Delayed Diagnosis of Congenital Combined Pituitary Hormone Deficiency including Severe Growth Hormone Deficiency in Children with Persistent Neonatal Hypoglycemia—Case Reports and Review

Apart from stimulation of human growth and cell proliferation, growth hormone (GH) has pleiotropic metabolic effects in all periods of life. Severe GH deficiency is a common component of combined pituitary hormone deficiency (CPHD). CPHD may be caused by mutations in the genes encoding transcription factors and signaling molecules involved in normal pituitary development; however, often its genetic cause remains unknown. Symptoms depend on which hormone is deficient. The first symptom of GH or adrenocorticotropic hormone (ACTH) deficiency may be persistent hypoglycemia in apparently healthy newborns, which is often neglected. Diagnosing CPHD is based on decreased concentrations of hormones secreted by the anterior pituitary and peripheral endocrine glands. Findings in magnetic resonance imaging vary widely, including anterior pituitary hypoplasia/aplasia or pituitary stalk interruption syndrome (PSIS). Delayed diagnosis and treatment can be life-threatening. GH therapy is necessary to recover hypoglycemia and to improve auxological and psychomotor development. We present two girls, diagnosed and treated in our departments, in whom the diagnosis of CPHD was delayed, despite persistent neonatal hypoglycemia; and a review of similar cases, with attention paid to progress in the genetic assessments of such patients, since the introduction of whole exome sequencing that is especially important for PSIS