[A case from practice (169). Liquorice-induced pseudohyperaldosteronism in a previously alcoholic woman caused by the drinking of an alcohol-free Pastis substitute beverage].
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Adult↗
Biomedical subjects
B N Trost
Publications and source records attributed to B N Trost.
Glucose metabolism and calcium antagonists.
High blood pressure, but also diabetes mellitus and even glucose intolerance are well known risk factors for premature cardiovascular morbidity and mortality. To counteract these sequelae, it is obvious that drug treatment of hypertension should not adversely affect the glucose homeostasis in nondiabetic as well as in diabetic patients. Therefore, the findings that calcium antagonists could dose-dependently throttle the insulin output after addition of glucose in pancreas perfusion experiments in vitro were of considerable concern. Within the last years, most of more than 100 short-term and long-term trials in diabetic and non-diabetic patients were able to show that different calcium antagonists at their "usual" antihypertensive dosages did not impair the glucose metabolism, whereas results of acute studies, especially with higher doses and after a glucose challenge, were more controversial. However, in all of the 13 long-term follow-up trials (up to 5 years) with determinations of the glycated hemoglobin published to date, this most relevant parameter remained unchanged. Thus, currently available data indicate that calcium antagonists do not alter glucose handling at a clinically relevant degree, both in non-diabetic or diabetic patients, so that it is not justified to withhold the benefits of these medications from hypertensives out of fear to introduce a deterioration in their carbohydrate homeostasis.
Animals↗
[Antihypertensive therapy in patients with diabetes mellitus].
A relative systemic hyperinsulinism, sodium retention as well as an increased cardiovascular reactivity to norepinephrine and angiotensin II in diabetics may explain the prognostically unfavorable frequent association of diabetes with high blood pressure. The first therapeutic approach against hypertension is omission of smoking and exaggerated alcohol consumption as well as of drugs which elevate blood pressure. An attempt to reach a normal body weight by means of a sodium restricted diabetes-diet is next. If blood pressures remain elevated an antihypertensive drug is prescribed in monotherapy, nowadays preferably a calcium antagonist or an ACE-inhibitor, because both of them cause few side effects, do not impair glucose and lipid homeostases and are easy to handle with a once-a-day regimen. A therapeutic algorithm is presented and consideration of the total risks of morbidity and mortality in these patients stressed.
Antihypertensive Agents↗
Hypertension in the diabetic patient. Selection and optimum use of antihypertensive drugs.
Understanding of the pathophysiology of hypertension and diabetes mellitus and their association is at present fragmentary at best. Optimal antihypertensive drug therapy of patients with both disorders is therefore based on limited experimental data, practical experience and educated guesswork, and needs to be tailored to each (often multimorbid) individual. In most patients monotherapy would be preferred, and would begin with a calcium antagonist or a converting enzyme inhibitor at a low to moderate dosage. If this is not effective an alpha 1-adrenoceptor inhibitor, a cardioselective beta-blocker or a diuretic, always at a low to moderate dosage, should be tried. If still unsuccessful, low dose combinations of 2 of these drugs are next. The (long term) regimen should be as simple as possible, and its effects--desired and undesired--monitored as closely as the carbohydrate disorder.
Antihypertensive Agents↗
Metabolic effects of calcium antagonists in humans, with emphasis on carbohydrate, lipid, potassium, and uric acid homeostases.
Since metabolic side effects of conventional antihypertensive drugs could be one reason for the lack of improvement of cardiac morbidity and mortality, metabolic neutrality has become an important postulate of newer products such as the calcium antagonists (CA). Carbohydrate homeostasis--in spite of an anticipated deterioration derived from early in vitro experiments--has mostly been unaffected by CA therapy in humans, nondiabetic and diabetic. This was found in long-term studies in particular, whereas in acute or short-term trials with high dosages, minor alterations of insulin secretion and/or action were sometimes noted. These are negligible from a clinical point of view. Serum lipid profiles also were generally not disturbed by CA treatment, since most of the controlled long-term trials showed no change or even a potentially beneficial change. Minor lowering of plasma potassium levels during a CA regimen was exceptional and a rise of plasma uric acid values never reported; the latter may even decrease under certain circumstances. Thus, after reviewing more than 150 pertinent publications, we can state that the benefit of antihypertensive or antianginal treatment with a CA is in all likelihood not compromised by introducing known untoward metabolic cardiovascular risks.
Calcium Channel Blockers↗
Serum lipoproteins during treatment with antihypertensive drugs.
