The predictive role of intraoperative parathyroid hormone measurement on postoperative parathyroid function in patients undergoing total thyroidectomy

Abstract

Hypocalcemia is a common complication of thyroidectomy, particularly total thyroidectomy. The higher incidence of hypocalcemia following total thyroidectomy is primarily due to inadvertent damage to the parathyroid glands during surgery. This study aims to investigate the predictive value of intraoperative parathyroid hormone (IOPTH) in determining hypocalcemia during hospitalization and the recovery of parathyroid function after total thyroidectomy, as well as the factors that may influence IOPTH. In this retrospective study, we analyzed a cohort of 164 patients who underwent total thyroidectomy at our institution between 2018 and 2019. IOPTH was measured either 15 min after bilateral thyroidectomy combined with area VI lymph node dissection, or 15 min after bilateral thyroidectomy alone. We plotted ROC curves for IOPTH and ΔPTH% in relation to hypocalcemia during hospitalization and recovery of parathyroid function. Additionally, we explored risk factors for the development of hypocalcemia during hospitalization and factors that may influence IOPTH. IOPTH and ΔPTH% demonstrated good specificity and sensitivity for predicting hypocalcemia during hospitalization and for assessing recovery of parathyroid function. Lower preoperative PTH levels, chronic lymphocytic thyroiditis, and intraoperative parathyroid auto-transplantation were identified as risk factors for IOPTH < 15 pg/mL. IOPTH and ΔPTH% are predictive of hypocalcemia during the postoperative hospital stay and recovery of parathyroid function. Patients with chronic lymphocytic thyroiditis, intraoperative parathyroid auto-transplantation, and low preoperative PTH levels should be closely monitored for the recovery of parathyroid function after surgery.

Introduction

Hypoparathyroidism is one of the most common complications following thyroid surgery, particularly after total thyroidectomy(TT)¹. Its primary manifestation is hypocalcemia², which not only prolongs hospital stays but also significantly impacts patients’ quality of life due to the need for long-term calcium supplementation. Factors influencing parathyroid hormone (PTH) secretion include both intrinsic and environmental factors. It has been reported that smoking, vitamin D and calcium intake are associated with decreased PTH levels, whereas higher body mass index(BMI) and physical activity are linked to increased PTH levels³. However, the accidental removal of the parathyroid glands, intraoperative damage, or impaired blood supply are the main causes of hypoparathyroidism⁴. The risk of hypoparathyroidism is primarily increased by surgical factors such as central group lymph node dissection, thyroiditis, and intraoperative parathyroid damage⁵. Surgical duration, intravenous fluid volume, and intraoperative handling of the thyroid gland are additional factors that can elevate the risk of transient hypocalcemia⁶. Therefore, surgeons should classify the risk of hypoparathyroidism in post-thyroidectomy patients into high-risk and low-risk groups to enable more targeted management.

PTH and blood calcium levels are commonly used to assess parathyroid function. However, there is no consensus on the optimal timing and standardization of PTH measurement. Due to its short half-life, IOPTH measurement has been widely adopted in evaluating treatment outcomes in patients with primary or secondary hyperparathyroidism. Generally, a decrease in IOPTH levels indicates successful control of hyperparathyroidism. Similarly, rapid intraoperative monitoring of parathyroid hormone during TT is an effective means of identifying low-risk patients with postoperative parathyroid dysfunction and candidates for early safe discharge⁷. When the IOPTH level is ≥ 15 ng/L after TT, more than one-third of patients experience transient hypocalcemia, the majority of whom recover spontaneously without treatment⁸.

In light of these considerations, we conducted a retrospective analysis of patients undergoing thyroidectomy using the IOPTH technique to identify risk factors for hypoparathyroidism and factors that may influence IOPTH levels.

Patients and methods

The study was approved by the Institutional Review Board of China-Japan Union Hospital of Jilin University (approval number: 2022-KYYS-078). Informed consent was obtained from the patients or their legal guardians prior to surgery. The study adhered to the principles outlined in the Declaration of Helsinki.

Patients

This retrospective study reviewed 164 patients admitted to our center between October 2018 and October 2019 who underwent TT, with or without dissection of zone VI or lateral neck lymph nodes, and IOPTH measurement. Preoperative evaluation of suspicious thyroid nodules and lateral neck lymph nodes was performed using ultrasound or fine needle aspiration. According to Chinese guidelines⁹, if the patient was diagnosed with differentiated thyroid cancer(DTC), at least ipsilateral central lymph node dissection was performed during surgery. Therapeutic lateral cervical lymph node dissection, rather than prophylactic dissection, was performed in patients with DTC. Patients with benign thyroid disease underwent lobectomy only.

Patients were included in the analysis if they: (1) underwent an initial TT with or without area VI or lateral neck dissection, and (2) had blood collected intraoperatively for IOPTH measurement. Patients were excluded if they had a history of neck surgery, received preoperative calcium prophylaxis, had known hyperparathyroidism, chronic renal insufficiency, or were pregnant. Additionally, patients with concomitant serious illness requiring hospitalization during the perioperative period or those with incomplete biochemical data were excluded.

Surgical technique

Following intravenous aspiration combined with general anesthesia, the patient was positioned supine with the neck in hyperextension. A curved incision was made at the upper transverse line of the sternoclavicular joint, and dissection was performed layer by layer to expose the thyroid capsule. Intraoperative nerve monitoring equipment was routinely used during the procedure. Fine dissection of the thyroid capsule was performed to correctly identify and protect the parathyroid glands. Intraoperatively, we adhered to the 1 + X principle (i.e., each parathyroid gland was treated as the only one or the last, with efforts to protect as many parathyroid glands as possible), as recommended by the Chinese Consensus¹⁰. In addition, the use of a sternocleidomastoid muscle autograft was employed to address parathyroid glands that were inadvertently removed.

Blood samples were taken 15 min after bilateral thyroidectomy combined with zone VI lymph node dissection, or 15 min after bilateral thyroidectomy alone, to determine serum PTH levels (IOPTH). The change in PTH (ΔPTH) was calculated as follows: ΔPTH% = (pre-PTH − IOPTH)/pre-PTH × 100%.

Perioperative management and postoperative follow-up

In accordance with the Chinese expert consensus¹⁰ on parathyroid gland protection, all patients routinely received intravenous calcium following thyroid surgery. A gradual transition to oral calcium supplementation or discontinuation was made based on the patient’s clinical symptoms, serum PTH, and calcium levels. All patients were given intravenous calcium gluconate postoperatively, with a daily tapering regimen, and were monitored for calcium levels. Based on Chinese guidelines¹¹ and the American Thyroid Association statement¹² on postoperative hypoparathyroidism, an oral calcium supplementation protocol was developed. Patients with IOPTH < 15 pg/mL were treated with oral calcium carbonate and calcitriol, while those with IOPTH ≥ 15 pg/mL were treated with oral calcium carbonate alone. Patients with blood calcium levels > 2.10 mmol/L and no signs or symptoms of hypocalcemia were discharged.

PTH and blood calcium levels were monitored at 1 month, 2–3 months, and 4–6 months postoperatively. If PTH levels ≥ 15 pg/mL, oral supplementation was discontinued; if PTH remained < 15 pg/mL, patients continued their original oral regimen.

Laboratory determinations

Serum PTH levels were measured using electrochemiluminescence immunoassay with the Roche cobas6000 e60 system. The normal reference ranges at our center are as follows: Serum PTH: 15–65 pg/mL; Ca: 2.10–2.65 mmol/L; Albumin: 35–52 g/L; 25-OH-vitamin D: 3–29 ng/mL.

Definition

The following definitions are based on the American Thyroid Association’s Statement on Postoperative Hypoparathyroidism: Diagnosis, Prevention, and Management in Adults 12. Hypoparathyroidism (HPT) is defined as a condition where serum PTH levels fall below 15 pg/mL. To maintain normal blood calcium levels, oral supplementation with calcium and/or vitamin D is often required. Transient HPT refers to cases where PTH levels fall below 15 pg/mL during the postoperative follow-up period, but return to normal within six months following surgery. Normal blood calcium levels can be maintained without oral calcium or vitamin D supplementation.

