|Year : 2020 | Volume
| Issue : 3 | Page : 81-86
Complications following thyroidectomy for benign thyroid diseases and their correlation with clinical, anatomical, and biochemical parameters
Aswin Prabhakaran, Riju Ramachandran, Pradeep Jacob, Misha J C Babu, Gopalakrishnan C Nair
Department of General and Endocrine Surgery, Amrita Institute of Medical Sciences, Kochi, Kerala, India
|Date of Submission||26-Jun-2019|
|Date of Decision||24-Sep-2019|
|Date of Acceptance||11-Mar-2020|
|Date of Web Publication||30-May-2020|
Dr. Riju Ramachandran
AG1, Sterling Sarovar Apartments, Kosseri Lane, Edapally, Kochi, Kerala
Source of Support: None, Conflict of Interest: None
Background: Hypocalcemia and recurrent laryngeal nerve (RLN) palsy are common complications following thyroidectomy. The study was designed to assess the effect of preoperative clinical and biochemical features and the intraoperative anatomical features on the rate of complications following total thyroidectomy (TT) for benign thyroid disease.
Materials and Methods: The prospective observational study was conducted on patients undergoing TT for benign thyroid diseases. All patients underwent complete assessment followed by the estimation of thyroid function (free T4 and thyroid-stimulating hormone). Ultrasound imaging of the neck and guided aspiration from the suspicious area for cytology were performed routinely. All patients were followed for minimum 6 months. Parameters used for the analysis included demographic features, feel of the gland, presence of adhesions to surrounding soft tissue, presence of retrosternal extension, and anatomical features of laryngeal nerves and parathyroid glands.
Results: One hundred and twenty-five eligible candidates were included in the study and temporary hypocalcemia and temporary RLN palsy occurred in 48 (38%) and 9 (6.5%) patients, respectively. None of the patients had permanent complications. Failure to identify all four parathyroids was associated with a higher incidence of hypocalcemia (P < 0.001). Anatomical variation of RLN such as prelaryngeal branching and anterior relation to inferior thyroid artery were associated with a higher incidence of RLN palsy (P < 0.001).
Conclusion: Meticulous surgical dissection and thorough knowledge of anatomy prevent the development of both hypocalcemia and RLN palsy in TT for benign thyroid disorders.
Keywords: Hypoparathyroidism, surgical complication, thyroid disease
|How to cite this article:|
Prabhakaran A, Ramachandran R, Jacob P, Babu MJ, Nair GC. Complications following thyroidectomy for benign thyroid diseases and their correlation with clinical, anatomical, and biochemical parameters. Formos J Surg 2020;53:81-6
|How to cite this URL:|
Prabhakaran A, Ramachandran R, Jacob P, Babu MJ, Nair GC. Complications following thyroidectomy for benign thyroid diseases and their correlation with clinical, anatomical, and biochemical parameters. Formos J Surg [serial online] 2020 [cited 2020 Jul 5];53:81-6. Available from: http://www.e-fjs.org/text.asp?2020/53/3/81/285400
| Introduction|| |
Benign thyroid nodules are found in 5%–15% of the general population in India and about 47 million people are affected by thyroid disorders. Thyroid surgery has become increasingly common in the population. Major complications of thyroidectomy include hypocalcemia and laryngeal nerve palsy. The incidence of transient hypocalcemia and permanent hypocalcemia following thyroidectomy is about 27% (19%–83%) and 1% (0%–3%), respectively.,
Predictors of hypocalcemia include female sex, recurrent goiter, need for re-exploration, Graves' disease, and failure to identify more than two parathyroid glands. Vascular injury is probably more frequent than inadvertent removal of parathyroid glands., Long-term management of permanent hypocalcemia necessitates high dose of calcium supplementation with Vitamin D analogs and close monitoring. These patients are at risk of developing hypercalciuria, nephrocalcinosis, or ectopic calcification in soft tissues. Hence, preserving functional parathyroid glands is of paramount importance during thyroid surgery. Conventional therapy of hypocalcemia with supplementation of calcium and active Vitamin D does not improve quality of life parameters significantly nor does it reverse abnormalities in bone remodeling characteristic of the disease.
Biochemical evidence of hypocalcemia is detected by 1st postoperative day in the majority of patients but delayed manifestations are also rarely seen. Patients with transient hypocalcemia recover usually within 4 weeks. Patients with permanent hypocalcemia require lifelong supplementation of calcium and Vitamin D metabolites (calcitriol or 1, 25-[OH]2 Vitamin D).,
Recurrent laryngeal nerve (RLN) palsy is a potentially devastating complication of thyroidectomy and occurs in 5%–8%, becoming permanent in 0.3%–3% patients.. Mechanisms of injury to the RLN include complete or partial transection, traction, contusion, crush, burn, misplaced ligature, and compromised blood supply. The consequence of an RLN injury is true vocal fold paresis or paralysis.
