Accepted Manuscript Inadvertent Parathyroidectomy: Incidence, Risk Factors and Outcomes Hannah Y. Zhou, MD, Jack C. He, MD, Christopher R. McHenry, MD PII:
S0022-4804(16)30140-8
DOI:
10.1016/j.jss.2016.06.019
Reference:
YJSRE 13817
To appear in:
Journal of Surgical Research
Received Date: 3 February 2016 Revised Date:
18 May 2016
Accepted Date: 7 June 2016
Please cite this article as: Zhou HY, He JC, McHenry CR, Inadvertent Parathyroidectomy: Incidence, Risk Factors and Outcomes, Journal of Surgical Research (2016), doi: 10.1016/j.jss.2016.06.019. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Inadvertent Parathyroidectomy: Incidence, Risk Factors and Outcomes
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Hannah Y. Zhou1,3, MD, Jack C. He, MD1,3, Christopher R. McHenry, MD2,3
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Department of Surgery, University Hospitals Case Medical Center, Cleveland, OH 44106, USA Department of Surgery, MetroHealth Medical Center, Cleveland, OH 44109, USA 3 Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
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Corresponding Author: Christopher R. McHenry, M.D. Vice Chairman, Department of Surgery Director, Division of General Surgery MetroHealth Medical Center, H-918 2500 MetroHealth Drive Cleveland, OH 44109 [email protected] (216) 778-8917
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AUTHOR CONTRIBUTIONS
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Dr. Zhou was involved in the design of this study, performed data collection and analysis and was involved in the authorship of all sections of the manuscript. Dr. He was involved with data analysis and revision of the manuscript. Dr. McHenry was involved in the design of the study, supervised the data collection, data analysis and was involved in the authorship of all sections of the manuscript. ABSTRACT
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Introduction Parathyroid glands are ≤ 5mm, often subcapsular or intrathyroidal, and obscured by lymph nodes, making preservation a challenge. The purpose of this study was to determine the incidence of inadvertent parathyroidectomy (IP) and whether it contributes to hypoparathyroidism following thyroidectomy.
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Materials and methods A retrospective review of all thyroidectomies by a single surgeon from January, 2010 to August, 2014 was completed to determine the rate of IP and permanent hypoparathyroidism. Medical records were assessed for demographics, extent of thyroidectomy, central compartment neck dissection, thyroid gland weight, parathyroid autotransplantation, reoperation, pathology, postoperative calcium levels and number of parathyroid glands removed.
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Results A total of 386 patients underwent thyroidectomy. Mean age was 52 years and 327 (85%) patients were female. There were 25 (7%) patients who underwent reoperation, 40 (10%) who underwent central compartment neck dissection and 128 (33%) who underwent parathyroid autotransplantation. IP occurred in 78 (20%) patients. Permanent hypoparathyroidism occurred in 7 (2.7%) of 258 patients following total or completion thyroidectomy, 4 (6.7%) with IP compared to 3 (1.5%) without IP (p = 0.033). Logistic regression analysis revealed that female gender (odds ratio = 2.768, p = 0.040), central compartment neck dissection (odds ratio = 9.584, p = 0.001) and thyroid gland weight (odds ratio = 0.994, p = 0.022) were independent factors associated with IP.
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Conclusions IP, which occurred in 20% of patients undergoing thyroidectomy, is a potentially remediable factor associated with a higher rate of hypoparathyroidism. Central compartment neck dissection is an independent risk factor for IP. KEY WORDS
Inadvertent parathyroidectomy, hypoparathyroidism, central compartment neck dissection
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1. Introduction
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Thyroidectomy is performed for a variety of indications, including thyroid cancer, nodular thyroid disease with an indeterminate or nondiagnostic fine needle aspiration biopsy, a symptomatic goiter or a goiter with tracheal or esophageal impingement, substernal extension and thyrotoxicosis. The estimated number of thyroidectomies performed yearly in the United States exceeds 92,000 [1]. As with any operation, challenges include minimizing complications. The major complications of thyroidectomy include recurrent laryngeal nerve injury (1.2-7.6%) [2-4], bleeding requiring reoperation (0.6-1.6%) [2, 3, 5, 6] and permanent hypoparathyroidism (1.2-5.5%) [2, 7-10].
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The parathyroid glands can be challenging to identify intraoperatively. A parathyroid gland weighs approximately 35 mg, measures 5 mm in maximum dimension and is usually surrounded by adipose and loose connective tissue. Parathyroid glands can become discolored with bleeding and can be mistaken for thyroid, nodal or adipose tissue. Parathyroid glands that are subcapsular may be flattened in appearance, making them more difficult to identify and more vulnerable to removal during thyroidectomy. Parathyroid glands are often embedded with lymph nodes and can be more difficult to identify in patients with enlarged lymph nodes in the central compartment of the neck from cancer or Hashimoto’s thyroiditis. Hypoparathyroidism is reported to be higher in patients undergoing thyroidectomy with central compartment neck dissection [8, 9, 11], suggesting that parathyroid glands may be more vulnerable to removal during central compartment neck dissection compared to thyroidectomy alone. Parathyroid glands may also be intrathyroidal and their removal cannot be prevented.
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Embryologically, the parathyroid glands develop from the third and fourth branchial pouches. The superior parathyroid glands arise from the fourth branchial pouch along with the lateral lobes of the thyroid gland. The inferior parathyroid glands develop from the third branchial pouch along with the thymus. The normal anatomic location of the superior parathyroid gland is fairly constant, with 80% of superior glands found near the posterior aspect of the upper thyroid lobe at the level of the cricoid cartilage where the recurrent laryngeal nerve enters the larynx posterior to the inferior pharyngeal constrictor muscle [12]. It is typically posterior and superior to the recurrent laryngeal nerve, approximately 1 cm cephalad to the junction of the inferior thyroid artery and the recurrent laryngeal nerve [13]. Ectopic superior glands can be found in the tracheoesophageal groove, in a paraesophageal, retroesophageal or retropharyngeal location, in the posterior mediastinum, within the carotid sheath or within the thyroid gland [14]. The normal anatomic location of an inferior parathyroid gland is approximately 1 cm caudal to the junction of the inferior thyroid artery and the recurrent laryngeal nerve and anterior to the recurrent laryngeal nerve on the posterior aspect of the inferior pole of the lobe of thyroid gland [13]. Because of its more extensive migration during embryologic development, an inferior parathyroid gland is more likely to be found in an ectopic location. An ectopic inferior parathyroid gland may be found in the thymus, the thyrothymic ligament, the anterior mediastinum, undescended in a submandibular location or within the thyroid gland [14]. Due to the small size and variable location of the parathyroid glands, preservation of the parathyroid glands can be a challenge during thyroidectomy. The purpose of this study was to
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determine the incidence of inadvertent parathyroidectomy (IP) during thyroidectomy at our institution, its risk factors and whether it is associated with the development of hypoparathyroidism. 2. Materials and Methods
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A retrospective review of electronic medical records and a prospectively maintained database was completed for a consecutive group of patients who underwent thyroidectomy by a single surgeon from January 2010 through August 2014. The pathology reports for all study patients were reviewed to determine if one or more parathyroid glands were unexpectedly found in the specimen submitted to pathology. During the study period, a routine protocol for processing the thyroid gland was followed at our institution. Pathologists completed a gross examination of the thyroid gland and the excised contents of the central compartment of the neck. A routine pathologic examination of all thyroid nodules as well as one representative section for every 1 cm of the remainder of the thyroid gland was completed. IP was defined as the unrecognized removal of a parathyroid gland or any parathyroid tissue that was found in the specimen submitted for paraffin evaluation. The determination of an incidentally discovered parathyroid gland or parathyroid tissue was made on the basis of microscopic pathologic examination. An intrathyroidal parathyroid gland was defined as a gland that was completely surrounded by thyroid parenchyma.
