Patterns of Adrenal Secretion and Urinary Excretion of Aldosterone and Plasma Renin Activity in Normal and Hypertensive Subjects

In this report we present 302 measurements of either the adrenal secretion of aldosterone or the urinary excretion rate of the acid-labile conjugate of the hormone in 168 patients with various forms and stages of hypertensive disease. The measurements were compared with results obtained in normal subjects studied under similar circumstances of sodium balance. Studies of 73 consecutive patients with essential hypertension provided no indication that an abnormality in aldosterone secretion or metabolism participates in the pathogenesis of this condition. Furthermore, no instances of occult primary aldosteronism were discovered. These results give no support to the claims of other groups of a 20 to 44% incidence of aldosteronism in uncomplicated benign essential hypertension. Our total experience indicates that primary aldosteronism is a rare cause of hypertensive vascular disease. Increased aldosterone secretion was frequently observed in the more advanced forms and stages of hypertensive diseases. Oversecretion occurred in certain patients with the hypertension of unilateral renal disease, it was more common in more advanced hypertensive disease, and it was practically always present in malignant hypertension. These findings suggest that excess aldosterone secretion is probably not critically related to the initiation or maintenance of the hypertensive process. However, when increased secretion develops, it may accelerate the pace and severity of the disease. This possibility is supported by a good correlation between the degree of aldosteronism and the severity of the hypertensive condition. In 40 patients studied with essential, renal, advanced, or malignant hypertension, a direct correlation was observed between the rate of aldosterone secretion and plasma renin levels. This pattern suggests that increased plasma renin is usually the basis for the aldosteronism. There was no evidence in the group for the reverse relationship, characteristic of primary adrenal overactivity, i.e., for plasma renin to be suppressed when aldosterone secretion is increased. Indeed, in essential hypertension, when plasma renin levels were low, aldosterone secretion also tended to be low. The adrenal cortex has an unusual capacity to form nodules and adenomas. This tendency seems more pronounced in hypertensive subjects, especially when the disease has been of long duration. Because of this and because, at least in the population that we have examined, oversecretion of aldosterone usually appeared to be secondary to increased renin levels, the possibility has been raised that at least some adrenal nodules might arise from extra-adrenal stimulation. One patient with aldosteronism and bilateral adrenal hyperplasia was greatly improved following a total adrenalectomy. The presence of markedly swollen and degranulated juxtaglomerular cells suggests that a unique renal mechanism may have been involved in the pathogenesis of this particular hypertensive disorder. Full understanding of the sequential participation of renin, angiotensin, and aldosterone in hypertensive diseases will depend on a more complete understanding of the many factors which seem to be involved in this complex hormonal interaction.