ESPE Abstracts

Background: Microdeletion of 14q22q23 results in a rare chromosomal disorder associated with microphthalmia/anophthalmia, pituitary anomalies, polydactyly/syndactyly, micrognathia, growth restriction and mental retardation. Haploinsufficiency of the genes OTX2 (orthodenticle homeobox 2) and BMP4 (bone morphogenetic protein 4) are responsible for most of the phenotypic features in the 14q22q23 microdeletion syndrome. There are only a few reports about liver dysfunction induced by levothyroxine in childhood.

Case presentation: The patient was born at 38 weeks and 5 days. His birth length and weight were 41.5cm (-3.5SD) and 1946g (-2.5SD). He showed bilateral anophthalmia, micrognathia, low set ears, micropenis, cryptorchidism at birth. He also had respiratory failure, hypoglycemia and bilateral hearing loss. The brain magnetic resonance imaging revealed anterior pituitary hypoplasia, ectopic posterior pituitary, bilateral anophthalmia and severe micrognathia. Endocrine examination revealed combined pituitary hormone deficiency. GH level was 1.2 ng/ml after arginine stimulation and IGF-1 level was low (11 ng/ml). His cortisol (1.0µg/dl) and FT4 (0.74 ng/dl) levels were low. LH, FSH and testosterone were undetectable. His karyotype was 46,XY. Array CGH revealed 7.6Mb microdeletion of 14q22.1q23.1 including OTX2 and BMP4 genes. Levothyroxine sodium powder and hydrocortisone administration started at 1 month and GH therapy started at 4 months. After starting levothyroxine sodium powder administration, he showed liver dysfunction. The levels of AST and ALT increased gradually and reached 1547 U/l and 688U/l at 3 months old. Liver dysfunction was reversed with discontinuation of levothyroxine sodium powder administration. The drug-induced lymphocyte stimulation test (DLST) using levothyroxine was positive. Instead of it, we started liothyronine at 4 months. It is difficult to control thyroid function using liothyronine because there are not appropriate markers. We changed to powdered levothyroxine tablet at 7 months. He did not show liver dysfunction under administration of these. After starting GH therapy, his growth rate improved a little. He also needed tracheotomy and gastrostomy because he could not extubate and showed difficulty in swallowing because of severe micrognathia.

Conclusion: GH therapy slightly improved growth rate in this case, but since GH deficiency was probably not only factor responsible for growth retardation, in patients with 14q22q23 deletion, GH therapy was not completely effective in stimulating normal growth. This finding is not unexpected because previous reports showed there were patients with growth retardation in the absence of GH deficiency and growth was difficult to correct with GH therapy in patients with GH deficiency.