Pharmacological and Physiological Growth Hormone (GH) Stimulation Tests to Predict Successful GH Therapy in Children

Abstract

Although the current use of growth hormone (GH) stimulation tests (GHSTs) is still subject to debate, the tests are widely used to diagnose GH deficiency. This literature review evaluates primarily the sensitivity, specificity and reliability of GHSTs and secondarily their convenience. Single pharmacological tests typically address only a single pathway in the complex physiological regulation of GH secretion and are therefore characterized by lower sensitivity, specificity and reliability than combined pharmacological tests or physiological tests. In spite of the high levels of sensitivity, specificity and reliability, physiological tests require considerably more effort to perform, from the physician as well as from the child. Therefore, a need for an alternative, convenient, physiological GHST still remains. Oral ingestion of dietary protein is convenient in practice and may induce more physiological stimulation of GH secretion, hence may be a promising valuable addition to the existing GHSTs in GH deficiency.

Height Gain at Adult-Height Age in 184 Short Patients Treated with Growth Hormone from Prepubertal Age to Near Adult-Height Age is Not Related to GH Secretory Status at GH Therapy Onset

“…These data concur with those previously reported indicating that many factors may confound the GH secretion evaluation by GH-release stimuli, which may cast doubt on the clinical usefulness of these stimuli [1,3,9,10,11,12,13,14]. Indeed, these stimuli represent a high degree of stress and discomfort for patients and are potentially dangerous [3,13,14]. Furthermore, in addition to the clinical and endocrine assessment, neuroradiology and molecular studies are mandatory to differentiate idiopathic from organic or genetic isolated GH deficiency.…”

“…Moreover, in almost 30% of patients, dissociated GH-release peaks were observed (GH peak >10 ng/ml after one stimulus and lower after the other) with heterogeneity in patient response to the same stimulus (in some patients a GH peak >10 ng/ml was observed after one stimulus and in other patients after the other, and the same occurred for a GH peak <10 ng/ml) (data not shown). These data concur with those previously reported indicating that many factors may confound the GH secretion evaluation by GH-release stimuli, which may cast doubt on the clinical usefulness of these stimuli [1,3,9,10,11,12,13,14]. Indeed, these stimuli represent a high degree of stress and discomfort for patients and are potentially dangerous [3,13,14].…”

“…These results, together with the fact that GH secretory stimuli are non-physiologic, irreproducible and potentially dangerous, place in doubt the use of these stimuli to be able to decide on GH therapy in these patients [1,3,9,10,11,12,13,14]. By contrast, anthropometric data referred to current well-established longitudinal prepubertal and pubertal growth studies, together with safety criteria, may aid the clinical decision to start, continue or stop GH therapy in these prepubertal children.…”

“…However, they are used for diagnosis and for deciding on GH therapy since no better alternatives are currently available for the evaluation of GH secretion in clinical practice [1,3,9,10,11,12,13,14]. …”

Growth Hormone Secretory Status Evaluated by Growth Hormone Peak after Two Pharmacological Growth Hormone Release Stimuli Did Not Significantly Influence the Two-Year Catch-Up Growth Induced by Growth Hormone Therapy in 318 Prepubertal Short Children with Idiopathic Growth Retardation

“…In prepubertal short children with idiopathic growth retardation, GH peak release after GH provocative stimuli is currently used to evaluate GH secretory status and to decide on GH therapy. However, GH release after stimuli varies and arbitrary cutoffs are used to classify patients as growth hormone-deficient (GHD) or non-GHD [1,2,3,4,5,6,7,8,9]. …”