What labs should be checked for a patient presenting with potential thyroid and depression issues?

Laboratory Testing for Thyroid and Depression

For patients presenting with potential thyroid dysfunction and depression, order TSH and free T4 as the initial screening tests, followed by thyroid antibodies (TPO and thyroglobulin) if hypothyroidism is confirmed. 1

Initial Laboratory Panel

The essential initial workup should include:

• TSH (Thyroid-Stimulating Hormone) - This is the primary screening test for thyroid dysfunction 1
• Free T4 (Free Thyroxine) - Required to differentiate subclinical from overt thyroid dysfunction 1
• Complete metabolic panel - Including electrolytes, calcium, magnesium, blood urea nitrogen, and serum creatinine 1
• Complete blood count - To assess for anemia and other hematologic abnormalities 1
• Fasting blood glucose or glycohemoglobin (HbA1c) - To evaluate for diabetes mellitus 1
• Lipid profile - As dyslipidemia commonly coexists with both conditions 1
• Liver function tests - To assess hepatic function before potential medication initiation 1

Thyroid-Specific Testing Algorithm

When TSH is Abnormal:

For elevated TSH (hypothyroidism):

• Confirm with repeat TSH and free T4 testing 1
• Add thyroid peroxidase (TPO) antibody testing to identify autoimmune thyroiditis (Hashimoto's disease) 1
• Consider thyroglobulin antibody testing, though TPO is more predictive 1

For suppressed TSH (hyperthyroidism/thyrotoxicosis):

• Measure free T4 or total T3 levels 1
• Add thyroid-stimulating immunoglobulin (TSI) or TSH receptor antibody (TRAb) to differentiate Graves' disease from thyroiditis 1
• Consider TPO antibody testing 1

Timing Considerations:

• Perform testing in the morning (around 8 AM) for optimal accuracy, particularly if evaluating for central causes 1
• If testing at initial presentation during acute depression or metabolic instability, repeat after achieving metabolic stability to avoid misleading results from "euthyroid sick syndrome" 1
• Confirm abnormal results with repeat testing over 3-6 months before initiating treatment 1

Evidence Supporting the Thyroid-Depression Connection

The relationship between thyroid dysfunction and depression is clinically significant:

• Both low TSH (<0.5 mIU/L) and very elevated TSH (≥10 mIU/L) are associated with increased odds of clinically relevant depression 2
• Research suggests an optimal TSH cut-off of 2.5 mIU/L based on depression symptoms, with 89.66% sensitivity for detecting depression 3
• Approximately 4-6.5% of depressed patients have some degree of hypothyroidism, though overt thyroid disease is rare 4, 5
• The comorbidity between anxiety disorders and thyroid disorders is significant, with blunted TSH responses commonly observed 1

Important Clinical Caveats

Avoid these common pitfalls:

• Do not rely solely on TSH if central hypothyroidism (hypophysitis) is suspected—the pattern shows low TSH with low free T4, requiring additional pituitary hormone testing (ACTH, cortisol, FSH, LH, testosterone/estradiol) 1
• Depression symptoms overlap significantly with both hypothyroidism (fatigue, weight gain, cold intolerance, constipation) and hyperthyroidism (anxiety, palpitations, heat intolerance, tremors) 1
• Subclinical hypothyroidism (elevated TSH with normal T4) may still contribute to depressive symptoms and warrants consideration for treatment 3, 6
• Autoimmune thyroiditis can coexist with depression even when thyroid function tests are normal, suggesting shared autoimmune mechanisms 6

Additional Testing in Specific Scenarios

If hypophysitis or central thyroid dysfunction is suspected (headache, fatigue, low TSH with low free T4):

• Morning ACTH and cortisol (or cosyntropin stimulation test) 1
• Gonadal hormones (testosterone in men, estradiol in women) 1
• FSH and LH 1
• MRI of the sella with pituitary cuts 1

Note: If both adrenal insufficiency and hypothyroidism are present, steroids must be started before thyroid hormone replacement to avoid precipitating adrenal crisis 1