The salient mechanism for thiazidein duced hyponatremia is related to the reduction in the renal free water clearance. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free. In addition, potassium depletion and urinary salt loss have been postulated to play a role in diureticinduced hyponatremia. Hyponatremia defined as a serum sodium level free water clearance was not more significantly reduced in the patients, an expected accompaniment when serum sodium is. However, hyponatremia rarely results from excessive water intake, unless the kidney is unabie to excrete free water, such as in patients on thiazide diuret.
Hyponatremia in elderly subjects is mainly induced by medications more frequently thiazides and antidepressants, the syndrome of inappropriate antidiuretic hormone secretion siad or endocrinopathies. A loop diuretic is much less likely to induce this problem unless the diuretic has induced volume depletion or water intake is very high since loop diuretics partially impair urinary. A recent study by leung and colleagues addresses this issue. We report a case of duloxetine induced hyponatremia in.
Clinical studies thiazide induced hyponatremia associated with death or neurologic damage in outpatients nasim ashraf, m. Hence, tah occurs in a heterogeneous group of patients, and thiazides may not be directly responsible in all. It has been reported in patients receiving diuretics as a physiological consequence of the therapy. Hyponatremia and hypernatremia are common findings in the inpatient and outpatient settings. Thiazideassociated hyponatremia, report of the hyponatremia. Thiazideinduced hyponatremia associated with death or. This is a particular problem in patients who despite a history of thiazide. Ashraf et al 2 x 2 ashraf, n, locksley, r, and arieff, a. Here, we have studied the phenotypic and genetic characteristics of patients hospitalized with tih. Jun 30, 2010 hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as. Rarely, such patients develop severe, lifethreatening hyponatremia within a few weeks after the initiation of a thiazide diuretic. It can be induced by a marked increase in water intake primary polydipsia andor by impaired water excretion due, for example, to advanced renal failure or persistent release of antidiuretic hormone adh.
Among the various causes of druginduced hyponatremia, thiazideinduced hyponatremia comprises a main cause, while loop diuretics only occasionally induce. Limiting free water intake and increasing protein intake are often not. The importance of thiazide induced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline treatment of essential hypertension have been introduced. We report a case of duloxetineinduced hyponatremia in. However, some patients given thiazides develop thiazide induced hyponatremia tih 5. Tih occur in up to 15% of treated adults and is one of the most common causes of severe hyponatremia in adults. On the other hand, whether thiazideinduced severe hyponatremia without symptoms is more common in women than in men has not been proven. Clinical studies thiazideinduced hyponatremia associated with death or neurologic damage in outpatients nasim ashraf, m. Thiazide diuretics are among the most widely used treatments for hypertension, but thiazide induced hyponatremia tih, a clinically significant adverse effect, is poorly understood.
Managing drug induced hyponatraemia in adults spiros fourlanos, fellow in endocrinology, royal melbourne hospital, and peter greenberg, department of general medicine and department of diabetes and endocrinology, royal melbourne hospital, and university of melbourne department of medicine, royal melbourne hospital, melbourne synopsis. The risk factors for the development of thiazideassociated hyponatremia are shown in table 1. Phenotypic and pharmacogenetic evaluation of patients with. Sodium disorders are associated with an increased risk. Thiazide diureticcaused hyponatremia in the elderly hypertensive. Reproducibility by single dose rechallenge and an analysis of pathogenesis. The effect most responsible for thiazideinduced hyponatremia is the induced reduction of free water clearance by the kidneys. Reduced renal capacity to excrete free water, usually age. Hyponatremia is the most frequent electrolyte disorder. Hypertension affects more than 30% of the worlds adult population and thiazide and thiazidelike diuretics are amongst the most widely used, effective, and least costly treatments available, with allcause mortality benefits equivalent to angiotensinconverting enzyme inhibitors or calcium channel antagonists. Managing druginduced hyponatraemia in adults spiros fourlanos, fellow in endocrinology, royal melbourne hospital, and. A minority of patients develop thiazideinduced hyponatremia tih and this is.
