Abstract-Hypertension guidelines advise limiting the dose of thiazide diuretics and avoiding combination with ␤-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. Two double-blind, placebo-controlled, crossover studies were performed. In study 1 (41 patients), we found that changes in glucose during a 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with bendroflumethiazide. In study 2, 37 patients with essential hypertension received, in random order, 4 weeks of once-daily treatment with hydrochlorothiazide (HCTZ) 25 to 50 mg, nebivolol 5 to 10 mg, combination (HCTZ 25-50 mgϩnebivolol 5-10 mg), amiloride (10 -20 mg), and placebo. Each drug was force titrated at 2 weeks and separated by a 4-week placebo washout. At each visit, we recorded blood pressure and performed a 75-g oral glucose tolerance test. Primary outcome was the difference in glucose (over the 2 hours of the oral glucose tolerance test) between 0 and 4 weeks, when HCTZ and amiloride were compared by repeated-measures analysis. For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (PϽ0.0001). Nebivolol did not impair glucose tolerance, either alone or in combination. There was a negative correlation between ⌬potassium and ⌬2-hour glucose (rϭϪ0.28; PϽ0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K 1 Outcome trials have shown cardiovascular benefits from the use of thiazides in essential hypertension, which are similar to those achieved with other antihypertensive agents. However, there has been recent recognition that currently used doses are smaller than those used in most of the outcome trials.3-5 The main adverse effects limiting the use of thiazides are metabolic, including hypokalemia, hyponatremia, hyperuricemia, and hyperglycemia.

Paper AbstractThe diagnosis of primary hyperaldosteronism due to microadenoma or unilateral adrenal hyperplasia can be challenging, since hypokalaemic alkalosis, high plasma aldosterone and a definite adenoma on imaging may all be absent. Method and result. We describe three cases of resistant hypertension (on > 5 antihypertensives) where hyperaldosteronism was suspected because of a suppressed plasma renin level despite treatment with multiple drugs which normally elevate renin. Renin mass was measured by a double-site chemi-immunoluminometric assay.All patients had normal plasma aldosterone levels. Hypokalaemia was present in the first two cases but computed tomography did not show clear cut adenomas.Adrenal vein sampling (AVS) revealed lateralisation (> 4 times higher aldosterone to cortisol ratio (ACR) on the affected than contra-lateral side).The third patient was normokalaemic and AVS showed only minimal lateralisation (ACR 1.3:1).The severe hypertension in all cases was reversed by adrenalectomy, with blood pressure falling to target despite withdrawal of all but one to two drugs. Conclusions. The robotic assay of renin mass permits rapid detection of patients in whom plasma renin is suppressed below the normal range.A suppressed plasma renin indicates abnormal Na + -retention, and -when not overcome by drugs such as angiotensinconverting enzyme-inhibitors or angiotensin receptor blockers -may be the only clue to a curable adrenal adenoma.AVS is required to demonstrate lateralisation of aldosterone secretion, justifying adrenalectomy.

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