Does exposing all parathyroids during total thyroidectomy with central lymph node dissection protect long-term function? A prospective cohort study

Abstract

Background

Hypoparathyroidism (HypoPT) is the most common complication after total thyroidectomy (TT) and central lymph node dissection (CLND) for thyroid carcinoma. However, there’s still no effective surgical strategy to prevent its incidence. This study evaluated the impact of sufficient intraoperative exposure of the parathyroid glands (PG) on postoperative parathyroid function, the rate of parathyroid autotransplantation, and incidental parathyroidectomy.

Methods

Prospective data from 133 consecutive patients who underwent TT and CLND by a single surgeon at the First Affiliated Hospital of Zhejiang University School of Medicine were systematically collected. All patients were categorized into sufficient exposure (exposed) group and insufficient exposure (control) group based on whether all 4 PGs were identified during surgery. PG exposure and autotransplantation were recorded intraoperatively, while incidental parathyroidectomy was determined via routine pathology reports. Postoperative parathyroid hormone (PTH) levels, serum calcium levels, and hypocalcemia-related symptoms (limb numbness/tetany) were monitored for at least six months. Continuous variables were compared using independent samples t-test for normally distributed data., while categorical variables were analyzed using Pearson’s chi-square test. A two-sided P-value < 0.05 was considered statistically significant.

Results

No patients in the sufficient exposure group developed permanent hypoPT, while 2 patients in the insufficient exposure group exhibited biochemical hypoPT. Mean PTH levels were significantly higher in the sufficient exposure group (33.22 ± 16.48 pg/ml vs. 26.48 ± 10.94 pg/ml, P = 0.048) within six months. Parathyroid autotransplantation was more frequent in the sufficient exposure group (26.0% vs. 8.3%, P = 0.008). For transient hypoPT, incidental parathyroidectomy or clinical symptoms, there was no significant difference between groups (P > 0.05).

Conclusion

Sufficient exposure of the PGs during surgery can potentially protect parathyroid function in terms of PTH level without increasing transient hypoPT, indicating PG sufficient exposure is a practical way to protect parathyroid function.

Introduction

Hypoparathyroidism (HypoPT) is the most common complication following total thyroidectomy (TT), with 20% to 30% of patients experiencing transient hypoPT and 0.8% to 7.3% developing permanent hypoPT [1–4]. In patients with thyroid carcinoma undergoing prophylactic or therapeutic central lymph node dissection (CLND), the incidence rates can further increase to at least 14% for transient hypoPT, while permanent hypoPT may even reach up to 16.2% [5–7].

Reasons of postoperative hypoPT include intraoperative parathyroid glands (PG) mechanical injury, such as incidental parathyroidectomy, traction, compression, and interruption of the gland’s blood supply [8, 9]. It commonly presents with acute hypocalcemia symptoms due to decreased parathyroid hormone (PTH) levels, characterized by neuromuscular hyperexcitability, such as limb numbness and tetany. These symptoms severely affect postoperative quality of life and increase the financial burden on patients, especially in cases of permanent hypoPT. Long-term consequences of permanent hypoPT include chronic kidney disease, basal ganglia calcification, and an increased risk of infections, further complicating patient outcomes. Therefore, preventing postoperative hypoPT is an urgent concern for thyroid surgeons [1, 10, 11].

The debate remains on whether more extensive exposure of the PGs during surgery causes more damage or offers better protection. Some studies suggest that active identification and preservation of PGs can reduce the risk of incidental parathyroidectomy and improve long-term gland function [2, 3, 12]. Conversely, other reports indicate that excessive manipulation may compromise the gland’s vascular supply, leading to transient or permanent dysfunction [13, 14]. Current literature presents mixed conclusions regarding whether PGs should be actively exposed and fully identified during thyroid surgery. The American Thyroid Association (ATA) statement on postoperative hypoparathyroidism emphasizes the need for standardized surgical approaches to mitigate the risk of hypoPT but does not provide a consensus on the degree of PG exposure required during thyroidectomy [1]. This current study is to explore the impact of all 4 PGs exposure on postoperative parathyroid function, focusing on both transient and permanent hypoPT outcomes.