While cases of thiazideinduced hyponatremia are well documented, this severity of hyponatremia is unusual. Hyponatremia is one of the most common electrolyte abnormalities and is associated with many conditions. Diuretic induced hyponatremia in hypertensive patients. Thiazide diureticinduced hyponatremia is an important adverse effect. Medline abstracts for references 17 of diureticinduced. Pdf the importance of thiazideinduced hyponatremia tih is reemerging. Thiazideinduced hyponatremia associated with death or neurologic damage in outpatients. It is also surprising that the free water clearance was not more significantly reduced in the patients, an expected accompaniment when serum sodium is diluted. The addition of thiazide diuretics to the metabolic milieu, with their. Hyponatremia defined as a serum sodium level hyponatremia. Dec 01, 2017 of these, the mechanism of thiazide induced hyponatremia tih is poorly understood. Eleven patients with thiazide induced kaluril hydrochlorothiazide, 50 mg. Thiazideinduced hyponatremia and vasopressin release. Water restriction in one patient attenuated serum sodium reduction.
Thiazideinduced hyponatremia annals of internal medicine. Of these, 118 met criteria for true thiazideinduced hyponatremia tih. Elderly patients may have increased sodium diuresis and are especially susceptible to thiazideinduced hyponatremia, particularly when they have a preexisting defect in renal capacity to excrete free water. Treatment of severe hyponatremia kidney international. To examine whether a subgroup of patients is particularly susceptible to this complication. The risk factors for the development of thiazide associated hyponatremia are shown in table 1.
Hyponatremia is the most frequently occurring electrolyte abnormality and can lead to lifethreatening complications. A minority of patients develop thiazideinduced hyponatremia tih and this. Sodium plus potassium concentration in urine exceeds that in the plasma, which directly lowers plasma sodium concentration. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. Tih cases demonstrated an exaggerated free water reabsorption. Forty patients will be enrolled and receive a bottle of a protein supplement daily, providing 120 mmol of solutes and permitting an extra 163 ml free water loss, for 4 weeks. The thiazide may be directly responsible, termed thiazideinduced hyponatremia by the hyponatremia registry, which encompasses more than 5,000 patients with serum sodium levels. When both dehydration and hyponatremia are documented, query the provider if the relationship between the dehydration and hyponatremia can be linked or be further specified. Jun 15, 2003 severe hyponatremia as a result of thiazide diuretic.
Risk of thiazideinduced hyponatremia in patients with. Jun 30, 2010 the importance of thiazide induced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline treatment of essential hypertension have been introduced. Hyponatremia and thiazides, journal of clinical hypertension. Thiazide induced hyponatremia in the postoperative total joint replacement patient. Neoplasms in rats treated with pituitary growth hormone. Tih occurs when the intake of free water is greater than the amount the.
Thiazide effects reduction in free water clearance renal sodium loss stimulation of antidiuretic hormone secretion potassium depletion 2. Phenotypic and pharmacogenetic evaluation of patients with thiazideinduced hyponatremia. Overview of the treatment of hyponatremia in adults uptodate. Carlos ayus, md, in the july issue of the archives. Virtually all cases of severe diuretic induced hyponatremia have been due to a thiazide type diuretic. The management of hyponatremia norbert lameire, 2015. Hyponatremia occurs when the concentration of sodium in your blood is abnormally low. We use cookies to offer you a better experience, personalize content, tailor advertising, provide social media features, and better understand the use of our services. Son francisco, california from the nephrology section, department of medicine, veterans administration medical center and the university of california school of medicine, san francisco, california.
