What is the diagnosis and treatment for a patient with elevated Thyroid-Stimulating Hormone (TSH) levels and normal Free Triiodothyronine (FT3) and Free Thyroxine (FT4) levels, indicating subclinical hypothyroidism?

Subclinical Hypothyroidism: Elevated TSH with Normal FT3 and FT4

Diagnosis

This presentation represents subclinical hypothyroidism, defined biochemically as an elevated TSH with normal free T4 and free T3 levels. 1, 2

Before confirming the diagnosis, you must:

• Repeat TSH and free T4 after 3-6 weeks, as 30-60% of elevated TSH values normalize spontaneously on repeat testing 1
• Measure anti-TPO antibodies to identify autoimmune etiology (Hashimoto's thyroiditis), which predicts higher progression risk to overt hypothyroidism: 4.3% per year versus 2.6% in antibody-negative patients 1, 3
• Exclude transient causes: recent illness, medications (glucocorticoids, dopamine), recovery from thyroiditis, or recent iodine exposure 1, 4

Treatment Algorithm Based on TSH Level

TSH >10 mIU/L: Treat Immediately with Levothyroxine

Initiate levothyroxine therapy regardless of symptoms or age for confirmed TSH >10 mIU/L with normal free T4. 1, 5, 2 This threshold carries approximately 5% annual risk of progression to overt hypothyroidism and is associated with increased cardiovascular risk. 1, 3

Starting dose:

• Patients <70 years without cardiac disease: Start with full replacement dose of approximately 1.6 mcg/kg/day 1
• Patients >70 years OR with cardiac disease/multiple comorbidities: Start with 25-50 mcg/day and titrate gradually 1, 3

Monitoring: Recheck TSH and free T4 every 6-8 weeks during titration, targeting TSH within 0.5-4.5 mIU/L. 1, 5 Once stable, monitor annually or sooner if symptoms change. 1

TSH 4.5-10 mIU/L: Selective Treatment

Routine levothyroxine treatment is NOT recommended for asymptomatic patients with TSH 4.5-10 mIU/L. 1, 5 Instead, monitor thyroid function every 6-12 months. 1

Consider treatment in these specific situations:

• Symptomatic patients with fatigue, weight gain, cold intolerance, or constipation—offer a 3-4 month trial with clear evaluation of benefit 1, 2
• Positive anti-TPO antibodies, indicating higher progression risk 1, 5
• Women planning pregnancy or currently pregnant—treat any TSH elevation immediately, targeting TSH <2.5 mIU/L in first trimester 1
• Patients with goiter 3
• Infertility concerns 3

Do NOT treat patients >85 years with TSH ≤10 mIU/L, as evidence suggests potential harm in this age group. 3, 5

Critical Safety Considerations

Before Starting Levothyroxine:

Rule out concurrent adrenal insufficiency, especially if central hypothyroidism is suspected (low or inappropriately normal TSH with low free T4). Starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1, 3 If adrenal insufficiency is present, start physiologic dose steroids 1 week prior to thyroid hormone replacement. 1

Risks of Overtreatment:

Approximately 25% of patients on levothyroxine are unintentionally overtreated with TSH fully suppressed, which increases risk for: 1

• Atrial fibrillation (3-5 fold increased risk, especially in patients >60 years) 1, 2
• Osteoporosis and fractures, particularly in postmenopausal women 1, 2
• Increased cardiovascular mortality 1
• Ventricular hypertrophy and abnormal cardiac output 1

If TSH becomes suppressed (<0.1 mIU/L) during treatment: Reduce levothyroxine dose by 25-50 mcg immediately. 1 If TSH is 0.1-0.45 mIU/L, reduce by 12.5-25 mcg, particularly in elderly or cardiac patients. 1

Levothyroxine Administration

Take levothyroxine on an empty stomach, 30-60 minutes before breakfast, at least 4 hours apart from iron, calcium supplements, antacids, or proton pump inhibitors, which impair absorption. 6 Soybean flour, cottonseed meal, walnuts, and dietary fiber may also decrease absorption. 6

Common Pitfalls to Avoid

• Never treat based on a single elevated TSH value—confirm with repeat testing 1, 4
• Never assume hypothyroidism is permanent without reassessment—consider transient thyroiditis, especially in recovery phase 1
• Never start at full replacement dose in elderly patients with cardiac disease—this can precipitate myocardial infarction, heart failure, or fatal arrhythmias 1
• Never adjust doses more frequently than every 6-8 weeks—steady state is not reached before this interval 1
• Never overlook medication-induced TSH changes—review all medications, particularly recent dose adjustments 4