Thyroidectomy in children and adolescents: a systematic review

Introduction

Pediatric thyroid disease includes either benign or malignant situations. The most frequent benign pathologies involve Graves’ disease, toxic adenoma, congenital hyperthyroidism, thyroid nodules and goiter. Additionally, differentiated thyroid cancers (TCs) such as papillary, follicular and myeloid cancer are the most commonly malignancies in children. In case of medullary cancer, familial syndromes should be investigated (1,2).

For TC as well as for some benign thyroid disorders, total and subtotal thyroidectomy is the treatment option in pediatric patients, while prophylactic procedure is left for high-risk cancer development in the future. Since thyroid pathology favors malignancy in younger ages, lymph node dissection is common (3).

Endocrine surgery in patients under 18 years of age has similar philosophy as adult surgery concerning the surgical techniques. Major complications from thyroidectomy include recurrent laryngeal nerve (RLN) or superior laryngeal nerve palsy, respiratory complications, trauma infection, bleeding and hematoma, permanent and temporary hypoparathyroidism. The procedure type, referring to lobectomy, total thyroidectomy with or without node dissection, affects complication rates and hospital length of stay. Hospitalization of underage patients usually requires accompany of a family member during hospitalization due to the emotional charge of the patient. One day hospitalization after pediatric thyroidectomy is the common practice (4,5).

In this review we aimed to evaluate the field of thyroid surgical practice in patients less than 18 years old. Our objective was to emphasize the value of preoperative examinations, the type of the procedure, the increasing preference of surgery instead of more conservative treatment, the recurrence rate and follow-up needed. We present this article in accordance with the PRISMA reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-24-16/rc).

Methods

The literature search was conducted in the PubMed, Scopus and Embase databases until March 2023 using the following Mesh terms: (thyroidectomy) AND (pediatric), (thyroidectomy) AND (children), (thyroidectomy) AND (adolescence), (thyroidectomy) using the age frame child (from birth to 18 years old age). The search was limited to articles written in English without any restriction on period. Studies included patients older than 18 years old were excluded.

Data including time period, study design, patients’ demographics, indication for thyroid surgery, surgical procedures, postoperative complications, and outcomes were collected.

Results

The literature search identified 11,225 articles, 11,108 of which were excluded from title and abstract screening and an additional 81 articles were excluded by the full text. Thirty-seven retrospective studies were included in our systematic review (Figure 1).

Figure 1 The PRISMA flowchart.

A literature review was performed and 37 articles of thyroid surgery in pediatric population were selected and summarized in (Table 1).

In this systematic review, we added cases from our Department and descriptive statistics was applied. The percentage of criteria fulfillment is shown in Table 2.

The main results were as follow:

Demographics

In our study, 12,728 patients were enrolled, from whom 9,848 were females (77.4%). The mean age was 13.4±1.93 years old.

Indication for surgery

The indications for thyroid surgery were divided in two main categories; benign disease and malignancy. Benign disease included toxic adenoma, goiter, thyroid nodules, Graves’ disease and congenital hyperthyroidism, which were found in 6,281/12,008 cases (52.3%). Malignant tumors (papillary, follicular and sporadic medullary TC) were found in 4,979/12,008 cases (41.5%), while prophylactic thyroidectomy for multiple endocrine neoplasia type 2 syndrome (MEN-2) was found in 295/12,008 cases (2.5%).

Type of procedures

The most common type of procedure was total thyroidectomy in 7,866/12,109 cases (64.9%), followed by hemithyroidectomy (HT) in 3,214/12,109 cases (26.5%). The percentage of lobectomy was 5.7% (693/12,109 cases), while near-total thyroidectomies were performed in 0.4% (48/12,109 cases). Completion thyroidectomy after HT or lobectomy was performed in 129/12,109 cases (1.1%), due to carcinoma in the final pathology report. The percentage of central and lateral lymph node dissection were 6% (732 cases) and 1.1% (128 cases), respectively.

Complications

The most common complication was hypoparathyroidism (HP) in 1,218/12,728 cases (9.6%), from which 148 cases had permanent HP (12.2%). The second most common complication was RLN palsy in 153/12,728 cases (1.2%), from which 25 cases had permanent nerve injury (16.3%). Other rare complications were wound infection in 18/12,728 (0.14%) cases, keloid formation in 32/12,728 cases (0.25%), hematoma in 8/12,756 cases (0.06%) and chylous leak in 1/12,728 cases (0.008%).

