OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off

Introduction Inborn severe GHD is caused by rare disorders of pituitary morphogenesis or function and frequently associated with additional pituitary hormone deficiencies. Affected newborns commonly present with recurrent hypoglycemia; therefore early diagnosis and therapy is warranted. The GH content of the newborn screening card is a reliable indicator of severe neonatal GHD. Here, we studied the GH content in screening cards and the history of 25 newborns with severe GHD. In addition, we determined the reference range of the GH content in screening cards from 282 healthy preterm newborns. Patients and Methods Since 2010, a total of 110 screening cards from hospitalized ill newborns were sent to our laboratory for measuring GH content. Using a questionnaire we obtained relevant clinical information from senders in 61 cases. Severe GHD was defined by the presence of recurrent neonatal hypoglycemia with either a significant cerebral MRI morphology or two additional pituitary hormone deficiencies. In addition, the GH content of screening cards from 282 healthy newborns born preterm with a gestational age at birth from 34.0 to 37.9 weeks was prospectively analyzed. The GH concentration of the eluate from the screening card was measured by a highly sensitive ELISA (Mediagnost, Germany); the GH serum concentration was calculated. Results In 25 patients, the definition of severe GHD of the newborn was fulfilled; based on recurrent hypoglycemia in combination with ectopia of the neurohypophysis in 17, septum pellucidum agenesis plus opticus hypoplasia in two, severely hypoplastic pituitary gland in two, and combined TSH and ACTH deficiency with no cMRI findings in four newborns. Five newborns with severe GHD were preterm. The median GH concentration of the term newborns with severe GHD (n=20) was 3.9 µg/l (range; 1.1 to 11.8). This was significantly below the previously reported reference data from healthy term newborns (n=269) (median 16.4 µg/l; 95% reference range 7.0 to 39.4) (p<0.001). Using ROC plot analysis a GH serum concentration of 7.0 µg/l was identified as cut-off with the highest accuracy (90.0% sensitivity and 98.7% specificity). The median GH concentration of the 5 preterm newborns with severe GHD was 7.7 µg/l (range; 2.1 to 9.9). The newly determined 95% reference range for healthy newborns born preterm with a gestational age from 34.0 to 37.9 weeks (n=282) spanned from 7.9 to 41.1 µg/l with a median of 20.3 µg/l. Conclusions A GH content below 7.0 ng/ml in the newborn screening card identified severe GHD with 90% sensitivity and 98.7% specificity. In preterm newborns, the lower limit of the 95% reference interval was by 0.9 µg/l higher than in term newborns. The newborn screening card is a valuable source for the diagnosis of GH deficiency in newborns and young infants.