DIAGNOSTIC AND TREATMENT IN TETANY: EXPLORING NON-HYPOCALCEMIC CAUSES AND CLINICAL CHALLENGES
Abstract
Normocalcemic tetany is a clinical condition characterized by neuromuscular hyperexcitability in the absence of overt hypocalcemia, resulting from disturbances in ionized calcium, magnesium, potassium, or acid–base balance. Although tetany is most commonly associated with hypocalcemia, cases with normal total calcium levels pose diagnostic challenges and are frequently underrecognized. This review consolidates current knowledge regarding the etiology, clinical manifestations, diagnostic evaluation, and management of normocalcemic tetany. The etiology includes hereditary renal tubulopathies such as Gitelman and Bartter syndromes, hyperventilation-related alkalosis, magnesium deficiency, and rare autoimmune disorders involving antibodies against the voltage-gated potassium channel complex (CASPR2). Clinical presentations range from overt tetanic seizures with characteristic carpopedal spasms to latent tetany detectable via Chvostek and Trousseau signs or ischemia-induced EMG abnormalities. Case reports highlight unusual scenarios, including tetany triggered by vomiting, postoperative parathyroidectomy, and hereditary neuromuscular hypersensitivity, emphasizing that serum total calcium may remain normal while ionized calcium or other electrolytes fluctuate. Management strategies focus on prompt recognition, correction of underlying electrolyte disturbances—particularly calcium, magnesium, and potassium—and supportive care. Early administration of intravenous calcium, alongside addressing precipitating factors, is critical for rapid symptom relief. Latent or recurrent tetany in the context of normal electrolytes warrants consideration of genetic, neurologic, or autoimmune etiologies, and may require specialized testing including EMG, antibody panels, or genetic analysis. Increased awareness among clinicians, timely evaluation of ionized calcium and other electrolytes, and early intervention are essential to prevent severe complications, including life-threatening muscle spasms, rhabdomyolysis, and cardiovascular instability. This review underscores the need for further population-based studies to define the prevalence, at-risk groups, and optimal management of normocalcemic tetany.
References
OpenStax. (2024). Positive Chvostek’s sign and Trousseau’s sign. In Medical‑Surgical Nursing (Ch. 10.3). LibreTexts. https://med.libretexts.org/Bookshelves/Nursing/Medical-Surgical_Nursing_(OpenStax)/10%3A_Fluid_Electrolyte_and_Acid-Base_Imbalances/10.03%3A_Electrolyte_Imbalance
Sikora, P., Zaniew, M., Zawadzki, J., & Drabczyk, R. (2025). Zespół Gitelmana. W Interna Szczeklika. Medycyna Praktyczna. https://www.mp.pl/interna/chapter/B16.II.14.5.6
Sikora, P., Zaniew, M., Zawadzki, J., & Drabczyk, R. (2025). Zespół Barttera. W Interna Szczeklika. Medycyna Praktyczna. https://www.mp.pl/interna/chapter/B16.II.14.5.11
Santra, G., & Barman, H. (2017). Etiological spectrum of tetany in a teaching institution of western part of West Bengal – a cross-sectional study. Journal of Current Research in Scientific Medicine, 3(1), 45–50. https://doi.org/10.4103/jcrsm.jcrsm_20_17
Gryglas, A., Dudkowiak, R. K., & Śmigiel, R. (2015). Tetany as a frequent cause of an emergency consultations – etiology, symptoms and cure. Przegląd Lekarski, 72(1), 20–24. https://pubmed.ncbi.nlm.nih.gov/26076573/
Sehgal, V., Pathak, A., Singh, J., Singh, A., & Bansal, V. (2011). Normocalcaemic tetany. European Journal of Emergency Medicine, 18(5), 159‑161. https://doi.org/10.1097/MEJ.0b013e32834eeda0
Isgreen, W. P. (1976). Normocalcemic tetany: A problem of erethism. Neurology, 26(9), 825–834. https://doi.org/10.1212/WNL.26.9.825
Day, J. W., & Parry, G. J. (1990). Normocalcemic tetany abolished by calcium infusion. Annals of Neurology, 27(4), 438-440. https://doi.org/10.1002/ana.410270413
Fowweather, F. S., Davidson, C. L., & Ellis, L. (1940, September 21). Spontaneous hyperventilation tetany. British Medical Journal, 2(4159), 373-376. https://doi.org/10.1136/bmj.2.4159.373
