Research Article
Volume 10 Issue 6 - 2021
Lessons from ACTH Tolerance Testing: Androgens and Hypertension
Fred Chasalow1,2*
1IOMA LLC, California, USA
2Visiting Professor, Department of Laboratory Medicine, VAMC, San Francisco, CA, USA
*Corresponding Author: Fred Chasalow, IOMA LLC, California, USA.
Received: May 08, 2021; Published: May 27, 2021




Abstract

The 17α-hydroxylase-17,20-lyase enzyme has a key role in adrenal steroid synthesis. The same protein catalyzes both functions. The lyase is needed for synthesis of adrenal androgens while the 17α-hydroxylase is needed for synthesis of cortisol. However, there is little understanding of the regulatory process that determines how [a] adrenal androgen production (DHEA-sulfate) is initiated and/or [b] what controls whether the adrenal produces cortisol or corticosterone.

This article describes a method to evaluate adrenal function and illustrates the results obtained in different disorders. Of particular importance, was the result in children with growth hormone deficiency. These children oversecreted corticosterone in response to ACTH and the response reverted to normal after 3 days of GH replacement therapy. The control group was children with short stature but who were not GH deficient. In that group, the 3 day course of GH therapy, did not change the corticosterone response to ACTH. We concluded that GH stimulated 17α-hydroxylase-17,20-lyase activity and GH deficient individuals would be expected to have low DHEA-S levels, low cortisol levels and elevated corticosterone levels. In fact, many studies have shown that GH secretion decreases as we grow older and that DHEA-S serum levels decrease with age. We propose that these are not independent observations but are related as cause and consequence.

Although the function of DHEA-S remains unknown, the same is not true for corticosterone because it functions as a mineralocorticoid. Individuals with GH deficiency have elevated corticosterone levels. This initiates the mineralocorticoid receptor cascade: [a] synthesis of epithelial sodium channels, [b] hypokalemia, [c] spiral steroid synthesis, [d] Na-K-ATPase regulation and [e] hypertension. Prior to the discovery of the spiral steroids (step c) and their function, when other causes of hypertension were eliminated, patients were diagnosed as having essential hypertension or, perhaps, low renin hypertension. We knew all along there had to be a cause of essential hypertension. Potentially, we can now diagnose and monitor essential hypertension by measuring spiral steroids, the missing link in the endocrine cascade. Thus, one cause of essential hypertension may be inadequate 17α-hydroxylase due to GH deficiency.

Keywords: ACTH; Premature Adrenarche; Corticosterone; PTSD; Hypertension; Spiral Steroids; GH Deficiency

References

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Citation: Fred Chasalow. “Lessons from ACTH Tolerance Testing: Androgens and Hypertension”. EC Paediatrics 10.6 (2021): 45-51.

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