Spurious Electrolyte Disorders: A Diagnostic Challenge for Clinicians

Liamis, Georgé; Liberopoulos, Evangelos N.; Barkas, Fotios; Elisaf, Moses

doi:10.1159/000351804

Cited by 182 publications

(83 citation statements)

References 62 publications

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“…It is well known that when the proportion of a serum sample occupied by substances other than water and electrolytes (such as lipids and proteins) exceeds the usual value of 7%, serum sodium levels measured by ion-selective electrodes using the indirect method are falsely lower than true values [9][10][11][12][13]. Thus, in patients with lipemic serum and severe hypertriglyceridemia, sodium levels should be measured by direct potentiometry in blood gas panels.…”

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confidence: 99%

Hyponatremia in Diabetes Mellitus: Clues to Diagnosis and Treatment

Vasilios¹

2015

J Diabetes Metab

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Hyponatremia is the most common electrolyte abnormality in clinical practice and is associated with increased morbidity and mortality [1,2]. Even small decreases of serum sodium are associated with increased probability for adverse outcomes (cognitive impairment, falls, osteoporosis and fractures) [3].Decreased serum sodium levels are occasionally observed in patients with diabetes mellitus and can be attributed to numerous underlying pathogenetic mechanisms (Table 1) [4,5].The direct measurement of serum osmolality (Posm) can differentiate between hypotonic hyponatremia (with decreased Posm) and hyponatremia associated with normal or even increased tonicity. In the latter case hyponatremia is usually due to the coexistent hyperglycemia [6]. In fact, glucose is an osmotic active substance. Thus, in cases of marked hyperglycemia Posm is increased leading to movement of water out of cells and subsequently to a reduction of serum sodium levels (dilutional hyponatremia). In such cases the corrected, for the degree of hyperglycemia, serum sodium value should be calculated. Thus, to obtain the "true" sodium level in cases of extreme hyperglycemia, the addition of 2.4 mEq/L to the measured concentration for every 100 mg/dl increment in plasma glucose above normal levels is required [7]. This corrected serum sodium level should be used during treatment of severe hyperglycemic states [8]. In patients with dilutional hyponatremia the treatment of hyperglycemia is usually followed by a normalization of serum sodium levels [4].No hypotonic hyponatremia (with a normal measured Posm) can also be due to pseudohyponatremia associated with hyperglycemiainduced severe hypertriglyceridemia and perhaps hypovolemiainduced hyperproteinemia. It is well known that when the proportion of a serum sample occupied by substances other than water and electrolytes (such as lipids and proteins) exceeds the usual value of 7%, serum sodium levels measured by ion-selective electrodes using the indirect method are falsely lower than true values [9][10][11][12][13]. Thus, in patients with lipemic serum and severe hypertriglyceridemia, sodium levels should be measured by direct potentiometry in blood gas panels. This method does not include a predilution step and is not susceptible to the aforementioned errors [13]. Diagnosis of pseudohyponatremia is necessary to avoid dangerous overtreatment. It should be mentioned that pseudohyponatremia does not produce any of the symptoms classically attributed to hyponatremia. Improvement in glycemic control is associated with a rapid decrease in serum triglycerides resulting in the correction of pseudohyponatremia. Thus, no specific treatment is required [4,6].The most common cause of hypotonic hyponatremia in patients with diabetes is osmotic diuresis-induced hypovolemia [4]. It should be mentioned that in patients with diabetic ketoacidosis the excretion of β-hydroxybutyrate and acetoacetate obligate urine sodium losses resulting in aggravation of hypovolemia [14]. Hypovolemia can also be due to diabetes mel...

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confidence: 99%

Hyponatremia in Diabetes Mellitus: Clues to Diagnosis and Treatment

Vasilios¹

2015

J Diabetes Metab

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“…Another important step in the approach of any patient with hyponatremia is to exclude the possibility that the decreased serum sodium levels are due to an artifact. Potential causes of pseudohyponatremia in patients with hypothyroidism are dyslipidemia (especially if diabetes mellitus coexists) and hypergammaglobulinemia (in hypothyroidism of autoimmune origin) (44). Consequently, hyponatremia of multifactorial origin may be seen in patients with hypothyroidism and the presence of common causes or superimposed factors should be meticulously investigated.…”

