Hypothyroidism Treatment Approach
First-Line Treatment: Levothyroxine Monotherapy
Levothyroxine is the standard treatment for hypothyroidism, with dosing and monitoring strategies that must be tailored to patient age, cardiac status, and TSH severity. 1, 2, 3
Initial Dosing Strategy
For Patients <70 Years Without Cardiac Disease
- Start levothyroxine at 1.6 mcg/kg/day as a single morning dose on an empty stomach 1, 3
- This full replacement dose rapidly normalizes thyroid function and prevents cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration 1
For Patients >70 Years OR With Cardiac Disease
- Start at 25-50 mcg/day and titrate gradually 1, 4, 3
- Lower starting doses prevent unmasking coronary ischemia, precipitating arrhythmias, or triggering heart failure decompensation 1, 3
- Elderly patients with underlying coronary disease face increased risk of cardiac decompensation even with therapeutic levothyroxine doses 1
Treatment Thresholds Based on TSH Level
TSH >10 mIU/L
- Initiate levothyroxine immediately regardless of symptoms 1, 2
- This threshold carries approximately 5% annual risk of progression to overt hypothyroidism 1
- Treatment may prevent complications including cardiovascular dysfunction and improve LDL cholesterol 1
TSH 4.5-10 mIU/L (Subclinical Hypothyroidism)
- Do NOT routinely treat 1, 5
- Monitor TSH every 6-12 months instead 1
- Consider treatment in specific situations:
Confirm Diagnosis First
- Repeat TSH after 3-6 weeks before initiating treatment, as 30-60% of elevated TSH levels normalize spontaneously 1, 5
- Measure both TSH and free T4 to distinguish subclinical (normal T4) from overt (low T4) hypothyroidism 1
Critical Safety Considerations
Rule Out Adrenal Insufficiency FIRST
Never start levothyroxine before excluding adrenal insufficiency, as thyroid hormone can precipitate life-threatening adrenal crisis. 1, 6, 7
- Check morning cortisol and ACTH in patients with suspected central hypothyroidism or hypophysitis 6
- If adrenal insufficiency is present, start hydrocortisone (15 mg morning, 5 mg at 3 pm) at least 1 week before levothyroxine 6
- This is especially critical in patients on immune checkpoint inhibitors 6
Pregnancy Considerations
- Increase levothyroxine dose by 25-50% immediately upon pregnancy confirmation 4, 3
- Target TSH <2.5 mIU/L in first trimester 1, 3
- Monitor TSH every 4 weeks until stable, then at minimum once per trimester 1, 4
- Untreated maternal hypothyroidism increases risk of spontaneous abortion, preeclampsia, stillbirth, premature delivery, and adverse fetal neurocognitive development 4, 2, 3
Monitoring Protocol
During Dose Titration
- Recheck TSH and free T4 every 6-8 weeks after any dose adjustment 1, 2, 3
- Adjust dose by 12.5-25 mcg increments based on results 1
- Use smaller increments (12.5 mcg) for elderly patients or those with cardiac disease 1
After Stabilization
- Monitor TSH annually once target range achieved 1, 2, 3
- Target TSH: 0.5-4.5 mIU/L with normal free T4 1, 7
- Recheck sooner if symptoms change 1
Common Pitfalls and How to Avoid Them
Overtreatment (Iatrogenic Hyperthyroidism)
- Approximately 25% of patients on levothyroxine are unintentionally overtreated with TSH fully suppressed 1, 2
- TSH <0.1 mIU/L increases risk of:
- If TSH <0.1 mIU/L: reduce dose by 25-50 mcg immediately 1
- If TSH 0.1-0.45 mIU/L: reduce dose by 12.5-25 mcg, especially in elderly or cardiac patients 1
Treating Transient Hypothyroidism
- Failure to recognize transient thyroiditis (including recovery phase) leads to unnecessary lifelong treatment 1, 5
- Consider transient causes: acute illness, recent iodine exposure, recovery from destructive thyroiditis, certain medications 1
Adjusting Doses Too Frequently
- Wait 6-8 weeks between dose adjustments to reach steady state 1, 2
- Adjusting sooner leads to inappropriate dosing 1
Special Populations
Patients on Immune Checkpoint Inhibitors
- Thyroid dysfunction occurs in 6-9% with anti-PD-1/PD-L1 therapy and 16% with combination immunotherapy 1
- Consider treatment even for subclinical hypothyroidism if fatigue or other symptoms present 1
- Continue immunotherapy in most cases; thyroid dysfunction rarely requires treatment interruption 1
- Monitor TSH every 4-6 weeks for first 3 months, then every second cycle 1
Secondary (Central) Hypothyroidism
- Never use TSH to monitor therapy—TSH remains suppressed or inappropriately normal regardless of treatment 6
- Monitor with free T4 levels, targeting upper half of normal range 6, 7
- Evaluate all other pituitary hormones, as isolated secondary hypothyroidism is rare 6
- Always assess hypothalamic-pituitary-adrenal axis before starting levothyroxine 6, 7
Cardiac Patients
- Start at 12.5-25 mcg/day in patients with coronary artery disease, recent MI, or heart failure 1, 3
- Obtain baseline ECG to screen for arrhythmias 1
- Monitor closely for angina, palpitations, dyspnea, or worsening heart failure 1
- Atrial fibrillation is the most common arrhythmia with levothyroxine overtreatment in elderly patients 4
Medication Administration
- Take levothyroxine on an empty stomach, 30-60 minutes before breakfast 3, 8
- Separate from iron, calcium supplements, or antacids by at least 4 hours 1
- Enzyme inducers reduce levothyroxine efficacy 5