Background: Combine pituitary hormone deficiency (CPHD) may be caused by many factors. One them is PROP1 gene mutation, that causes maldevelopment of GH, TSH, LH, FSH prolactin but not ACTH, producing cells (CPHDPROP1).
Objective and hypotheses: The details of possible differences between phenotypes of CPHDPROP1 and CPHD of other reasons (CPHDnonPROP1) are not clear to date. The aim of the study was to determine the frequency of PROP1 gene mutation in CPHD patients and to compare the phenotypes of patients with CPHDPROP1 and CPHDnon PROP1.
Method: In 74 (32 ♀) CPHD patients retrospective analysis of growth pattern, puberty, hormonal function, MRI of pituitary, PROP1 gene investigation were performed.
Results: PROP1 gene mutations were stated in 43 patients (58%), in remaining patients CPHD was caused by other inborn defects. CPHDPROP1 in comparison to CPHDnon PROP1 patients presented with: higher birth weight (0.2 vs −0.3 SDS, P=0.02), perinatal abnormalities (n=1 vs 17), younger age at diagnosis (4.9 vs 8 years, P=0.006), less frequent neonatal hypoglycaemia (n=0 vs 4). At the moment of diagnosis there was no significant differences in height SDS (−4.1 vs −4.3), BMI SDS (0.22 vs 0.01). All patients presented with secondary hypothyroidism. The CPHDPROP1 in comparison to CPHDnon PROP1 patients presented higher median GH peak value in stimulation tests (1.26 vs 0.87 ng/ml, P=0.02), less frequent secondary adrenal insufficiency (SAI) (2.4 vs 74%), however in 55% of CPHDPROP1 patients SAI was recognized at later age. 92% of CPHDnon PROP1 and all CPHDPROP1 patients who reached the age of puberty presented with hypogonadotrophic hypogonadism. In all CPHDPROP1 patients MRI examination revealed smaller, normal or enlarged pituitary, ectopy of the posterior lobe in one CPHDPROP1 patient and in eight CPHDnon PROP1.
Conclusions: PROP 1 gene mutation is the most common cause of CPHD in Polish population. Analysis of the birth, growth data, as well as hormonal status at the moment of diagnosis may indicate on PROP1 gene mutation. PROP1 gene investigation in CPHD patients might be helpful in order to anticipate SAI at later age.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology