Idiopathic Edema Research Articles

Influence of previous diuretic intake on the humoral and hormonal profile of idiopathic oedema.

Three groups of women underwent water loading tests: normal subjects, idiopathic oedema patients who had taken no medication for at least 3 months, and a second oedema group with recent diuretic intake. Idiopathic oedema in drug-free patients was characterized by an abnormal capillary permeability, lower basal protein values, a dramatic drop in urinary output in the upright position due to reduced glomerular filtration, enhanced reabsorption of sodium and water and stimulation of aldosterone and antidiuretic hormone (AVP) secretions. In these idiopathic oedema cases, osmolar AVP regulation was disrupted but AVP control by plasma volume was maintained. In the basal state, patients with recent diuretic intake were characterized by a gain in body weight and by depletion of plasma volume and plasma potassium. In these subjects, urinary output in the upright posture was as insufficient as in drug-free patients but was due to higher sodium reabsorption. Renal insensitivity to AVP action was also observed. Osmolar regulation and volume regulation of AVP were both disrupted in these cases with recent diuretic intake.

Comparative Studies of Urinary Electrolyte Excretion, the Renin-Angiotensin-Aldosterone System and Plasma Dopamine-β-Hydroxylase Activity in Patients with Idiopathic Edema and Normal Subjects during the Menstrual Cycle

The changes of circumferential size of legs, urine output, the amount of urinary Na and K excretion, tubular rejection fraction of Na (TRF Na), urinary Na/K ratio, plasma renin activity (PRA), plasma aldosterone concentration (PAC), the amount of urinary aldosterone excretion (UAE) and plasma dopamine-beta-hydroxylase activity (DBH) were studied in 7 patients with idiopathic edema and 5 normal subjects from the recumbent to upright positions by a water loading test (oral ingestion of 1 L of water) in the follicular and luteal phase of the menstrual cycle. The increase in circumferential size of legs in the patients with idiopathic edema was greater than in normal subjects. The percent reduction in urine output, urinary Na excretion, TRF Na and urinary Na/K ratio (upright versus supine) in patients with idiopathic edema tended to be greater than that in normal subjects. However, these indices showed no significant differences between the follicular and luteal phase both in patients with idiopathic edema and normal subjects. PRA and PAC, on the subjects' being tilted to the upright position after water loading, were not significantly different between patients with idiopathic edema and normal subjects during the menstrual cycle, while increases in PAC and UAE were noted in patients with idiopathic edema in the upright position, especially in the follicular phase. Interestingly, plasma DBH activity in patients with idiopathic edema was significantly lower than that in normal subjects in both the follicular and luteal phases. These results indicate that posturally induced anti-diuresis and anti-natriuresis seems not to be related to the phase of the menstrual cycle, and abnormal mechanisms of the dopaminergic autonomic nervous system might exist in this disorder.

Furosemide-induced edema in the patients with idiopathic edema. Exaggerated increase in renin-angiotensin-aldosterone system.

Furosemide is now commonlyprescribed for the patients with idiopathic edema and is known as a powerful stimulus to the renin-angiotensin-aldosterone system. We report here two patients with idiopathic edema who had episodes of furosemide-induced edema. In these patients exaggerated increase in the activity of reninangiotensin-aldosterone system was observed in response to the combined stimuli of furosemide administration and erect posture. This could be explained as a cause of fusosemide-induced edema. Therefore attention should be paid that administration of furosemide increases edema in somepatients with idiopathic edemaand makes the patients dependent on its continued administration.

Idiopathic edema.

Idiopathic edema is a common disorder in younger women. In some cases, edema may be induced by abuse of diuretics for the purpose of weight reduction. In other cases, the pathogenesis of edema is obscure. Increased orthostatic fluid retention secondary to abnormal orthostatic venous 'pooling' and shifting of intravascular fluid into the interstitial space may play a role. Secondary hyperaldosteronism, if present, is usually due to diuretic treatment. Abnormalities in prolactin secretion are probably not a cause of idiopathic edema.

