Arunabha Ganguly

Stimulation of aldosterone secretion by metoclopramide in humans: Apparent independence of renal and pituitary mediation

Metoclopramide (MP), a dopamine antagonist, stimulates secretion of aldosterone by a mechanism which has not been defined. We examined a potential role for either the kidney or the pituitary to mediate MPs effect on aldosterone secretion. Responses to MP administered i.v. were measured in six anephric and six hypopituitary patients as well as in six normal subjects. MP increased the plasma aldosterone concentration (PAC) in normal subjects in a fashion similar to what had previously been reported. MP produced no increase in plasma levels of renin activity (PRA), cortisol, potassium, or sodium. Three of six anephric patients (all of whom had undetectable PRA) responded to MP with increases in PAC; the magnitude of these responses correlated with the plasma potassium concentration. All six hypopituitary patients showed increases in PAC after MP administration. MP increased plasma prolactin levels in normal subjects and anephric patients; one hypopituitary patient had high basal plasma prolactin levels which increased with MP. In conclusion, neither the kidney nor the pituitary is involved in the mechanism for MP stimulated aldosterone production. These observations suggest that MP may act on the adrenal to evoke secretion of aldosterone.

Triamterene‐thiazide combination: Alternative therapy for primary aldosteronism

The hypertension and hypokalemia of primary aldosteronism are related to excessive aldosterone secretion. Spironolactone, an aldosterone antagonist, is used in high doses to treat the disorder, but it may induce a number of side effects that can limit its use. We investigated the feasibility of treating a group of eight patients with hyperaldosteronism with a triamterene‐thiazide combination to induce volume depletion and increase serum potassium concentration. All patients responded with normalization or near normalization of blood pressure. Serum potassium could be maintained within the normal range with or without potassium supplements in all but one patient. The effectiveness of the therapy suggests that thiazide‐triamterene treatment may offer an alternative in some patients with primary aldosteronism who do not tolerate spironolactone.

Response to growth hormone-releasing hormone in adult renal failure patients on hemodialysis☆☆☆

Exogenous synthetic growth hormone-releasing hormone (GHRH [hpGRF-40]), 1 microgram/kg body weight, was administered intravenously (IV) to eight men with chronic renal failure on chronic hemodialysis and to seven men matched for age (control group). Basal and stimulated growth hormone (GH) concentrations following GHRH (hpGRF-40) in renal failure patients were significantly higher than in controls. Basal prolactin and somatomedin C/insulin-like growth factor-1 (SmC/IGF-1) concentrations were significantly higher in the renal failure patients compared with controls. Following GHRH there was no further increase in serum concentration of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, SmC/IGF-1, or cortisol. GH appears to be the only pituitary hormone where there is an exaggerated response to its specific releasing hormone in adults with renal failure.

Juxtaglomerular cells in renal angiomyolipoma Ultrastructural observation

We have studied a case of renal angiomyolipoma by electron microscopy and found juxtaglomerular cells with typical rhomboid and spherical granules, in addition to smooth muscle cells, fat cells, and abnormal blood vessels. To our knowledge, this is the first ultrastructural demonstration of juxtaglomerular cells in renal angiomyolipoma.

Hyperaldosteronism Due to Unsuspected Adrenal carcinoma: Discovery During Investigation of hypertension in a Young Woman

During investigation for hypertension a 19-year-old black woman was found to have an unsuspected adrenal carcinoma. Hyperaldosteronism was established as the cause of the hypertension by observing suppressed plasma renin activity and nonsuppressible plasma aldosterone concentration. The causal relationship was confirmed by a cure of the hypertension and a return in the responsiveness of the renin-angiotensin-aldosterone axis to normal after removal of the carcinoma. This report emphasizes the value of a comprehensive investigation of hypertension, especially in young patients.

The renin-angiotensin-aldosterone system and hypertension in primary hyperparathyroidism.

To evaluate the role of the renin-angiotensin-aldosterone system in the hypertension associated with primary hyperparathyroidism, we measured plasma renin activity and aldosterone concentration before and after maneuvers to suppress and stimulate this system in 11 hypertensive patients with primary hyperparathyroidism. We also measured plasma or urinary norepinephrine concentration to examine the role of catecholamines in the hypertension. The results were compared with an age- and race-matched control population. While the mean plasma aldosterone concentrations were normal, the mean plasma renin activity in response to furosemide stimulation was subnormal in subjects with hyperparathyroidism. Plasma or urinary norepinephrine concentrations were within the normal range. Thus a specific abnormality of the renin-angiotensin-aldosterone system or catecholamines could not be identified in these hypertensives with primary hyperparathyroidism.

M and L forms of 18-hydroxy-11-deoxycorticosterone and 18-hydroxycorticosterone: Factors influencing conversion, stability and immunological properties

Abstract The precise mechanisms conducive to the formation of the less polar (L forms) of 18-OH-DOC and 18-OH-B from their respective, more polar (M forms) were investigated. The conversion to the L form during storage appeared to be related to the presence of organic acid impurities in the solvent. Room temperature and temperature of 37°C favored more rapid transformation to the L form than 4°C. The predicatable method of obtaining M and L forms of the steroids and their convenient separation by LH-20 column chromatography permitted further studies of their solubility and immunological characteristics. L forms of both steroids failed to show any binding to an antiserum generated against 18-OH-DOC. These studies provide important insight into the complexity of interconversions of these 18-hydroxylated steroids and will facilitate further studies.

Differences between adrenal adenoma causing primary aldosteronism and other adrenal tissues in the incorporation of labeled steroid precursors into their products

The incorporation and conversion of several labeled steroid precursors into their products were examined in slices of adrenal tissue from two patients with primary aldosteronism and compared with that in normal adrenal tissue and adrenal tissues from a patient with Cushings syndrome. The products of the incorporation were separated by Sephadex LH-20 column chromatography. The major products of conversion in the adenomatous tissue of primary aldosteronism were 18-hydroxycorticosterone and lesser amounts of aldosterone. Smaller amounts of 18-hydroxycorticosterone were isolated from all other adrenal tissues studied. No aldosterone could be recovered after incubating any of the adrenal tissue studied with labeled 18-hydroxy-11-deoxycorticosterone or 18-hydroxycorticosterone as precursor steroid. These in vitro results seem to suggest that there is increased 18-hydroxylation in the adenoma of primary aldosteronism compared with other tissues and that relatively more 18-hydroxycorticosterone is produced in such tissue than aldosterone.