Permanent HPT is diagnosed when PTH levels remain below 15 pg/mL for a period exceeding six months, at which point long-term oral calcium and/or vitamin D treatment is recommended. Hypocalcemia is defined as postoperative blood calcium levels below 2.10 mmol/L.

Statistical analysis

Continuous variables with a normal distribution are expressed as the mean and standard deviation, and inter-group comparisons were performed using the independent sample t-test. For numerical variables exhibiting a skewed distribution, the median, P25, and P75 values were used as descriptive statistics, with inter-group comparisons made using the Mann–Whitney U test. Categorical variables are presented as proportions or constituent ratios. The chi-squared test or Fisher’s exact test was used to compare dichotomous variables between groups. Statistically significant variables were further analyzed using binary logistic regression to identify independent risk factors for hypocalcemia during hospitalization, as well as for transient and permanent HPT during the follow-up period. The receiver operating characteristic (ROC) curve was constructed using intact osteocalcin-to-total calcium ratio (IOPTH) and the percentage change in intact PTH (ΔPTH%). The optimal cut-off points, along with corresponding sensitivity and specificity, were determined. IOPTH and ΔPTH% were used to predict the cutoff values for postoperative hypocalcemia, transient HPT, and permanent HPT by comparing diagnostic efficacy based on the area under the curve (AUC). All statistical analyses were performed using IBM SPSS Statistics software, version 27.0. A p-value of less than 0.05 was considered statistically significant.

Results

Descriptive characteristics of the study population

A total of 164 patients were included in the study. Among these, 27 were male (16.5%) and 137 were female (83.5%), yielding a male-to-female ratio of 1:5. The mean age of the patients was 45 years, ranging from 17 to 66 years. The mean preoperative serum calcium (pre-Ca) level was 2.36 ± 0.09 mmol/L, and the mean pre-PTH level was 43.77 ± 11.36 pg/mL. Three patients with benign thyroid disease underwent TT, while the remaining patients with DTC underwent TT combined with central lymph node dissection, with or without lateral lymph node dissection. Of the total patient cohort, 31.7% (52/164) were diagnosed with chronic lymphocytic thyroiditis, and 40.2% (66/164) underwent at least one parathyroid autotransplantation due to inadvertent injury or other reasons. The mean duration of surgery was 132.95 ± 57.24 min, and the mean length of hospital stay was 2.91 ± 0.85 days (Table 1).

Table 1.

Demographic, clinical, and biochemical characteristics of patients.

Characteristic	Value
Age (yrs) ± SD (range)	44.88 ± 10.39
Sex (male/female)	27/137
BMI (kg/m2) ± SD (range)	24.22 ± 3.37
Pre-Ca(mmo1/1)	2.36 ± 0.09
Pre-PTH(pg/ml)	43.77 ± 11.36
Thyroid pathology (Benign/DTC)	3/161
Surgical duration(min)	132.95 ± 57.24
Parathyroid auto-transplantation(Yes/No)	66/98
Chronic lymphocytic thyroiditis (Yes/No)	52/112
Type of procedure
TT	3
TT + CLND	127
TT + CLND + LLND	34
Hospitalisation (days) ± SD (range)	2.91 ± 0.85

DTC Differentiated Thyroid Carcinoma; CLND Central Lymph Node Dissection; LLND Lateral Lymph Node Dissection.

