Mechanisms of Edema Formation in Myxedema — Increased Protein Extravasation and Relatively Slow Lymphatic Drainage

Abstract

We assessed extravascular accumulation of albumin and fluid in primary myxedema by measuring metabolic turnover and transcapillary escape of 131I-labeled human albumin in seven patients. In the hypothyroid state, we found a low plasma volume (P less than 0.05), a reduced rate of albumin synthesis and catabolism (P less than 0.01), an increased transcapillary escape rate of albumin (P less than 0.01), a remarkable increase in the extravascular mass of albumin (1500 micronmol; P less than 0.01) and a longer mean transit time through the extravascular spaces in primary myxedema than in other states of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain the formation of exudates in the serous cavities that are well known in myxedema.

Thyrotoxic Pericardial Effusion Complicating Graves' Disease in Pregnancy

“…8,21 The pathophysiology of thyrotoxic pericardial effusion has been demonstrated to be similar to that of pretibial myxedema, with a characteristic serous effusion attributed to the transudation of albumin and decreased lymphatic clearance of interstitial fluid proteins. 22 On occasion, the effusion can also appear serosanguinous, as in our patient. 11,12 This purported underlying pathophysiologic mechanism is the basis for several reports stating the potential benefit of prednisone in these patients.…”

An unusual case of pericardial tamponade in primary hypothyroidism

“…The amount of fluid in the pericardial effusions associated with hypothyroidism can be as large as 5 -6 L. 8 Inadequate lymphatic drainage may be the mechanism by which the exudates are produced in the serous cavities of patient with hypothyroidism. 9 The primary phenomenon in tamponade is a compression of all cardiac chambers after the pericardial content reaches the limit of pericardial reserve volume. With smaller cardiac chambers, the myocardial diastolic compliance is reduced and cardiac inflow becomes limited, ultimately equalizing mean diastolic pericardial and chamber pressures.…”

Changes in heart rate variability and QT dispersion in patients with overt hypothyroidism

“…Other processes can contribute to an increased QT dispersion. Vascular smooth muscle cells swelling and water accumulation in the myocardial wall due to protein deposition in extracellular space could be a source of increased QT dispersion (19,20).…”