Provocative growth hormone testing in children: how did we get here and where do we go now?

Abstract

Objectives Provocative growth hormone (GH) tests are widely used for diagnosing pediatric GH deficiency (GHD). A thorough understanding of the evidence behind commonly used interpretations and the limitations of these tests is important for improving clinical practice. Content To place current practice into a historical context, the supporting evidence behind the use of provocative GH tests is presented. By reviewing GH measurement techniques and examining the early data supporting the most common tests and later studies that compared provocative agents to establish reference ranges, the low sensitivity and specificity of these tests become readily apparent. Studies that assess the effects of patient factors, such as obesity and sex steroids, on GH testing further bring the appropriateness of commonly used cutoffs for diagnosing GHD into question. Summary and Outlook Despite the widely recognized poor performance of provocative GH tests in distinguishing GH sufficiency from deficiency, limited progress has been made in improving them. New diagnostic modalities are needed, but until they become available, clinicians can improve the clinical application of provocative GH tests by taking into account the multiple factors that influence their results.

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

“…This remark is in line with the previously discussed proposal of Wit et al [5]. Also Kamoun et al [81] have summed up the limitations of GH stimulation tests and have stressed the need for developing new diagnostic modalities in future, while now improving the clinical application of GH stimulation tests by taking into account all factors that may influence their results. Very recently, Rodari at al.…”

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

“…This remark is in line with the previously discussed proposal of Wit et al [5]. Moreover, Kamoun et al [14] summed up the limitations of GH stimulation tests and stressed the need for developing new diagnostic modalities in future, while now improving the clinical application of GH stimulation tests by taking into account all factors that may influence their results. The authors pointed to the poor performance of provocative GH tests in diagnosing GHD, as well as at the limited progress in overcoming the existing problems over the years.…”

“…Unfortunately, most of these issues still remain relevant today, after more than a quarter of a century. The most recent review, confirming the topicality of these problems, was published by Kamoun et al in 2021 [14].…”

The influence of growth hormone on pediatric body composition: A systematic review

“…Historically, clinical guidelines have recommended several different stimulation tests for the diagnosis of GHD, e.g., ITT, arginine stimulation test, clonidine stimulation test, clonidine-betaxolol test, levodopa stimulation test, GH-releasing hormone (GHRH)-arginine stimulation test, and the glucagon stimulation test; all of which carry their respective advantages and limitations ( 38 ). GH levels are measured at different times following drug administration, depending on drug type.…”

“…Additionally, as no single test is 100% effective in eliciting GH release ( 39 ), two GH provocation tests are typically conducted. GH levels typically peak 30–90 minutes after insulin administration or onset of arginine infusion, 30–120 minutes after levodopa administration, 60–90 minutes after clonidine administration, and 120–180 minutes after glucagon administration ( 38 ). The definition of a ‘normal’ GH response is somewhat arbitrary; generally, a stimulated GH level >10 ng/mL (>10 mcg/L) is sufficient to rule out classic GHD ( 40 , 41 ).…”