Blood calcium during hospitalization and recovery of parathyroid function

The mean minimum blood calcium (Ca_min) level during hospitalization following surgery was 2.14 ± 0.15 mmol/L. The patients were divided into two groups, designated as Group I and Group II, based on the occurrence of hypocalcemia during hospitalization. The results of the comparison between the two groups are as follows: age (P = 0.653), BMI (P = 0.983), pre-Ca (P = 0.389), pre-PTH (P = 0.649), number of lymph nodes dissected in the VI region (P = 0.144), number of lymph node metastases in region VI (P = 0.496), number of lymph nodes dissected in the lateral cervical region (P = 0.479). The number of lymph nodes dissected in the VI region and the number of lymph node metastases in the lateral cervical region were not found to be statistically significant between patients with hypocalcemia and those with normal serum calcium levels during the postoperative hospitalization period. Patients who developed hypocalcemia (Group I) had a longer hospitalization period compared to those without hypocalcemia (Group II). The differences in IOPTH (P < 0.001) and ΔPTH% (P < 0.001) between the two groups were statistically significant. The median IOPTH level of patients with postoperative hypocalcemia (8.90 pg/mL) was significantly lower than that of patients with normal blood calcium levels (20.83 pg/mL), while the median ΔPTH% in the hypocalcemia group (78%) was higher than that in the normal calcium group (47%). The Pearson correlation test revealed a moderately positive correlation between IOPTH and Camin (r = 0.31), as well as between ΔPTH% and Camin. Additionally, a moderate negative correlation was observed between ΔPTH% and Camin (r =  − 0.35), both of which were statistically significant (P < 0.001).

The categorical variables of gender, chronic lymphocytic thyroiditis, and parathyroid auto-transplantation were analyzed using the chi-squared (χ²) test. Gender was not found to be statistically significant between patients with hypocalcemia and those with normal calcium levels during hospitalization (P = 0.75). However, patients who underwent intraoperative parathyroid auto-transplantation (P = 0.031) or had concurrent chronic lymphocytic thyroiditis (P = 0.028) were more likely to develop hypocalcemia during hospitalization (Table 2).

Table 2.

Comparison of clinicopathological and biochemical parameters between group I (hypocalcemia) and group II (normocalcemia).

Characteristic	Group I (n = 59)	Group II (n = 105)	P value
Age(yrs) ± SD (range)	45.37 ± 11.12	44.61 ± 10.00	0.653
Sex(male/female)	9/50	18/87	0.754
BMI (kg/m2) ± SD (range)	24.21 ± 3.09	24.22 ± 3.53	0.983
Pre-Ca (mmol/l) ± SD (range)	2.36 ± 0.10	2.37 ± 0.09	0.389
Pre- PTH (pg/ml) ± SD (range)	44.31 ± 10.66	43.46 ± 11.77	0.649
Hospitalisation(days) ± SD (range)	3.51 ± 0.77	2.58 ± 0.69	< 0.001
IOPTH (P25, P75) (pg/ml)	8.90(6.85,12.77)	20.83(9.22,31.87)	< 0.001
ΔPTH(P25, P75) (%)	78(67,84)	47(28,75)	< 0.001
Number of lymph nodes dissection in region IV	11(5.5,14.5)	6(4,11.75)	0.144
Number of lymph nodes metastases in region IV	5(1.5,8)	2.5(1,5.75)	0.496
Number of lymph nodes dissection in lateral cervical	16(15,34.5)	2(1,5)	0.610
Number of lymph nodes metastases in lateral cervical	3(2,6.5)	5.08 ± 6.06	0.479
Parathyroid auto-transplantation (Yes/No)	31/28	37/68	0.031
Chronic lymphocytic thyroiditis (Yes/No)	25/34	27/78	0.028
Intravenous fluid volume (P25, P75) (ml)	1500(1100,1800)	1500(1200,1700)	0.630
Surgical duration(min)	126.68 ± 58.26	136.48 ± 56.53	0.294

At the one-month, three-month, and six-month postoperative follow-up visits, the mean blood calcium levels were 2.38 mmol/L, 2.37 mmol/L, and 2.36 mmol/L, respectively. The mean PTH values at these time points were 26.33 pg/mL, 29.50 pg/mL, and 33.48 pg/mL, respectively. A total of 83 patients exhibited low IOPTH following TT. The majority of these patients (65 cases, 78.3%) demonstrated recovery of PTH levels within one month. An additional 8 cases (9.6%) showed recovery within three months, while 6 cases (7.2%) recovered within six months. Four cases (4.8%) did not recover by the end of the six-month observation period. Figure 1 illustrates the recovery of PTH, and Fig. 2 depicts the temporal changes in blood calcium and PTH levels.

