When to start thyroxin (levothyroxine) in patients with subclinical hypothyroidism (elevated Thyroid Stimulating Hormone (TSH) level < 10)?

Indications for Starting Thyroxine When TSH is <10 mIU/L

Start levothyroxine for subclinical hypothyroidism (TSH <10 mIU/L) in pregnant women, women planning pregnancy, symptomatic patients with TSH 7-10 mIU/L, and patients with positive anti-TPO antibodies plus goiter or symptoms. For asymptomatic patients with TSH 4.5-10 mIU/L without these features, monitor every 6-12 months rather than treat. 1

Confirm the Diagnosis First

Before considering treatment, confirm the elevated TSH with repeat testing after 2-3 months, as 30-60% of elevated TSH levels normalize spontaneously. 1, 2, 3 Measure both TSH and free T4 to distinguish subclinical hypothyroidism (normal free T4) from overt hypothyroidism (low free T4). 1

Treatment Algorithm Based on TSH Level and Clinical Context

TSH 7-10 mIU/L

• Treat if the patient has symptoms suggestive of hypothyroidism (fatigue, weight gain, cold intolerance, constipation) with a 3-4 month trial of levothyroxine. 1, 3, 4
• Treat if positive anti-TPO antibodies are present, as this indicates a 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative patients. 1, 5
• Treat all pregnant women or women planning pregnancy regardless of symptoms, as subclinical hypothyroidism is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring. 1, 5
• For asymptomatic patients without antibodies, monitor TSH every 6-12 months rather than initiating treatment, as randomized trials show no symptom improvement with levothyroxine in this group. 1, 4

TSH 4.5-7 mIU/L

• Do not routinely treat asymptomatic patients in this range, as evidence shows no benefit from levothyroxine therapy. 1, 3, 4
• Consider treatment only for pregnant women, women planning pregnancy, or symptomatic patients with positive anti-TPO antibodies and goiter. 1, 5
• Monitor TSH every 6-12 months to detect progression. 1

Special Populations Requiring Different Approaches

Elderly Patients (>70-80 Years)

• Avoid treatment in patients over 80-85 years with TSH ≤10 mIU/L, as treatment may be harmful rather than beneficial in this age group. 5, 3, 4
• Age-specific TSH reference ranges should be used, with the upper limit of normal reaching 7.5 mIU/L for patients over age 80. 4
• If treatment is necessary, start with 25-50 mcg/day rather than full replacement doses. 1, 5

Patients on Immunotherapy

• Consider treatment for symptomatic patients on immune checkpoint inhibitors even with mild TSH elevation, as thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy. 1
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption. 6, 1
• Monitor TSH every cycle for the first 3 months, then every second cycle thereafter. 6

Patients with Cardiac Disease

• Exercise extreme caution when treating patients with coronary artery disease or atrial fibrillation, as even therapeutic levothyroxine doses can unmask or worsen cardiac ischemia. 1, 5
• Start with 25-50 mcg/day and titrate slowly. 1, 5
• Consider that cardiovascular events may be reduced in patients under age 65 with treatment, but treatment may be harmful in elderly patients. 4

Dosing and Monitoring When Treatment Is Initiated

• For patients <70 years without cardiac disease, start with 1.6 mcg/kg/day (approximately 100-125 mcg for most adults). 1, 5
• For elderly patients or those with cardiac disease, start with 25-50 mcg/day and increase by 12.5-25 mcg every 6-8 weeks. 1, 5
• Recheck TSH and free T4 in 6-8 weeks after each dose adjustment, targeting TSH in the lower half of the reference range (0.4-2.5 mIU/L). 1, 3
• Once stable, monitor TSH every 6-12 months. 1, 3

Critical Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing, as transient elevations are common. 1, 2, 3
• Do not attribute non-specific symptoms to mild TSH elevation (4.5-7 mIU/L) in asymptomatic patients, as treatment rarely improves these symptoms. 2, 4
• Avoid overtreatment, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, and fractures, especially in the elderly. 1, 2
• Rule out adrenal insufficiency before starting levothyroxine in patients with suspected central hypothyroidism, as thyroid hormone can precipitate adrenal crisis. 1
• Recognize transient hypothyroidism (post-thyroiditis, drug-induced) to avoid unnecessary lifelong treatment. 2, 7

When to Reassess Treatment Decisions

• For symptomatic patients started on levothyroxine with TSH 4.5-10 mIU/L, reassess response after 3-4 months once TSH is normalized. 1, 3
• If symptoms do not improve, discontinue levothyroxine and explore other causes for symptoms. 1, 3
• This approach prevents unnecessary lifelong treatment in patients whose symptoms are unrelated to mild thyroid dysfunction. 2, 7