Role of endocrinological factors in the pathogenesis of idiopathic edema.

In order to investigate the etiology of idiopathic edema, clinical findings and endocrinological abnormalities were analyzed in twenty-seven patients, and the following results were obtained. An easy occurrence of subcutaneous bleeding and positive Rumpel-Leede phenomenon were observed in the majority of the patients. ADH, plasma renin activity and plasma aldosterone concentration in the patients did not show abnormalities following water loading in the supine position when compared with normal controls. But the results obtained in the present study suggested that they might contribute to water and sodium retention in the upright position. In the patients, plasma prolactin levels were not decreased, but rather increased and urinary excretion of kallikrein and kinin was reduced significantly after water loading in the upright position. Thus, prolactin and urinary kallikrein-kinin system might also contribute to water and sodium retention in idiopathic edema, directly or indirectly through the augmentation of the action of ADH and of aldosterone. It was concluded that the increased vascular permeability and endocrinological polyfactors play a role, in a cooperative fashion, in the mechanism of this disease.

Abnormal regulation of antidiuretic hormone in idiopathic edema

Idiopathic edema is characterized by impaired water excretion, particularly in the upright posture. Indirect evidence has shown that antidiuretic hormone is involved in this disease. For this reason, we measured urinary arginine vasopressin by radioimmunoassay before and during water loading (15 ml/kg) in 10 normal women and in 10 subjects with idiopathic edema in both the supine and upright postures. Daily sodium intake was 100 meq. Renin and aldosterone were concomitantly investigated, and abnormally high values were observed both in the recumbent and upright postures. Basal values for urinary arginine vasopressin were identical in control subjects and in patients with idiopathic edema. The water load significantly reduced urinary arginine vasopressin in normal women in both positions, but in those with idiopathic edema only in the supine position. In those with idiopathic edema, assumption of the upright posture was accompanied by a transient decrease in glomerular filtration, a major decrease in osmolar clearance and no decrease in urinary arginine vasopressin after water loading. Significant correlations were established between urinary arginine vasopressin and osmolar or volemic parameters in normal women, but these correlations were not found in those with idiopathic edema in either position. Arginine vasopressin regulation was abnormal in idiopathic edema, and this hormone was believed to play a part in the pathogenesis of this disease.

Idiopathic oedema: a study of the effects of bromocriptine.

We have studied the effect of bromocriptine in seven patients with idiopathic oedema. Two patients were unable to tolerate the drug; the remaining five were maintained on doses of between 5 and 7.5 mg a day. Symptomatic improvement was noted in two patients and in both of these and one other there was a significant improvement in mean diurnal weight gain. The fall in free water and sodium clearance on standing was reduced by bromocriptine, but there was no significant change in the excessive fall in plasma volume.

Idiopathic edema as a cause of nonarticular rheumatism

Six women, aged 24 to 53, presented with symptoms of diffuse aching, morning stiffness, and fatigue, but demonstrated no objective abnormalities on joint examination or in laboratory studies. Each was found to have idiopathic edema, a disorder of fluid retention probably related to an abnormality of capillary permeability in which transudation of fluid into the subcutaneous tissues of dependent parts may result in swelling and discomfort. The rheumatic symptoms improved when therapeutic measures were directed against the accumulation of edema fluid. This syndrome may account for a minority of cases of nonarticular rheumatism in women.

THE RELATIONSHIP BETWEEN THE ‘IDIOPATHIC OEDEMA SYNDROME’ AND SUBCLINICAL HYPOTHYROIDISM

Thyroid function has been studied in eleven patients with the 'idiopathic oedema syndrome'. Six patients have been shown to have subclinical hypothyroidism associated with the presence of thyroid antibodies. All responded to treatment with sodium thyroxine. Five patients had normal thyroid function, absence of thyroid antibodies and failed to respond to treatment with sodium thyroxine.

