|Year : 2017 | Volume
| Issue : 1 | Page : 45-50
Etiological spectrum of tetany in a teaching institution of western part of West Bengal - A cross-sectional study
Gouranga Santra, Himanshu Barman
Department of Medicine, Midnapore Medical College, Paschim Medinipur, West Bengal, India
|Date of Submission||06-May-2017|
|Date of Acceptance||16-May-2017|
|Date of Web Publication||12-Jul-2017|
Block-P, Flat No. 306, Binayak Enclave, 59 Kalicharan Ghosh Road, Kolkata - 700 050, West Bengal
Source of Support: None, Conflict of Interest: None
Introduction: Studies describing etiological distribution of tetany are rare, and awareness regarding it is poor among physicians. Our study describes different causes of tetany beyond the decrease in total serum calcium level.
Methods: Patients with overt or latent tetany were evaluated clinically and from laboratory investigations. Initial investigations done were serum calcium, potassium, and arterial blood gas analysis. Both ionized and total calcium were assessed and corrected according to serum albumin level. Depending on initial reports, further tests were done such as serum phosphate, alkaline phosphatase, parathyroid hormone and magnesium levels; and urine potassium, calcium and chloride levels.
Results: Gitelman's syndrome (GS), Bartter's syndrome (BS), recurrent vomiting, anxiety hyperventilation, Vitamin D3deficiency (VDD), idiopathic hypoparathyroidism (IHP), postoperative hypoparathyroidism (PHP), acute pancreatitis, tumor lysis syndrome (TLS), and hypomagnesemia were the different causes of tetany identified. Out of 53 patients, total serum calcium was normal in 41 patients with metabolic or respiratory alkalosis (GS, BS, recurrent vomiting, and anxiety hyperventilation). Total calcium was low only in 12 patients (in VDD, IHP, PHP, acute pancreatitis, TLS, and hypomagnesemia). Ionized calcium was low in all patients. GS was the most common (38%). Recurrent vomiting (19%), anxiety hyperventilation (13%), and VDD (11%) were also common. PHP was less common (4%); acute pancreatitis, TLS, hypomagnesemia, and IHP were uncommon.
Conclusion: Tetany has diverse etiologies. Both metabolic and respiratory alkalosis cause decrease in ionized calcium and are responsible for the majority of cases of tetany. Causes other than decreased total calcium should be kept in mind for early etiological diagnosis of tetany.
Keywords: Hyperventilation, hypocalcemia, Gitelman's syndrome, Vitamin D3deficiency, vomiting
|How to cite this article:|
Santra G, Barman H. Etiological spectrum of tetany in a teaching institution of western part of West Bengal - A cross-sectional study. J Curr Res Sci Med 2017;3:45-50
|How to cite this URL:|
Santra G, Barman H. Etiological spectrum of tetany in a teaching institution of western part of West Bengal - A cross-sectional study. J Curr Res Sci Med [serial online] 2017 [cited 2021 Mar 1];3:45-50. Available from: https://www.jcrsmed.org/text.asp?2017/3/1/45/210341
| Introduction|| |
Tetany is characterized by variable combinations of features including circumoral numbness, muscle twitching, cramps, paresthesias of hands and feet, carpopedal spasm, laryngeal stridor, and convulsions (due to cerebral vasoconstriction). Trousseau sign (carpopedal spasm observed following application of inflated blood pressure cuff over brachial artery 20 mmHg above systolic blood pressure for 3 min) and Chvostek sign (twitching of circumoral muscles with tapping on facial nerve below zygomatic process 2 cm anterior to earlobe) unmask latent tetany in patients with tingling, numbness, and cramps in extremities. The decrease in serum calcium causing tetany is well known. However, decrease in ionized calcium is more important than total calcium level, as it is the biologically active component. In different causes of tetany, total serum calcium may be normal when ionized calcium is low.
Awareness regarding the etiological spectrum of tetany is very poor among physicians. Studies on the etiological distribution of tetany are rare in literature and are absent from rural West Bengal. We conducted the study from rural area of western part of West Bengal to identify the relative frequencies of different causes of tetany and to make the primary care physicians aware about the different causes of tetany beyond the decrease in total serum calcium level.
| Methods|| |
Both male and female patients admitted as inpatients in general medical ward in our institution over 2 years period with symptoms or signs of overt or latent tetany were included in the study. Patients with movement disorders or epilepsy were excluded from the study to avoid confusion.
