- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor Emeritus
- University of Rochester School of Medicine and Dentistry
Idiopathic edema is a syndrome of fluid retention with swelling of the face, hands, trunk, and limbs, occurring in premenopausal women in the absence of cardiac, hepatic, or renal disease [1-4]. Diabetes, obesity and emotional problems (including depression and neurotic symptoms) are commonly part of this syndrome [5,6]. There is also an association with purging behaviors (use of diuretics, laxatives, or vomiting) to achieve weight loss, which has led some authors to question whether idiopathic edema is truly an independent entity .
Three major theories, each of which may apply to some patients, have been proposed to explain the fluid retention in idiopathic edema: capillary leak; refeeding; and diuretic-induced edema.
Capillary leak — Many women with idiopathic edema have an abnormal response to assumption of the upright posture. Normal subjects develop a mild degree of plasma volume depletion in this setting due to pooling of extracellular fluid in the lower extremities. As a result, there is a fall in urinary sodium excretion  and a daytime weight gain that averages 0.5 to 1.5 kg [1,2]. In comparison, women with idiopathic edema lose much more fluid from the vascular space with standing , leading to often marked elevations in the release of the "hypovolemic" hormones renin, norepinephrine, and ADH, and to a larger morning-to-evening weight gain that can exceed 5 kg in severe cases [1-3].
These observations have led to the suggestion that idiopathic edema may represent a capillary leak syndrome, in which increased capillary permeability favors the movement of fluid out of the vascular space, a response that is exaggerated by gravity when standing . This primary tendency to plasma volume depletion also explains why the jugular venous pressure is in the low-normal range in idiopathic edema and why pulmonary edema does not occur, even in the presence of marked peripheral edema. (See "Idiopathic systemic capillary leak syndrome".)
The factors responsible for fluid leakage out of the capillaries are not well understood: either altered capillary hemodynamics or, in selected cases, primary capillary injury could be responsible . It is possible, for example, that dilatation of the precapillary sphincter plays a central role by permitting more of the systemic pressure to be transmitted to the capillary, thereby increasing the capillary hydraulic pressure. Such a response could be humorally mediated. Women with idiopathic edema often have impaired hypothalamic function, resulting in abnormal release of prolactin, luteinizing hormone, and perhaps other hormones .To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Badr KF. Idiopathic edema. In: Contemporary Issues in Nephrology (Body Fluid Homeostasis), Brenner BM, Stein JH, Churchill Livingstone, New York 1987. Vol 16.
- Streeten DH. Idiopathic edema: pathogenesis, clinical features, and treatment. Metabolism 1978; 27:353.
- Edwards OM, Bayliss RI. Idiopathic oedema of women. A clinical and investigative study. Q J Med 1976; 45:125.
- Kay A, Davis CL. Idiopathic edema. Am J Kidney Dis 1999; 34:405.
- Pelosi AJ, Sykes RA, Lough JR, et al. A psychiatric study of idiopathic oedema. Lancet 1986; 2:999.
- Dunnigan MG, Henderson JB, Hole D, Pelosi AJ. Unexplained swelling symptoms in women (idiopathic oedema) comprise one component of a common polysymptomatic syndrome. QJM 2004; 97:755.
- EPSTEIN FH, GOODYER AV, LAWRASON FD, RELMAN AS. Studies of the antidiuresis of quiet standing: the importance of changes in plasma volume and glomerular filtration rate. J Clin Invest 1951; 30:63.
- Docci D, Turci F, Salvi G. Therapeutic response of idiopathic edema to captopril. Nephron 1983; 34:198.
- Coleman M, Horwith M, Brown JL. Idiopathic edema. Studies demonstrating protein-leaking angiopathy. Am J Med 1970; 49:106.
- Young JB, Brownjohn AM, Chapman C, Lee MR. Evidence for a hypothalamic disturbance in cyclical oedema. Br Med J (Clin Res Ed) 1983; 286:1691.
- Sowers J, Catania R, Paris J, Tuck M. Effects of bromocriptine on renin, aldosterone, and prolactin responses to posture and metoclopramide in idiopathic edema: possible therapeutic approach. J Clin Endocrinol Metab 1982; 54:510.
- Idiopathic edema: role of diuretic abuse. Kidney Int 1981; 19:881.
- Baum M. Insulin stimulates volume absorption in the rabbit proximal convoluted tubule. J Clin Invest 1987; 79:1104.
- Friedberg CE, van Buren M, Bijlsma JA, Koomans HA. Insulin increases sodium reabsorption in diluting segment in humans: evidence for indirect mediation through hypokalemia. Kidney Int 1991; 40:251.
- Mitchell JE, Pomeroy C, Seppala M, Huber M. Pseudo-Bartter's syndrome, diuretic abuse, idiopathic edema, and eating disorders. Int J Eat Disord 1988; 7:225.
- Bihun JA, McSherry J, Marciano D. Idiopathic edema and eating disorders: evidence for an association. Int J Eat Disord 1993; 14:197.
- MacGregor GA, Markandu ND, Roulston JE, et al. Is "idiopathic" edema idiopathic? Lancet 1979; 1:397.
- de Jonge JW, Knottnerus JA, van Zutphen WM, et al. Short term effect of withdrawal of diuretic drugs prescribed for ankle oedema. BMJ 1994; 308:511.
- Pelosi AJ, Czapla K, Duncan A, et al. The role of diuretics in the aetiology of idiopathic oedema. QJM 1995; 88:49.
- Kim YG, Kim B, Kim MK, et al. Medullary nephrocalcinosis associated with long-term furosemide abuse in adults. Nephrol Dial Transplant 2001; 16:2303.
- Shichiri M, Shiigai T, Takeuchi J. Long-term furosemide treatment in idiopathic edema. Arch Intern Med 1984; 144:2161.
- Riemenschneider T, Bohle A. Morphologic aspects of low-potassium and low-sodium nephropathy. Clin Nephrol 1983; 19:271.
- Suzuki H, Fujimaki M, Nakane H, et al. Effect of the angiotensin converting enzyme inhibitor, captopril (SQ14,225), on orthostatic sodium and water retention in patients with idiopathic edema. Nephron 1985; 39:244.
- Edwards OM, Dent RG. Idiopathic edema. Lancet 1979; 1:1188.
- SPELLER PJ, STREETEN DH. MECHANISM OF THE DIURETIC ACTION OF D-AMPHETAMINE. Metabolism 1964; 13:453.
- Edwards BD, Hudson WA. A novel treatment for idiopathic oedema of women. Nephron 1991; 58:369.
- Hopkins DF, Cotton SJ, Williams G. Effective treatment of insulin-induced edema using ephedrine. Diabetes Care 1993; 16:1026.
- Kalambokis GN, Tsatsoulis AA, Tsianos EV. The edematogenic properties of insulin. Am J Kidney Dis 2004; 44:575.
- Soudet S, Lambert M, Lefèvre G, et al. Long term use of metformin in idiopathic cyclic edema, report of thirteen cases and review of the literature. Pharmacol Res 2017; 119:237.
- Valensi P, Behar A, Andre P, et al. The effects of metformin on the capillary permeability to albumin in women patients with cyclic edema. Angiology 1995; 46:401.