Investigating the Cause of Hypothyroidism
The best approach to investigate the cause of hypothyroidism is to begin with a comprehensive thyroid function panel including TSH, Free T4, and thyroid antibodies (TPO and TGA), followed by additional testing based on clinical presentation and initial results. 1
Initial Diagnostic Workup
Primary Laboratory Tests
- Thyroid Function Panel:
- TSH (elevated in primary hypothyroidism)
- Free T4 (decreased in overt hypothyroidism, normal in subclinical)
- Thyroid antibodies: TPO (thyroid peroxidase) and TGA (thyroglobulin antibodies) 1
- Positive antibodies suggest autoimmune thyroiditis (Hashimoto's), the most common cause of hypothyroidism in iodine-sufficient areas
Secondary Laboratory Tests
- Complete Blood Count (CBC) with differential
- Comprehensive Metabolic Panel
- Vitamin levels (B12, Folate, Vitamin D)
- Iron studies
- Inflammatory markers (ESR, CRP) 1
Identifying Specific Causes
1. Autoimmune Thyroiditis (Hashimoto's)
- Characterized by positive thyroid antibodies (TPO and/or TGA)
- Most common cause in iodine-sufficient regions
- Screen for other autoimmune conditions, particularly in patients with confirmed autoimmune thyroid disease:
- Adrenal insufficiency (21OH-Ab/ACA)
- Celiac disease
- Type 1 diabetes 1
2. Iatrogenic Causes
- Medication history review for:
- Amiodarone
- Lithium
- Immune checkpoint inhibitors
- Tyrosine kinase inhibitors 2
- History of radioactive iodine treatment
- Previous thyroid surgery 2
3. Iodine-Related Causes
- Assess iodine status in regions with known deficiency
- Iodine deficiency remains the most common worldwide cause of hypothyroidism 3
- Paradoxically, excessive iodine intake can also cause hypothyroidism
4. Central (Secondary) Hypothyroidism
- If TSH is low or inappropriately normal with low Free T4:
- Pituitary MRI to evaluate for pituitary pathology
- Additional pituitary hormone testing (cortisol, LH/FSH, prolactin)
- TRH stimulation test can help differentiate between pituitary and hypothalamic causes 4
Special Considerations
Pregnancy
- Pregnant women require special attention as thyroid requirements increase during pregnancy
- Monitor TSH monthly during pregnancy using trimester-specific reference ranges 1
Elderly Patients
- More likely to progress from subclinical to overt hypothyroidism
- May require more aggressive monitoring 1
Cardiovascular Disease
- Patients with cardiovascular disease may benefit from treatment at lower TSH thresholds 1
Common Pitfalls to Avoid
Relying solely on TSH: While TSH is the most sensitive test, a complete thyroid panel provides more comprehensive information about thyroid function and etiology 1
Overlooking non-thyroidal illness: Sick euthyroid syndrome can confuse laboratory interpretation in acutely ill patients 5
Inadequate follow-up: Repeat testing within 3 months is recommended for patients with subclinical hypothyroidism 1
Missing concomitant autoimmune disorders: Patients with autoimmune thyroid disease have higher risk of other autoimmune conditions 1
Ignoring medication effects: Many medications can affect thyroid function and laboratory test interpretation 2
The American College of Radiology notes that imaging studies generally have no role in the initial workup of hypothyroidism in adults, as the diagnosis is primarily biochemical 1. However, thyroid ultrasound may be helpful in cases where nodules are palpable or to assess thyroid size and echogenicity.