Effect of Metoclopramide, a Dopaminergic Inhibitor, on Renin and Aldosterone in Idiopathic Edema: Possible Therapeutic Approach with Levodopa and Carbidopa

Metoclopramide, a dopaminergic inhibitor, was injected (10 mg iv) in 15 normal women and in 9 patients with clinical evidence of idiopathic edema, while on a 130 meq sodium and 50-70 meq potassium diet. The subjects kept a recumbent position during the test. PRA slightly increased at 45 min (p < 0.01) in normal women, A low sodium diet (20–40 meq/day) seemed to accelerate the PRA response, which was significant at 20 min (P < 0.05). In patients with idiopathic edema, PRA consistently increased at 20, 30, and 45 min (P < 0.05). Plasma aldosterone (PA) increased significantly at 10, 20, 30, 45, and 60 min (P < 0.005) both in normal women and in patients. The absolute change of PA from 0–10 min was significantly higher in patients with idiopathic edema (P < 0.001) and preceded the increase of PRA. In 5 normal women, urinary sodium decreased and urinary potassium increased after metoclopramide. Serum electrolytes were not modified. In 2 patients with idiopathic edema and hypokalemia, the treatment with a cent...

II Clinics of Edema (5) A Role of Endocrinological Factors in Edema of Unknown Etiology with Special Reference to Idiopathic Edema

II Clinics of Edema (5) A Role of Endocrinological Factors in Edema of Unknown Etiology with Special Reference to Idiopathic Edema

Sodium and Water Homeostasis

In fewer than 250 pages, this little monograph covers the major disturbances of water and salt metabolism occurring in a variety of diseases. It has chapters on hyponatremia and hypernatremia, describing their causes, classifications, consequences, and methods of treatment. It reviews the factors regulating renal sodium excretion, tells which segment of the nephron does what, and explains where the various diuretic drugs exert their action. It comprehensively discusses the mechanisms of sodium retention in heart failure, nephrotic syndrome, nephritis, and idiopathic edema. There is a chapter on the causes and homeostatic disturbances of extracellular fluid depletion. There is also an excellent chapter on the effects of liver disease—complete with 150 references—describing the renal disturbances in various forms of hepatic disease and critically sifting the enormous mass of frequently conflicting or contradictory evidence for various pathogenetic mechanisms. The book is written for nephrologists, urologists, internists, and pediatricians, but should also appeal

Idiopathic edema: Pathogenesis, clinical features, and treatment

Previously published findings are reviewed and new data are presented relating to the clinical features, pathophysiology, and treatment of the idiopathic edemas, a group of disorders diagnosed by exclusion of the known causes of edema. The disorders occur almost exclusively in women, show diurnal (postural), not “cyclic” fluctuations in severity, often cause discomfort and occasionally pain, and may be aggravated by prolonged orthostasis, hot environments, menses, and some drugs. Among the pathophysiologic factors known to be important in edema formation, in general: (1) Hypoproteinemia is more commonly the result than the cause of idiopathic edema; (2) elevated capillary hydrostatic pressure is seldom the primary cause, except perhaps in rare cases of occult congestive heart failure; (3) changes in tissue pressure may limit the progression of, but do not initiate, the edema; (4) changes in capillary wall permeability and (5) changes in capillary diffusion area, perhaps because of excessive dilatation of precapillary sphincters appear to be of importance; (6) abnormalities of lymphatic flow are not demonstrable; and (7) the upright posture is an important contributor to the excessive transudation in over 80% of the patients studied (“orthostatic edema”) but not in the remaining minority of patients (“nonorthostatic edema”). By balance studies with constant diets and by an abbreviated “posture test”, it has been shown that (A) the majority of patients with “orthostatic edema” have excessive orthostatic sodium (Na) retention that results from an excessive orthostatic fall in glomerular filtration rate, frequently associated with excessive renal tubular reabsorption of the subnormal filtered Na load because of orthostatic hyperaldosteronism, and (B) about 30%–40% of patients with orthostatic edema have “orthostatic water retention”, demonstrable by an inability to excrete more than 55% of a 20 ml/kg water load during 4 hr in the upright posture. In most of these patients but not in most other types of edema, orthostatic excretion of the water load is restored to normal by ethanol (a known inhibitor of vasopressin release). Improvement in orthostatic renal excretion by external compression of the legs and persistence of excessive orthostatic changes in leg volume despite restricted Na intake support microscopic evidence that a capillary “leak” may be the primary cause of most orthostatic edemas. Reduced dopamine excretion has been reported and linked to the causation of some types of idiopathic edema. Obesity is often associated with edema that differs from other idiopathic edemas in that it usually disappears with caloric restriction and weight loss. In occasional patients, undue sensitivity to heat may play a role as important as that of posture. Treatment of idiopathic edema includes avoidance of excessive salt intake, reduction of the duration of standing and sitting, and administration of conventional diuretics, preferably at 7 or 8 p.m., followed by recumbency for several hours before sleep. Hyperaldosteronism has responded to subtotal adrenalectomy (which is not recommended) and constitutes a strong indication for the use of spironolactone, which facilitates recumbent excretion of Na retained in the upright posture. Sympathomimetic amines (ephedrine, phenylephrine, and preferably dextroamphetamine) are the only agents that will usually significantly reduce the excessive weight gain from morning to evening (the hallmark of orthostatic edema), perhaps by preventing excessive capillary pooling and transudation. They have been used safely, effectively, and without loss of their efficacy, for up to 20 yr in several patients. Elastic stockings and garments are occasionally useful and regular exercise, especially swimming, may be beneficial.

