What is the recommended management for hypothyroidism?

Hypothyroidism Management

Diagnostic Confirmation

Measure both TSH and free T4 to distinguish between overt hypothyroidism (elevated TSH with low free T4) and subclinical hypothyroidism (elevated TSH with normal free T4). 1

• TSH is the most sensitive screening test with sensitivity above 98% and specificity greater than 92% 1
• Consider anti-TPO antibody testing to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt hypothyroidism (4.3% vs 2.6% per year in antibody-negative individuals) 1, 2
• Confirm elevated TSH with repeat testing after 3-6 weeks, as 30-60% of high TSH levels normalize spontaneously 2

Critical Pre-Treatment Safety Assessment

In patients with suspected central hypothyroidism or hypophysitis, always initiate corticosteroids BEFORE starting levothyroxine to prevent adrenal crisis. 1

• Evaluate morning cortisol and ACTH if central hypothyroidism is suspected 1
• This is a life-threatening pitfall that must be avoided in all cases of suspected pituitary or hypothalamic disease 2

Initial Levothyroxine Dosing

For patients <70 years without cardiac disease: Start levothyroxine 1.6 mcg/kg/day as full replacement dose. 1, 2

For patients >70 years OR with cardiac disease/atrial fibrillation: Start at 25-50 mcg/day and titrate gradually. 1, 2, 3

• The lower starting dose in elderly and cardiac patients prevents cardiac complications including angina, arrhythmias, and cardiac decompensation 1, 3
• Atrial fibrillation is the most common arrhythmia observed with levothyroxine overtreatment in elderly patients 3

Treatment Algorithm Based on TSH Levels

TSH >10 mIU/L with Normal Free T4 (Subclinical Hypothyroidism)

Initiate levothyroxine therapy regardless of symptoms, as this level carries approximately 5% annual risk of progression to overt hypothyroidism. 2

• Treatment may improve symptoms and lower LDL cholesterol 2
• Positive anti-TPO antibodies further support treatment decision 2

TSH 4.5-10 mIU/L with Normal Free T4

Routine levothyroxine treatment is NOT recommended; instead, monitor thyroid function tests at 6-12 month intervals. 2

• Consider treatment in specific situations: symptomatic patients, women planning pregnancy, presence of goiter, or positive anti-TPO antibodies 2, 4
• For patients already on levothyroxine with TSH in this range, dose adjustment is reasonable to normalize TSH into reference range (0.5-4.5 mIU/L) 2

Overt Hypothyroidism (Elevated TSH with Low Free T4)

Treat all patients with overt hypothyroidism with levothyroxine immediately. 1, 5, 4

Dose Adjustment Protocol

Adjust levothyroxine dose by 12.5-25 mcg increments based on current dose. 1, 2

• Larger adjustments may lead to overtreatment and should be avoided, especially in elderly patients or those with cardiac disease 1
• For patients <70 years without cardiac disease, more aggressive titration using 25 mcg increments may be appropriate 2
• For patients >70 years or with cardiac disease, use smaller increments (12.5 mcg) to avoid cardiac complications 2

Monitoring Schedule

Recheck TSH and free T4 every 6-8 weeks after initiating therapy or changing dose until TSH normalizes to 0.5-4.5 mIU/L. 1, 2

• Once adequately treated with stable dose, repeat TSH testing every 6-12 months 1, 2
• Free T4 can help interpret ongoing abnormal TSH levels during therapy, as TSH may take longer to normalize 2
• For patients with atrial fibrillation, cardiac disease, or serious medical conditions, consider more frequent monitoring within 2 weeks of dose adjustment 2

Special Population Considerations

Pregnancy

Levothyroxine should not be discontinued during pregnancy, and hypothyroidism diagnosed during pregnancy should be promptly treated. 3

• Pregnancy may increase levothyroxine requirements by 25-50% above pre-pregnancy doses 2, 3
• TSH should be monitored and levothyroxine dosage adjusted during pregnancy 3
• Untreated maternal hypothyroidism is associated with spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, premature delivery, and adverse effects on fetal neurocognitive development 3
• Postpartum, return to pre-pregnancy dose immediately after delivery 3

Immune Checkpoint Inhibitor-Induced Hypothyroidism

Continue checkpoint inhibitors while treating hypothyroidism with standard levothyroxine replacement. 1

• Most patients develop permanent hypothyroidism requiring lifelong treatment 1
• Consider treatment even for subclinical hypothyroidism if fatigue or other hypothyroid symptoms are present 2

Pediatric Patients

Initiate levothyroxine therapy immediately upon diagnosis in children to prevent adverse effects on cognitive development and physical growth. 3

• Closely monitor infants during the first 2 weeks of therapy for cardiac overload and arrhythmias 3
• Levothyroxine is generally continued for life unless transient hypothyroidism is suspected 3

Critical Risks of Inadequate Treatment vs Overtreatment

Undertreatment Risks

• Persistent hypothyroid symptoms, cardiovascular dysfunction, and increased cardiovascular mortality 1, 5
• In pregnancy: increased risk of preeclampsia, low birth weight, and adverse neurodevelopmental outcomes 2, 3

Overtreatment Risks

Approximately 25% of patients on levothyroxine are unintentionally maintained on doses sufficient to fully suppress TSH, significantly increasing morbidity risks. 2

• Atrial fibrillation and cardiac arrhythmias, especially in elderly patients 1, 2, 3, 4
• Osteoporosis and fractures, particularly in postmenopausal women 1, 2, 4
• Increased cardiovascular mortality 2
• Left ventricular hypertrophy and abnormal cardiac output 2

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value without confirmation testing 2
• Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism 1, 2
• Avoid adjusting doses too frequently before reaching steady state—wait 6-8 weeks between adjustments 2
• Do not overlook medication interactions, malabsorption syndromes, or non-compliance as causes of persistently elevated TSH despite adequate dosing 4, 6
• Avoid excessive dose increases that could lead to iatrogenic hyperthyroidism 2, 4

Alternative Therapy Considerations

Levothyroxine monotherapy remains the standard treatment and is preferred over combination therapy with liothyronine (T3). 4, 6, 7, 8

• Combination LT4 + T3 therapy has not demonstrated consistent superiority in randomized controlled trials 7, 8
• Most patients achieve excellent outcomes with LT4 monotherapy when properly dosed and monitored 6, 7
• Some patients may carry polymorphisms in deiodinase enzymes (DIO2) that could theoretically benefit from combination therapy, but this remains investigational 8