Factors affecting the rates of incidental parathyroidectomy during thyroidectomy

Background The most important factors affecting the development of postoperative hypocalcaemia (PH) include intraoperative trauma to the parathyroid glands, incidental parathyroidectomy (IP), and the surgeon's experience. In this study, we aimed to determine the incidence of IP, evaluate its effect on postoperative calcium levels and investigate the effect of surgeon experience and volume on IP incidence and postoperative calcium levels. Methods This retrospective study included 645 patients who underwent thyroid surgery at the Department of General Surgery, Kütahya Health Sciences University between September 2016 and March 2020. All patients underwent surgery at a single clinic by general surgeons experienced in thyroid surgery and their residents (3–5 years). Results Normal parathyroid glands were reported in 58 (8.9%) of 645 patients. In 5 (8.6%) of 58 patients the parathyroid gland was detected in the intrathyroidal region. PH developed in ten patients (17.2%) with incidental removal of the parathyroid glands. A statistically significant difference was found between the number of incidentally removed parathyroid glands and the development of hypocalcaemia (p<0.05). Normal parathyroid glands were reported in the pathology of 37 (7.9%) patients operated on by general surgeons and 22 (12.6%) patients operated on by their residents. PH developed in 39 (8.2%) patients operated on by general surgeons and in 8 (4.5%) patients operated on by their residents. Conclusions We found that the complication rate during the resident training process was the same as that of experienced general surgeons. A thyroidectomy can be safely performed by senior residents during residential training.


Introduction
Thyroidectomy is the most common endocrine surgery.The standardisation of thyroidectomy techniques and advances in perioperative management have led to significant reductions in overall mortality and morbidity in the 21st century.2][3] A complication is postoperative hypocalcaemia (PH).Defined as a serum calcium level lower than normal, PH requires calcium/ vitamin D replacement therapy within 24h after surgery or when discharged from the hospital. 3PH remains the most common complication of thyroid surgery, with a prevalence ranging from 1.5% to 50%, depending on the definition of low serum calcium levels.
][6] Symptoms of hypocalcaemia appear within the first 24-48h after surgery.PH may be associated with operative stress, calcitonin secretion due to surgery, vitamin D deficiency due to postoperative alkalosis resulting from hyperventilation triggered by postoperative pain, or haemodilution.The most important factors affecting the development of PH include intraoperative trauma to the parathyroid gland or vascular system, failure to identify the parathyroid gland during surgery, acute parathyroid insufficiency resulting from incidental parathyroidectomy (IP), and surgeon experience.
Hypocalcaemia resolves spontaneously in many patients, but if irreversible damage occurs in the parathyroid gland, hypocalcaemia may be permanent. 3,6,7P has been defined in the literature as parathyroid tissue found in a postoperative specimen and is a relatively common finding in thyroid pathology reports, even in the hands of experienced endocrine surgeons, with an incidence of 2.9-31%.][6][7] Variations in the number and anatomical location of parathyroid glands increase the risk of IP.Various anatomical variants of the parathyroid glands exist, especially in the inferior parathyroid glands. 6,7There is no consensus on biochemical and clinical outcomes or on identifying predisposing factors and high-risk patients.The development of hypocalcaemia as a result of incidental excision of the parathyroid glands is not necessary, but may be followed by biochemical or clinical hypocalcaemia. 5,7n this study, we aimed to determine the incidence of IP in patients who have undergone thyroid surgery in our clinic, evaluate its effect on postoperative calcium levels, investigate the effect of surgeon experience and volume on IP incidence and postoperative calcium levels, and determine possible risk factors in the light of preoperative and intraoperative factors.

