Elevated parathyroid hormone levels in normocalcemic patients after parathyroidectomy for primary hyperparathyroidism: What risk factors should be considered?

Elevated parathyroid hormone levels in normocalcemic patients after parathyroidectomy for primary hyperparathyroidism: What risk factors should be considered? | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Elevated parathyroid hormone levels in normocalcemic patients after parathyroidectomy for primary hyperparathyroidism: What risk factors should be considered? Jun Yang, Zhuo He, Pingping Zhou, Xili Lu, Wanwen Weng, Cheng Ding, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7022277/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Mar, 2026 Read the published version in BMC Endocrine Disorders → Version 1 posted 12 You are reading this latest preprint version Abstract Objective Normocalcemia with elevated parathyroid hormone levels (NCePTH) after successful parathyroidectomy in patients with primary hyperparathyroidism (PHPT) has drawn attention during the postoperative period and remain a clinical conundrum. Patients and methods: We retrospectively studied 539 consecutive patients with PHPT who underwent parathyroid surgery from August 2017 to December 2023. Results The mean age of the patients was 53.3 years, and 66.3% of the patients were female. After a median follow-up of 12 months, 9.9% of the patients were diagnosed with NCePTH. Compared with patients who were cured after surgery, those with NCePTH had high preoperative serum PTH levels (median [quartile], 228 pg/mL [126, 387] vs. 150 pg/mL [108.65, 251.5], p = 0.039) and PTH levels on the first postoperative day (median [quartile], 23.5 pg/mL [8.1, 35.6] vs. 9.7 pg/mL [4, 21.15], p = 0.000). Patients with NCePTH after surgery did not differ from those with normal PTH levels in terms of sex, age, body mass index, history of thyroid/parathyroid surgery, calcium, phosphorus, and creatinine levels and parathyroid lesion size. According to the multivariable analysis, a preoperative PTH concentration ≥ 191 pg/mL (odds ratio [OR], 8.78; p = 0.003) and PTH concentration ≥ 16.4 pg/mL (odds ratio [OR], 12.47; p = 0.0004) on the first day after surgery remained risk factors for NCePTH. Conclusions The incidence rate of NCePTH after successful parathyroidectomy in patients with PHPT was 9.9%. A preoperative PTH concentration ≥ 191 pg/mL and a PTH concentration ≥ 16.4 pg/mL on the first day after surgery were identified as risk factors for NCePTH after parathyroidectomy. normocalcemic elevated parathyroid hormone parathyroidectomy primary hyperparathyroidism risk factors Figures Figure 1 Background Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by the hypersecretion of parathyroid hormone (PTH) by a pathological parathyroid gland, leading to elevated serum calcium levels [ 1 ]. The prevalence of PHPT may be 1–3% in the general population (2). Individuals with PHPT can present with varying degrees of disease, ranging from asymptomatic to severe musculoskeletal, renal, and neuropsychiatric manifestations [ 1 , 3 ]. Parathyroidectomy remains the only curative treatment, with a cure being defined as normal calcium homeostasis at 6 months postsurgery [ 4 ]. Long-term cure rates > 97% have been reported for patients for whom advanced preoperative imaging locations and intraoperative PTH-guided strategies are used, particularly those undergoing surgeries at high-volume institutions [ 1 , 5 ]. However, the regular monitoring of PTH and serum calcium concentrations during the follow-up of patients who undergo successful parathyroidectomy has drawn attention to the group of patients with normocalcemia with elevated parathyroid hormone levels (NCePTH) compared with cured patients (normal calcium and PTH levels) or patients with recurrent hyperparathyroidism (elevated calcium and PTH levels). NCePTH remains a conundrum for both clinicians and patients because the results of studies on its natural history and long-term consequences are inconclusive [ 6 ]. The incidence of NCePTH after curative parathyroidectomy ranges from 3‒46% according to the literature due to differences in the study population included and the timepoints at which the measurements were made [ 6 – 11 ]. Many factors, including older age, high preoperative PTH levels, vitamin D deficiency, high serum creatinine levels, and greater adenoma weight, have been reported to be associated with NCePTH [ 12 – 15 ]. The purpose of our study was to determine the incidence rate of NCePTH and to identify associated clinicopathological risk factors. A full understanding of the natural history of NCePTH in patients who undergo successful parathyroidectomy is increasingly important for both clinicians and patients. Patients and methods Study subjects Institutional review board approval and a waiver for the requirement of consent was obtained in this retrospective study. We conducted a retrospective review of consecutive patients who underwent parathyroidectomy at our institution from August 2017 to December 2023. A total of 536 patients diagnosed with sporadic PHPT according to laboratory tests and clinical evidence from guidelines were included, and patients with secondary or tertiary hyperparathyroidism were excluded. Patients who met any of the following criteria were excluded from the study: (1) were younger than 18 years, (2) were diagnosed with a genetic syndrome, (3) had a final pathological diagnosis of parathyroid carcinoma, (4) had negative surgical outcomes, (5) had a follow-up of less than 6 months, or (6) had persistent and recurrent hyperparathyroidism for at least 6 months. Clinicopathological factors, such as age, sex, body mass index (BMI), symptoms, laboratory results (preoperatively and on the first postoperative day), autoimmune thyroid disease status (hyper/hypothyroidism, Hashimoto’s thyroiditis), thyroid nodules (> 5 mm), preoperative imaging localization, and the number, location and size of parathyroid lesions according to the operative and pathological reports, were obtained. All patients routinely underwent preoperative imaging, including cervical ultrasonography and a combination of 99mTc-sestamibi SPECT/CT, to localize parathyroid lesions and/or screen for possible coexisting thyroid nodules/diseases. The surgical procedure was selected on the basis of the patient’s clinical characteristics, the results of all the imaging modalities and the surgeon’s clinical preference. Correct localization was defined as the parathyroid lesion described in the imaging report matching the surgical finding with respect to the exact anatomical location identified during the operation. Localizations with at least one imaging report that conflicted with the surgical pathology findings were defined as incorrect localizations. Patients were evaluated on the first day after surgery, at 4 weeks and 6 months after surgery for serum calcium and PTH levels, and then at regular