The prospective study was aimed to identify the impact of clinical, biochemical and intraoperative features on the incidence of hypocalcemia and recurrent nerve palsy.
| Materials and Methods|| |
The prospective study was conducted on patients undergoing total thyroidectomy (TT) for benign thyroid diseases. Patients with clinical and cytological evidence of benign thyroid disease were included in the study. Patients who were found to have incidental thyroid cancer during operation (evidenced by frozen section) were excluded. Patients who did not agree for stipulated follow-up regimen and those with cytological suspicion of malignancy and with recurrent goiters were excluded.
All patients underwent complete clinical examination followed by the estimation of serum-free thyroxine (FT4) and thyroid-stimulating hormone. Ultrasound imaging of neck was done routinely and aspiration for cytology was done from suspicious area. When clinical features of tracheal compression were present a plain computerized tomography of neck and mediastinum was performed. Indirect laryngoscopy was done for the preoperative assessment of vocal cords.
Thyroidectomy was done by an experienced surgical team that performs more than 300 operations annually. Thyroidectomy was done under general anesthesia administered by endotracheal intubation. All patients underwent direct laryngeal examination after extubation and indirect laryngoscopy in the postoperative period. Flexible strobolaryngoscopy was done when indirect laryngoscopy was inconclusive. Those who were found to have defective vocal cord movement were reviewed every month for 6 months. Serum-corrected calcium was estimated at 6 am on postoperative days and hypocalcemia is defined as serum corrected calcium level <8.5 mg/dl. Patients with hypocalcemia were followed for 6 months with monthly estimation of serum corrected calcium.
The clinical features considered to influence the rate of complications were the presence of tracheal compression, mediastinal extension, and hyperthyroidism. Intraoperative features included consistency of the goiter, adhesions to the perithyroid soft tissue, type of external division of superior laryngeal nerve (Cernea classification), course of RLN and its relation to inferior thyroid artery (ITA), and the number of parathyroid glands identified and preserved. The consistency of the gland was recorded based on the subjective assessment of the surgeon and graded as firm when goiter was not yielding to pressure and difficult to retract medially.
This study was conducted between September 2009 and August 2010. This study was approved by the institutional ethics committee (approval letter obtained on 2nd February 2012) and has been performed in accordance with the ethical standards as laid down in the 1964 declaration of Helsinki and its later amendments or comparable ethical standards.
Statistical analysis was performed using SPSS Statistics for Windows, Version 17.0. SPSS Inc., Chicago, USA. For all categorical variables, Pearson's Chi-square test was performed. For all the continuous variables, the results are given in mean ± standard deviation (SD). Probability value (P value) ≤ 0.05 was considered statistical significance. All tests of statistical significance were two-tailed.
| Results|| |
Initial cohort included 137 patients, but two were excluded since papillary thyroid cancer with central compartment nodal metastases was established. Another 10 patients were excluded since they did not comply with the stipulated follow up protocol. The study group included 125 patients with a mean age of 48.40 (SD: 12.646) and 93.6% (n: 117) of females. There were 14 patients with overt hyperthyroidism and 41 (32.8%) with radiological evidence of mediastinal extension of the goiter. Ten (8%) had signs and symptoms suggestive of tracheal compression. Majority of the goiters were firm to feel (n: 112; 90%) and 46 (37%) showed adhesions to the perithyroid soft tissues during operation.
There was no incidence of postoperative surgical site infection or of bleeding requiring exploration. The overall incidence of complication was 40% (n: 50) [Table 1]. Forty-eight (38%) had biochemical evidence of hypocalcemia, but of this, 10 (8%) were symptomatic. Nine (7%) showed defective movement of unilateral vocal cord on laryngoscopy and 3 were symptomatic. The overall complication rate showed a trend toward younger age group (45.74 years SD: 12.615 vs. 50.17 SD: 12.435; P = 0.054). The rate of overall complications was not significantly different in the sex groups (M-37.5% vs. F 40%; P = 0.881).
There was no incidence of permanent hypocalcemia, and all patients recovered after 1 month. All the nine with defective movement of vocal cord recovered after 1 month.
