R Fraser

Comparison of surgery and prolonged spironolactone therapy in patients with hypertension, aldosterone excess, and low plasma renin.

The effect of prolonged preoperative treatment with spironolactone has been studied in a series of 67 patients with hypertension, aldosterone excess, and low plasma renin. In the series as a whole a highly significant reduction in both systolic and diastolic pressures was achieved, with no evidence of escape from control during therapy lasting several years in some cases. The drug was equally effective in controlling blood pressure in patients with and without adrenocortical adenomata. Occasional unresponsive patients were encountered in both groups; pretreatment blood urea levels in these were significantly higher than in the responsive patients. The hypotensive effect of spironolactone usually predicted the subsequent response to adrenal surgery. Spironolactone in all cases corrected plasma electrolyte abnormalities; significant increases in total exchangeable (or total body) potassium and significant reductions in total exchangeable sodium, total body water, extracellular fluid, and plasma volumes were seen. Plasma urea rose during treatment and there was a slight fall in mean body weight. Significant increases in peripheral venous plasma renin and angiotensin II concentrations occurred during treatment. In two patients no increase in aldosterone secretion rate was found during treatment, although plasma aldosterone rose in three of four subjects studied. Severe side effects were rare; in only two of the 67 patients did the drug have to be stopped. In addition to its routine preoperative use, spironolactone can now be advised as long-term therapy in selected patients.

Sodium and potassium in essential hypertension.

A study was carried out of arterial pressure and body content of electrolytes in 91 patients with essential hypertension and 121 normal controls. Exchangeable sodium was found to be positively correlated with arterial pressure in the patients, the correlation being closest in older patients; values of exchangeable sodium were subnormal in young patients; and plasma, exchangeable, and total body potassium correlated inversely with arterial pressure in the patients, the correlations being closest in young patients. Three hypotheses were proposed to explain the mechanisms relating electrolytes and arterial pressure in essential hypertension--namely, a cell-salt hypothesis, a dietary salt hypothesis, and a kidney-salt hypothesis. It was concluded that two mechanisms probably operate in essential hypertension. In the early stages of the disease blood pressure is raised by an abnormal process related more closely to potassium than to sodium. A renal lesion develops later, possibly as a consequence of the hypertension. This lesion is characterised by resetting of pressure natriuresis and is manifest by an abnormal relation between body sodium and arterial pressure and by susceptibility to increased dietary sodium intake.

Results of adrenal surgery in patients with hypertension, aldosterone excess, and low plasma renin concentration.

Fifty patients with hypertension, aldosterone excess, and low plasma renin concentration underwent adrenal surgery. There was a highly significant fall in mean systolic and diastolic pressures after the operation. The mean postoperative diastolic pressure fell to strictly normal levels, however, in only 19 out of 38 patients from whom an adrenocortical adenoma was removed and in only two out of 10 non-tumour patients. There was a significant correlation between the fall in blood pressure during spironolactone treatment and after adrenal surgery though levels were generally slightly lower during the former therapy. It is suggested that removal of an aldosterone-producing adenoma is the treatment of choice provided a good preoperative hypotensive response to spironolactone occurs, while the treatment of choice for non-tumour patients is often long-term spironolactone.

Falsely High Plasma Potassium Values in Patients with Hyperaldosteronism

The common practice of encouraging forearm exercise as an aid to venepuncture is a potent source of erroneously high plasma potassium levels. This may be sufficient to obscure a suspicion of hyperaldosteronism, with possible serious repercussions in hypertensive patients, in whom the diagnosis of hyperaldosteronism has important therapeutic implications. Plasma is preferable to serum for potassium estimations, and forearm exercise should be avoided before venepuncture for potassium measurements.

Recurrent Hyperkalaemia due to Selective Aldosterone Deficiency: Correction by Angiotensin Infusion

A patient with recurrent weakness and blurring of consciousness associated with hyperkalaemia due to aldosterone deficiency is reported. The plasma concentrations of renin, angiotensin II, and aldosterone were low and did not increase during sodium deprivation. Blood angiotensin I was also low while renin-substrate concentration was normal. Infusion of angiotensin produced a distinct rise in plasma aldosterone. The patient was treated successfully with fludrocortisol. The results support the concept that the renin-angiotensin system is an important regulator of aldosterone secretion and that in the syndrome of acquired selective hypoaldosteronism the primary abnormality may be a deficiency of renin. It is suggested that a selective lack of aldosterone should be considered in all cases of otherwise unexplained hyperkalaemia.