intervals at the discretion of the surgeon. Patients with NCePTH were defined as having normal serum calcium levels, with concurrent elevated PTH levels during the last follow-up. The patients were divided into two groups according to their postoperative PTH and serum calcium levels: the NCePTH group and the cured PHPT group (normal serum calcium and PTH levels at the last follow-up and at more than 6 months of follow-up). Statistical methods Continuous variables are expressed as medians (interquartile ranges) and means ± standard deviations on the basis of their distributions. Categorical variables are expressed as counts (percentages). For continuous variables, an independent samples t test was used for normally distributed data, and the Mann‒Whitney rank sum test was used for nonnormally distributed data. Clinicopathological characteristics were compared between the NCePTH group and the cured PHPT group via the chi-square test or Fisher’s exact test for categorical variables. The optimal cutoff points for preoperative PTH levels and PTH levels on the first day after surgery were identified when the Youden index was at its maximum. To identify clinicopathological factors contributing to NCePTH, these factors were assessed using univariate and multivariable logistic regression analyses. A bidirectional stepwise method was used to select the final multivariate model due to the small event size. All multivariate models used a Cox regression model with the Firth penalized maximum likelihood method for bias correction. A p value < 0.05 was considered statistically significant. All the statistical analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA). Results Patient characteristics A total of 536 patients underwent surgery for PHPT during the study period, and the final cohort consisted of 395 patients. Figure 1 shows the study exclusion and inclusion criteria. Table 1 summarizes the patients’ clinical, laboratory, imaging, operative, pathological and demographic characteristics. The mean age of the patients was 53.3 years (range: 18–85 years), and 66.3% of the patients were female. Seven patients had previously undergone thyroid surgery: one underwent subtotal thyroidectomy for hyperthyroidism, two underwent thyroid lobectomy for microscopic papillary thyroid carcinoma, and four underwent hemithyroidectomies for thyroid nodules. The median BMI was 22.9 kg/m2 in the 386 patients with available data. Two patients had a history of parathyroidectomy for PHPT. The median calcium and phosphorus levels were 2.74 mmol/L (range 2.50–4.37; normal, 2.11–2.52) and 0.85 mmol/L (range 0.36–1.91; normal, 0.85–1.51), respectively. The median PTH level was 157.7 pg/mL (range 54.9–3510; normal, 12–65). There were 304 patients with available data on 25-vitamin D3 levels, with a median of 40.0 nmol/L (range 7.9–109; normal, 15.6–125). Fifty-two (13.16%) patients had autoimmune thyroid disease (AITD; hyper/hypothyroidism, Hashimoto’s thyroiditis), 10 had hyperthyroidism, 12 had hypothyroidism, and 30 had Hashimoto’s thyroiditis. Among the 395 patients, 373 (94.4%) had SGD, and 22 (5.6%) had MGD. Among the patients with MGD (n = 22), 19 (86.4%) had double adenomas or hyperplasia, and 3 (13.6%) had three abnormal glands. All patients had follow-up information for at least 6 months. The median follow-up time was 12 months (range 6–69 months). Table 1 Clinicopathologic demographics of patients with primary hyperparathyroidism Parameter Total (n = 395) Cure (n = 356) NCePTH (n = 39) P value Age, median (rang), y 55 (18–85) 55 (18–85) 55 (22–68) 0.220 Female, No. (%) 262 (66.33) 240 (67.42) 22 (56.41) 0.167 Previous thyroidectomy or parathyroidectomy No. (%) 9 (2.28) 8 (2.25) 1 (2.56) 1 BMI, median (quartile) * 22.86 (21.03, 25.04) 22.79 (20.96, 25.07) 23.31 (21.14, 24.98) 0.751 Thyroid nodule, No. (%) 170 (43.04) 154 (43.26) 16 (41.03) 0.789 AITD, No. (%) 52 (13.16) 48 (13.48) 4 (10.26) 0.572 Calcium, median (quartile), mmol/L 2.74 (2.60, 2.91) 2.74 (2.60, 2.91) 2.74 (2.59, 3.01) 0.834 Phosphorus, median (quartile), mmol/L 0.85 (0.74, 0.96) 0.85 (0.74, 0.96) 0.87 (0.77, 0.98) 0.501 Preoperative PTH, median (quartile), pg/mL 157.7 (110, 264) 150 (108.65, 251.5) 228 (126, 387) 0.039 Alkaline phosphates, median (quartile), (U/L) 105 (81, 143) 103.5 (81, 141) 115 (84, 168) 0.278 Creatinine, median (quartile), (µmol/L) 68 (56, 87) 68 (56, 88) 68 (56, 82) 0.732 25-hydroxyvitamin D, median (quartile), nmol/L** 40 (29.1, 51.05) 40.2 (29.6, 51.3) 37.4 (28.3, 45.2) 0.287 Confirmatory localization Ultrasonography confirmation, No. (%) 248 (62.78) 222 (62.36) 26 (66.67) 0.597 Sestmibi SPECT/CT confirmation, No. (%) 319 (80.76) 289 (81.18) 30 (76.92) 0.522 2-imaging contradictory localization, No. (%) 169 (42.78) 151 (42.42) 18 (46.15) 0.654 SGD, No. (%) 373 (94.43) 338 (94.94) 35 (89.74) 0.256 Parathyroid lesion size, median (quartile), mm 18 (13, 25) 16.5 (13, 25) 20 (15, 25) 0.125 First-day after surgery calcium, median (quartile), mmol/L 2.21 (2.11, 2.34) 2.21 (2.11, 2.34) 2.18 (2.08, 2.35) 0.618 First-day after surgery PTH, median (quartile), pg/mL 10.2 (4.3, 22.7) 9.7 (4, 21.15) 23.5 (8.1, 35.7) 0.000 Follow up, median (quartile), months 12 (8, 21) 12 (8, 21) 9 (6, 24) 0.184 Abbreviation: BMI, body mass index; AITD, autoimmune thyroid disease; PTH, parathyroid hormone; Calcium, normal range: 2.11–2.52; Phosphorus, normal range: 0.85–1.51; PTH, normal range: 12.0–65.0; Alkaline phosphates, normal range: 40–150; Creatinine, normal range: 44–80; 25-hydroxyvitamin D, normal range:15.6–125; SGD, single gland disease. * Data was available for 386 patients; ** Data was available for 304 patients. Clinicopathological factors associated with NCePTH Among the 395 patients, 39 (9.9%) patients were diagnosed with NCePTH, whereas the remaining 356 (90.1%) had normal serum PTH and calcium levels. Compared with patients who were cured after surgery, those with NCePTH had high preoperative serum PTH levels (median [quartile], 228 pg/mL [126, 387] vs. 150 pg/mL [108.65, 251.5], p = 0.039) and high PTH levels on the first postoperative day (median [quartile], 23.5 pg/mL [8.1, 35.6] vs. 9.7 pg/mL [4, 21.15], p = 0.000). The 25-hydroxyvitamin D level in the NCePTH group was lower than that in the cured group (median, 37.4 nmol/L vs. 40.2 nmol/L), but the difference was not significant (p = 0.287). The alkaline phosphate levels in the NCePTH group were greater than those in the cured group (median, 115 U/L vs. 105.3 U/L), but this difference was also not significant (p = 0.278). We observed no significant difference in the type of imaging modality (ultrasonography and Sestmibi SPECT/CT) used preoperatively for these patients. Age, female sex, BMI, history of thyroid/parathyroid surgery, AITD status, thyroid nodule status, calcium, phosphorus, and creatinine levels, and parathyroid lesion size were not associated with NCePTH group or cure status (Table 1 ). Youden index analysis revealed that a