Introduction
In experienced hands, thyroidectomy is associated with a morbidity as low as 2%[1] if parathyroid glands and laryngeal nerves are identified and preserved. Awareness of the anatomic relationship of parathyroid gland to the thyroids is important in preventing postoperative hypocalcemia. In the literature, the incidence of temporary hypocalcemia after thyroid surgery ranges from 1.6% to 50%, and permanent hypocalcemia occurs after 1.5% to 4% of surgeries.[2–6] The etiology includes surgical trauma, devascularization, and inadvertent parathyroid excision (IPE). The aim of this study was to determine the risk factors for IPE during total thyroidectomy, the incidence of intracapsular parathyroid glands, and the serum calcium levels and hospital stay of patients with IPE.
Patients and Methods
To determine the risk factors for IPE and the outcome of patients with IPE, we retrospectively reviewed the charts of all patients who had undergone total thyroidectomy from 2004 to 2006. Patients who underwent completion thyroidectomy for papillary/follicular carcinoma were also analyzed under a separate category. All surgeries were done by a surgical consultant or by a registrar under the supervision of a consultant.
Data collected on each patient included age; sex; previous surgical history; diagnosis; preoperative serum calcium levels; type of operation; postoperative serum calcium levels on days 2, 3, and 4 after surgery; and length of hospital stay. Histopathology reports were scrutinized for gland weight, final diagnosis, presence of Hashimoto's thyroiditis, presence of extrathyroidal spread, presence of parathyroid gland, location of the parathyroid gland (intrathyroidal or extrathyroidal), and the pathologic features of the gland. At the time of the study, capsular dissection was used for complete removal of both lobes of the thyroid and the pyramidal lobe, with preservation of parathyroid vascularity; there was no policy of autotransplantation for devascularized glands. All visualized parathyroid glands were preserved in situ, and subcapsular glands were not sought on the thyroid specimen. Central compartment nodes were routinely dissected for medullary carcinoma and nodes that were palpable for papillary carcinoma. Palpable lateral lymph nodes were removed by a modified radical neck dissection type III.
All patients routinely began receiving calcium supplements on the day after surgery, regardless of the serum calcium levels. If a patient was found to be clinically symptomatic, 1-alpha-hydroxycholecalciferol was added. Hypocalcemia was defined as a corrected serum calcium level < 8 mg/dL. Temporary hypocalcemia (biochemical) was defined as a serum calcium level <8 g/dL occurring during the postoperative period and resolving within 6 months. Permanent hypocalcemia was identified in patients requiring calcium and vitamin D supplements to maintain normal calcium levels more than 6 months after surgery.
Data were analyzed by using SPSS software version 11.0 (SPSS Inc, Chicago, Illinois). Descriptive statistics are expressed as frequencies (percentages) for categorical variables and as means (standard deviations [SDs]) for continuous variables. A chi-square test was done to find an association between the categorical clinical measures and IPE. Thyroid gland weight was compared between the 2 groups by using a Mann-Whitney test (this nonparametric test was used because the data were not normally distributed), while all other continuous variables were compared by using an independent t-test.
Results
A total of 365 total thyroidectomies, including completion thyroidectomy, were performed between 2004 and 2006 (3 years) and were included in the analysis. The patients consisted of 95 men (26.1%) and 269 women (73.9%), with an age range of 24–68 years (mean, 41.57 [SD, 12.77] years). Preoperative calcium levels had a normal distribution: mean, 9.1 (SD, 0.488) mg/dL. The mean postoperative calcium level on day 2 was 8.6 (SD, 7.4) mg/dL. The glands were benign in 215 (58.9%) of patients and malignant in 150 (41.09%). The most common malignancy was papillary carcinoma, and the most common benign pathologic abnormality was multinodular goiter (Table 1). Fifty-three patients (14.6%) had undergone completion thyroidectomy after hemithyroidectomy. Seventy patients (19.2%) underwent modified radical neck dissection type III, and 54 (14.8%) patients had total thyroidectomy and central compartment neck dissection. Table 2 reports the incidence of extrathyroidal spread and Hashimoto's thyroiditis.
Table 1.