Methods
This retrospective study included 645 patients who underwent thyroid surgery at the Department of General Surgery, Kütahya Health Sciences University between September 2016 and March 2020.Permission for the study was obtained from the Non-Interventional Clinical Research Ethics Committee of Kütahya Health Sciences University (Ethics Committee Decision No: 2021/11-35).The Declaration of Helsinki was adhered to and no patient's personal information was disclosed during the study.
Patients diagnosed with multinodular goitre or nodular goitre, patients diagnosed with Graves' disease, patients with thyroid cancer, male and female patients aged 19-84 years, and patients with American Society of Anesthesiologists scores of I, II and III were included in the study.Pregnant women, patients younger than 18 years of age, patients with a history of preoperative laryngeal surgery, patients with a history of radiotherapy to the neck region, patients detected to have preoperative parathyroid pathology, patients that are not preoperatively normocalcaemic and patients with stage 3 and above chronic kidney disease were not included in the study.
All patients underwent preoperative and postoperative vocal cord examinations using a flexible fibre optic laryngoscope by a specialist in the Otorhinolaryngology Clinic.All patients underwent surgery at a single clinic by general surgeons experienced in thyroid surgery and their residents (3-5 years experience).Preoperative hospital records, age, sex, comorbidities, laboratory results, preoperative calcium (mg/dl) and albumin (g/dl) levels, ultrasonography findings and ear, nose, and throat (ENT) consultations were collected retrospectively.
The type and duration of the operation, the person performing the operation, intraoperative nerve monitoring (IONM), the condition of the parathyroid glands, recurrent laryngeal nerve (RLN) visualisation and drain usage were examined from the archives and recorded.In addition, postoperative complications, pathology results, calcium values at the eighth hour and sixth month, and vocal cord movements detected during the ENT consultation were examined and recorded from archives and files.
We analysed retrospectively 684 patients who underwent thyroid surgery between 2016 and 2020; 16 patients with missing records, 22 without preoperative normocalcaemia and 1 with preoperative hypoparathyroidism were excluded from the study.A total of 645 patients with complete preoperative, intraoperative and postoperative records were included in this study.
The first calcium and albumin measurements in all patients were made at the eighth postoperative hour.Calcium values were corrected according to albumin values and recalculated.The corrected total blood calcium level was calculated using the following formula 8 : Total blood calcium value corrected (mg / dl) = 0.8 × [normal albumin value 4 g/dl -patient ′ s albumin value (g/dl)] + total blood calcium value Patients with or without symptoms whose corrected calcium levels (normal range 8.8-10.2mg/dl)were measured below 8.8mg/dl were considered to be hypocalcaemic.Patients with symptomatic hypocalcaemia were treated with oral calcium and vitamin D preparations, and intravenous calcium gluconate.All patients with hypocalcaemia were referred to the endocrinology clinic.Patients reported to have normal parathyroid tissue on pathology were evaluated for IP, and their number and anatomical location were recorded to evaluate their relationship with the development of hypocalcaemia.

Surgical technique
All patients underwent surgery under general anaesthesia with endotracheal intubation.Sevoflurane was used as the main medication, and rocuronium was used as the muscle relaxant.Full-dose rocuronium and remifentanil were used in those operated on using the conventional direct visualisation technique, and low-dose rocuronium and remifentanil were used in those operated on using IONM.Patients underwent surgery in a semi-sitting position with a classic Kocher incision.The subcutaneous tissue and platysma muscle were dissected intraoperatively.The strap muscles were dissected longitudinally and retracted laterally using retractors.First, the middle thyroid vein was sealed with an energy device, and the upper pole was dissected.In all patients, the upper poles were tied using 2/0 Vicryl sutures.
In all study patients, the RLN was dissected and visualised in the tracheoesophageal groove.All parathyroid glands were observed and preserved.Finally, the ligamentous structures between the trachea and thyroid gland were cut, and hemithyroidectomy was completed.The same steps and procedures were applied to other lobes, and a total thyroidectomy (TT) was completed.In a near-TT, one lobe was removed completely, whereas <1cm of thyroid tissue was left behind in the other lobe.In these cases, the RLN was visualised.In addition, negative-pressure Hemovac drains were placed in the operative area for the postoperative follow-up of all patients.

Statistical analysis
Data obtained from the patients were recorded using the IBM SPSS (Statistical Package for the Social Sciences) Statistics 20 program in Excel.All statistical analyses were performed using this program.Descriptive measures (mean, standard deviation, etc) were used to analyse the quantitative (numerical) data of the variables.For the analysis of qualitative (categorical) variables, frequency tables with numbers and percentages were used.Crosstabs were created to show variations in the two qualitative variables relative to each other.The row percentages are provided in the crosstabs.The chi-square test was used to compare the proportions between two or more groups.The phi coefficient, Cramer's V coefficient, and normality coefficient values, which are the coefficients for unordered qualitative data, were obtained.Statistical significance was set at p<0.05.In other words, statistical evaluation was carried out with a 0.05 margin of error and a confidence level of 0.95.
Normal parathyroid glands were reported in 58 (8.9%) of the 645 patients and PH developed in 47 (7.2%).PH developed in ten patients (17.2%) with incidental removal of the parathyroid glands.This rate was 6.3% (n=37) in the group that did not have normal parathyroid glands.This difference was statistically significant (p=0.003)(Table 1).
Of the 645 patients, 73% (n=471) were operated on by general surgeons experienced in thyroid surgery and 27% (n=174) were operated on by residents under the supervision of specialists.PH developed in 39 (8.2%) patients operated on by general surgeons and in 8 (4.5%) patients operated on by residents under the supervision of specialists.There was no statistically significant difference between surgeries performed by residents and specialists in the development of hypocalcaemia (p=0.110)(Table 2).
Normal parathyroid glands were reported in the pathology of 37 (7.9%) patients operated on by general surgeons and 22 (12.6%)patients operated on by residents under the supervision of specialists.Although the percentage of unintentionally removed parathyroid glands was higher among residents than among specialists, no statistically significant correlation was found between the presence of unintentionally removed parathyroid glands and the surgeon performing the surgery (p>0.05)(Table 3).
In 5 (8.6%) of the 58 patients who were reported to have normal parathyroid glands in their pathology, the parathyroid gland was detected in the intrathyroidal region.
A statistically significant difference was found between the number of incidentally removed parathyroid glands and the development of hypocalcaemia (p<0.05).While the rate of PH development was 6.3% (n=37) in the group in which the parathyroid gland was not excised incidentally, this rate was 14% (n=7) in the group in which one parathyroid gland was excised incidentally and 28.6% in the group in which two parathyroid glands were excised incidentally (n=2), and the rate of hypocalcaemia development was 100% in the only patient whose three parathyroid glands were incidentally excised (Table 4).

