Differential Diagnosis

The patient's laboratory results and clinical history suggest a complex thyroid function disorder. Here's a categorized differential diagnosis:

• Single most likely diagnosis

  • Thyroid Hormone Resistance: This condition is characterized by elevated levels of thyroid hormones (free T4 and free T3) with an inappropriately elevated TSH level, despite the patient being on levothyroxine. The normal pituitary MRI and lack of other pituitary hormone abnormalities support this diagnosis. The history of similar labs and cycles of normal and abnormal thyroid function tests also points towards a resistance issue rather than an overproduction or exogenous source of thyroid hormones.

• Other Likely diagnoses

  • TSH-secreting Pituitary Adenoma: Although the pituitary MRI is normal, very small adenomas can sometimes be missed. The elevated TSH with high free T4 and free T3 levels could be indicative of a TSH-secreting adenoma, especially if the adenoma is not visible on the MRI or if the MRI was not of high enough resolution.
  • Familial Dysalbuminemic Hyperthyroxinemia (FDH): This is a rare condition but could be considered given the elevated free thyroid hormone levels with an elevated TSH. However, FDH typically presents with elevated total T4 and T3 but normal free T4 and T3 levels due to abnormal binding proteins.
  • Exogenous Thyroid Hormone Ingestion: Although the patient is on levothyroxine, the possibility of taking additional thyroid hormone should be considered, especially given the fluctuating lab results. However, this would typically suppress TSH, not elevate it.

• Do Not Miss (ddxs that may not be likely, but would be deadly if missed.)

  • Pituitary Macroadenoma with Thyroid Stimulation: Even though the MRI is normal, a very small or atypical adenoma could be present. If a macroadenoma is missed, it could lead to significant morbidity due to local effects (e.g., compression of surrounding structures) or due to excessive hormone secretion.
  • Metastatic Disease to the Pituitary: Although rare, metastatic disease to the pituitary gland could cause abnormal hormone secretion, including TSH. This would be particularly concerning in patients with a known history of cancer.

• Rare diagnoses

  • Thyroid Hormone Resistance due to Transporter Defects: Defects in the transport of thyroid hormones into cells could mimic resistance at the receptor level. This is a rare condition and would require specific testing to diagnose.
  • Generalized Resistance to Thyroid Hormone (GRTH): A condition where there is resistance to thyroid hormone action in peripheral tissues but not in the pituitary, leading to elevated TSH and thyroid hormone levels. This condition is rare and typically presents with goiter and other signs of hyperthyroidism despite elevated TSH.