Materials and methods

Study design

This prospective study analyzed data from patients undergoing TT and CLND (including lateral lymph node dissection, LLND) at the Department of Surgical Oncology, First Affiliated Hospital of Zhejiang University School of Medicine, between January 2020 and June 2024. A total of 211 patients were initially enrolled, all of whom were over 18 years old and operated on by a single surgeon to ensure consistency in surgical technique. A comprehensive thyroid surgery database was established and regularly updated to include surgical details, preoperative and postoperative laboratory tests, and pathological findings, such as intraoperative PG exposure, gland location, evidence of damage or excision, serum calcium levels, and parathyroid hormone (PTH) concentrations.

Patients were divided into two groups according to whether the PGs were systematically exposed: the sufficient exposure group (all 4 PGs exposed) and the insufficient exposure group (fewer than 4 glands exposed). The primary outcomes assessed were hypoPT, categorized as transient or permanent (with a 6-month cutoff), intraoperative parathyroid autotransplantation, and incidental parathyroidectomy (defined as parathyroid tissue identified in routine pathology reports without prior autotransplantation). HypoPT was further classified as biochemical hypoPT (PTH < 12 pg/mL accompanied by new-onset hypocalcemia, defined as serum calcium < 2.11 mmol/L) or clinical hypoPT (biochemical hypoPT with associated symptoms and/or signs of hypocalcemia) [1].

Exclusion criteria included a history of thyroid surgery, preoperative thyroid or parathyroid dysfunction, distant metastasis, and incomplete follow-up data. After applying these criteria, 133 patients were included in the final analysis, allowing for a focused evaluation of the relationship between PG exposure and postoperative outcomes.

Surgical technique

Thyroidectomies were performed using the capsular dissection technique. This method involves careful dissection of the soft tissue from the thyroid capsule to preserve the PGs in situ after retraction of the fascia and muscles and elevation of the thyroid’s upper and lower poles. Special attention was given to identifying PGs located on or adjacent to the thyroid capsule, particularly near the Zuckerkandl tubercle and the recurrent laryngeal nerve [13]. Once identified, the PGs were meticulously dissected away from the thyroid while preserving their vascular supply as much as possible. Each operation aimed to expose all 4 PGs. Thyroidectomy specimens were carefully examined to identify PGs that were either adherent to or embedded within the thyroid tissue. Similarly, the thyroid bed was inspected for PGs that were completely devascularized or appeared discolored. As described, any devascularized or discolored glands, as well as inadvertently excised parathyroid tissue, were autotransplanted into the ipsilateral sternocleidomastoid muscle [15, 16]. All autotransplanted PGs were confirmed intraoperatively by frozen section analysis of a representative portion of the excised tissue.

Central neck dissection (level VI) was performed en bloc, extending from the hyoid bone to the innominate vein and laterally to the carotid sheaths, including prelaryngeal, pretracheal, and bilateral paratracheal nodes. Lateral neck dissection (levels II–Vb) involved systematic removal of fibrofatty tissue within anatomical compartments, preserving the sternocleidomastoid muscle, internal jugular vein, and spinal accessory nerve. Dissection proceeded from level IIa superiorly to level Vb inferiorly, guided by preoperative imaging and intraoperative findings [17, 18]. Lymph nodes removed from each anatomical compartment were submitted separately for pathological evaluation.

Data collection

Collected data included patient demographics (gender, age, medical history), preoperative and postoperative laboratory values (PTH, serum calcium, phosphorus, magnesium, and potassium levels), and surgical details (extent of surgery—number of PGs exposed intraoperatively, whether CLND or LLND was performed, and whether parathyroid autotransplantation was conducted). Clinical follow-up data were gathered through outpatient visits and telephone consultations, with a minimum follow-up duration of six months for all patients. Patients were considered lost to follow-up if three telephone attempts at different times were unsuccessful.

The presence of incidental parathyroidectomy was initially identified by reviewing postoperative pathology reports and was further corroborated through cross-referencing with surgical records, intraoperative frozen section analyses, and final pathology evaluations. This multilayered verification aimed to enhance the accuracy of incidental parathyroidectomy detection and minimize reporting errors.