Fig. 1.

PTH recovery status in a total of 164 patients.

Fig. 2.

Ca²⁺ and PTH change curve with time. (A) Preoperative serum calcium and PTH; (B) Ca_min during hospitalization period and IOPTH. (C) Calcium and PTH at 1 months after surgery; (D) Calcium and PTH at 3 months after surgery. (E) Calcium and PTH at 6 months after surgery.

Predictive value of IOPTH for blood calcium during hospitalization and recovery of parathyroid function

In our study, 11 out of 164 patients (6.7%) exhibited elevated IOPTH compared to their preoperative PTH levels, with the highest elevation being 62% and the lowest being 1%. One of these patients (pre-PTH = 41.35 pg/mL, IOPTH = 54.78 pg/mL) developed hypocalcemia on the first postoperative day, but none of the patients in this group developed temporary or permanent hypoparathyroidism. Among the 164 patients, 37 (23%) exhibited low IOPTH levels during hospitalization, and hypocalcemia was observed in only 13 cases (8%). Forty-six patients (28%) exhibited both low blood calcium and low IOPTH, while 68 patients (41%) demonstrated normal serum calcium and IOPTH levels. The incidence of postoperative hypocalcemia during hospitalization was 36% (59/164), transient hypoparathyroidism (HPT) occurred in 12.8% (21/164) of patients, and permanent HPT occurred in 2.4% (4/164) (Table 3).

Table 3.

Relationship between IOPTH and serum calcium and parathyroid function recovery.

IOPTH	Camin (mmol/l)		Transient hypoparathyroidism		Permanent hypoparathyroidism
	Hypocalcemia	Normal	Yes	No	Yes	No
IOPTH ≥ 15 pg/ml	13(8%)	68(41%)	5(3%)	76(46%)	0	81(49.4%)
IOPTH < 15 pg/ml	46(28%)	37(23%)	16(10%)	67(41%)	4(2.4%)	79(48.2%)
P value	P < 0.001		0.012		0.121

An ROC curve was constructed to assess the diagnostic accuracy of IOPTH levels and the percentage change in total parathyroid hormone (ΔPTH%) for predicting hypocalcemia following TT. The results indicated that an IOPTH threshold of 14.24 pg/mL yielded an AUC of 0.703 (P < 0.001), with sensitivity and specificity values of 0.780 and 0.676, respectively. For ΔPTH%, a threshold of 64.59% produced an AUC of 0.716 (P < 0.001), with sensitivity and specificity of 0.797 and 0.648, respectively (Fig. 3A). Among patients with postoperative hypocalcemia, ΔPTH% exceeded 80% in 47 of 59 cases, while IOPTH was less than 78% of the reference value in 46 of 59 cases. In predicting in-hospital postoperative hypocalcemia, ΔPTH% demonstrated slightly superior diagnostic performance (AUC = 0.716) compared to IOPTH (AUC = 0.703). Additionally, ΔPTH% showed marginally higher sensitivity (0.797) than IOPTH (0.780).

Fig. 3.

ROC curves of IOPTH and ΔPTH% for blood calcium during hospitalization and recovery of parathyroid function.

The diagnostic performance of IOPTH and ΔPTH% for predicting transient and permanent HPT following TT was further evaluated by constructing ROC curves. For transient HPT, an IOPTH threshold of 12.32 pg/mL yielded an AUC of 0.680 (P = 0.008), with sensitivity and specificity values of 0.762 and 0.587, respectively. A ΔPTH% threshold of 60.36% produced an AUC of 0.664 (P = 0.015), with higher sensitivity (0.905) but lower specificity (0.510) (Fig. 3B). Among the 21 patients who developed transient HPT, 90% (19/21) had a ΔPTH% ≥ 60.36%, and 76% (16/21) had IOPTH values below 12.32 pg/mL. While ΔPTH% (AUC = 0.664) and IOPTH (AUC = 0.680) showed no significant difference in overall diagnostic efficacy for transient HPT, ΔPTH% exhibited significantly higher sensitivity (0.905) than IOPTH (0.762). For permanent HPT, an IOPTH threshold of 7.59 pg/mL yielded an AUC of 0.882 (P = 0.009), with perfect sensitivity (1.0) and a specificity of 0.787 (Fig. 3C). A ΔPTH% threshold of 74.96% had an AUC of 0.806 (P = 0.037), also achieving perfect sensitivity (1.0) but with lower specificity (0.644). All four patients who developed permanent HPT had a ΔPTH% above 74.96% and IOPTH levels below 7.59 pg/mL. For predicting permanent HPT, IOPTH showed superior diagnostic efficacy with an AUC of 0.882 compared to ΔPTH% with an AUC of 0.806.