Pathologic Features of Parathyroid Glands
| Pathologic Finding | Number of Patients |
|---|---|
| Benign | |
| Multinodular goiter | 179 |
| Cyst | 2 |
| Thyroiditis | 29 |
| Hurthle-cell adenomas | 5 |
| Total | 215 |
| Malignant | |
| Papillary carcinoma | 127 |
| Follicular carcinoma | 10 |
| Medullary carcinoma | 5 |
| Anaplastic carcinoma | 7 |
| Lymphoma | 1 |
| Total | 150 |
Table 2.
Demographic and Clinical Data of Study Patients
| Variable | Number (Percentage) of Patients | Number (Percentage) of Patients With IPE | P Value |
|---|---|---|---|
| Sex | |||
| Male | 96 (26.1) | 6 (6.3) | .02 |
| Female | 269 (73.9) | 41 (15.2) | |
| Pathologic features | |||
| Benign | 215 (58.9) | 17 (8) | .001 |
| Malignant | 150 (41.09) | 30 (19.7) | |
| Extrathyroidal spread | |||
| Yes | 68 (18.6) | 10 (14.7) | .625 |
| No | 297 (91.09) | 37 (12.5) | |
| Hashimoto's thyroiditis | |||
| Yes | 89 (24.1) | 13 (14.8) | .55 |
| No | 276 (75.6) | 34 (12.3) | |
| Radical neck dissection | |||
| Yes | 70 (19.17) | 10 (14.3) | .703 |
| No | 295 (80.82) | 37 (12.6) | |
| Central compartment clearance | |||
| Yes | 54 (14.79) | 13 (24.1) | .008 |
| No | 311 (85.20) | 34 (11) |
The parathyroid gland was inadvertently removed in 47 of 365 thyroidectomies (12.91%). In most of these cases (44 patients), only 1 gland had been inadvertently removed. Three patients with multiple glands removed had undergone modified radical neck dissection type III and central compartment dissection for papillary carcinoma and were found to have extrathyroidal spread of tumor and multiple metastatic nodes. Of the 49 parathyroid glands, 24 were extrathyroidal and21 were intrathyroidal/intracapsular; details of the remaining 2 were not available. Histopathologic findings of the incidentally removed parathyroid glands were normal in all but 1 case, which was an adenoma.
The risk factors for IPE assessed were age, sex, pathologic features, extrathyroidal spread, thyroiditis, and associated lateral/central neck dissection. Female sex, malignancy, central neck dissection, and smaller size of the gland were found to be associated with a significantly higher incidence of IPE, according to the chi-square test (Table 2).
The incidence of biochemical hypocalcemia on the first day after surgery was 28.2% (102 of 364). A significantly higher proportion of patients with IPE, 40.43% (19 of 47), had hypocalcemia vs26.1% (83 of 317) of patients without IPE(P< .05). Symptomatic hypocalcemia could not be assessed because of lack of data. A significantly higher percentage of patients with IPE (8.5% [4 of 47]) also developed permanent hypocalcemia compared with the other group (2.8% [9 of 317]) (P < .05). The overall incidence of permanent hypocalcemia in our study was 3.57%.
The mean length of hospital stay for all patients was 3.1 (SD, 1.58) days. Length of hospital stay did not increase for patients with IPE (mean, 2.5 days vs. 3 days in other group; P = .757). This finding indicates that inadvertent removal of parathyroids does not increase hospital stay.
Discussion
A thyroid surgeon is always surprised to find parathyroid glands identified on histopathologic examination; this finding reportedly occurs in up to 21% of cases.[7–15] The parathyroid glands may not be identified during surgery even by a careful capsular dissection technique because they could be intrathyroidal, flattened subcapsular, hidden in the internodular grooves, or infiltrated by thyroid tumor. It is difficult to predict which patients have a risk for IPE and whether these patients develop hypocalcemia. Previous reports have tried to minimize the effect of IPE by showing that clinically symptomatic hypocalcemia was less severe in patients with IPE.[7–14] Table 3 and Table 4 compare the findings from previous studies with ours.
Table 3.
