Is Preoperative Vitamin D Deficiency a Risk Factor for Postoperative Symptomatic Hypocalcemia in Thyroid Cancer Patients Undergoing Total Thyroidectomy Plus Central Compartment Neck Dissection?

Abstract

Background:

Although some studies have reported that preoperative vitamin D deficiency (VDD) is a risk factor for hypocalcemia after total thyroidectomy (TT) in patients with nontoxic multinodular goiter or Graves' disease, the association between VDD and postoperative hypocalcemia in thyroid cancer patients undergoing TT plus central compartment neck dissection (CCND) remains unclear. This study evaluated whether preoperative VDD was associated with postoperative symptomatic hypocalcemia.

Materials and Methods:

Data were collected prospectively between September 2012 and May 2013. A total of 267 consecutive thyroid cancer patients who underwent TT with CCND were analyzed. Patients were divided into two groups—VDD or non-VDD—by preoperative vitamin D level of <10 or ≥10 ng/mL. Symptomatic hypocalcemia was defined as serum calcium <8.2 mg/dL and symptoms or signs of hypocalcemia. The rates of postoperative symptomatic hypocalcemia and clinicopathological features were compared between the two patient groups.

Results:

The rate of postoperative symptomatic hypocalcemia was higher in the VDD group than in the non-VDD group (43.8% vs. 30.4%, p=0.043). By logistic regression analysis, predictive factors for postoperative symptomatic hypocalcemia included a preoperative vitamin D level of <10 ng/mL (p=0.007; odds ratio=3.00). In patients who had postoperative intact parathyroid hormone (iPTH) levels <15 pg/mL, symptomatic hypocalcemia was more common in the VDD group than in the non-VDD group (77.5% vs. 53.2%, p=0.008). The findings show that a preoperative vitamin D threshold level of >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% when compared with patients with VDD (p=0.003).

Conclusion:

VDD is significantly associated with postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. VDD was predictive for symptomatic hypocalcemia when patients had postoperative serum iPTH levels <15 pg/mL. Thus, preoperative supplementation with oral vitamin D should be considered to minimize postoperative symptomatic hypocalcemia.

Introduction

Postoperative hypocalcemia, a common complication after total thyroidectomy (TT), causes uncomfortable symptoms and results in longer hospital stays and ongoing laboratory tests. Hypocalcemia is transient and occurs in 10–50% of patients who undergo TT. However, permanent hypocalcemia lasting more than six months occurs in 0.5–2% of patients (1,2).

Postoperative hypocalcemia is a multifactorial phenomenon. Although hemodilution secondary to surgical stress with elevation of urinary calcium (Ca) excretion and bone hunger resulting from hyperthyroidism, hypercalcitoninemia, or vitamin D deficiency (VDD) may play a role in a few patients (3 –5), acute hypoparathyroidism is considered the major factor contributing to symptomatic hypocalcemia after TT (6,7). This acute parathyroid dysfunction is due to devascularization, stunning, or injury of the parathyroid glands during thyroidectomy or secondary to inadvertent resection of parathyroid tissue (8,9). Central compartment neck dissection (CCND) in thyroid cancer patients has been reported to increase the rate of postoperative hypocalcemia (10 –13). Therefore, to minimize acute parathyroid dysfunction, a thorough knowledge of parathyroid anatomy and meticulous surgical technique is essential for preserving viable parathyroid glands.

The health implications of VDD have become a key area of interest owing to the association of VDD with bone disease, cancer, lipid metabolism defects, diabetes, and heart disease. Activated vitamin D plays a central role in the regulation Ca and parathyroid hormone (PTH) levels in the body. It increases serum Ca by directly increasing the intestinal Ca absorption and bone resorption while it regulates PTH secretion via its effects on serum Ca. Hence, preoperative vitamin D levels have an impact on the perioperative Ca and PTH kinetics after TT. Recently, some studies have reported that VDD is a risk factor for postoperative hypocalcemia after TT in patients with nontoxic multinodular goiter or Graves' disease (2,5,14 –16). Moreover, some authors have recommended routine or selective postoperative Ca and vitamin D supplementation in order to lessen the risk of symptomatic hypocalcemia (12,17 –21).