Analysis of factors affecting IOPTH

To determine the predictive value of IOPTH for parathyroid function recovery, we initially conducted an analysis of potential risk factors. Groups I and II were classified according to the presence or absence of IOPTH levels below 15 pg/ml. As illustrated in Table 3, patients in the IOPTH < 15 pg/ml group exhibited reduced pre-PTH levels (40.75 pg/ml ± 10.34 vs. 46.86 ± 11.58 pg/ml, respectively; P < 0.001) and a higher number of lymph node dissections (8.86 ± 5.66 vs. 6.77 ± 5.11, respectively; P = 0.014). Furthermore, this group demonstrated a higher prevalence of thyroiditis (43.4% vs. 19.8%, respectively; P = 0.001) and parathyroid auto-transplantation (53.0% vs. 29.6%, respectively; P = 0.002). In a multivariate logistic regression analysis model, a lower pre-PTH level (OR = 0.955, 95%CI = 0.926–0.985, P = 0.004), as combined thyroiditis (OR = 2.692, 95%CI = 1.233–5.877, P = 0.013), and combined parathyroid auto-transplantation (OR = 2.582, 95%CI = 1.300–5.134, P = 0.007) were identified as independent risk factors (Table 4, Fig. 4).

Table 4.

Univariate and multivariate analysis among risk factors of IOPTH < 15 pg/mL (n = 164).

Variable	IOPTH < 15	IOPTH ≥ 15	Univariate analysis, P value	Multivariate analysis
				B	OR	95% CI	P value
Female, n (%)	67(80.72)	70(86.42)	0.325	–	–	–	–
Age	44.58 ± 10.26	45.20 ± 10.57	0.704	–	–	–	–
BMI	24.35 ± 3.28	24.09 ± 3.48	0.630	–	–	–	–
Preoperative PTH	40.75 ± 10.34	46.86 ± 11.58	< 0.001	-0.046	0.955	0.926–0.985	0.004
Preoperative serum calcium	2.36 ± 0.10	2.37 ± 0.09	0.533	–	–	–	–
Thyroiditis, n (%)	36(43.37)	16(19.75)	0.001	0.990	2.692	1.233–5.877	0.013
Combined LND	63(75.90)	64(79.01)	0.634	–	–	–	–
Number of lymph nodes dissection in region IV	7(5,12)	6(3.5,9)	0.008	0.036	1.037	0.969–1.110	0.294
Number of lymph nodes metastases in lateral cervical	1(0,5)	1(0,3)	0.272	–	–	–	–
Combined parathyroid auto-transplantation	44(53.01)	24(29.63)	0.002	0.949	2.582	1.299–5.134	0.007
Intravenous fluid volume	1500(1200,1800)	1500(1150,1500)	0.352	–	–	–	–
Surgical duration	136.49 ± 61.91	129.32 ± 52.16	0.423	–	–	–	–

Fig. 4.

Multivariate Logistic regression forest plots describing the independent risk factors of IOPTH < 15 pg/ml.

