Management of Elevated TSH in Patients on Levothyroxine

Increase the levothyroxine dose by 12.5–25 µg and recheck TSH in 6–8 weeks to normalize thyroid function. 1

Step 1: Confirm Non-Adherence and Medication Interference

Assess adherence directly: Ask whether the patient takes levothyroxine on an empty stomach, 30–60 minutes before breakfast, and at least 4 hours apart from iron, calcium supplements, or antacids 1, 2
Review all medications and supplements: Iron, calcium, proton pump inhibitors, bile acid sequestrants, sucralfate, and fiber supplements reduce levothyroxine absorption 2, 3
Check for recent iodine exposure: CT contrast or amiodarone can transiently alter thyroid function tests 1
Rule out gastrointestinal disorders: Celiac disease, Helicobacter pylori infection, atrophic gastritis, inflammatory bowel disease, and bariatric surgery all impair levothyroxine absorption 2, 3

Recheck TSH and free T4 after 3–6 weeks if the initial elevation is mild (TSH 4.5–10 mIU/L), because 30–60% of elevated TSH values normalize spontaneously 1
Do not delay retesting if TSH >10 mIU/L with symptoms or low free T4, as this represents overt or severe subclinical hypothyroidism requiring prompt dose adjustment 1
Measure anti-TPO antibodies if not previously done, as positive antibodies predict a 4.3% annual progression risk to overt hypothyroidism versus 2.6% in antibody-negative patients 1

Increase levothyroxine by 25 µg for patients <70 years without cardiac disease 1
Increase by 12.5 µg for patients >70 years or with cardiac disease to avoid precipitating angina or arrhythmias 1
This TSH threshold carries ~5% annual risk of progression to overt hypothyroidism and is associated with cardiac dysfunction, elevated LDL cholesterol, and increased cardiovascular risk 1

Increase levothyroxine by 12.5–25 µg if the patient is already on replacement therapy, as dose adjustment is reasonable to normalize TSH into the reference range (0.5–4.5 mIU/L) 1
Consider treatment for symptomatic patients, pregnant women, or those with positive anti-TPO antibodies 1
Monitor without treatment for asymptomatic patients with negative antibodies, rechecking TSH every 6–12 months 1

Recheck TSH and free T4 in 6–8 weeks after any dose change, as this interval is required to reach steady state 1, 4
Target TSH 0.5–4.5 mIU/L with normal free T4 for primary hypothyroidism 1
Once stable, monitor TSH every 6–12 months or sooner if symptoms change 1, 4

If TSH remains elevated after confirmed adherence and appropriate dose increases:

Perform a levothyroxine absorption test: Administer a single 1000 µg dose of levothyroxine and measure free T4 at baseline and 2–4 hours post-dose; failure to increase free T4 indicates malabsorption 2, 3
Screen for celiac disease: Measure anti-endomysial and anti-tissue transglutaminase antibodies 2, 3
Test for Helicobacter pylori infection and atrophic gastritis with anti-parietal cell antibodies 2, 3
Consider switching to liquid or soft-gel levothyroxine formulations if malabsorption is confirmed 2
Rule out heterophilic anti-TSH antibodies causing falsely elevated TSH if free T4 is normal or high 2, 3

Measure morning cortisol and ACTH before increasing levothyroxine in patients with suspected central hypothyroidism, hypophysitis, or autoimmune polyendocrine syndrome 1
Start hydrocortisone 20 mg AM and 10 mg PM for at least one week before increasing levothyroxine if adrenal insufficiency is confirmed, as thyroid hormone accelerates cortisol metabolism and can precipitate adrenal crisis 1

Do not treat based on a single elevated TSH value without confirmation, as 30–60% normalize spontaneously 1
Do not increase levothyroxine too aggressively in elderly patients or those with cardiac disease, as this can unmask coronary ischemia or trigger arrhythmias 1, 5
Do not adjust doses more frequently than every 6–8 weeks, as levothyroxine has a long half-life and steady state is not reached sooner 1, 6
Do not overlook transient causes of TSH elevation: Acute illness, recovery from thyroiditis, recent iodine exposure, or medications (lithium, amiodarone, interferon) can transiently raise TSH 1
Do not ignore symptoms of overtreatment: Approximately 25% of patients on levothyroxine are unintentionally overtreated with suppressed TSH, increasing risk for atrial fibrillation, osteoporosis, fractures, and cardiovascular mortality 1, 7

Increase levothyroxine by 25–50% immediately upon pregnancy confirmation for patients with pre-existing hypothyroidism 1, 4
Target TSH <2.5 mIU/L in the first trimester and within trimester-specific reference ranges thereafter 1, 4
Monitor TSH every 4 weeks until stable, then at minimum once per trimester 1, 4

Start at 25–50 µg daily and titrate by 12.5 µg increments every 6–8 weeks 1, 5
Accept slightly higher TSH targets (up to 5–6 mIU/L) in very elderly patients to avoid overtreatment risks 1

Start at 25–50 µg daily and increase by 12.5 µg every 6–8 weeks 1, 5
Obtain baseline ECG to screen for arrhythmias before dose escalation 1
Monitor closely for angina, palpitations, or worsening heart failure during titration 1