Risk of Hypocalcemia and the Need to Augment Calcium Supplementation After Total Thyroidectomy

Abstract

Hypocalcemia is the most common complication after total thyroidectomy. The aim of this study was to determine the predictors of postoperative hypocalcemia requiring augmentation of routine calcium supplementation. Prospectively collected data of 61 patients who underwent total thyroidectomy from December 2018 to June 2019 was considered for the study. All patients received calcium and vitamin D supplementation after the surgery. In the postoperative period, serum calcium and parathormone (PTH) levels were monitored. The need of additional oral or intravenous (i.v.) calcium supplementation was evaluated as an outcome measure. This cohort comprised 61 patients with median age of 46 years (range 16–80 years) and 49 (80%) females. Central compartment clearance (CCC) was done in 32 patients. Escalation to increased oral and intravenous calcium was required in 15 patients (24.6%) and 2 patients (3.3%), respectively. Serum parathormone level of 11.5 pg/ml on postoperative day 1 predicted the requirement of additional calcium with a sensitivity of 82.4% and specificity of 77.3%. On univariate analysis, serum PTH (p < 0.001), CCC (p = 0.018), and intraoperative parathyroid gland congestion (p = 0.021) predicted the need for escalation of calcium supplementation. On multivariate analysis, only serum PTH showed a significant impact on the need for augmentation of calcium supplementation (p = 0.003). The need for calcium dose augmentation after total thyroidectomy was significantly associated with CCC, parathyroid gland congestion, and serum PTH levels. Intraoperative identification of parathyroid gland congestion and postoperative serum PTH levels is effective in predicting postoperative hypocalcemia with implications on time and cost.

Introduction

Hypocalcemia is the most common complication after total thyroidectomy, which may result due to unintentional removal or devascularization of parathyroid glands leading to hypoparathyroidism. This leads to prolonged hospital stay, requiring repetitive biochemical tests and necessitating administration of both calcium and vitamin D [1–3]. Postoperative hypocalcemia is temporary in most cases, but it may take months to resolve [4]. There have been various causes of hypocalcemia after total thyroidectomy including excessive urinary excretion of calcium due to surgical stress; hungry bone syndrome (due to reversal of toxic thyroid dystrophy); and more commonly, physical damage to parathyroid glands during surgery either by direct injury, devascularization, or unintentional removal [5]. Postoperative hypocalcemia has been reported in 10–50% of patients undergoing thyroid surgery, and 0.5–2% of these patients have hypocalcemia, which persists for more than 1 year, defined as permanent hypocalcemia [1, 6–10]. There are various side effects of hypocalcemia including Chvostek’s sign, Trousseau’s sign, numbness, and paresthesia that can be worrisome for the patients and may lead to prolonged hospital stays. Long-term hypocalcemia can also lead to skeletal abnormalities [11, 12]. The aim of this study was to determine the predictors of postoperative hypocalcemia requiring augmentation of routine calcium supplementation.

Materials and Methods

Patient and Study Design

This was an audit of prospectively collected data of 61 patients who underwent total thyroidectomy with or without central compartment node clearance (CCC) and/or lateral neck dissection (LND) for malignant or benign conditions in the department of Head and Neck Surgery at a tertiary care hospital in eastern India from December 2018 to June 2019. In order to maintain uniformity of surgical technique, study patients were assigned to the same set of experienced surgeons who performed all the surgeries and evaluated the status of parathyroid glands intraoperatively. All patients received a protocol-mandated dose of calcium (1.5 g/day) and vitamin D3 (0.5 mcg/day) from 1st postoperative day (POD).

Monitoring of Hypocalcemia

Patients were evaluated for clinical signs and symptoms of hypocalcemia, namely, tingling, numbness, paresthesia, tetany, or Chvostek’s sign from POD 1 till the day of discharge. Serum parathyroid hormone (PTH) and calcium levels were measured at 6 AM on POD 1, and serum calcium levels were repeated at POD 2/3, PODs 4–7, PODs 8–14, and PODs 15–21. Hypocalcemia was categorized as clinical or biochemical (serum calcium level < 8.5 mg/dl in the presence of normal serum albumin), either during the hospital stay or any time after discharge from hospital during postoperative outpatient clinic visits. The need of additional oral or intravenous (i.v.) calcium supplementation over and above the protocol-mandated dose was evaluated as an outcome measure.

Assessment of Parathyroid Status

Number and color of parathyroid glands identified intraoperatively was recorded. Color of the parathyroid glands was noted at the end of surgery and recorded as congested or non-congested. The need to re-implant unintentionally removed parathyroid gland into the sternocleidomastoid muscle was also documented.

Statistical Analysis

Descriptive analysis was done for basic epidemiological characteristics. Pearson’s chi-square test was used for categorical variables. Logistic regression was used for multivariate analysis. SPSS 17 (SPSS, Inc., Chicago, IL) was used to analyze the data. p value of < 0.05 was considered significant.

Results

A total of 61 patients underwent total thyroidectomy with or without CCC and/or LND at our institution during the study period. Out of these 61 patients, 80% were females (Table 1). Median age at the time of presentation was 46 years (range 16–80 years). A total of 53 patients (86.89%) underwent surgery for thyroid cancer, while the remaining 8 (13.11%) underwent surgery for benign conditions. There were 44 patients (72.1%) who did not require alteration in routine calcium supplementation, 15 patients (24.6%) required an increase in oral calcium supplementation, while 2 patients (3.3%) were escalated to i.v. calcium supplementation for correction of hypocalcemia. Augmentation of calcium supplementation was not found to be associated with gender (p = 0.602), tumor pathology (benign or malignant) (p = 0.169), or lymph node dissection status (p = 0.820) on univariate analysis. Bilateral CCC was found to be significantly associated with the need for dose augmentation (p = 0.018), with 8 patients needing only oral calcium, while 2 patients needed intravenous correction.

Table 1.

Factors predicting requirement of augmentation in calcium supplementation

Factor		Augmentation in Calcium Supplementation			p-value#
		Not required (n=44)	Oral calcium (n=15)	Intravenous calcium (n=2)
Gender	Male (12)	8 (66.7%)	4 (33.3%)	0	0.602
	Female (49)	36 (73.5%)	11 (22.4%)	2 (4.1%)
Pathology	Benign (8)	8 (100%)	0	0	0.169
	Malignant (53)	36 (67.9%)	15(28.3%)	2 (3.8%)
Lateral Neck Dissection	Not done (39)	29 (74.4%)	9 (23.1%)	1 (2.6%)	0.820
	Unilateral (9)	6 (66.7%)	3 (33.3%)	0
	Bilateral (13)	9 (69.2%)	3 (23.1%)	1 (7.7%)
Central Compartment Clearance	Not done (29)	25 (86.2%)	4 (13.8%)	0	0.018
	Unilateral (14)	11 (78.6%)	3 (21.4%)	0
	Bilateral (18)	8 (44.4%)	8 (44.4%)	2 (11.1%)
Parathyroid Congestion	At least 1 congested (15)	8 (53.3%)	5 (33.3%)	2 (13.3%)	0.021
	None congested (46)	36 (78.3%)	10 (21.8%)	0
PTH level*	Low (< 11.5pg/ml) [24]	10 (41.7%)	12 (50%)	2 (8.3%)	<0.001
	High (> 11.5pg.ml) [37]	34 (91.9%)	3 (8.1%)	0

*ROC curve showing sensitivity of 82.4% and specificity of 77.3% at cutoff of 11.5 pg/ml

# Univariate analysis

There was a significant correlation between the number of congested parathyroid glands at the end of surgery and the requirement of calcium augmentation. Among patients with at least 1 parathyroid gland congested (15 patients), 5 patients required augmentation of oral calcium and 2 patients required i.v. administration for their symptoms (p = 0.021).

