Background: Combined pituitary hormone deficiency (CPHD) may be congenital or acquired disorder, which affects more than one hormonal axis. Congenital hipopituitarism includes heterogenic group of disturbances. It may be result of mutations or deletions in genes for signaling and transcription factors responsible for pituitary development. The disorder might affect one or multiple family members. The age of appearance and intensity of the first hormone deficiency symptoms may depend on type of mutation. Some particular mutations may result in specific phenotype, form syndromes or show characteristic abnormalities in neuroimaging. We present group of 25 patients with combined pituitary hormone deficiency. In some of the patients delivery complications, neonatal adverse events such as hypoglycemia or intrahepatic cholestasis appeared, in others later on in childhood CPHD manifested as growth or puberty retardation. The symptoms observed in the youngest patients are non characteristic for hipopituitarism, what is the cause of difficulties and delayed diagnosis in this group. CPHD should be considered in neonates/infants presenting hypoglycemia, cholestasis, severe distress in course of infection, thermoregulation disturbances and dimorphic features.
Objective and hypotheses: Characterisation of CPHD patients group and determination of genetic cause of CPHD.
Method: Assessment of pituitary imaging, hormonal function and molecular analysis of genes for transcription factors PROP 1 and OTX 2.
Results: Patients with CPHD are heterogeneous group. Mutations in gene encoding PROP 1 were found in five of 21 analyzed patients. The analysis of OTX 2 gene was negative in the patient with CPHD and microphthalmia.
Conclusion: The variety of phenotypes and symptoms intensity poses serious problem for indication of the one characteristic genetic mutation. Defect in PROP 1 gene constitutes only part of possible genetic causes responsible for CPHD. Determining of specific gene mutations at early diagnostic stage enables to establish proper prognosis and adjust the optimal treatment.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology