What is the appropriate initial evaluation and management for a patient with suspected hypothyroidism?

Evaluation of Hypothyroidism

Initial Laboratory Testing

Measure TSH and free T4 simultaneously as the initial diagnostic tests for suspected hypothyroidism. 1, 2

• TSH is the most sensitive screening test with sensitivity >98% and specificity >92% for detecting thyroid dysfunction 1, 2
• Free T4 distinguishes between subclinical hypothyroidism (normal FT4) and overt hypothyroidism (low FT4), which determines treatment urgency 1, 2
• Add anti-TPO antibodies to confirm autoimmune etiology (Hashimoto thyroiditis), which predicts 4.3% annual progression to overt hypothyroidism versus 2.6% in antibody-negative patients 1, 2

Diagnostic Interpretation Algorithm

Overt Hypothyroidism

• TSH >4.5 mIU/L + Low FT4 = Overt hypothyroidism requiring immediate treatment 1, 2
• Common symptoms include fatigue (68-83%), weight gain (24-59%), cognitive impairment (45-48%), and menstrual irregularities (23%) 3

Subclinical Hypothyroidism

• TSH >4.5 mIU/L + Normal FT4 = Subclinical hypothyroidism 1, 2
• Confirm with repeat testing after 3-6 weeks, as 30-60% of elevated TSH values normalize spontaneously 1

Critical Pre-Treatment Safety Assessment

Before initiating levothyroxine, rule out concurrent adrenal insufficiency—especially in suspected central hypothyroidism—as starting thyroid hormone before corticosteroids can precipitate life-threatening adrenal crisis. 1, 4

• Obtain morning (8 AM) serum cortisol and ACTH if central hypothyroidism suspected 1
• Start hydrocortisone 1 week before levothyroxine if adrenal insufficiency present 1, 4

Treatment Decision Algorithm

Immediate Treatment Required

Initiate levothyroxine immediately for: 1, 4, 3

• TSH >10 mIU/L regardless of symptoms (5% annual progression risk to overt hypothyroidism) 1, 5
• Any TSH elevation with low FT4 (overt hypothyroidism) 1, 3
• Pregnant women or those planning pregnancy with any TSH elevation (target TSH <2.5 mIU/L first trimester) 1, 4
• Symptomatic patients with any degree of TSH elevation 1, 4

Individualized Treatment Consideration

For TSH 4.5-10 mIU/L with normal FT4, consider treatment if: 1, 4, 6

• Positive anti-TPO antibodies (higher progression risk) 1, 2
• Symptomatic (fatigue, weight gain, cold intolerance) 1, 4
• Infertility or goiter present 4
• Age <65 years with cardiovascular risk factors 6, 5

Monitor without treatment if: 1, 6

• Asymptomatic with TSH 4.5-10 mIU/L 1
• Age >85 years (avoid treatment in this group) 4
• Recheck TSH every 6-12 months 1

Levothyroxine Dosing Strategy

Standard Dosing

• Full replacement dose: 1.6 mcg/kg/day for patients <70 years without cardiac disease 1, 4
• Target TSH: 0.5-4.5 mIU/L (or 0.5-2.0 mIU/L per some guidelines) 1, 4

Conservative Dosing (High-Risk Patients)

Start with 25-50 mcg/day and titrate slowly for: 1, 4, 3

• Age >70 years 1, 2
• Coronary artery disease or cardiac comorbidities 1, 4, 3
• Long-standing severe hypothyroidism 4
• Atrial fibrillation 1, 3

Monitoring Protocol

During Dose Titration

• Recheck TSH and free T4 every 6-8 weeks after any dose adjustment until TSH reaches target range 1, 2, 4
• Adjust dose by 12.5-25 mcg increments based on response 1
• Free T4 helps interpret ongoing abnormal TSH during therapy, as TSH normalization may lag 1, 2

Maintenance Monitoring

• Once stable, recheck TSH every 6-12 months or sooner if symptoms change 1, 2, 4
• Annual monitoring sufficient for stable patients 1

Special Population Considerations

Pregnancy

• Increase levothyroxine dose by 25-50% immediately upon pregnancy confirmation in women with pre-existing hypothyroidism 1, 2
• Monitor TSH every 4 weeks until stable, then at least once per trimester 1, 2
• Target TSH <2.5 mIU/L in first trimester 1, 2

Elderly with Cardiac Disease

• Start 25-50 mcg/day to avoid unmasking cardiac ischemia or precipitating arrhythmias 1, 2, 4
• Use 12.5 mcg increments for titration 1
• Consider slightly higher TSH targets (up to 5-6 mIU/L may be acceptable in very elderly) 1

Critical Pitfalls to Avoid

Do not treat based on single elevated TSH value without confirmation—30-60% normalize spontaneously, representing transient thyroiditis in recovery phase 1, 6

Approximately 25% of patients on levothyroxine are unintentionally overtreated (TSH fully suppressed), increasing risks for atrial fibrillation (3-5 fold), osteoporosis, fractures, and cardiovascular mortality 1, 3

Never start thyroid hormone before ruling out adrenal insufficiency in suspected central hypothyroidism—this can precipitate adrenal crisis 1, 4

Avoid excessive dose increases—overtreatment occurs in 14-21% of treated patients and carries significant morbidity 1