What is the typical treatment for hypothyroidism?

Treatment of Hypothyroidism

Levothyroxine monotherapy is the standard treatment for hypothyroidism, administered as a single daily dose on an empty stomach, 30-60 minutes before breakfast. 1, 2, 3, 4

Diagnosis and Confirmation

Before initiating treatment, confirm the diagnosis with repeat testing after 3-6 weeks, as 30-60% of elevated TSH levels normalize spontaneously 1. Measure both TSH and free T4 to distinguish between:

• Overt hypothyroidism: Elevated TSH with low free T4 1, 2
• Subclinical hypothyroidism: Elevated TSH with normal free T4 1, 4

Initial Dosing Strategy

For Patients Under 70 Years Without Cardiac Disease

Start with full replacement dose of 1.6 mcg/kg/day 1, 3, 4. This allows rapid normalization of thyroid function and prevents cardiovascular dysfunction, adverse lipid profiles, and quality of life deterioration 1.

For Patients Over 70 Years or With Cardiac Disease

Start with 25-50 mcg/day and titrate gradually by 12.5-25 mcg increments every 6-8 weeks 1, 2, 4. Rapid normalization in elderly patients or those with coronary artery disease can unmask cardiac ischemia, precipitate myocardial infarction, or trigger fatal arrhythmias 1.

Treatment Thresholds Based on TSH Levels

TSH >10 mIU/L

Initiate levothyroxine therapy immediately regardless of symptoms 1, 2, 4. This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with increased cardiovascular risk 1.

TSH 4.5-10 mIU/L

Treatment decisions require individualization 1, 4:

• Treat if: Symptomatic, pregnant or planning pregnancy, positive anti-TPO antibodies (4.3% vs 2.6% annual progression risk), or infertility 1, 4
• Monitor without treatment if: Asymptomatic, no antibodies, not pregnant 1
• Recheck TSH every 6-12 months 1

Monitoring Protocol

During Dose Titration

Recheck TSH and free T4 every 6-8 weeks after any dose adjustment 1, 2. This represents the time needed to reach steady state 1. Adjusting doses more frequently is a common pitfall that leads to inappropriate dose changes 1.

After Stabilization

Once TSH reaches target range (0.5-4.5 mIU/L), monitor every 6-12 months or sooner if symptoms change 1, 2.

Critical Safety Considerations

Rule Out Adrenal Insufficiency First

Always evaluate for adrenal insufficiency before starting levothyroxine in suspected central hypothyroidism 1. Starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis 1. If adrenal insufficiency is present, start physiologic dose steroids 1 week prior to thyroid hormone replacement 1.

Pregnancy Considerations

• Treat any TSH elevation immediately in pregnant women or those planning pregnancy 1, 5, 4
• Target TSH <2.5 mIU/L in first trimester 1
• Increase pre-pregnancy levothyroxine dose by 25-50% immediately upon pregnancy confirmation 1, 5
• Monitor TSH every 4 weeks until stable, then at minimum once per trimester 1
• Untreated maternal hypothyroidism increases risk of preeclampsia, low birth weight, and permanent neurodevelopmental deficits in the child 1, 5

Risks of Overtreatment

Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH 1, 2. This creates serious risks:

• Atrial fibrillation: 3-5 fold increased risk, especially in patients over 60 years 1
• Osteoporosis and fractures: Particularly in postmenopausal women with TSH ≤0.1 mIU/L 1
• Cardiovascular mortality: Up to 2.2-fold increase in patients over 60 with TSH <0.5 mIU/L 1
• Ventricular hypertrophy and abnormal cardiac output 1, 6

Managing Overtreatment

• If TSH <0.1 mIU/L: Reduce levothyroxine by 25-50 mcg immediately 1
• If TSH 0.1-0.45 mIU/L: Reduce by 12.5-25 mcg, particularly in elderly or cardiac patients 1

Risks of Undertreatment

Inadequate treatment leads to 1, 2, 7:

• Persistent hypothyroid symptoms (fatigue, weight gain, cognitive impairment)
• Adverse cardiovascular effects including heart failure
• Abnormal lipid metabolism
• Menstrual irregularities and infertility
• Decreased quality of life

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 are present 1. Continue immunotherapy in most cases, as thyroid dysfunction rarely requires treatment interruption 1.

Patients with Hashimoto's Thyroiditis

Positive anti-TPO antibodies predict higher progression risk to overt hypothyroidism (4.3% vs 2.6% per year in antibody-negative individuals) 1. This autoimmune etiology justifies earlier treatment consideration for TSH levels between 4.5-10 mIU/L 1.

Common Pitfalls to Avoid

• Never treat based on single elevated TSH value without confirmation testing 1
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1
• Avoid adjusting doses before 6-8 weeks have elapsed since the last change 1
• Do not ignore suppressed TSH in elderly patients, especially those with osteoporotic fractures—this creates direct cause-and-effect relationship for bone loss 1
• Never assume hypothyroidism is permanent without reassessment; consider transient thyroiditis, especially in recovery phase 1

Alternative Therapy Considerations

Combination levothyroxine plus liothyronine therapy has been evaluated in 15 clinical trials 8. While some studies showed beneficial effects on mood and quality of life, levothyroxine monotherapy should remain the treatment of choice until clear advantages of combination therapy are demonstrated 8. The potential for adverse events from liothyronine addition outweighs uncertain benefits 8.