Discussion

The introduction of intraoperative nerve monitoring devices has significantly improved the protection of nerves during thyroid surgery; however, challenges remain in safeguarding the parathyroid glands. Consequently, the occurrence of HPT continues to be a major concern postoperatively¹³. A meta-analysis of the literature reported that the incidence of transient and permanent HPT following thyroidectomy ranges from 19 to 38% and from 0 to 3%, respectively¹⁴. In the present study, the incidence of transient HPT was 12.8%, and the incidence of permanent HPT was 2.4%, which aligns with previous findings. Parathyroid localization techniques commonly employed in clinical practice offer both benefits and limitations. For example, the use of carbon nanoparticles for visualizing the parathyroid glands through lymph node visualization has been shown to negatively affect outcomes¹⁵. Furthermore, while near-infrared fluorescent imaging with indocyanine green can visualize parathyroid gland hemodynamics, the necessity for an additional light source introduces practical limitations^16,17. Previous research has identified perioperative PTH levels, preoperative vitamin D status, and postoperative changes in biochemical markers as potential predictors of hypocalcemia following TT¹⁸. In this study, we focused on examining the predictive role of IOPTH levels in forecasting the risk of hypocalcemia during hospitalization and the recovery of parathyroid function postoperatively.

The primary factor limiting the discharge of postoperative thyroid cancer patients is hypocalcemia during hospitalization. Additionally, the need for long-term oral calcium supplementation due to hypoparathyroidism can diminish quality of life for these patients. Previous studies have shown that central lymph node dissection (CND), combined with thyroiditis and intraoperative parathyroid damage, increases the likelihood of hypoparathyroidism. Although CND has been shown to raise the risk of transient hypoparathyroidism, it does not seem to increase the risk of permanent hypoparathyroidism. Patients with thyroiditis, however, face an elevated risk of developing permanent hypoparathyroidism⁵. Research⁶ has indicated that prolonged surgical duration (over 123 min) and a high volume of intravenous fluid (over 1085 mL) are associated with a greater risk of transient hypocalcemia after TT, though these factors do not appear linked to permanent hypocalcemia. Additionally, studies across different populations report a higher incidence of postoperative hypocalcemia in elderly patients, potentially due to vitamin D deficiency. Levels of 25-OH-vitamin D may also serve as predictors of postoperative hypocalcemia². Given the high incidence of thyroid cancer among women, female gender may be an independent risk factor for postoperative hypocalcemia¹⁹. Some studies^20–22 have suggested that routine oral calcium and vitamin D supplementation post-surgery can mitigate hypocalcemia due to “secondary injury”²³, which may relate to the pronounced fluctuation in PTH and the prolonged recovery period, as observed in this study, compared to blood calcium changes. The use of post-operative oral calcium could reduce the average length of stay²⁴. In addition, previous research²⁵ has recommended initial elemental calcium supplementation of at least 1000 mg for patients with postoperative PTH levels below 15 pg/mL. While there is awareness of the risk of excessive calcium supplementation, more targeted predictors are needed to identify high-risk patients for more effective supplementation strategies. In this study, our preventive calcium supplementation approach followed relevant guidelines but was somewhat empirical, potentially introducing a degree of bias into the results.

Regarding the timing of PTH measurement, some studies²⁶ have suggested that a serum PTH level of < 10 pg/mL measured 4 h post-surgery is optimal for accurately predicting a serum calcium level below 2.0 mmol/L following TT. Patients with PTH ≥ 6.3 pg/mL on the first postoperative day did not develop permanent hypoparathyroidism²⁷. Nevertheless, postoperative PTH measurement only allows for calcium supplementation, which may help reduce the risk of excessive calcium supplementation but does not permit intraoperative intervention. Consequently, intraoperative PTH measurement could serve as a valuable predictor for parathyroid auto-transplantation. Research has shown that measuring parathyroid hormone 20 min after thyroidectomy provides an accurate and reliable method for predicting clinically significant hypocalcemia. Patients with PTH levels above 9 pg/mL at this time point had a lower likelihood of developing severe hypocalcemia²⁸. A study demonstrated that a decrease in PTH levels of more than 70% on the first postoperative day may indicate the potential for permanent hypoparathyroidism²⁹. Another study³⁰ have suggested that a long duration of surgery, a PTH level of less than 6.3 pg/mL on postoperative day 1, and a large thyroid weight are important risk factors for the development of permanent hypoparathyroidism after TT. Although there is no consensus on the timing of PTH measurement, it is generally accepted that IOPTH can better guide intraoperative procedures such as autotransplantation of potentially non-viable parathyroid glands and early postoperative prophylactic calcium supplementation to provide earlier relief of postoperative discomfort and reduce the possibility of “secondary damage” to the parathyroid glands caused by low calcium.

