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Reliability of provocative tests to assess growth hormone secretory status. Study in 472 normally growing children
E Ghigo1, J Bellone, G Aimaretti
1Department of Internal Medicine, University of Turin, Italy.
Insights
Diagnosing growth hormone (GH) deficiency in children is challenging due to unreliable GH secretion tests. Combining growth hormone-releasing hormone (GHRH) with pyridostigmine (PD) or arginine (ARG) offers a more reliable method for assessing GH secretory capacity.
Area of Science:
- Pediatric Endocrinology
- Growth Hormone Physiology
- Diagnostic Testing
Background:
- The reliability of provocative stimuli for growth hormone (GH) secretion in diagnosing GH deficiency remains controversial.
- Establishing normative values for GH response to various stimuli has been a significant challenge in pediatric endocrinology.
Purpose of the Study:
- To evaluate the reliability of various GH secretion stimuli in children and adolescents.
- To determine the most effective diagnostic tests for GH deficiency in pediatric populations.
Main Methods:
- Studied GH response in 472 children and adolescents (normal stature and short stature) to 10 different stimuli.
- Stimuli included physical exercise, insulin-induced hypoglycemia, arginine (ARG), clonidine, levodopa, glucagon, pyridostigmine (PD), GHRH, PD + GHRH, and ARG + GHRH.
- Analyzed peak GH responses in micrograms/L for each stimulus.
Main Results:
- Conventional GH secretion stimuli frequently failed to elicit adequate GH levels, often falling below the assumed minimum normal peak of 7 or 10 micrograms/L.
- Growth hormone-releasing hormone (GHRH) combined with pyridostigmine (PD) or arginine (ARG) demonstrated the highest GH responses, consistently exceeding 19 micrograms/L.
- These combined tests showed potential in differentiating normal children from those with GH deficiency.
Conclusions:
- Growth hormone-releasing hormone (GHRH) combined with pyridostigmine (PD) or arginine (ARG) represents the most potent diagnostic approach for assessing somatotrope cell secretory capacity.
- While effective in differentiating many cases, these combined tests cannot definitively rule out GH hyposecretory states due to hypothalamic dysfunction.
- Further research is needed to establish definitive normative values and refine diagnostic criteria for GH deficiency.
Abstract:
The reliability of provocative stimuli of GH secretion in the diagnosis of GH deficiency is still controversial. Until now, normative values of GH response to various stimuli have not been established properly. In 472 children and adolescents with normal stature (n = 295, height SDS range -1.5 to 1.2) or normal short stature (n = 177, height SDS range -3.7 to -1.8), we studied the GH response to physical exercise, insulin-induced hypoglycemia, arginine (ARG), clonidine, levodopa, glucagon, pyridostigmine (PD), GHRH, PD + GHRH, and ARG + GHRH. The peak GH responses (range) to various stimuli were: 1) physical exercise: 3.0-28.3 micrograms/L; 2) insulin-induced hypoglycemia: 2.7-46.4 micrograms/L; 3) ARG: 0.5-48.4 micrograms/L; 4) clonidine: 3.8-86.0 micrograms/L; 5) levodopa: 1.9-40.0 micrograms/L; 6) glucagon: 1.9-49.5 micrograms/L; 7) PD: 2.5-35.0 micrograms/L; 8) GHRH: 2.7-102.7 micrograms/L; 9)PD + GHRH: 19.6-106.0 micrograms/L; and 10) ARG + GHRH: 19.4-120.0 micrograms/L. Our results show that all conventional stimuli of GH secretion frequently failed to increase GH levels, showing values lower than that arbitrarily assumed, so far, as minimum normal GH peak, i.e. 7 or 10 micrograms/L. When combined with PD or ARG (substances inhibiting hypothalamic somatostatin release), GHRH becomes the most powerful test to explore the secretory capacity of somatotrope cells (the GH response being always higher than 19 micrograms/L). Therefore, only GHRH combined with PD or ARG may be able to clearly differentiate normal children from patients with GH deficiency, though a normal GH response to these tests cannot rule out the existence of GH hyposecretory state because of hypothalamic dysfunction.