What target serum thyroid‑stimulating hormone (TSH) range should be aimed for in an adult who develops hypothyroidism after neck or head‑and‑neck radiation, and how should it be adjusted for coronary artery disease, congestive heart failure, or age over 65?

Target TSH for Post-Radiation Hypothyroidism

For adults who develop hypothyroidism after head or neck radiation, target a TSH of 0.5–4.5 mIU/L with normal free T4, using the same replacement goals as primary hypothyroidism—but adjust the starting dose and titration speed based on age, cardiac disease, and heart failure status. 1

Standard TSH Target Range

• The goal TSH is 0.5–4.5 mIU/L for all patients with post-radiation hypothyroidism, identical to the target for primary hypothyroidism from other causes 1, 2
• This range applies whether the patient has overt hypothyroidism (elevated TSH with low free T4) or subclinical hypothyroidism (elevated TSH with normal free T4) 1
• Free T4 should be maintained within the normal reference range alongside normalized TSH 1

Adjustments for Cardiac Disease

Coronary Artery Disease (CAD)

• Start levothyroxine at 25–50 mcg/day in patients with known CAD, regardless of age, to avoid unmasking cardiac ischemia or precipitating myocardial infarction 1
• Titrate slowly by 12.5–25 mcg increments every 6–8 weeks until TSH reaches 0.5–4.5 mIU/L 1
• Monitor closely for new or worsening angina, palpitations, dyspnea, or arrhythmias at each follow-up 1
• The same TSH target of 0.5–4.5 mIU/L applies, but the path to reach it must be gradual 1

Congestive Heart Failure (CHF)

• Use the same conservative starting dose of 25–50 mcg/day as for CAD patients 1
• Hypothyroidism worsens heart failure through bradycardia, decreased ventricular filling, decreased contractility, and increased systemic vascular resistance—so treatment is beneficial, but must be cautious 1
• Levothyroxine improves cardiovascular function and prognosis in heart failure patients with hypothyroidism 1
• Monitor for signs of overtreatment or cardiac decompensation, including worsening dyspnea or heart failure symptoms 1
• Target TSH remains 0.5–4.5 mIU/L, but avoid TSH suppression below 0.45 mIU/L, which increases atrial fibrillation risk 3–5 fold 1

Adjustments for Age Over 65

• For patients >70 years or >65 years with multiple comorbidities, start at 25–50 mcg/day even without overt cardiac disease 1
• Elderly patients are at higher risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses 1
• Use smaller dose increments (12.5 mcg) every 6–8 weeks rather than 25 mcg jumps 1
• The TSH target of 0.5–4.5 mIU/L is unchanged, though slightly higher targets (up to 5–6 mIU/L) may be acceptable in very elderly patients to avoid overtreatment risks, but this is not standard practice 1
• Approximately 12% of persons aged ≥80 years have TSH >4.5 mIU/L without thyroid disease, so age-adjusted interpretation is important 1

Combined Risk Factors (Age >65 + CAD or CHF)

• When multiple risk factors coexist, use the most conservative approach: start at 25 mcg/day and increase by 12.5 mcg every 6–8 weeks 1
• Consider repeating thyroid function tests within 2 weeks (rather than 6–8 weeks) after dose adjustment in patients with atrial fibrillation, cardiac disease, or serious medical conditions 1
• The TSH target remains 0.5–4.5 mIU/L, but reaching it safely takes precedence over speed 1

Monitoring Protocol

• Check TSH and free T4 every 6–8 weeks during dose titration until TSH reaches the target range 1
• Once stable, repeat 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

Post-Radiation Specific Considerations

Incidence and Timing

• Hypothyroidism occurs in 26–51% of patients at 10 years after head and neck radiation 3, 4
• Onset may be as early as 4 weeks or as late as 5–10 years post-treatment 5
• Check TSH every 6 months for the first 5 years, then yearly thereafter in all patients who received neck radiation 3, 6

Treatment Threshold

• Initiate levothyroxine for any TSH >4.5 mIU/L after radiation, regardless of symptoms 3, 6
• This is the same threshold as primary hypothyroidism, but surveillance must be more vigilant given the high incidence 3

Risk Factors for Post-Radiation Hypothyroidism

• Whole thyroid in radiation field increases risk compared to partial thyroid irradiation 4, 7
• Laryngectomy significantly increases risk of both clinical and subclinical hypothyroidism 4
• Stage 3 or 4 cancer is associated with higher hypothyroidism rates (odds ratio 5.0) 7
• **V50Gy <75%** (i.e., keeping >75% of thyroid volume below 50 Gy) may reduce hypothyroidism risk 7

Critical Pitfalls to Avoid

• Never start at full replacement dose (1.6 mcg/kg/day) in elderly patients or those with cardiac disease—this can precipitate myocardial infarction, heart failure, or fatal arrhythmias 1
• Do not ignore suppressed TSH (<0.1 mIU/L) during treatment—this increases atrial fibrillation risk 3–5 fold, especially in elderly patients, and increases fracture risk in postmenopausal women 1
• Avoid adjusting doses too frequently—wait 6–8 weeks between adjustments to reach steady state 1
• Do not assume hypothyroidism is permanent without reassessment—30–60% of elevated TSH values normalize spontaneously, though this is less common in post-radiation cases 1
• Approximately 25% of patients on levothyroxine are unintentionally overtreated with fully suppressed TSH, increasing serious complication risks 1

Algorithm Summary

1. Confirm hypothyroidism: TSH >4.5 mIU/L with or without low free T4 1, 3
2. Assess cardiac and age risk:
   • Age >70 OR cardiac disease OR CHF → start 25–50 mcg/day 1
   • Age <70 AND no cardiac disease → start 1.6 mcg/kg/day (full replacement) 1
3. Titrate cautiously:
   • High-risk patients: increase by 12.5–25 mcg every 6–8 weeks 1
   • Low-risk patients: increase by 25 mcg every 6–8 weeks 1
4. Target TSH 0.5–4.5 mIU/L with normal free T4 in all cases 1
5. Monitor TSH/free T4 every 6–8 weeks until stable, then every 6–12 months 1
6. Reduce dose if TSH <0.1 mIU/L (by 25–50 mcg) or TSH 0.1–0.45 mIU/L (by 12.5–25 mcg) to avoid cardiac and bone complications 1