preoperative PTH level ≥ 191 pg/mL and a PTH level ≥ 16.4 pg/mL on the first day after surgery were optimal cutoff points for identifying patients at risk for NCePTH. In univariate analysis, clinicopathological factors associated with NCePTH after parathyroidectomy findings included a preoperative PTH level ≥ 191 pg/mL (odds ratio [OR], 8.68; 95% CI 1.41–5.49, p = 0.003) and a PTH level ≥ 16.4 pg/mL (odds ratio [OR], 13.75; 95% CI 1.85–7.37, p = 0.0002) on the first day after surgery. BMI, 5-hydroxyvitamin D, creatinine, and alkaline phosphate levels and the type of imaging modality used for localization were not statistically significant predictors. In the multivariable analysis, a preoperative PTH level ≥ 191 pg/mL (odds ratio [OR], 8.78; 95% CI 1.52–57.74; p = 0.003) and a PTH level ≥ 16.4 pg/mL (odds ratio [OR], 12.47; 95% CI 1.93–10.03; p = 0.0004) on the first day after surgery remained risk factors for NCePTH (Table 2 ). Table 2 Univariate and multivariate analysis for predictors of NCePTH after parathyroidectomy Variable Univariate analysis Multivariate analysis Odd ratio 95% CI P value Odd ratio 95% CI P value BMI 0.02 0.99–1.11 0.902 5-hydroxyvitamin D * 1.28 0.96–1.01 0.258 Creatinine 0.12 0.99–1.01 0.726 Alkaline phosphates 1.06 0.10-1.00 0.303 Ultrasonography confirmation, 0.28 0.60–2.43 0.598 Sestmibi SPECT/CT confirmation 0.41 0.35–1.70 0.523 2-imaging contradictory localization 0.20 0.44–1.67 0.654 Preoperative PTH ≥ 191 pg/mL 8.68 1.41–5.49 0.003 8.78 1.52–7.74 0.003 First-day after surgery PTH ≥ 16.4 pg/mL 13.75 1.85–7.37 0.0002 12.46 1.93–10.03 0.0004 CI, confidence interval; BMI, body mass index; * Data was available for 304 patients; PTH, parathyroid hormone Discussion With the increasing number of patients diagnosed with PHPT and surgeries for biochemical screening and precise preoperative localization, emerging data suggest that a substantial number of patients will develop NCePTH after successful parathyroidectomy. In this study, which included many patients and rigorous criteria, the incidence rate of NCePTH was 9.9%, with a median follow-up time of 12 months. We observed that preoperative PTH levels ≥ 191 pg/mL and PTH levels ≥ 16.4 pg/mL on the first day after surgery were risk factors for NCePTH. Our data provide information for clinicians and provide a full understanding of medical management plans for patients with NCePTH. In our study, 9.9% (39/395) of the patients developed NCePTH after successful parathyroidectomy with a median of 12 months of follow-up. Our results are consistent with those of previous reports. For example, Wan et al. followed 768 patients for more than 6 months after successful parathyroidectomy: 76 patients (8%) demonstrated persistent elevated PTH levels and normocalcemia [ 11 ]. In one cohort of 99 patients with solitary parathyroid adenomas who underwent successful parathyroidectomy, 16% had NCePTH 5 years after surgery [ 16 ]. Another study reported an isolated increase in PTH levels in 23% of 547 patients with PHPT at 12 months after surgery [ 17 ]. A review of 33 studies revealed that the prevalence of NCePTH was 3–46% at greater than 6 months after surgery [ 6 ]. Compared with previous studies, our study defined NCePTH as an elevated PTH level during the last follow-up at least 6 months after surgery, and different studies had different inclusion and exclusion criteria, which led to different prevalences. The increasing number of patients with NCePTH raises clinical questions about the etiology of NCePTH and whether it can be used to predict the relationships among clinicopathological factors. Previous studies have shown that high preoperative PTH levels [ 17 , 18 – 21 ], vitamin D deficiency [ 13 , 15 , 20 , 22 ], impaired renal function [ 6 , 18 , 19 , 22 – 24 ], severe bone disease [ 13 , 17 , 21 ] and larger adenomas [ 18 , 20 , 22 ] are potential risk factors for NCePTH. Our data revealed that high PTH levels preoperatively and on the first day after surgery were correlated with an increased risk of NCePTH. These results are consistent with those of previous reports. For example, Bergenflz et al demonstrated that the preoperative PTH level correlated with the postoperative PTH level at one year (r = 0.36; p < 0.01) [ 22 ]. In one cohort of 407 patients who underwent parathyroidectomy for PHPT, the presurgical PTH level was significantly greater (p < 0.001) in those with NCePTH (156.5 pg/mL) than in those with a presurgical level of 102.5 pg/mL in whom the PTH level normalized [ 25 ]. A retrospective analysis revealed that, in 1037 patients with PHPT, NCePTH was linked to greater preoperative PTH levels at 6 months [ 26 ]. Our data also revealed that the preoperative PTH level in the NCePTH group was greater than that in the cured group (228 pg/mL vs. 150 pg/mL, p = 0.039). Mandal et al reported that the PTH levels on the first day of the operation were significantly greater (20 ± 6 vs. 10 ± 2 pg/mL) in 12% of the 78 patients with NCePTH (27). Our study also revealed that the PTH levels on the first day after surgery in the NCePTH group (23.5 vs. 9.7 pg/mL, p = 0.000) were greater than those in the cured group. The etiology of NCePTH remains uncertain, but it is likely multifactorial. Some studies speculate that the impaired responsiveness of PTH may be due to PTH receptor downregulation in patients with higher preoperative PTH concentrations. When PTH levels decrease immediately after successful parathyroidectomy, patients may have an altered set point for PTH release for calcium homeostasis, resulting in parathyroid hormone resistance (higher PTH release) and/or decreased sensitivity of the calcium-sensing receptor. Another potential mechanism for NCePTH is vitamin D deficiency. Some studies have shown that patients with vitamin D deficiency are more likely to exhibit NCePTH [ 13 , 15 , 20 , 22 ]. Beyer et al reported that a significantly lower incidence of NCePTH was observed when patients were treated postoperatively with calcitriol [ 15 ]. Another retrospective analysis revealed that uncontrolled calcium supplementation in patients with NCePTH may lead to normalization of PTH in some patients [ 12 ]. Our study revealed that 25-hydroxyvitamin D levels were lower (37.4 nmol/L vs. 40.2 nmol/L) in the NCePTH group than in the control group, but this difference was not significant. These inconsistencies with the literature may be due to the incomplete 25-hydroxyvitamin D data in our study and the nonroutine measurement of vitamin D levels after surgery. Our study revealed no evidence for associations of older age, BMI, impaired renal function, severe bone disease, or larger adenomas with NCePTH. This study has certain limitations. First, this was a single-center retrospective study, and some clinicopathological variables, such as 25-hydroxyvitamin D, BMI and bone density measurements, as well as the weight of parathyroid lesions, were incomplete, which may have influenced the statistical