DIAGNOSTIC PITFALLS AND THERAPEUTIC CHALLENGES IN HYPONATREMIA IN ADULTS: A SYSTEMATIC REVIEW
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.6623Keywords:
Hyponatremia, SIAD, Diagnostic Pitfalls, Hypertonic Saline, Osmotic Demyelination, Thiazide-associated HyponatremiaAbstract
Hyponatremia is the most common disorder of water and electrolyte balance in adult clinical practice and remains a frequent cause of diagnostic uncertainty and treatment-related harm. Although the definition of hyponatremia is straightforward, its interpretation requires assessment of tonicity, chronicity, symptoms, volume status, renal water handling, medications, endocrine disease, and the risk of overly rapid correction. This systematic review summarizes current evidence on diagnostic pitfalls and therapeutic challenges in adult hyponatremia, with particular emphasis on hypotonic hyponatremia, syndrome of inappropriate antidiursis, thiazide-associated hyponatremia and severe symptomatic presentations. PubMed/MEDLINE and PubMed Central were searched for English-language publications concerning adult hyponatremia, diagnostic pathways, correction strategies, and treatment complications. Clinical guidelines, reviews, systematic reviews, randomized trials, and observational studies were included. The literature indicates that common errors include failure to exclude pseudohyponatremia or hypertonic hyponatremia, overreliance on clinical volume assessment, delayed measurement of urine osmolality and urine sodium, under-recognition of drug-induced causes, and inadequate monitoring during therapy. Therapeutic challenges include balancing urgent treatment of cerebral edema against prevention of osmotic demyelination, managing unpredictable water diuresis, and individualizing therapy in SIAD, heart failure, cirrhosis and thiazide-associated disease. A structured, physiology-based approach can improve diagnostic accuracy and reduce avoidable harm.
References
Adrogue, H. J., & Madias, N. E. (2000). Hyponatremia. New England Journal of Medicine, 342(21), 1581–1589. https://doi.org/10.1056/NEJM200005253422107
Adrogue, H. J., Tucker B. M., Madias N. E. (2022). Diagnosis and management of hyponatremia: A review. JAMA, 328(3), 280–291. https://doi.org/10.1001/jama.2022.11176
Baek, S. H., Jo, Y. H., Ahn, S., Medina-Liabres, K., Oh, Y. K., Lee, J. B., & Kim, S. (2021). Risk of overcorrection in rapid intermittent bolus vs slow continuous infusion therapies of hypertonic saline for patients with symptomatic hyponatremia: The SALSA randomized clinical trial. JAMA Internal Medicine, 181(1), 81–92. https://doi.org/10.1001/jamainternmed.2020.5519
Bastos, A. P., & Rocha, P. N. (2024). Osmotic demyelination as a complication of hyponatremia correction: A systematic review. Jornal Brasileiro de Nefrologia, 46(1), 47–55. https://doi.org/10.1590/2175-8239-JBN-2022-0114en
Clayton, J. A., Le Jeune, I. R., & Hall, I. P. (2006). Severe hyponatraemia in medical in-patients: Aetiology, assessment and outcome. QJM: An International Journal of Medicine, 99(8), 505–511. https://doi.org/10.1093/qjmed/hcl071
Corona, G., Giuliani, C., Parenti, G., Norello, D., Verbalis, J. G., Forti, G., Maggi, M., & Peri, A. (2009). Moderate hyponatremia is associated with increased risk of mortality: Evidence from a meta-analysis. PLoS ONE, 8(12), e80451. https://doi.org/10.1371/journal.pone.0080451
Dineen, R., Thompson, C. J., & Sherlock, M. (2017). Hyponatraemia: Presentations and management. Clinical Medicine, 17(3), 263–269. https://doi.org/10.7861/clinmedicine.17-3-263
Warren, A. M., Grossmann, M., Christ-Crain, M., & Russell, N. (2023). Syndrome of inappropriate antidiuresis: From pathophysiology to management. Endocrine Reviews, 44(5), 819–861. https://doi.org/10.1210/endrev/bnad010
