Treatment for TSH >100 mIU/L
Initiate levothyroxine immediately at full replacement dosing for patients under 70 years without cardiac disease, or start at 25-50 mcg/day for elderly patients or those with cardiac conditions, as a TSH >100 mIU/L represents severe overt hypothyroidism requiring urgent treatment. 1
Immediate Assessment Before Treatment
Before starting levothyroxine, you must rule out concurrent adrenal insufficiency, particularly if central hypothyroidism is suspected, as initiating thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1 If adrenal insufficiency is present or suspected, start physiologic dose steroids at least 1 week prior to thyroid hormone replacement. 1
Confirm the diagnosis by measuring both TSH and free T4—with TSH >100 mIU/L, you will find low free T4, confirming overt hypothyroidism rather than subclinical disease. 1 Consider measuring anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk and confirms the likely permanence of the condition. 1
Initial Levothyroxine Dosing Strategy
For Patients <70 Years Without Cardiac Disease
Start with full replacement dosing at approximately 1.6 mcg/kg/day, which typically translates to 100-150 mcg/day for women and 125-175 mcg/day for men. 1, 2 This aggressive approach is appropriate because the patient has severe hypothyroidism with TSH >100 mIU/L, and delaying normalization prolongs cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration. 1
For Patients >70 Years or With Cardiac Disease
Start conservatively at 25-50 mcg/day and titrate gradually. 1, 2 Elderly patients with underlying coronary disease face increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic levothyroxine doses, as thyroid hormone can unmask or worsen cardiac ischemia. 1 Use 12.5 mcg increments for dose adjustments in this population to avoid cardiac complications. 1
Monitoring and Dose Titration
Recheck TSH and free T4 in 6-8 weeks after initiating therapy, as this represents the time needed to reach steady state given levothyroxine's long half-life. 1, 2 Target TSH within the reference range (0.5-4.5 mIU/L) with normal free T4 levels. 1
If TSH remains elevated after 6-8 weeks, increase the dose by 12.5-25 mcg based on the patient's age and cardiac status. 1 For younger patients without cardiac disease, use 25 mcg increments; for elderly or cardiac patients, use 12.5 mcg increments. 1
Continue monitoring TSH and free T4 every 6-8 weeks during dose titration until TSH normalizes. 1, 2 Once adequately treated with stable TSH in the target range, repeat testing every 6-12 months or sooner if symptoms change. 1, 2
Special Populations Requiring Modified Approach
Pregnant Patients or Women Planning Pregnancy
For pregnant patients with TSH >100 mIU/L, start levothyroxine immediately at 1.6 mcg/kg/day, as inadequate treatment is associated with preeclampsia, low birth weight, and potential neurodevelopmental effects in offspring. 1, 2 Monitor TSH every 4 weeks during pregnancy and adjust dosage to maintain TSH within trimester-specific reference ranges. 2 Levothyroxine requirements typically increase 25-50% during pregnancy. 1
Patients on Immune Checkpoint Inhibitors
Even with severe hypothyroidism, continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption. 1 Start levothyroxine as outlined above and monitor TSH every cycle for the first 3 months, then every second cycle thereafter. 1
Critical Pitfalls to Avoid
Never start thyroid hormone before ruling out adrenal insufficiency in patients with suspected central hypothyroidism or hypophysitis. 1 This can precipitate adrenal crisis and is potentially fatal.
Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism, which increases risk for atrial fibrillation, osteoporosis, fractures, abnormal cardiac output, and ventricular hypertrophy. 1 Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, creating these risks. 1
Do not adjust doses more frequently than every 6-8 weeks, as levothyroxine has a long half-life and steady state is not reached earlier. 1, 2 Adjusting too frequently leads to overcorrection and instability.
For patients with cardiac disease, never start at full replacement doses—even therapeutic doses can unmask or worsen cardiac ischemia in elderly patients with underlying coronary disease. 1 Always start low (25-50 mcg/day) and titrate slowly in this population.
Long-Term Management Considerations
Once TSH normalizes and the patient is on a stable maintenance dose, annual monitoring suffices unless clinical status changes. 1, 2 The goal is to maintain TSH in the reference range (0.5-4.5 mIU/L) with normal free T4 levels. 1
Ensure patients take levothyroxine on an empty stomach, as certain drugs (iron, calcium) reduce gastrointestinal absorption, and enzyme inducers reduce its efficacy. 3 Patients should take levothyroxine consistently at the same time each day, preferably in the morning before breakfast.
With TSH >100 mIU/L, this represents severe overt hypothyroidism that will require lifelong treatment in most cases, particularly if anti-TPO antibodies are positive indicating autoimmune etiology. 1 However, recognize that transient hypothyroidism can occur (post-thyroiditis, drug-induced), so reassessment after initial stabilization may be warranted in select cases. 1