Differential Diagnosis for Low TSH with Normal T3 and T4

Single Most Likely Diagnosis

• Subclinical Hyperthyroidism: This condition is characterized by a low TSH level with normal T3 and T4 levels. It can be due to various causes, including early stages of hyperthyroidism, thyroid hormone resistance, or the effect of certain medications. The absence of TPO and thyrotropin antibodies makes an autoimmune cause less likely, but it does not rule out other forms of subclinical hyperthyroidism.

Other Likely Diagnoses

• Non-Thyroidal Illness (NTI): Also known as euthyroid sick syndrome, NTI can present with low TSH and normal T3 and T4 levels, especially in the context of systemic illness. The mechanism is complex and involves alterations in the hypothalamic-pituitary-thyroid axis.
• Thyroid Hormone Resistance: A rare condition, but it can present with a similar laboratory profile. It is characterized by reduced sensitivity to thyroid hormones, leading to elevated or normal thyroid hormone levels with a low TSH.
• Exogenous Thyroid Hormone Ingestion: Accidental or intentional ingestion of thyroid hormone can suppress TSH production while maintaining normal T3 and T4 levels, especially if the dose is not high enough to elevate these hormones above the normal range.

Do Not Miss Diagnoses

• Pituitary Adenoma (TSH-Producing or Non-Functioning): Although less likely, a pituitary adenoma could potentially cause alterations in TSH secretion. A non-functioning adenoma could compress the normal pituitary tissue, affecting TSH production, while a TSH-producing adenoma is rare but could lead to hyperthyroidism symptoms.
• Thyroiditis (in the Recovery Phase): After an episode of thyroiditis, the thyroid gland may go through a phase of recovery where TSH is low due to the initial hyperthyroid phase, followed by a return of T3 and T4 to normal levels as the gland recovers.

Rare Diagnoses

• Familial Dysalbuminemic Hyperthyroxinemia: A rare condition characterized by abnormal binding of T4 to albumin, leading to elevated total T4 but normal free T4 and T3 levels. TSH can be low due to the feedback mechanism.
• Struma Ovarii: A rare ovarian tumor that contains thyroid tissue, which can produce thyroid hormones, leading to low TSH and potentially normal T3 and T4 levels if the production is not excessive.
• HCG-Producing Tumors: Certain tumors that produce human chorionic gonadotropin (hCG) can stimulate the thyroid gland, leading to increased production of thyroid hormones and a subsequent decrease in TSH.