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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 conte...

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Autores principales: Binder, Gerhard, Weber, Karin, degree, no, Rieflin, Nora, Steinruck, Louis, Franz, Axel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209635/
http://dx.doi.org/10.1210/jendso/bvaa046.499
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author Binder, Gerhard
Weber, Karin
degree, no
Rieflin, Nora
degree, no
Steinruck, Louis
degree, no
Franz, Axel
author_facet Binder, Gerhard
Weber, Karin
degree, no
Rieflin, Nora
degree, no
Steinruck, Louis
degree, no
Franz, Axel
author_sort Binder, Gerhard
collection PubMed
description 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.
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spelling pubmed-72096352020-05-13 OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off Binder, Gerhard Weber, Karin degree, no Rieflin, Nora degree, no Steinruck, Louis degree, no Franz, Axel J Endocr Soc Pediatric Endocrinology 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. Oxford University Press 2020-05-08 /pmc/articles/PMC7209635/ http://dx.doi.org/10.1210/jendso/bvaa046.499 Text en © Endocrine Society 2020. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Pediatric Endocrinology
Binder, Gerhard
Weber, Karin
degree, no
Rieflin, Nora
degree, no
Steinruck, Louis
degree, no
Franz, Axel
OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
title OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
title_full OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
title_fullStr OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
title_full_unstemmed OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
title_short OR10-02 Diagnosis of Severe GH Deficiency in Newborns: New Reference Range for the Preterm and Confirmation of the GH Cut-Off
title_sort or10-02 diagnosis of severe gh deficiency in newborns: new reference range for the preterm and confirmation of the gh cut-off
topic Pediatric Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7209635/
http://dx.doi.org/10.1210/jendso/bvaa046.499
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