What is the step‑by‑step algorithm for treating hyperthyroidism and hypothyroidism based on thyroid‑stimulating hormone and free thyroxine (and free triiodothyronine) results, including medication dosages, dose adjustments, follow‑up timing, additional laboratory tests to order, precautions, contraindications, and alternative treatment options?

Algorithm for Treating Hyperthyroidism and Hypothyroidism Based on Thyroid Panel Results

HYPOTHYROIDISM MANAGEMENT

Initial Diagnostic Confirmation

Confirm elevated TSH with repeat testing after 3–6 weeks before initiating treatment, as 30–60% of elevated TSH values normalize spontaneously. 1

• Measure both TSH and free T4 to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4) 1
• Check anti-TPO antibodies to identify autoimmune etiology—positive antibodies predict 4.3% annual progression to overt hypothyroidism versus 2.6% in antibody-negative patients 1
• Critical safety step: Before starting levothyroxine, measure morning cortisol and ACTH to exclude adrenal insufficiency, as initiating thyroid hormone before corticosteroid coverage can precipitate life-threatening adrenal crisis 1

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L with Normal Free T4 (Subclinical Hypothyroidism)

Initiate levothyroxine immediately regardless of symptoms, as this threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with cardiac dysfunction and adverse lipid profiles. 1

Initial dosing:

• Patients <70 years without cardiac disease: Start full replacement dose of 1.6 mcg/kg/day 1
• Patients >70 years OR with cardiac disease/multiple comorbidities: Start 25–50 mcg/day and titrate gradually by 12.5–25 mcg every 6–8 weeks 1
• Pregnant women or planning pregnancy: Treat immediately, targeting TSH <2.5 mIU/L in first trimester; increase pre-pregnancy dose by 25–50% upon pregnancy confirmation 1

TSH 4.5–10 mIU/L with Normal Free T4 (Mild Subclinical Hypothyroidism)

Routine levothyroxine treatment is NOT recommended for asymptomatic patients, as randomized controlled trials show no symptomatic benefit. 1

Consider treatment in specific situations:

• Symptomatic patients (fatigue, weight gain, cold intolerance, constipation)—offer 3–4 month trial with clear evaluation of benefit 1
• Pregnant women or planning pregnancy 1
• Positive anti-TPO antibodies (4.3% annual progression risk) 1
• Patients on immune checkpoint inhibitors with fatigue or hypothyroid symptoms 1

If not treating: Monitor TSH every 6–12 months 1

Overt Hypothyroidism (Elevated TSH + Low Free T4)

Initiate levothyroxine immediately without delay to prevent cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration. 1

Dosing same as above based on age and cardiac status 1

Dose Adjustments and Monitoring

Recheck TSH and free T4 every 6–8 weeks after any dose adjustment until TSH reaches target range of 0.5–4.5 mIU/L. 1

Dose adjustment increments:

• Standard patients: 12.5–25 mcg based on current dose 1
• Elderly or cardiac patients: Use smaller 12.5 mcg increments 1
• Never adjust doses more frequently than every 6–8 weeks—levothyroxine requires this interval to reach steady state 1

Once stable: Monitor TSH every 6–12 months or sooner if symptoms change 1

Additional Laboratory Tests

• Anti-TPO antibodies: Identifies autoimmune etiology and predicts progression risk 1
• Lipid panel: Subclinical hypothyroidism affects cholesterol levels 1
• Morning cortisol and ACTH: Mandatory before starting levothyroxine to exclude adrenal insufficiency 1
• Vitamin B12: Screen periodically in autoimmune thyroid disease patients 1
• Calcium and vitamin D: Ensure adequate intake (1200 mg/day calcium, 1000 units/day vitamin D) for patients on long-term therapy 1

Precautions and Contraindications

Absolute contraindication: Untreated adrenal insufficiency—always start hydrocortisone at least 1 week before levothyroxine in suspected central hypothyroidism or hypophysitis. 1

Cardiac precautions:

• Elderly patients with coronary disease risk cardiac decompensation, angina, or arrhythmias even with therapeutic doses 1
• Start 25–50 mcg/day in ALL patients with any cardiac disease regardless of age 1
• Obtain baseline ECG to screen for arrhythmias 1
• Monitor closely for angina, palpitations, or worsening heart failure 1

Drug interactions requiring dose separation:

• Take levothyroxine 30–60 minutes before food on empty stomach 1
• Separate by at least 4 hours from iron, calcium supplements, or antacids 1

Common Pitfalls to Avoid

• Do NOT treat based on single elevated TSH—confirm with repeat testing 1
• Do NOT start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1
• Do NOT use full replacement dose in elderly or cardiac patients—start low and titrate slowly 1
• Approximately 25% of patients are unintentionally overtreated with TSH fully suppressed, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications 1

Managing Overtreatment (TSH Suppression on Levothyroxine)

If TSH <0.1 mIU/L: Reduce levothyroxine by 25–50 mcg immediately 1

If TSH 0.1–0.45 mIU/L: Reduce by 12.5–25 mcg, especially in elderly or cardiac patients 1

Risks of prolonged TSH suppression:

• 3–5 fold increased risk of atrial fibrillation, especially in patients >60 years 1
• Accelerated bone loss and osteoporotic fractures, particularly in postmenopausal women 1
• Increased cardiovascular mortality 1

Recheck TSH and free T4 in 6–8 weeks after dose reduction 1

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HYPERTHYROIDISM MANAGEMENT

Initial Diagnostic Confirmation

Repeat TSH measurement along with free T4 and free T3 within 3–6 weeks to confirm persistent hyperthyroidism, as transient TSH suppression can occur. 2, 3

• For patients with cardiac disease, atrial fibrillation, or serious medical conditions: Repeat testing within 2 weeks rather than 3–6 weeks 1
• Establish etiology using radioactive iodine uptake and scan to distinguish Graves disease, toxic nodules, or destructive thyroiditis 2, 3
• Check TSH-receptor antibodies if Graves disease suspected 3

Treatment Algorithm Based on TSH and Free T4/T3 Levels

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

First-line treatment options are antithyroid drugs, radioactive iodine ablation, or thyroid surgery—treatment choices should be individualized based on etiology, patient age, comorbidities, and preferences. 3

Antithyroid medications (methimazole or propylthiouracil):

• Methimazole is preferred except in first trimester pregnancy or thyroid storm 3
• Monitor for agranulocytosis—instruct patients to report fever, sore throat, or mouth sores immediately 2
• Typical duration: 12–18 months for Graves disease 3

Radioactive iodine ablation:

• Definitive treatment for Graves disease and toxic nodules 3
• Contraindicated in pregnancy and breastfeeding 3
• Most patients become hypothyroid and require lifelong levothyroxine 3

Surgery (thyroidectomy):

• Indicated for large goiters causing compressive symptoms, suspected malignancy, or patient preference 3
• Requires lifelong levothyroxine replacement 3

Symptomatic management:

• Beta-blockers (propranolol 20–40 mg three times daily or atenolol 25–100 mg daily) for palpitations, tremor, anxiety 2, 3

Subclinical Hyperthyroidism (TSH <0.45 mIU/L + Normal Free T4 and T3)

Management depends on TSH level and patient risk factors:

TSH <0.1 mIU/L (Severe Subclinical Hyperthyroidism):

Treatment is strongly recommended, especially in patients >60 years, due to 3–5 fold increased risk of atrial fibrillation and up to 3-fold increased cardiovascular mortality. 2, 4

Additional high-risk features warranting treatment:

• Postmenopausal women with osteopenia/osteoporosis (significant bone mineral density loss and increased fracture risk) 2
• Pre-existing cardiac disease 2
• Symptoms of hyperthyroidism (palpitations, tremor, weight loss, heat intolerance) 2

Treatment options same as overt hyperthyroidism based on etiology 2

TSH 0.1–0.45 mIU/L (Mild Subclinical Hyperthyroidism):