Hypertension and certain alterations in serum lipoproteins such as a decrease in high density lipoprotein-cholesterol (HDL-C), an increase in low density lipoprotein-cholesterol (LDL-C) and perhaps also elevated triglycerides (Tg), are complementary coronary risk factors. Moreover, it has become evident that several of the drugs used for standard antihypertensive therapy may also interact with lipoprotein metabolism. The following has been observed after 1 to 12 months of treatment. Various diuretics can significantly increase LDL-C and/or very LDL-C and total C/HDL-C ratio, while HDL-C is often largely unchanged; Tg also are often elevated. LDL-C increased in diuretic-treated men and in chlorthalidone-treated postmenopausal women but not in chlorthalidone-treated premenopausal women. The latter may be protected from this side effect. Drug dosages were usually high in these studies. Indapamide, given at a dose of 2.5 mg/day, seems to exert no relevant effect on the lipoproteins. It is not established whether this difference is related to the nature of the drugs or the doses used. There is little doubt that the dose of chlorthalidone used was greater than that required for a full antihypertensive effect of this drug. Several beta-blockers given as monotherapy induce significant increases in Tg and a tendency for decreases in HDL-C. These changes are most prominent on non-selective beta 1+2-blockers without partial intrinsic sympathomimetic activity (ISA), less pronounced on highly selective beta 1-blockers without ISA, and even more discrete or absent on beta-blockers with distinct ISA. Other sympatholytics such as reserpine, methyldopa, debrisoquine, urapidil, clonidine, labetalol, or postsynaptic alpha-blockers (prazosin, trimazosin, doxazosin etc.) did not affect or, postsynaptic alpha-blockers in particular, sometimes even slightly decreased Tg or LDL-C and very LDL-C values. During combination therapy, diuretic-induced increases in LDL-C were at short term prevented or reversed by the concomitant administration of certain beta-blockers, but not by sympatholytics such as reserpine, methyldopa or clonidine. With combined diuretic-prazosin treatment, a tendency for slightly higher HDL-C was reported. Angiotensin converting enzyme inhibitors (captopril, enalapril) and calcium channel blockers (verapamil, nifedipine, nitrendipine, diltiazem) seem to be largely devoid of undesirable effects on serum lipoproteins. Monotherapy with the potent direct vasodilator carprazidil improved blood pressure and significantly increased HDL-C. Whether and to what extent the observed variations in lipoproteins may persist beyond 1 year of treatment is as yet unclear.(ABSTRACT TRUNCATED AT 400 WORDS)
Antihypertensive Agents↗
Comparative effects of doxazosin and hydrochlorothiazide on serum lipids and blood pressure in essential hypertension.
The efficacy and safety of doxazosin (mean dosage 6.9 mg, range 1 to 16) in the treatment of essential hypertension were compared in a double-blind study with those of hydrochlorothiazide (HCTZ) (mean dosage, 84.6 mg, range 25 to 100) in 104 hypertensive patients treated once daily for 6 months. Thirty-five patients were also assessed for comparative effects of the 2 agents on serum lipid parameters. Doxazosin produced potentially favorable changes from baseline in the concentrations of serum lipid fractions (total triglycerides, total cholesterol, high density lipoprotein [HDL] cholesterol and the derived HDL/total cholesterol ratio) compared with HCTZ. The decreases in total triglyceride and total cholesterol concentrations and an increase in the HDL/total cholesterol ratio were significantly different (p less than 0.006) from the opposite changes observed with HCTZ. Clinically relevant decreases from baseline in supine and standing blood pressures at 24 hours after administration did not significantly differ between the 2 agents. The incidence and severity of side effects were similar for both drugs. Three patients receiving doxazosin and 6 receiving HCTZ were withdrawn due to drug-related clinical side effects including 2 patients receiving HCTZ who were withdrawn because of laboratory test abnormalities. Eight HCTZ- and 1 doxazosin-treated patients developed hypokalemia and 6 HCTZ-treated patients developed hyperuricemia. These findings indicate that doxazosin and HCTZ provide comparable antihypertensive efficacy after 6 months of treatment using a once-daily regimen, but doxazosin produces a beneficial effect on the serum lipid profile as well as fewer biochemical aberrations.
Adrenergic alpha-Antagonists↗
Effects of calcium antagonists on glucose homeostasis and serum lipids in non-diabetic and diabetic subjects: a review.
