Hypocalcaemia after Total Thyroidectomy

Objective: To determine whether postoperative hypocalcemia after total thyroidectomy is more frequent in malignant disease than benign disease. Methods: This is a Cross sectional study. The sample size is 126. All the patients were selected according to the eligibility criteria by purposive sampling. Patients were analyzed for age, gender, thyroid pathology, preoperative serum calcium, postoperative serum calcium. Results: Postoperative hypocalcemia was found in 37 (29.37%) patients. Most patients were female (Male: Female= 1: 4.2). Patients having low preoperative serum calcium had developed more postoperative hypocalcemia (p<0.03). Postoperative hypocalcemia was associated with thyroid pathology (p<0.009) and age (p<0.006), not associated with sex (p<0.907). In multivariate analysis very little association between malignant disease and postoperative hypocalcemia was found (p<0.07). Conclusion: The incidence of postoperative hypocalcemia following total thyroidectomy is 29.4% that is higher than the anticipated but is comparable to other published series. For total thyroidectomy surgeons should be aware of postoperative hypocalcemia but prophylactic calcium and vitamin D supplement is not mandatory in all cases.


Introduction:
Complications of thyroid surgery can be classified into different ways like-early, intermediate and late; local and general; those specific to the operation. Early complications include haemorrhage, voice change, airway obstruction and temporary hypoparathyroidism. The intermediate ones include seroma formation, infection and temporary palsy of the recurrent laryngeal nerve and the external branch of the superior laryngeal nerve. Late complications include subclinical hypothyroidism, permanent hypoparathyroidism, permanent injury to the recurrent laryngeal nerve, the external branch of the superior laryngeal nerve, the cutaneous nerves C2 and C3 and the accessory nerve and a poor scar. 1 Hypocalcemia after thyroid surgery occurs due to hypofunction of parathyroid gland. Parathyroid gland dysfunction occurs due to inadvertent excision of the gland or impaired vascularity of the gland. 2 The postoperative stress causing hemodilution and antidiuretic hormone secretion also lowers total serum calcium levels. 3,4 Hungry bone syndrome may occasionally contribute to the immediate post-operative hypocalcemia. 5,6 Sometimes calcitonin release is thought to be a cause of hypocalcemia. 7,8 Vascular impairment of parathyroid gland may occur during the dissection especially while securing upper pole viens. 9 Sometimes the parathyroid glands may be impossible to identify as they may lie beneath the thyroid capsule or completely within the thyroid gland. 10,11 The normal range for total calcium, about 8.6-10.2 mg/dl (2.15-2.54 mmol/l). Normal values and reference ranges may vary among laboratories as much as 0.5 mg/dl. 12 About 50% of total serum calcium is in ionized form, 40% is albumin-bound and 10% is complexed to phosphate or citrate. 9 The physiologically and clinically important fraction of the serum total calcium is the ionized calcium. 13 But it is costly and facility is not available everywhere. Almost all laboratories, only total calcium is routinely measured, and ionized calcium concentration is calculated based on calcium, protein or albumin concentrations for many plasma samples. 14 Adjusted calcium = calcium -albumin + 4·0, where calcium is in mg/100 ml and albumin in g/100 ml. 15 Another formula also used corrected calcium (mg/dl) = total calcium (mg/dl) + 0.8 × [4 -serum albumin (g/dl)]. 16 Hypocalcemia is a clinical situation where there is an electrolyte imbalance is noted with a low serum calcium level which may or may not produce clinical symptoms. There are different studies that use different cut off values for low serum calcium level for defining hypocalcemia. 17 So incidence of hypocalcemia differs from study to study.
When calcium level falls below the normal range it does not produces clinical symptoms. Only one third of the biochemical hypocalcemia produces symptoms. Most common symptoms of hypocalcemia are paresthesia, muscle spasms, cramps, tetany, circumoral numbness, and seizures. Hypocalcemia can also present with laryngospasm, neuromuscular irritability, cognitive impairment, personality disturbances, prolonged QT intervals, electrocardiographic changes that mimic myocardial infarction, or heart failure. [18][19][20] Now-a-days paradigm of surgical practice is being shifted to day care and outpatient procedures. Total thyroidectomy is also being performed as a short-stay or even an outpatient procedure. 21 Evidence based parameters are need to define which patients are eligible to undergo outpatient total thyroidectomy safely. 22 For this, preoperative prediction of complications of total thyroidectomy can help to define this criteria. 23,24 Early detection of hypocalcemia is crucial for its management. So early prediction hypocalcemia can make the thyroid surgeons more confident in management of these patients.
This study has evaluated the frequency of hypocalcemia after total thyroidectomy. Associated risk factors for the development of hypocalcemia was also tried to be found out.
The main objective of this study was to evaluate post-thyroidectomy hypocalemia in relation to thyroid gland pathology.
Study procedure: This is a Cross sectional study and was conducted in the department of Otorhinolaryngology-head & neck surgery of Dhaka Medical College hospital from January 2017 to December 2017. All the patients who underwent total thyroidectomy at the department had been considered as the study population. We excluded the patients underwent total thyroidectomy with preoperative hypocalcemia, with neck dissection, due to parathyroid gland pathology, unwilling to comply with study protocol. Following inclusion and exclusion criteria sample was enrolled by consecutive purposive random sampling.
Thyroid gland has been assessed by palpation in all the patients. Detailed history and clinical examination was done to determine any obvious clinical features of malignancy and any feature of thyroid dysfunction are recorded.
FNAC and Ultrasonography of thyroid gland were performed outside the department. Serum calcium, albumin, FT4, TSH concentration has been measured preoperatively. Operation procedure and findings were noted. No oral calcium with/ without calcitrol or intravenous calcium gluconate were given unless patients had symptoms. In first postoperative day serum calcium and serum albumin were also measured. Here serum Free T4 was calculated in picomol/liter. (Conversion rate 1pmol/l = 0.0777 ng/dl. 1ng/dl = 12.872 pmol/ l.) and TSHwas measured in mili IU/L or micro IU/ml. Serum calcium was measured in mg/dl. Payny's formula was used to calculate corrected calcium.
Ethical issues: Ethical clearance for the study was taken from the institutional review board and concern authority of Dhaka Medical College.
Statistical analysis: Statistical package for social science (SPSS) 16.0 for windows (SPSS Inc., IL, USA) was used for statistical analysis. Mean values were calculated for continuous variables. The quantitative observations were indicted by frequencies and percentages. A P value less than 0.05 (P<0.05) was considered to be statistically significant.