Alanazi, M., Alabdulgader, A., Alotaibi, A., Bin Ahmed, I., & Maskati, M. (2023). Tetany in a Young Female Not Resulting From Hypocalcemia. Cureus, 15(8), e43521. https://doi.org/10.7759/cureus.43521
Fonseca, V. A., Bloom, R. D., Dick, R., & Dandona, P. (1987). Tetany despite normocalcaemia and normomagnesaemia following parathyroidectomy. Postgraduate Medical Journal, 63(744), 885-886. https://doi.org/10.1136/pgmj.63.744.885
Boulding, R., Stacey, A., Niven, R., & Fowler, S. J. (2016). Dysfunctional breathing: A review of the literature and proposal for classification. European Respiratory Review, 25(141), 287‑294. https://doi.org/10.1183/16000617.0074-2016
Gardner, W. N., Bass, C., & Moxham, J. (1992). Recurrent hyperventilation tetany due to mild asthma. Respiratory Medicine, 86(4), 349‑351. https://doi.org/10.1016/S0954‑6111(06)80036‑3
McGillicuddy, C., & Molins, C. (2023). The effect of hyperventilation syndrome on ionized and serum calcium: A case presentation in the emergency department. Cureus, 15(7), e42310. https://doi.org/10.7759/cureus.42310
Williams, A., Liddle, D., & Abraham, V. (2011). Tetany: A diagnostic dilemma. Journal of Anaesthesiology Clinical Pharmacology, 27(3), 393–394. https://doi.org/10.4103/0970-9185.83691
Vazhakalayil, S. T. J., Veer, S., Badam, B., & Mane, J. (2025). The domino effect: hyperventilation, hypocapnia, and tetany in airway management. Journal of Clinical & Diagnostic Research, 19(7), UD04‑UD06. https://doi.org/10.7860/JCDR/2025/78982.21167
Fulchiero, R., & Seo‑Mayer, P. (2019). Bartter syndrome and Gitelman syndrome. Pediatric Clinics of North America, 66(1), 121‑134. https://doi.org/10.1016/j.pcl.2018.08.010
Fujihara, K., Miyoshi, T., Yamaguchi, Y., Araki, T., & Tanaka, K. (1990).Tetany as a sole manifestation in a patient with Bartter's syndrome and a successful treatment with indomethacin Rinsho shinkeigaku = Clinical neurology, 30(5), 529–532. https://pubmed.ncbi.nlm.nih.gov/2401113/
Suitsu, N., Kita, S., Okamoto, S., Kimura, S., & Shiozaki, Y. (1984).Development of tetany in siblings suffered from Bartter's syndrome. No to shinkei = Brain and nerve, 36(8), 749–754. https://pubmed.ncbi.nlm.nih.gov/6498022/
Blanchard, A., Bockenhauer, D., Bolignano, D., Calò, L. A., Cosyns, E., Devuyst, O., Ellison, D. H., Karet Frankl, F. E., Knoers, N. V., Konrad, M., & Lin, S.‑H. (2017). Gitelman syndrome: Consensus and guidance from a Kidney Disease: Improving Global Outcomes (KDIGO) controversies conference. Kidney International, 91(1), 24–33. https://doi.org/10.1016/j.kint.2016.09.046
Gitelman, H. J., Graham, J. B., & Welt, L. G. (1966). A new familial disorder characterized by hypokalemia and hypomagnesemia. Transactions of the Association of American Physicians, 79, 221‑235. https://doi.org/10.1111/j.1749-6632.1969.tb13015.x
Knoers, N. V. A. M., & Levtchenko, E. N. (2008). Gitelman syndrome. Orphanet Journal of Rare Diseases, 3, 22. https://doi.org/10.1186/1750-1172-3-22
Gandhi, K., Prasad, D., Malhotra, V., & Agrawal, D. (2016). Gitelman’s syndrome presenting with hypocalcemic tetany. Saudi Journal of Kidney Diseases and Transplantation, 27(5), 1026–1028. https://doi.org/10.4103/1319-2442.190881
Desai, M., Kolla, P. K., & Reddy, P. L. V. P. (2013). Calcium unresponsive hypocalcemic tetany: Gitelman syndrome with hypocalcemia. Case Reports in Medicine, 2013, 197374. https://doi.org/10.1155/2013/197374
Kalsi, H. S., Kim, M., & Alkhamesi, A. (2013). Localised normocalcaemic tetany secondary to dehydration in an individual with Gitelman syndrome. BMJ Case Reports, 2013, bcr2013008926. https://doi.org/10.1136/bcr-2013-008926
Lance, J. W., Burke, D., & Pollard, J. (1979). Hyperexcitability of motor and sensory neurons in neuromyotonia. Annals of Neurology, 5(6), 523‑532. https://doi.org/10.1002/ana.410050605
Imbrici, P., Accogli, A., Blunck, R., Altamura, C., Iacomino, M., D'adamo, M. C., Allegri, A., Pedemonte, M., Brolatti, N., Vari, S., Cataldi, M., Capra, V., Gustincich, S., Zara, F., Desaphy, J. F., & Fiorillo, C. (2021). Musculoskeletal Features without Ataxia Associated with a Novel de novo Mutation in KCNA1 Impairing the Voltage Sensitivity of Kv1.1 Channel. Biomedicines, 9(1), 75. https://doi.org/10.3390/biomedicines9010075
