What is the diagnostic approach for hypothyroidism?

Diagnosing Hypothyroidism

The diagnosis of hypothyroidism is confirmed by measuring TSH and free T4 levels, with serial measurements required as a single abnormal TSH value is insufficient for diagnosis. 1

Diagnostic Approach

Initial Laboratory Testing

• First-line test: Serum TSH measurement
  • If TSH is elevated, follow up with free T4 (FT4) measurement 1
  • TSH levels can vary by up to 50% day-to-day, requiring serial measurements 1
  • Variations occur based on age, race/ethnicity, and sex 1

Interpretation of Results

1. Primary hypothyroidism (most common):

   • Elevated TSH + Low free T4 = Overt hypothyroidism
   • Elevated TSH + Normal free T4 = Subclinical hypothyroidism 1

2. Secondary (central) hypothyroidism:

   • Low/normal TSH + Low free T4 1

Diagnostic Criteria Table

Condition	TSH	Free T4	Diagnosis
Subclinical Hypothyroidism	Elevated	Normal	Mild hypothyroidism
Overt Hypothyroidism	Elevated	Low	Severe hypothyroidism

Confirmatory Testing

• Repeat testing in 2 weeks to 3 months to confirm the diagnosis 1
• Anti-thyroid peroxidase (anti-TPO) antibodies may be considered to identify autoimmune etiology, though not routinely recommended 1

Clinical Limitations

It's important to note that physical examination alone is insufficient for diagnosing hypothyroidism. A 2004 study showed that no single physical sign or combination of signs could reliably discriminate between euthyroid and hypothyroid patients 2. Common symptoms like fatigue, weight gain, cold intolerance, constipation, and dry skin are nonspecific 3, 4.

Special Considerations

Pregnancy

• Measure serum TSH and free-T4 as soon as pregnancy is confirmed and during each trimester 5
• Maintain serum TSH in trimester-specific reference ranges 5

Elderly Patients

• Higher prevalence of hypothyroidism in older populations 3
• Increased risk of cardiovascular complications with treatment 5
• Symptoms may be more subtle or attributed to aging 4

Monitoring After Diagnosis

• During treatment adjustments: Monitor TSH and free T4 every 6-8 weeks 1
• Once stable: Evaluate clinical and biochemical response every 6-12 months 5
• For pediatric patients: More frequent monitoring is required, especially during growth phases 5

Common Pitfalls to Avoid

1. Relying solely on physical examination

   • Physical signs have poor sensitivity and specificity for hypothyroidism 2

2. Making diagnosis based on a single TSH measurement

   • Serial measurements are essential due to natural variations 1

3. Overlooking secondary hypothyroidism

   • In pituitary/hypothalamic failure, TSH may be normal or low with low free T4 6

4. Failing to consider subclinical hypothyroidism

   • May progress to overt hypothyroidism at a rate of 2.6-4.3% per year 1
   • May require treatment when TSH exceeds 10 mIU/L 4

5. Missing hypothyroidism in pregnancy

   • Can lead to serious complications including preeclampsia, preterm delivery, heart failure, and miscarriage 1

By following this systematic approach to diagnosis, hypothyroidism can be accurately identified and appropriate treatment initiated to prevent complications and improve quality of life.