Statistical analysis

Data were analyzed using SPSS version 27.0. Descriptive statistics, including counts and percentages, were employed to summarize patient characteristics and surgical outcomes. Continuous variables were compared using independent samples t-tests, while categorical variables were analyzed with chi-square tests in univariate analyses. A two-sided significance threshold was set at 0.05 for all statistical tests. All the figures in this article were drawn using Python 3.10.13.

Results

Baseline characteristics of the patients enrolled

The baseline characteristics and relevant laboratory test results of the enrolled patients are summarized in Table 1. A total of 133 patients undergoing total thyroidectomy were included in the final analysis. All patients were newly diagnosed, over 18 years of age, and had confirmed malignant tumors via postoperative pathological examination. All patients underwent lymph node dissection. The mean age was 45.4 ± 11.2 years, with a predominance of female patients (90/133, 67.7%).

Table 1.

Baseline characteristics of patients enrolled

Variables	Classification	All cases (N = 133, %)	Sufficient exposure		P
			Yes (N = 73, %)	No (N = 60, %)
Total		133(100)	73(100)	60(100)
Gender	Male	43(32.3)	24(32.9)	19(31.7)	0.882
	Female	90(67.7)	49(67.1)	41(68.3)
Age	< 55y	99(74.4)	57(78.1)	42(70)	0.288
	≥ 55y	34(25.6)	16(21.9)	18(30)
No. of parathyroids exposure	2	11(8.3)	0(0)	11(18.3)	NA
	3	49(36.8)	0(0)	49(81.7)
	4	73(54.9)	73(100)	0(0)
Multifocality	Yes	83(62.4)	46(63)	37(61.7)	0.873
	No	50(37.6)	27(37)	23(38.3)
Bilaterality	Yes	75(56.4)	43(58.9)	32(53.3)	0.519
	No	58(43.6)	30(41.1)	28(46.7)
Lymph node dissection	CLND	104(78.2)	56(76.7)	48(80)	0.648
	CLND+LLND	29(21.8)	17(23.3)	12(20)
Capsule invasion	Yes	96(72.2)	52(71.2)	44(73.3)	0.788
	No	37(27.8)	21(28.8)	16(26.7)
gETE	Yes	15(11.3)	9(12.3)	6(10)	0.673
	No	118(88.7)	64(87.7)	54(90)
T stage	T1	101(75.9)	57(78.1)	44(73.3)	0.267
	T2	8(6)	6(8.2)	2(3.3)
	T3 + T4	24(18)	10(13.7)	14(23.3)
N stage	N0	56(42.1)	32(43.8)	24(40)	0.410
	N1a	50(37.6)	24(32.9)	26(43.3)
	N1b	27(20.3)	17(23.3)	10(16.7)

Abbreviation: CLND Central lymph node dissection, LLND Lateral lymph node dissection, gETE gross extrathyroidal extension, NA Not available

Patients were stratified into two groups: the sufficient exposure group (all 4 PGs exposed intraoperatively) and the insufficient exposure group (fewer than 4 glands exposed). No significant differences were observed between the two groups concerning age, gender, tumor multifocality, bilaterality, lymph node dissection extent, capsule invasion, extrathyroidal extension, TNM stage, or history of radioactive iodine treatment (P > 0.05).

Parathyroid function in both groups

Among the 133 patients, the sufficient exposure group demonstrated a transient biochemical hypoPT rate of 15.1% (n = 11/73) compared to 16.7% (n = 10/60) in the insufficient exposure group (P = 0.801). Similarly, clinical manifestations of transient hypoPT were observed in 9.6% (n = 7/73) of the sufficient exposure group versus 11.7% (n = 7/60) of the insufficient exposure group (P = 0.698). Regarding permanent hypoparathyroidism, the insufficient exposure group showed a 3.3% incidence rate (n = 2/60) for biochemical hypoparathyroidism, while no cases (0%) were identified in the sufficient exposure group (P = 0.202). Neither group reported any cases of clinically apparent permanent hypoPT (Table 2).

Table 2.