Dopamine-sodium relationship: is dopamine a part of the endogenous natriuretic system?

A possible role of DA as an endogenous natriuretic hormone was reviewed under three aspects: (1) its excretion in response to saline vs. albumin-induced volume expansion, (2) the origin of urinary free DA and (3) urinary free DA excretion in an unexplained salt-retaining condition, idiopathic edema. We have shown (1) that the urinary free DA excretion increase in response to saline is specifically related to salt and does not occur when the same degree of volume expansion is induced by albumin, (2) that this increase in free DA originates in the kidney and (3) that idiopathic edema patients excrete less free DA than control subjects. It is proposed that free DA originating in the kidney is a rather sal than volume-dependent endogenous natriuretic factor. Its deficiency may contribute to excessive sodium retention in idiopathic edema. However, DA is probably not the single natriuretic hormone but a part of a natriuretic system, components of which are other renal vasodilating and natriuretic substances such as prostaglandins and kallikrein-bradykinin.

Diurnal variation of plasma renin activity, aldosterone and cortisol in idiopathic edema.

The plasma levels of aldosterone (PA), renin activity (PRA) and cortisol were measured every 30 min in the supine position in 4 women with idiopathic edema. The circadian rhythm of PA was similar to that previously reported in normal subjects: peak secretory episodes occurred during the latter part of sleep and shortly after awakening. Moreover the levels of PA were statistically significantly correlated with PRA and cortisol in 3 of the 4 patients (P < .005). Secretory spikes followed meals by 30 min and furosemide administration by 4 h. It is concluded that, 1) as in normals, a central nervous system rhythm may be important in control of PA, and 2) potassium is suggested as the secretagogue of aldosterone after meals. Comparison of the circadian hormone levels in the patients with those previously found in normals revealed only one subject who had significantly lower PRA than normals, and one patient with a higher PA during the midnight to 0800 h period than controls. The other levels were not significa...

Catamnestic and endocrinological investigations in women with idiopathic edema (author's transl)

The clinical picture and the course of idiopathic edema is described after evaluating catamnestic questionnaires on 39 patients. It appears that the syndrome often occurs in other female family members, especially in mothers of propositi and that two thirds of patients have also suffered from symptoms of allergy. In contrast to observations of other groups, diabetes mellitus and slight hypoalbuminemia were found only in a few patients. Secondary hyperaldosteronism was almost exclusively observed in patients who had been taking diuretics during the last few days before the measurements were done. The plasma concentrations of 6 other adrenal steroidal hormones were measured in 33 patients. Only in few of them, mostly patients who had taken diuretics, increased level of 11-deoxycorticosterone, 18-OH-11-deoxycorticosterone and corticosterone were observed. Idiopathic edema does not seem to be a disease entity, but some prediposing factor related to the female reproductive system is likely to exist. Results of systematic psychosomatic studies in our patients will be reported later on.