In our study, when the IOPTH concentration reached 14.24 pg/mL, the AUC was 0.707 (P < 0.001), with sensitivity and specificity values of 0.78 and 0.676, respectively. At a ΔPTH% of 64.59%, the AUC increased slightly to 0.716 (P < 0.001). These findings, along with previous research, demonstrate that IOPTH is an effective predictor of postoperative hypocalcemia and hypoparathyroidism following thyroid surgery. Although a standardized threshold has not been universally established, it is generally accepted that a lower IOPTH value is indicative of a greater rate of decline and a slower recovery of PTH after surgery³¹. Selective autologous parathyroid transplantation has been shown to effectively reduce the risk of postoperative hypocalcemia and hypoparathyroidism in patients with IOPTH < 10 ng/L when measured 10–20 min after TT³². some studies recommend initiating autologous parathyroid transplantation when PTH levels decrease by 75% to 80% during surgery⁷. A previous study³³ demonstrated that preserving at least one parathyroid gland with an intact blood supply can effectively prevent permanent hypoparathyroidism in cases where auto-transplantation is not performed. One study³⁴ on endoscopic thyroidectomy recommended limiting the number of parathyroid grafts to two. Our study adhered to the Chinese consensus¹⁰ on parathyroid protection, and the findings indicate that patients with preoperative PTH levels below the normal range, chronic lymphocytic thyroiditis, and intraoperative parathyroid auto-transplantation are more likely to exhibit postoperative IOPTH levels below 15 pg/mL. Therefore, prioritizing the recovery of parathyroid function in these patients is crucial following surgical intervention. It is also possible that unintentional surgical manipulation could lead to false-positive or elevated IOPTH measurements. It is worth noting that intraoperative PTH measurement did not significantly increase the financial burden of patients at our centre. And this technique has some value in suggesting intraoperative parathyroid autotransplantation, in addition to suggesting potential postoperative hypocalcaemia and hypoparathyroidism. We need a larger sample size in future studies to explore whether an IOPTH target for prophylactic parathyroid autotransplantation can be found.

It should be noted that this study does have limitations. The relatively small sample size and data collection from a single center may introduce bias into the results. Furthermore, the empirical nature of our calcium supplementation approach could further influence the study’s outcomes.

Conclusions

Our study demonstrated that both IOPTH and ΔPTH% effectively predict hypocalcemia during the postoperative hospital stay and aid in assessing parathyroid function recovery. In addition, patients with chronic lymphocytic thyroiditis, those who underwent intraoperative parathyroid auto-transplantation, and those with low preoperative PTH levels require particular attention to support the recovery of parathyroid function following surgery.

Author contributions

Yushuai Zhang: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Project administration, Software, Writing– original draft, Writing– review & editing. Yishen Zhao: Writing– original draft, Funding acquisition, Writing– review & editing. Hong Tang: Writing– review & editing, Formal Analysis, Validation, Visualization. Hongrui Zou: Writing– review & editing, Data curation, Writing– original draft. Yang Li: Writing-review & editing. Xuehai Bian: Investigation, Methodology, Writing– review & editing. Jie Tan: Investigation, Methodology, Writing– review & editing. Yingying Wang: Investigation, Methodology, Writing– review & editing.

Funding

This work was supported by Science and Technology Research Project of Education Department of Jilin Province, China,[No.JJKH20221065KJ]; Beijing Cihua Medical Development Foundation[J2023107004].

Data availability

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

Declarations

Competing interests

The authors declare no competing interests.

Ethical approval

The study was approved by the Institutional Review Board of China-Japan Union Hospital of Jilin University (approval number: 2022-KYYS-078). The patients or their legal guardians signed a detailed informed consent form before surgery.