Evaluation of growth hormone provocative tests in Egyptian children with growth hormone-related short stature

BACKGROUND: Diagnosing growth hormone deficiency (GHD) in children remains challenging because of the considerable variability in the results of growth hormone (GH) provocative tests. AIM: To evaluate the validity of different GH provocative tests, determine the sampling time associated with the peak GH response, and identify optimal GH cut-off values for excluding GHD. METHODS: This cohort study included 50 children aged 5-16 years presenting with proportionate short stature. GH secretion was stimulated using the insulin tolerance test, clonidine test, and levodopa (L-DOPA) test. Serum GH and insulin-like growth factor-1 levels were measured using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Among the studied participants, 48% were diagnosed with GHD, while 52% were classified as having idiopathic short stature. The clonidine stimulation test showed the highest median GH level at 90 minutes, followed by the insulin-induced peak at 45 minutes and the L-DOPA peak at 60 minutes. A statistically significant positive correlation was observed between the insulin-like growth factor-1 Z-score and the GH level measured at 90 minutes during the clonidine test. Receiver operating characteristic curve analysis demonstrated optimal GH cut-off values of 7.54 ng/mL for the insulin test, 8.48 ng/mL for the clonidine test, and 4.63 ng/mL for the L-DOPA test. These cut-offs showed sensitivities of 59.3%, 77.8%, and 80%, and specificities of 91.3%, 82.6%, and 70%, respectively. CONCLUSION: Oral clonidine and L-DOPA stimulation tests appear to be useful and safe alternatives for diagnosing GHD, avoiding the risk of hypoglycemia associated with the insulin tolerance test. Lower GH peak cut-off values may improve the diagnostic performance of these provocative tests.