Euthyroid athyroxinemia - a novel endocrine syndrome

Area of Science:

• Endocrinology
• Genetics
• Molecular Biology

Background:

• A 55-year-old female presented with abnormal thyroid function tests (TFTs), including undetectable free thyroxine (FT4) despite normal free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH).
• She had a long-standing, large, soft, lobulated goiter and was clinically euthyroid.
• Family history revealed similar thyroid abnormalities in two of her children.

Purpose of the Study:

• To investigate a previously unreported form of dyshormonogenesis.
• To characterize the progressive loss of thyroxine (T4) synthesis while preserving triiodothyronine (T3) production.
• To demonstrate the functional thyroid deficit using recombinant human TSH (rhTSH).

Main Methods:

• Thyroid function tests (TFTs), including FT4, FT3, and TSH, were monitored.
• Radioactive iodine uptake scans (Tc-99) were performed.
• Recombinant human TSH (rhTSH) stimulation test was administered to assess thyroid response.
• Thyroid function and scans were evaluated in the patient's children.

Main Results:

• The patient's FT4 remained undetectable (<3.3 pmol/L) even after rhTSH stimulation, which paradoxically increased FT3 and TSH levels.
• Thyroxine (T4) replacement therapy normalized FT4 levels and suppressed TSH.
• Two of the patient's children exhibited goiters and elevated Tc-99 uptake, with one son showing low FT4 and normal TSH.

Conclusions:

• A novel form of dyshormonogenetic goiter is identified, characterized by a progressive inability to synthesize T4 but not T3.
• The condition appears to have a familial component.
• The rhTSH test effectively demonstrated the specific defect in T4 synthesis.