Length of hospitalization

The median length of hospitalization postoperatively was 2,35 days (range, 6 hours to 8.8 days) and the extension was due to postoperative hypocalcemia that emerged intravenous calcium supplementation.

Discussion

Key findings

Thyroidectomy is the treatment option for pediatric TC as well as for some benign thyroid conditions like Graves’ disease and benign thyroid nodules. In cases where there’s an increased risk of future TC, especially within familial syndromes, prophylactic thyroidectomy may be a consideration (19).

Indication for surgery

Bussières et al. in a series of 96 patients found that the most common indication for thyroidectomy in children is thyroid nodules (64%), as well Almosallam et al. and Chen et al. (21,29,33). Dream et al. in a study of 55 patients considered Graves’ disease as the most common indication for operation (55%), followed by TC (17%), thyroid nodule (11%), multinodular goiter (7%), Hashimoto’s disease (6%), and toxic adenoma (4%) (23). According to Fahrner et al., thyroid nodules and Graves’ disease were the leading indication for surgery (75%), while malignancy or familiar MEN-2 were indications in 25%; the incidence of TC was 17% (36). Among 271 patients treated by Nordenström et al., indications for surgery were Graves’ disease in 78.1%, other benign disease 9.9% and TC 12% (27). In a large series of 175 patients, Scholz et al. reported thyroid nodules as the leading indication for thyroidectomy (83%), followed by hyperthyroidism (7%) and goiter (7%); cancer was found in 36%, and thus papillary TC in 85% (38). In Bukarica et al. retrospective observational study, the prevalence of TC increased in adolescence (14). Al-Qurayshi et al. studied 361 patients operated over a period of 5 years in multiple centers; thyroid diseases included 19% TC, 5.4% MEN-2, 33.6% toxic nodular disease, and 42% non-toxic benign disease (17).

Thyroidectomy was conducted preventively in all cases where there was a familial background of medullary thyroid carcinoma by Akkari et al. and in three cases without clinical signs of thyroid tumor with diagnosed RET gene mutation by Astl et al. (35,37). In Raval et al.'s study, the majority of patients who underwent total thyroidectomy for benign conditions either had unsuccessful outcomes with long-term medical treatment (33%) or encountered thyroid storm despite medical management (27%). The efficacy of antithyroid medications like propylthiouracil and methimazole is constrained by issues related to patient compliance, frequent relapses, the onset of hypothyroidism, and the potential for toxicity, including rare instances of fatality. There remains a preference to minimize radioactivity exposure due to theoretical concerns of cancer in radioactive iodine treatment. Besides, total thyroidectomy and near-total thyroidectomy are safe and effective in Graves’ disease in children (39).

Pediatric population with TC often present with advanced disease, namely cervical lymph node involvement (31.5%) and lung metastases (5.7%) (3,29,32,37,40).

Type of surgery

Thyroidectomy is more frequent in female patients (up to 80%) and approximately in individuals aged 14 years old (14,17,19,21,24,25).

Procedures of thyroid gland surgery by Almosallam et al. included total thyroidectomy (50%), HT (17%), completion thyroidectomy (31%), and subtotal thyroidectomy (2%) (21). Patel et al. demographic study of 720 cases stated 245 HT, 376 total thyroidectomies, and 99 total thyroidectomies with central neck dissection (25). Scholz and colleagues reserved near-total thyroidectomy for those patients with confirmed papillary TC. For individuals with unilateral nodules or intermediate cytologic abnormalities (Bethesda III and IV), they recommended lobectomy, followed by completion thyroidectomy if cancer diagnosis is confirmed through operative histology. Preventive total thyroidectomy was performed in 3 patients for MEN-2 syndrome. Another ten patients group underwent completion thyroidectomy for TC after lobectomy (38). According to Spinelli et al., patients with unilateral lesions <2 cm, confined to one lobe, not demonstrating extrathyroidal invasion in neck ultrasound, and with no evidence of distant metastasis were selected for lobectomy. Nodal involvement did not rule out lobectomy (32). Astl et al. accept HT in differentiated TC conforming to T1 N0 M0 classification. Total thyroidectomy is suggested in medullary cancer or advanced papillary cancer. In case of lymph node metastases, therapeutic neck dissection is recommended (40). Bilić et al. advice total thyroidectomy along with occasionalparatracheal neck dissection, while lateral cervical lymph node dissection is only deemed essential when lymph nodes tested positive in fine-needle aspiration (FNA) (22).

