I have an elevated thyroid‑stimulating hormone (TSH); what does this indicate and how should it be evaluated and treated?

Elevated TSH: Evaluation and Management

For an elevated TSH, confirm the result with repeat testing in 3–6 weeks along with free T4 measurement, then initiate levothyroxine if TSH remains >10 mIU/L or if TSH is lower but the patient is symptomatic, pregnant, or has positive anti-TPO antibodies. 1

Initial Confirmation and Assessment

Before making any treatment decisions, you must confirm the elevated TSH is persistent:

• Repeat TSH and measure free T4 after 3–6 weeks, as 30–60% of elevated TSH values normalize spontaneously on repeat testing 1
• This confirmation step is critical because transient TSH elevations occur commonly during recovery from acute illness, after iodine exposure (such as CT contrast), or due to certain medications 1
• Measure both TSH and free T4 together to distinguish between subclinical hypothyroidism (elevated TSH with normal free T4) and overt hypothyroidism (elevated TSH with low free T4) 1

Diagnostic Workup

Once persistent elevation is confirmed:

• Check anti-TPO antibodies to identify autoimmune thyroiditis, which predicts higher progression risk to overt hypothyroidism (4.3% per year versus 2.6% in antibody-negative individuals) 1
• Review medication history for drugs that affect thyroid function, including lithium, amiodarone, and immune checkpoint inhibitors 1, 2
• Rule out adrenal insufficiency before starting levothyroxine, especially in patients with suspected central hypothyroidism, by measuring morning cortisol and ACTH—starting thyroid hormone before adequate corticosteroid coverage can precipitate life-threatening adrenal crisis 1, 3, 4

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L with Normal Free T4

Initiate levothyroxine therapy regardless of symptoms 1, 4:

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

TSH 4.5–10 mIU/L with Normal Free T4

Routine levothyroxine treatment is NOT recommended for asymptomatic patients, as randomized trials show no symptomatic benefit 1, 5:

However, consider treatment in specific situations 1:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation—offer a 3–4 month trial with clear evaluation of benefit 1
• Pregnant women or those planning pregnancy—treat any TSH elevation, targeting TSH <2.5 mIU/L in first trimester 1, 4
• Patients with positive anti-TPO antibodies (higher progression risk) 1
• Patients with goiter or infertility 1

Monitor without treatment by rechecking TSH every 6–12 months if none of the above criteria are met 1

Overt Hypothyroidism (Elevated TSH + Low Free T4)

Start levothyroxine immediately without delay to prevent cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration 1, 6

Levothyroxine Dosing Strategy

For Patients <70 Years Without Cardiac Disease

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1
• This allows more rapid normalization of thyroid function 1

For Patients >70 Years OR With Cardiac Disease/Comorbidities

• Start low at 25–50 mcg/day and titrate gradually 1, 4:
  • Rapid normalization can unmask or worsen cardiac ischemia 1
  • Increase by 12.5–25 mcg every 6–8 weeks based on TSH response 1
  • Target TSH 0.5–4.5 mIU/L, though slightly higher targets (up to 5–6 mIU/L) may be acceptable in very elderly patients 1

Special Dosing Considerations

• In patients with suspected adrenal insufficiency: Start hydrocortisone 20 mg morning and 10 mg afternoon for at least one week before initiating levothyroxine 1, 3
• In patients on immune checkpoint inhibitors: Even subclinical hypothyroidism warrants treatment consideration if fatigue or other complaints are present; continue immunotherapy in most cases 1

Monitoring Protocol

During Dose Titration

• Recheck TSH and free T4 every 6–8 weeks after any dose adjustment 1, 4
• This interval is necessary because levothyroxine requires 6–8 weeks to reach steady state 1
• Free T4 helps interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

After Achieving Target TSH

• Monitor TSH every 6–12 months once stable dose is established 1, 6
• Recheck sooner if symptoms change or clinical status alters 1
• Target TSH range is 0.5–4.5 mIU/L with normal free T4 1, 4

Critical Pitfalls to Avoid

Do Not Treat Based on Single Elevated TSH

• 30–60% of elevated TSH values normalize spontaneously—always confirm with repeat testing 1, 5
• Transient elevations are common during recovery from illness, thyroiditis, or after iodine exposure 1

Avoid Overtreatment

• Approximately 25% of patients on levothyroxine are unintentionally overtreated with suppressed TSH 1:
  • TSH <0.1 mIU/L increases risk of atrial fibrillation (3–5 fold), osteoporosis, fractures, and cardiovascular mortality 1
  • If TSH falls below 0.1 mIU/L, reduce levothyroxine by 25–50 mcg immediately 1
  • For TSH 0.1–0.45 mIU/L, decrease by 12.5–25 mcg, especially in elderly or cardiac patients 1

Never Start Thyroid Hormone Before Ruling Out Adrenal Insufficiency

• In patients with suspected central hypothyroidism or hypophysitis, always start corticosteroids before levothyroxine to prevent adrenal crisis 1, 3, 4

Recognize Age-Adjusted Reference Ranges

• Approximately 12% of persons aged ≥80 years have TSH >4.5 mIU/L without thyroid disease 1
• The upper limit of normal TSH shifts upward with age, reaching 7.5 mIU/L in patients over 80 1
• Treatment decisions in elderly patients should account for this physiologic shift 5

Special Populations

Pregnancy

• Treat any TSH elevation in pregnant women or those planning pregnancy 1, 4
• Target TSH <2.5 mIU/L in first trimester 1
• Levothyroxine requirements typically increase by 25–50% during pregnancy 1
• Untreated hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental effects in offspring 1

Elderly Patients (>85 Years)

• Limited evidence suggests treatment of subclinical hypothyroidism with TSH ≤10 mIU/L should probably be avoided in those aged >85 years 4
• Treatment may be harmful in elderly patients with subclinical hypothyroidism 5
• Use conservative dosing (25–50 mcg/day starting dose) if treatment is indicated 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 present 1
• Continue immunotherapy in most cases—thyroid dysfunction rarely requires treatment interruption 1

Unusual Pattern: Elevated TSH with Elevated T4

If both TSH and T4 are elevated (uncommon pattern) 2:

• Do not initiate levothyroxine—this does not represent typical hypothyroidism 2
• Confirm with repeat testing in 4–6 weeks, as 30–60% normalize spontaneously 2
• Consider assay interference, thyroid hormone resistance syndrome, recovery from non-thyroidal illness, or TSH-secreting pituitary adenoma 2
• If pattern persists, refer to endocrinology 2
• For symptomatic hyperthyroid features, beta-blockers may provide relief 2