Routine treatment with antithyroid medications is NOT recommended, as evidence does not establish clear association between this mild degree of hyperthyroidism and adverse clinical outcomes. 2

Management approach:

• Repeat thyroid function tests at 3–12 month intervals until TSH normalizes or condition stabilizes 2
• 50% of patients with TSH 0.1–0.45 mIU/L normalize spontaneously 2
• Consider treatment in elderly patients (>65 years) due to possible increased cardiovascular mortality 2

Treat immediately if:

• TSH falls below 0.1 mIU/L on repeat testing 2
• Development of atrial fibrillation or cardiac arrhythmias 2
• Symptomatic hyperthyroidism develops 2

Destructive Thyroiditis (Thyrotoxic Phase)

Antithyroid drugs are NOT indicated—thyroiditis typically resolves spontaneously and often progresses to hypothyroidism. 2, 3

Management:

• Symptomatic treatment with beta-blockers if needed 2
• Monitor thyroid function every 3–6 months for progression to hypothyroidism 2
• Do NOT use antithyroid drugs empirically without establishing etiology, as destructive thyroiditis will not respond and unnecessarily exposes patients to drug risks including agranulocytosis 2

Monitoring During Treatment

For patients on antithyroid drugs:

• Check TSH, free T4, and free T3 every 4–6 weeks initially until euthyroid 3
• Once stable, monitor every 3–6 months 3
• Instruct patients to report fever, sore throat, or mouth sores immediately due to agranulocytosis risk 2

For patients post-radioactive iodine or surgery:

• Most become hypothyroid—monitor TSH and free T4 every 6–8 weeks initially 3
• Once stable on levothyroxine, monitor every 6–12 months 1

Additional Laboratory Tests

• TSH-receptor antibodies: Confirms Graves disease 3
• Radioactive iodine uptake and scan: Distinguishes Graves disease (diffuse uptake), toxic nodules (focal uptake), or thyroiditis (low uptake) 2, 3
• Complete blood count: Baseline before starting antithyroid drugs and if fever/sore throat develops 2
• Liver function tests: Baseline before antithyroid drugs 3
• ECG: Screen for atrial fibrillation, especially in patients >60 years with TSH <0.1 mIU/L 2
• Bone density scan: Consider in postmenopausal women with persistent TSH <0.1 mIU/L 2

Precautions and Contraindications

Antithyroid drugs:

• Agranulocytosis risk (0.2–0.5%)—instruct patients to stop medication and seek immediate medical attention for fever, sore throat, or mouth sores 2, 3
• Hepatotoxicity (more common with propylthiouracil) 3
• Contraindicated in severe liver disease 3

Radioactive iodine:

• Absolute contraindication in pregnancy and breastfeeding 3
• Avoid in patients with active Graves ophthalmopathy (may worsen eye disease) 3
• Caution with iodine exposure (CT contrast) in patients with nodular thyroid disease—may precipitate overt hyperthyroidism 2

Common Pitfalls to Avoid

• Do NOT treat subclinical hyperthyroidism based on single TSH measurement—confirm with repeat testing in 3–6 weeks 2
• Do NOT use antithyroid drugs for destructive thyroiditis—it will not respond and exposes patients to unnecessary drug risks 2
• Do NOT ignore cardiac symptoms—even mild palpitations warrant immediate evaluation, as subclinical hyperthyroidism increases atrial fibrillation risk 2.8–5 fold when TSH <0.1 mIU/L 2
• Do NOT delay treatment if TSH <0.1 mIU/L in patients >60 years—this threshold represents significantly higher cardiovascular and bone risks 2

Alternative Treatment Options

For patients who cannot tolerate or refuse standard treatments:

• Beta-blockers alone for symptomatic management (does not treat underlying hyperthyroidism) 2, 3
• Observation with close monitoring if mild subclinical hyperthyroidism (TSH 0.1–0.45 mIU/L) in low-risk patients 2

For Graves disease specifically:

• Antithyroid drugs for 12–18 months achieve remission in 30–50% of patients 3
• If relapse after medication course, radioactive iodine or surgery recommended 3