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W. Reid Litchfield, Francesco Fallo, Robert G. Dluhy, Impaired Potassium-Stimulated Aldosterone Production: A Possible Explanation for Normokalemia in Glucocorticoid-Remediable Aldosteronism—Authors’ Responsef, The Journal of Clinical Endocrinology & Metabolism, Volume 82, Issue 12, 1 December 1997, Page 4277, https://doi.org/10.1210/jcem.82.12.4466-6
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Thank you for forwarding the comments of Dr. Ganguly regarding our paper. In general we concur with the comments and appreciate the opportunity to respond to them.
As Dr. Ganguly suggests, an absence of a potassium-induced increase in aldosterone secretion in our GRA patients suggests it is the zona fasciculata that produces hyperaldosteronism in this disorder. It is precisely this ectopic location of aldosterone synthase activity, imparted by the chimeric 11-hydroxylase/aldosterone synthase gene, that differentiates GRA from other forms of primary aldosteronism. However, these observations are functional in nature. There is little data documenting the precise histomorphological characteristics of adrenal cells in GRA. It is still unclear if this represents complete sequestration of aldosterone production to the zona fasciculata, or the formation of a hybrid cell that shares the characteristics of the zona glomerulosa and zona fasciculata.
Our colleague points out the different baseline aldosterone levels in the two patient groups, yet still agree that the renal kaliuretic response to both potassium and fludrocortisone were equivalent in the two patient groups. We feel this effectively rules out the presence of an impaired kaliuretic capacity of the kidney in GRA. We concede that our study does not prove conclusively that normokalemia in GRA is due to GRA representing a milder form of primary aldosteronism relative to other types of hyperaldosteronism. Our study was not designed to test this hypothesis. Studies that directly compare potassium homeostasis in both GRA patients and other patients with primary aldosteronism will be needed to definitively address this hypothesis.