Results from early in vitro experiments have led to the assumption that a deterioration in carbohydrate metabolism must be expected if diabetic patients are treated with calcium antagonists. In order to determine the truth of this assumption, we reviewed 74 publications reporting effects on glucose homeostasis from acute, short-term and long-term therapy with calcium antagonists in non-diabetic patients, and 35 papers and abstracts dealing with the same problem in diabetic patients. The analogous question concerning the influence of calcium antagonists on the serum lipid profile was pursued in 43 recent communications. Long-term studies in particular suggest that although minor transitory changes under special circumstances cannot be excluded, in all likelihood neither glucose nor lipid homeostases are unfavourably altered by current clinical dosages of calcium antagonists in non-diabetic subjects or in patients with diabetes mellitus. Therefore, the benefit of antihypertensive or anti-anginal treatment with these medications is not compromised by untoward metabolic cardiovascular risks.
Blood Glucose↗
[Pulsatile long-term gonadotropin-releasing hormone (GnRH) therapy in the male: natural induction of puberty in a 20-year-old boy].
Successful induction of puberty by means of a pulsatile long-term therapy with GnRH--the variant closest to nature--can be performed on an outpatient basis without changing habits and lifestyle, as was demonstrated clinically and biochemically in a 20-year-old previously untreated boy with hypothalamic hypogonadism of unknown etiology. Unusual in this patient's course was the slow--and modest--increase in plasma FSH levels. Evidence that puberty did not occur spontaneously but was in fact due to treatment was gained from gonadotropin profiling by night and day before and after therapy withdrawal.
Adult↗
Pathogenesis and treatment of hypertension associated with diabetes.
The pathogenesis of hypertension accompanying diabetes mellitus (DM) may involve abnormalities in at least two major blood pressure (BP)--regulating systems. Exchangeable sodium (Naex) and the cardiovascular pressor responsiveness to norepinephrine are often increased, while blood volume is normal or low, regardless of age, insulin-dependence or non-dependence, or the presence or absence of retinopathy or clinical nephropathy. In hypertensive DM, systolic BP correlated (P less than 0.001) with Naex; diuretic treatment improved norepinephrine responsiveness, Naex and BP, while calcium entry blockade improved cardiovascular responsiveness and BP without changing Naex. Plasma catecholamine, renin and aldosterone levels are usually normal or sometimes low in stable DM. Antihypertensive therapy in DM is based on 3 legs, namely antidiabetic treatment, general measured aimed at reducing BP and associated risk correlates, and if necessary BP-lowering drugs. Due to their metabolic side effects, thiazide-diuretics given in moderate to high doses are not ideal step 1 drugs in DM. Certain beta 1-blockers have fewer, although still some, unwanted side effects. Preliminary data suggest that certain calcium antagonists may often lower BP without causing relevant metabolic impairment. These agents and converting enzyme inhibitors deserve further evaluation in the treatment of DM-associated hypertension.
Angiotensin II↗
[Hirsutism].
The symptom of hirsutism, i.e. excessive sexual hair of the male pattern for the individual woman, must be strictly differentiated from hypertrichosis, which is not androgendependent and occurs in both sexes, and also from the disease of virilization. The suffering derives from a divergence from the feminine ideal rather than from reality, and most forms of solitary hirsutism are probably to be assigned to the outer area of a Gaussian curve of sexual hair growth in normal women, by analogy to baldness in men. Although slightly elevated androgen levels are by no means rare, receptorial and postreceptorial processes in the hair follicle cells are at least of equal importance; both are modulated by a variety of partial factors. The salient point in workup is to exclude virilization and other primary diseases: this is usually possible on clinical grounds and by limited hormone measurements. Longterm therapy of solitary hirsutism is chiefly cosmetic, if there is no simultaneous wish for contraception. If this is desired, and if the hirsutism is mild, an initial low-dose cyproterone acetate-estrogen combination may be (appropriate. A higher dosage of cyproterone acetate Hammerstein 's regimen) over many years should be confined to severe forms.
Adult↗
Effects of nitrendipine and other calcium antagonists on glucose metabolism in man.
Some calcium antagonists, including nitrendipine, were noted to cause a dose-dependent and reversible inhibition of insulin release in certain animal models. Therefore, it is important to know the effects of clinical treatment with calcium antagonists in nondiabetic or diabetic man. A review of the literature allows the following conclusions: Acute and short-term therapy with calcium antagonists in nondiabetic and diabetic individuals did not change glucose homeostasis assessed with or without a glucose load. Nevertheless, higher doses of calcium antagonists were occasionally noted to slightly impair glucose homeostasis in nondiabetics, whereas, in some studies of diabetics, a slight amelioration or deterioration of glucose tolerance was variably reported. In long-term studies, the longest extending over 5 years, no change in basal or in glucose-stimulated carbohydrate metabolism was apparent in nondiabetic or diabetic subjects. These results are corroborated by our placebo-controlled observations during antihypertensive monotherapy with nitrendipine in Type II diabetics. Thus, glucose and insulin profiles and areas under the curve, before and following standard breakfast, were not altered following nitrendipine treatment periods of 6 weeks and 6 months, respectively. Concomitant blood levels of HbA1 on nitrendipine also were not different from those on placebo. The available information indicates that calcium antagonists probably do not affect glucose homeostasis to a clinically relevant degree, although some minor influences especially of higher dosages cannot be excluded.
