Ann Pediatr Endocrinol Metab.  2021 Mar;26(1):46-52. 10.6065/apem.2040110.055.

Novel function of adrenocorticotropic hormone in the stimulation of vascular endothelial growth factor release in healthy children and adolescents: a proof-of-concept study

• Heksch R
• Bowden S
• Hoffman R

• KMID: 2514152
• DOI: http://doi.org/10.6065/apem.2040110.055

Abstract

Purpose
To assess the effect of adrenocorticotropic hormone (ACTH) on plasma vascular endothelial growth factor (VEGF) levels in healthy children and adolescents and to inform future work on the effects of ACTH on VEGF in bone.
Methods
An Institutional Review Board-approved prospective study of 10 healthy subjects, ages 9–17, was conducted to assess the effect of ACTH on plasma VEGF levels. VEGF levels were collected at baseline and every 30 minutes for 3 hours. Cosyntropin (a synthetic ACTH analogue) was administered at a low-dose (1 μg) given at t=0 minutes and a high-dose (250 μg) given at t=60 minutes. A Friedman test was performed comparing baseline to peak VEGF levels after stimulation with low-dose and high-dose cosyntropin.
Results
Peak plasma VEGF levels significantly increased after high-dose cosyntropin compared with baseline (P=0.042). Peak plasma VEGF levels did not significantly increase after low-dose cosyntropin compared to baseline.
Conclusion
To our knowledge, this is the first study to demonstrate that ACTH administration causes a significant increase in plasma VEGF levels in humans. This finding may have important implications in the protective effects of ACTH on bone. Decreased bone mineral density and adrenal suppression are common side effects of glucocorticoid use in pediatrics. VEGF increases vascularity and may play a role in reducing glucocorticoid-induced bone disease. Animal studies have shown that ACTH stimulates release of VEGF in osteoblasts, though this effect has yet to be evaluated in humans.

Keyword

Bone density; Glucocorticoids; Adrenocorticotropic hormone; Vascular endothelial growth factor; Adrenal insufficiency

Figure

• 

  Fig. 1. Paired vascular endothelial growth factor (VEGF) levels at each time point for every subject. Each subject’s plasma VEGF levels are shown at each time point denoted by a different symbol for each subject. Baseline VEGF was at t=0 minutes, the response to the low-dose (1 μg) cosyntropin was t=30 and 60 minutes, and the response to the high-dose (250 μg) cosyntropin was at t=90, 120, 150, and 180 minutes.

• 

  Fig. 2. Mean and peak vascular endothelial growth factor (VEGF) at each time point. The solid line denotes the mean (±standard error) VEGF level of all of the subjects at each time point. Cosyntropin was given right after the t=0 and t=60-minute blood draws. The bars denote how many subjects had their highest peak VEGF level at that time point.

• 

  Fig. 3. Baseline compared to peak vascular endothelial growth factor (VEGF) level after cosyntropin administration. Mean, median, and interquartile ranges for VEGF levels at baseline and peak after stimulation by low- and high-dose cosyntropin. NS, not significant. **Statistically significant increase from baseline (P=0.042). X denotes mean value.

• 

  Fig. 4. Baseline and peak cortisol levels for each subject. Baseline compared with peak cortisol for each patient after low-dose (LD) and high-dose (HD) cosyntropin administration. Solid horizontal line denotes a value of 15.5 μg/dL (428 nmol/L, passing cutoff for ACTH stimulation test). Subject numbers 2, 6, and 7 did not have a peak cortisol above 15.5 μg/dL (428 nmol/L) after the low-dose stimulation, but all subjects had a peak above 15.5 μg/dL (428 nmol/L) after the high-dose stimulation.

Reference

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