Development and Internal Validation of a Predictive Model for Adult GH Deficiency Prior to Stimulation Tests.

Fabio Bioletto,Silvia Grottoli,Valeria Cambria,Alessandro Maria Berton,Nunzia Prencipe,Mirko Parasiliti-Caprino,Valentina Gasco,Ezio Ghigo

doi:10.3389/fendo.2021.737947

Abstract

BackgroundThe diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results.MethodsEighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests.ResultsAn independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (<25%) pre-test GHD probability could be predicted when IGF-I SDS > +0.91 in the presence of other pituitary deficits or IGF-I SDS > -0.52 in the absence of other pituitary deficits. A high (>75%) pre-test GHD probability could be predicted when IGF-I SDS < -0.82 in the presence of other pituitary deficits or IGF-I SDS < -2.26 in the absence of other pituitary deficits.ConclusionThis is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis.

Highlights

Adult GH deficiency (GHD) is a heterogeneous disorder that may result from a variety of causes, including structural lesions, genetic abnormalities, traumas, infiltrative diseases, surgery or irradiation to the pituitary gland and/or hypothalamus [1,2,3,4,5]
insulin tolerance test (ITT) was performed by intravenous injection of 0.1-0.15 IU/kg of regular insulin at 0 min in normal weight and overweight/obese subjects, respectively; blood sampling for GH was performed every 15 min from 0 to +90 min; adequate hypoglycemia was defined as the achievement of a glucose level < 40 mg/dl
One hundred and twenty-three patients underwent both ITT and GHRH + ARG test in our Center between January 2017 and January 2019, in the appropriate clinical context for the suspicion of GHD according to the international guidelines [1]

Summary

Introduction

Adult GH deficiency (GHD) is a heterogeneous disorder that may result from a variety of causes, including structural lesions, genetic abnormalities, traumas, infiltrative diseases, surgery or irradiation to the pituitary gland and/or hypothalamus [1,2,3,4,5]. The most relevant stimulation tests to this scope are the insulin tolerance test (ITT), the GH-releasing-hormone + arginine (GHRH + ARG) test, the GHRH + GH-releasing-peptide-6 (GHRH + GHRP-6) test, and the glucagon test [1, 16,17,18] Their accuracy for GHD diagnosis, though high, is not perfect. This can make the recognition of GHD challenging, and may possibly result in a wrong diagnosis This picture is further complicated by the interaction between GHD and body mass index (BMI); obesity is a state of functional relative reduction of GH production, both in terms of spontaneous secretion [23,24,25] and in terms of responsiveness to stimulation tests [26, 27]. Their diagnostic accuracy, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results

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