Incidence of postoperative complications according to parathyroid gland sufficient exposure

	Complications	Sufficient exposure		P
		Yes (N = 73, %)	No (N = 60, %)
Transient changes (< 6months)	Biochemical hypoPT	11(15.1)	10(16.7)	0.801
	Clinical hypoPT	7(9.6)	7(11.7)	0.698
	Hypocalcemia	22(30.1)	21(35)	0.551
	PTH level(< 12pg/ml)	39(53.4)	28(46.7)	0.438
	Numbness/Tetany	13(17.8)	10(16.7)	0.862
Permanent changes (≥ 6 months)	Biochemical hypoPT	0(0)	2(3.3)	0.202
	Clinical hypoPT	0(0)	0(0)	NA
	Hypocalcemia	2(2.7)	5(8.3)	0.243
	PTH level(< 12ng/ml)	2(2.7)	2(3.3)	1.000
	Numbness/Tetany	1(1.4)	2(3.3)	0.589

Abbreviations: hypoPT Hypoparathyroidism, PTH Parathyroid hormone, NA Not available

Follow-up analyses of PTH and serum calcium levels showed no significant differences between the two groups at 1 day, 1 month, and 3 months postoperatively. However, at 6 months post-surgery, PTH levels were significantly higher in the sufficient exposure group (33.22 ± 16.48 pg/ml vs. 26.48 ± 10.94 pg/ml, P = 0.048) (Fig. 1).

Fig. 1.

PTH and serum calcium values before and after surgery. a PTH level. b Serum calcium level. The asterisk (*) denotes P value less than 0.05. Abbreviation: PTH, parathyroid hormone

Parathyroid autotransplantation in both groups

Intraoperative parathyroid autotransplantation was performed in 24 patients (18.0%). Of these, 19 cases occurred in the sufficient exposure group, while only 5 cases were reported in the insufficient exposure group. The sufficient exposure group, which showed a significantly higher rate of autotransplantation (26.0% vs. 8.3%, P = 0.008), was associated with more timely intraoperative identification of compromised PGs. However, parathyroid autotransplantation was found significantly associated with a higher incidence of clinical symptoms within 6 months (37.5% vs. 12.8%, P = 0.007) and transient clinical hypoPT specifically (25.0% vs. 7.3%, P = 0.021) (Table 3), but no significant differences were observed in PTH and serum calcium levels between patients who underwent autotransplantation and those who did not within the first six months postoperatively (P > 0.05).

Table 3.

Incidence of postoperative outcomes according to number of parathyroid autotransplantation

	Complications	Parathyroid autotransplantation		P
		Yes (N = 24, %)	No (N = 109, %)
Transient changes (< 6months)	Biochemical hypoPT	2(8.3)	19(17.4)	0.364
	Clinical hypoPT	6(25)	8(7.3)	0.021*
	Hypocalcemia	4(16.7)	39(35.8)	0.070
	PTH level(< 12pg/ml)	13(54.2)	56(51.4)	0.804
	Numbness/Tetany	9(37.5)	14(12.8)	0.007*
Permanent changes (≥ 6 months)	Biochemical hypoPT1	0(0)	2(1.8)	1.000
	Clinical hypoPT	0(0)	0(0)	NA
	Hypocalcemia	3(12.5)	4(3.7)	0.111
	PTH level(< 12ng/ml)	2(8.3)	2(1.8)	0.149
	Numbness/Tetany	1(4.2)	2(1.8)	0.452

Abbreviations: hypoPT Hypoparathyroidism, PTH Parathyroid hormone, NA Not available The asterisk (*) denotes P value less than 0.05

Rate of incidental parathyroidectomy in both groups

Chi-square analysis indicated no significant difference in the occurrence of incidental parathyroidectomy between the sufficient and insufficient exposure groups (17.8% vs. 18.3%, P = 0.938). The overall incidence of incidental parathyroidectomy was 17.8%(n = 13/73). The accuracy of visual identification for PGs during thyroidectomy was 82.2%, as determined by postoperative pathological confirmation.