Section: Discussionmentioning

confidence: 99%

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment

Liamis

Filippatos

Liontos

et al. 2017

European Journal of Endocrinology

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Background: Patients with moderate to severe hypothyroidism and mainly patients with myxedema may exhibit reduced sodium levels (<135 mmol/L). Summary: The aim of this short review is the presentation of the mechanisms of hyponatremia and of the available data regarding its implications and treatment in patients with hypothyroidism. Hypothyroidism is one of the causes of hyponatremia, thus thyroid-stimulating hormone determination is mandatory during the evaluation of patients with reduced serum sodium levels. The main mechanism for the development of hyponatremia in patients with chronic hypothyroidism is the decreased capacity of free water excretion due to elevated antidiuretic hormone levels, which are mainly attributed to the hypothyroidism-induced decrease in cardiac output. However, recent data suggest that the hypothyroidism-induced hyponatremia is rather rare and probably occurs only in severe hypothyroidism and myxedema. Other possible causes and superimposed factors of hyponatremia (e.g. drugs, infections, adrenal insufficiency) should be considered in patients with mild/moderate hypothyroidism. Treatment of hypothyroidism and fluid restriction are usually adequate for the management of mild hyponatremia in patients with hypothyroidism. Patients with possible hyponatremic encephalopathy should be urgently treated according to current guidelines. Conclusions: Severe hypothyroidism may be the cause of hyponatremia. All hypothyroid patients with low serum sodium levels should be evaluated for other causes and superimposed factors of hyponatremia and treated accordingly.

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“…Other triggers include hyperlipidemia, hyperbilirubinemia, and hemolysis (17,18). Pseudohyperphosphatemia may result in improper treatment and inadvertent reductions of serum phosphorus levels to levels below the normal range (16).…”

Section: Discussionmentioning

confidence: 99%

Case-Control Study and Case Series of Pseudohyperphosphatemia during Exposure to Liposomal Amphotericin B

Bohm

Hoover

Wahlquist

et al. 2015

Antimicrob Agents Chemother

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A mphotericin B is a polyene antifungal indicated for the treatment of invasive fungal infections, including aspergillosis, candidiasis, cryptococcosis, and zygomycosis (1). Several generic formulations of this drug are available in the United States, including amphotericin B deoxycholate, or conventional amphotericin B (CAmB), amphotericin B colloidal dispersion (ABCD), and amphotericin B lipid complex (ABLC; Ablecet). The liposomal formulation of amphotericin B (LAmB; AmBisome) may be preferred over other formulations due to a more favorable side effect profile and enhanced tissue penetration, but it is still associated with hypokalemia, likely attributable to increased tubular permeability to monovalent cations, and hypomagnesemia, for which the mechanism is less certain (1-3). Although the drug is known to cause hypophosphatemia as well, several reports of hyperphosphatemia and pseudohyperphosphatemia have been published (1, 4-9).The first case of severe hyperphosphatemia was in a child with acute lymphocytic leukemia who was treated with LAmB for a mixed fungal infection (4). It was postulated that the electrolyte abnormality was caused by a sudden load of exogenous phosphorus coupled with inadequate clearance by the kidneys. Later, Bailey and Chan proposed the possibility of an artifactual elevation of serum phosphorus during LAmB therapy after two patients were found to have falsely elevated phosphorus levels subsequently shown to be normal by treating the serum samples with a lipemic cleansing agent (5). An ensuing case series described 4 pediatric patients who developed hyperphosphatemia while receiving LAmB (6). In that report, transitioning from LAmB to ABLC at the onset of hyperphosphatemia led to normalization of the serum phosphorus level, leading the authors to conclude that any interference with the PHOSm assay must be specific to the liposomal formulation. Another group reported that ultrafiltration of the serum may be an effective method to obtain a more accurate serum phosphorus measurement (7). Two in vitro studies demonstrated a dose-dependent, linear rise in phosphorus measurements when serum was spiked with LAmB. A 0.0072-to 0.0090-mmol/liter increase in phosphorus correlated with a 1-mg/liter increase in LAmB concentration (8,10). No effect was observed using a comparable placebo molecule without active drug, leading the authors to conclude that active drug in the liposomal formulation (LAmB) is involved in the assay interference (10). In 2008, pseudohyperphosphatemia caused by LAmB was detailed in a product corrective action statement released by Beckman and Coulter, Inc., to hospital laboratories that use Synchron chemistry systems to measure serum phosphorus by the PHOSm assay. The product information for AmBisome was updated in 2012 to reflect

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Spurious Electrolyte Disorders: A Diagnostic Challenge for Clinicians

Cited by 182 publications

References 62 publications

Hyponatremia in Diabetes Mellitus: Clues to Diagnosis and Treatment

Hyponatremia in Diabetes Mellitus: Clues to Diagnosis and Treatment

MANAGEMENT OF ENDOCRINE DISEASE: Hypothyroidism-associated hyponatremia: mechanisms, implications and treatment

Case-Control Study and Case Series of Pseudohyperphosphatemia during Exposure to Liposomal Amphotericin B

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