Discussion
This study compared the presence, localisation and number of IP in the postoperative pathology reports of patients who underwent thyroid surgery by general surgeons and resident physicians under the supervision of experienced surgeons in a centre, and their effects on PH.
To the best of our knowledge, this is the first study to compare IP rates between senior resident physicians and experienced surgeons at the same centre.Our findings show that IP is common, with a rate of 7.9%, even among experienced surgeons.Since 8.6% of incidentally removed glands are intrathyroidal, it is not possible to completely avoid IP despite careful dissection and good anatomical knowledge.In this study, papillary carcinoma and nodular hyperplasia were identified as possible risk factors for IP, and the presence and number of incidental parathyroidectomies were associated with the development of PH.Evaluating these risk factors during the surgery will increase surgeons' awareness of IP and minimise the number of other preventable IP cases.
0][11][12][13][14][15][16][17][18][19][20][21] Our data show that IP occurred at a rate of 8.9%.This result is consistent with rates reported in the literature.Although variable locations and numbers of parathyroid glands make intraoperative identification difficult and increase the risk of IP, several authors recommend careful examination of the specimen for the presence of parathyroid glands and autotransplantation into the adjacent sternocleidomastoid muscle. 9,21In a cadaver dissection of 942 individuals, a fifth parathyroid gland was found in 5% of cases and three parathyroid glands (instead of four) in 2% of cases. 22he intrathyroidal location of parathyroid glands is often an inevitable cause of IP.6][27][28] This higher incidence and wide range in the literature can be explained by thyroid malignancies, which could potentially lead pathologists to examine the thyroid tissue in more detail than in cadaver studies. 29In the present study, the rate was 8.6%.
Although the relationship between PH and IP has not been determined clearly in the literature, 5,13,30,31 the incidence of PH in the IP group was approximately three times higher than that in the non-IP group in our study (16.9% vs 6.3%, p<0.003).3][34] In a prospective study of 207 patients who underwent thyroid surgery, Youssef et al found no significant difference in the incidence of postoperative biochemical hypocalcaemia between patients with and without IP (7.7% vs 8.8%, p=0.55). 34he latter study involved a series of patients with high rates of lobectomy and near-TT (40.1%).In contrast, recent studies involving multiple cases of TT and patients with thyroid cancer, in whom all four glands were at risk, reported that patients with IP were more likely to develop postoperative biochemical hypocalcaemia. 13,17,20,25,26,35everal studies have concluded that thyroid malignancies increase the risk of IP. 12,14,28,36 However, in other studies, thyroid malignancies reduced the risk of IP. 9,12,13,31 In this study, according to univariate analysis, the incidence of thyroid malignancy and nodular hyperplasia, especially papillary carcinoma, was significantly higher in patients with IP.In our study, malignancy was found as the last pathology in 180 patients (27.9%).The high incidence of malignancy may indicate that it is an additional risk factor for IP.These results can be explained by the fact that patients with suspected thyroid malignancies can be treated with TT, reoperation for complete resection, or concomitant cervical lymph node dissection (CLND).Therefore, we believe that careful monitoring during thyroidectomy in patients with a preliminary diagnosis of papillary carcinoma and nodular hyperplasia may reduce the risk of IP.
In our study, the number of incidentally resected parathyroid glands was associated with the risk of hypocalcaemia.Patients with two resected parathyroid glands had a significantly higher risk of hypocalcaemia than those with only one gland resected incidentally (28.6% vs 14%, p<0.01).Furthermore, patients with three incidentally resected parathyroid glands had a significantly higher incidence of hypocalcaemia than those with two incidentally resected parathyroid glands (100% vs 28.6%, p<0.01).This result is consistent with those of other recent publications. 19,37,38Lorente-Poch et al published a prospective study of incidental parathyroidectomies. 38 In the present study, the prevalence of hypocalcaemia and persistent hypoparathyroidism was associated with the number of parathyroid glands left in place.In addition, studies have reported that removing one or two glands does not significantly affect PH. 11,26,39everal studies have reported that TT is a risk factor for IP. 13,17,20,26,28In our study, 85.58% of the patients underwent TT, and no significant difference was found between the groups in terms of the surgical method used for IP (p=0.576).Our results are consistent with those of previous studies reporting that TT does not increase the IP rate. 9,11,12,14,21In this case, a statistically accurate analysis could not be performed because of the reduced use of other surgical methods.
Few articles in the literature discuss the effect of surgeon volume and experience on the incidence of IP and the development of PH.When the data of Lin et al and Manouras et al were analysed, 13,40 there was no significant difference in the incidence of IP based on surgeon volume.In a retrospective study by Barrios et al, 41 in which 1,114 thyroidectomies were examined, a higher case volume was associated with a lower incidence of unintentional parathyroidectomy for both thyroidectomy and CLND.
In our study, surgeon volume and experience were not associated with the incidence of incidentally removed parathyroid glands or PH.PH developed in 39 (8.2%) patients operated on by general surgeons and in 8 (4.5%) patients operated on by senior residents under the guidance of specialists.There was no statistically significant difference between the residents and specialists performing the surgery in terms of the development of hypocalcaemia (p=0.11).Normal parathyroid glands were reported in the pathology of 37 (7.9%) patients operated on by general surgeons and 22 (12.6%)patients operated on by residents.Although the percentage of unintentionally removed parathyroid glands was higher among residents than among specialists, no statistically significant correlation was found between the presence of unintentionally removed parathyroid glands and the surgeon performing the surgery (p>0.05).
We believe that the complication rate during the resident training process was the same as that of the specialists.
However, patients managed by an experienced surgeon may have been more complicated cases, such as locally advanced thyroid malignancy, massive goitre, substernal goitre, and recurrent surgery.

