Risk Factors of Postoperative Hypocalcemia after Total Thyroidectomy of Papillary Thyroid Carcinoma Patients

Ji Young Seong; Cho Rok Lee; Min Jhi Kim; Tae Hyung Kim; Seul Gi Lee; Jung Bum Choi; Eun Jeong Ban; Sang-Wook Kang; Jandee Lee; Jong Ju Jeong; Kee-Hyun Nam; Woong Youn Chung; Cheong Soo Park

doi:10.16956/kjes.2016.16.3.70

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Seong, Lee, Kim, Kim, Lee, Choi, Ban, Kang, Lee, Jeong, Nam, Chung, and Park: Risk Factors of Postoperative Hypocalcemia after Total Thyroidectomy of Papillary Thyroid Carcinoma Patients

Original Article

Korean Journal of Endocrine Surgery 2016; 16(3): 70-78.

Published online: 30 September 2016

DOI: https://doi.org/10.16956/kjes.2016.16.3.70

Risk Factors of Postoperative Hypocalcemia after Total Thyroidectomy of Papillary Thyroid Carcinoma Patients

Ji Young Seong, Cho Rok Lee, Min Jhi Kim, Tae Hyung Kim, Seul Gi Lee, Jung Bum Choi, Eun Jeong Ban, Sang-Wook Kang, Jandee Lee, Jong Ju Jeong, Kee-Hyun Nam, Woong Youn Chung, Cheong Soo Park

Department of Surgery, Yonsei University College of Medicine, Seoul, Korea.

Correspondence: Kee-Hyun Nam. Department of Surgery, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. Tel: +82-2-2228-2100, Fax: +82-2-313-8289, khnam@yuhs.ac

Received 20 July 2016 Revised 29 August 2016 Accepted 6 September 2016

(open-access):

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

Postoperative hypocalcemia is a common complication of thyroidectomy. This study evaluated the incidence and predisposing risk factors for postoperative permanent hypocalcemia after total thyroidectomy.

Methods

There were 1,247 consecutive patients undergoing total thyroidectomy and complete treatment and observation for differentiated thyroid cancer between January 2012 to December 2012 who were enrolled in this study. Patients were divided into two groups, those remaining normalcalcemic (Group I-824 pts) and those who had hypocalcemia requiring treatment (Groups II-423 pts). Group II was subdivided into a transient hypocalcemic group (Group IIA-409 pts) and a permanent hypocalcemic group (Group IIB-14 pts).

Results

Female gender, thyroiditis, preserved parathyroid number, lateral lymph node metastasis, RAI treatment, preoperative parathyroid hormone and preoperative vitamin D were significantly associated with the development of postoperative hypocalcemia by multivariate analysis. Comparing patients with transient versus permanent hypocalcemia, tumor size and multiplicity were significantly related to the development of permanent hypocalcemia by multivariate analysis. RAI treatment and parathyroid hormone level on the postoperative third day were significantly related to recovery from transient hypocalcemia to normo-calcemia.

Conclusion

Risk factors of postoperative hypocalcemia were associated with preoperative patient factors and advanced thyroid cancer. Advanced thyroid cancer was a risk factor for permanent hypocalcemia. To prevent postoperative hypocalcemia, we should focus on patient condition and need to preserve parathyroid gland more carefully in thyroid surgery.

Keywords: Hypocalcemia, Risk factors, Total thyroidectomy, Papillary thyroid cancer

Figures and Tables

Fig. 1

Time to resolution of transient hypocalcemia.

Table 1

Clinicopathologic characteristics of the patients (1)