analysis and made it difficult to fully rule out secondary hyperparathyroidism. Second, some patients returned to their primary care providers after successful parathyroidectomy and returned to our tertiary referral center because of abnormal laboratory values. This could lead to some patients being lost to follow-up and bias in the incidence rate of NCePTH. Finally, the follow-up period was relatively short, and other possible causes of elevated PTH levels, such as vitamin D status or renal function, were not assessed throughout the follow-up period. Further multicenter, controlled prospective studies with larger samples are needed to address the limitations of our study. In conclusion, in this large retrospective series, the incidence rate of NCePTH after successful parathyroidectomy in patients with PHPT was 9.9%. A preoperative PTH concentration ≥ 191 pg/mL and a PTH concentration ≥ 16.4 pg/mL on the first day after surgery were identified as risk factors for NCePTH after parathyroidectomy. Our data highlight the importance of clinicopathological factors in the prediction of postoperative NCePTH and help the endocrine community refine surveillance strategies for these patients. Abbreviations NCePTH Normocalcemia with elevated parathyroid hormone levels PHPT primary hyperparathyroidism PTHparathyroid hormone BMI body mass index AITD autoimmune thyroid disease SPECT/CT single photon emission computed tomography/computed tomography SGD single gland disease MGD multigland disease Declarations Author contributions Conceptualization and manuscript writing: Jun Yang, Zhuo He, Xinhui Su. Data collection and organization: Pingping Zhou, Xili Lu, Wanwen Weng, MD, Haohao Wang. Data analysis and statistics: Cheng Ding. Critical revision of the manuscript: Jun Yang, Zhuo He, Xinhui Su. Approval of the final version of the manuscript on behalf of all the authors: Xinhui Su. Acknowledgements The authors thank Weiyi Wang, BA and Shuangzhi Lv, BA, for their follow-up assistance. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Conflict of interest The authors declare no completing interests. Ethics approval and consent to participate This work was carried out in accordance with the Helsinki Declaration and approved by the Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (IIT-20241294A). Because this study was retrospective, the requirement of informed consent was waived. It was performed in accordance with the Declaration of Helsinki. Clinical trial number Not applicable. Consent for Publication Not applicable. References Walker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14(2):115–25. Yeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013;98(3):1122–9. Bilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F. Primary hyperparathyroidism. Nat Rev Dis Primers. 2016;2(1):16033. Bilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561–3569. Udelsman R, Lin Z, Donovan P. The superiority of minimally invasive parathyroidectomy based on 1650 consecutive patients with primary hyperparathyroidism. Ann Surg. 2011;253:585–91. de la Plaza Llamas R, Ramia A´ ngel JM, Arteaga Peralta V, Garc´ıa Amador C, Lo´ pez Marcano AJ, et al. Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review. Eur Arch Otorhinolaryngol. 2018;275(3):659–69. Goldfarb M, Gondek S, Irvin GL III, Lew JI. Normocalcemic parathormone elevation after successful parathyroidectomy: long-term analysis of parathormone variations over 10 years. Surgery. 2011;150:1076–82. Ning L, Sippel R, Schaefer S, Chen H. What is the clinical significance of an elevated parathyroid hormone level after curative surgery for primary hyperparathyroidism? Ann Surg. 2009;249:469–72. Solorzano CC, Mendez W, Lew JI, Rodgers SE, Montano R, Carneiro-Pla DM, et al. Long-term outcome of patients with elevated parathyroid hormone levels after successful parathyroidectomy for sporadic primary hyperparathyroidism. Arch Surg. 2008;143:659–63. Lang BH, Wong IY, Wong KP, Lo C. Eucalcemic parathyroid hormone elevation after parathyroidectomy for primary sporadic hyperparathyroidism: risk factors, trend, and outcome. Ann Surg Oncol. 2012;1:584–90. Wang TS, Ostrower ST, Heller KS. Persistently elevated parathyroid hormone levels after parathyroid surgery. Surgery. 2005;138:1130–5. Carty SE, Roberts MM, Virji MA, Haywood L, Yim JH. Elevated serum parathormone level after concise parathyroidectomy for primary sporadic hyperparathyroidism. Surgery. 2002;132(6):1086–92. Denizot A, Pucini M, Chagnaud C, Botti G, Henry JF. Normocalcemia with elevated parathyroid hormone levels after surgical treatment of primary hyperparathyroidism. Am J Surg. 2001;182(1):15–9. Westerdahl J, Valdemarsson S, Lindblom P, Bergenfelz A. Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption. World J Surg. 2000;24(11):1323–9. Beyer TD, Solorzano CC, Prinz RA, Babu A, Nilubol N, Patel S. Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism. Surgery. 2007;141(6):777–83. Nordenström E, Westerdahl J, Bergenfelz A. Long-term follow-up of patients with elevated PTH levels following successful exploration for primary hyperparathyroidism. World J Surg. 2004;28(6):570–5. Lavryk OA, Siperstein AE. Pattern of calcium and parathyroid hormone normalization at 12-months follow-up after parathyroid operation. Surgery. 2017;161(4):1139–48. Yamashita H, Noguchi S, Moriyama T, Takamatsu Y, Sadanaga K, Uchino S, et al. Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: Importance of decreased renal parathyroid hormone sensitivity. Surgery. 2005;137:419–25. Mittendorf EA, McHenry CR. Persistent parathyroid hormone elevation following curative parathyroidectomy for primary hyperparathyroidism. Arch Otolaryngol Head Neck Surg. 2002;128:275–9. Stewart ZA, Blackford A, Somervell H, Friedman K, Garrett-Mayer E, Dackiw AP, et al. 25-hydroxyvitamin D deffciency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy. Surgery. 2005;138:1018–25. Dhillon KS, Cohan P, Darwin C, Van Herle A, Chopra IJ. Elevated serum parathyroid hormone concentration in eucalcemic patients after parathyroidectomy for primary hyperparathyroidism and its relationship to vitamin D profile. Metabolism. 2004;53:1101–6. Bergenfelz A, Valdemarsson S, Tibblin S. Persistent elevated serum levels of intact parathyroid hormone after operation for sporadic parathyroid adenoma: Evidence of detrimental effects of severe parathyroid disease. Surgery. 1996;119:624–33. Beyer TD, Chen EL, Nilubol N, Prinz RA, Solorzano CC. Short-term outcomes of parathyroidectomy in patients with or without 25-hydroxy vitamin D insufffciency. J Surg Res. 2007;143:145–50. Nordenström E, Westerdahl J, Isaksson A, Lindblom P, Bergenfelz A. Patients with elevated serum parathyroid hormone levels after parathyroidectomy: Showing signs of decreased peripheral parathyroid hormone sensitivity. World J Surg. 2003;27:212–5. Caldwell M, Laux J, Clark M, Kim L, Rubin J. Persistently Elevated PTH After Parathyroidectomy at One Year: Experience in a Tertiary Referral Center. J Clin Endocrinol Metab. 