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A systematic search for parathyroid glands, that were not identified during the course of the normal operative dissection, was not performed. The distal branches of the inferior thyroid artery were ligated adjacent to the thyroid gland. Ligation of the trunk of the inferior thyroid artery was avoided. If a parathyroid gland could not be preserved in situ or was thought to be devascularized during the course of the thyroidectomy, confirmation of parathyroid tissue was obtained with a frozen section examination and the remainder of the gland was minced and autotransplanted into the ipsilateral sternocleidomastoid muscle. A parathyroid gland that was removed and later autotransplanted did not constitute IP.
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Patient medical records were assessed for potential risk factors that might contribute to IP and to determine if IP contributed to the development of hypoparathyroidism. Data that was obtained included demographics, extent of thyroidectomy, central compartment neck dissection, thyroid gland weight, retrosternal goiter, parathyroid autotransplantation, reoperative thyroidectomy, pathology and postoperative calcium levels. Serum calcium levels were measured on the first postoperative day in all patients who underwent total or completion thyroidectomy. Follow-up calcium levels were obtained in an outpatient setting for patients with hypocalcemia, patients placed on calcium supplementation and patients who developed symptoms of hypocalcemia. A patient was determined to have permanent hypoparathyroidism if he or she required vitamin D and/or calcium for maintenance of eucalcemia for 6 months following thyroidectomy. Statistical analyses were performed using IBM SPSS© version 22 (IBM, Armonk, NY) software. Continuous variables were compared using the Student’s t-test or Mann-Whitney U test. Categorical data were compared using Chi-squared test or Fisher’s exact test. Multivariate logistic regression analysis was performed to determine the independent risk factors for IP. Means are reported as mean ± standard deviation. Median values with the interquartile ranges
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(25th percentile, 75th percentile) were also reported. Odds ratios (OR) are reported with 95% confidence intervals (CIs). The C-statistic is also reported. A p-value ≤ 0.05 was considered statistically significant. The institutional review board at MetroHealth Medical Center approved the study.
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3. Results
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The study population consisted of 386 patients who underwent thyroidectomy, including total thyroidectomy in 241, completion thyroidectomy in 17 and thyroid lobectomy and isthmusectomy in 145 patients. The mean age was 52 ± 14 years and 327 (84.7%) patients were female. The mean and median thyroid gland weight were 69 ± 79.7 g and 38 (19, 96) g, respectively. Demographic data and clinical characteristics for the study population are presented in Table 1. Twenty-five (6.5%) patients underwent reoperation, 40 (10.4%) patients underwent central compartment neck dissection and 128 (33.2%) patients underwent parathyroid gland autotransplantation. IP occurred in 78 (20.2%) patients, of which 12 (15.4%) had intrathyroidal glands.
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In patients with and without IP, the mean postoperative calcium levels were 8.24 ± 0.59 mg/dL and 8.37 ± 0.52 mg/dL (p = 0.071) and the median postoperative calcium levels were 8.3 (7.8, 8.5) mg/dL and 8.3 (8.1, 8.7) mg/dL, respectively. Table 2 compares patients who underwent IP to those who did not with respect to gender, operative details, pathology, thyroid gland weight and hypoparathyroidism. Univariate analysis revealed that female gender, total thyroidectomy, substernal thyroid gland, malignancy, central compartment neck dissection and low thyroid gland weight were significant factors associated with IP. In patients with malignancy, the mean thyroid gland weight in those with or without IP were 36.3 g ± 37.3 g and 77.3 g ± 85.3 g, respectively (p < 0.001), and the median thyroid gland weight in those with or without IP were 22.5 (15, 37.4) g and 21 (15, 55) g, respectively (p = 0.054).
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4. Discussion
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Multivariate logistic regression analysis revealed that female gender, central compartment lymph node dissection, and thyroid gland weight were independent variables associated with IP (Table 3). The C-statistic was determined to be 0.724. Permanent hypoparathyroidism occurred in 7 (2.7%) of 258 patients following total or completion thyroidectomy, 4 (6.7%) with IP compared to 3 (1.5%) without IP (p = 0.033).
Temporary hypocalcemia and permanent hypoparathyroidism have been reported in 5.4-29.1% and 0.5-4.7% of patients who have undergone total thyroidectomy, respectively [3, 7, 15, 16]. Higher rates of permanent hypoparathyroidism have been reported in patients who have undergone total thyroidectomy in combination with central compartment neck dissection [11, 17] and reoperative thyroidectomy [18, 19]. Permanent hypoparathyroidism is a major complication of thyroidectomy associated with both short and long-term sequelae. Short-term sequelae include numbness, paresthesias, muscle cramps, tetany, seizures, malformation of the teeth, impaired kidney function and arrhythmias. Long-term sequelae include slowing of growth and mental development, cataracts and calcifications in the basal ganglia with seizures and disturbances of balance.
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The etiology of permanent hypoparathyroidism following thyroidectomy is usually multifactorial. Factors which may predispose to permanent hypoparathyroidism include crush injury to the parathyroid glands, interruption of the blood supply, thermal injury and inadvertent removal of one or more parathyroid glands. In our study, IP was unexpectedly found to occur in 20% of patients undergoing thyroid lobectomy or total thyroidectomy. Our incidence of IP is similar to what is reported in the literature, ranging from 4-22% (Table 4). The incidence of IP that has been previously published may be an underestimate as not all studies account for intrathyroidal parathyroid glands [20]. Some exclude parathyroid glands that are removed along with tumor [21, 22] and others exclude patients with central compartment neck dissection, invasive carcinoma and/or reoperative thyroidectomy [23, 24]. Our patient population may have been at higher risk for IP given that 7% of patients underwent reoperative thyroidectomy and 10% underwent concomitant central compartment neck dissection, both of which have been reported to be associated with a higher risk of IP [11]. In addition, our pathological reports do not clearly distinguish between parathyroid glands and parathyroid gland fragments, which may include remnant tissue from a parathyroid gland that was ultimately autotransplanted. The rate of permanent hypoparathyroidism in our series was 2.7% and this was calculated excluding patients who underwent thyroid lobectomy. Patients with parathyroid glands that were inadvertently removed during thyroidectomy were more likely to develop permanent hypoparathyroidism, a finding that has also been documented in only a minority of studies [20, 22]. Most studies have not found a relationship between IP and permanent hypoparathyroidism [10, 21, 23, 25-30].