Considering that thyroid carcinoma in children often occurs multifocal, and with early lymph node metastasis, Zong et al. found that total thyroidectomy did not have higher complication rate compared to lobectomy, except for the length of hospitalization that was shorter in lobectomy group. Contrariwise, the morbidity increased in staged operation following initial lobectomy because of the risk to identify the parathyroid glands and the RLN during the operation. Therefore, they recommended a primary total thyroidectomy in children with unilateral thyroid carcinoma (30). Multifocality in pediatric TC has been proved not to decrease disease free survival in highly selected cases after total thyroidectomy (41).

Type of TC

Papillary carcinoma (PTC) accounts for the majority of cases of TC (4). De Jong et al. reported 79.2% papillary and 20.8% follicular carcinoma (FTC), similarly Spinelli and Bilić found 90% PTC (4,20,22,31).

Thyroid nodule histology of 146 patients in Scholz et al. study was: TC in 52 cases (Papillary 44, Follicular 5, Clear cell 1, Medullary 2), Benign nodule(s) in 88 cases (Cyst 14, Adenoma 66, Colloid 8, Other 6 (Thyroiditis 5, Histiocytosis 1) (38).

Complications

RLN injury stands out undoubtedly as the most important complication -linked to thyroid surgery (34). Permanent RLN injury is extremely rare in all series reported. De Jong et al. reported a rate of 2.8% of RLN injury (20). Spinelli et al. reported bilateral RLN injury in two of 250 patients (0.8%) operated for papillary TC requiring an urgent tracheostomy (32). Sinha et al. reported two RLNs injury in their series of 61 patients with benign disease. Therefore, they suggested that referring patients for surgery earlier could prevent complications in benign thyroid disease (34). Bukarica et al. reported two transient RLN paralyses in their series of 19 operations, which were successfully treated with neurotropic medicines, glucocorticoids and vasodilators (14). In Scholz et al. series permanent unilateral vocal cord paralysis was documented in 2 children after resection for malignancy (38). Continuous intraoperative laryngeal nerve monitoring (if only it can be detected) has been used by many authors as standard care (22,39). Although intraoperative RLN monitoring may be applied, RLN palsy could still occur (35). According to American Head and Neck Society, intraoperative RLN monitoring should be discussed in every case of thyroid surgery in pediatric population (42).

The most frequent complication observed in pediatric thyroidectomy is either transient or permanent HP (17,20,33,34). HP leads to hypocalcemia of which its expression will be proportional to its severity and speed of onset. Studies reported transient HP after thyroidectomy in individuals under 18 years old from 13.6% to 34.1%, while permanent HP from 1.5% to 23.8% (17).

De Jong et al. claimed that the only factor associated with HP after total thyroidectomy in children was the number of parathyroid glands preserved in situ. HP can occur, and even be permanent, even parathyroid glands remain in situ but not intact (e.g., devascularization) (4,20). The frequency of HP in a 39 patients’ study by García-García et al. was 4 out of 4 when two parathyroids were dissected, 2 out of 10 when only one was dissected, and 6 out of 25 when none were dissected (16). Scholz et al. reported permanent HP up to 4.7%, found only in individuals with bilateral resection; no incidence of permanent HP was found in the remaining operations (38). Nordenström et al. reported an overall incidence of permanent HP after total thyroidectomy in 273 patients up to 7.3% which is higher compared to previous studies (1.5%). This study did not identify any statistically significant risk factors for permanent hypoparathyroidism, and the autotransplantation of parathyroid glands did not prevented it (27). Chen et al. in a cohort of 171 patients reported 12.9% transient HP with 7.0% requiring intravenous calcium correction; only one patient (0.9%) presented with permanent hypoparathyroidism; the risk factors correlated to this included total thyroidectomy, central and bilateral lateral neck dissection, Graves’ disease, and malignancy (33). In Sinha et al. cohort (61 patients), transient hypocalcemia was infrequent following HT. However, its occurrence notably rose with total thyroidectomy, particularly when coupled with lymph node dissection (34). In a series of 29 total thyroidectomies for thyroid malignancy, permanent HP was only seen in patients who underwent lymph node dissection (19).