Basic demographic data of the patients were collected. For establishing the etiology of tetany, detailed history of patients was taken including present and past h/o recurrent vomiting, anxiety disorder, weakness of limbs, thyroid and neck surgeries, presence of polyuria and polydipsia, abdominal pain, chemotherapy for malignant disorders, family h/o similar disorders, h/o drug intake, and addiction to alcohol. The detailed clinical examination was done to find out any features such as hyperventilation, loss of muscle power, scar mark of thyroidectomy (to exclude accidental parathyroidectomy), malignancies, and abdominal tenderness. Features of any autoimmune disorder like vitiligo were searched.
After history taking and clinical examination, laboratory investigations were done to reach the diagnosis. Initial investigations done were serum calcium, albumin, arterial blood gas (ABG) analysis, serum sodium, and potassium levels. Both ionized and total serum calcium levels were assessed and corrected according to serum albumin levels. Depending on the initial investigation reports, further tests were done such as serum phosphate, alkaline phosphatase (ALP), intact parathyroid hormone (iPTH) and serum magnesium levels; and urinary potassium, calcium, and chloride levels. Serum magnesium was assessed when possibility of either Gitelman's syndrome (GS) or Bartter's syndrome (BS) was considered and when calcium infusion failed to correct tetany.
Tetany due to Vitamin D3 deficiency (VDD) was diagnosed in the presence of decreased serum calcium and phosphate and increased ALP level and confirmed after assessment of 25-hydroxy (25(OH))-cholecalciferol level. Hypoparathyroidism (idiopathic hypoparathyroidism [IHP] or postoperative hypoparathyroidism [PHP]) was diagnosed in the presence of decreased serum calcium, increased phosphate, and decreased/inappropriately normal iPTH. Hyperventilation-induced tetany was diagnosed if ABG showed respiratory alkalosis. Recurrent vomiting (as the cause of tetany) was diagnosed in the presence of metabolic alkalosis with decreased urinary chloride level. GS was diagnosed if metabolic alkalosis was associated with hypokalemia, hypomagnesemia, decreased urinary calcium, and increased urinary potassium and chloride levels. BS was diagnosed in the presence of metabolic alkalosis associated with hypokalemia with or without hypomagnesemia and increased urinary calcium, potassium, and chloride levels.
After different causes of tetany were identified, frequency of different etiologies and their salient features were tabulated.
All the procedures followed in the study were in accordance with the ethical standards of responsible committee on human experimentation and with the Helsinki Declaration on 1975, as revised in 2010. Informed consent was taken from all patients for being included in the study.
For description of data, we used percentage (%), mean value, 95% confidence interval (CI), and standard deviation. GraphPad QuickCalcs online statistical calculator (GraphPad Software Inc., La Jolla, California, USA) was used for data analysis (http://www.graphpad.com/quickcalcs).
| Results|| |
A total of 53 patients were included in the study. The majority of the patients were from rural area (91%) and of lower socioeconomic status (79%) with education level below tenth standard in most (74%). Female patients outnumbered the male patients. [Table 1] shows the demographic features of study patients.
GS, BS, recurrent vomiting, anxiety hyperventilation, VDD, IHP, PHP, acute pancreatitis, tumor lysis syndrome (TLS), and hypomagnesemia were the different causes of tetany identified. [Table 2] shows the frequencies of different causes of tetany and some of their salient features. Total serum calcium was normal in 41 (77%) patients with metabolic and respiratory alkalosis including GS, BS, recurrent vomiting, and anxiety hyperventilation. Total serum calcium was low only in 12 (23%) patients (including VDD, IHP, PHP, acute pancreatitis, TLS, and hypomagnesemia). Ionized calcium was low in all 53 (100%) patients. Overt tetany (22 cases, 42% of total) was associated with spontaneous carpopedal spasm. All the latent cases (31 cases, 58% of total) had Trousseau sign positive, but Chvostek sign was positive only in six cases (11% of total). GS was the most common cause of tetany (38%), followed by recurrent vomiting with metabolic alkalosis (19%). Anxiety hyperventilation was common (13%), especially in females with features of overt tetany. VDD (11%) was associated with latent tetany in the majority (five out of six patients). PHP cases were due to the removal of parathyroid glands during total thyroidectomy and had persistent hypocalcemia after 6 months of surgery. The case of hypomagnesemia was chronic alcoholic. TLS case had nonHodgkin's lymphoma (NHL) and developed tetany during chemotherapy and succumbed to death. Tetany in acute pancreatitis (2% of total) and IHP (2%) was uncommon.
