Etiology and outcome of non-estrogen associated hyperthyroxinemia in euthyroid patients at the San Juan City Hospital.

INTRODUCTION: Hyperthyroxinemia does not always equate to hyperthyroidism. Laboratory tests should always be correlated with the clinical picture. A mismatch should make one doubt true hyperthyroidism. The purpose of our study was to assess the etiology of euthyroid hyperthyroxinemia not associated with estrogen use or pregnancy and to review the outcome of those erroneously treated.

METHODS: The medical records of thirteen euthyroid patients with non estrogen associated hyperthyroxinemia were reviewed. They had a complete set of thyroid function tests including free T3 and free T4 by membrane dialysis, TRH stimulation test and thyroid hormone binding panel.

RESULTS: Two diagnostic groups were identified: Hyperthyroxinemia secondary to binding abnormalities (7/13), better known as familial dysalbuminemic hyperthyroxinemia (FDH) and hyperthyroxinemia secondary to Thyroid Hormone Resistance (THR) (6/13). The FDH group had an elevated T4 and FTI, with normal T3RU, TSH, TRH stimulation test but an abnormal thyroid hormone binding panel which was used to confirm the diagnosis. The THR group had two laboratory presentations: Four patients presented with all the thyroid hormone tests elevated (T4, T3, T3RU, FTI) including a free T3 and free T4 by membrane dialysis with a normal TSH and TRH stimulation test and a normal T4 binding panel. This presentation is typical for a TRH patient with a nuclear receptor defect where all the precursos to the defect accumulate. Two patients with THR presented elevated T4 and free T4 but normal T3 and free T3, localizing the defect at the level of the active T4 transport mechanism across the cellular membrane. These two patients had a normal TSH, TRH stimulation test and T4 binding panel. Two patients were treated erroneously with radioactive iodine and became extremely hypothyroid in spite of normal TFTs. Very high dose of thyroid hormone replacement were required to restore euthyroidism.

CONCLUSION: One must suspect these two entities in patients clinically euthyroid who have elevated T4 but non-suppressed TSH. A normal TSH and TRH test confirm euthyroidism. A thyroid hormone binding panel differentiates FDH from THR. Neither group require treatment. If treated erroneously and T4 drops to normal values, one must again induce hyperthyroxinemia to restore euthyroidism in these patients.