No correlation between the incidence of HP and indication for surgery was found. Total thyroidectomy and neck dissection carry an increased risk of postoperative hypocalcemia (26).

The increased incidence of postoperative hypocalcemia among patients with Graves’ disease in comparison to the remaining nonmalignant group could be ascribed to the localized thyroiditis-induced inflammation, which leads to greater adherence of the parathyroid glands and renders surgical dissection more challenging (33,35).

Van Rooijen et al. administered active vitamin D (calcitriol) preoperatively to patients undergoing total thyroidectomy in order to mitigate the risk of postoperative hypocalcemia. They also suggested intraoperative localization of the parathyroid glands by fluorescence (19).

Age, cancer type, type of surgery, reoperation, central neck dissection or lateral neck dissection are not significant reasons for these complications. On the contrary, Scholfield et al. showed that N stage and central neck dissection were independent factors for HP and RLN injury (5,10). Aggressive dissection of the central compartment is a risk factor of RLN injury and permanent hypoparathyroidism, or sporadic hemorrhage and readmission to the operation room (23,43).

Explanations of findings

In our study, we found that the most common type of surgery in pediatric population indicated for thyroid surgery was total thyroidectomy, which is in concordance with American and European Thyroid Associations Guidelines (44,45). Papillary thyroid carcinoma seems to be the most common type of TC in pediatric population, which in comparison to adults, pediatric individuals frequently exhibit advanced disease at the time of diagnosis, characterized by increased lymph node involvement, distant metastasis, and multifocal disease (45). There is no consensus about HT and lobectomy oncological outcomes in cases of microcarcinoma and further studies should be applied (45).

In our study, the most common indication for surgery was benign disease, in compliance with most studies in the international literature (17,21,29,38). What should be discussed is that in some studies the main indication for surgery was Graves’ disease, for which medical treatment has been already proposed except for the cases of a thyroid nodule in a background of Graves’ thyroiditis which indicates FNA and surgery (23,27,36,46). Only Raval et al. indicates surgery for Graves’ disease after medical treatment failure (39).

Regarding complications, the most common complication found in our systematic review was transient HP in 9.5% of cases, while in the literature this ranges from 13.6% to 34.1% (17). The percentage of permanent HP in our study was 12.2%, which is claimed as high but in concordance with the literature (1.5% to 23.8%) (17). Nordenström et al. found the rate of permanent HP 7.3% (27). The RLN injury was found in 1.2% of cases, which justifies its rarity. Among these cases, the percentage of permanent nerve palsy was 16.3%, a high one, meaning that in case of nerve injury in children, the palsy is permanent in the majority of cases, may be due to anatomical differences of the young nerve compared to adult cases. Intraoperative neuromonitoring is advised in pediatric thyroid surgery (42).

Pediatric thyroid surgery should be performed by high-volume endocrine surgeons with experience in both pediatric and adult endocrine surgery and of course in endocrine surgical oncology (47). Pediatric thyroid patients have better outcomes when operated on by higher volume surgeons, while Moreno Alfonso et al. suggest that surgeons even if below high-volume threshold but specialized in pediatric surgery can perform thyroidectomies without increase in morbidity and mortality (15,48). Although the UK consensus on pediatric endocrine surgery supports high-volume surgeon to perform thyroidectomies in pediatric population, there is still a debate in the international literature (47,49). In our experience, we suggest pediatric thyroid surgery to be performed by high-volume endocrine surgeons with great experience in both pediatric and adult endocrine surgery.

Conclusions

Thyroidectomy in children and adolescence is a secure and efficient procedure regardless of its being total, HT, or lobectomy. It remains safe even if it is accompanied by central and/or lateral neck dissection. Nowadays, total thyroidectomy has also become the treatment of choice for benign pathology of the thyroid gland. Thyroid gland surgery in patients younger than 18 years is rare, most centers do not have adequate experience, nevertheless surgeons have made the procedure simple, not requiring extra armament, complications are rare or extremely rare, length of stay is short, and the burden on the health system is low. It is of great importance to direct pediatric thyroid surgery in reference with adult centers in order to reduce oncological malpractice, risk of complications and recurrence. The family of these younger patients is emotionally charged but this lasts for only 1 to 2 days.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the PRISMA reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-24-16/rc

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-24-16/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-24-16/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

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