Differential Diagnosis for Chronically Abnormal T3 and T4 but Normal TSH

Single Most Likely Diagnosis

• Thyroid Hormone Resistance: This condition is characterized by reduced sensitivity to thyroid hormones, leading to elevated levels of T3 and T4 with a normal or slightly elevated TSH. It's a genetic disorder affecting the thyroid hormone receptor beta (TRβ) gene, making it a plausible explanation for the described lab findings.

Other Likely Diagnoses

• T3 and T4 Toxicity due to Exogenous Thyroid Hormone Intake: Intentional or accidental ingestion of thyroid hormones can lead to elevated T3 and T4 levels. The body may not increase TSH in response to exogenous hormones, especially if the intake is recent or intermittent.
• Pituitary or Hypothalamic Disease: Certain conditions affecting the pituitary or hypothalamus can disrupt the normal feedback loop, leading to abnormal thyroid hormone levels without the expected TSH response. However, these conditions are less common and often present with other symptoms.
• Thyroid Hormone Binding Protein Abnormalities: Alterations in the proteins that bind thyroid hormones (e.g., thyroxine-binding globulin, TBG) can affect the measured levels of T3 and T4 without altering their biologically active, free fractions. This can be due to genetic variations, liver disease, or other conditions affecting protein production.

Do Not Miss Diagnoses

• Pituitary Tumor (Especially TSH-Producing Adenoma): Although less likely, a TSH-producing pituitary adenoma could potentially present with normal TSH levels if the tumor produces an inactive form of TSH or if there's a mixed population of TSH-producing and non-functioning cells. Missing this diagnosis could lead to delayed treatment of a potentially serious condition.
• Thyroiditis: Certain forms of thyroiditis, such as subacute or silent thyroiditis, can cause fluctuations in thyroid hormone levels. Initially, there might be a phase of thyrotoxicosis (elevated T3 and T4) followed by a hypothyroid phase. The TSH can be normal or slightly elevated during the thyrotoxic phase, especially if the condition is in its early stages.

Rare Diagnoses

• Familial Dysalbuminemic Hyperthyroxinemia (FDH): A rare genetic condition characterized by an abnormal albumin that has a high affinity for T4, leading to elevated total T4 levels without affecting free T4 or TSH levels.
• Selective Pituitary Resistance to Thyroid Hormone: A rare condition where the pituitary gland is resistant to thyroid hormone, leading to an inappropriate secretion of TSH. However, this typically presents with elevated TSH rather than normal TSH levels, making it less likely in this scenario.
• Other Genetic Disorders: Various genetic disorders can affect thyroid hormone metabolism, transport, or action, leading to abnormal thyroid function tests. These are rare and often present with additional clinical features beyond abnormal thyroid function tests.