Diagnosing Growth Hormone Deficiency: Can a Combined Arginine and Clonidine Stimulation Test Replace 2 Separate Tests?

Tal Oron, Avihu Krieger, Michal Yakobovich-Gavan, Ariel Tenenbaum, Rotem Diamant, Moshe Phillip, Liora Lazar

Research output: Contribution to journalArticlepeer-review


Objective: Given the large number of false-positive growth hormone deficiency (GHD) diagnoses from a single growth hormone (GH) stimulation test in children, 2 different pharmacologic tests, performed on separate days or sequentially, are required. This study aimed to assess the reliability and safety of a combined arginine-clonidine stimulation test (CACST). Methods: This was a retrospective, single-center, observational study. During 2017-2019, 515 children aged >8 years underwent GH stimulation tests (CACST: n = 362 or clonidine stimulation test [CST]: n = 153). The main outcome measures used to compare the tests were GH response (sufficiency/deficiency) and amplitude and timing of peak GH and safety parameters. Results: Population characteristics were as follows: median age of 12.2 years (interquartile range [IQR]: 10.7, 13.4), 331 boys (64%), and 282 prepubertal children (54.8%). The GHD rate was comparable with 12.7% for CACST and 14.4% for CST followed by a confirmatory test (glucagon or arginine) (P =.609). Peak GH was higher and occurred later in response to CACST compared with CST (14.6 ng/mL [IQR: 10.6, 19.4] vs 11.4 ng/mL [IQR: 7.0, 15.8], respectively, P <.001; 90 minutes [IQR: 60, 90] vs 60 minutes [IQR: 60, 90], respectively, P <.001). No serious adverse events occurred following CACST. Conclusion: Our findings demonstrate the reliability and safety of CACST in detecting GHD in late childhood and adolescence, suggesting that it may replace separate or sequential GH stimulation tests. By diminishing the need for the second GH stimulation test, CACST saves time, is more cost-effective, and reduces discomfort for children, caregivers, and medical staff.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalEndocrine Practice
Issue number1
StatePublished - Jan 2022


  • GH deficiency
  • GH stimulation test
  • arginine
  • clonidine
  • combined test
  • growth


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