According to a 2008 study (the Korea National Health and Nutrition Examination Survey [KNHANES]), vitamin D insufficiency (VDI) is common in South Korea, with rates of 47.3% in males and 64.5% in females (22). Moreover, the incidence of thyroid cancer is rapidly increasing in Korea. The age-standardized incidence rate of thyroid cancer in 2007 was 32.8 per 100,000 (9.9/100,000 men and 55.6/100,000 women) and the second most common cancer (sixth most common cancer in men and most common cancer in women) (23). Therefore, TT with CCND is one of the most frequently performed operations for Korean thyroid cancer patients. As a result, these patients are exposed to three risk factors for postoperative hypocalcemia before surgery: VDI, TT, and CCND.

Despite the evidence of the relationship of VDD with postoperative hypocalcemia in benign thyroid disorders (2,5,14 –16), no large-scale studies have examined the association in thyroid cancer patients undergoing TT plus CCND (12,17,18). Thus, the first goal of this study was to evaluate the association between preoperative VDD and postoperative hypocalcemia in these patients. The second was to determine the threshold vitamin D level at which the risk of hypocalcemia is increased so that vitamin D replacement therapy can be given in a judicious, goal-directed fashion.

Materials and Methods

Patients

This is a retrospective study using data collected prospectively by use of the endocrine surgery database at Yonsei University College of Medicine. This study was approved by the university's institutional review board (IRB No: 4-2014-0122). The medical records of 404 consecutive patients who underwent thyroidectomy for papillary thyroid cancer (PTC) between September 2012 and May 2013 were reviewed. According to World Health Organization (WHO) criteria, serum 25-hydroxyvitamin D (25OHD) levels <10 ng/mL are defined as deficient and levels <20 ng/mL as insufficient (14,24).

A total of 267 patients who underwent TT with CCND were enrolled in this study for analysis of the correlation between preoperative vitamin D levels and postoperative hypocalcemia. In this study, the rates of VDD and VDI according to the WHO definition were 27.3% (73/267) and 49.8% (133/267), respectively. No patients received prophylactic oral Ca and vitamin D before surgery.

Surgical technique

TT was performed by extracapsular dissection by one experienced endocrine surgeon (K.H.N.) who used the conventional open technique. In all patients, great effort was made by the surgeon to identify and preserve all parathyroid glands. In addition, every attempt was made to preserve the posterior branch of the superior thyroid artery carefully in order to maintain the vasculature into the parathyroid glands. Ligation of the inferior thyroid artery was always carried out at the level of the distal branches near the thyroid capsule. Devascularized or inadvertently resected parathyroid glands that could not be preserved in situ were chopped into 1 mm³ fragments and autotransplanted into the ipsilateral sternocleidomastoid muscle according to the technique of Wells et al. (25,26). This surgical technique led to the preservation of at least three parathyroid glands in situ in all patients; 48 patients (18%, 48/267) with preservation of three parathyroid glands did not undergo autotransplantation of the remaining one parathyroid gland that was invaded by PTC. All patients underwent ipsilateral CCND, and some patients with possible metastasis to contralateral central nodes also underwent contralateral CCND. Modified radical neck dissection was performed in 37 cases with lateral node metastases.

