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Osmoregulatory Mechanisms Differentiate MDMA-Associated Hyponatremia from Psychogenic Polydipsia
The Journal of Emergency Medicine, Vol. -, No. -, p. 1, 2014 Copyright Ó 2014 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
Letter to the Editor , OSMOREGULATORY MECHANISMS DIFFERENTIATE MDMA-ASSOCIATED HYPONATREMIA FROM PSYCHOGENIC POLYDIPSIA
supported the clinical findings, including hyperthermia, dilated pupils, recent MDMA use, and lack of any psychiatric history. It is also noteworthy that while nonosmotic release of ADH is considered a major cause for hyponatremia in MDMA users, several other mechanisms have also been implicated, including MDMA-induced polydipsia, hyperthermia, rigorous physical activity, and excessive perspiration. Therefore, the biological and clinical features of hyponatremic MDMA users (eg, urine sodium level) could be different from those typical clinical scenarios in which the decrease in solute-free water clearance is exclusively due to overproduction of ADH (eg, lung mass). Concerning the point on the use of mannitol for treatment of MDMA-induced acute symptomatic hyponatremia, osmotic diuresis is not advocated as the first line of therapy in this clinical setting. As mentioned in our article, the rarity of this phenomenon precludes any evidence-based specific consensus for its management, and current recommendations are primarily based on extrapolation of available data on any state of acute hyponatremia. Although a variety of regimens, including saline solutions, furosemide, and water restriction, have been used for the previously reported cases of MDMAassociated hyponatremia, mannitol has rarely been used in this setting. Therefore, based on the biological plausibility and the clinical success of the two reported cases, it would be sound to consider its use in cases where other therapeutic options are not readily available.
, To the Editor: Dr. Ligtenberg and colleagues have raised two interesting points regarding the diagnosis and treatment of 3,4-methylenedioxymethamphetamine (MDMA) associated hyponatremia. In order to maintain the plasma osmolality within a very narrow range (i.e., 275 290 mosmol/kg), despite significant variations that exist in the fluid and solute intake of a normal individual, kidneys show an amazing capability to substantially modify water clearance and urine osmolality on a continuous basis; urine osmolality can vary from 50 to 1200 mosmol/kg in normal adults. In psychogenic polydipsia and excessive water intake, where the osmoregulatory mechanisms are intact, plasma hypo-osmolality results in suppression of antidiuretic hormone (ADH), which then leads to significant excretion of free water through maximally diluted urine to correct hyponatremia. Therefore, urine osmolality typically falls to < 100 mosmol/kg (and specific gravity to < 1.003) in these cases. In contrast, values greater than these in a hyponatremic patient point to aberrancy in the osmoregulatory mechanisms and the inability of the kidneys to excrete solute-free water (aquaresis), most commonly driven by elevated levels of ADH. In our patient with severe hyponatremia, urine osmolality was found to be as high as 505 mosmol/kg (and a specific gravity of 1.013). This indicates lack of appropriate suppression of ADH levels, despite plasma hypoosmolality, and is incompatible with a diagnosis of psychogenic polydipsia. These laboratory data further
Amir Kazory, MD Division of Nephrology Hypertension, and Renal Transplantation University of Florida Gainesville, FL http://dx.doi.org/10.1016/j.jemermed.2014.07.055
1
Letter to the Editor , OSMOREGULATORY MECHANISMS DIFFERENTIATE MDMA-ASSOCIATED HYPONATREMIA FROM PSYCHOGENIC POLYDIPSIA
supported the clinical findings, including hyperthermia, dilated pupils, recent MDMA use, and lack of any psychiatric history. It is also noteworthy that while nonosmotic release of ADH is considered a major cause for hyponatremia in MDMA users, several other mechanisms have also been implicated, including MDMA-induced polydipsia, hyperthermia, rigorous physical activity, and excessive perspiration. Therefore, the biological and clinical features of hyponatremic MDMA users (eg, urine sodium level) could be different from those typical clinical scenarios in which the decrease in solute-free water clearance is exclusively due to overproduction of ADH (eg, lung mass). Concerning the point on the use of mannitol for treatment of MDMA-induced acute symptomatic hyponatremia, osmotic diuresis is not advocated as the first line of therapy in this clinical setting. As mentioned in our article, the rarity of this phenomenon precludes any evidence-based specific consensus for its management, and current recommendations are primarily based on extrapolation of available data on any state of acute hyponatremia. Although a variety of regimens, including saline solutions, furosemide, and water restriction, have been used for the previously reported cases of MDMAassociated hyponatremia, mannitol has rarely been used in this setting. Therefore, based on the biological plausibility and the clinical success of the two reported cases, it would be sound to consider its use in cases where other therapeutic options are not readily available.
, To the Editor: Dr. Ligtenberg and colleagues have raised two interesting points regarding the diagnosis and treatment of 3,4-methylenedioxymethamphetamine (MDMA) associated hyponatremia. In order to maintain the plasma osmolality within a very narrow range (i.e., 275 290 mosmol/kg), despite significant variations that exist in the fluid and solute intake of a normal individual, kidneys show an amazing capability to substantially modify water clearance and urine osmolality on a continuous basis; urine osmolality can vary from 50 to 1200 mosmol/kg in normal adults. In psychogenic polydipsia and excessive water intake, where the osmoregulatory mechanisms are intact, plasma hypo-osmolality results in suppression of antidiuretic hormone (ADH), which then leads to significant excretion of free water through maximally diluted urine to correct hyponatremia. Therefore, urine osmolality typically falls to < 100 mosmol/kg (and specific gravity to < 1.003) in these cases. In contrast, values greater than these in a hyponatremic patient point to aberrancy in the osmoregulatory mechanisms and the inability of the kidneys to excrete solute-free water (aquaresis), most commonly driven by elevated levels of ADH. In our patient with severe hyponatremia, urine osmolality was found to be as high as 505 mosmol/kg (and a specific gravity of 1.013). This indicates lack of appropriate suppression of ADH levels, despite plasma hypoosmolality, and is incompatible with a diagnosis of psychogenic polydipsia. These laboratory data further
Amir Kazory, MD Division of Nephrology Hypertension, and Renal Transplantation University of Florida Gainesville, FL http://dx.doi.org/10.1016/j.jemermed.2014.07.055
1