Faculty Bibliography

Classic features of thyrotoxicosis developed in three patients with no prior history of thyroid disease shortly after the discontinuation of therapy with or decrease in doseage of propranolol hydrochloride. Graves' disease probably developed fortuitously after propranolol therapy was instituted, but the beta-adrenergic blockade masked the clinical features of hyperthyroidism. On discontinuation of propranolol therapy or decrease in propranolol dosage, previously latent thyrotoxicosis became manifest. If hyperthyroidism masked by beta-blockade is not recognized before withdrawal of propranolol therapy in patients with ischemic heart disease, the sudden appearance of thyrotoxicosis may lead to symptoms of increased myocardial ischemia.

The role of the renin-angiotensin system in mediating the aldosterone response to sodium depletion was examined by administration of propranolol during dietary sodium restriction. The beta-adrenergic antagonist prevented the expected increase of plasma renin activity in response to sodium restriction in six of twelve studies. Plasma angiotensin II concentration failed to increase in four of five subjects in whom the renin response was abolished. Despite unchanged or decreased plasma renin activity and plasma angiotensin II concentration, plasma aldosterone concentration increased significantly in response to dietary sodium restriction. The increase in aldosterone production could not be attributed to changes in plasma sodium or potassium concentration or increased ACTH secretion. It is suggested that the aldosterone response to sodium restriction is mediated not only by increased plasma renin activity and angiotensin II concentration, but also another mechanism, possibly related to increased adrenal sensitivity to angiotensin during sodium depletion.

An intensive study of the course of lupus nephritis has been undertaken in 88 patients in whom strict morphologic criteria were utilized in classification. All were treated with steroid, and 17 received cytotoxic drugs in addition. Focal proliferative lupus nephritis generally follows a benign course except in the occasional instances when transition to the diffuse proliferative or membranous forms occurs. Membranous lupus nephritis, when characterized by persistent nephrotic syndrome, leads slowly to renal failure, but this progression is aborted in the one-third in whom remission of the nephrotic syndrome can be achieved. A fatal outcome occurs within five years in the majority of those with diffuse proliferative lupus nephritis and the nephrotic syndrome, often in association with necrotizing renal vasculitis, severe hypertension and accelerated renal failure. A small number with the diffuse proliferative form have a remission and then show only mesangial abnormalities, usually, however, with the appearance of glomerular sclerosis. Progressive glomerular sclerosis is observed in some patients and may be a sequel of the remission of the diffuse or focal proliferative lesions, or it may represent still another form of lupus nephritis. Mesangial immune deposits with or without proliferation, at times in the absence of clinical renal disease, are observed early in the course of systemic lupus erythematosus (SLE) and may proceed to the diffuse proliferative or membranous forms. The present observations serve to emphasize the importance of strict morphologic classification in the comparison of different treatment regimens for lupus nephritis. In view of the grave prognosis of established diffuse proliferative lupus nephritis, which probably evolves from a mesangial involvement common to all patients with SLE from its onset, early therapy may be the key to the management of lupus nephritis

Exaggerated natriuresis in response to hypertonic saline infusion occurs with great regularity in patients with documented previous attacks of poststreptococcal glomerulonephritis. Five patients were studied before and after 1 week of dietary sodium restriction in order to examine the possibility that increased extracellular fluid volume might play a role in the response to acute saline infusion. Plasma renin activity (PRA) and PRA responsiveness to sodium depletion were normal, suggesting that extracellular fluid volume was not increased. In all patients, extracellular fluid volume decreased during sodium restriction, as judged by weight loss, cumulative negative sodium balance, small decreases in measured plasma volume, and appropriate increases of PRA and plasma aldosterone concentration. Hypertonic saline infusion provoked exaggerated natriuresis in all patients equally as well after dietary sodium restriction as before. Exaggerated natriuresis in poststreptococcal glomerulonephritis occurs without evidence of chronic expansion of extracellular fluid volume and is not affected by reduction of extracellular fluid volume

One hundred fifty of 490 patients undergoing open heart surgery had renal failure attributable to cardiopulmonary bypass. In 69, serum creatinine concentrations did not exceed 2 mg/dl and returned to normal by the fourth postoperative day. In 60 patients, serum creatinine attained levels between 2 and 5 mg/dl, oliguria did not develop, and recovery of renal function occurred within 4 to 37 days. Serum creatinine increased to levels exceeding 5 mg/dl in 21 patients, 11 of whom were oliguric. Despite dialysis, 14 of these patients died from cardiac causes or sepsis. Prolonged cardiopulmonary bypass time, hypotension, oliguria, low output syndrome, and hemoglobinemia during open heart surgery correlated with the development of renal failure postoperatively. Although severe renal failure was an uncommon complication after open heart surgery, its occurrence carried a grave prognosis

To examine the hypothesis that des-Asp-1-angiotensin II (angiotensin III) may be an important mediator of various responses to angiotensin II, both peptides were given sequentially at 25 ng/kg per min by systemic infusion to conscious rabbits, and the effects on blood pressure, plasma aldosterone concentration, and plasma renin activity were compared. The mean arterial pressure increased with angiotensin II infusion an average of 18.2 mm Hg, and with angiotensin III infusion only 3.2 mm Hg. Both peptides, however, produced a six- to sevenfold increase in plasma aldosterone concentration, and a threefold decrease in plasma renin activity. Renal clearance data suggest that the suppression of renin activity was not a consequence of renal hemodynamic change or altered sodium transport, but of direct inhibition through a receptor mediating a short feedback loop. These data in the intact rabbit, taken together with in vitro studies by others, suggest that the responses of these three organ systems to angiotensin peptides are mediated by receptors of varied specificity: those mediating vasoconstriction exhibit a greater response to angiotensin II than to angiotensin III; those mediating the secretion of aldosterone exhibit a lesser response to angiotensin II than to angiotensin III; and those mediating the suppression of renin release do not appear to discriminate between the two peptides.