Edward G. Biglieri

17-hydroxylation deficiency in man.

The biosynthesis of steroid hormones 1 requires a number of hydroxylating enzymes. Deficiency of these enzymes is demonstrated by increased or decreased amounts of certain steroid metabolites in blood and urine and is best exemplified by the deficiency of 11,8-hydroxylase (1) and 21-hy-droxylase (2) in patients with congenital adrenal hyperplasia. 17a-Hydroxylase activity is present in these disorders because of the increases in secretion of androgens and excretion of preg-nanetriol. In addition, a lack of 3-hydroxysteroid dehydrogenase has also been described (3). 17-Hydroxylation is essential not only to the bio-synthesis of cortisol but also to the formation of *

RENAL-VEIN RENIN IN VARIOUS FORMS OF RENAL HYPERTENSION

Abstract Renal and peripheral venous plasmarenin activities were determined by radioimmunoassay of angiotensin I in 13 hypertensive patients with radiologically normal kidneys and in 110 patients with suspected renal hypertension. Renal-artery stenosis was present in 78 patients, while 32 had other abnormalities, including unilateral hydronephrosis, segmental renal infarction, and intrarenal vascular malformations. The results in 41 surgically treated patients confirm the predictive value of a renal-vein-renin ratio greater than 1·5 in patients with renal-artery stenosis and suggest that this ratio is also useful in patients with other types of renal hypertension. Evidence of suppression of renin release from the contralateral kidney seems to have additional value in predicting a response to surgery, but peripheral renin levels were normal in 14 out of 34 patients who benefited from surgery. The immunoassay has a high degree of precision, and the chance of an apparently significant ratio resulting from assay variation is negligible.

Isolated hypoaldosteronism in adults. A renin-deficiency syndrome.

Abstract To clarify the mechanism causing isolated hypoaldosteronism in adults, we studied six patients with unexplained hyperkalemia. On a normal sodium intake, excretion of tetrahydrodeoxycorticosterone, tetrahydrocorticosterone, and 17-hydroxycorticoids was normal and increased normally with ACTH stimulation. Excretion of metabolites of aldosterone and 18-hydroxycorticosterone was subnormal or barely normal, and aldosterone excretion failed to respond normally to sodium depletion and ACTH. Plasma renin activity (PRA) and concentration were subnormal and failed to increase normally with upright posture and sodium depletion; furosemide increased PRA in only one patient. Restoration of normal serum potassium with cation exchange resin failed to increase PRA in the three patients studied. Plasma renin substrate was normal or slightly elevated. The patients studied differ from patients with Addisons disease and infants with enzymatic defects in aldosterone biosynthesis in whom PRA is increased. The data su...

Studies on the expanded extracellular fluid and the responses to various stimuli in primary aldosteronism

Abstract Two patients with primary aldosteronism, accompanied by hypertension, hypernatremic, hypokalemic alkalosis and severe potassium depletion, were demonstrated to have an increased volume of extracellular fluid. A marked rise in plasma volume without any change in red cell volume was observed. Changes in sodium intake failed to alter the expanded state. Only minimal responses to salt-retaining hormones were present. Rapid infusion of isotonic saline solution produced a rapid rise in the filtered load, with rapid excretion of sodium and maintenance of the status quo in aldosterone secretion. The rapid changes in glomerular filtration rate appear to be a factor in limiting further increases of this chronically expanded state and would explain, in part at least, the lack of edema observed in these patients. In contrast, the tumors were shown to respond to changes in plasma volume, corticotropin, SU-4885 and spirolactone, thus demonstrating their physiologic responsiveness to uncompensated stimuli. Growth hormone was shown to have a sodium-retaining action independent of aldosterone secretion.

Use of Computed Tomography in Diagnosing the Cause of Primary Aldosteronism

Abstract We performed computed tomography (CT) in 22 consecutive patients with primary aldosteronism to evaluate the usefulness of this technique in diagnosing and locating aldosterone-producing ad...

Location of Aldosterone-Producing Adenomas with 131I-19-Iodocholesterol

We used 131I-19-iodocholesterol as an adrenal-imaging agent in 27 hypertensive patients who had biochemical evidence of abnormalities in the renin-angiotensin-aldosterone system. In 10 of 12 patients in whom the biochemical findings suggested the presence of an aldosterone-producing adenoma the adrenal uptake was asymmetric. The adenoma was subsequently confirmed in all eight patients in this group who underwent operation. In contrast, the adrenal uptake was asymmetric in only one of 13 patients with biochemical evidence of iodopathic hyperaldosteronism or low-renin essential hypertension. Two patients with adrenal carcinoma causing primary aldosteronism did not concentrate the isotope in their tumors. When metabolic studies suggest an aldosterone-producing adenoma, adrenal imaging with 131I-19-iodocholesterol may locate the tumor before operation.