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Although a routine systematic search for the parathyroid glands was not routinely performed in our series, one-third of patients underwent autotransplantation of one or more parathyroid glands that were identified and were unable to be preserved in situ. The variable location of the parathyroid glands may contribute to the risk of IP, particularly when a central compartment neck dissection is performed. In 15% of our patients with IP, IP was due to removal of a parathyroid gland that was intrathyroidal and thus was not preventable. Autopsy studies have documented intrathyroidal parathyroid glands in 2-5% of patients [12, 31].
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Independent risk factors for IP were female sex, central compartment lymph node dissection and a lower thyroid gland weight. Of these risk factors, only central compartment lymph node dissection is modifiable. Other authors have also found central compartment neck dissection to be a risk factor for IP [10, 11, 28, 30]. In our study, 25 (63%) of 40 patients who underwent central compartment neck dissection had a parathyroid gland inadvertently removed. A central compartment neck dissection includes removal of the prelaryngeal, pretracheal and bilateral paratracheal lymph nodes (level VI) and a routine transcervical thymectomy to ensure clearance of the anterior mediastinal lymph nodes (level VII). As a result, the inferior parathyroid glands, which are often found in ectopic locations including the thyrothymic ligament, the thymus and the anterior mediastinum, are particularly susceptible to removal during a central compartment neck dissection. Parathyroid glands can be embedded with lymph nodes, making them difficult to identify. This is an important consideration when weighing the risks and benefits of performing a prophylactic central compartment lymph node dissection in
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patients with thyroid cancer who have no clinical, radiographic or intraoperative evidence of lymph node metastases. The results of this study emphasize the need for performing a systematic search for the inferior parathyroid glands and autotransplanting them as needed prior to performing a therapeutic central compartment neck dissection. It is also important to examine the specimen from the central compartment neck dissection for parathyroid glands that can be autotransplanted. Other authors have also found that female sex is a risk factor for IP [25, 27]. The reason for this is unclear. Manouras and colleagues have suggested that the reason may be that intrathyroidal parathyroid glands are more common in women [27], although this has never been verified.
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In our series, lower thyroid gland weight was also a risk factor for IP. Sorgato and colleagues also found a significant correlation between low gland weight and IP [10]. It may be that parathyroid glands are more likely to be located within the capsule or in juxtaposition to the thyroid gland when the gland is smaller, and thus more vulnerable to inadvertent removal. It may also be related to the fact that patients with thyroid cancer have smaller thyroid glands and they undergo a more complete resection than patients with benign multinodular goiter, making the parathyroid glands more vulnerable to removal. In our series, thyroid cancer was found to be predictive of IP on univariate analysis and patients with thyroid cancer had a lower mean gland weight. Other studies have suggested that malignant thyroid disease may be a risk factor for IP [10, 20, 22, 24, 28, 32, 33].
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5. Conclusions
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Our study has several limitations. All thyroidectomies were performed by a single surgeon at a single institution, and as a result, our findings may not be generalizable to a larger population. The study was retrospective in nature. The location of the incidentally discovered parathyroid glands (intrathyroidal, subcapsular, within the central compartment tissue, etc.) and whether the parathyroid tissue identified was a fragment or a whole gland was not always delineated in the pathology report.
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In conclusion, it is important for surgeons to recognize that it is not uncommon to remove one or more parathyroid glands during thyroidectomy and a significant percentage may be due to an intrathyroidal location. It is also important to recognize that IP is associated with a higher rate of permanent hypoparathyroidism, a complication associated with significant short and long-term sequelae. Central compartment neck dissection is an independent and remediable risk factor for IP. Prior to completing a central compartment neck dissection, a thorough search for the inferior parathyroid glands and routine autotransplantation may help to reduce IP and permanent hypoparathyroidism. 6. Disclosures. None of the authors have any conflicts of interest to report.
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7. References [1] Sun GH, DeMonner S, Davis MM. Epidemiological and economic trends in inpatient and outpatient thyroidectomy in the United States, 1996-2006. Thyroid. 2013;23(6):727-733.
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[2] Rosato L, Avenia N, De Palma M, et al. Complications of total thyroidectomy: incidence, prevention and treatment. Chirurgia Italiana. 2002;54(5):635-642. [3] Bhattacharyya N, Fried MP. Assessment of the morbidity and complications of total thyroidectomy. Arch Otolaryngol Head Neck Surg. 2002;128(4):389-392.
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[4] Lo CY, Kwok KF, Yuen PW. A prospective evaluation of recurrent laryngeal nerve paralysis during thyroidectomy. Arch Surg. 2000;135(2):204-207.
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[5] Rosenbaum MA, Haridas M, McHenry CR. Life-threatening neck hematoma complicating thyroid and parathyroid surgery. Am J Surg. 2008;195(3):339-343. [6] Lang BH, Yih PC, Lo CY. A review of the risk factors and timing for postoperative hematoma after thyroidectomy: is outpatient thyroidectomy really safe? World J Surg. 2012;36(10):2497-2502. [7] Gonzalez-Botas JH, Piedrahita DL. Hypocalcemia after total thyroidectomy: incidence, control and treatment. Acta Otorrinolaringologica Espanola. 2013;64(2):102-107.
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[8] Paek SH, Lee YM, Min SY, Kim SW, Chung KW, Young YK. Risk factors of hypoparathyroidism following total thyroidectomy for thyroid cancer. World J Surg. 2013;37(1):94-101.
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[9] Asari R, Passler C, Kaczirek K, Scheuba C, Niederle B. Hypoparathyroidism after total thyroidectomy: a prospective study. Arch Surg. 2008;143(2):132-137. [10] Sorgato N, Pennelli G, Boschin IM, et al. Can we avoid inadvertent parathyroidectomy during thyroid surgery? In vivo. 2009;23:433-440.
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[11] Lin DT, Patel SG, Shaha AR, et al. Incidence of inadvertent parathyroid removal during thyroidectomy. The Laryngoscope. 2002;112:608-611. [12] Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human parathyroid glands. Surg. 1984;95:14. [13] McHenry CR. Open neck exploration for hyperparathyroidism. In: Operative Techniques in Surgery. Mulholland MW(ed) Wolters Kluwer Health, Philadelphia, PA, 2015: 1700-1710. [14] Phitayakorn Roy, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg. 2006;191(3):418-423.