2019;104(10):4473–80. Carsello CB, Yen TW, Wang TS. Persistent elevation in serum parathyroid hormone levels in normocalcemic patients after parathyroidectomy: does it matter? Surgery. 2012;152(4):575–81. Mandal AK, Udelsman R. Secondary hyperparathyroidism is an expected consequence of parathyroidectomy for primary hyperparathyroidism: a prospective study. Surgery. 1998;124(6):1021–6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 07 Mar, 2026 Read the published version in BMC Endocrine Disorders → Version 1 posted Editorial decision: Revision requested 23 Sep, 2025 Reviewers agreed at journal 21 Sep, 2025 Reviews received at journal 20 Sep, 2025 Reviewers agreed at journal 12 Sep, 2025 Reviews received at journal 08 Sep, 2025 Reviewers agreed at journal 06 Sep, 2025 Reviewers agreed at journal 28 Aug, 2025 Reviewers invited by journal 06 Jul, 2025 Editor invited by journal 03 Jul, 2025 Editor assigned by journal 03 Jul, 2025 Submission checks completed at journal 03 Jul, 2025 First submitted to journal 01 Jul, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7022277","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":481923524,"identity":"51716569-b8ee-465b-946a-f1557a58b473","order_by":0,"name":"Jun Yang","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Jun","middleName":"","lastName":"Yang","suffix":""},{"id":481923525,"identity":"429a5e70-7ccd-4767-867c-3c765cea6dff","order_by":1,"name":"Zhuo He","email":"","orcid":"","institution":"the First hospital of Hunan University of Chinese Medicine","correspondingAuthor":false,"prefix":"","firstName":"Zhuo","middleName":"","lastName":"He","suffix":""},{"id":481923526,"identity":"4cf57bb0-742e-4c80-9512-52fca28ebea7","order_by":2,"name":"Pingping Zhou","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Pingping","middleName":"","lastName":"Zhou","suffix":""},{"id":481923527,"identity":"832854ec-9f24-4496-b39e-b3dc7db20e7b","order_by":3,"name":"Xili Lu","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xili","middleName":"","lastName":"Lu","suffix":""},{"id":481923528,"identity":"da1be310-03ed-442d-bb29-67df6d5211b9","order_by":4,"name":"Wanwen Weng","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Wanwen","middleName":"","lastName":"Weng","suffix":""},{"id":481923529,"identity":"6b85b8b1-9fe9-4610-99fb-955688959825","order_by":5,"name":"Cheng Ding","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Ding","suffix":""},{"id":481923530,"identity":"8bb33925-f40a-48a8-b0eb-c1c4f325f83d","order_by":6,"name":"Haohao Wang","email":"","orcid":"","institution":"Zhejiang University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Haohao","middleName":"","lastName":"Wang","suffix":""},{"id":481923531,"identity":"0b2d2178-1f40-4d67-80d3-3a07da7d5cb0","order_by":7,"name":"Xinhui Su","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0klEQVRIie3RsQrCMBCA4StCu0S6RlB8hUhAhA6+SkKhXYrg5uAQEOLYVd/EMRJwirj2CToL7mIsglubboL5pxvuIwcB8Pl+NBUIQDEAs/OgBxmJPgQsAaKa0YFMD8VMr096TG+qxrBJuIiuqpWQKmP6aDSaK5VhMDkXaMXaCU6VHkpLziLDgdRcYEQ6DuOiIXQHljwdCFSfV0j4JsKBEFMzS3KEDaQLdsmpREXHYfuCPoYyWcal4dV9m0zKyHQc9g2x5jND131bpHos+3w+3z/1AumiQ/MJg7YWAAAAAElFTkSuQmCC","orcid":"","institution":"Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Xinhui","middleName":"","lastName":"Su","suffix":""}],"badges":[],"createdAt":"2025-07-01 16:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7022277/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7022277/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12902-026-02228-8","type":"published","date":"2026-03-07T15:57:42+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86628637,"identity":"e0bf4be5-ba98-46fe-9b1b-19ddbb454063","added_by":"auto","created_at":"2025-07-14 05:47:18","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":622187,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart of consecutive patients with primary hyperparathyroidism and the inclusion and exclusion criteria.\u003c/p\u003e","description":"","filename":"Figure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7022277/v1/4ca68b73161e6ac448b27a0c.jpeg"},{"id":104250908,"identity":"44533d30-1759-4ac9-9085-59f5ca63d042","added_by":"auto","created_at":"2026-03-09 16:11:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1305083,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7022277/v1/ebd7b587-6b4b-44ab-934d-c8cb411fc3df.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Elevated parathyroid hormone levels in normocalcemic patients after parathyroidectomy for primary hyperparathyroidism: What risk factors should be considered?","fulltext":[{"header":"Background","content":"\u003cp\u003ePrimary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by the hypersecretion of parathyroid hormone (PTH) by a pathological parathyroid gland, leading to elevated serum calcium levels [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence of PHPT may be 1\u0026ndash;3% in the general population (2). Individuals with PHPT can present with varying degrees of disease, ranging from asymptomatic to severe musculoskeletal, renal, and neuropsychiatric manifestations [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Parathyroidectomy remains the only curative treatment, with a cure being defined as normal calcium homeostasis at 6 months postsurgery [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Long-term cure rates\u0026thinsp;\u0026gt;\u0026thinsp;97% have been reported for patients for whom advanced preoperative imaging locations and intraoperative PTH-guided strategies are used, particularly those undergoing surgeries at high-volume institutions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, the regular monitoring of PTH and serum calcium concentrations during the follow-up of patients who undergo successful parathyroidectomy has drawn attention to the group of patients with normocalcemia with elevated parathyroid hormone levels (NCePTH) compared with cured patients (normal calcium and PTH levels) or patients with recurrent hyperparathyroidism (elevated calcium and PTH levels).\u003c/p\u003e\u003cp\u003eNCePTH remains a conundrum for both clinicians and patients because the results of studies on its natural history and long-term consequences are inconclusive [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The incidence of NCePTH after curative parathyroidectomy ranges from 3‒46% according to the literature due to differences in the study population included and the timepoints at which the measurements were made [\u003cspan additionalcitationids=\"CR7 CR8 CR9 CR10\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Many factors, including older age, high preoperative PTH levels, vitamin D deficiency, high serum creatinine levels, and greater adenoma weight, have been reported to be associated with NCePTH [\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe purpose of our study was to determine the incidence rate of NCePTH and to identify associated clinicopathological risk factors. A full understanding of the natural history of NCePTH in patients who undergo successful parathyroidectomy is increasingly important for both clinicians and patients.