Inpatient management

Serum 25OHD levels were determined within one month before surgery in all patients. Serum Ca levels were determined before surgery, at one hour after surgery, and every morning for three days after surgery (corresponding to the hospital stay). Serum Ca levels were corrected for albumin concentration (corrected calcium=0.8×(4.0 – serum albumin)+serum calcium; reference range 8.2–10.2 mg/dL) (27). The level of intact parathyroid hormone (iPTH) was determined before surgery, one hour after, and the morning following surgery by standard radioimmunometric assay (Nichols Institute, San Clemente, CA; reference value at the authors' institution 15–65 pg/mL). Biochemical hypocalcemia was defined as serum Ca <8.2 mg/dL without symptoms or signs of hypocalcemia. Symptomatic hypocalcemia was defined as serum Ca <8.2 mg/dL along with the presence of any symptoms or signs of hypocalcemia, such as numbness and paresthesias of the fingertips, toes, and perioral area, Chvostek's sign, Trousseau's sign, or tetany. Time after TT to onset of hypocalcemic symptoms after surgery were recorded, and the lowest levels of serum Ca and iPTH were measured during the postoperative hospital stay. All patients developing biochemical hypocalcemia were treated with oral Ca (3–6 g/day). Symptomatic hypocalcemia was treated with parenteral Ca and an oral 1,25-dihydroxy vitamin D3 (calcitriol) supplementation of 1–1.5 g/day. Those patients with biochemical hypocalcemia were discharged on oral Ca, whereas patients with symptomatic hypocalcemia were discharged on oral Ca and/or calcitriol at doses modified relative to serum Ca level.

Follow-up strategy

After discharge, serum Ca and iPTH levels were measured on postoperative days 10, 30, 60, 90, and 180 in the outpatient clinic. At every follow-up visit, all patients were asked about hypocalcemic symptoms and evaluated with the goal of controlling serum Ca and phosphorous levels by titrating the replacement therapy. All patients were seen at least every three months in the authors' department until their serum Ca and PTH levels had normalized after Ca or vitamin D therapy was withdrawn for one week or more. Permanent hypoparathyroidism was defined as the requirement for vitamin D or Ca supplementation (or both) to maintain normocalcemia for more than six months after thyroidectomy.

Outcome assessment

Patients were divided into two groups based on WHO criteria for VDD: the VDD group (73 patients; serum 25OHD <10 ng/mL) and the non-VDD group (194 patients; serum 25OHD ≥10 ng/mL). The two groups were compared with respect to demographic and pathological findings, extent of lymph node dissection, TNM stage, number of preserved parathyroid glands, symptomatic hypocalcemia, onset of hypocalcemic symptoms and signs, and perioperative laboratory findings.

In determining an appropriate vitamin D threshold level at which the risk of hypocalcemia is increased, odd ratios (OR) were used according to preoperative serum 25OHD levels.

Statistical analysis

Data are expressed as mean±standard deviation, proportions, or absolute numbers. SPSS Statistics for Windows v20.0 (IBM Corp., Armonk, NY) was used for statistical analysis. Statistical differences between the two groups were assessed using the Student's t-test or Mann–Whitney U-test for continuous variables, depending on distribution. Inter-arm comparisons of categorical variables were performed using the chi-square test. Pearson's correlation coefficient was used for bivariate correlation analysis. Odds ratios were used to compare the risk of symptomatic hypocalcemia between the independent factors using linear logistic regression analysis. A p-value of <0.05 was accepted as a significant difference.

Results

The number of parathyroid glands preserved in situ is one of the predictors of postoperative hypocalcemia. However, there were no significant differences in the two groups regarding mean number of parathyroid glands preserved in situ, parathyroid glands identified in situ at surgery, and parathyroid glands identified on histological examination (Table 1).

Table 1.

Preservation Status of Parathyroid Glands in the Two Groups

	VDD (N=73)	Non-VDD (N=194)	p
Mean no. of parathyroid glands preserved in situ	3.79±0.44	3.8±0.45	0.875
4 PG	59 (80.8%)	160 (82.4%)	0.754
3 PG	14 (19.2%)	34 (17.5%)
Parathyroid glands identified in situ at surgery
5 PG	0	0
4 PG	73 (100%)	194 (100%)
3 PG	0	0
Parathyroid glands identified on histological examination			0.754
1 PG	14 (19.2%)	34 (17.5%)
2 PG	0	0

Note: Autotransplantation of a parathyroid gland that was suspected to be invaded or invaded by PTC was not performed.