Mineralocorticoid production in hyperadrenocorticism: Role in pathogenesis of hypokalemic alkalosis

Abstract Patterns of mineralocorticoid production were determined in two states characterized by increased adrenocorticotropin secretion and hypokalemic alkalosis. Secretion of desoxycorticosterone (DOC) and corticosterone (B), and excretion of their metabolites were markedly increased in seven patients with ectopic ACTH syndrome and in four patients with 17-hydroxylation deficiency syndrome. Aldosterone production was generally within the normal range or decreased in both groups. Excretion of cortisol metabolites was increased in the patients with ectopic ACTH syndrome but was virtually absent in the patients with 17-hydroxylation deficiency. Although increased production of cortisol or related glucocorticoids has been suggested as a possible cause of the hypokalemic alkalosis noted in some patients with Cushings syndrome, a more obvious correlation between increased secretion of DOC and B and the electrolyte abnormalities was noted in our studies.

Determination of Plasma Renin Concentration by Angiotensin I Immunoassay Diagnostic Import of Precise Measurement of Subnormal Renin in Hyperaldosteronism

Radioimmunoassay of angiotensin I was applied to the estimation of renin concentration after incubation of human plasma with an excess of renin substrate from plasma of anephric sheep. With this method markedly subnormal plasma renin levels were accurately measured. The technique was used in the study of 18 patients with proven aldosterone-producing adenoma (APA), 5 with hyperaldosteronism associated with bilateral adrenal hyperplasia, and 23 with essential hypertension. Plasma renin concentration (PRC) was extremely low in APA, and a significantly higher mean basal level of PRC was seen in hyperplastic aldosteronism (P <0.01). Postural responses were seen in both groups, and PRC was least variable during recumbency. Comparison of basal recumbent PRC with urinary aldosterone after three days of desoxycorticosterone acetate (DOCA) accentuated the distinction between APA and hyperplasia. It is suggested that the prediction of a distinct APA can best be made in patients with hyperaldosteronism when the exact extent of renin suppression is taken into account and when DOCA is used to assess suppressibility of aldosterone. While such evaluation may defer surgery in some patients with correctable hypertension, it may reduce the number with persistent hypertension after bilateral adrenalectomy.

Abnormalities of Renal Function and Circulatory Reflexes in Primary Aldosteronism

The renal response to intravenous administration of isotonic saline solution and circulatory reflex reactivity was studied in nine patients with primary aldosteronism before and after surgical removal of an adrenal adenoma. In preoperative tests, infusion of saline was followed by abnormally rapid renal excretion of sodium and water, such as occurs in patients with autonomic insufficiency. Circulatory reflex function was also abnormal in all patients; the most severe impairment was shown by two patients with hypokalemia and weakness of long duration. Postoperatively, both renal and circulatory reflex responses returned to normal or near normal. In preoperative tests on three patients, potassium repletion effected a similar correction of both renal and circulatory reflex abnormalities. The cause of these abnormalities in patients with primary aldosteronism is not known. Potassium depletion may be a factor, althougha general disturbance of autonomic cardiovascular function cannot be excluded.

Role of renin and aldosterone in hypertension due to a renin-secreting tumor☆

Abstract A renin-secreting renal tumor is a rare cause of curable hypertension characterized clinically by hypertension, hypokalemia, hyperaldosteronism and increased plasma renin activity (PRA). Prior subtotal adrenalectomy in such a patient allowed examination of the role of hyperreninemia in the absence of excessive aldosterone secretion. Hypertension was severe, but serum potassium and aldosterone production were normal. PRA was markedly increased under all conditions studied, with a persistent increase noted with changes in posture. Renal vein renin studies were critical in localizing the renal tumor, and unilateral nephrectomy resulted in a prompt fall in PRA to subnormal levels and dramatic cure of the hypertension. Renin content of the renal tumor was more than 500 times higher than in the adjacent kidney, and histologic studies confirmed that the tumor was of juxtaglomerular cell origin. This case demonstrates that severe hypertension can occur in this syndrome despite subtotal adrenalectomy and further illustrates an association of renin overproduction with a specific type of hypertension.