\u003c/p\u003e"},{"header":"Patients and methods","content":"\u003cp\u003e\u003cb\u003eStudy subjects\u003c/b\u003e\u003c/p\u003e\u003cp\u003e Institutional review board approval and a waiver for the requirement of consent was obtained in this retrospective study. We conducted a retrospective review of consecutive patients who underwent parathyroidectomy at our institution from August 2017 to December 2023. A total of 536 patients diagnosed with sporadic PHPT according to laboratory tests and clinical evidence from guidelines were included, and patients with secondary or tertiary hyperparathyroidism were excluded. Patients who met any of the following criteria were excluded from the study: (1) were younger than 18 years, (2) were diagnosed with a genetic syndrome, (3) had a final pathological diagnosis of parathyroid carcinoma, (4) had negative surgical outcomes, (5) had a follow-up of less than 6 months, or (6) had persistent and recurrent hyperparathyroidism for at least 6 months.\u003c/p\u003e\u003cp\u003eClinicopathological factors, such as age, sex, body mass index (BMI), symptoms, laboratory results (preoperatively and on the first postoperative day), autoimmune thyroid disease status (hyper/hypothyroidism, Hashimoto\u0026rsquo;s thyroiditis), thyroid nodules (\u0026gt;\u0026thinsp;5 mm), preoperative imaging localization, and the number, location and size of parathyroid lesions according to the operative and pathological reports, were obtained. All patients routinely underwent preoperative imaging, including cervical ultrasonography and a combination of 99mTc-sestamibi SPECT/CT, to localize parathyroid lesions and/or screen for possible coexisting thyroid nodules/diseases. The surgical procedure was selected on the basis of the patient\u0026rsquo;s clinical characteristics, the results of all the imaging modalities and the surgeon\u0026rsquo;s clinical preference. Correct localization was defined as the parathyroid lesion described in the imaging report matching the surgical finding with respect to the exact anatomical location identified during the operation. Localizations with at least one imaging report that conflicted with the surgical pathology findings were defined as incorrect localizations. Patients were evaluated on the first day after surgery, at 4 weeks and 6 months after surgery for serum calcium and PTH levels, and then at regular intervals at the discretion of the surgeon. Patients with NCePTH were defined as having normal serum calcium levels, with concurrent elevated PTH levels during the last follow-up. The patients were divided into two groups according to their postoperative PTH and serum calcium levels: the NCePTH group and the cured PHPT group (normal serum calcium and PTH levels at the last follow-up and at more than 6 months of follow-up).\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical methods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eContinuous variables are expressed as medians (interquartile ranges) and means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviations on the basis of their distributions. Categorical variables are expressed as counts (percentages). For continuous variables, an independent samples t test was used for normally distributed data, and the Mann‒Whitney rank sum test was used for nonnormally distributed data. Clinicopathological characteristics were compared between the NCePTH group and the cured PHPT group via the chi-square test or Fisher\u0026rsquo;s exact test for categorical variables. The optimal cutoff points for preoperative PTH levels and PTH levels on the first day after surgery were identified when the Youden index was at its maximum. To identify clinicopathological factors contributing to NCePTH, these factors were assessed using univariate and multivariable logistic regression analyses. A bidirectional stepwise method was used to select the final multivariate model due to the small event size. All multivariate models used a Cox regression model with the Firth penalized maximum likelihood method for bias correction. A p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. All the statistical analyses were performed using SAS 9.4 (SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003ePatient characteristics\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 536 patients underwent surgery for PHPT during the study period, and the final cohort consisted of 395 patients. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the study exclusion and inclusion criteria. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the patients\u0026rsquo; clinical, laboratory, imaging, operative, pathological and demographic characteristics. The mean age of the patients was 53.3 years (range: 18\u0026ndash;85 years), and 66.3% of the patients were female. Seven patients had previously undergone thyroid surgery: one underwent subtotal thyroidectomy for hyperthyroidism, two underwent thyroid lobectomy for microscopic papillary thyroid carcinoma, and four underwent hemithyroidectomies for thyroid nodules. The median BMI was 22.9 kg/m2 in the 386 patients with available data. Two patients had a history of parathyroidectomy for PHPT. The median calcium and phosphorus levels were 2.74 mmol/L (range 2.50\u0026ndash;4.37; normal, 2.11\u0026ndash;2.52) and 0.85 mmol/L (range 0.36\u0026ndash;1.91; normal, 0.85\u0026ndash;1.51), respectively. The median PTH level was 157.7 pg/mL (range 54.9\u0026ndash;3510; normal, 12\u0026ndash;65). There were 304 patients with available data on 25-vitamin D3 levels, with a median of 40.0 nmol/L (range 7.9\u0026ndash;109; normal, 15.6\u0026ndash;125). Fifty-two (13.16%) patients had autoimmune thyroid disease (AITD; hyper/hypothyroidism, Hashimoto\u0026rsquo;s thyroiditis), 10 had hyperthyroidism, 12 had hypothyroidism, and 30 had Hashimoto\u0026rsquo;s thyroiditis. Among the 395 patients, 373 (94.4%) had SGD, and 22 (5.6%) had MGD. Among the patients with MGD (n\u0026thinsp;=\u0026thinsp;22), 19 (86.4%) had double adenomas or hyperplasia, and 3 (13.6%) had three abnormal glands. All patients had follow-up information for at least 6 months. The median follow-up time was 12 months (range 6\u0026ndash;69 months).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinicopathologic demographics of patients with primary hyperparathyroidism\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;395)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eCure\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;356)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNCePTH\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;39)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge, median (rang), y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55 (18\u0026ndash;85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55 (18\u0026ndash;85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e55 (22\u0026ndash;68)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.220\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e262 (66.