Results of Related Studies
| Author | Number of Cases | Incidence (%) | Number (Percentage) of Glands Removed | Position of Glands (%) |
|---|---|---|---|---|
| Lee et al.[8] | 414 | 11 | 1 (80) | IC: 42 |
| 2 (13) | ||||
| 3 (7 | ||||
| Sasson et al.[9] | 144 | 15 | 1 (81) | IC: 31 |
| 2 (19) | IT: 50 | |||
| EC: 19 | ||||
| Lin et al.[7] | 220 | 9 | 1 (70) | IC: 15 |
| 2 (25) | IT: 5 | |||
| 3 (5) | EC: 80 | |||
| Gagner et al.[14] | 515 | 18 | NA | NA |
| Rix and Sinha[12] | 126 | 17 | 1 (100) | IC: 13.6 |
| EC: 86.4 | ||||
| Sakorafas et al.[10] | 158 | 17 | 1 (86) | IC: 36 |
| 2 (14) | IT: 21 | |||
| EC: 43 | ||||
| Sippel et al.[11] | 513 | 6.4 | 1 (85) | NA |
| 2 (15) | ||||
| Manouras et al.[21] | 508 | 19.7 | NA | NA |
| Sciume et al.[23] | 313 | 0.95 | NA | NA |
| Page and Strunski[24] | 351 | 5.2 | 1 (100) | IC: 22.7 |
| EC: 77.3 | ||||
| Abboud et al.[25] | 307 | 12 | NA | IC: 39 |
| IT: 24 | ||||
| EC: 37 | ||||
| Gourgiotis et al.[26] | 315 | 21.6 | 1 (67.6) | IC: 40 |
| 2 (32.3) | IT: 33 | |||
| EC: 27 | ||||
| Current study | 364 | 12.9 | 1 (93.6) | IT: 44.6 |
| 2 (6.4) | EC: 55.4 |
EC = extracapsular; IC = intracapsular; IT = intrathyroidal; NA = not available.
Table 4.
Risk Factors for IPE and Incidence of Hypoglycemia in Patients With IPE Reported in Related Studies
| Author | Statistically Significant Risk Factors | Incidence of Hypocalcemia in IPE Group (%) |
|---|---|---|
| Lee et al.[8] | Reoperation, central compartment dissection | Temporary: 0 |
| Permanent: 0 | ||
| Sasson et al.[9] | Total thyroidectomy, radical neck dissection | Temporary:5 |
| Permanent: 0 | ||
| Lin et al.[7] | Reoperation, central compartment dissection | Temporary:0 |
| Permanent: 0 | ||
| Bergamaschi et al.[15] | NA | Temporary: 23.8 |
| Permanent:2.9 | ||
| Rix and Sinha[12] | Reoperation | Temporary: 0 |
| Permanent: 0 | ||
| Sakorafas et al.[10] | Female sex, malignancy | Temporary: 21 |
| Permanent: 0 | ||
| Sippel et al.[11] | Young age, total thyroidectomy, malignancy | Temporary: 24 |
| Permanent: 0 | ||
| Manouras et al.[21] | Male sex | Temporary: 3 |
| Permanent: 0 | ||
| Sciume et al.[23] | NA | NA |
| Page and Strunski[24] | NA | Temporary: 1.99 |
| Permanent: 0 | ||
| Abboud et al.[25] | Thyroiditis | NA |
| Gourgiotis et al.[26] | Total thyroidectomy, malignancy, radical neck dissection, central compartment clearance | Temporary: 22 |
| Permanent: 0 |
No studies reported significant hypocalcemia.
NA = not available.
Most authors would advise routinely attempting to identify and preserve the parathyroid glands while doing thyroidectomy to prevent inadvertent parathyroidectomy.[4–6,16] There is no correlation between the number of parathyroids identified and postoperative calcium values,[15,17] and the number of glands does not predict the incidence of IPE or the duration of calcium supplementation needed if the calcium level is low.[9] The inferior parathyroid glands are more variable in location than are the superior glands. The parathyroids can be intracapsular/intrathyroidal or extracapsular. All the previous studies have reported the position of the parathyroid glands (Table 3); the proportion of glands in the intracapsular position was high as 42%.[7–14] In our study, the incidence of intracapsular glands was 44.6%, suggesting that improvement in surgical technique that leads to routine identification of all extrathyroidal parathyroid glands on the surface of the thyroid gland may reduce the risk for IPE by half and minimize the incidence of hypocalcemia. In most patients, only 1 parathyroid gland was accidentally removed. Table 3 compares the numbers of glands removed in published studies. Therefore, it is advisable to anticipate inadvertent removal, carefully inspect the specimen for the presence of parathyroid glands, and autotransplant them into adjacent sternomastoid muscle. Autotransplantation reduces the incidence of permanent hypoparathyroidism to <1%.[15,18–20] Although some authors advocate early routine autotransplantation during high-risk surgery,[20] a selective approach can also be followed.[11]