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[15] Pattou F, Combemale F, Fabre S, et al. Hypocalcemia following thyroid surgery: incidence and prediction of outcome. World J Surg. 1998;22(7):718-724. [16] Youngwirth L, Benavidez J, Sippel R, et al. Parathyroid hormone deficiency after total thyroidectomy: incidence and time. J Surg Res. 2010;163(1):69-71.
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[17] McHenry CR, Stulberg JJ. Prophylactic central compartment neck dissection for papillary thyroid cancer. Surg Clin N Am. 2014;94(3):529-540. [18] Calo PG, Pisano G, Medas F, Tatti A, Tuveri M, Nicolosi A. Risk factors in reoperative thyroid surgery for recurrent goitre: our experience. G Chir. 2012;33(10):335-338.
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[19] Lefevre JH, Tresallet C, Leenhardt L, Jublanc C, Chigot JP, Menegaux F. Reoperative surgery for thyroid disease. Langenbecks Arch Surg. 2007;392(6):685-691.
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[20] Sippel RS, Ozgul O, Hartig GK, Mack EA, Chen H. Risks and consequences of incidental parathyroidectomy during thyroid resection. ANZ J Surg. 2007;77(1-2):33-36. [21] Sasson AR, Pingpank JF, Wetherington RW, Hanlon AL, Ridge JA. Incidental parathyroidectomy during thyroid surgery does not cause transient symptomatic hypocalcemia. Arch Otolaryngol Head Neck Surg. 2001;127(3):304-308.
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[22] 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(7):1047-1051. [23] 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(9):2324-2328.
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[24] 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(4):143-148.
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[25] Sakorafas GH, Stafyla V, Bramis C, Kotsifopoulos N, Kolettis T, Kassaras G. Incidental parathyroidectomy during thyroid surgery: an underappreciated complication of thyroidectomy. World J Surg. 2005;29(12):1539-1543. [26] Gourgiotis S, Moustafellos P, Dimopoulos N, et al. Inadvertent parathyroidectomy during thyroid surgery: the incidence of a complication of thyroidectomy. Langenbecks Arch Surg. 2006;391:557-560. [27] Manouras A, Markogiannakis H, Lagoudianakis E, et al. Unintentional parathyroidectomy during total thyroidectomy. Head Neck. 2008;30(4):497-502.
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[28] 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(3):207-211. [29] Erbil Y, Barbaros U, Ozbey N, Aral F, Ozarmagan S. Risk factors of incidental parathyroidectomy after thyroidectomy for benign thyroid disorders. Int J Surg. 2009;7(1):58-61.
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[30] Cavanagh JP, Bullock M, Hart RD, Trites JR, MacDonald K, Taylor SM. Incidence of parathyroid tissue in level VI neck dissection. J Otolaryngol Head Neck Surg. 2011;40(1):27-33.
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[31] Akerstrom G, Rudberg C, Grimelius L, Johansson H, Lundstrom B, Rastad J. Causes of failed primary exploration and technical aspects of re-operation in primary hyperparathyroidism. World J Su [32] Spiliotis J, Vaxevanidou A, Sergouniotis F, et al. Risk factors and consequences of incidental parathyroidectomy during thyroidectomy. Am Surg. 2010;76(4):436-441.
REFEREES
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[33] Lee NJ, Blakey JD, Bhuta S, Calcaterra TC. Unintentional parathyroidectomy during thyroidectomy. Laryngoscope. 1999;109(8):1238-1240.
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Submit names and institutional email addresses of several potential referees. The editor retains the sole right to decide whether or not the suggested reviewers are used. Herbert Chen, M.D. [email protected] Bryan Richmond, M.D. [email protected] John I Lew, M.D. [email protected]
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Table 1. Demographic and descriptive data for patients undergoing thyroidectomy. Number of patients
Percentage of patients
59 327
15.3 84.7
52 ± 14 52 (42, 61)
Mean age (years) Median age (years)
Pathology Benign Malignant
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Parathyroid glands inadvertently removed One Two Three Intrathyroidal parathyroid glands
37.6 62.4 6.5 4.4 46.4 10.4 33.2
69 ± 80 38 (19, 96)
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Mean thyroid gland weight (g) Median thyroid gland weight (g)
145 241 25 17 179 40 128
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Thyroid lobectomy and isthmusectomy (includes completion thyroidectomy) Total thyroidectomy Reoperative thyroidectomy Completion thyroidectomy Substernal goiter Central compartment neck dissection Parathyroid autotransplantation
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Thyroidectomy
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Variable Gender Male Female
306 80
79.3 20.7
78 66 11 1 12
84.6 14.1 1.3 15.4
Table 2. Comparison of patients with and without inadvertent parathyroidectomy (IP). Variable (number of patients involved) Mean thyroid gland weight (g) Median thyroid gland weight (g) Female gender (327) Total thyroidectomy (241) Reoperative thyroidectomy (25) Completion thyroidectomy (17) Substernal goiter (179)
Patients (%) with IP, n=78 42.4 ± 45 29.6 (16.4, 46) 72 (92.3) 56 (71.8) 4 (5.1) 4 (5.1) 28 (35.9)
Patients (%) without IP, n=308 75.7 ± 85.1 40 (20, 109) 255 (82.8) 185 (60) 21 (6.8) 13 (4.2) 151 (49)
p value 0.001 0.001 0.036 0.049 0.797 0.758 0.042
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15 (4.9) 43 (14) 34 (11) 21 (6.8)
< 0.001 < 0.001 0.294 0.797
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25 (32.1) 37 (47.4) 5 (6.4) 4 (5.1)
Central compartment neck dissection (40) Malignant pathology (80) Graves’ disease (39) Hashimoto’s thyroiditis (25)
Table 3. Independent variables associated with inadvertent parathyroidectomy (IP). Odds ratio 2.768 9.584 0.994
95% confidence interval 1.045 - 7.33 4.485 - 20.481 0.989 - 0.999
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Variable Female gender Central compartment neck dissection Thyroid gland weight
p value 0.04 < 0.001 0.02
Table 4. Other authors’ reported incidence of inadvertent parathyroidectomy (IP). Incidence of IP, % 9 11 15 9.1 17.7 21.6 17.4 3.7 12.4 6.4 19.7 10.9 12.9 7.9 12.6 9.5
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Number of patients 1163 414 141 220 158 315 126 273 307 513 508 440 365 882 207 126
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Year 1998 1999 2001 2002 2005 2006 2006 2007 2007 2007 2008 2009 2009 2009 2010 2013
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Author Bergamaschi Lee Sasson Lin Sakorafas Gourgiotis Rix Irkorucu Abboud Sippel Manouras Erbil Rajinikanth Sorgato Youssef Sheahan
S0022-4804(16)30140-8
DOI:
10.1016/j.jss.2016.06.019
Reference:
YJSRE 13817
To appear in:
Journal of Surgical Research
Received Date: 3 February 2016 Revised Date:
18 May 2016
Accepted Date: 7 June 2016
Please cite this article as: Zhou HY, He JC, McHenry CR, Inadvertent Parathyroidectomy: Incidence, Risk Factors and Outcomes, Journal of Surgical Research (2016), doi: 10.1016/j.jss.2016.06.019. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Inadvertent Parathyroidectomy: Incidence, Risk Factors and Outcomes
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Hannah Y. Zhou1,3, MD, Jack C. He, MD1,3, Christopher R. McHenry, MD2,3
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Department of Surgery, University Hospitals Case Medical Center, Cleveland, OH 44106, USA Department of Surgery, MetroHealth Medical Center, Cleveland, OH 44109, USA 3 Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA
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Corresponding Author: Christopher R. McHenry, M.D. Vice Chairman, Department of Surgery Director, Division of General Surgery MetroHealth Medical Center, H-918 2500 MetroHealth Drive Cleveland, OH 44109 [email protected] (216) 778-8917
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AUTHOR CONTRIBUTIONS
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Dr. Zhou was involved in the design of this study, performed data collection and analysis and was involved in the authorship of all sections of the manuscript. Dr. He was involved with data analysis and revision of the manuscript. Dr. McHenry was involved in the design of the study, supervised the data collection, data analysis and was involved in the authorship of all sections of the manuscript. ABSTRACT
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Introduction Parathyroid glands are ≤ 5mm, often subcapsular or intrathyroidal, and obscured by lymph nodes, making preservation a challenge. The purpose of this study was to determine the incidence of inadvertent parathyroidectomy (IP) and whether it contributes to hypoparathyroidism following thyroidectomy.
