Differential Diagnosis for Elevated TSH and Low Free T4

Single Most Likely Diagnosis

• Primary Hypothyroidism: This is the most common cause of an elevated TSH level combined with a low free T4 level. It occurs when the thyroid gland does not produce enough thyroid hormones, leading to an increase in TSH as the pituitary gland attempts to stimulate the thyroid to produce more hormones.

Other Likely Diagnoses

• Subclinical Hypothyroidism with Decreased Free T4: Although subclinical hypothyroidism typically presents with a normal free T4 level, some cases may have a slightly decreased free T4, especially if the condition is progressing towards overt hypothyroidism.
• Pituitary Resistance to Thyroid Hormones: A rare condition where the pituitary gland is less responsive to negative feedback from thyroid hormones, leading to elevated TSH despite normal or low thyroid hormone levels.
• Thyroid Hormone Resistance: Similar to pituitary resistance but involves resistance at the tissue level, leading to elevated TSH and low free T4 in some cases.

Do Not Miss Diagnoses

• Pituitary Tumor (TSH-Secreting Adenoma): Although rare, a TSH-secreting pituitary adenoma can cause elevated TSH and low free T4 levels. Missing this diagnosis could lead to unnecessary treatment with thyroid hormone replacement instead of addressing the pituitary tumor.
• Hypothalamic or Pituitary Disease: Other diseases affecting the hypothalamus or pituitary gland, such as infiltrative diseases or apoplexy, can disrupt normal thyroid hormone regulation, leading to abnormal TSH and free T4 levels.

Rare Diagnoses

• Thyroid Hormone Deficiency Due to Medication: Certain medications, such as amiodarone or lithium, can affect thyroid function, leading to hypothyroidism.
• Congenital Hypothyroidism in Adults: Although typically diagnosed in infancy, some cases of congenital hypothyroidism may not be diagnosed until adulthood, presenting with elevated TSH and low free T4.
• Iodine Deficiency: Severe iodine deficiency can lead to hypothyroidism, although this is rare in areas where iodized salt is commonly used.
• Thyroid Dysgenesis or Agenesis: Abnormal development of the thyroid gland, which can lead to hypothyroidism, is usually diagnosed in childhood but can occasionally be found in adults.