VDD, vitamin D deficiency; PG, parathyroid gland.

Clinicopathological findings of both groups are shown in Table 2. Non-VDD patients were significantly older than VDD patients (M=45.32 vs. 49.05 years, p=0.016). There were no differences in the two groups regarding sex, histology findings, curative intent and extent of neck dissection, mean number of neck nodes removed and metastases, and TNM stage (Table 2).

Table 2.

Demographic and Pathologic Parameters of Patients in the Two Groups

	VDD (N=73)	Non-VDD (N=194)	p
Sex (female:male)	61:12	141:53	0.078
Age (years)	45.32±11.2	49.05±11.3	0.016
Tumor size (cm)	1.01±0.53	0.97±0.52	0.614
Extracapsular invasion	40 (55.6%)	116 (59.8%)	0.576
Bilaterality	23 (31.9%)	65 (33.5%)	0.911
Neck dissection			0.831
CCND only	65 (89%)	165 (85.1%)
CCND+MRND	8 (11.0%)	29 (14.9%)
Curative intent of CCND			0.902
Prophylactic	52 (71.2%)	137 (70.6%)
Therapeutic	21 (29.8%)	57 (28.8%)
Extent of CCND			0.673
Unilateral	63 (86.3%)	172 (88.7%)
Bilateral	10 (13.7%)	22 (11.3%)
Mean no. of central nodes removed (n)	6.6±5.0	6.2±5.0	0.500
Mean no. of central node metastases (n)	1.7±3.2	1.5±2.7	0.512
Histology			0.652
PTC	73 (100%)	194 (100%)
PTMC	33 (45.2%)	109 (56.2%)
FVPTC	3 (4.1%)	15 (7.7%)
DSVPTC	1 (1.4%)	2 (1.0%)
Stage
T1/T2/T3/T4a	32 (43.8%)/1 (1.4%)/39 (53.4%)/1 (1.4%)	77 (39.7%)/0/114 (58.8%)/3 (1.5%)	0.385
N0/N1a/N1b	38 (52.0%)/27 (37.0%)/8 (11.0%)	110 (56.7%)/56 (28.9%)/28 (14.4%)	0.488
Stage I/III/IVa/IVc	44 (60.2%)/27 (37.0%)/1 (1.4%)/1 (1.4%)	108 (55.7%)/70 (36.1%)/15 (7.7%)/1 (0.5%)	0.352

CCND, central compartment neck dissection; DSVPTC, diffuse sclerosing variant PTC; FVPTC, follicular variant PTC; MRND, modified radical neck dissection; PTC, papillary thyroid cancer; PTMC, papillary thyroid microcarcinoma.

The mean vitamin D level of the entire cohort was 15.3±7.1 ng/mL. Of the patients, 133 (50%, 133/267) had serum 25OHD levels of 10–20 ng/mL, 73 (28%) had serum 25OHD levels of <10 ng/mL, and 61 (22%) had serum 25OHD levels of >20 ng/mL.

Perioperative laboratory findings for the two groups are summarized in Table 3. Preoperative serum 25OHD levels were lower in the VDD group than in the non-VDD group (7.62 vs. 18.27 ng/mL, p=0.001). Preoperative serum iPTH levels were higher in the VDD group than in the non-VDD group (53.4 vs. 44.78 pg/mL, p=0.001), whereas preoperative serum Ca levels were lower in the VDD group than in the non-VDD group (9.08 vs. 9.21 mg/mL, p=0.026).

Table 3.

Biochemical Parameters of Patient Groups in the Two Groups

	VDD (N=73)	Non-VDD (N=194)	p
Preoperative vitamin D (ng/mL)	7.62±1.52	18.27±6.25	0.001
Preoperative PTH (pg/mL)	53.4±26.2	44.8±15.1	0.001
Preoperative calcium (mg/dL)	9.08±0.44	9.21±0.4	0.026
Postoperative PTH<15 pg/mL, n (%)	40 (54.8%)	109 (56.2%)	0.89
Postoperative PTH (pg/mL)	15.8±11.1	14.7±9.9	0.439
Postoperative PTH 3 months	46.6±24.6	39.3±16.5	0.007
Postoperative calcium (mg/dL)	7.46±0.69	7.67±0.65	0.027
Biochemical hypocalcemia, n (%)	54 (74.0%)	117 (60.3%)	0.045
Symptomatic hypocalcemia, n (%)	32 (43.8%)	59 (30.4%)	0.043
Onset of hypocalcemia symptoms and signs after TT (h)	34.34±15.29	42.64±14.34	0.012
Hospital stay (days)	3.7±1.8	3.7±1.7	0.764

Statistically significant values are shown in bold.

PTH, parathyroid hormone; TT, total thyroidectomy.

No patients in either group developed permanent hypocalcemia during the six months of follow-up. All patients with symptomatic hypocalcemia recovered to normocalcemia within three months by titration and withdrawal of the replacement therapy. The rate of symptomatic hypocalcemia requiring Ca replacement was significantly higher in the VDD group than in the non-VDD group (43.8% vs. 30.4%, p=0.043). The rate of biochemical hypocalcemia was also significantly higher in the VDD group than in the non-VDD group (74.0% vs. 60.3%, p=0.045). The two groups had similar postoperative iPTH levels of <15 pg/mL and postoperative mean serum iPTH levels one day after surgery. However, the mean serum iPTH level three months after surgery was significantly higher in the VDD group than in the non-VDD group (46.6±24.6 vs. 39.3±16.5 pg/mL, p=0.007). The onset of hypocalcemic symptoms and signs was significantly earlier in the VDD group than in the non-VDD group (34.34±15.29 vs. 42.64±14.34 h, p=0.012). However, length of hospital stay did not differ in the two groups (3.7±1.8 vs. 3.7±1.7 days, p=0.764).

In terms of postoperative Ca kinetics, although there was no correlation between preoperative 25OHD and postoperative Ca (r=0.09, p=0.139), there was a direct correlation between postoperative iPTH and postoperative Ca levels (r=0.731, p=0.01; Fig. 1) and between preoperative 25OHD values and the onset of hypocalcemic symptoms (r=0.308, p=0.003; Fig. 2).

FIG. 1.

Direct correlation between postoperative intact parathyroid hormone (iPTH) and postoperative serum calcium levels.

FIG. 2.

Correlation between preoperative vitamin D level and onset of hypocalcemic symptoms.

Linear logistic regression analysis showed that preoperative VDD was significantly associated with postoperative symptomatic hypocalcemia (OR=3.0, p=0.007 [CI 1.4–6.6]). Moreover, the combination of preoperative VDD and postoperative serum iPTH levels of <15 pg/mL was more likely to be associated with symptomatic hypocalcemia (OR=9.6, p<0.001 [CI 4.3–21.3]), although the findings confirm that acute hypoparathyroidism (serum iPTH levels <15 pg/mL) after TT was the strongest risk factor for symptomatic hypocalcemia (OR=102.4, p<0.001 [CI 23.7–442.6]; Table 4).

Table 4.

Linear Logistic Regression Analysis Between Symptomatic Hypocalcemia and Independent Parameters

Dependent variable	Independent variable	Odds ratio	CI	p
Symptomatic hypocalcemia	Preoperative serum vit D level <10 ng/mL	3.0	1.4–6.6	0.007
	Postoperative serum PTH level <15 pg/mL	102.4	23.7–442.6	<0.001
	Preoperative serum vit D level <10 ng/mL+postoperative serum PTH level <15 pg/mL	9.6	4.3–21.3	<0.001

Statistically significant values are shown in bold.

Cross-analysis of symptomatic hypocalcemia based on preoperative VDD and postoperative iPTH levels showed that postoperative symptomatic hypocalcemia caused by acute hypoparathyroidism (serum iPTH levels <15 pg/mL) was more prominent in the VDD group than in the non-VDD group (77.5% vs. 53.2%, p=0.008; Table 5).

Table 5.

Cross-Analysis of Symptomatic Hypocalcemia by Parathyroid Hormone Level and Vitamin D Status

		Symptomatic hypocalcemia
Postoperative serum PTH level	Vit D status	No	Yes	p
≥15 pg/mL	Non-VDD	84	1 (1%)	0.483
	VDD	32	1 (3.0%)
<15 pg/mL	Non-VDD	51	58 (53.2%)	0.008
	VDD	9	31 (77.5%)

Note: Data are n (%). Statistically significant values are shown in bold.

In determining an appropriate vitamin D threshold level at which the risk of hypocalcemia is increased so that vitamin D replacement can be given in a judicious, goal-directed fashion, this study revealed that serum vitamin D levels >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% (OR=0.28, p=0.003 [CI 0.12–0.66]) as compared with the VDD group (Table 6).

Table 6.

Logistic Regression Analysis Between Preoperative Serum Vitamin D Level and Hypocalcemia

Dependent variable	Preoperative serum vit D level	OR [CI]	p-Value
Symptomatic hypocalcemia	<10 ng/mL	1 (referent)
	10 to <20 ng/mL	0.45 [0.18–1.17]	0.101
	≥20 ng/mL	0.28 [0.12–0.66]	0.003

Statistically significant values are shown in bold.

Discussion

The KNHANES study found that VDD and VDI are prevalent in the Korean population (22). The present study confirms that both VDD and VDI applied by WHO definition are also common in Korean thyroid cancer patients with rates of 25.7% for VDD and 52% for VDI patients.

There is much debate about the correct definition of VDD. According to WHO criteria, serum 25OHD levels <10 ng/mL are deficient because both serum 1,25(OH)₂D and Ca absorption decline significantly at this level (28,29), and a level of <10 ng/mL is associated with low cortical bone mineral density and high intact PTH concentrations in females (30). However, more recently, others have defined VDD as a serum 25OHD concentration of <20 ng/mL and VDI as <30 ng/mL on the basis that serum PTH, which is inversely related to serum 25OHD levels, decreases as serum 25OHD increases and plateaus at a serum 25OHD level of approximately 30 ng/mL (16). However, this definition is also controversial because studies show a large variation in the plateau level of PTH ranging from a serum 25OHD concentration of 18 ng/mL (31) to 30 ng/mL (28). Because of these differing definitions, the WHO criteria for VDD were adopted.

Lin et al. (32) reported that vitamin D levels did not predict hypocalcemia after near-TT in a series of 152 patients. However, all patients in that study were routinely prescribed calcium carbonate and cholecalciferol (vitamin D) postoperatively. Chia et al. (33) reported no association between vitamin D level and postoperative hypocalcemia in a series of 103 patients. However, this was a heterogeneous group in which a large number of patients underwent parathyroidectomy and only 27 underwent TT. Griffin et al. (34) reported that vitamin D levels did not appear to have a significant effect on the risk of post-thyroidectomy hypocalcemia in a series of 149 patients undergoing TT or complete thyroidectomy. However, this too was a heterogeneous group; many patients had benign tumors, and just 41 had thyroid cancer. Furthermore, among the 41 thyroid cancer patients, only 16 underwent CCND. Unlike those studies, the present data show that VDD increases the rate of symptomatic hypocalcemia after TT. This discordance between the current findings and those of others may be explained by the fact that all patients in this study had PTC requiring radical resection and CCND, and among them, 37 (13.9%) underwent modified radical neck dissection.

Two studies found that the rapid PTH assay could monitor parathyroid function during thyroidectomy and identify patients at risk for clinically significant hypocalcemia (35,36). Grodski and Serpell reported that postoperative PTH could be used to stratify the risk of hypocalcemia after thyroidectomy (37). The present too found a positive correlation between postoperative PTH and postoperative Ca levels (r=0.731, p=0.01), indicating that acute hypoparathyroidism (serum iPTH levels <15 pg/mL), regardless of the preoperative vitamin D level, was the strongest risk factor for symptomatic hypocalcemia (OR=102.4, p<0.001 [CI 23.7–442.6]).

Kirkby-Bott et al. (15) pointed out the unreliability of PTH levels for predicting symptomatic hypocalcemia because serum PTH levels do not uniformly correlate with hypocalcemia. This finding may be explained by the fact that perioperative Ca kinetics is affected both by the iPTH level and by the vitamin D level. The present study also confirms that the serum PTH level as a predictor of hypocalcemia is dependent on the vitamin D level by showing that preoperative VDD led to higher pre- and postoperative PTH levels due to secondary hyperparathyroidism despite a greater risk of hypocalcemia.

The authors previously reported that earlier onset of hypocalcemic symptoms is associated with longer recovery from hypocalcemia, and earlier onset of postoperative hypocalcemic symptoms reflects more severe reduction in functional parathyroid parenchyma after surgery (38). The current study also found that VDD patients showed an earlier onset of postoperative hypocalcemic symptoms than non-VDD patients, and the proportion of hypocalcemia patients with serum iPTH levels <15 pg/mL was higher in the VDD group than in the non-VDD group. This suggests that VDD can render patients especially susceptible to postoperative symptomatic hypocalcemia due to acute hypoparathyroidism. VDD patients absorb less Ca from the gut and can be more dependent on PTH-mediated bone and kidney resorption of Ca (14,16,39 –41). Temporary reduction of PTH secretion after TT (even in experienced hands) predisposes VDD patients to more marked hypocalcemia because their Ca regulation is more sensitive to circulating serum PTH levels than that of persons with normal vitamin D levels.

Roh et al. reported that postoperative hypocalcemia can be prevented by routine postoperative supplementation with oral Ca and vitamin D (12), and Sanabaria et al. also suggested that routine administration of vitamin D plus Ca could decrease the incidence of symptomatic hypocalcemia (17). However, neither study evaluated preoperative serum vitamin D levels. Kirkby-Bott et al. reported a possible dose-dependent relationship between vitamin D level and risk of hypocalcemia after thyroidectomy and proposed that 20 ng/mL of vitamin D was a reasonable level to reduce the postoperative risk of hypocalcemia (15). The present results are similar in that >20 ng/mL of vitamin D reduced the risk of symptomatic hypocalcemia by 72%. Thus, measuring a patient's vitamin D level would be an inexpensive way to identify an easily correctable risk factor that could be addressed before surgery.

The current study demonstrates a link between VDD and risk of postoperative hypocalcemia. However, the retrospective nature of the analysis and a single surgeon's experience are study limitations. The appropriate dose and duration of preoperative vitamin D supplementation need to be evaluated in future prospective studies.

The study found that preoperative VDD is significantly associated with postoperative symptomatic hypocalcemia in thyroid cancer patients undergoing TT plus CCND. VDD is predictive of symptomatic hypocalcemia in cases of acute hypoparathyroidism (serum iPTH levels <15 pg/mL). Serum vitamin D levels >20 ng/mL reduced the risk of symptomatic hypocalcemia by 72% when compared with VDD patients. Therefore, preoperative supplementation of oral vitamin D should be considered as a way to minimize postoperative symptomatic hypocalcemia in thyroid cancer patients with preoperative VDD.

Footnotes

Acknowledgments

This article was orally presented at the 84th meeting of American Thyroid Association in 2014. This study was supported by a faculty research grant of Yonsei University College of Medicine for 6-2012-0143.

Author Disclosure Statement

No authors have any conflicts of interest regarding this article.

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