What is the pathophysiological mechanism by which hypothyroidism causes pitting edema?

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Last updated: June 17, 2025View editorial policy

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From the Research

Hypothyroidism causes pitting edema through a complex interplay of mechanisms related to thyroid hormone deficiency, including decreased cardiac output, increased capillary permeability, and accumulation of hydrophilic glycosaminoglycans, which collectively lead to fluid retention and edema formation. The pathophysiological mechanism underlying this condition involves multiple factors, such as:

  • Decreased cardiac output and reduced renal blood flow, leading to activation of the renin-angiotensin-aldosterone system, which promotes sodium and water retention 1
  • Increased capillary permeability, allowing more fluid to leak into interstitial spaces, as evidenced by studies demonstrating increased transcapillary escape rate of albumin in patients with hypothyroidism 2
  • Accumulation of hydrophilic glycosaminoglycans, particularly hyaluronic acid, in the dermis and other tissues, which bind water and contribute to the characteristic myxedematous appearance 3
  • Decreased metabolism of proteins, resulting in lower plasma oncotic pressure, further promoting fluid shift from the vascular compartment to the interstitium These mechanisms are supported by various studies, including a case report of a patient with silent thyroiditis who developed pitting edema, which was successfully treated with angiotensin II receptor blockade 1. Additionally, a study on patients with mild hypothyroidism found that treatment with thyroxine reduced capillary permeability and edema 2. Overall, the development of pitting edema in hypothyroidism is a multifactorial process, and treatment with appropriate thyroid hormone replacement therapy can help resolve the edema by correcting the underlying metabolic abnormalities.

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