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Materials and methods A retrospective review of all thyroidectomies by a single surgeon from January, 2010 to August, 2014 was completed to determine the rate of IP and permanent hypoparathyroidism. Medical records were assessed for demographics, extent of thyroidectomy, central compartment neck dissection, thyroid gland weight, parathyroid autotransplantation, reoperation, pathology, postoperative calcium levels and number of parathyroid glands removed.
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Results A total of 386 patients underwent thyroidectomy. Mean age was 52 years and 327 (85%) patients were female. There were 25 (7%) patients who underwent reoperation, 40 (10%) who underwent central compartment neck dissection and 128 (33%) who underwent parathyroid autotransplantation. IP occurred in 78 (20%) patients. Permanent hypoparathyroidism occurred in 7 (2.7%) of 258 patients following total or completion thyroidectomy, 4 (6.7%) with IP compared to 3 (1.5%) without IP (p = 0.033). Logistic regression analysis revealed that female gender (odds ratio = 2.768, p = 0.040), central compartment neck dissection (odds ratio = 9.584, p = 0.001) and thyroid gland weight (odds ratio = 0.994, p = 0.022) were independent factors associated with IP.
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Conclusions IP, which occurred in 20% of patients undergoing thyroidectomy, is a potentially remediable factor associated with a higher rate of hypoparathyroidism. Central compartment neck dissection is an independent risk factor for IP. KEY WORDS
Inadvertent parathyroidectomy, hypoparathyroidism, central compartment neck dissection
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1. Introduction
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Thyroidectomy is performed for a variety of indications, including thyroid cancer, nodular thyroid disease with an indeterminate or nondiagnostic fine needle aspiration biopsy, a symptomatic goiter or a goiter with tracheal or esophageal impingement, substernal extension and thyrotoxicosis. The estimated number of thyroidectomies performed yearly in the United States exceeds 92,000 [1]. As with any operation, challenges include minimizing complications. The major complications of thyroidectomy include recurrent laryngeal nerve injury (1.2-7.6%) [2-4], bleeding requiring reoperation (0.6-1.6%) [2, 3, 5, 6] and permanent hypoparathyroidism (1.2-5.5%) [2, 7-10].
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The parathyroid glands can be challenging to identify intraoperatively. A parathyroid gland weighs approximately 35 mg, measures 5 mm in maximum dimension and is usually surrounded by adipose and loose connective tissue. Parathyroid glands can become discolored with bleeding and can be mistaken for thyroid, nodal or adipose tissue. Parathyroid glands that are subcapsular may be flattened in appearance, making them more difficult to identify and more vulnerable to removal during thyroidectomy. Parathyroid glands are often embedded with lymph nodes and can be more difficult to identify in patients with enlarged lymph nodes in the central compartment of the neck from cancer or Hashimoto’s thyroiditis. Hypoparathyroidism is reported to be higher in patients undergoing thyroidectomy with central compartment neck dissection [8, 9, 11], suggesting that parathyroid glands may be more vulnerable to removal during central compartment neck dissection compared to thyroidectomy alone. Parathyroid glands may also be intrathyroidal and their removal cannot be prevented.
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Embryologically, the parathyroid glands develop from the third and fourth branchial pouches. The superior parathyroid glands arise from the fourth branchial pouch along with the lateral lobes of the thyroid gland. The inferior parathyroid glands develop from the third branchial pouch along with the thymus. The normal anatomic location of the superior parathyroid gland is fairly constant, with 80% of superior glands found near the posterior aspect of the upper thyroid lobe at the level of the cricoid cartilage where the recurrent laryngeal nerve enters the larynx posterior to the inferior pharyngeal constrictor muscle [12]. It is typically posterior and superior to the recurrent laryngeal nerve, approximately 1 cm cephalad to the junction of the inferior thyroid artery and the recurrent laryngeal nerve [13]. Ectopic superior glands can be found in the tracheoesophageal groove, in a paraesophageal, retroesophageal or retropharyngeal location, in the posterior mediastinum, within the carotid sheath or within the thyroid gland [14]. The normal anatomic location of an inferior parathyroid gland is approximately 1 cm caudal to the junction of the inferior thyroid artery and the recurrent laryngeal nerve and anterior to the recurrent laryngeal nerve on the posterior aspect of the inferior pole of the lobe of thyroid gland [13]. Because of its more extensive migration during embryologic development, an inferior parathyroid gland is more likely to be found in an ectopic location. An ectopic inferior parathyroid gland may be found in the thymus, the thyrothymic ligament, the anterior mediastinum, undescended in a submandibular location or within the thyroid gland [14]. Due to the small size and variable location of the parathyroid glands, preservation of the parathyroid glands can be a challenge during thyroidectomy. The purpose of this study was to
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determine the incidence of inadvertent parathyroidectomy (IP) during thyroidectomy at our institution, its risk factors and whether it is associated with the development of hypoparathyroidism. 2. Materials and Methods
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A retrospective review of electronic medical records and a prospectively maintained database was completed for a consecutive group of patients who underwent thyroidectomy by a single surgeon from January 2010 through August 2014. The pathology reports for all study patients were reviewed to determine if one or more parathyroid glands were unexpectedly found in the specimen submitted to pathology. During the study period, a routine protocol for processing the thyroid gland was followed at our institution. Pathologists completed a gross examination of the thyroid gland and the excised contents of the central compartment of the neck. A routine pathologic examination of all thyroid nodules as well as one representative section for every 1 cm of the remainder of the thyroid gland was completed. IP was defined as the unrecognized removal of a parathyroid gland or any parathyroid tissue that was found in the specimen submitted for paraffin evaluation. The determination of an incidentally discovered parathyroid gland or parathyroid tissue was made on the basis of microscopic pathologic examination. An intrathyroidal parathyroid gland was defined as a gland that was completely surrounded by thyroid parenchyma.
