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The most common clinical situation is a small elderly woman taking a thiazide diuretic for hypertension. Patients may be asymptomatic or complain of weakness, lethargy, or occasionally confusion due to hyponatremia.


  1. One of the most common causes of hyponatremia

  2. Often associated with more severe hyponatremia than frequently seen in other etiologies (mean serum sodium, 116 mEq/L)

  3. Most commonly seen with thiazide diuretics; rarely seen with loop diuretics

  4. More common in patients over 70 years (OR 3.9), and patients with a low body mass index

  5. 56–70% of patients are women

  6. Hyponatremia can be multifactorial; pathogenesis may vary in different patients.

  7. Usually develops within 2 weeks of initiation but may occur later if other risk factors for hyponatremia develop

  8. Pathophysiology

    1. Thiazide diuretics interfere with NaCl transport in cortical diluting segments, causing natriuresis and interfering with the generation of free water within the tubule. This limits free water excretion.

    2. The natriuresis results in hypovolemia.

    3. Hypovolemia may increase ADH levels, and interfere with free water clearance.

    4. Hypovolemia also reduces the GFR, which increases proximal sodium reabsorption, leading to reduced distal sodium delivery and reduced free water clearance.

    5. In some patients, hyponatremia develops due to a combination of increased water intake coupled with ADH independent water retention. Such patients appear clinically euvolemic.

  9. NSAID use may increase the risk of thiazide-induced hyponatremia.

  10. Hyponatremia may persist for 1 month after discontinuation of thiazide.


  1. The diagnosis is based on history of thiazide use.

  2. Clinical dehydration is evident in only 24% of patients.

  3. Symptoms include lethargy 49%, dizziness 47%, vomiting 35%, confusion 17%, and seizures 0.9%.

  4. Despite volume depletion, urine sodium concentration may be elevated if diuretic action is still present.


  1. Electrolytes should be check shortly after initiating thiazide diuretics.

  2. Symptomatic hyponatremia: See Table 24-2

  3. Asymptomatic hyponatremia: Stopping the diuretic is usually adequate. Thiazides should not be reinitiated later. Rapid and dangerous hyponatremia often recurs.

  4. Hypovolemic patients

    1. Consider careful volume resuscitation with normal saline.

    2. Unlike euvolemic or hypervolemic patients, fluid resuscitation in a hypovolemic patient restores volume and thereby suppresses ADH. The fall in ADH may result in rapid water losses and an overly rapid and dangerous correction of the serum sodium concentration resulting in ODS (Table 24-3). Serum sodium levels should be monitored closely and electrolyte replacement may need to be terminated (and free water administered) if serum sodium levels or urinary output rise abruptly (see Table 24-2).

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