Congenital hypothyroidism with gland in situ: diagnostic revaluation.

In the past, most Congenital Hypothyroidism (CH) children with thyroid gland in situ were considered to be affected by hormonogenesis defect. Nowadays, the improved sensitivity of neonatal screening, novel insights into the pathogenic mechanisms and the advances of genetic analyses have reopened the discussion about the etiology of CH with thyroid in situ. We report the etiological revaluation of 31 children with thyroid in situ, who had been identified by the CH screening program. The purpose of this revaluation was to investigate the definitive diagnosis and pathogenic mechanism of CH with thyroid in situ in eligible children suspected of dyshormonogenic defect and to verify the adequacy of the treatment schedules. Thirty out of thirty-one children were affected with permanent hypothyroidism and only one child was euthyroid at revaluation (transient CH). I-123 scintigraphy with perchlorate discharge test showed 13 children with iodine organification defects. In patients without iodine organification defect, analyses of TSH-receptor and PAX8 genes showed an inactivating TSH-receptor gene mutation in one patient. Thyroid hormone organification defect were present only in half of the CH patients with thyroid in situ. A higher prevalence of partial defects of iodine organification than severe or complete forms was found. So far, genetic analyses have provided etiological diagnosis in a limited subset of patients. Some questions remain unanswered concerning the proper treatment of mild and borderline forms of CH