Inherited abnormal thyroid hormone-binding protein causing selective increase of total serum thyroxine

Area of Science:

• Endocrinology
• Human Genetics
• Biochemistry

Background:

• Thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are crucial for metabolism and development.
• Thyroid hormone transport in blood is primarily mediated by thyroxine-binding globulin (TBG), T4-binding prealbumin (TBPA), and albumin.
• Abnormalities in TBG levels or function can lead to altered total and free thyroid hormone concentrations, potentially affecting thyroid status interpretation.

Observation:

• A 9-year-old euthyroid male presented with elevated serum T4 and free T4 index, but normal total T3.
• Reduced thyroxine-binding globulin (TBG) levels were detected, with T4 binding predominantly to an albumin-like protein.
• This abnormal binding protein exhibited low affinity and high capacity for T4, distinct from normal TBG.

Findings:

• The patient demonstrated an increased T4 bound to free ratio, leading to elevated total T4 despite normal free T4 levels.
• The abnormal protein showed low affinity for T3 compared to TBG.
• The condition was familial, suggesting an autosomal dominant inheritance pattern of a novel T4-binding protein replacing normal TBG.

Implications:

• This case highlights a unique genetic defect in thyroid hormone transport, leading to misinterpretation of thyroid function tests.
• Understanding this abnormal T4-binding protein is crucial for accurate diagnosis and management of thyroid disorders.
• Further characterization of this protein could offer insights into thyroid hormone regulation and binding mechanisms.