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A systematic search for parathyroid glands, that were not identified during the course of the normal operative dissection, was not performed. The distal branches of the inferior thyroid artery were ligated adjacent to the thyroid gland. Ligation of the trunk of the inferior thyroid artery was avoided. If a parathyroid gland could not be preserved in situ or was thought to be devascularized during the course of the thyroidectomy, confirmation of parathyroid tissue was obtained with a frozen section examination and the remainder of the gland was minced and autotransplanted into the ipsilateral sternocleidomastoid muscle. A parathyroid gland that was removed and later autotransplanted did not constitute IP.
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Patient medical records were assessed for potential risk factors that might contribute to IP and to determine if IP contributed to the development of hypoparathyroidism. Data that was obtained included demographics, extent of thyroidectomy, central compartment neck dissection, thyroid gland weight, retrosternal goiter, parathyroid autotransplantation, reoperative thyroidectomy, pathology and postoperative calcium levels. Serum calcium levels were measured on the first postoperative day in all patients who underwent total or completion thyroidectomy. Follow-up calcium levels were obtained in an outpatient setting for patients with hypocalcemia, patients placed on calcium supplementation and patients who developed symptoms of hypocalcemia. A patient was determined to have permanent hypoparathyroidism if he or she required vitamin D and/or calcium for maintenance of eucalcemia for 6 months following thyroidectomy. Statistical analyses were performed using IBM SPSS© version 22 (IBM, Armonk, NY) software. Continuous variables were compared using the Student’s t-test or Mann-Whitney U test. Categorical data were compared using Chi-squared test or Fisher’s exact test. Multivariate logistic regression analysis was performed to determine the independent risk factors for IP. Means are reported as mean ± standard deviation. Median values with the interquartile ranges
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(25th percentile, 75th percentile) were also reported. Odds ratios (OR) are reported with 95% confidence intervals (CIs). The C-statistic is also reported. A p-value ≤ 0.05 was considered statistically significant. The institutional review board at MetroHealth Medical Center approved the study.
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3. Results
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The study population consisted of 386 patients who underwent thyroidectomy, including total thyroidectomy in 241, completion thyroidectomy in 17 and thyroid lobectomy and isthmusectomy in 145 patients. The mean age was 52 ± 14 years and 327 (84.7%) patients were female. The mean and median thyroid gland weight were 69 ± 79.7 g and 38 (19, 96) g, respectively. Demographic data and clinical characteristics for the study population are presented in Table 1. Twenty-five (6.5%) patients underwent reoperation, 40 (10.4%) patients underwent central compartment neck dissection and 128 (33.2%) patients underwent parathyroid gland autotransplantation. IP occurred in 78 (20.2%) patients, of which 12 (15.4%) had intrathyroidal glands.
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In patients with and without IP, the mean postoperative calcium levels were 8.24 ± 0.59 mg/dL and 8.37 ± 0.52 mg/dL (p = 0.071) and the median postoperative calcium levels were 8.3 (7.8, 8.5) mg/dL and 8.3 (8.1, 8.7) mg/dL, respectively. Table 2 compares patients who underwent IP to those who did not with respect to gender, operative details, pathology, thyroid gland weight and hypoparathyroidism. Univariate analysis revealed that female gender, total thyroidectomy, substernal thyroid gland, malignancy, central compartment neck dissection and low thyroid gland weight were significant factors associated with IP. In patients with malignancy, the mean thyroid gland weight in those with or without IP were 36.3 g ± 37.3 g and 77.3 g ± 85.3 g, respectively (p < 0.001), and the median thyroid gland weight in those with or without IP were 22.5 (15, 37.4) g and 21 (15, 55) g, respectively (p = 0.054).
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4. Discussion
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Multivariate logistic regression analysis revealed that female gender, central compartment lymph node dissection, and thyroid gland weight were independent variables associated with IP (Table 3). The C-statistic was determined to be 0.724. Permanent hypoparathyroidism occurred in 7 (2.7%) of 258 patients following total or completion thyroidectomy, 4 (6.7%) with IP compared to 3 (1.5%) without IP (p = 0.033).
Temporary hypocalcemia and permanent hypoparathyroidism have been reported in 5.4-29.1% and 0.5-4.7% of patients who have undergone total thyroidectomy, respectively [3, 7, 15, 16]. Higher rates of permanent hypoparathyroidism have been reported in patients who have undergone total thyroidectomy in combination with central compartment neck dissection [11, 17] and reoperative thyroidectomy [18, 19]. Permanent hypoparathyroidism is a major complication of thyroidectomy associated with both short and long-term sequelae. Short-term sequelae include numbness, paresthesias, muscle cramps, tetany, seizures, malformation of the teeth, impaired kidney function and arrhythmias. Long-term sequelae include slowing of growth and mental development, cataracts and calcifications in the basal ganglia with seizures and disturbances of balance.
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The etiology of permanent hypoparathyroidism following thyroidectomy is usually multifactorial. Factors which may predispose to permanent hypoparathyroidism include crush injury to the parathyroid glands, interruption of the blood supply, thermal injury and inadvertent removal of one or more parathyroid glands. In our study, IP was unexpectedly found to occur in 20% of patients undergoing thyroid lobectomy or total thyroidectomy. Our incidence of IP is similar to what is reported in the literature, ranging from 4-22% (Table 4). The incidence of IP that has been previously published may be an underestimate as not all studies account for intrathyroidal parathyroid glands [20]. Some exclude parathyroid glands that are removed along with tumor [21, 22] and others exclude patients with central compartment neck dissection, invasive carcinoma and/or reoperative thyroidectomy [23, 24]. Our patient population may have been at higher risk for IP given that 7% of patients underwent reoperative thyroidectomy and 10% underwent concomitant central compartment neck dissection, both of which have been reported to be associated with a higher risk of IP [11]. In addition, our pathological reports do not clearly distinguish between parathyroid glands and parathyroid gland fragments, which may include remnant tissue from a parathyroid gland that was ultimately autotransplanted. The rate of permanent hypoparathyroidism in our series was 2.7% and this was calculated excluding patients who underwent thyroid lobectomy. Patients with parathyroid glands that were inadvertently removed during thyroidectomy were more likely to develop permanent hypoparathyroidism, a finding that has also been documented in only a minority of studies [20, 22]. Most studies have not found a relationship between IP and permanent hypoparathyroidism [10, 21, 23, 25-30].