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e240 (67.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22 (56.41)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.167\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrevious thyroidectomy or parathyroidectomy No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (2.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8 (2.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (2.56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI, median (quartile) *\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.86 (21.03, 25.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.79 (20.96, 25.07)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.31 (21.14, 24.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.751\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThyroid nodule, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e170 (43.04)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e154 (43.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16 (41.03)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.789\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAITD, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52 (13.16)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48 (13.48)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4 (10.26)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.572\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium, median (quartile), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.74 (2.60, 2.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.74 (2.60, 2.91)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.74 (2.59, 3.01)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.834\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhosphorus, median (quartile), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.85 (0.74, 0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.85 (0.74, 0.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.87 (0.77, 0.98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.501\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative PTH, median (quartile), pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e157.7 (110, 264)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150 (108.65, 251.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e228 (126, 387)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlkaline phosphates, median (quartile), (U/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e105 (81, 143)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e103.5 (81, 141)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e115 (84, 168)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.278\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine, median (quartile), (\u0026micro;mol/L)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e68 (56, 87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68 (56, 88)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e68 (56, 82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.732\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e25-hydroxyvitamin D, median (quartile), nmol/L**\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40 (29.1, 51.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.2 (29.6, 51.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37.4 (28.3, 45.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.287\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eConfirmatory localization\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasonography confirmation, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e248 (62.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e222 (62.36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e26 (66.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.597\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSestmibi SPECT/CT confirmation, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e319 (80.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e289 (81.18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e30 (76.92)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.522\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2-imaging contradictory localization, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e169 (42.78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e151 (42.42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e18 (46.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.654\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSGD, No. (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e373 (94.43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e338 (94.94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e35 (89.74)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.256\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParathyroid lesion size, median (quartile), mm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (13, 25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.5 (13, 25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (15, 25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.125\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst-day after surgery calcium, median (quartile), mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.21 (2.11, 2.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.21 (2.11, 2.34)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.18 (2.08, 2.35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.618\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst-day after surgery PTH, median (quartile), pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.2 (4.3, 22.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.7 (4, 21.15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e23.5 (8.1, 35.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFollow up, median (quartile), months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (8, 21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (8, 21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9 (6, 24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.184\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eAbbreviation: BMI, body mass index; AITD, autoimmune thyroid disease; PTH, parathyroid hormone; Calcium, normal range: 2.11\u0026ndash;2.52; Phosphorus, normal range: 0.85\u0026ndash;1.51; PTH, normal range: 12.0\u0026ndash;65.0; Alkaline phosphates, normal range: 40\u0026ndash;150; Creatinine, normal range: 44\u0026ndash;80; 25-hydroxyvitamin D, normal range:15.6\u0026ndash;125; SGD, single gland disease. * Data was available for 386 patients; ** Data was available for 304 patients.