Glaudemans, B., van der Wijst, J., Scola, R. H., Lorenzoni, P. J., Heister, A., van der Kemp, A. M. W., Knoers, N. V., Hoenderop, J. G., & Bindels, R. J. (2009). A missense mutation in the Kv1.1 voltage‑gated potassium channel‑encoding gene KCNA1 is linked to human autosomal dominant hypomagnesemia. The Journal of Clinical Investigation, 119(4), 936‑942. https://doi.org/10.1172/JCI36948
Bianchi, F., Simoncini, C., Brugnoni, R., Ricci, G., & Siciliano, G. (2020). Neuromuscular tetanic hyperexcitability syndrome associated to a heterozygous Kv1.1 N255D mutation with normal serum magnesium levels. Acta Myologica, XXXIX(1), 36–39. https://doi.org/10.36185/2532-1900-007
Famularo, G., De Filippis, V., & Minisola, G. (2012). Tetany, hypomagnesemia, and proton-pump inhibitors. The American Journal of Medicine, 125(10), 1015–1017. https://doi.org/10.1016/j.amjmed.2012.00351
Smets, Y. F., Bokani, N., de Meijer, P. H., & Meinders, A. E. (2004). Tetanie bij overmatig alcoholgebruik: mogelijk een magnesiumtekort [Tetany due to excessive use of alcohol: a possible magnesium deficiency]. Nederlands tijdschrift voor geneeskunde, 148(14),641–644. https://pubmed.ncbi.nlm.nih.gov/15106311/
Gragossian, A., Bashir, K., Bhutta, B. S., & Friede, R. (2023). Hypomagnesemia. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK500003/
Ahmed, F., & Mohammed, A. (2019). Magnesium: The forgotten electrolyte—A review on hypomagnesemia. Medical Sciences, 7(4), 56. https://doi.org/10.3390/medsci7040056
Warren E. C. Wacker, Moore, F. D., Ulmer, D. D., et al. (1962). Normocalcemic magnesium deficiency tetany. JAMA, 180(2), 161–163. https://doi.org/10.1001/jama.1962.03050150000018b
Estep, H., Shaw, W. A., Watlington, C., Hobe, R., Holland, W., & Tucker, S. G. (1969). Hypocalcemia due to hypomagnesemia and reversible parathyroid hormone unresponsiveness. The Journal of Clinical Endocrinology & Metabolism, 29(6), 842–848. https://doi.org/10.1210/jcem-29-6-842
Plantone, D., Renna, R., & Koudriavtseva, T. (2016). Neurological diseases associated with autoantibodies targeting the voltage‑gated potassium channel complex: Immunobiology and clinical characteristics. Neuroimmunology and Neuroinflammation, 3(3), 69‑78. https://doi.org/10.4103/2347‑8659.169883
Moura, J., Antenucci, P., Coutinho, E., Bhatia, K. P., Rocchi, L., & Latorre, A. (2025). Neuromyotonia and CASPR2 antibodies: Electrophysiological clues to disease pathophysiology. Biomolecules, 15(9), 1262. https://doi.org/10.3390/biom15091262
Die (Krypto-)Pyrrolurie in der Umweltmedizin: eine valide Diagnose? Mitteilung der Kommission "Methoden und Qualitätssicherung in der Umweltmedizin" [The (crypto-)pyrroluria in environmental medicine: a valid diagnosis? Report of the "Methods and Quality Assurance in Environmental Medicine" Committee] ]. (2007). Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 50(10), 1324–1330. https://doi.org/10.1007/s00103-007-0340-5
Johnson, M. M., Patel, S., & Williams, J. (2019). Don't Take It 'Lytely': A Case of Acute Tetany. Cureus, 11(10), e5845. https://doi.org/10.7759/cureus.5845
Marie, B. D., Sow, M. S., Diack, A., Diallo, C. O., Barkire, I., Dieng, F. K., & Fall, M. D. (2017). Spasmophilia in the cardiological outpatient department: A retrospective study of 228 sub‑Saharan Africans over 5 years. Journal of Thrombosis and Circulation: Open Access, 3(3), 121. https://doi.org/10.4172/2572-9462.1000121
Deecke, L., Müller, B., & Conrad, B. (1983). Zur Standardisierung des elektromyographischen Tetanietests in der Diagnostik der normokalzämischen Tetanie: 10minütiger Trousseau bei Patienten und Gesunden [Standardization of the electromyographic tetany test in the diagnosis of normocalcemic tetany: the 10-minute Trousseau test in patients and healthy humans]. Archiv fur Psychiatrie und Nervenkrankheiten, 233(1), 23–37. https://doi.org/10.1007/BF00540035
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