Differential Diagnosis for Low TSH and Low to Normal Free T4 and Free T3

Single Most Likely Diagnosis

• Non-Thyroidal Illness (NTI): Also known as euthyroid sick syndrome, this condition is characterized by low TSH and low to normal free T4 and free T3 levels in patients with acute or chronic systemic illnesses, not due to primary thyroid disease. The body's response to stress and illness can alter thyroid hormone levels without actual thyroid dysfunction.

Other Likely Diagnoses

• Thyroid Hormone Resistance: A rare condition where the thyroid hormone receptors are less sensitive to thyroid hormones, leading to elevated thyroid hormone production and thus low TSH. However, free T4 and free T3 levels might be low to normal due to the body's attempt to compensate for the resistance.
• Subclinical Hyperthyroidism with Concurrent Illness: Although less common, patients with subclinical hyperthyroidism (low TSH with normal free T4 and free T3) who develop an acute or chronic illness might show a pattern of low TSH with low to normal free thyroid hormones due to the illness's effect on thyroid function tests.
• Recent Thyroid Hormone Withdrawal: In patients who have been on thyroid hormone replacement therapy, recent withdrawal can lead to a temporary state of low TSH and low to normal free T4 and free T3 as the body readjusts.

Do Not Miss Diagnoses

• Pituitary or Hypothalamic Disease: Although less likely, diseases affecting the pituitary or hypothalamus (e.g., tumors, infiltrative diseases) can lead to central hypothyroidism, which might present with low TSH and low to normal free T4 and free T3. Missing these diagnoses can have significant consequences due to the potential for mass effect and hormonal imbalances.
• Thyroiditis: Certain forms of thyroiditis, especially in the recovery phase, can present with a low TSH and variable free T4 and free T3 levels. It's crucial not to miss this diagnosis as it can have implications for long-term thyroid function.

Rare Diagnoses

• Familial Dysalbuminemic Hyperthyroxinemia (FDH): A rare condition characterized by abnormal thyroid hormone binding proteins, leading to altered measurements of free thyroid hormones. It might present with low TSH and low to normal free T4 and free T3 due to the laboratory measurement anomalies.
• Certain Genetic Disorders: Rare genetic disorders affecting thyroid hormone metabolism or action, such as MCT8 deficiency, can present with unusual thyroid function test patterns, including low TSH with low to normal free T4 and free T3.