Gender predilection was seen in anxiety hyperventilation and PHP cases. Anxiety hyperventilation was seen more in females. PHP was also seen in females because of high prevalence of thyroid diseases in females. Acute pancreatitis and hypomagnesemia were seen in males because of higher prevalence of alcoholism in males. However, no definite gender predilection was seen in GS, BS, and recurrent vomiting cases. VDD was seen more in higher socioeconomic group with lower sunlight exposure in comparison to lower socioeconomic group (majority being farmers). Despite being more educated, they had VDD. PHP cases were from higher socioeconomic group and so they afforded surgical expenses of total thyroidectomy. Except VDD and PHP, all other cases were from lower socioeconomic group and with lower education level. Fifty percent (three out of six cases) cases of VDD were from urban area. All other cases were usually from rural areas. The majority of all cases were in third or fourth decades of life. IHP case was in the second decade, and hypomagnesemia case was in the sixth decade of life. BS cases were in the second or third decades.
| Discussion|| |
Serum calcium level is expressed as total serum calcium, corrected calcium (measured total Ca [mg/dL] + 0.8 * [4.0 − serum albumin (g/dL)]), and ionized calcium. The total calcium concentration in plasma is 8.7–10.2 mg/dl (2.2–2.6 mmol/L). Fifty percent of plasma calcium is ionized, 40% is bound to proteins (90% to albumin), and 10% is bound to anions (e.g., phosphate, carbonate, citrate, lactate, and sulfate). Normal ionized calcium level is 1.12–1.32 mmol/L (4.5–5.3 mg/dL). Tetany is usually seen when ionized calcium level is lower than 1.1 mmol/L or corrected total serum calcium level falls below 7.0 mg/dL. Decrease in corrected total serum calcium is usually associated with decreased ionized calcium. Ionized calcium is the biologically active component responsible for tetany. Alkalosis increases calcium binding to albumin, which decreases ionized calcium. Hence, tetany may occur even in the presence of normal total serum calcium.
Causes of tetany may vary in different geographic locations according to the prevalence of diseases. However, studies describing the etiological distribution of tetany are rarely found in literature except case reports or case series of individual diseases. Our study describes different causes of tetany from a rural area of West Bengal. As there is no other study found, comparison is not possible.
GS is the most common cause of tetany in our study. Tetany is an important feature of GS apart from hypokalemic paralysis and other features of dyselectrolytemia. In GS and BS, decreased ionized calcium due to metabolic alkalosis precipitates tetany. However, it may be aggravated by associated hypomagnesemia. Hypomagnesemia is almost always associated with GS, and 20% of BS patients have hypomagnesemia. In GS, total serum calcium is usually normal. However, rare case reports show hypocalcemic tetany in GS., BS is relatively rare than GS especially in adults and tetany is less frequent. However, tetany has been reported in literature in BS cases., We have also found BS patients with tetany (8%).
The second most common cause of tetany in our study was metabolic alkalosis due to recurrent vomiting. In a case series, tetany was caused by surreptitious vomiting leading to metabolic alkalosis, and BS was excluded by low urinary chloride level. Anxiety hyperventilation leads to respiratory alkalosis and is an important cause of tetany, and reports are prevalent especially after spinal anesthesia.,,,, Anxiety hyperventilation was also common in our study (13%) having overt tetany in six out of seven patients and was predominant in females.
Hypocalcemia and tetany due to VDD are also common. Malnutrition, malabsorption disorders such as Celiac disease, decreased sunlight exposure, and urbanization are associated with VDD. Indians are prone to VDD. In our study, VDD was responsible for tetany in 11% of patients.
Pancreatitis is a frequent cause of hypocalcemia. Mechanism of hypocalcemia in acute pancreatitis is not well established. It is postulated to be due to saponification of calcium by free fatty acids usually in areas of fat necrosis or dissolved or suspended in ascitic fluid. Hypocalcemic tetany has a bad prognostic significance in acute pancreatitis. Only single case of alcohol-induced acute pancreatitis presented with overt tetany in our study. TLS can cause acute kidney injury (AKI). AKI causes hyperphosphatemia that can lead to metastatic deposition of calcium phosphate leading to hypocalcemia and tetany. In our study, one NHL patient developed tetany during chemotherapy due to TLS.