Filippatos, T. D., Liamis, G., Christopoulou, F., & Elisaf, M. S. (2016). Ten common pitfalls in the evaluation of patients with hyponatremia. European Journal of Internal Medicine, 29, 22–25. https://doi.org/10.1016/j.ejim.2015.11.022
Hoorn, E. J., & Ellison, D. H. (2025). Thiazide-induced hyponatremia. Kidney International, 108(4), 571–582. https://doi.org/10.1016/j.kint.2025.05.003
Hoorn, E. J., & Zietse, R. (2017). Diagnosis and treatment of hyponatremia: Compilation of the guidelines. Journal of the American Society of Nephrology, 28(5), 1340–1349. https://doi.org/10.1681/ASN.2016101139
Huda, M. S. B., Boyd, A., Skagen, K., Wile, D., van Heyningen, C., Watson, I., Wong, S., & Gill, G. (2006). Investigation and management of severe hyponatraemia in a hospital setting. Postgraduate Medical Journal, 82(965), 216–219. https://pubmed.ncbi.nlm.nih.gov/16517805/
MacMillan, T. E., Cavalcanti, R. B., & Forster, A. J. (2024). Correction rates and clinical outcomes in hospitalized adults with severe hyponatremia: A systematic review and meta-analysis. JAMA Network Open, 7(11), e2441665. https://pubmed.ncbi.nlm.nih.gov/39556338/
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., … Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, n71. https://doi.org/10.1136/bmj.n71
Shepshelovich, D., Schechter, A., & Rozen-Zvi, B. (2025). Hyponatremia correction and osmotic demyelination syndrome risk: A systematic review and meta-analysis. Kidney Medicine, 7(4), 100960. https://pubmed.ncbi.nlm.nih.gov/39967825/
Spasovski, G., Vanholder, R., Allolio, B., Annane, D., Ball, S., Bichet, D., Decaux, G., Fenske, W., Hoorn, E. J., Ichai, C., Joannidis, M., Soupart, A., Zietse, R., Haller, M., van der Veer, S., Van Biesen, W., & Nagler, E. (2014). Clinical practice guideline on diagnosis and treatment of hyponatraemia. Intensive Care Medicine, 40(3), 320–331. https://doi.org/10.1007/s00134-014-3210-2
Sterns, R. H. (2018). Treatment of severe hyponatremia. Clinical Journal of the American Society of Nephrology, 13(4), 641–649. https://doi.org/10.2215/CJN.10440917
Sterns, R. H., Hix, J. K., & Silver, S. (2010). Treating profound hyponatremia: A strategy for controlled correction. American Journal of Kidney Diseases, 56(4), 774–779. https://doi.org/10.1053/j.ajkd.2010.04.020
Sterns, R. H., Rondon-Berrios, H., & Berl, T. (2024). Treatment guidelines for hyponatremia: Stay the course. Kidney360, 5(1), 129–135. https://pubmed.ncbi.nlm.nih.gov/37379081/
Thompson, C. J., Hoorn, E. J., Ellison, D. H., & Verbalis, J. G. (2016). The syndrome of inappropriate antidiuresis. New England Journal of Medicine, 375(8), 793–794. https://pubmed.ncbi.nlm.nih.gov/27156757/
Verbalis, J. G., Goldsmith, S. R., Greenberg, A., Korzelius, C., Schrier, R. W., Sterns, R. H., & Thompson, C. J. (2013). Diagnosis, evaluation, and treatment of hyponatremia: Expert panel recommendations. American Journal of Medicine, 126(10 Suppl 1), S1–S42. https://doi.org/10.1016/j.amjmed.2013.07.006
Wald, R., Jaber, B. L., Price, L. L., Upadhyay, A., & Madias, N. E. (2010). Impact of hospital-associated hyponatremia on selected outcomes. Archives of Internal Medicine, 170(3), 294–302. https://doi.org/10.1001/archinternmed.2009.513
Ware, J. S., Wain, L. V., Channavajjhala, S. K., Jackson, V. E., Edwards, E., Lu, R., Siew, K., Jia, W., Shrine, N., Kinnear, S., O'Connor, B. J., John, C., Soler Artigas, M., Tobin, M. D., & Lunnon, K. (2017). Clinical and molecular features of thiazide-induced hyponatremia. Current Hypertension Reports, 19(9), 75. https://doi.org/10.1007/s11906-017-0773-5
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Copyright (c) 2026 Aleksandra Golec, Emilia Koziara, Mateusz Gadzina, Wojciech Sontag, Julia Gawlak, Zofia Tarnawska, Karolina Figiel, Mateusz Gawin, Mateusz Zawisza, Mateusz Krzesimir Kuświk

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