1-0.5 mIU/L 1
• Structural incomplete response: target TSH <0.1 mIU/L 1
• Consult with endocrinologist before dose adjustment in thyroid cancer patients 1

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Common Pitfalls to Avoid

Do not treat based on a single abnormal TSH value—confirm with repeat testing after 3-6 weeks. 1, 2

Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism, as this can precipitate adrenal crisis. 1

Avoid overtreatment, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, fractures, and cardiac complications. 1, 2

Do not ignore suppressed TSH in elderly patients with osteoporotic fractures—this is a direct cause-and-effect relationship requiring immediate dose reduction. 1

Recognize transient causes of TSH elevation: acute illness, recent iodine exposure (CT contrast), recovery from thyroiditis, or certain medications (lithium, amiodarone, interferon). 1

For pregnant women with hypothyroidism, increase levothyroxine dose by 25-50% immediately upon pregnancy confirmation, as requirements increase during pregnancy. 1