Development and Validation of a Prediction Rule for Growth Hormone Deficiency Without Need for Pharmacological Stimulation Tests in Children With Risk Factors

CLEMENT, FLORENCIA; ROMINA GRINSPON; YANKELEVICH DANIEL; MARTÍN BENÍTEZ SABRINA; DE LA OSSA SALGADO, MARÍA CAROLINA; ROPELATO MG; BALLERINI MG; ANA KESELMAN; DEBORA BRASLAVSKY; PATRICIA A. PENNISI; IGNACIO BERGADÁ; FINKIELSTAIN GABRIELA; REY RODOLFO

Frontiers in Endocrinology

Frontiers Media

Lugar: Lausanne; Año: 2021

1664-2392

Introduction: Practice guidelines cannot recommend establishing a diagnosis of growthhormone deficiency (GHD) without performing growth hormone stimulation tests (GHST)in children with risk factors, due to the lack of sufficient evidence.Objective: Our goal was to generate an evidence-based prediction rule to diagnose GHDin children with growth failure and clinically identifiable risk factors.Methods: We studied a cohort of children with growth failure to build the predictionmodel, and a second, independent cohort to validate the prediction rule. To this end, weassessed the existence of: pituitary dysgenesis, midline abnormalities, (supra)sellar tumor/surgery, CNS infection, traumatic brain injury, cranial radiotherapy, chemotherapy, geneticGHD, pituitary hormone deficiencies, and neonatal hypoglycemia, cholestasis, orhypogenitalism. Selection of variables for model building was performed using artificialintelligence protocols. Specificity of the prediction rule was the main outcome measure inthe validation set.Results: In the first cohort (n=770), the resulting prediction rule stated that a patient wouldhave GHD if (s)he had: pituitary dysgenesis, or two or more anterior pituitary deficiencies,or one anterior pituitary deficiency plus: neonatal hypoglycemia or hypogenitalism, ordiabetes insipidus, or midline abnormalities, or (supra)sellar tumor/surgery, or cranialradiotherapy ≥18 Gy. In the validation cohort (n=161), the specificity of the prediction rulewas 99.2% (95% CI: 95.6?100%).Conclusions: This clinical rule predicts the existence of GHD with high specificity inchildren with growth disorders and clinically identifiable risk factors, thus providing compelling evidence to recommend that GHD can be safely diagnosed without recurringto GHST in neonates and children with growth failure and specific comorbidities.Keywords: multiple pituitary hormone deficiencies, pituitary dysgenesis, short stature, growth failure, midline abnormalities