John P. Cain

Studies of the control of plasma aldosterone concentration in normal man: I. Response to posture, acute and chronic volume depletion, and sodium loading

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.

Nelson's Syndrome: Frequency, Prognosis, and Effect of Prior Pituitary Irradiation

Previous reports differ regarding the frequency and course of pituitary tumors occurring after adrenalectomy for bilateral adrenal hyperplasia (Nelsons syndrome). In this report, 120 patients who were adrenalectomized for bilateral adrenal hyperplasia were followed for 2 to 20 years. Nine of the 120 developed Nelsons syndrome (8%), the tumors appearing 6 months to 16 years after adrenalectomy. In the majority of cases, the course was benign; seven patients are living an average of 9.7 years after discovery of their tumors. Finally, contrary to previous reports, pituitary irradiation before adrenalectomy did not prevent Nelsons syndrome. Twenty of 120 patients had pituitary irradiation as the initial treatment for bilateral adrenal hyperplasia and two subsequently developed pituitary tumors. Thus, after adrenalectomy for bilateral adrenal hyperplasia, all patients, regardless of previous pituitary irradiation, should be followed indefinitely with periodic X rays of the sella turcica for the possible occurrence of Nelsons syndrome.

Relation of age, diastolic pressure and known duration of hypertension to presence of low renin essential hypertension

Plasma renin activity and aldosterone secretion rates were measured in 100 patients with essential hypertension in response to a low sodium diet and upright posture. Plasma renin activity showed a subnormal response in 22 percent of patients, and a greater than normal response in 4 percent. In contrast to findings in 50 normal subjects, there was a significant positive correlation between the incidence of subnormal renin response and patient age and level of diastolic blood pressure. There was no correlation between renin response and known duration of hypertension. Comparison of several clinical and biochemical variables among the renin study subgroups revealed no differences except that the group with a low level of renin activity excreted a greater amount of sodium. These data support the hypothesis that a low renin activity level may evolve with time in patients with essential hypertension.

The regulation of aldosterone secretion in primary aldosteronism

Abstract Twenty patients with primary aldosteronism were studied under various conditions known to influence aldosterone secretion. All patients presented with the classic findings of hypertension, hypokalemia, suppressed plasma renin activity and nonsuppressible aldosterone secretion. At surgery all patients had adrenal adenomas, and hypertension disappeared or diminished in all but one case. Further study of these patients was performed to determine the factors controlling aldosterone secretion in this disease. Aldosterone responses to dietary alterations of sodium or potassium, saline infusion, dexamethasone suppression, volume depletion, ACTH stimulation both in vivo and in vitro, and angiotensin stimulation in vitro were evaluated. Aldosterone secretion was altered by all direct acting stimuli (ACTH, potassium and angiotensin II) but not by those working indirectly through volume expansion or depletion. Thus, these tumors were still responsive to regulatory factors despite suppression of the renin-angiotensin system. Although these patients had a normal diurnal rhythm of aldosterone indicative of an ACTH effect, the major determinants of the daily output were probably potassium and the size and biosynthetic capacity of the tumor. This altered regulatory mechanism has important diagnostic considerations since it means that dietary intake of both sodium and potassium and the hypokalemia induced by sodium loading may alter aldosterone secretion or plasma levels.

Gigantism with hypopituitarism: A reevaluation

Abstract A forty-one year old man described in 1963 as having hypo-pituitarism with gigantism due to normal or excessive growth hormone secretion associated with a deficiency of other pituitary hormones was reevaluated with specific tests of growth hormone reserve. Deficiency of thyrotropin, corticotropin and gonadotropins was confirmed. Immunoreactive growth hormone was virtually absent in the fasting state and failed to be released during insulin-induced hypoglycemia or with the administration of arginine, glucagon or Pitressin®. These new methods for the direct measurement of pituitary hormones suggest that this patient has insufficiency of all pituitary hormones, including growth hormone, and that his tall stature was due to eunuchoid growth rather than to pituitary gigantism.