IHP is a rare cause of hypocalcemic tetany. If immune etiology is identified, it is called autoimmune hypoparathyroidism. Autoimmune hypoparathyroidism may occur in isolation or as a part of a polyglandular endocrinopathy., Hypoparathyroidism is associated with hypocalcemia, hyperphosphatemia, and low or inappropriately normal iPTH levels. Only single case of IHP was seen in our study with latent tetany who presented at the second decade of life (18 years of age). Thyroid surgery is an important cause of tetany due to hypoparathyroidism despite major surgical advances. Transient hypocalcemia is common (range, 19%–38% after thyroidectomy)., However, hypoparathyroidism and hypocalcemia may be permanent in 0%–6% cases after total thyroidectomy., Hypoparathyroidism is due to unintentional removal or damage of the parathyroid glands or their vascular supply during thyroidectomy or neck surgery. Persistent hypocalcemia with low or inappropriately normal PTH levels 6 months after surgery confirms permanent hypoparathyroidism. In our study, two PHP cases with persistent hypocalcemia were found and they were due to the removal of parathyroid glands during total thyroidectomy.
Chronic alcoholism may lead to tetany by hypomagnesemia. However, hypomagnesemic tetany is rarely reported. Chronic alcohol intake may result in hypomagnesemia by decreasing renal tubular reabsorption and causing malabsorption from the gastrointestinal tract. Hypomagnesemia causes peripheral parathyroid hormone resistance and impairs parathyroid function; and thus causes hypocalcemia. In case of tetany due to hypomagnesemia, patient responds to magnesium injection but not to calcium therapy. Hypomagnesemia also causes kaliuresis leading to hypokalemia which can aggravate symptoms of tetany. The only case of hypomagnesemia in our study was chronic alcoholic and responded only to magnesium therapy.
Many drugs can lead to hypocalcemia, including bisphosphonates, cisplatin, antiepileptics, aminoglycosides, diuretics, and proton pump inhibitors. Hypocalcemia can develop with bisphosphonate therapy, especially in individuals with inadequate 25(OH) cholecalciferol levels. However, drug-induced hypocalcemia was absent in our study. Different acute emergencies such as sepsis can lead to dyselectrolytemia and acid-base disorders, and consequently, tetany may develop in these situations. In our study, we did not get such cases. Hungry bone syndrome causing tetany after parathyroidectomy in hyperparathyroidism was not found in our study. Usually, hypokalemia causes tetany in association with alkalosis. However, hypokalemia has also been reported to cause tetany in the absence of alkalosis. Isolated hypokalemia causing tetany was absent in our study.
In our study, latent tetany was more prevalent than overt tetany (31 vs. 22 cases). In GS, BS, recurrent vomiting, and VDD, latent tetany was more common. In anxiety hyperventilation, overt tetany was more common than latent tetany. Rapid changes in ionized calcium in anxiety hyperventilation causing increased neuromuscular irritability may be responsible for it. Severity of hypocalcemia is also responsible for latent and overt features of tetany. Trousseau sign is usually more sensitive for detecting latent tetany than Chvostek sign. In our study, Trousseau sign was 100% sensitive (100%), but Chvostek sign had only 19% sensitivity for detecting latent tetany. In our study, ionized calcium level (mean ± standard deviation [SD]) of latent tetany cases (n = 31) was 0.84 ± 0.04 mmol/L (95% CI: 0.82–0.86). Corrected total serum calcium level (mean ± SD) of latent tetany cases without acid-base disorder (n = 7) was 6.69 ± 0.24 mg/dL (95% CI: 6.46–6.91).
In our study, the majority of VDD cases (five out of six patients) had latent tetany. As the process of developing VDD is prolonged, calcium level decreases slowly. Patients get time to be diagnosed early in latent tetany stage. Neuromuscular irritability may also be less because of slow changes of serum calcium level.
Our study has many limitations. It is a small single center study. It does not represent all the regions of India. Spectrum of tetany may vary according to disease prevalence in different geographic locations, ethnic groups, climate variations, age groups, and emergency or nonemergency health care settings. A large study involving multiple centers can identify the etiological spectrum of tetany more accurately with the identification of regional, ethnic, and other differences.
Tetany has diverse etiologies. Both metabolic and respiratory alkalosis cause decrease in ionized calcium and are responsible for the majority of cases of tetany. Causes other than decreased total serum calcium should be kept in mind for early and proper diagnosis and management of tetany and underlying disorders.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Fong J, Khan A. Hypocalcemia: Updates in diagnosis and management for primary care. Can Fam Physician 2012;58:158-62.
Ismail HM, Jagadeesh T, Bhat RV. Gitelman's syndrome. J R Soc Med 2001;94:299-300.
Bandyopadhyay SK, Datt S, Pal SK, Saha AK. Gitelman's syndrome: A differential diagnosis of normocalcemic tetany. J Assoc Physicians India 2010;58:395.