	Total (n=1,247)	Group I Normal (n=824)	Group IIA Transient (n=409)	Group IIB Permanent (n=14)	P value
Age (year), mean±SD	46.39±12.71 (14~86)	46.94±12.61 (17~86)	45.45±12.84 (14~83)	41.21±12.68 (20~60)	0.019
<45	579 (46.4%)	370 (44.9%)	201 (49.1%)	8 (57.1%)	0.268
≥45	668 (53.6%)	454 (55.1%)	208 (50.9%)	6 (42.9%)
Male/female ratio	260/987 (20.9%/79.19%)	194/630 (23.5%/76.5%)	64/345 (15.6%/84.4%)	2/12 (14.3%/85.7%)	0.004
T size (cm), mean±SD	1.10±0.73 (0.07~7)	1.07±0.68 (0.1~5.9)	1.13±0.74 (0.07~7)	1.85±1.79 (0.5~7)	0.000
≤1	712 (57.1%)	477 (57.9%)	228 (55.7%)	7 (50.0%)	0.033
>1, ≤2	443 (35.5%)	292 (35.4%)	148 (36.2%)	3 (21.4%)
>2	92 (7.4%)	55 (6.7%)	33 (8.1%)	4 (28.6%)
Calcium (mg/dl), mean±SD
Preop	9.2 (±0.5)	9.2 (±0.5)	9.1 (±0.4)	9.1 (±0.5)	0.495
Postop (POD#1)	7.8 (±0.6)	8.1 (±0.5)	7.5 (±0.6)	7.4 (±0.4)	0.000
Postop (POD#3)	8.0 (±0.8)	8.2 (±0.8)	7.6 (±0.9)	7.7 (±0.5)	0.017
Parathyroid hormone (pg/ml), mean±SD
Preop	40.9 (±18.9)	42.9 (±17.5)	39.9 (±19.6)	37.9 (±11.7)	0.022
Postop (POD# 3)	21.3 (±14.5)	26.5 (±14.3)	11.1 (±8.1)	11.8 (±10.4)	0.000
Vitamin D (ng/ml), mean±SD	27.04 (±15.1)	28.97 (±18.25)	23.08 (±13.41)	27.83 (±15.06)	0.324
Thyroiditis (%)					0.005
Yes	405 (32.5%)	243 (29.5%)	155 (37.9%)	7 (50.0%)
No	842 (67.5%)	581 (70.5%)	254 (62.1%)	7 (50.0%)
Multiplicity (%)					0.102
Yes	553 (44.3%)	358 (43.4%)	185 (45.2%)	10 (71.4%)
No	694 (55.7%)	466 (56.6%)	224 (54.8%)	4 (28.6%)
Bilaterality					0.067
Yes	407 (32.6%)	257 (31.2%)	142 (34.7%)	8 (57.1%)
No	840 (67.4%)	567 (68.8%)	267 (65.3%)	6 (42.9%)
Extrathyroid invasion					0.496
Yes	793 (63.6%)	524 (63.6%)	258 (63.1%)	11 (78.6%)
No	454 (36.4%)	300 (36.4%)	151 (36.9%)	3 (21.4%)
Bilateral CCND					0.673
Yes	386 (31.0%)	252 (30.6%)	130 (31.8%)	10 (71.4%)
No	861 (69.1%)	572 (69.4%)	279 (68.2%)	4 (28.6%)
Central LN metastasis					0.670
Yes	592 (47.5%)	386 (46.8%)	198 (48.4%)	8 (57.1%)
No	655 (52.5%)	438 (53.2%)	211 (51.6%)	6 (42.9%)
Lateral LN metastasis					0.008
Yes	207 (16.6%)	118 (14.3%)	87 (21.3%)	2 (14.3%)
No	1,040 (83.4%)	706 (85.7%)	322 (78.7%)	12 (85.7%)
Retreived CLN count	6.8 (±5.0)	6.3 (±4.8)	7.7 (±5.4)	8.2 (±3.2)	0.000
Metastatic CLN count	1.6 (±2.6)	1.4 (±2.4)	1.9 (±3.0)	2.1 (±2.6)	0.000
LN ratio	0.23 (±0.31)	0.22 (±0.31)	0.23 (±0.31)	0.23 (±0.29)	0.017
<0.4	503 (76.6%)	325 (77.0%)	175 (76.1%)	3 (60.0%)	0.657
≥0.4	154 (23.4%)	97 (23.0%)	55 (23.9%)	2 (40.0%)
Parathyroid in specimen					0.000
Yes	429 (34.4%)	252 (30.6%)	172 (42.1%)	5 (35.7%)
No	818 (65.6%)	572 (69.4%)	237 (57.9%)	9 (64.3%)
Preserved parathyroid count	3.65 (±0.49)	3.70 (±0.46)	3.57 (±0.52)	3.64 (±0.50)	0.000

CCND = central compartment node dissection; LN = lymph node; CLN = central lymph node.

Table 2

Clinicopathologic characteristics of the patients (2)

	Total (n=1,247)	Group I Normal (n=824)	Group IIA Transient (n=409)	Group IIB Permanent (n=14)	P value
RAI treatment dose					0.002
No	324 (26.0%)	233 (28.3%)	90 (22.0%)	1 (7.1%)
Low	639 (51.2%)	429 (52.1%)	202 (49.4%)	8 (57.1%)
High	284 (22.8%)	162 (19.7%)	117 (28.6%)	5 (35.7%)
T stage					0.693
T1	440 (35.3%)	289 (35.1%)	148 (36.2%)	3 (21.4%)
T2	14 (1.1%)	11 (1.3%)	3 (0.7%)	0
T3	761 (61.0%)	505 (61.3%)	245 (59.9%)	11 (78.6%)
T4	32 (2.6%)	19 (2.3%)	13 (3.2%)	0
N stage					0.023
N0	616 (49.4%)	417 (50.6%)	194 (47.4%)	5 (35.7%)
N1a	424 (34.0%)	289 (35.1%)	128 (31.3%)	7 (50.0%)
N1b	207 (16.6%)	118 (14.3%)	87 (21.3%)	2 (14.3%)
M stage					0.773
M0	1,246 (99.9%)	823 (99.9%)	409 (100.0%)	14 (100.0%)
M1	1 (0.1%)	1 (0.1%)	0	0
TNM stage
Stage I	757 (60.7%)	496 (60.2%)	253 (61.9%)	8 (57.1%)	0.769
Stage II	3 (0.2%)	2 (0.2%)	1 (0.2%)	0
Stage III	398 (31.9%)	274 (33.3%)	119 (29.1%)	5 (35.7%)
Stage IVa	88 (7.1%)	51 (6.2%)	36 (8.8%)	1 (7.1%)
Stage IVc	1 (0.1%)	1 (0.1%)	0	0

RAI = radioactive iodine.

Table 3

Univariate & multivariate analysis: risk factors for postoperative hypocalcemia

	No hypocalcemia (n=824)	Hypocalcemia (n=423)	Univariate analysis		Multivariate analysis
	No hypocalcemia (n=824)	Hypocalcemia (n=423)	OR (95% CI)	P value	OR (95% CI)	P value
Age ≥45	454 (55.1%)	214 (50.6%)	0.990 (0.981~0.999)	0.032	0.928 (0.971~0.996)	0.067
Gender (female)	630 (76.5%)	357 (84.4%)	1.666 (1224~2.266)	0.001	1.818 (1.328~2.487)	0.000
Tumor size (N)			1.175 (1.005~1.375)	0.044
Thyroiditis	243 (29.5%)	162 (38.3%)	1.563 (1.168~2.093)	0.003	1.441 (1.068~1.944)	0.017
Preserved parathyroid number			0.595 (0.469~0.755)	0.000	0.583 (0.457~0.744)	0.000
Multiplicity	358 (43.4%)	195 (46.1%)	1.113 (0.880~1.409)	0.372
Bilaterality	257 (31.2%)	150 (35.5%)	1.212 (0.946~1.553)	0.128
Extrathyroid invasion	524 (63.6%)	269 (63.6%)	1.000 (0.784~1.276)	0.513
Retreived CLN number			1.055 (1.031~1.080)	0.000
Metastatic CLN number			1.064 (1.019~1.111)	0.005
LN ratio (≥0.4)	97 (23.0%)	57 (24.3%)	1.740 (1.261~2.400)	0.001	1.258 (0.885~1.787)	0.200
CLN metastasis	386 (46.8%)	206 (48.7%)	1.077 (0.852~1.362)	0.535
Lateral LN metastasis	118 (14.3%)	89 (21.0%)	1.594 (1.176~2.162)	0.003	1.569 (1.140~2.158)	0.006
RAI treatment	591 (71.7%)	332 (78.5%)	1.928 (1.376~2.702)	0.010	2.044 (1.247~3.352)	0.016
Preop PTH			0.263 (0.207~0.333)	0.016	0.471 (0.268~0.828)	0.001
Preop calcium			0.660 (0.515~0.846)	0.001	0.804 (0.617~1.047)	0.105
Preop vitamin D			0.889 (0.875~0.903)	0.000	0.920 (0.899~0.842)	0.000

OR = odd ratio; CI = confidence interval; CLN = central lymph node; LN = lymph node; RAI = radioactive iodine; PTH = parathyroid hormone.

Table 4

Univariate & multivariate analysis: risk factors for postoperative permanent hypocalcemia

	No permanent hypocalcemia (n=1,233)	Permanent hypocalcemia (n=14)	Univariate analysis		Multivariate analysis
	No permanent hypocalcemia (n=1,233)	Permanent hypocalcemia (n=14)	OR (95% CI)	P value	OR (95% CI)	P value
Age ≥45	662 (53.7%)	6 (42.9%)	0.647 (0.223~1.875)	0.423
Gender (female)	975 (79.1%)	12 (85.7%)	1.588 (0.353~7.139)	0.547
Tumor size (N)			1.892 (1.324~2.704)	0.000	1.927 (1.338~2.773)	0.015
Thyroiditis	398 (32.3%)	7 (50.0%)	2.303 (0.645~8.226)	0.199
Preserved parathyroid number			0.962 (0.327~2.831)	0.944
Multiplicity	543 (44.0%)	10 (71.4%)	3.177 (1.991~10.184)	0.042	3.382 (1.045~10.941)	0.038
Bilaterality	399 (32.4%)	8 (57.1%)	2.787 (0.961~8.086)	0.059
Extrathyroid invasion	782 (63.4%)	11 (78.6%)	2.115 (0.587~7.620)	0.252
Retreived CLN number			1.049 (0.960~1.146)	0.289
Metastatic CLN number			1.060 (0.897~1.253)	0.491
LN ratio (≥0.4)	152	2	1.134 (0.219~5.877)	0.881
CLN metastasis	584 (47.4%)	8 (57.1%)	1.482 (0.511~4.296)	0.469
Lateral LN metastasis	205 (16.6%)	2 (14.3%)	0.836 (0.1860~3.762)	0.815
RAI treatment	910 (73.0%)	13 (27.0%)	5.789 (0.672~49.843)	0.278
Preop PTH			0.984 (0.953~1.016)	0.326
Preop calcium			0.714 (0.244~2.088)	0.538
Preop vitamin D			1.033 (0.997~1.070)	0.073

OR = odd ratio; CI = confidence interval; CLN = central lymph node; LN = lymph node; RAI = radioactive iodine; PTH = parathyroid hormone.

Table 5

Univariate & multivariate analysis of factors affect to recovery from transient hypocalcemia to normal

		Initial period (N=321) (78.5%)	Long term (N=88) (21.5%)	Univariate analysis			Multivariate analysis
		Initial period (N=321) (78.5%)	Long term (N=88) (21.5%)	P value	OR	CI	P value	OR	CI
Age ≥45		166 (79.8%)	42 (20.2%)	0.623	1.005	0.986~1.023
Gender (female)		268 (77.7%)	77 (22.3%)	0.361	1.384	0.689~2.780
Tumor size				0.085	0.420	0.079~1.452
Thyroiditis		121 (78.1%)	34 (21.9%)	0.872	1.041	0.641~1.690
Parathyroid in specimen		130 (75.6%)	42 (24.4%)	0.224	1.341	0.835~2.155
CLN metastasis		160 (80.0%)	38 (19.2%)	0.269	1.308	0.813~2.103
Retreived CLN				0.627	0.980	0.904~1.063
Metastatic CLN				0.974	1.001	0.958~1.045
LN ratio (≥0.4)				0.673	0.975	0.866~1.097
Lateral LN metastasis		65 (74.7%)	22 (25.3%)	0.336	1.313	0.754~2.285
Multicentricity		146 (78.9%)	39 (21.1%)	0.846	0.954	0.594~1.533
Bilaterality		113 (79.6%)	29 (20.4%)	0.695	1.105	0.549~1.492
Extrathyroid invasion		204 (79.1%)	54 (20.9%)	0.706	1.098	0.676~1.784
RAI treatment		259 (81.2%)	60 (18.8%)	0.013	1.949	1.151~3.303	0.010	2.057	1.188~3.563
PTH	Preop			0.187	0.990	0.976~1.005
PTH	POD #3			0.000	0.864	0.803~0.930	0.000	0.862	0.798~0.932
Calcium	Preop			0.291	0.741	0.425~1.292
	POD #1			0.000	0.449	0.298~0.677	0.364	0.666	0.277~1.602
	POD #3			0.136	1.234	0.936~1.627
Vitamin D	Preop			0.291	0.991	0.975~1.008

OR = odd ratio; CI = confidence interval; CLN = central lymph node; LN = lymph node; RAI = radioactive iodine; PTH = parathyroid hormone.

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