Resistance to thyroid hormone in a patient with thyroid dysgenesis

We report a patient with the unusual coincidence of two rare congenital disorders, lingual ectopy of the thyroid gland and resistance to thyroid hormone (RTH), resulting in impaired thyroid hormone production and action, respectively. The proposita had a positive thyrotropin (TSH) newborn screening test (350 mU/L, confirmed) with normal thyroxine (T4) and no clinical signs of hypothyroidism. A scintiscan revealed lingual but no orthotopic thyroid tissue. Levothyroxine (LT4) replacement failed to reduce TSH and was discontinued after four months owing to significantly elevated free T4. Her physical and mental development was unremarkable, and she was considered to be clinically euthyroid throughout childhood, even though she received either no T4 or a dose insufficient to lessen hyperthyrotropinemia. At the age of 15 years, T4 was gradually increased to a supraphysiological dose of 300 microg/d, resulting in the normalization of the serum TSH level, and subjective improvements in her ability to concentrate. The proposita's mother was clinically euthyroid, had a palpable diffuse goiter, and thyroid function tests consistent with RTH. This diagnosis was confirmed by detection of a heterozygous mutation (R320H) in the thyroid hormone receptor-beta (TR-beta) gene found in both the proposita and her mother. Under the high-dose T4 regimen, the patient's TSH and free T4 values resembled those of untreated patients with TRbeta R320H mutation, suggesting that a compensated state could be achieved, at least at the pituitary level. In the proposita, treatment of hyperthyrotropinemia is clearly mandatory because of potential complications inflicted by TSH-stimulated growth of the lingual tissue. To our knowledge, this represents the first report of congenital hypothyroidism secondary to thyroid dysgenesis complicated by coincidental RTH.