Desai M, Kolla PK, Reddy PL. Calcium unresponsive hypocalcemic tetany: Gitelman syndrome with hypocalcemia. Case Rep Med 2013;2013:197374.
Gandhi K, Prasad D, Malhotra V, Agrawal D. Gitelman's syndrome presenting with hypocalcemic tetany and hypokalemic periodic paralysis. Saudi J Kidney Dis Transpl 2016;27:1026-8.
] [Full text]
Fujihara K, Miyoshi T, Yamaguchi Y, Araki T, Tanaka K. Tetany as a sole manifestation in a patient with Bartter's syndrome and a successful treatment with indomethacin. Rinsho Shinkeigaku 1990;30:529-32.
Ataş B, Çaksen H, Tuncer O, Kırımi E, Erol M, Yuca SA. A case of Bartter's syndrome associated with nephrocalcinosis presenting with tetany. J Pediatr Neurol 2004;2:45-7.
Richardson RM, Forbath N, Karanicolas S. Hypokalemic metabolic alkalosis caused by surreptitious vomiting: Report of four cases. Can Med Assoc J 1983;129:142-6.
Williams A, Liddle D, Abraham V. Tetany: A diagnostic dilemma. J Anaesthesiol Clin Pharmacol 2011;27:393-4.
] [Full text]
Moon HS, Lee SK, Chung JH, In CB. Hypocalcemia and hypokalemia due to hyperventilation syndrome in spinal anesthesia – A case report. Korean J Anesthesiol 2011;61:519-23.
Schneider D. Hyperventilation-induced tetany: A case report and brief review of the literature. Neurol Bull 2009;1:11-3.
Ray N, Camann W. Hyperventilation-induced tetany associated with epidural analgesia for labor. Int J Obstet Anesth 2005;14:74-6.
Parasa M, Saheb SM, Vemuri NN. Cramps and tingling: A diagnostic conundrum. Anesth Essays Res 2014;8:247-9. [Full text]
Kubota T, Kotani T, Miyoshi Y, Santo Y, Hirai H, Namba N, et al.
A spectrum of clinical presentations in seven Japanese patients with vitamin d deficiency. Clin Pediatr Endocrinol 2006;15:23-8.
Hopper AD, Hadjivassiliou M, Butt S, Sanders DS. Adult coeliac disease. BMJ 2007;335:558-62.
Conwell DL, Banks P, Greenberger NJ. Acute and chronic pancreatitis. In: Kasper DL, Hause SL, Jameson JL, Fauci AS, Longo DL, Loscalzo J, editors. Harrison's Principles of Internal Medicine. 19th
ed. New York: McGraw-Hill Education; 2015. p. 2090-102.
Chhabra P, Rana SS, Sharma V, Sharma R, Bhasin DK. Hypocalcemic tetany: A simple bedside marker of poor outcome in acute pancreatitis. Ann Gastroenterol 2016;29:214-20.
Palkar AV, Mewada M, Thakur S, Shrivastava MS. Dyselectrolytemia in acute kidney injury causing tetany and quadriparesis. BMJ Case Rep 2011;2011. pii: Bcr0620114332.
Ahmed YB. Idiopathic hypoparathyroidism: A case study. Zanco J Med Sci 2014;18:683-5.
Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med 2008;359:391-403.
Marx SJ. Hyperparathyroid and hypoparathyroid disorders. N Engl J Med 2000;343:1863-75.
Edafe O, Antakia R, Laskar N, Uttley L, Balasubramanian SP. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia. Br J Surg 2014;101:307-20.
Demeester-Mirkine N, Hooghe L, Van Geertruyden J, De Maertelaer V. Hypocalcemia after thyroidectomy. Arch Surg 1992;127:854-8.
Smets YF, Bokani N, de Meijer PH, Meinders AE. Tetany due to excessive use of alcohol: A possible magnesium deficiency. Ned Tijdschr Geneeskd 2004;148:641-4.
Ramage IJ, Ray M, Paton RD, Logan RW, Beattie TJ. Hypomagnesaemic tetany. J Clin Pathol 1996;49:343-4.
Liamis G, Milionis HJ, Elisaf M. A review of drug-induced hypocalcemia. J Bone Miner Metab 2009;27:635-42.
Jacob J, De Buono B, Buchbinder E, Rolla AR. Tetany induced by hypokalemia in the absence of alkalosis. Am J Med Sci 1986;291:284-5.
[Table 1], [Table 2]