Study limitations
This study has some limitations.The first limitation is it is retrospective in design.Second, when the surgical records were examined, most surgeons did not document the number and localisation of the parathyroid glands that they identified and preserved perioperatively.Therefore, the relationship between the parathyroid definition and IP could not be evaluated.However, the assessment of the absence or presence of parathyroid glands identified during surgery was not objective and may differ between surgeons and studies.Third, the study was conducted at a single centre, which limits the generalisability of the statistics; however, the strength of our study is that the number of patients was sufficient for a single centre.Fourth, central CLND is the risk factor for IP reported most commonly in the literature. 21,36In our study, only one patient underwent CLND; therefore, the relationship between CLND and IP could not be evaluated.
Finally, we did not evaluate the effects of IP on the development of postoperative hypoparathyroidism.In addition, the lack of long-term follow-up of these patients did not allow us to identify the long-term sequelae of IP, which is a significant disadvantage.

Conclusions
Because most parathyroid glands are extracapsular, the incidence of IP can be reduced by careful and meticulous dissection and strict adherence to anatomical and surgical principles.Of the incidentally excised parathyroid glands, 8.6% were classified as postoperative intrathyroid glands.The inability to perform autotransplantation in these cases indicates that complete elimination of the IP is difficult with the current surgical techniques.Papillary carcinoma and nodular hyperplasia have been identified as potential risk factors for IP.The presence and number of incidental parathyroidectomies were associated with the development of PH.
Age, sex and surgical technique were not identified as risk factors for IP.Surgeons should also consider anatomical variations in the parathyroid glands to avoid mechanical and thermal injury, devascularisation or resection of the parathyroid tissue.Patients should be warned about the possibility of accidental removal of the parathyroid gland during the consent process, as they can review the operative notes.These results suggest that investigating techniques aimed at identifying parathyroid glands intraoperatively may reduce the prevalence of this complication.We found that the complication rate during the resident training process was the same as that of experienced general surgeons.
A thyroidectomy can be performed safely by senior residents during residential training.Open Access This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, reproduction, and adaptation in any medium, provided the original work is properly attributed.

Table 2
Relationship between development of PH and surgeon

Table 1
Relationship between presence of incidentally removed parathyroid gland and development of hypocalcemia

Table 3
Relationship between presence of an incidentally removed parathyroid gland and surgeon

Table 4
Relationship between number of incidentally removed parathyroid glands and development of PH Ann R Coll Surg Engl 2024; 106: 454-460

Table 5
Relationship between postoperative pathological diagnosis of patients and presence of incidentally removed parathyroid glands