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Although a routine systematic search for the parathyroid glands was not routinely performed in our series, one-third of patients underwent autotransplantation of one or more parathyroid glands that were identified and were unable to be preserved in situ. The variable location of the parathyroid glands may contribute to the risk of IP, particularly when a central compartment neck dissection is performed. In 15% of our patients with IP, IP was due to removal of a parathyroid gland that was intrathyroidal and thus was not preventable. Autopsy studies have documented intrathyroidal parathyroid glands in 2-5% of patients [12, 31].
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Independent risk factors for IP were female sex, central compartment lymph node dissection and a lower thyroid gland weight. Of these risk factors, only central compartment lymph node dissection is modifiable. Other authors have also found central compartment neck dissection to be a risk factor for IP [10, 11, 28, 30]. In our study, 25 (63%) of 40 patients who underwent central compartment neck dissection had a parathyroid gland inadvertently removed. A central compartment neck dissection includes removal of the prelaryngeal, pretracheal and bilateral paratracheal lymph nodes (level VI) and a routine transcervical thymectomy to ensure clearance of the anterior mediastinal lymph nodes (level VII). As a result, the inferior parathyroid glands, which are often found in ectopic locations including the thyrothymic ligament, the thymus and the anterior mediastinum, are particularly susceptible to removal during a central compartment neck dissection. Parathyroid glands can be embedded with lymph nodes, making them difficult to identify. This is an important consideration when weighing the risks and benefits of performing a prophylactic central compartment lymph node dissection in
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patients with thyroid cancer who have no clinical, radiographic or intraoperative evidence of lymph node metastases. The results of this study emphasize the need for performing a systematic search for the inferior parathyroid glands and autotransplanting them as needed prior to performing a therapeutic central compartment neck dissection. It is also important to examine the specimen from the central compartment neck dissection for parathyroid glands that can be autotransplanted. Other authors have also found that female sex is a risk factor for IP [25, 27]. The reason for this is unclear. Manouras and colleagues have suggested that the reason may be that intrathyroidal parathyroid glands are more common in women [27], although this has never been verified.
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In our series, lower thyroid gland weight was also a risk factor for IP. Sorgato and colleagues also found a significant correlation between low gland weight and IP [10]. It may be that parathyroid glands are more likely to be located within the capsule or in juxtaposition to the thyroid gland when the gland is smaller, and thus more vulnerable to inadvertent removal. It may also be related to the fact that patients with thyroid cancer have smaller thyroid glands and they undergo a more complete resection than patients with benign multinodular goiter, making the parathyroid glands more vulnerable to removal. In our series, thyroid cancer was found to be predictive of IP on univariate analysis and patients with thyroid cancer had a lower mean gland weight. Other studies have suggested that malignant thyroid disease may be a risk factor for IP [10, 20, 22, 24, 28, 32, 33].
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5. Conclusions
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Our study has several limitations. All thyroidectomies were performed by a single surgeon at a single institution, and as a result, our findings may not be generalizable to a larger population. The study was retrospective in nature. The location of the incidentally discovered parathyroid glands (intrathyroidal, subcapsular, within the central compartment tissue, etc.) and whether the parathyroid tissue identified was a fragment or a whole gland was not always delineated in the pathology report.
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In conclusion, it is important for surgeons to recognize that it is not uncommon to remove one or more parathyroid glands during thyroidectomy and a significant percentage may be due to an intrathyroidal location. It is also important to recognize that IP is associated with a higher rate of permanent hypoparathyroidism, a complication associated with significant short and long-term sequelae. Central compartment neck dissection is an independent and remediable risk factor for IP. Prior to completing a central compartment neck dissection, a thorough search for the inferior parathyroid glands and routine autotransplantation may help to reduce IP and permanent hypoparathyroidism. 6. Disclosures. None of the authors have any conflicts of interest to report.
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7. References [1] Sun GH, DeMonner S, Davis MM. Epidemiological and economic trends in inpatient and outpatient thyroidectomy in the United States, 1996-2006. Thyroid. 2013;23(6):727-733.
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[2] Rosato L, Avenia N, De Palma M, et al. Complications of total thyroidectomy: incidence, prevention and treatment. Chirurgia Italiana. 2002;54(5):635-642. [3] Bhattacharyya N, Fried MP. Assessment of the morbidity and complications of total thyroidectomy. Arch Otolaryngol Head Neck Surg. 2002;128(4):389-392.
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[4] Lo CY, Kwok KF, Yuen PW. A prospective evaluation of recurrent laryngeal nerve paralysis during thyroidectomy. Arch Surg. 2000;135(2):204-207.
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[5] Rosenbaum MA, Haridas M, McHenry CR. Life-threatening neck hematoma complicating thyroid and parathyroid surgery. Am J Surg. 2008;195(3):339-343. [6] Lang BH, Yih PC, Lo CY. A review of the risk factors and timing for postoperative hematoma after thyroidectomy: is outpatient thyroidectomy really safe? World J Surg. 2012;36(10):2497-2502. [7] Gonzalez-Botas JH, Piedrahita DL. Hypocalcemia after total thyroidectomy: incidence, control and treatment. Acta Otorrinolaringologica Espanola. 2013;64(2):102-107.
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[8] Paek SH, Lee YM, Min SY, Kim SW, Chung KW, Young YK. Risk factors of hypoparathyroidism following total thyroidectomy for thyroid cancer. World J Surg. 2013;37(1):94-101.
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[9] Asari R, Passler C, Kaczirek K, Scheuba C, Niederle B. Hypoparathyroidism after total thyroidectomy: a prospective study. Arch Surg. 2008;143(2):132-137. [10] Sorgato N, Pennelli G, Boschin IM, et al. Can we avoid inadvertent parathyroidectomy during thyroid surgery? In vivo. 2009;23:433-440.
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[11] Lin DT, Patel SG, Shaha AR, et al. Incidence of inadvertent parathyroid removal during thyroidectomy. The Laryngoscope. 2002;112:608-611. [12] Akerstrom G, Malmaeus J, Bergstrom R. Surgical anatomy of human parathyroid glands. Surg. 1984;95:14. [13] McHenry CR. Open neck exploration for hyperparathyroidism. In: Operative Techniques in Surgery. Mulholland MW(ed) Wolters Kluwer Health, Philadelphia, PA, 2015: 1700-1710. [14] Phitayakorn Roy, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg. 2006;191(3):418-423.