Hypocalcemia was the major immediate complication following thyroidectomy (n = 48; 38.4%) of the 125 patients, 3 or more parathyroid glands were identified and preserved in 110 (88%) patients and <3 glands were identified in 15 patients [Table 2]. There was no significant difference in the failure to localize the glands based on the location (right superior - 5, right inferior - 4, left inferior - 5, and left superior - 6).
Failure to identify all four glands significantly influenced rate of hypocalcemia (n = 14; 93% P = 0.000).
Linear regression with variable showing significant association with hypocalcemia revealed retrosternal extension (β = 0.314; P = 0.001) perithyroid adhesions (β = 0.253, P = 0.005) and failure to localize <3 parathyroid glands (β = 183, P = 0.029) as significant predictors of postoperative hypocalcemia.
RLNs were identified and traced to their point of entry in all patients on both sides [Table 3].
Vocal cords movements
Cord palsy was seen in 7% (n: 8) female patients and 12% (n: 1) of male (P = 0.549). Vocal cord palsy occurred to younger patients (mean 42.8; SD: 9.984 vs. 48.84; SD: 12.766; P = 0.002). Vocal cord palsy was equally distributed on either side [Table 4].
Characteristics of recurrent laryngeal nerve and its impact on nerve palsy
Right side: 114 (91%) coursed posterior to ITA, 10 (8%) coursed anterior to the artery. There was one (0.8%) nonrecurrent nerve on the right side. A single trunk was found in 108 (86%), and two divisions in 10 (8%) and multiple prelaryngeal divisions in 7 (6%). The laryngeal entry was anterior and closer to the thyroid gland in 111 (89%) patients, while in 14 (11%) entry was posterior to the posterior border of gland.
Left side: 119 (95%) coursed posterior to ITA and prelaryngeal branching were noted in 11 (10%). The nerve coursed close to the thyroid in the ligament of berry in 112 (92%).
| Discussion|| |
The overall complication rate of the present study is 40% and is comparable to the previous reported series. The marginal increase in the rate of complication is due to the high incidence of transient hypocalcemia.
Postoperative hypocalcemia lengthens the duration of hospitalization and increases the overall cost of a thyroidectomy. Symptomatic patients require parenteral calcium supplementation and prolonged oral administration of to attain a stable serum calcium levels to prevent serious long-term complications. Although hypocalcemia reverses spontaneously in most patients, it can remain permanent when caused by irreversible injury to the parathyroid glands.,,,,,,
Various clinical, biologic, and surgical factors may contribute to decreased serum calcium after thyroid operation.,, Asymptomatic hypocalcemia is frequently observed within 12 h of operation, but it resolves spontaneously by 24 h. Simultaneously, serum phosphorus decreases marginally at 24 h., Hemodilution during the perioperative period may be responsible for these changes and may explain their occurrence with other extracervical operations of the same magnitude and duration as thyroidectomy. The elevation of serum calcitonin secondary to manipulation of the thyroid was also initially suspected to participate in this calcium decrease, but this has not been confirmed in recent studies.,,,
Postoperative hypocalcemia after TT has been reported to range from 1% to 40%., This wide range is likely due to difference in the definition of hypocalcemia and as well lack of homogeneity in the subjects studied. The high incidence of hypocalcemia in the present series was due to setting the threshold of hypocalcemia at a higher level. Previous studies have reported higher incidence of hypocalcemia among females., However, the present study did not find female preponderance in patients with hypocalcemia. There was no increase in the incidence of hypocalcemia among patients with pressure symptoms.
Hyperthyroidism was found to increase risk of postoperative hypocalcemia., In patients with hyperthyroidism, the postoperative reversal of osteodystrophy and the accretion of calcium in bones may also contribute to decreased serum calcium. When normal parathyroid function can be documented, this hungry bone syndrome appears to be the most probable cause of hypocalcemia., The present study could not find a significant high rate of postoperative hypocalcemia in hyperthyroid patients.
Mobilization and dissection of the thyroid lobe are difficult when the gland is firm and unyielding. In our study, 40% of patients with firm consistency of thyroid developed hypocalcemia as against 11.8% with soft gland (P = 0.024). We could not find other studies correlating this parameter with hypocalcemia. Adhesions increase the technical difficulty in thyroidectomy and may result in hypocalcemia. In our study, cases with adhesions had an increased incidence of postoperative hypocalcemia (70.2%) as opposed to 18.9% in cases without adhesions. The difference was very highly significant (P < 0.001).
Retrosternal extension increases the technical difficulty in thyroidectomy and may result in hypocalcemia. In our study, cases with retrosternal extension had an increased incidence of postoperative hypocalcemia (75.6%) as opposed to 19.8% in cases without retrosternal extension. The difference was very highly significant (P < 0.001). We could not find other studies correlating this parameter with hypocalcemia.
