Euthyroid hyperthyroxinemia and thyroxine-binding prealbumin excess in islet cell carcinoma

Area of Science:

• Endocrinology
• Oncology
• Biochemistry

Background:

• Thyroid hormone levels are regulated by binding proteins, primarily thyroxine-binding globulin (TBG) and transthyretin (TTR, also known as thyroxine-binding prealbumin or TBPA).
• Euthyroid hyperthyroxinemia can occur due to abnormalities in these binding proteins, leading to elevated total thyroxine (T4) without clinical hyperthyroidism.

Observation:

• A 73-year-old male patient with metastatic islet cell carcinoma presented with hyperthyroxinemia (total serum T4: 18.5 µg/dL) despite normal free T4 and thyroid-stimulating hormone (TSH) levels.
• Electrophoresis revealed significantly increased [125I]T4 binding to TBPA (52.0% vs. normal 30.0%) and a markedly elevated serum TBPA concentration (189 mg/dL vs. normal 18-40 mg/dL).

Findings:

• The patient's hyperthyroxinemia was attributed to elevated serum TBPA, not increased thyroid hormone production or TBG abnormalities.
• Family members and other islet cell carcinoma patients showed normal TBPA levels, except for one patient with insulinoma who had mildly elevated TBPA.
• These findings suggest that islet cell carcinoma may rarely produce a TBPA-like protein, leading to elevated serum TBPA and consequently euthyroid hyperthyroxinemia.

Implications:

• This case highlights a rare cause of euthyroid hyperthyroxinemia associated with specific cancers.
• Measuring serum TBPA levels can be valuable in diagnosing unexplained hyperthyroxinemia, especially in patients with a history of islet cell carcinoma.
• Further research is warranted to elucidate the exact nature of the TBPA-like protein produced by islet cell tumors and its clinical significance.