Diagnosing growth hormone deficiency- Can a combined arginine and clonidine stimulation test replace two separate tests?

Abstract

Objective: Given a large number of false-positive growth hormone deficiency (GHD) diagnoses from a single GH stimulation test (GHST) in normal children, two different pharmacological tests, performed on separate days or sequentially, are required. This study aims to assess the reliability and safety of a combined clonidine-arginine stimulation test (CACST).

Design: Retrospective, single-center, observational study

Methods: During 2017-2019, 515 children aged >8 years underwent GHSTs in our tertiary endocrine center [CACST-362; clonidine-first stimulation test (CST)-153]. The main outcome measures evaluated comparing the tests are GH response (sufficiency/deficiency), amplitude and timing of peak GH, and safety parameters.

Results: Population characteristics: median age - 12.2 years (IQR 10.7,13.4), boys -331 (64%), prepubertal - 364 (70.7%). GHD rate was comparable in both GHSTs: CACST -12.7%; CST followed by confirmatory tests with glucagon or arginine - 14.4%, P=0.609. GH response was characterized by a higher peak following CACST compared to CST [14.6 ng/ml (IQR 10.6,19.4) vs. 11.4 ng/ml (IQR 7.0, 15.8), P<0.001]; a late GH peak in the CACST relative to CST [90 min (IQR 60,90) vs. 60 min (IQR 60,90), P<0.001]. GH response was not affected by puberty. No serious adverse events occurred.

Conclusion: The CACST is reliable and safe in detecting GHD in prepubertal and adolescent children suggesting it may replace separate or sequential GHSTs. By minimizing the need for a second GHST, the CACST reduces discomfort for the patients and their caregivers, saves time, and is more cost-effective.