PTH level on POD 1 was measured in all patients with a median value of 15.9 pg/ml (range 1.2–69.9 pg/ml). On the receiver operating characteristic (ROC) curve analysis, a PTH level on 11.5 pg/ml on POD 1 predicted the requirement of additional calcium with a sensitivity of 82.4% and specificity of 77.3%. Area under curve was 82.2% (95% confidence interval 71.4 to 92.9%) (Fig. 1). The patients were divided into two groups (high PTH and low PTH) based on the PTH level of 11.5 pg/ml. Out of 24 patients in the low PTH group, 12 patients (50%) required increase in oral calcium supplementation and 2 patients (8.3%) required i.v. calcium correction for hypocalcemia. While in the high PTH group (37 patients), only 3 patients (8.1%) required increase in oral calcium, none requiring i.v. calcium correction. This difference was statistically significant (p < 0.001).

Fig. 1.

Receiver operating characteristics (ROC) curve for the role of serum parathormone (PTH) in predicting escalation of calcium supplementation

On multivariate analysis, only serum PTH showed a significant impact on the need for augmentation of calcium supplementation (p = 0.003).

Discussion

The evolution of surgical techniques has led to decrease in several complications related to thyroid surgery such as hemorrhage and recurrent laryngeal nerve palsy. In many centers, day-case thyroid surgery has become the norm [13]. Hypocalcemia and its attending tetany continue to deter the surgeon’s quest for a shorter hospital stay. Symptoms of hypocalcemia after total thyroidectomy usually evolve within the first 24–48 h [14]. Identification of perioperative risk factors associated with high risk of postoperative symptomatic hypocalcemia is therefore important in selecting patients for an early and safe discharge [15].

We have used oral calcium and vitamin D supplementation from POD 1 as routine practice after total thyroidectomy in order to preempt or mitigate the symptoms of hypocalcemia. In spite of this intervention, patients still develop postoperative symptomatic hypocalcemia and require administration of additional calcium, either orally or through the i.v. route.

Roh et al. in 2009 published that patients after total thyroidectomy with CCC for papillary carcinoma have a higher incidence of hypocalcemia as compared with patients with total thyroidectomy alone. Routine use of oral calcium and vitamin D supplementation was shown to significantly reduce the incidence of postoperative hypocalcemia [16]. He showed that in a group of 148 patients who underwent total thyroidectomy with CCC, the incidence of symptomatic and laboratory hypocalcemia was 26% and 44%, respectively, if they did not receive calcium and vitamin D supplementation (n = 50). This incidence reduced to 2% and 8%, respectively, if patients received calcium and vitamin D (n = 50), and to 12.2% and 24.5%, respectively, in patients receiving calcium alone (n = 49). This difference was statistically significant. The present study reflected similar findings with patients requiring a central compartment clearance in addition to total thyroidectomy having a significantly higher incidence of postoperative hypocalcemia and subsequent escalation of calcium dose compared with patients who had total thyroidectomy alone (p = 0.018).

We also found that congestion of the parathyroid gland at the end of total thyroidectomy was significantly associated with a high risk of developing postoperative hypocalcemia and escalation of the prophylactic calcium dose (p = 0.021).

Additionally, we also found that patients with low serum PTH levels (< 11.5 pg/ml) on POD 1 were significantly associated with a high risk of developing hypocalcemia and subsequently higher chances of calcium dose escalation (p = 0.001).

While hypoparathyroidism is a well-known and documented complication of thyroid surgery, it is important to identify a subset of patients with a low risk of developing hypocalcemia, in whom repeated blood sampling may be avoided and early discharge may be contemplated. Inspection and documentation of the parathyroid gland for congestion at the end of total thyroidectomy help in identifying patients with a high risk of developing hypocalcemia. The limitation of this method is that the extent of damage may not be apparent immediately, as the gland is exposed to view only during the duration of the surgery. The intensity of congestion may worsen or even improve at a later point of time after the surgery is over. Moreover, the description of a congested gland is fraught with a particular surgeon’s bias. We therefore feel that a twin approach, using both parathyroid color and PTH levels, might help to better predict which patients possess a high risk of developing hypocalcemia.

Conclusion

The risk of developing hypocalcemia and the need for calcium dose augmentation after total thyroidectomy was significantly associated with CCC, parathyroid gland congestion, and serum PTH levels. Identifying parathyroid gland congestion at the end of surgery and measurement of the serum PTH levels are effective strategies in the reduction of morbidity from postoperative hypocalcemia with implications on time and cost.