Discussion

In this prospective study including 133 patients who underwent TT and CLND, exposure of all 4 PGs neither increased transient hypoPT (15.1% vs. 16.7%; P = 0.801) nor permanent hypoPT (0% vs. 3.3%; P = 0.202). More importantly, the fully exposed cohort exhibited a higher mean serum PTH concentration at six months (33.2 ± 16.5 vs. 26.5 ± 10.9 pg/mL; P = 0.048), underscoring that deliberate visualization safeguards immediate endocrine integrity and accelerates long-term functional recovery.

To our knowledge, this is the first report confined to a TT + CLND population, a setting intrinsically more demanding than the mixed or pure thyroidectomy cohorts previously studied. The safety signal we observed echoes findings from Mehta et al. (transient hypocalcemia 18.0% with ≥ 2 glands identified vs. 19.2% with ≤ 1 gland; P = 0.84) and Sitges-Serra et al. (14.3% vs. 15.8%; P = 0.78), whereas Riordan et al. linked identification of ≥ 3 glands to a 70% higher odds of biochemical hypocalcemia (OR 1.7, 95% CI 1.1–2.9). That series, however, excluded CLND, thereby examining a less complex surgical situation. Our data therefore extend earlier work by demonstrating that, even under the heightened ischemic risk imposed by CLND, visualization does not confer harm and may in fact be protective.

Systematic exposure inevitably heightened intra-operative recognition of devascularized glands, yielding a higher autotransplantation rate in our cohort (26.0% vs. 8.3%). Although graft recipients experienced more transient symptomatic hypocalcemia, this trade-off mirrors prior endoscopic TT + CLND data—Cheng et al. reported a similar early dip in PTH yet no disadvantage beyond the first postoperative week [19]. By 1 month, re-implanted tissue begins secreting hormone; experimental perfusion studies show functional recovery is largely complete within 4–8 weeks, with serum PTH rising in parallel [20]. Consistent with these kinetics, a population study of 342 thyroidectomies found that autotransplantation shortened the median time to biochemical normalization from 32 days to 7 days and eliminated permanent hypoPT [21]. By contrast, two recent single-center analyses failed to demonstrate a reduction in permanent disease; their cohorts transplanted predominantly “doubtful” tissue after prolonged manipulation, a practice associated with lower graft viability [22, 23]. Collectively, prompt reimplantation of PGs effectively speed endocrine recovery and may avert permanent hypoPT.

This study has several limitations. As a single-center study, the findings may not be generalizable to broader clinical settings. In addition, the relatively small number of patients with permanent hypoPT limited the ability to draw definitive conclusions regarding long-term outcomes. Larger, multicenter studies with extended follow-up are needed to validate these results and to further investigate factors influencing postoperative parathyroid function.

Conclusion

In patients undergoing TT+CLND for thyroid cancer, sufficient exposure of PGs is beneficial to the recovery of postoperative PTH level, and does not increase the incidence of temporary hypoPT. While our findings support the safety of sufficient PG exposure in CLND-containing procedures, future studies should aim to establish the optimal balance between adequate visualization for gland preservation and excessive dissection that might compromise vascular integrity.

Abbreviations

ATA

American Thyroid Association

CI

Confidence interval

CLND

Central lymph node dissection

gETE

Gross extrathyroidal extension

HypoPT

Hypoparathyroidism

LLND

Lateral lymph node dissection

NA

Not available

OR

Odds ratio

PG

parathyroid gland(s)

PTH

Parathyroid hormone

TT

Total thyroidectomy

Authors’ contributions

Xinguang Jin and Zehang Xu wrote the main manuscript text and collected clinical datas and performed statistical analysis. Liping Wen and Xianmeng Chen collected clinical datas and prepared Tables 1, 2 and 3; figure 1. Shitu Chen, Haijie Huang and Weibin Wang collected and reviewed clinical datas. Lisong Teng and Xiongfei Yu reviewed and edited the draft. All authors have reviewed the manuscript.

Data availability

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Declarations

Ethics approval and consent to participate

This study was conducted following the ethical standards of the 1964 Declaration of Helsinki and approved by the Ethics Review Committee of the First Affiliated Hospital of Zhejiang University, Ethical approval number: [2025B] IIT Ethics Approval No.0386. Informed consent was obtained from all participants of the study.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.