Blood Glucose↗
[Cushing's disease: do patients remain dependent upon substitution therapy following microsurgical exstirpation of hypophyseal adenomas?].
Data on 4 patients with Cushing's disease (2 microadenomas, 2 macroadenomas with chiasma syndromes) demonstrate that a few months after microsurgical extirpation of the pituitary adenoma (and, in macroadenomas, irradiation) the previously suppressed normal ACTH-producing cells recuperate and react adequately to stimulation. Because of the similar behaviour of the remainder of the gland, none of the 4 patients needed hormonal substitution and all were back at work full time about 1 year after the operation. This is in contrast to the obligatory need for corticoid substitution after bilateral epinephrectomy, and affords ground to consider pituitary microsurgery the treatment of choice in these patients.
Adenoma↗
[Antihypertensive therapy in diabetes mellitus].
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Antihypertensive Agents↗
Virilization of a post-menopausal woman by a testosterone-secreting Leydig cell type adrenal adenoma.
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17-Ketosteroids↗
Uptake and metabolism of serotonin by rat adrenal tissue in vitro.
After incubation of separate zones of rat adrenals with radioactively labelled serotonin--at concentrations at which the amine had been previously shown to stimulate aldosterone biosynthesis--the tissue radioactivity was several times higher in the capsular ("zona glomerulosa") than in the decapsulated portions of the glands. High doses of unlabelled serotonin diminished the accumulation of radioactivity, but only when added simultaneously with the tracer. In the course of the incubation, radioactive 5-hydroxy-3-indoleacetic acid, i.e. the deaminated metabolite of serotonin, rapidly appeared in the medium. Most of the radioactive material accumulated by the adrenal was recovered in the cytosol fraction and was no longer identical with serotonin, but consisted mainly of 5-hydroxy-3-indoleacetic acid and another, unidentified metabolite. Unaltered serotonin was found in capsular adrenal tissue extracts only when a monoamine oxidase inhibitor (nialamide) has been added to the incubation medium. Rapid uptake and metabolism thus appeared to be the predominant features of the interaction of incubated adrenal tissue with serotonin. These events may have obscured the possible binding of very small amounts of serotonin to receptor sites. The observed accumulation of radioactivity in adrenal tissue was mainly due to delayed outflow of intracellulary formed metabolite, since 5-hydroxy-3indoleacetic acid was neither taken up by incubated adreanls nor bound by adrenal cytosol. No evidence of serotonin storage in the zona glomerulosa was found in these studies.
Adrenal Glands↗
[Posture weakness, pulmonary function and use of leisure time in school children].
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Body Height↗
Antihypertensive therapy in diabetic patients.
Hypertension in diabetic patients is more common than in controls, contributes substantially to their increased cardiovascular morbidity and mortality, and should be treated as accurately as diabetes mellitus itself. After appropriate exclusion of secondary forms, the first therapeutic step consists of reduction of overweight, salt intake, and smoking; the omission of interfering drugs; and adequate instruction. Step 2 has usually been the prescription of a diuretic drug, in spite of its known side effects on carbohydrate and lipid metabolism. A new possible alternative may be a calcium antagonist. Results in 10 hypertensive diabetic persons suggest that at a dose that normalizes blood pressure, neither carbohydrate nor lipid metabolism is altered, uric acid decreases, the exaggerated cardiovascular reactivity toward norepinephrine becomes normal, and the pressor dose for angiotensin II tends to rise. Body weight, blood volume, exchangeable sodium, as well as plasma and urinary sodium, potassium, and creatinine levels were unchanged. The third therapeutic step is the addition of a cardioselective beta blocker in a moderate dose. This avoids the disadvantages of beta 2-adrenergic blockade such as decreased insulin output, prolonged hypoglycemia, diminished glucagon secretion, and increased vasospasticity during hypoglycemic states, as well as aggravation of peripheral vascular disease. Alternatives are other sympatholytics with their known tendency to cause or increase orthostatic and sexual problems or, again, a calcium antagonist. In step 4, a hydralazine-type drug or prazosine is added. The fifth step, which adds minoxidil or captopril to the previous drugs, should only be taken after a specialist reevaluates the overall situation.
Adrenergic beta-Antagonists↗