Objective: Congenital isolated ACTH deficiency (IAD) is a rare autosomal recessive disorder that is characterised by low levels of plasma ACTH and cortisol with normal pituitary structure and hormones. Clinical presentation can occur in the neonatal period, as well as later in childhood. Here, we report a patient with IAD due to a novel TPIT mutation.
Case: A 48/12 years old girl presented with loss of concioussness and found to be hypoglycemic with a capillary glucose of 25 mg/dl (1.4 mmol/l). The parents were first degree cousins. Patient was born at term with a birth weight of 3800 g (1.6 SDS) and had been hospitalized for 10 days in a neonatal care unit for her mild respiratory problems and the history of unidentified siblings death. She had several hospitalizations for hypoglycemia and episodes of abdominal pain and vomiting before her diagnosis is established. At her presentation to our clinic, her weight and height were 23.1 kg (1.8 SDS) and 116.5 cm (2.2 SDS), respectively. Weight for height was 0.8 SDS. Her mother and fathers height SDSs were −1.6 and −0.2, respectively. Cardiac and abdominal examination were normal, she was prepubertal. No hyperpigmentation was detected. Bone age was 7.8 years at admission. Laboratory investigations confirmed hypoglycemia, serum glucose 25 mg/dl (1.4 mmol/l), with a low-normal sodium (135 mmol/l) and normal potassium (4.5 mmol/l). Hyperinsulinemia was excluded. The child was hypocortisolemic (<0.1 μg/dl) with an extremely low ACTH level (<5 pg/ml). Insufficient cortisol response was detected in the low-dose ACTH stimulation test. Other anterior pituitary hormones were normal. A diagnosis of IAD was made and hydrocortisone treatment (10 mg/m2 per day) was started. Her hypoglycemic episodes and recurrent infections disappeared after replacement. Magnetic resonance imaging of the pituitary was normal. Whole exome sequencing revealed a novel homozygous c.302 G>A (p.Trp101Ter) mutation in TBX19 gene. In two years follow-up, her growth velocity was 4.6 cm/year. In the first and second year of her diagnosis height SDS was 1.6 and 1.3, respectively.
Conclusion: We reported a new mutation in the TBX19 gene in a patient with isolated ACTH deficiency. While overgrowth is a known feature of some types of familial glucocorticoid deficiency, it may be a novel feature for IAD as in our patient.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology