Original Research—Endocrine Surgery
Incidental Parathyroidectomy during Thyroid Surgery Using Capsular Dissection Technique
Otolaryngology– Head and Neck Surgery 2014, Vol. 150(5) 754–761 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599814521365 http://otojournal.org
Pavol Prazˇenica, MD, PhD1,2, Kieran O’Driscoll, FRCSI, FCS(ECSA) ORL Hon2, and Richard Holy´, MD1
No sponsorships or competing interests have been disclosed for this article.
Abstract Objective. To identify incidence, preoperative features, surgical factors, and postoperative events of incidental parathyroidectomy (IP) during thyroidectomy. Study Design. A total of 1068 consecutive patients who underwent thyroidectomy performed by a single surgeon between January 2003 and April 2012 were enrolled in retrospective study with prospectively collected data. Setting. University hospital. Subjects and Methods. To assess the impact of IP on study variables, patients were stratified into 2 study groups: IP group and non-IP group. Univariate and multivariate analyses identified significant correlates of IP. Results. In all, 5.4% patients experienced IP. Significant difference (P \.001) was in incidence of temporary hypocalcemia between IP group (36.2%) and non-IP group (16.8%). Multivariable logistic regression model identified total thyroidectomy (odds ratio 3.937, 95% confidence interval [CI] 1.462-10.601, P = .007) and Graves’ disease (odds ratio 2.192, 95% CI 1.157-4.158, P = .016) as risk-adjusted factors associated with IP. Multivariate analysis of repeated measures identified statistically significant difference of repeated total calcium level (P \ .001) and ionized calcium level (P = .020) between study groups. Conclusion. IP during thyroidectomy might be potential complication. Total thyroidectomy, Graves’ disease, longer operation time, and identification 3 and more parathyroid glands seemed to be predictive factors for IP. IP is significantly associated with temporary hypocalcemia, but not with permanent hypoparathyroidism.
Keywords incidental parathyroidectomy, thyroidectomy, thyroid, hypocalcemia, capsular dissection Received November 26, 2013; revised December 17, 2013; accepted January 7, 2014.
Introduction Thyroidectomy is a very common surgical procedure. Despite meticulous surgical technique, parathyroid dysfunction during thyroidectomy may occur and makes this operation challenging. Many factors may contribute to this inconvenience.1-4 Nevertheless, every surgeon is sporadically disappointed by a histopathology report indicating parathyroid tissue along with the thyroid specimen. Although it has been stated that removal of 1 or 2 parathyroid glands does not necessarily lead to hypoparathyroidism,5-8 theoretically, avoiding the parathyroid glands incidentally removed may lower the incidence of postoperative hypocalcemia. This fact might be of high importance for a surgeon in terms of identifying the risk factors that may potentially bring about the incidental removal of parathyroid glands. The present study was designed to evaluate the clinical significance and the incidence of incidental parathyroidectomy during total thyroidectomy and, furthermore, to assess potential risk factors associated with this undesirable incident.
Material and Methods Patient Characteristics and Study Variables Consecutive patients undergoing thyroidectomy (total thyroidectomy, completion thyroidectomy, or lobectomy) performed at the Department of Otolaryngology in the Military University Hospital, Prague, Czech Republic, between January 2003 and April 2012, were enrolled in this retrospective study with prospectively collected data. A single surgeon carried out all operations. Informed written consent was required from all patients to collect their data and to be included in the trial. The institutional review board of the Military University Hospital in Prague under the patronage of the Ministry of Health of the Czech Republic approved the study. Patients with central neck dissection were included in 1 Department of Otolaryngology, 3rd Medical Faculty of the Charles University, Military University Hospital, Prague, Czech Republic 2 Department of Otolaryngology, Midland Regional Hospital, Tullamore, Ireland
Corresponding Author: Pavol Prazˇenica, MD, PhD, Department of Otolaryngology, 3rd Medical Faculty of the Charles University, Military University Hospital, U vojenske´ nemocnice 1200, 16902 Prague 6, Czech Republic. Email: [email protected]
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the study. Exclusion criteria involved the following conditions: revision surgery for recurrent disease, modified or radical neck dissection, extensive thyroid procedures extending to surrounding structures, and procedures for hyperparathyroidism. All relevant data regarding patients’ demographics, preoperative findings, surgical procedure, histological analysis, and postoperative and follow-up events were gathered.
Brief Surgical Comments in Relation to the Parathyroid Glands All operations were performed in a similar fashion throughout the study period strictly following the capsular principle of dissection.9 The preservation by meticulous dissection of the parathyroid glands was attempted. All terminal branches of the superior and inferior thyroid arteries were ligated distally as close to the thyroid capsule as possible. The aim of this technique was liberating the parathyroid glands from the surface of the thyroid gland with an uncompromised vascular supply. Excessive dissection to identify all the glands was avoided as this approach could potentially lead to jeopardizing of vascularization of the remaining gland. After removal of the thyroid lobe, all parathyroid glands left in situ were examined for any signs of devascularization. The resected thyroid gland was inspected for any unintentionally removed parathyroid glands. If this happened, all devascularized or removed glands were autotransplanted into the muscle pocket created in the sternocleidomastoid muscle after mincing into small pieces at the end of the procedure. Histological examination was performed in all resected thyroid glands. For histological analysis of the thyroid specimens, 5 mm serial sectioning was used.
Postoperative Follow-up All patients were closely monitored for postoperative clinical or biochemical hypocalcemia. Serum total calcium, ionized calcium, phosphorus and parathyroid hormone (PTH) levels were collected before the procedure and at 2 hours, 24 hours, 3 days, and 5 days after the operation. We define hypocalcemia as a total calcium level less than 2.00 mmol/l (normal range 2.05-2.75 mmol/L) or ionized calcium less than 1.00 mmol/l (normal range 1.00-1.3 mmol/L) obtained on at least 1 postoperative measurement, with or without clinical symptoms. Normal range for phosphorus level in our laboratory is 0.65-1.6 mmol/L, while the normal PTH assay is 1.6-6.9 pmol/L (to convert to pg/mL, multiply 9.43). Patients with hypocalcemia for more than 2 measurements commenced oral calcium substitution with Calcium carbonate (1500 to 3000 mg daily). In case of severe symptomatic hypocalcemia intravenous Calcium gluconate and vitamin D (1.25-dihydroxycholecalciferol 0.25-0.50 mg daily) were administered. The dose was then adjusted to achieve normal calcium level. All patients who developed either biochemical or clinical hypocalcemia were repeatedly monitored for calcium, ionized calcium, and phosphorus and PTH levels until final termination of substitutive therapy with the last measurement 2 weeks after complete
withdrawal of substitution therapy. Hypocalcemia was considered as permanent when requiring oral calcium or vitamin D (1.25-dihydroxycholecalciferol) substitution regardless PTH level more than 1 year after operation.
Statistical Analysis The design of the study allowed collecting data prospectively in a determined computer database (Microsoft Office Excel). Statistical analysis was performed using SPSS 21.0 software package (SPSS, Chicago, Illinois). To evaluate the impact of incidental parathyroidectomy on study variables, patients were stratified into 2 study groups as a result of the incidental parathyroidectomy: that without incidental parathyroidectomy (non-IP group) and that with incidental parathyroidectomy (IP group), and univariate analysis between these groups was performed. Continuous data are reported as mean 6 SD, medians, and interquartile range, as appropriate. Two-sample Mann–Whitney test was used to compare differences between patients with or without incidental parathyroidectomy. Categorical and dichotomous variables are presented as frequencies or percents and are compared using Fisher’s exact test. Multivariable regression logistic model with stepwise elimination was developed to test the difference between groups with or without incidental parathyroidectomy. In this model, the main binary dependant variables included incidental parathyroidectomy and the covariates included preoperative characteristics, and operative features. Covariates serving as a confounding factor or as an effect-influencing modifier were included. Confounder-adjusted measures of association are reported as odds ratios (OR) with a 95% confidence interval. Data regarding calcium, ionized calcium, phosphorus, and PTH levels in relation to groups with or without incidental parathyroidectomy were evaluated by the univariate analysis of variance (ANOVA) and the multivariate analysis of variance (MANOVA) for repeated measures. All statistical tests were 2-sided, and P \ .05 was considered statistically significant.
Results A total of 1068 consecutive patients who underwent thyroidectomy during the study period were included in the study. Patients’ demographics, operative details, histological findings, and postoperative hypocalcemia data are reported in Table 1. Data concerning incidentally removed parathyroid glands are summarized in Table 2. The number of patients with 0, 1, 2, 3, 4 parathyroid glands identified was 51, 229, 461, 234, 93, respectively. Table 3 provides the summary of univariate analysis of diverse variables and incidental parathyroidectomy. The mean number of parathyroid glands identified in IP group versus non-IP group (2.4 vs 2.07) was statistically significant (P = .010). Similarly, the risk of incidental removal was significantly higher when 0-2 versus 3-4 parathyroid glands were identified (P = .019). The statistically significant difference (P \ .001) was observed between the
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Table 1. Patients’ Preoperative Findings, Surgical Procedure, Histological Analysis, Postoperative Complications. Total Number of Patients (N = 1068)a
Variable Preoperative diagnosis Benign Malignant Procedure Total thyroidectomy Lobectomy Completion thyroidectomy Mini invasive thyroidectomy Yes No Central neck dissection Yes No Biclamp hemostasis Yes No Thyroid gland weight (g) Mean 6 SD Median (range) Substernal extension Yes No Tracheal deviation Yes No Operation time (minutes) Mean 6 SD Median (range) Final thyroid histology Multinodular goiter Graves’ disease Hashimoto thyroiditis Follicular adenoma Thyroid cancer Total number of identified parathyroid glands 0-2 3-4 Parathyroid autotransplantation Yes No Temporary hypocalcemia Yes No Permanent hypoparathyroidism Yes No
964 (90.3) 104 (9.7) 756 (70.8) 281 (26.3) 31 (2.9) 54 (5.1) 1014 (94.9) 71 (6.6) 997 (93.4) 323 (30.2) 745 (69.8) 27.1 6 24.1 20.0 (3-200) 85 (8.0) 983 (92.0) 135 (12.6) 933 (87.4)
Table 2. Characteristics of Incidentally Removed Parathyroids Glands. Variable Incidental parathyroidectomy (total number of patients) Number of removed parathyroid glands One removed parathyroid gland Two removed parathyroid glands Total number of removed parathyroid glands Number of identified parathyroid glands Mean 6 SD Median Range Diameter of removed parathyroid gland (mm) Mean 6 SD Median Range Location of removed parathyroid gland Extracapsular Intracapsular Intrathyroidal Histological features of removed parathyroid gland Normal Adenomatous Hyperplastic
Valuea 58 (5.4)
46 (79.3) 12 (20.7) 70 2.23 6 0.95 2 0-4
3.6 6 1.9 3,4 0.9-7.5
41 (58.6) 15 (21.4) 14 (20.0)
54 (93.1) 3 (5.2) 1 (1.7)
a
Data are presented as number (percentage) unless indicated otherwise.
116 6 34.3 115 (45-240) 605 220 77 43 123
(56.7) (20.6) (7.2) (4.0) (11.5)
741 (69.4) 327 (30.6) 79 (7.4) 989 (92.6) 185 (17.3) 883 (82.7) 16 (1.5) 1052 (98.5)
a
Data are presented as number (percentage) unless indicated otherwise.
incidence of temporary hypocalcemia between IP group (36.2%) and non-IP group (16.8%).
The results of stepwise multivariate logistic regression analysis are presented in Table 4. This revealed statistically significant correlation between Graves’ disease (OR 2.192, 95% confidence interval [CI] 1.157-4.158, P = .016) and incidental parathyroidectomy, and between total thyroidectomy (OR 3.937, 95% CI 1.462-10.601, P = .007) and incidental parathyroidectomy. The results of the ANOVA are presented in Table 5. The statistical significant difference reached the following measures: the total calcium levels measured at 2 hours, 3 days, and 5 days postoperatively, the ionized calcium levels measured at 24 hours and 3 days postoperatively, and PTH levels measured at 2 hours, 24 hours, and 5 days postoperatively. The MANOVA revealed the difference of repeated total calcium level and ionized calcium level between IP and non-IP groups being statistically significant (P \ .001, Figure 1; P = .020, Figure 2, respectively). Serum total calcium level in patients with incidental parathyroidectomy decreased from a preoperative mean level of 2.42 mmol/L to a mean level of 2.13 mmol/L at 2 hours postoperatively, with a continual decline to a mean level of 2.07 mmol/L at 24 hours postoperatively (with a maximum slope of 14.7% from the preoperative value). Then the decreased level increased and reached a mean
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Table 3. Univariate Analysis of Patients’ Preoperative Characteristics, Operative Variables, and Postoperative Events in Relation to Incidental Parathyroidectomy. Variable Gender Male Female Age (y) mean 6 SD (range) Preoperative diagnosis Benign Malignant Procedure Total thyroidectomy Mini invasive thyroidectomy Yes No Central neck dissection Yes No Biclamp hemostasis Yes No Thyroid gland weight (g) mean 6 SD (range) Substernal extension Yes No Tracheal deviation Yes No Operation time (minutes) mean 6 SD (range) Final thyroid histology Graves’ disease Total number of identified parathyroid glands 0-2 3-4 Mean number of identified parathyroid glands Mean 6 SD (range) Parathyroid autotransplantation Yes No Temporary hypocalcemia Yes No Permanent hypoparathyroidism Yes No Total calcium recovery time (days) Mean 6 SD (range) Parathyroid hormone recovery time (days) Mean 6 SD (range)
Incidental Parathyroidectomy Group (n = 58)a
No Incidental Parathyroidectomy Group (n = 1010)a
6 (10.3) 52 (89.7) 50.2 6 14,28 (24-79)
137 (13.6) 873 (89.7) 50.8 6 14.25 (22-86)
.690
51 (87.9) 7 (12.1)
914 (95.5) 96 (12.1)
.492
52 (89.7)
704 (69.7)
.003*
1 (1.7) 57 (98.3)
53 (5.2) 957 (94.8)
.357
7 (12.1) 51 (87.9)
64 (6.3) 946 (93.7)
.099
305 (30.2) 705 (69.8) 28.1 6 24.6 (2-200)
.884
82 (8.1) 928 (91.9)
.617
18 (31.0) 40 (69.0) 25.9 6 23.6 (4-144) 3 (5.2) 55 (94.8) 4 (6.9) 54 (93.1) 121.6 6 3.0 (50-240)
131 (13.0) 879 (87.0) 111.0 6 35.6 (45-240)
P Value
.687
.593
.223 .017*
22 (38.0)
198 (19.6)
.007*
32 (55.2) 26 (44.8)
709 (70.2) 301 (29.8)
.019*
2.4 6 0.93 (0-4)
2.07 6 0.98 (0-4)
.010*
4 (6.9) 54 (93.1)
75 (7.4) 935 (92.6)
.999
21 (36.2) 37 (63.8)
170 (16.8) 840 (83.2)
\.001*
1 (1.7) 57 (98.3)
15 (1.5) 995 (98.5)
.593
56.7 6 83.9 (1-300)
32.4 6 56.2 (1-365)
.058
40.0 6 42.5 (1-200)
20.9 6 37.4 (1-365)
.009*
a
Data are presented as number (percentage) for each group unless indicated otherwise. *Statistically significant.
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Table 4. Multivariate Stepwise Logistic Regression Analysis for Incidental Parathyroidectomy. 95% Confidence Interval Variable Age Thyroid gland weight (g) Mean number of identified parathyroid glands Operation time (minutes) Gender Preoperative diagnosis benigna Mini invasive thyroidectomy Substernal extension Tracheal deviation Total number of identified parathyroid glands (3-4)b Biclamp hemostasis Final thyroid histologyc Graves’ disease Hashimoto thyroiditis Follicular adenoma Thyroid cancer Central neck dissection Procedured Total thyroidectomy Completion thyroidectomy
Odds Ratio
Lower
Upper
P Value
0.998 0.989 1.089 1.003 1.240 4.075 2.040 1.161 1.299 1.230 1.029
0.978 0.972 0.636 0.991 0.483 0.191 0.254 0.276 0.386 0.448 0.558
1.019 1.007 1.864 1.014 3.186 86.891 16.383 4.885 4.370 3.379 1.894
.860 .225 .755 .659 .654 .368 .502 .838 .673 .688 .929
2.192 3.577 0.389 3.577 13.770
1.157 0.346 0.914 0.0510 0.762
4.158 3.187 13.994 2.960 248.577
.016* .932 .067 .362 .076
3.937 0.0
1.462 0.0
10.601 —
.007* .984
a
Versus malignant preoperative diagnosis. Versus 0-2 parathyroid glands identified intraoperatively. c Versus multinodular goiter. d Versus lobectomy. *Statistically significant. b
level of 2.14 mmol/L at 3 days postoperatively, with a maximum increase of 2.20 mmol/L at 5 days postoperatively. On the other hand, total calcium level in non-IP group declined from a preoperative mean value of 2.39 mmol/L to 2.19 mmol/L detected at 2 hours postoperatively and of 2.18 mmol/L at 24 hours postoperatively (with a maximum slope of 8.8% from the preoperative value). Then the decrease returned to positivity with a mean total calcium level of 2.23 mmol/L at 3 days and of 2.29 mmol/L at 5 days postoperatively. Serum ionized calcium level in patients with incidental parathyroidectomy dropped from a preoperative mean level of 1.19 mmol/L to a mean level of 1.14 mmol/L at 2 hours postoperatively, and continued to decline to a mean level of 1.13/mmol/L at 24 hours and at 3 days postoperatively (with a maximum slope of 5.0% from the preoperative value). Then the decreased level slowly increased to a mean level of 1.16 mmol/L at 5 days postoperatively. Conversely, ionized calcium level in non-IP group dropped from a preoperative mean level of 1.19 mmol/L to a mean level of 1.16 mmol/L detected both at 2 hours and at 24 hours postoperatively (with a maximum slope of 2.5% from the preoperative value). Then the decline returned to positivity with a mean level of 1.17 mmol/L at 3 days and of 1.18 mmol/L at 5 days postoperatively.
Although the measurements of repeated phosphorus level and PTH level differed between IP an non-IP groups and copied similar declines as total calcium and ionized calcium levels, these 2 variables failed to reach statistical significance (P = .082, Figure 3; P = .067, Figure 4, respectively).
Discussion There is no doubt that postoperative hypocalcemia remains the major concern following thyroidectomy. Apparently, the reported incidence for temporary hypocalcemia and permanent hypoparathyroidism varies widely in the literature from 5.4% to 52.5%,1,3,10-12 and from 0% to 5.5%,3,10,11,13-16 respectively. In our study, overall temporary hypocalcemia and permanent hypoparathyroidism occurred in 17.3% and 1.5%, respectively. The importance of systemic identification of all 4 parathyroid glands during thyroid surgery remains controversial.3,6,7,13,17-20 To the best of our knowledge, only a few studies investigated the potential impact of parathyroid glands identification on the occurrence of incidental parathyroidectomy.6,11 Univariate analysis identified that visualization of 3-4 parathyroid glands was associated with a higher risk of incidental parathyroidectomy in comparison when 0-2 glands were visualized, and this difference was statistically significant (P = .019). We might assume that
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Table 5. Univariate ANOVA of Preoperative and Postoperative Laboratory Data in Relation to Incidental Parathyroidectomy. Variable Total calcium (mmol/l) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days Total phosphorus (mmol/l) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days Ionized calcium (mmol/l) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days Parathyroid hormone (pmol/ml) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days
Incidental Parathyroidectomy Group (n = 58)a
No Incidental Parathyroidectomy Group (n = 1010)a
P Value
2.42 6 2.13 6 2.07 6 2.14 6 2.20 6
0.12 0.19 0.21 0.18 0.17
2.39 6 0.13 2.19 6 0.17 2.18 6 0.19 2.23 6 0.19 2.29 6 0.17
.064 .010* 1.638 \.001* \.001*
1.15 6 0.87 6 1.07 6 1.19 6 1.23 6
0.17 0.23 0.27 0.24 0.28
1.12 6 0.19 0.93 6 0.27 1.10 6 0.25 1.17 6 0.27 1.18 6 0.24
.228 .077 .312 .679 .167
1.19 6 1.14 6 1.13 6 1.13 6 1.16 6
0.06 0.09 0.07 0.09 0.10
1.19 6 0.08 1.16 6 0.08 1.16 6 0.08 1.17 6 0.09 1.18 6 0.08
.824 .068 .024* .002* .254
5.27 6 2.86 6 3.05 6 3.11 6 3.06 6
1.45 2.47 2.18 2.07 2.00
5.26 6 1.94 3.56 6 2.05 3.61 6 1.84 3.57 6 1.77 3.68 6 1.74
.981 .012* .023* .056 .009*
a
Data are presented as mean 6 SD. *Statistically significant.
Figure 1. Changes in total calcium level before and after total thyroidectomy in 2 study groups. All values shown are means (P \ .001, MANOVA test).
Figure 2. Changes in ionized calcium level before and after total thyroidectomy in 2 study groups. All values shown are means (P = .020, MANOVA test).
this finding has something to do with intracapsular localization of parathyroid glands which are firmly adherent to the thyroid surface and therefore more damageable. Although intracapsulary located parathyroid glands are encountered easily, on the other hand their vascular supply or the parenchyma itself is more vulnerable to potential traumatic changes. In the present study, which is believed the largest one in a sample size published so far, the incidence of incidental parathyroidectomy was 5.4%, which well compares with
other reported studies.5,21-24 The relationship between incidental parathyroidectomy and postoperative hypocalcemia is debated in the literature.5,11,21-30 In our study, univariate analysis identified incidental parathyroidectomy as being significantly associated with temporary hypocalcemia (P \ .001). This finding is supported by a statistically significant correlation between postoperative repeated biochemical measurements and incidental parathyroidectomy. Such an assessment, using ANOVA and MANOVA analyses, has not been reported, until now, in the literature.
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Figure 3. Changes in phosphorus level before and after total thyroidectomy in 2 study groups. All values shown are means (P = .082, MANOVA test).
a wide range of indications, and assorted types of surgical procedures. Second, total calcium level were not adjusted for serum albumin level. We did, however, utilize ionized calcium level as a further diagnostic criterion of hypocalcemia. In addition, we comprehensively analyzed the association between parathyroid glands identification and serial postoperative total calcium, ionized calcium, phosphorus, and PTH measurements. Third, the assessment of the absence or the presence of parathyroid glands identified during surgery is an explicitly nonobjective appraisal and can differ among surgeons, and among reported studies. Fourth, 5 mm serial sectioning of thyroid specimen during histological analysis was performed. Finally, inherent selection bias in reported results must be accounted for in a nonmatched case control study design. Undefined confounding factors, in defiance of covariates applied in regression analysis with backward elimination, might influence the result.
Conclusions
Figure 4. Changes in parathyroid hormone (PTH) level before and after total thyroidectomy in 2 study groups. All values shown are means (P = .067, MANOVA test).
Incidentally excised parathyroid glands have been reported in an intrathyroidal location from 15% to 58%.5,6,23,31,32 In our study the reported incidence of intrathyroidally located parathyroid glands were 20% and intracapsular location accounted for 21.4%. This variable location of the parathyroid glands assuredly contributes to the risk of incidental removal. Thus, even in the hands of experienced thyroid surgeons this complication can occur and is questionable whether incidental parathyroidectomy is thoroughly avoidable. We found significant correlation between total thyroidectomy and incidental parathyroidectomy (P = .003), and between longer operation time and the incidence of incidental parathyroidectomy (P = .017). This seems in accordance with common anticipation, when more advanced operations require longer operation time, but potentially result in more frequent postoperative complications. Furthermore, univariate analysis (P = .007) and multivariate analysis (P = .016) revealed Graves’ disease as a factor being significantly associated with incidental parathyroidectomy. This is likely related to the typical morphological features of Graves’ disease, which causes the dissection more difficult due to fragility, increased vascularity, and higher bleeding tendency. Thus, more focused vigilance while performing thyroidectomy in patients with Graves’ disease might reduce the jeopardy of incidental parathyroidectomy. There are several limitations of the current study. First, although large, the study population is nonhomogenous due to inclusion of patients undergoing thyroid surgery for
The incidence of incidental parathyroidectomy was 5.4% in our study. Most of these parathyroid glands were in extracapsular (58.6%) and intracapsular (21.4%) locations, but 20.0% parathyroid glands were located intrathyroidally thus a certain percentage of this incident is apparently unavoidable. Total thyroidectomy, Graves’ disease, longer operation time, and identification of more than 3 parathyroid glands seemed to be univariate predictive factors for incidental parathyroidectomy. Independent predictors of incidental parathyroidectomy identified by multivariate analysis were total thyroidectomy and Graves’ disease. Our results showed that incidental parathyroidectomy is significantly associated with temporary hypocalcemia, but not with permanent hypoparathyroidism. Every effort should be made to maximally reduce this awkward but preventable complication during thyroid surgery. Author Contributions Pavol Prazˇenica, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of the manuscript for important intellectual content, final approval of manuscript version to be published; Kieran O’Driscoll, analysis and interpretation of data, drafting of manuscript, final approval of manuscript version to be published; Richard Holy´, acquisition of data, critical revision of the manuscript for important intellectual content, final approval of manuscript version to be published.
Disclosures Competing interests: None. Sponsorships: None. Funding source: None.
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32.
minimizes the risk of permanent hypoparathyroidism. Zentralbl Chir. 2002;127:439-442. Abboud B, Sargi Z, Akkam M, Sleilaty F. Risk factors for postthyroidectomy hypocalcemia. J Am Coll Surg. 2002;195: 456-461. Bergamaschi R, Becouarn G, Ronceray J, Arnaud JP. Morbidity of thyroid surgery. Am J Surg. 1998;176:71-75. Page C, Strunski V. Parathyroid risk in total thyroidectomy for bilateral, benign, multinodular goitre: report of 351 surgical cases. J Laryngol Otol. 2007;121:237-241. Sheahan P, Mehanna R, Basheeth N, Murphy MS. Is systematic identification of all four parathyroid glands necessary during total thyroidectomy? A prospective study. Laryngoscope. 2013; 123:2324-2328. Erbil Y, Barbaros U, Ozbey N, et al. Risk factors of incidental parathyroidectomy after thyroidectomy for benign thyroid disorders. Int J Surg. 2009;7:58-61. Irkorucu O, Tascilar O, Cakmak GK, et al. Inadvertent parathyroidectomy and temporary hypocalcemia: an adverse natural outcome or a true complication during thyroidectomy? Endocr Regul. 2007;41:143-148. Lee NJ, Blakey JD, Bhuta S, Calcaterra TC. Unintentional parathyroidectomy during thyroidectomy. Laryngoscope. 1999; 109:1238-1240. Manouras A, Markogiantpdnakis H, Lagoudianakis E, et al. Unintentional parathyroidectomy during total thyroidectomy. Head Neck. 2008;30:497-502. Rix TE, Sinha P. Inadvertent parathyroid excision during thyroid surgery. Surgeon. 2006;4:339-342. Qasaimeh GR, Al Nemri S, Al Omari AK. Incidental extirpation of the parathyroid glands at thyroid surgery: risk factors and post-operative hypocalcemia. Eur Arch Otorhinolaryngol. 2011;268:1047-1051. Sippel RS, Ozgu¨l O, Hartig GK, et al. Risks and consequences of incidental parathyroidectomy during thyroid resection. Aust N Z J Surg. 2007;77:33-36. Spiliotis J, Vaxevanidou A, Sergouniotis F, et al. Risk factors and consequences of incidental parathyroidectomy during thyroidectomy. Am Surg. 2010;76:436-441. Sitges-Serra A, Ruiz S, Girvent M, et al. Outcome of protracted hypoparathyroidism after total thyroidectomy. Br J Surg. 2010;97:1687-1695. Khairy GA, Al-Saif A. Incidental parathyroidectomy during thyroid resection: incidence, risk factors, and outcome. Ann Saudi Med. 2011;31:274-278. Lin DT, Patel SG, Shaha AR, et al. Incidence of inadvertent parathyroid removal during thyroidectomy. Laryngoscope. 2002;112:608-611. Youssef T, Gaballah G, Abd-Elaal E, El-Dosoky E. Assessment of risk factors of incidental parathyroidectomy during thyroid surgery: a prospective study. Int J Surg. 2010;8: 207-211.
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Incidental Parathyroidectomy during Thyroid Surgery Using Capsular Dissection Technique
Otolaryngology– Head and Neck Surgery 2014, Vol. 150(5) 754–761 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599814521365 http://otojournal.org
Pavol Prazˇenica, MD, PhD1,2, Kieran O’Driscoll, FRCSI, FCS(ECSA) ORL Hon2, and Richard Holy´, MD1
No sponsorships or competing interests have been disclosed for this article.
Abstract Objective. To identify incidence, preoperative features, surgical factors, and postoperative events of incidental parathyroidectomy (IP) during thyroidectomy. Study Design. A total of 1068 consecutive patients who underwent thyroidectomy performed by a single surgeon between January 2003 and April 2012 were enrolled in retrospective study with prospectively collected data. Setting. University hospital. Subjects and Methods. To assess the impact of IP on study variables, patients were stratified into 2 study groups: IP group and non-IP group. Univariate and multivariate analyses identified significant correlates of IP. Results. In all, 5.4% patients experienced IP. Significant difference (P \.001) was in incidence of temporary hypocalcemia between IP group (36.2%) and non-IP group (16.8%). Multivariable logistic regression model identified total thyroidectomy (odds ratio 3.937, 95% confidence interval [CI] 1.462-10.601, P = .007) and Graves’ disease (odds ratio 2.192, 95% CI 1.157-4.158, P = .016) as risk-adjusted factors associated with IP. Multivariate analysis of repeated measures identified statistically significant difference of repeated total calcium level (P \ .001) and ionized calcium level (P = .020) between study groups. Conclusion. IP during thyroidectomy might be potential complication. Total thyroidectomy, Graves’ disease, longer operation time, and identification 3 and more parathyroid glands seemed to be predictive factors for IP. IP is significantly associated with temporary hypocalcemia, but not with permanent hypoparathyroidism.
Keywords incidental parathyroidectomy, thyroidectomy, thyroid, hypocalcemia, capsular dissection Received November 26, 2013; revised December 17, 2013; accepted January 7, 2014.
Introduction Thyroidectomy is a very common surgical procedure. Despite meticulous surgical technique, parathyroid dysfunction during thyroidectomy may occur and makes this operation challenging. Many factors may contribute to this inconvenience.1-4 Nevertheless, every surgeon is sporadically disappointed by a histopathology report indicating parathyroid tissue along with the thyroid specimen. Although it has been stated that removal of 1 or 2 parathyroid glands does not necessarily lead to hypoparathyroidism,5-8 theoretically, avoiding the parathyroid glands incidentally removed may lower the incidence of postoperative hypocalcemia. This fact might be of high importance for a surgeon in terms of identifying the risk factors that may potentially bring about the incidental removal of parathyroid glands. The present study was designed to evaluate the clinical significance and the incidence of incidental parathyroidectomy during total thyroidectomy and, furthermore, to assess potential risk factors associated with this undesirable incident.
Material and Methods Patient Characteristics and Study Variables Consecutive patients undergoing thyroidectomy (total thyroidectomy, completion thyroidectomy, or lobectomy) performed at the Department of Otolaryngology in the Military University Hospital, Prague, Czech Republic, between January 2003 and April 2012, were enrolled in this retrospective study with prospectively collected data. A single surgeon carried out all operations. Informed written consent was required from all patients to collect their data and to be included in the trial. The institutional review board of the Military University Hospital in Prague under the patronage of the Ministry of Health of the Czech Republic approved the study. Patients with central neck dissection were included in 1 Department of Otolaryngology, 3rd Medical Faculty of the Charles University, Military University Hospital, Prague, Czech Republic 2 Department of Otolaryngology, Midland Regional Hospital, Tullamore, Ireland
Corresponding Author: Pavol Prazˇenica, MD, PhD, Department of Otolaryngology, 3rd Medical Faculty of the Charles University, Military University Hospital, U vojenske´ nemocnice 1200, 16902 Prague 6, Czech Republic. Email: [email protected]
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the study. Exclusion criteria involved the following conditions: revision surgery for recurrent disease, modified or radical neck dissection, extensive thyroid procedures extending to surrounding structures, and procedures for hyperparathyroidism. All relevant data regarding patients’ demographics, preoperative findings, surgical procedure, histological analysis, and postoperative and follow-up events were gathered.
Brief Surgical Comments in Relation to the Parathyroid Glands All operations were performed in a similar fashion throughout the study period strictly following the capsular principle of dissection.9 The preservation by meticulous dissection of the parathyroid glands was attempted. All terminal branches of the superior and inferior thyroid arteries were ligated distally as close to the thyroid capsule as possible. The aim of this technique was liberating the parathyroid glands from the surface of the thyroid gland with an uncompromised vascular supply. Excessive dissection to identify all the glands was avoided as this approach could potentially lead to jeopardizing of vascularization of the remaining gland. After removal of the thyroid lobe, all parathyroid glands left in situ were examined for any signs of devascularization. The resected thyroid gland was inspected for any unintentionally removed parathyroid glands. If this happened, all devascularized or removed glands were autotransplanted into the muscle pocket created in the sternocleidomastoid muscle after mincing into small pieces at the end of the procedure. Histological examination was performed in all resected thyroid glands. For histological analysis of the thyroid specimens, 5 mm serial sectioning was used.
Postoperative Follow-up All patients were closely monitored for postoperative clinical or biochemical hypocalcemia. Serum total calcium, ionized calcium, phosphorus and parathyroid hormone (PTH) levels were collected before the procedure and at 2 hours, 24 hours, 3 days, and 5 days after the operation. We define hypocalcemia as a total calcium level less than 2.00 mmol/l (normal range 2.05-2.75 mmol/L) or ionized calcium less than 1.00 mmol/l (normal range 1.00-1.3 mmol/L) obtained on at least 1 postoperative measurement, with or without clinical symptoms. Normal range for phosphorus level in our laboratory is 0.65-1.6 mmol/L, while the normal PTH assay is 1.6-6.9 pmol/L (to convert to pg/mL, multiply 9.43). Patients with hypocalcemia for more than 2 measurements commenced oral calcium substitution with Calcium carbonate (1500 to 3000 mg daily). In case of severe symptomatic hypocalcemia intravenous Calcium gluconate and vitamin D (1.25-dihydroxycholecalciferol 0.25-0.50 mg daily) were administered. The dose was then adjusted to achieve normal calcium level. All patients who developed either biochemical or clinical hypocalcemia were repeatedly monitored for calcium, ionized calcium, and phosphorus and PTH levels until final termination of substitutive therapy with the last measurement 2 weeks after complete
withdrawal of substitution therapy. Hypocalcemia was considered as permanent when requiring oral calcium or vitamin D (1.25-dihydroxycholecalciferol) substitution regardless PTH level more than 1 year after operation.
Statistical Analysis The design of the study allowed collecting data prospectively in a determined computer database (Microsoft Office Excel). Statistical analysis was performed using SPSS 21.0 software package (SPSS, Chicago, Illinois). To evaluate the impact of incidental parathyroidectomy on study variables, patients were stratified into 2 study groups as a result of the incidental parathyroidectomy: that without incidental parathyroidectomy (non-IP group) and that with incidental parathyroidectomy (IP group), and univariate analysis between these groups was performed. Continuous data are reported as mean 6 SD, medians, and interquartile range, as appropriate. Two-sample Mann–Whitney test was used to compare differences between patients with or without incidental parathyroidectomy. Categorical and dichotomous variables are presented as frequencies or percents and are compared using Fisher’s exact test. Multivariable regression logistic model with stepwise elimination was developed to test the difference between groups with or without incidental parathyroidectomy. In this model, the main binary dependant variables included incidental parathyroidectomy and the covariates included preoperative characteristics, and operative features. Covariates serving as a confounding factor or as an effect-influencing modifier were included. Confounder-adjusted measures of association are reported as odds ratios (OR) with a 95% confidence interval. Data regarding calcium, ionized calcium, phosphorus, and PTH levels in relation to groups with or without incidental parathyroidectomy were evaluated by the univariate analysis of variance (ANOVA) and the multivariate analysis of variance (MANOVA) for repeated measures. All statistical tests were 2-sided, and P \ .05 was considered statistically significant.
Results A total of 1068 consecutive patients who underwent thyroidectomy during the study period were included in the study. Patients’ demographics, operative details, histological findings, and postoperative hypocalcemia data are reported in Table 1. Data concerning incidentally removed parathyroid glands are summarized in Table 2. The number of patients with 0, 1, 2, 3, 4 parathyroid glands identified was 51, 229, 461, 234, 93, respectively. Table 3 provides the summary of univariate analysis of diverse variables and incidental parathyroidectomy. The mean number of parathyroid glands identified in IP group versus non-IP group (2.4 vs 2.07) was statistically significant (P = .010). Similarly, the risk of incidental removal was significantly higher when 0-2 versus 3-4 parathyroid glands were identified (P = .019). The statistically significant difference (P \ .001) was observed between the
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Table 1. Patients’ Preoperative Findings, Surgical Procedure, Histological Analysis, Postoperative Complications. Total Number of Patients (N = 1068)a
Variable Preoperative diagnosis Benign Malignant Procedure Total thyroidectomy Lobectomy Completion thyroidectomy Mini invasive thyroidectomy Yes No Central neck dissection Yes No Biclamp hemostasis Yes No Thyroid gland weight (g) Mean 6 SD Median (range) Substernal extension Yes No Tracheal deviation Yes No Operation time (minutes) Mean 6 SD Median (range) Final thyroid histology Multinodular goiter Graves’ disease Hashimoto thyroiditis Follicular adenoma Thyroid cancer Total number of identified parathyroid glands 0-2 3-4 Parathyroid autotransplantation Yes No Temporary hypocalcemia Yes No Permanent hypoparathyroidism Yes No
964 (90.3) 104 (9.7) 756 (70.8) 281 (26.3) 31 (2.9) 54 (5.1) 1014 (94.9) 71 (6.6) 997 (93.4) 323 (30.2) 745 (69.8) 27.1 6 24.1 20.0 (3-200) 85 (8.0) 983 (92.0) 135 (12.6) 933 (87.4)
Table 2. Characteristics of Incidentally Removed Parathyroids Glands. Variable Incidental parathyroidectomy (total number of patients) Number of removed parathyroid glands One removed parathyroid gland Two removed parathyroid glands Total number of removed parathyroid glands Number of identified parathyroid glands Mean 6 SD Median Range Diameter of removed parathyroid gland (mm) Mean 6 SD Median Range Location of removed parathyroid gland Extracapsular Intracapsular Intrathyroidal Histological features of removed parathyroid gland Normal Adenomatous Hyperplastic
Valuea 58 (5.4)
46 (79.3) 12 (20.7) 70 2.23 6 0.95 2 0-4
3.6 6 1.9 3,4 0.9-7.5
41 (58.6) 15 (21.4) 14 (20.0)
54 (93.1) 3 (5.2) 1 (1.7)
a
Data are presented as number (percentage) unless indicated otherwise.
116 6 34.3 115 (45-240) 605 220 77 43 123
(56.7) (20.6) (7.2) (4.0) (11.5)
741 (69.4) 327 (30.6) 79 (7.4) 989 (92.6) 185 (17.3) 883 (82.7) 16 (1.5) 1052 (98.5)
a
Data are presented as number (percentage) unless indicated otherwise.
incidence of temporary hypocalcemia between IP group (36.2%) and non-IP group (16.8%).
The results of stepwise multivariate logistic regression analysis are presented in Table 4. This revealed statistically significant correlation between Graves’ disease (OR 2.192, 95% confidence interval [CI] 1.157-4.158, P = .016) and incidental parathyroidectomy, and between total thyroidectomy (OR 3.937, 95% CI 1.462-10.601, P = .007) and incidental parathyroidectomy. The results of the ANOVA are presented in Table 5. The statistical significant difference reached the following measures: the total calcium levels measured at 2 hours, 3 days, and 5 days postoperatively, the ionized calcium levels measured at 24 hours and 3 days postoperatively, and PTH levels measured at 2 hours, 24 hours, and 5 days postoperatively. The MANOVA revealed the difference of repeated total calcium level and ionized calcium level between IP and non-IP groups being statistically significant (P \ .001, Figure 1; P = .020, Figure 2, respectively). Serum total calcium level in patients with incidental parathyroidectomy decreased from a preoperative mean level of 2.42 mmol/L to a mean level of 2.13 mmol/L at 2 hours postoperatively, with a continual decline to a mean level of 2.07 mmol/L at 24 hours postoperatively (with a maximum slope of 14.7% from the preoperative value). Then the decreased level increased and reached a mean
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Table 3. Univariate Analysis of Patients’ Preoperative Characteristics, Operative Variables, and Postoperative Events in Relation to Incidental Parathyroidectomy. Variable Gender Male Female Age (y) mean 6 SD (range) Preoperative diagnosis Benign Malignant Procedure Total thyroidectomy Mini invasive thyroidectomy Yes No Central neck dissection Yes No Biclamp hemostasis Yes No Thyroid gland weight (g) mean 6 SD (range) Substernal extension Yes No Tracheal deviation Yes No Operation time (minutes) mean 6 SD (range) Final thyroid histology Graves’ disease Total number of identified parathyroid glands 0-2 3-4 Mean number of identified parathyroid glands Mean 6 SD (range) Parathyroid autotransplantation Yes No Temporary hypocalcemia Yes No Permanent hypoparathyroidism Yes No Total calcium recovery time (days) Mean 6 SD (range) Parathyroid hormone recovery time (days) Mean 6 SD (range)
Incidental Parathyroidectomy Group (n = 58)a
No Incidental Parathyroidectomy Group (n = 1010)a
6 (10.3) 52 (89.7) 50.2 6 14,28 (24-79)
137 (13.6) 873 (89.7) 50.8 6 14.25 (22-86)
.690
51 (87.9) 7 (12.1)
914 (95.5) 96 (12.1)
.492
52 (89.7)
704 (69.7)
.003*
1 (1.7) 57 (98.3)
53 (5.2) 957 (94.8)
.357
7 (12.1) 51 (87.9)
64 (6.3) 946 (93.7)
.099
305 (30.2) 705 (69.8) 28.1 6 24.6 (2-200)
.884
82 (8.1) 928 (91.9)
.617
18 (31.0) 40 (69.0) 25.9 6 23.6 (4-144) 3 (5.2) 55 (94.8) 4 (6.9) 54 (93.1) 121.6 6 3.0 (50-240)
131 (13.0) 879 (87.0) 111.0 6 35.6 (45-240)
P Value
.687
.593
.223 .017*
22 (38.0)
198 (19.6)
.007*
32 (55.2) 26 (44.8)
709 (70.2) 301 (29.8)
.019*
2.4 6 0.93 (0-4)
2.07 6 0.98 (0-4)
.010*
4 (6.9) 54 (93.1)
75 (7.4) 935 (92.6)
.999
21 (36.2) 37 (63.8)
170 (16.8) 840 (83.2)
\.001*
1 (1.7) 57 (98.3)
15 (1.5) 995 (98.5)
.593
56.7 6 83.9 (1-300)
32.4 6 56.2 (1-365)
.058
40.0 6 42.5 (1-200)
20.9 6 37.4 (1-365)
.009*
a
Data are presented as number (percentage) for each group unless indicated otherwise. *Statistically significant.
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Table 4. Multivariate Stepwise Logistic Regression Analysis for Incidental Parathyroidectomy. 95% Confidence Interval Variable Age Thyroid gland weight (g) Mean number of identified parathyroid glands Operation time (minutes) Gender Preoperative diagnosis benigna Mini invasive thyroidectomy Substernal extension Tracheal deviation Total number of identified parathyroid glands (3-4)b Biclamp hemostasis Final thyroid histologyc Graves’ disease Hashimoto thyroiditis Follicular adenoma Thyroid cancer Central neck dissection Procedured Total thyroidectomy Completion thyroidectomy
Odds Ratio
Lower
Upper
P Value
0.998 0.989 1.089 1.003 1.240 4.075 2.040 1.161 1.299 1.230 1.029
0.978 0.972 0.636 0.991 0.483 0.191 0.254 0.276 0.386 0.448 0.558
1.019 1.007 1.864 1.014 3.186 86.891 16.383 4.885 4.370 3.379 1.894
.860 .225 .755 .659 .654 .368 .502 .838 .673 .688 .929
2.192 3.577 0.389 3.577 13.770
1.157 0.346 0.914 0.0510 0.762
4.158 3.187 13.994 2.960 248.577
.016* .932 .067 .362 .076
3.937 0.0
1.462 0.0
10.601 —
.007* .984
a
Versus malignant preoperative diagnosis. Versus 0-2 parathyroid glands identified intraoperatively. c Versus multinodular goiter. d Versus lobectomy. *Statistically significant. b
level of 2.14 mmol/L at 3 days postoperatively, with a maximum increase of 2.20 mmol/L at 5 days postoperatively. On the other hand, total calcium level in non-IP group declined from a preoperative mean value of 2.39 mmol/L to 2.19 mmol/L detected at 2 hours postoperatively and of 2.18 mmol/L at 24 hours postoperatively (with a maximum slope of 8.8% from the preoperative value). Then the decrease returned to positivity with a mean total calcium level of 2.23 mmol/L at 3 days and of 2.29 mmol/L at 5 days postoperatively. Serum ionized calcium level in patients with incidental parathyroidectomy dropped from a preoperative mean level of 1.19 mmol/L to a mean level of 1.14 mmol/L at 2 hours postoperatively, and continued to decline to a mean level of 1.13/mmol/L at 24 hours and at 3 days postoperatively (with a maximum slope of 5.0% from the preoperative value). Then the decreased level slowly increased to a mean level of 1.16 mmol/L at 5 days postoperatively. Conversely, ionized calcium level in non-IP group dropped from a preoperative mean level of 1.19 mmol/L to a mean level of 1.16 mmol/L detected both at 2 hours and at 24 hours postoperatively (with a maximum slope of 2.5% from the preoperative value). Then the decline returned to positivity with a mean level of 1.17 mmol/L at 3 days and of 1.18 mmol/L at 5 days postoperatively.
Although the measurements of repeated phosphorus level and PTH level differed between IP an non-IP groups and copied similar declines as total calcium and ionized calcium levels, these 2 variables failed to reach statistical significance (P = .082, Figure 3; P = .067, Figure 4, respectively).
Discussion There is no doubt that postoperative hypocalcemia remains the major concern following thyroidectomy. Apparently, the reported incidence for temporary hypocalcemia and permanent hypoparathyroidism varies widely in the literature from 5.4% to 52.5%,1,3,10-12 and from 0% to 5.5%,3,10,11,13-16 respectively. In our study, overall temporary hypocalcemia and permanent hypoparathyroidism occurred in 17.3% and 1.5%, respectively. The importance of systemic identification of all 4 parathyroid glands during thyroid surgery remains controversial.3,6,7,13,17-20 To the best of our knowledge, only a few studies investigated the potential impact of parathyroid glands identification on the occurrence of incidental parathyroidectomy.6,11 Univariate analysis identified that visualization of 3-4 parathyroid glands was associated with a higher risk of incidental parathyroidectomy in comparison when 0-2 glands were visualized, and this difference was statistically significant (P = .019). We might assume that
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Table 5. Univariate ANOVA of Preoperative and Postoperative Laboratory Data in Relation to Incidental Parathyroidectomy. Variable Total calcium (mmol/l) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days Total phosphorus (mmol/l) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days Ionized calcium (mmol/l) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days Parathyroid hormone (pmol/ml) Preoperative Postoperative 2 hours Postoperative 24 hours Postoperative 3 days Postoperative 5 days
Incidental Parathyroidectomy Group (n = 58)a
No Incidental Parathyroidectomy Group (n = 1010)a
P Value
2.42 6 2.13 6 2.07 6 2.14 6 2.20 6
0.12 0.19 0.21 0.18 0.17
2.39 6 0.13 2.19 6 0.17 2.18 6 0.19 2.23 6 0.19 2.29 6 0.17
.064 .010* 1.638 \.001* \.001*
1.15 6 0.87 6 1.07 6 1.19 6 1.23 6
0.17 0.23 0.27 0.24 0.28
1.12 6 0.19 0.93 6 0.27 1.10 6 0.25 1.17 6 0.27 1.18 6 0.24
.228 .077 .312 .679 .167
1.19 6 1.14 6 1.13 6 1.13 6 1.16 6
0.06 0.09 0.07 0.09 0.10
1.19 6 0.08 1.16 6 0.08 1.16 6 0.08 1.17 6 0.09 1.18 6 0.08
.824 .068 .024* .002* .254
5.27 6 2.86 6 3.05 6 3.11 6 3.06 6
1.45 2.47 2.18 2.07 2.00
5.26 6 1.94 3.56 6 2.05 3.61 6 1.84 3.57 6 1.77 3.68 6 1.74
.981 .012* .023* .056 .009*
a
Data are presented as mean 6 SD. *Statistically significant.
Figure 1. Changes in total calcium level before and after total thyroidectomy in 2 study groups. All values shown are means (P \ .001, MANOVA test).
Figure 2. Changes in ionized calcium level before and after total thyroidectomy in 2 study groups. All values shown are means (P = .020, MANOVA test).
this finding has something to do with intracapsular localization of parathyroid glands which are firmly adherent to the thyroid surface and therefore more damageable. Although intracapsulary located parathyroid glands are encountered easily, on the other hand their vascular supply or the parenchyma itself is more vulnerable to potential traumatic changes. In the present study, which is believed the largest one in a sample size published so far, the incidence of incidental parathyroidectomy was 5.4%, which well compares with
other reported studies.5,21-24 The relationship between incidental parathyroidectomy and postoperative hypocalcemia is debated in the literature.5,11,21-30 In our study, univariate analysis identified incidental parathyroidectomy as being significantly associated with temporary hypocalcemia (P \ .001). This finding is supported by a statistically significant correlation between postoperative repeated biochemical measurements and incidental parathyroidectomy. Such an assessment, using ANOVA and MANOVA analyses, has not been reported, until now, in the literature.
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Figure 3. Changes in phosphorus level before and after total thyroidectomy in 2 study groups. All values shown are means (P = .082, MANOVA test).
a wide range of indications, and assorted types of surgical procedures. Second, total calcium level were not adjusted for serum albumin level. We did, however, utilize ionized calcium level as a further diagnostic criterion of hypocalcemia. In addition, we comprehensively analyzed the association between parathyroid glands identification and serial postoperative total calcium, ionized calcium, phosphorus, and PTH measurements. Third, the assessment of the absence or the presence of parathyroid glands identified during surgery is an explicitly nonobjective appraisal and can differ among surgeons, and among reported studies. Fourth, 5 mm serial sectioning of thyroid specimen during histological analysis was performed. Finally, inherent selection bias in reported results must be accounted for in a nonmatched case control study design. Undefined confounding factors, in defiance of covariates applied in regression analysis with backward elimination, might influence the result.
Conclusions
Figure 4. Changes in parathyroid hormone (PTH) level before and after total thyroidectomy in 2 study groups. All values shown are means (P = .067, MANOVA test).
Incidentally excised parathyroid glands have been reported in an intrathyroidal location from 15% to 58%.5,6,23,31,32 In our study the reported incidence of intrathyroidally located parathyroid glands were 20% and intracapsular location accounted for 21.4%. This variable location of the parathyroid glands assuredly contributes to the risk of incidental removal. Thus, even in the hands of experienced thyroid surgeons this complication can occur and is questionable whether incidental parathyroidectomy is thoroughly avoidable. We found significant correlation between total thyroidectomy and incidental parathyroidectomy (P = .003), and between longer operation time and the incidence of incidental parathyroidectomy (P = .017). This seems in accordance with common anticipation, when more advanced operations require longer operation time, but potentially result in more frequent postoperative complications. Furthermore, univariate analysis (P = .007) and multivariate analysis (P = .016) revealed Graves’ disease as a factor being significantly associated with incidental parathyroidectomy. This is likely related to the typical morphological features of Graves’ disease, which causes the dissection more difficult due to fragility, increased vascularity, and higher bleeding tendency. Thus, more focused vigilance while performing thyroidectomy in patients with Graves’ disease might reduce the jeopardy of incidental parathyroidectomy. There are several limitations of the current study. First, although large, the study population is nonhomogenous due to inclusion of patients undergoing thyroid surgery for
The incidence of incidental parathyroidectomy was 5.4% in our study. Most of these parathyroid glands were in extracapsular (58.6%) and intracapsular (21.4%) locations, but 20.0% parathyroid glands were located intrathyroidally thus a certain percentage of this incident is apparently unavoidable. Total thyroidectomy, Graves’ disease, longer operation time, and identification of more than 3 parathyroid glands seemed to be univariate predictive factors for incidental parathyroidectomy. Independent predictors of incidental parathyroidectomy identified by multivariate analysis were total thyroidectomy and Graves’ disease. Our results showed that incidental parathyroidectomy is significantly associated with temporary hypocalcemia, but not with permanent hypoparathyroidism. Every effort should be made to maximally reduce this awkward but preventable complication during thyroid surgery. Author Contributions Pavol Prazˇenica, acquisition of data, analysis and interpretation of data, drafting of manuscript, critical revision of the manuscript for important intellectual content, final approval of manuscript version to be published; Kieran O’Driscoll, analysis and interpretation of data, drafting of manuscript, final approval of manuscript version to be published; Richard Holy´, acquisition of data, critical revision of the manuscript for important intellectual content, final approval of manuscript version to be published.
Disclosures Competing interests: None. Sponsorships: None. Funding source: None.
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