Central hypothyroidism (CeH) can be defined as a lower than desirable secretion of thyroid hormone by a normal thyroid gland resulting from (quantitative or qualitative) insufficient TSH secretion. Causes are congenital and acquired functional or anatomic defects of the hypothalamus, pituitary gland or both. CeH can be difficult to diagnose, especially in children without a history of brain defects or brain damaging treatment (e.g. irradiation), and when plasma FT4 concentration lie around the lower border of the age specific reference interval. Congenital CeH can be detected by (total or free)T4+TSH-based neonatal screening programs. Analysis of the Dutch screening program showed the incidence of permanent congenital CeH to be approximately 1 in 18 000. Approximately 75 to 80% of detected neonates have additional anterior pituitary hormone deficiencies, like ACTH or GH deficiency, stressing the importance of early detection. Therefore, neonates with CeH need assessment of the integrity of their hypothalamo-pituitary adrenal and GH/IGF-1 axes. Mutations of the TRH receptor and TSH beta subunit genes are well known causes of isolated permanent congenital CeH. Recently, mutations in the IGSF1 gene were found to be a third genetic cause. Like primary (or thyroidal) hypothyroidism, CeH is an indication for thyroxine treatment. Thyroxine dose adjustments should be guided by measurement of the plasma or serum FT4 concentration. Unanswered questions with regard to treatment concern the best plasma FT4 concentration to aim at, and thyroid hormone target tissue parameters that might be helpful herein.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology