When should treatment for hypothyroidism (underactive Thyroid Stimulating Hormone (TSH) and free thyroxine (FT4) levels) be initiated?

When to Initiate Treatment for Hypothyroidism

Treat hypothyroidism when TSH is persistently >10 mIU/L regardless of symptoms, or when patients have overt hypothyroidism (elevated TSH with low free T4), or when subclinical hypothyroidism (TSH 4.5-10 mIU/L with normal free T4) occurs with symptoms, pregnancy, or positive anti-TPO antibodies. 1, 2

Confirm the Diagnosis First

• Always repeat TSH testing after 3-6 weeks before initiating treatment, as 30-60% of elevated TSH levels normalize spontaneously on repeat measurement 1, 3
• Measure both TSH and free T4 simultaneously to distinguish between overt hypothyroidism (low free T4) and subclinical hypothyroidism (normal free T4) 1, 4
• Check anti-TPO antibodies if TSH is elevated, as positive antibodies predict higher progression risk to overt hypothyroidism (4.3% vs 2.6% per year) and support treatment decisions 1, 2

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L with Normal Free T4

• Initiate levothyroxine therapy regardless of symptoms 1, 2, 5
• This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1, 4
• Treatment may prevent cardiovascular complications and improve lipid metabolism 1, 6

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

Treat in these specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or cognitive complaints—consider a 3-4 month trial of levothyroxine with clear evaluation of benefit 1, 5, 6
• Women who are pregnant or planning pregnancy, as subclinical hypothyroidism increases risk of preeclampsia, low birth weight, and neurodevelopmental effects in offspring 1, 7, 6
• Patients with positive anti-TPO antibodies, indicating autoimmune etiology with higher progression risk 1, 2, 5
• Patients with goiter or infertility 2, 5

Do not routinely treat:

• Asymptomatic patients with TSH <10 mIU/L, especially those >80-85 years old 1, 5
• Monitor these patients with repeat TSH every 6-12 months instead 1, 5

Overt Hypothyroidism (Elevated TSH with Low Free T4)

• Always treat with levothyroxine 2, 4, 6
• These patients are typically symptomatic and at risk for serious complications including heart failure and myxedema coma 4

Special Populations Requiring Modified Approach

Pregnant Women

• Treat at any level of TSH elevation to prevent adverse pregnancy outcomes 1, 7, 6
• Increase pre-pregnancy levothyroxine dose by 25-50% (or take one extra dose twice weekly) as soon as pregnancy is confirmed 7, 6
• Monitor TSH every 4 weeks during pregnancy, targeting trimester-specific reference ranges 7

Elderly Patients (>70 years) or Those with Cardiac Disease

• Start levothyroxine at lower doses (25-50 mcg/day) rather than full replacement dose to avoid cardiac decompensation 1, 7, 2
• For patients >80-85 years with TSH <10 mIU/L, consider watchful waiting rather than treatment 1, 5

Patients on Immune Checkpoint Inhibitors

• Consider treatment even for subclinical hypothyroidism if fatigue or other complaints are present, as thyroid dysfunction occurs in 5-10% with anti-PD-1/PD-L1 therapy and 20% with combination immunotherapy 8
• Continue checkpoint inhibitor therapy while treating hypothyroidism unless patient is severely unwell 8

Critical Safety Considerations Before Starting Treatment

Rule Out Central Hypothyroidism

• If TSH is normal or low with low free T4, suspect central (pituitary/hypothalamic) hypothyroidism rather than primary thyroid disease 9, 2
• Never start levothyroxine before ruling out and treating adrenal insufficiency in central hypothyroidism, as this can precipitate life-threatening adrenal crisis 1, 9, 2
• Measure morning ACTH and cortisol, obtain pituitary MRI, and check other pituitary hormones 9

Assess for Transient Hypothyroidism

• Consider recent iodine exposure from CT contrast, which can transiently affect thyroid function 1
• Recognize that some hypothyroidism is transient (lasting weeks to months) and does not require lifelong treatment 3, 2
• In immunotherapy-induced thyroiditis, subclinical hyperthyroidism (low TSH, normal free T4) often precedes hypothyroidism 8

Common Pitfalls to Avoid

• Do not treat based on a single elevated TSH value—always confirm with repeat testing 1, 3
• Do not attribute non-specific symptoms to mildly elevated TSH (4.5-7 mIU/L) without considering other causes 3
• Do not screen asymptomatic populations—targeted testing only for high-risk patients (type 1 diabetes, autoimmune disease, pregnancy) 4, 6
• Avoid overtreatment, which occurs in 14-21% of treated patients and increases risk for atrial fibrillation, osteoporosis, and fractures, especially in elderly patients 1, 2
• For symptomatic patients started on levothyroxine for TSH 4.5-10 mIU/L, review response after 3-4 months and discontinue if no symptom improvement 1, 5