Management of idiopathic oedema

Idiopathic oedema is well recognised in the USA and on the continent of Europe but is less commonly diagnosed in Britain. It occurs predominantly in women, the age of onset usually being between 20–40 years. In most patients symptoms consist of periodic ankle swelling and abdominal distension and sometimes swelling of the hands and face. Severely affected patients may develop pulmonary congestion or hypovolaemia. Symptoms are often worse premenstrually, in a warm environment and after prolonged standing, and are associated with headache, irritability and depression. The cause of idiopathic oedema is not known, but it is probably related to an excessive loss of fluid from the blood vessels that occurs when the patient is upright.1 Cardiac, hepatic, renal, allergic, nutritional and hyproprotein-aemic disease must be excluded.2 3

ENCEPHALOLOPATHIES IN CATTLE IN TASMANIA

Five central nervous diseases are described and their relationships to previously recorded conditions are discussed. The conditions are congenital inclusion-body encephalopathy probably caused by a paramyxovirus infection, idiopathic neuraxial oedema of a newborn calf, focal symmetrical encephalomalacia of a young calf, yacca (Xanthorrhoea spp) poisoning of adult cattle leading to spinal demyelination, and focal demyelination and neuropathy in an adult cow.

Idiopathic Oedema of Women: A CLINICAL AND INVESTIGATIVE STUDY

A clinical and investigative study is reported of 19 patients with 'idiopathic oedema of women'. The resons for defining this as a specific syndrome unrelated to the menstrual cycle are given, and the clinical features reviewed. During a forced water diuresis the flow and composition of the urine and the plasma volume were studied on tilting from the supine to the upright position seven premenopausal and four postmenopausal patients with this disorder. No differences were found in the results obtained in the follicular and luteal phases of the menstrual cycle or in the pre- and post-menopausal patients. The reductions in urinary volume and electrolyte excretion on upright tilting were greater than those observed under similar circumstances during the luteal phase of the menstrual cycle in normal female controls, and attributed to increased proximal renal tubular reabsorption. The rate of loss of isotopically labelled albumin from the intravascular compartment was greater in patients with idiopathic oedema than in control subjects. A reduction in blood volume on tilting occurred in control subjects and patients with idiopathic oedema, but was greater in the latter; and the larger the fall, the greater were the reductions in urinary flow and electrolyte excretion. The effect of administering 9-alpha-fluorohydrocortisone was studied in nine patients with idiopathic oedema. One patient failed to 'escape' from the sodium-retaining action of this mineralocorticoid and developed pulmonary oedema; the others 'escaped' normally. The pathophysiological disturbance in this condition is related to increased loss of fluid from the vascular compartment but the precise aetiological mechanism remains unknown.

Urinary and Plasma Cyclic Adenosine 3′,5′-Monophosphate in Patients with Idiopathic Edema

Urinary excretion and plasma concentrations of adenosine 3',5'-monophosphate were determined in idiopathic edema patients both at rest and after assumption of the upright position. Patients and normal subjects responded similarly to upright posture with decreases in urinary volume and creatine excretion and their urinary excretion of cyclic AMP was not significantly different. The plasma concentration of cyclic AMP was high in patients, both in the recumbent and upright positions, and its renal clearance (unlike that of creatinine) was low. Plasma cyclic AMP increased in response to upright posture both in patients and normal subjects. Even if the significance of elevated plasma cyclic AMP is unknown, its presence without an increase in urinary cyclic AMP suggests that the renal handling of cyclic AMP is abnormal is idiopathic edema; this may be related to an excessive beta-adrenergic tone.