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Prince Henry’s Institute of Medical Research, Monash Medical Centre, Clayton, 3168 Victoria, Australia
Address all correspondence and requests for reprints to: Dr. John W. Funder, Prince Henry’s Institute of Medical Research, P.O. Box 5152, Clayton 3168, Victoria, Australia. E-mail: susan.smith{at}med.monash.edu.au.
This year The Endocrine Society has adopted Cardiovascular Endocrinology as its theme for the annual meeting, in Philadelphia in June. At the same time, the Society journals are showcasing the area, in terms both of primary communications and minireviews. This issue of Endocrinology features six such minireviews, and in introducing them there are a number of important points to make.
First is the issue of turf. Each one of the reviews might normally be expected to be found elsewhere—the American Journal of Physiology, Hypertension, the Journal of Clinical Endocrinology & Metabolism, Atherosclerosis: there is no single journal of record in the area. Although cardiovascular endocrinology is a burgeoning area, this scattergun situation is likely to persist until we have a dedicated journal in the area to cover laboratory and clinical research.
Second is the re-emergence of an "old" area of endocrinology, that of metabolism. While people often bemoan the splintering of endocrinology with specialist meetings and journals (diabetes, thyroid, bone, reproductive, pediatric, neuroendocrine), the last major fission was that between nephrology and endocrinology, history to all but a handful of the oldest inhabitants of both domains. Metabolism somehow got slightly lost between the various subdivisions of endocrinology and the exponents of the whole-body calorimeter (for instance): now it is back with a vengeance. The reviews from the Evans and Hsueh laboratories, on peroxisome proliferator-activated receptors (PPARs) and adipocyte-derived hormones, respectively, cover only part of what is almost certainly the hottest growth area in endocrinology, that of metabolism in the first decade of the 21st century.
Third is primary aldosteronism, 2003. For many years, conventional wisdom had primary aldosteronism as a rare remediable cause of essential hypertension, with an incidence of well under 1%. Over the past decade, clinical endocrinologists working in hypertension clinics have used a ratio of aldosterone to renin to uncover autonomous aldosterone secretion and have shown in unselected hypertensive populations worldwide an incidence of approximately 10%. Most cases of primary aldosteronism reflect bilateral adrenal hyperplasia rather than a discrete adenoma, and are often normokalemic. Essential hypertension affects 15–20% of the population in developed countries; primary aldosteronism alone—not to mention resistant hypertension, hypertension in African-Americans, or isolated systolic hypertension—thus represents an enormous therapeutic target population. Even in developed countries, only half the patients with hypertension receive treatment, and only a quarter adequate treatment, a massive and growing public health challenge. Bill Young’s essay on the sea-change in diagnosis and treatment of primary aldosteronism should be read by all endocrinologists, basic and clinical alike.
And by our cardiological colleagues: fourth, again, is turf. Cardiologists are familiar and comfortable with the renin-angiotensin system, but not with aldosterone. Whereas a number of specialties—cardiology, nephrology, endocrinology, clinical pharmacology—are active in hypertension, heart failure is squarely the province of the cardiologist. Aldosterone blockade has been shown to improve morbidity and mortality in two recent clinical trials [RALES (1) and EPHESUS (2)], and aldosterone under particular circumstances has been shown to act as a proinflammatory, profibrotic hormone. A century ago, our forbears in research and medical practice began to specialize, reflecting the enormous growth in knowledge of particular tissue and organ systems. Now, as we enter an exponential phase of accruing information, we need to refocus on the organism as a whole, and break down the boundaries between disciplines where insight and therapeutic advantage depend on both.
Even for "old" hormones (renin was characterized over a century ago), there is new ground to tread: Julie Lavoie and Curt Sigmund review the tissue (thus paracrine rather than endocrine) renin-angiotensin system, and Takahashi et al. provide new evidence for the importance of bradykinin in the blood-pressure-lowering effect of angiotensin converting enzyme blockade. One of the findings to revolutionize classical endocrinology was the demonstration that the heart is an endocrine organ, secreting natriuretic peptides, inter alia. The aptly named Cardioendocrine Group in Christchurch (New Zealand) has pioneered the use of circulating brain natriuretic peptide (and subsequently brain natriuretic peptide fragments) as outcome predictors after myocardial infarction; in their review, Vicky Cameron and Leigh Ellmers explore possible roles for the natriuretic peptide in cardiac development.
Next year the theme for the Endocrine Meetings is obesity, in many ways an extension and amplification of both of the areas covered by this year’s minireviews. The constellation in the metabolic syndrome (also known as Syndrome X) of some or all of obesity, salt-sensitive hypertension, impaired glucose tolerance, and hyperlipidemia is a challenge for endocrinologists, cardiologists, and nephrologists alike. Boundaries and no-go zones are counterproductive; the trick is to identify the common enemy. France may have been considered ungovernable by Charles de Gaulle, on the basis of producing over 300 types of cheese; what unites the country is the ubiquitous graffiti, under every railway bridge, a bas Paris.
For those of us in cardiovascular endocrinology, the common enemy is the mortality and morbidity associated with myocardial infarction, peripheral vascular disease, and stroke, now and for the foreseeable future the major killer in developed societies, and predicted as the number-one cause of loss of disability-adjusted life years worldwide now through 2020 (3). This is a process in which hormones and cytokines, receptors and effectors, endocrine and paracrine, are central; a range of so-called primary disciplines has to be involved if we are to address the epidemics of obesity, diabetes, heart failure, and endstage renal disease. In cardiovascular endocrinology, we’re in it together; and if we’re going to make it work, we’re in it together for the long haul.
Received April 10, 2003.
Accepted for publication April 10, 2003.
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