High TSH with Normal T4: Subclinical Hypothyroidism
A high TSH with normal T4 indicates subclinical hypothyroidism, which requires levothyroxine treatment when TSH is persistently >10 mIU/L or when patients are symptomatic at any TSH elevation. 1
Diagnostic Confirmation
Before initiating treatment, confirm the diagnosis with repeat testing after 2-3 months, as 30-60% of elevated TSH levels normalize spontaneously. 1, 2 This step is critical to avoid unnecessary lifelong treatment for transient thyroid dysfunction. 1
Measure both TSH and free T4 on repeat testing to distinguish subclinical hypothyroidism (elevated TSH, normal free T4) from overt hypothyroidism (elevated TSH, low free T4). 1 Additionally, check thyroid peroxidase (TPO) antibodies, as positive antibodies indicate autoimmune etiology and predict higher progression risk to overt hypothyroidism (4.3% per year versus 2.6% in antibody-negative patients). 1, 3
Treatment Algorithm Based on TSH Level
TSH >10 mIU/L with Normal Free T4
Initiate levothyroxine therapy regardless of symptoms. 1, 4, 3 This threshold carries approximately 5% annual risk of progression to overt hypothyroidism, and treatment may prevent complications in patients who progress. 1
TSH 4.5-10 mIU/L with Normal Free T4
Treatment decisions should be individualized based on specific clinical factors:
Symptomatic patients: Consider a 3-4 month trial of levothyroxine for those with fatigue, weight gain, cold intolerance, or constipation. 5, 1, 3 If symptoms do not improve after achieving normal TSH, discontinue therapy. 3
Pregnant women or those planning pregnancy: Treat aggressively to normalize TSH, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring. 1, 4
Positive TPO antibodies: Consider treatment due to higher progression risk. 1, 4
Asymptomatic patients without risk factors: Monitor TSH every 6-12 months without treatment. 1, 3
Special Population Considerations
Elderly patients (>70-85 years): Use a conservative approach with watchful waiting for TSH ≤10 mIU/L, as treatment benefits are less clear and risks of overtreatment increase with age. 1, 3 If treatment is necessary, start with lower doses (25-50 mcg/day). 1, 4
Levothyroxine Dosing and Monitoring
Initial Dosing
Patients <70 years without cardiac disease: Start with full replacement dose of approximately 1.6 mcg/kg/day. 1
Patients >70 years or with cardiac disease: Start with 25-50 mcg/day and titrate gradually to avoid exacerbating cardiac symptoms. 1, 4, 2
Monitoring Protocol
Recheck TSH and free T4 every 6-8 weeks after any dose adjustment. 1, 6 TSH normalization may lag behind T4 normalization by several weeks, so avoid adjusting doses too frequently before reaching steady state. 6 Target TSH should be 0.5-2.5 mIU/L in the lower half of the reference range. 4, 3
Once stable, monitor TSH annually or sooner if symptoms change. 1
Critical Pitfalls to Avoid
Never treat based on a single elevated TSH: Always confirm with repeat testing to avoid treating transient thyroiditis. 1, 2
Rule out adrenal insufficiency before starting thyroid hormone: In patients with suspected central hypothyroidism or hypophysitis, always start corticosteroids before levothyroxine to avoid precipitating adrenal crisis. 5, 1
Avoid overtreatment: Approximately 25% of patients on levothyroxine are inadvertently maintained on doses that suppress TSH, increasing risk for atrial fibrillation, osteoporosis, and fractures. 1, 4, 2
Consider recent iodine exposure: CT contrast can transiently affect thyroid function tests, so review recent imaging studies before making treatment decisions. 5, 1
Monitor for falling TSH across measurements: A declining TSH with normal or low T4 may suggest pituitary dysfunction (hypophysitis), requiring cortisol assessment. 5
Risks of Untreated Subclinical Hypothyroidism
Persistent TSH elevation >10 mIU/L is associated with adverse cardiovascular effects, including delayed cardiac relaxation and abnormal cardiac output. 1 Treatment may improve cardiac function and lower LDL cholesterol in these patients. 1