It might be useful to identify a high-risk group to scrutinize during surgery. In previous studies, female sex[10] and young age[11] were shown to be risk factors. We found female sex as a significant risk factor (P = .02). Both Sippel and colleagues' study[11] and our study showed malignancy to be a risk factor (P = .001). Our study revealed that small thyroid glands (P = .032) could be a risk factor. The mean weight of the gland was 51.63 (SD, 61.722) g in patients with IPE and 73.10 (SD, 84.765) g in the other group; this finding was statistically significant by the Mann-Whitney test. Other studies[7,11,21] evaluated this variable and found it to be not significant. Incidentally, Sippel and colleagues[11] also reported that the glands were small in the IPE group, but they could not show a statistically significant difference. The association of reoperative surgery with IPE has been described earlier in other studies. While 3 studies showed strong statistical significance,[7,8,12] we did not find reoperation to be a strong risk factor (P = 0.122). Other factors, such as extrathyroidal spread of the tumor and Hashimoto's thyroiditis, were not found to be risk factors (Table 2).[7–12] There is no risk factor common to all the studies. However, central neck dissection is the most frequently identifiable risk factor, seen in our study as well as those by Lin,[7] Lee,[8] and Rix[12] and their colleagues. This indicates that utmost care is needed to identify and preserve parathyroids while doing central compartment dissection.
Three studies[11,15,22] found that IPE increased the risk for temporary hypocalcemia. But other studies that specifically evaluated risk factors for IPE[7,9] reported no association between IPE and postoperative hypocalcemia. Biochemical and symptomatic hypocalcemia are often poorly correlated because the causes are multifactorial. Since most patients have 4 parathyroid glands, it seems logical that removal of 1 should not lead to problems with calcium levels if the other 3 function adequately. Three of 5 patients in whom multiple parathyroids were inadvertently removed needed calcium supplementation for 6 months. In our study, the incidence of temporary hypocalcemia (calcium level <8 mg/dL) was 28.02% (102 of 364 patients), and the incidence of permanent hypocalcemia was 3.57% (13 of 364); these values are within the limits of those found in large cohort studies.[2–4,6] Bergamaschi and colleagues[15] reported a 2.9% incidence of permanent hypocalcemia in the IPE group, whereas other studies reported no patients with low calcium values after 6 months. It must be emphasized that central compartmental neck dissection, along with total thyroidectomy, led to a statistically significantly increased rate of temporary and permanent hypocalcemia, and this should be weighed against the probable benefit of prophylactic dissections in thyroid cancer.
Hypocalcemia can lengthen the duration of hospitalization and increases the need for biochemical tests.[22] The mean length of hospitalization for all patients was 3.1 (SD, 1.58) days. Hospital stay did not increase for patients with IPE (mean, 2.5 days vs3 days in the other group; P = .757).
Conclusion
In our study, the incidence of IPE was 12.9%. IPE caused significantly higher rates of temporary and permanent postoperative hypocalcemia. Removed parathyroids were intracapsular/intrathyroidal in 44.6% of cases. Steps should be taken to preserve more parathyroid glands by improving surgical technique and possibly by magnification. Intraoperative identification of removed parathyroids by peeling the posterior thyroid capsule after specimen removal may permit autotransplantation of these intracapsular glands. This technique has been shown to reduce the incidence of permanent hypocalcemia. The search for lower morbidity after total thyroidectomy is a worthwhile exercise for this technically challenging procedure.
Footnotes
Reader Comments on: Surgical Audit of Inadvertent Parathyroidectomy During Total Thyroidectomy: Incidence, Risk Factors, and Outcome See reader comments on this article and provide your own.
Contributor Information
J. Rajinikanth, Department of General Surgery and Endocrine Surgery, Christian Medical College and Hospital, Tamilnadu, India Author's email address: rajinikanth_j@cmcvellore.ac.in.
M.J. Paul, Department of General Surgery and Endocrine Surgery, Christian Medical College and Hospital, Tamilnadu, India.
Deepak T. Abraham, Department of General Surgery and Endocrine Surgery, Christian Medical College and Hospital, Tamilnadu, India.
C.K. Ben Selvan, Department of General Surgery and Endocrine Surgery, Christian Medical College and Hospital, Tamilnadu, India.
Aravindan Nair, Department of General Surgery and Endocrine Surgery, Christian Medical College and Hospital, Tamilnadu, India.
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