What is the approach to managing hypothyroidism (underactive Thyroid Stimulating Hormone (TSH) levels)?

Approach to Managing Hypothyroidism

Initial Diagnosis and Confirmation

For suspected hypothyroidism, measure TSH as the primary screening test, and if elevated, confirm with repeat testing after 3-6 weeks along with free T4 measurement, as 30-60% of elevated TSH levels normalize spontaneously. 1

• TSH is the most sensitive test for detecting hypothyroidism with sensitivity above 98% and specificity greater than 92% 1
• Measure both TSH and free T4 to distinguish between subclinical hypothyroidism (elevated TSH with normal free T4) and overt hypothyroidism (elevated TSH with low free T4) 1
• Consider measuring anti-TPO antibodies to identify autoimmune etiology, which predicts higher progression risk to overt hypothyroidism (4.3% per year vs 2.6% in antibody-negative individuals) 1

Critical Pitfall: Central Hypothyroidism

• If low free T4 is found with normal or low TSH, suspect central hypothyroidism from pituitary or hypothalamic dysfunction 2
• Before initiating thyroid hormone replacement in suspected central hypothyroidism, always evaluate for concurrent adrenal insufficiency first, as starting levothyroxine before corticosteroids can precipitate life-threatening adrenal crisis 3, 2, 4
• Conduct morning pituitary hormone panel (ACTH, cortisol, FSH, LH, testosterone/estradiol) and obtain MRI of the sella with pituitary cuts 3

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L (Regardless of Symptoms)

Initiate levothyroxine therapy immediately for all patients with TSH >10 mIU/L, as this threshold carries approximately 5% annual risk of progression to overt hypothyroidism and may prevent cardiovascular complications. 1

• This recommendation applies regardless of age or symptom status 1
• Treatment may improve symptoms and lower LDL cholesterol 1

TSH 4.5-10 mIU/L (Individualized Approach)

For TSH between 4.5-10 mIU/L with normal free T4, routine levothyroxine treatment is NOT recommended; instead monitor thyroid function every 6-12 months. 1

However, consider treatment in these specific situations:

• Pregnant women or those planning pregnancy (subclinical hypothyroidism associated with preeclampsia, low birth weight, and neurodevelopmental effects) 1
• Positive anti-TPO antibodies (4.3% annual progression risk vs 2.6% without antibodies) 1
• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation who may benefit from a 3-4 month trial 1
• Patients with goiter or infertility 5

Avoid treatment in patients >85 years with TSH ≤10 mIU/L, as treatment may be harmful in elderly patients 6

Levothyroxine Dosing Guidelines

Initial Dosing

For patients <70 years without cardiac disease:

• Start with full replacement dose of approximately 1.6 mcg/kg/day 1, 4

For patients >70 years OR with cardiac disease/multiple comorbidities:

• Start with lower dose of 25-50 mcg/day and titrate gradually 1, 4
• Elderly patients with coronary disease are at increased risk of cardiac decompensation, angina, or arrhythmias even with therapeutic doses 5

Special Populations

Pregnant patients with pre-existing hypothyroidism:

• Increase levothyroxine dose by 12.5-25 mcg/day as soon as pregnancy is confirmed 4
• Monitor TSH every 4 weeks during pregnancy to maintain trimester-specific reference ranges 4
• Reduce to pre-pregnancy dose immediately after delivery and recheck TSH 4-8 weeks postpartum 4

Pediatric patients (birth to 3 months):

• Start at 10-15 mcg/kg/day, adjusting based on clinical response 4
• For those at risk for cardiac failure, start lower and increase every 4-6 weeks 4

Dose Adjustment and Monitoring

During Titration Phase

• Adjust levothyroxine dose in increments of 12.5-25 mcg based on current dose 1
• Recheck TSH and free T4 every 6-8 weeks after dose changes 1, 4
• Target TSH within reference range of 0.5-4.5 mIU/L for most patients 1

Maintenance Phase

• Once stable, monitor TSH every 6-12 months or when symptoms change 1
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 1

Common Pitfall: Overtreatment

Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, increasing risks for atrial fibrillation, osteoporosis, fractures, and cardiac complications. 1

• If TSH <0.1 mIU/L: Decrease levothyroxine by 25-50 mcg 1
• If TSH 0.1-0.45 mIU/L: Decrease by 12.5-25 mcg, especially in elderly or those with cardiac disease 1
• Prolonged TSH suppression significantly increases risk for atrial fibrillation (especially in elderly), osteoporosis, and cardiovascular mortality 1

Managing Persistent Elevation Despite Treatment

If TSH remains elevated despite apparent adequate replacement:

1. Assess medication adherence first - most common cause of treatment failure 5
2. Review timing of levothyroxine administration - take on empty stomach, 30-60 minutes before breakfast 5
3. Check for drug interactions that impair absorption:
   • Calcium supplements, iron, proton pump inhibitors, bile acid sequestrants 5
   • Separate these medications by at least 4 hours from levothyroxine 5
4. Consider malabsorption disorders - celiac disease, inflammatory bowel disease, atrophic gastritis 5
5. Increase dose by 12.5-25 mcg and recheck in 6-8 weeks 1

Special Considerations for Immunotherapy Patients

For patients on immune checkpoint inhibitors (anti-PD-1/PD-L1, anti-CTLA-4):

• Thyroid dysfunction occurs in 6-20% of patients 3
• Monitor TSH every 4-6 weeks for first 3 months, then every second cycle 1
• In presence of both adrenal insufficiency and hypothyroidism, always start steroids before thyroid hormone to avoid adrenal crisis 3
• Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 3
• Consider treatment even for subclinical hypothyroidism if fatigue or other hypothyroid symptoms present 1

Central Hypothyroidism Management

For confirmed central hypothyroidism (low free T4 with normal/low TSH):

1. Rule out and treat adrenal insufficiency FIRST - start hydrocortisone before levothyroxine 3, 2
2. Evaluate for other pituitary hormone deficiencies (approximately 50% have panhypopituitarism) 3, 2
3. Start levothyroxine and monitor free T4 levels (NOT TSH) 2
4. Target free T4 in upper half of normal range 2, 5
5. Instruct patients with adrenal insufficiency to obtain medical alert bracelet 3

Long-Term Safety and Monitoring

When properly dosed, levothyroxine is safe for lifelong use, but overtreatment carries significant risks:

• Atrial fibrillation and cardiac arrhythmias (especially in elderly) 1
• Osteoporosis and fractures (particularly in postmenopausal women) 1
• Left ventricular hypertrophy and abnormal cardiac output 1
• Increased cardiovascular mortality 1

Critical monitoring points:

• Development of low TSH on therapy suggests overtreatment or recovery of thyroid function; reduce dose with close follow-up 1
• For patients with atrial fibrillation or serious cardiac conditions, consider repeating testing within 2 weeks rather than waiting 6-8 weeks after dose adjustments 1
• Avoid adjusting doses more frequently than every 6-8 weeks before reaching steady state 1