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[15] Pattou F, Combemale F, Fabre S, et al. Hypocalcemia following thyroid surgery: incidence and prediction of outcome. World J Surg. 1998;22(7):718-724. [16] Youngwirth L, Benavidez J, Sippel R, et al. Parathyroid hormone deficiency after total thyroidectomy: incidence and time. J Surg Res. 2010;163(1):69-71.
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[17] McHenry CR, Stulberg JJ. Prophylactic central compartment neck dissection for papillary thyroid cancer. Surg Clin N Am. 2014;94(3):529-540. [18] Calo PG, Pisano G, Medas F, Tatti A, Tuveri M, Nicolosi A. Risk factors in reoperative thyroid surgery for recurrent goitre: our experience. G Chir. 2012;33(10):335-338.
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[19] Lefevre JH, Tresallet C, Leenhardt L, Jublanc C, Chigot JP, Menegaux F. Reoperative surgery for thyroid disease. Langenbecks Arch Surg. 2007;392(6):685-691.
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[20] Sippel RS, Ozgul O, Hartig GK, Mack EA, Chen H. Risks and consequences of incidental parathyroidectomy during thyroid resection. ANZ J Surg. 2007;77(1-2):33-36. [21] Sasson AR, Pingpank JF, Wetherington RW, Hanlon AL, Ridge JA. Incidental parathyroidectomy during thyroid surgery does not cause transient symptomatic hypocalcemia. Arch Otolaryngol Head Neck Surg. 2001;127(3):304-308.
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[22] 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(7):1047-1051. [23] 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(9):2324-2328.
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[24] 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(4):143-148.
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[25] Sakorafas GH, Stafyla V, Bramis C, Kotsifopoulos N, Kolettis T, Kassaras G. Incidental parathyroidectomy during thyroid surgery: an underappreciated complication of thyroidectomy. World J Surg. 2005;29(12):1539-1543. [26] Gourgiotis S, Moustafellos P, Dimopoulos N, et al. Inadvertent parathyroidectomy during thyroid surgery: the incidence of a complication of thyroidectomy. Langenbecks Arch Surg. 2006;391:557-560. [27] Manouras A, Markogiannakis H, Lagoudianakis E, et al. Unintentional parathyroidectomy during total thyroidectomy. Head Neck. 2008;30(4):497-502.
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[28] 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(3):207-211. [29] Erbil Y, Barbaros U, Ozbey N, Aral F, Ozarmagan S. Risk factors of incidental parathyroidectomy after thyroidectomy for benign thyroid disorders. Int J Surg. 2009;7(1):58-61.
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[30] Cavanagh JP, Bullock M, Hart RD, Trites JR, MacDonald K, Taylor SM. Incidence of parathyroid tissue in level VI neck dissection. J Otolaryngol Head Neck Surg. 2011;40(1):27-33.
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[31] Akerstrom G, Rudberg C, Grimelius L, Johansson H, Lundstrom B, Rastad J. Causes of failed primary exploration and technical aspects of re-operation in primary hyperparathyroidism. World J Su [32] Spiliotis J, Vaxevanidou A, Sergouniotis F, et al. Risk factors and consequences of incidental parathyroidectomy during thyroidectomy. Am Surg. 2010;76(4):436-441.
REFEREES
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[33] Lee NJ, Blakey JD, Bhuta S, Calcaterra TC. Unintentional parathyroidectomy during thyroidectomy. Laryngoscope. 1999;109(8):1238-1240.
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Submit names and institutional email addresses of several potential referees. The editor retains the sole right to decide whether or not the suggested reviewers are used. Herbert Chen, M.D. [email protected] Bryan Richmond, M.D. [email protected] John I Lew, M.D. [email protected]
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Table 1. Demographic and descriptive data for patients undergoing thyroidectomy. Number of patients
Percentage of patients
59 327
15.3 84.7
52 ± 14 52 (42, 61)
Mean age (years) Median age (years)
Pathology Benign Malignant
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Parathyroid glands inadvertently removed One Two Three Intrathyroidal parathyroid glands
37.6 62.4 6.5 4.4 46.4 10.4 33.2
69 ± 80 38 (19, 96)
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Mean thyroid gland weight (g) Median thyroid gland weight (g)
145 241 25 17 179 40 128
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Thyroid lobectomy and isthmusectomy (includes completion thyroidectomy) Total thyroidectomy Reoperative thyroidectomy Completion thyroidectomy Substernal goiter Central compartment neck dissection Parathyroid autotransplantation
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Thyroidectomy
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Variable Gender Male Female
306 80
79.3 20.7
78 66 11 1 12
84.6 14.1 1.3 15.4
Table 2. Comparison of patients with and without inadvertent parathyroidectomy (IP). Variable (number of patients involved) Mean thyroid gland weight (g) Median thyroid gland weight (g) Female gender (327) Total thyroidectomy (241) Reoperative thyroidectomy (25) Completion thyroidectomy (17) Substernal goiter (179)
Patients (%) with IP, n=78 42.4 ± 45 29.6 (16.4, 46) 72 (92.3) 56 (71.8) 4 (5.1) 4 (5.1) 28 (35.9)
Patients (%) without IP, n=308 75.7 ± 85.1 40 (20, 109) 255 (82.8) 185 (60) 21 (6.8) 13 (4.2) 151 (49)
p value 0.001 0.001 0.036 0.049 0.797 0.758 0.042
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15 (4.9) 43 (14) 34 (11) 21 (6.8)
< 0.001 < 0.001 0.294 0.797
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25 (32.1) 37 (47.4) 5 (6.4) 4 (5.1)
Central compartment neck dissection (40) Malignant pathology (80) Graves’ disease (39) Hashimoto’s thyroiditis (25)
Table 3. Independent variables associated with inadvertent parathyroidectomy (IP). Odds ratio 2.768 9.584 0.994
95% confidence interval 1.045 - 7.33 4.485 - 20.481 0.989 - 0.999
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Variable Female gender Central compartment neck dissection Thyroid gland weight
p value 0.04 < 0.001 0.02
Table 4. Other authors’ reported incidence of inadvertent parathyroidectomy (IP). Incidence of IP, % 9 11 15 9.1 17.7 21.6 17.4 3.7 12.4 6.4 19.7 10.9 12.9 7.9 12.6 9.5
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Number of patients 1163 414 141 220 158 315 126 273 307 513 508 440 365 882 207 126
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Year 1998 1999 2001 2002 2005 2006 2006 2007 2007 2007 2008 2009 2009 2009 2010 2013
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Author Bergamaschi Lee Sasson Lin Sakorafas Gourgiotis Rix Irkorucu Abboud Sippel Manouras Erbil Rajinikanth Sorgato Youssef Sheahan
