Background: Congenital isolated ACTH-deficiency is a rare disorder characterized by low plasma ACTH and cortisol levels and normal secretion of other pituitary hormones. TBX19 is a t-box transcription factor with a specific role in the differentiation of corticotroph cells. TPIT gene mutations can be found in early onset isolated ACTH deficiency.
Case report: We report on a 2; 6 year old girl, offspring from consanguineous parents from Turkey, born at 40 weeks gestational age by caesarian section because of placental insufficiency. The girl developed severe hypoglycaemia in the 1st day of life and cholestasis in the first weeks. Muscular hypotonia made tube feeding necessary, no further hypoglycaemias occurred. Metabolic and infectious diagnostic work-up was performed without pathological findings. Psychomotor development was delayed, at the age of 8 months central hypothyroidism was diagnosed and levothyroxine substitution was started. At the age of 15 months severe hypoglycaemia with status epilepticus occurred, anticonvulsive treatment was begun. Although neonatal hypoglycaemia, prolonged jaundice due to cholestasis and muscular hypotonia are characteristic symptoms of congenital hypoadrenalism, the diagnosis hypocortisolism was delayed and made at the age of 2 years. Further diagnostic evaluation showed isolated ACTH deficiency. Growth was normal, IGF1 and IGFBP3 were in the upper normal range. The molecular genetic testing rendered a mutation in the TBX 19 gene: Homozygous for c.856C>T (p.Arg286*), exon 6. The mutation has been previously reported and is responsible for the isolated ACTH deficiency.
Conclusion: Isolated ACTH deficiency is a rare disease and is a possible cause of congenital hypoadrenalism. To our knowledge the TBX19 Mutation is not related to central hypothyroidism.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology