ESPE2014 Poster Category 2 Pituitary (10 abstracts)
Background: DAVID syndrome (deficit in anterior pituitary function and variable immune deficiency) (J Clin Endocrinol Metab 97 E121, 2012) can be caused by NFKB2 mutations (Am J Hum Genet 93 13, 2013). All patients have an orthotopic posterior pituitary (PP) and most only ACTH deficiency.
Objective and Hypothesis: To describe a girl with common variable immunodeficiency (CVID), ectopic PP (EPP) and multiple pituitary hormone deficiencies, and to demonstrate genetic heterogeneity of DAVID syndrome.
Case presentation: A 17-year-old girl with unexplained intellectual disability was admitted for glomerulonephritis and found to have CVID (Pediatr Nephrol 24 601, 2009). In addition, she had height at target, primary amenorrhea and Tanner B2P1. On ultrasound, the uterus was small but the ovaries were normal. The epiphyses were fused. MRI showed an EPP, a thin stalk and a small anterior pituitary. Cortisol was <11.1 nmol/l, DHEAS <0.5 μmol/l, and ACTH 0.8 pmol/l. Cortisol replacement was given. fT4 and total T3 were normal. IGF-I was 3.9 pmol/l and peak GH after arginine 0.02 μg/l. On LHRH testing, LH rose from 3.2 to 28.8 mUI/l and FSH from 5.3 to 13.5 mUI/l; on TRH testing, TSH rose from 7.2 to 31.2 mU/l at 30 min and remained high at 90 min (15.5 mU/l) while prolactin rose from 10.4 to 45.2 μg/l at 10 min. Pubertal induction was started. Between 17 and 20 years, BMI increased from 24 to 31 kg/m2. NFKB2 was normal.
Discussion: This patient has CVID and severe cortisol deficiency, as is the rule in DAVID syndrome, but also severe GHD and hypothalamic hypogonadism. The EPP suggests that the endocrinopathies are developmental rather than autoimmune.
Conclusion: DAVID syndrome is clinically and genetically heterogeneous. While a search for an alternative genetic etiology is underway, we suggest describing our patients condition as GOLIATH syndrome: GHD, obesity, low IQ, IgG, and ACTH deficiency, Triad and Hypogonadism.
18 Sep 2014 - 20 Sep 2014