What lab tests to order for a patient with low Thyroid-Stimulating Hormone (TSH) and low Thyroxine (T4) levels?

Laboratory Evaluation for Low TSH (0.39) and Low T4 (1.3)

For a patient with low TSH (0.39) and low T4 (1.3), you should order Free T3 (FT3) and thyroid antibodies (TPO, TRAb, TSI) to differentiate between central hypothyroidism and thyroiditis. 1, 2

Initial Diagnostic Approach

• Repeat thyroid function tests (TSH, Free T4) within 2-4 weeks to confirm persistence of abnormal values 1, 2
• Order Free T3 (FT3) or Total T3 to complete the thyroid hormone profile and help distinguish between different thyroid disorders 1, 3
• Test for thyroid antibodies including TPO (thyroid peroxidase), TRAb (TSH receptor antibody), and TSI (thyroid-stimulating immunoglobulin) to help determine etiology 2
• Consider radioactive iodine uptake measurement and scan to distinguish between destructive thyroiditis and hyperthyroidism due to Graves' disease or nodular goiter 1

Interpretation of Results

• Low TSH with low T4 suggests possible central hypothyroidism (pituitary or hypothalamic dysfunction) 1, 2
• If Free T3 is elevated despite low T4, consider T3-thyrotoxicosis 3, 4
• If all thyroid hormones (TSH, T4, T3) are low, evaluate for non-thyroidal illness syndrome (sick euthyroid syndrome) 1, 2
• If thyroid antibodies are positive, this may suggest autoimmune thyroid disease such as Hashimoto's thyroiditis in recovery phase 1, 2

Additional Testing Based on Clinical Context

• Morning cortisol testing should be considered to rule out concurrent adrenal issues, especially if central hypothyroidism is suspected 2
• TRH stimulation test may be helpful in distinguishing between primary and central causes of thyroid dysfunction, though this is less commonly used with modern sensitive TSH assays 5, 6
• Pituitary MRI should be considered if central hypothyroidism is suspected to evaluate for pituitary lesions 2

Follow-up Testing

• For confirmed abnormal values, continue monitoring thyroid function tests every 3-6 months until stabilized 1
• Be aware that thyroiditis often follows a pattern: initial thyrotoxic phase followed by hypothyroidism approximately 1-2 months later, requiring ongoing monitoring 1, 2
• If on levothyroxine therapy, TSH and Free T4 should be checked every 6-12 months once stable 1

Important Clinical Considerations

• Use third-generation TSH assays with functional sensitivity ≤0.01 mIU/L for accurate assessment of subtle thyroid dysfunction 5
• Individual variation in thyroid function tests is typically narrow, so significant changes from a patient's baseline may be clinically relevant even if values remain within reference ranges 7
• The T3:T4 ratio can help differentiate between Graves' disease (ratio >20 ng/μg) and painless thyroiditis (ratio <20 ng/μg) 4
• Consider endocrinology referral if the diagnosis remains unclear after initial testing 2