Converting-enzyme inhibitor enalapril (MK421) in treatment of hypertension with renal artery stenosis.

Enalapril maleate (MK421), a new inhibitor of angiotensin converting enzyme, in single daily doses of 1.25-40 mg was assessed in five patients with hypertension and renal artery stenosis. Only small falls in plasma angiotensin II concentrations were seen at doses less than 10 mg; even with 10 and 20 mg, angiotensin II concentrations had risen again 24 hours from the last dose. During long-term treatment with 10-40 mg daily all patients achieved good blood-pressure control. No significant changes of body sodium or potassium values were seen. The drug was well tolerated with no serious side effects. These findings are evidence of the efficacy and acceptability of enalapril in the medical management of hypertension with renal artery stenosis.

Captopril in renovascular hypertension: long-term use in predicting surgical outcome.

The angiotensin converting-enzyme inhibitor captopril was used as long-term preoperative treatment in a series of hypertensive patients with unilateral renal arterial disease. There were immediate and sustained falls in plasma angiotensin II and aldosterone concentrations, with converse increases in circulating renin and angiotensin I. In patients with sodium and potassium deficiency and secondary aldosterone excess before treatment captopril corrected the sodium and potassium deficits; in these cases the initial hypotensive response was profound but the later effect was less pronounced. When sodium and potassium state was initially normal it remained unchanged during captopril treatment, while the full hypotensive effect took up to three weeks to be attained. The immediate, but not long-term, falls in arterial pressure with captopril were proportional to the immediate decrements of plasma angiotensin II. Nevertheless, while the immediate blood-pressure reduction with captopril variously overestimated and underestimated the eventual surgical response, the absolute blood-pressure values during long-term captopril related well with those after operation. Pretreatment plasma renin and angiotensin II concentrations, while closely predicting the immediate captopril response, are fallible guides to surgical prognosis. In contrast, long-term treatment with converting-enzyme inhibitors may provide an accurate indication of surgical outcome.

Hypertension with aldosterone excess.

Symptoms other than pain-particularly dyspnoea, tiredness, faintness, and syncope-were occasionally the first indication of coronary heart disease. These symptoms are much less definite than pain and more often due to diseases other than of the coronary system. Fortunately in most cases of coronary origin the electrocardiogram was abnormal. Painless infarction may be commoner than our study indicates, but without the support of electrocardiographic or enzymic evidence the diagnosis can be only tentative.

Amiloride in primary hyperaldosteronism with chronic peptic ulceration.

Prolonged treatment with the aldosterone antagonist spironolactone is well-established in the syndrome of hypertension with aldosterone excess and low plasma renin (primary hyperaldosteronism) and is usually effective in lowering the blood pressure and correcting the electrolyte abnormalities in cases with adrenocortical adenoma or micronodular hyperplasia (Brown et al., 1965, 1969, 1971b, 1972; Spark and Melby, 1968; Crane and Harris, 1970). While serious side effects are in our experience rare, spironolactone may cause epigastric discomfort, and in one patient gastric ulceration developed during therapy and rapidly healed when the drug was withdrawn (Brown et al., 1971 b). We report the use of an alternative potassium-conserving diuretic, amiloride, in a patient with primary hyperaldosteronism in whom spironolactone could not be tolerated because of severe epigastric pain associated with peptic ulceration.

Spironolactone in hyperaldosteronism.

s of Efficiency Studies in the Hospital Service, 1966, No. 90. London, H.M.S.O. Fibrinolysis and Toxaemia of Pregnancy SIR,-The report by Drs. E. N. Wardle and I. S. Menon (7 June, p. 625) is of interest to those who associate pre-eclampsia with alterations in the coagulation and/or fibrinolytic systems. We have emphasized that much of the confusion and lack of basic knowledge regarding the pathogenesis of toxaemia stems from the fact that few investigators have clearly defined their test populations. Thus Drs. Wardle and Menon studied 20 patients with hypertension and 23 patients with pre-eclamptic toxaemia, . defined as proteinuria together with oedema