Background: Congenital isolated adrenocorticotrophic hormone (ACTH) deficiency (IAD) is a rare condition. It is characterized by low plasma and cortisol levels and preservation of all other pituitary hormones (2 cases described with transient partial growth hormone deficiency). The principal molecular cause is identified as TPIT mutation. We present here the case of a neonate with TPIT mutation and ACTH deficiency associated with probable growth hormone and thyrotropin deficiencies.
Results: The patient was the couples first child. Parents were first cousins. The boy was delivered at 37 weeks of gestation, with birth weight of 2750 g, from first cousins parents. He had immediate hypotonia, poor feeding, hypoglycemia (blood glucose 1.65 mmol/L), and early jaundice. Transfontanelar ultrasound and electroenkephalogram were normal. Total and direct bilirubin and gamma-glutamyl transpeptidase (GGT) were 300 μmol/L, 260 μmol/L and 186 UI/L respectively. At d12, TSH was 3.1 mUI/L (110), FT4 14.40 pmol/L (1828), suggesting thyrotropin deficiency; IGF1, IGFBP3, and baseline GH were 21 ng/mL (45150), 0.9 mg/L (1.23.0), and 7.60 ng/mL (730), respectively, suggesting GHD. ACTH, cortisol, and DHEA-S levels were < 1.0ng/L (549), 1 μg/L (18252), and 53 ng/mL (3602000), respectively, indicating corticotropin deficiency. Hydrocortisone, growth hormone, and thyroid hormone treatments were started, which allowed for a rapid improvement of hypotonia, jaundice, and blood glucose. Pituitary MRI was normal.
Conclusion: Given the apparent multiple pituitary hormone deficiencies, PROP1 and LHX3 genes were first screened for mutation (negative). Eventually, an homozygous TPIT mutation was found (c.383 C>A). Multiple pituitary hormone deficiencies may lead to the molecular diagnosis of TPIT mutation.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology