The compound heterozygotic mutations of the TPO gene (c.2268-2269 insT and c.2090 G>A) in two patients with congenital goiters hypothyroidism were demonstrated.
The main outcomes were TPOAb concentrations and positivity, thyroid hormone concentrations (TSH, free T4), and clinical thyroid diseases (subclinical and overt hypothyroidism and goiter).
Hypothyroid PPT patients were more often thyroid autoantibody-positive (P<0.005) and the TPO antibody median value was higher compared to hyperthyroid PPT patients (500 and 32 U/ml, P<0.0001).
Hyperthyroidism in Graves' disease is caused by thyroid-stimulating autoantibodies to the TSH receptor (TSHR), whereas hypothyroidism in Hashimoto's thyroiditis is associated with thyroid peroxidase and thyroglobulin autoantibodies.
No thyroid antibodies were present in the affected siblings in family A, while the male in family B with hypothyroidism had antibodies against thyroid peroxidase at diagnosis.
Thyroid peroxidase (TPO) defects, typically transmitted as autosomal recessive traits, result in hypothyroid goiters with failure to convert iodide into organic iodine.
Finally, TPO autoantibody epitopic fingerprints are distinctive for individual sera, are not associated with hypothyroidism, but are conserved over time (indicating a lack of B cell epitope spreading).
We investigated an adopted boy with iodide organification defect, who presented with florid hypothyroidism at the age of 4 mo, poorly complied with thyroxine treatment, and developed a compressive goiter necessitating partial resection at the age of 12 yr. Biochemical studies revealed the absence of TPO activity in the resected tissue.