Severe hyponatremia as a result of thiazide diuretic. Two cohorts of patients who developed hyponatremia while using thiazide diuretics were analyzed. Hyponatremia rhabdomyolysis thiazide diuretics creatine phosphokinase myoglobin myoglobinuria abstract background. Thiazideinduced hyponatremia in the postoperative total. This disorder may be present on admission to the intensive care setting or develop during hospitalization as a result of treatment or multiple comorbidities. Read risk of thiazideinduced hyponatremia in patients with hypertension, the american journal of medicine on deepdyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips. Hyponatremia is an occasional but potentially fatal complication of diuretic therapy. Sodium is an electrolyte, and it helps regulate the amount of water thats in and around your cells. The salient mechanism for thiazideinduced hyponatremia is related to the reduction in the renal free water clearance. As recently described by fichman et al and others, thiazideinduced hyponatremia may have the classic.
Hyponatremia is a known adverse effect of duloxetine, and it can lead to potentially lifethreatening complications. Hyponatremia endocrine and metabolic disorders msd manual. Clinical and molecular features of thiazideinduced hyponatremia. However, hyponatremia occasionally may develop in the course of treatment with drugs used in everyday. Hyponatremia is an uncommon, but serious, complication of diuretic therapy. Thiazide induced hyponatremia, occurs due to increased water intake, reduction in diluting ability and water excretion in distal tubule. The silent epidemic of thiazidea induced hyponatremia. Thiazideinduced hyponatremia in the postoperative total joint replacement patient. Thiazide induced hyponatremia associated with death or neurological damage in. I cannot agree with the treatment regimen for diureticinduced hyponatremia advocated in the editorial by j. Hyponatremia endocrine and metabolic disorders msd.
Thiazide diureticcaused hyponatremia in the elderly. Thiazide induced hyponatremia associated with death or neurologic damage in outpatients. In hyponatremia, one or more factors ranging from an underlying medical condition to drinking too much water cause the sodium in your body to become. Hyponatremia represents a relative excess of water in relation to sodium. Thiazide diuretics are among the most widely used treatments for hypertension, but thiazideinduced hyponatremia tih, a clinically significant adverse effect, is poorly understood. Altered prostaglandin signaling as a cause of thiazideinduced. Clinical and molecular features of thiazideinduced. When a euvolemic patient receiving a thiazide manifests hyponatremia, it should be termed thiazideassociated hyponatremia tah. Hyponatremia is common with use of thiazides, begins soon after initiation of thiazides, may be severe and is common in elderly females.
Interestingly tih is reproducible with drug rechallenge in some patients the hyponatremia can be induced with a single dose in susceptible patients. Risk factors for thiazideinduced hyponatraemia qjm. Risk of thiazideinduced hyponatremia in patients with hypertension. There was a high frequency of neurologic manifestation of thiazide induced hyponatremia, whereas clinical dehydration was not a discernible feature. In the absence of welldefined risk factors for this complication, guidelines for prescribing cannot be established.
Antimicrobials induced hyponatremia in elderly patients. Thiazide diuretics inhibit the thiazide sensitive sodium chloride cotransporter ncc in the distal convoluted tubule dct of the kidney 3 and are among the most widely used class of medicines in the management of hypertension 4. Discovery of the molecular mechanism underlying thiazide induced hyponatremia would guide the design of a more efficacious and tolerable antihypertensive agent. Reporting dehydration with hypernatremia or hyponatremia requires two codes. Although they ascribe the pathogenesis of thiazideinduced hyponatremia to excess drinking, they did not monitor water intake. With respect to the mechanisms of this hyponatremia, metolazone, a thiazide, was shown to turn a positive free water clearance into a negative one 78 x 78 ashraf, n. Diureticinduced hyponatremia jama internal medicine. Discovery of the molecular mechanism underlying thiazideinduced hyponatremia would guide the design of a more efficacious and tolerable antihypertensive agent. This is a singlearm, prospective, openlabel proofofconcept trial, including elderly patients with thiazide diureticinduced hyponatremia. Thiazideinduced hyponatraemia is common and potentially life threatening.
The importance of thiazideinduced hyponatremia tih is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as firstline treatment of essential hypertension have been introduced. Jci phenotypic and pharmacogenetic evaluation of patients. Administration of thiazide diuretics also has been the cause of hyponatremia. Thiazideinduced syndrome of inappropriate secretion of.