Differential Diagnosis for Normal TSH, Low T3, and Low T4

Single Most Likely Diagnosis

• Sick Euthyroid Syndrome (SES): Also known as non-thyroidal illness syndrome (NTIS), this condition is characterized by abnormal thyroid function tests in the setting of systemic illness, without actual thyroid disease. The normal TSH with low T3 and T4 levels is a common finding in critically ill patients, reflecting a adaptive response to severe illness.

Other Likely Diagnoses

• Pituitary or Hypothalamic Disease: Although less common, diseases affecting the pituitary gland or hypothalamus can lead to central hypothyroidism, where TSH is inappropriately normal due to decreased production or effect, alongside low T3 and T4 levels.
• Thyroid Hormone Resistance: A rare condition where the body's tissues are resistant to thyroid hormones, leading to variable presentations, including low T3 and T4 with a normal TSH.
• Glucocorticoid-Induced Thyroid Dysfunction: Prolonged use of glucocorticoids can suppress TSH secretion and affect thyroid hormone levels, potentially leading to a picture of low T3 and T4 with a normal TSH.

Do Not Miss Diagnoses

• Pituitary Apoplexy: A medical emergency where a pituitary tumor undergoes sudden hemorrhage or infarction, potentially leading to acute hypopituitarism, which could present with normal or low TSH and low thyroid hormone levels.
• Traumatic Brain Injury: Severe head injuries can disrupt the hypothalamic-pituitary axis, leading to central hypothyroidism among other hormonal deficiencies.
• Infiltrative Diseases (e.g., Sarcoidosis, Lymphocytic Hypophysitis): These conditions can infiltrate the pituitary gland or hypothalamus, leading to hormonal deficiencies, including thyroid hormone abnormalities.

Rare Diagnoses

• Familial Dysalbuminemic Hyperthyroxinemia (FDH): A rare condition affecting the binding of thyroid hormones to albumin, potentially leading to abnormal thyroid function tests, though typically T4 is more affected than T3.
• Thyroid Hormone-Binding Globulin (TBG) Deficiency: A genetic condition leading to low levels of TBG, which can result in low total T3 and T4 levels but normal free hormone levels and a normal TSH.
• Iodine Deficiency or Excess: Both can affect thyroid hormone production, though iodine deficiency typically leads to elevated TSH, and excess can lead to a variety of thyroid function test abnormalities.