Many authors consider that parathyroid vascularization remains intact even after ligation of all of the four thyroid arteries.,,, When the parathyroid gland is found discolored with suspicious viability implanting it in a muscle pouch is ideal. When three or more parathyroid glands could be identified and preserved in situ at operation, spontaneous recovery was observed in all cases. The number of parathyroid glands preserved during thyroidectomy appears to be a major determinant of the outcomes. We also observed that hypocalcemia was significantly associated with failure to identify <3 parathyroid glands.
Studies show an increased preponderance of hypocalcemia in Graves' disease.,, In our study, all patients with thyroiditis had hypocalcemia. This could be due to the presence of adhesions because all thyroiditis cases were found to have adhesions. The incidence was 50% in Graves' disease, 35.7% in colloid goiter, and 8.3% in adenoma. No comparable data were found in the literature regarding thyroiditis, colloid, or adenoma.
Vocal cord palsy
The reported incidence of permanent RLN injury was <2% in high volume centers. The incidence is higher when thyroidectomy is performed by a less experienced surgeon.,, This complication is generally unilateral and transient, but occasionally, it can be bilateral and permanent and it may be either deliberate or accidental., In our study, none of the patients had permanent vocal cord palsy. 6.6% of patients had transient unilateral vocal cord palsy. All the cases recovered completely by 1 month. None had bilateral palsy.
In our study, there was no statistically significant difference in the incidence of vocal cord palsy in cases with and without dysphagia or tracheal compression. Similarly, there was no statistically significant difference in the incidence of vocal cord palsy in cases with firm and soft consistency of the thyroid gland. We could not find other studies correlating this parameter with vocal cord palsy.
RLN injury is more common in hyperthyroidism due to the increased vascularity of the gland., In our study, none of the patients with hyperthyroidism had vocal cord palsy.
Chaudhary et al. and Aytac and Karamercan  reported an increased incidence of vocal cord palsy in TT than in hemithyroidectomy. In our study, none of the cases who underwent hemithyroidectomy had vocal cord palsy. 7.2% of total thyroidectomies had vocal cord palsy, but this difference was not statistically significant.
The presence of adhesions increases the chance of RLN injury., In our study, 12.8% of cases with adhesions had vocal cord palsy as opposed to 3.3% in case without adhesions. The difference was statistically significant (P = 0.034).
RLN trauma has been reported to increase in cases with retrosternal extension. In our study, 19.5% of cases with retrosternal extension had vocal cord palsy, it was only 1% in cases without retrosternal extension. The difference was statistically significant (P < 0.001).
Anatomical variations of RLN in relation to ITA are often encountered, and may predispose to nerve injury. In our study, 37.5% of cases with the nerve going anterior to the artery had vocal cord palsy, while this was 0.8% in those going posterior. The difference was statistically significant (P < 0.001). Although literature states that the anatomical variations can result in nerve injury, we could not find any study comparing the relation to ITA and RLN injury.
Literature shows that branched RLNs suffer more surgical injuries and are twice as likely to be associated with vocal cord dysfunction. In our study, 21.4% of cases with extra laryngeal branching had vocal cord palsy, as opposed to 1.3% of cases without branching. The difference was statistically significant (P < 0.001).
There was no statistically significant difference in the incidence of vocal cord palsy in cases with anterior (3.8%) and lateral (3.4%) entry to the larynx, though in majority of cases the nerve was seen entering the larynx anteriorly. We could not find any other study comparing this parameter with vocal cord palsy.
As reported in literature, patients with Graves' disease undergoing thyroidectomy have a higher chance of developing vocal cord palsy., In our study, all the vocal cord palsies were seen in colloid goiters. The difference was not statistically significant. This difference could be due to a very low number of cases with adenoma, Graves' disease, and thyroiditis.
| Conclusion|| |
Transient hypocalcemia and vocal cord palsy are fairly common complications of TT. Hyperthyroidism seems to have an increased predisposition for hypocalcemia. The presence of adhesions and retrosternal extension predisposes to postoperative hypocalcemia and vocal cord palsy. The identification of parathyroids is very important in thyroidectomy and an attempt should be made to identify all four parathyroids. Anterior relation to ITA and presence of branching are risk factors for RLN injury, hence care must be taken to define the anatomy of the nerve. Meticulous surgical dissection and thorough knowledge of anatomy can prevent the development of both hypocalcemia and RLN palsy in TT for benign thyroid disorders.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
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[Table 1], [Table 2], [Table 3], [Table 4]