Clinical characteristics of a pediatric cohort of patients with combined pituitary insufficiency caused by mutations of the PROP1 gene

Abstract The most commonly identified genetic cause of combined pituitary deficiency (CPHD) are PROP1 gene mutations. The aim of the study was to compare selected clinical features of patients with CPHD caused by mutations of the PROP1 gene (CPHD-PROP1) and patients with inborn CPHD of other etiology (CPHD-nonPROP1). Material and Methods: The retrospective analysis included childhood medical records of 74 patients (32 female) with CPHD, including 43 patients (23 female) with the mutation in the PROP1 gene. Results: Patients with CPHD-PROP1 compared to the CPHD-nonPROP1 presented with: significantly higher mean birth weight (0.2 vs. -0.3 SDS, p=0.019), lower growth velocity within 3 years preceding growth hormone administration (-2.7 vs. -0.8 SDS, p<0.05), higher mean maximal blood concentration of growth hormone in the stimulation (1.2 vs. 1.08 ng/mL, p=0.0025), lower TSH (1.8 μIU/mL vs. 2.4 μIU/mL, p=0.0002) and prolactin (128 vs. 416.3 μIU/mL, p<0.001) concentrations, and less frequent typical signs of hypogonadism at birth in boys (n=6; 30% vs. n=12, 54%, p=0.0002). Secondary adrenal insufficiency was less frequent in CPHD-PROP1 (20 vs. 25 cases, p=0.006), and occurred at a later age (13.4 vs. 10.4 years). MRI of the pituitary gland in CPHD-PROP1 revealed: small pituitary gland (21 cases), pituitary gland enlargement (8 cases), 1 pituitary stalk interruption and posterior lobe ectopy, in 9 cases normal. Conclusion: Patients with the PROP1 mutations present a clinical picture significantly different from other forms of congenital hypopituitarism.