Results:
In this study the mean age 42.47 + 14.16 years and the range is from 7 to 80 years. (Figure-1  Mean preoperative calcium level was 9.3 mg/ dl (+0.360) and the range is from 8.5 mg/dl to 10.2 mg/dl (Figure -2). And mean postoperative calcium level was 8.4 mg/dl (+0.86) and the range is from 6.5 mg/dl to 9.6 mg/dl.  Statistically significant at two sided P-value < 0.05. ô Association between pathological diagnosis of thyroid disease and post-operative hypocalcaemia adjusted for age and sex (n=126).

Discussion:
Among the complications of thyroid surgery postoperative hypocalcemia is of one of the most common complication that is considered for outcome audit. 25 If this hypocalcemia persists it significantly reduces the quality of life and is associated with various deleterious effects on general health. 26 Hypocalcemia can be classified in different ways like transient and permanent, biochemical and clinical. In our study we included all the transient and biochemical hypocalcemia cases. Permanent or persistent hypocalcemia is defined if hypocalcemia persists even after six month of thyroid surgery. 27 The symptoms of hypocalcemia usually manifes t 24 to 48 hours after surgery. 28 Symptoms are muscle cramps, perioral and peripheral paresthesias, carpopedal spasm or tetany and confusion. Signs of hypocalcemia are the Chvostek's sign and the Trousseau's sign. 26 only one-third of patients who developed biochemical hypocalcemia required treatment. 17 To do work with postoperative hypocalcemia first it difficult to define hypocalcemia. Normal range of any biochemical in human body usually includes mean and two standard deviations above and two standard deviation below. Usually its range for calcium is 8.6-10.2mg/dl. 16 In different study cut off level for hypocalcemia was defined differently. Shaha and Jaffe in their study used hypocalemia for the patient having serum calcium less than 2.1mmol/L during their first week followup after thyroidectomy. 29 Adjusted Serum Ca less than 2.0 mmol/l was calculated for hypocalcemia by Rix TE, Sinha P. in their study of Inadvertent parathyroid excision during thyroid surgery. 30 38,39 showed women had higher incidence of postoperative hypocalcemia. We found no relation between gender and postoperative hypocalcemia (p<0.907).
In our study we found that hypocalcemia is more frequent in the malignant disease than the benign (p<0.009), which is similar to the findings of Sousa et al. 39 But in multivariate analysis relationship with thyroid pathology and postoperative hypocalcemia is very close to significance (p<0.072). We could overcome this if the study would conducted with larger sample size. In our finding malignant pathology causes more postoperative hypocalcemia which might be due to some surgery related factors.

Conclusion:
The incidence of postoperative hypocalcemia following total thyroidectomy is 29.4% that is higher than the anticipated but is comparable to other published series. For total thyroidectomy surgeons should be aware of postoperative hypocalcemia but prophylactic calcium and vitamin D supplement is not mandatory in all cases. We can recommend routine postoperative calcium supplementation in elderly and malignant cases and the patient with low preoperative serum calcium and in these cases serum calcium should be done postoperatively.