Differential Diagnosis for Normal TSH and Low T4

Single Most Likely Diagnosis

• Euthyroid Sick Syndrome: This condition is characterized by low T4 levels in the presence of normal TSH, often seen in patients with acute or chronic systemic illnesses, such as severe infection, trauma, or malignancy. The body's response to stress leads to alterations in thyroid hormone levels without actual thyroid disease.

Other Likely Diagnoses

• Subclinical Hypothyroidism with Decreased T4 Production: Although TSH is normal, some individuals may have a mild decrease in thyroid hormone production, which can be due to early stages of hypothyroidism or variations in the hypothalamic-pituitary-thyroid axis.
• Thyroid Hormone Resistance: A rare condition where the body's tissues are resistant to thyroid hormones, leading to variable presentations, including low T4 with normal TSH.
• Pituitary or Hypothalamic Dysfunction: Mild or early dysfunction of the pituitary gland or hypothalamus can lead to abnormalities in thyroid hormone regulation, resulting in low T4 with a normal TSH.

Do Not Miss Diagnoses

• Pituitary Tumor or Mass Effect: Although less common, a tumor or mass in the pituitary gland can lead to compression or destruction of normal pituitary tissue, affecting TSH secretion and leading to abnormal thyroid hormone levels.
• Central Hypothyroidism: A condition where the pituitary gland does not produce enough TSH, leading to decreased thyroid hormone production. It's crucial to identify this condition as it requires different management compared to primary hypothyroidism.
• Thyroid-Binding Globulin (TBG) Deficiency: A genetic condition leading to low levels of TBG, a protein that binds thyroid hormones in the blood, resulting in low total T4 but normal free T4 and TSH.

Rare Diagnoses

• Familial Dysalbuminemic Hyperthyroxinemia (FDH): A rare genetic condition affecting the binding of thyroid hormones to albumin, potentially leading to abnormal thyroid function tests, including low T4 with normal TSH.
• Selective Pituitary Resistance to Thyroid Hormone: A rare condition where the pituitary gland is resistant to thyroid hormone, leading to elevated TSH and variable thyroid hormone levels, but can occasionally present with normal TSH and low T4 in certain contexts.
• Iatrogenic Causes: Certain medications, such as glucocorticoids or dopamine, can suppress TSH secretion, potentially leading to a picture of normal TSH with low T4, especially in the context of critical illness or medication overdose.