\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinicopathological factors associated with NCePTH\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmong the 395 patients, 39 (9.9%) patients were diagnosed with NCePTH, whereas the remaining 356 (90.1%) had normal serum PTH and calcium levels. Compared with patients who were cured after surgery, those with NCePTH had high preoperative serum PTH levels (median [quartile], 228 pg/mL [126, 387] vs. 150 pg/mL [108.65, 251.5], p\u0026thinsp;=\u0026thinsp;0.039) and high PTH levels on the first postoperative day (median [quartile], 23.5 pg/mL [8.1, 35.6] vs. 9.7 pg/mL [4, 21.15], p\u0026thinsp;=\u0026thinsp;0.000). The 25-hydroxyvitamin D level in the NCePTH group was lower than that in the cured group (median, 37.4 nmol/L vs. 40.2 nmol/L), but the difference was not significant (p\u0026thinsp;=\u0026thinsp;0.287). The alkaline phosphate levels in the NCePTH group were greater than those in the cured group (median, 115 U/L vs. 105.3 U/L), but this difference was also not significant (p\u0026thinsp;=\u0026thinsp;0.278). We observed no significant difference in the type of imaging modality (ultrasonography and Sestmibi SPECT/CT) used preoperatively for these patients. Age, female sex, BMI, history of thyroid/parathyroid surgery, AITD status, thyroid nodule status, calcium, phosphorus, and creatinine levels, and parathyroid lesion size were not associated with NCePTH group or cure status (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eYouden index analysis revealed that a preoperative PTH level\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL and a PTH level\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL on the first day after surgery were optimal cutoff points for identifying patients at risk for NCePTH. In univariate analysis, clinicopathological factors associated with NCePTH after parathyroidectomy findings included a preoperative PTH level\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL (odds ratio [OR], 8.68; 95% CI 1.41\u0026ndash;5.49, p\u0026thinsp;=\u0026thinsp;0.003) and a PTH level\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL (odds ratio [OR], 13.75; 95% CI 1.85\u0026ndash;7.37, p\u0026thinsp;=\u0026thinsp;0.0002) on the first day after surgery. BMI, 5-hydroxyvitamin D, creatinine, and alkaline phosphate levels and the type of imaging modality used for localization were not statistically significant predictors. In the multivariable analysis, a preoperative PTH level\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL (odds ratio [OR], 8.78; 95% CI 1.52\u0026ndash;57.74; p\u0026thinsp;=\u0026thinsp;0.003) and a PTH level\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL (odds ratio [OR], 12.47; 95% CI 1.93\u0026ndash;10.03; p\u0026thinsp;=\u0026thinsp;0.0004) on the first day after surgery remained risk factors for NCePTH (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and multivariate analysis for predictors of NCePTH after parathyroidectomy\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eUnivariate analysis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eMultivariate analysis\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOdd ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eOdd ratio\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eP value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.99\u0026ndash;1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.902\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e5-hydroxyvitamin D *\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.96\u0026ndash;1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.258\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCreatinine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.99\u0026ndash;1.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.726\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlkaline phosphates\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.10-1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.303\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUltrasonography confirmation,\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.28\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.60\u0026ndash;2.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.598\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSestmibi SPECT/CT confirmation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.35\u0026ndash;1.70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.523\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2-imaging contradictory localization\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.44\u0026ndash;1.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.654\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative PTH\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.41\u0026ndash;5.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.52\u0026ndash;7.74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFirst-day after surgery PTH\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.85\u0026ndash;7.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.0002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.93\u0026ndash;10.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.0004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"7\" nameend=\"c7\" namest=\"c1\"\u003e\u003cp\u003eCI, confidence interval; BMI, body mass index; * Data was available for 304 patients; PTH, parathyroid hormone\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith the increasing number of patients diagnosed with PHPT and surgeries for biochemical screening and precise preoperative localization, emerging data suggest that a substantial number of patients will develop NCePTH after successful parathyroidectomy. In this study, which included many patients and rigorous criteria, the incidence rate of NCePTH was 9.9%, with a median follow-up time of 12 months. We observed that preoperative PTH levels\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL and PTH levels\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL on the first day after surgery were risk factors for NCePTH. Our data provide information for clinicians and provide a full understanding of medical management plans for patients with NCePTH.\u003c/p\u003e\u003cp\u003eIn our study, 9.9% (39/395) of the patients developed NCePTH after successful parathyroidectomy with a median of 12 months of follow-up. Our results are consistent with those of previous reports. For example, Wan et al. followed 768 patients for more than 6 months after successful parathyroidectomy: 76 patients (8%) demonstrated persistent elevated PTH levels and normocalcemia [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. In one cohort of 99 patients with solitary parathyroid adenomas who underwent successful parathyroidectomy, 16% had NCePTH 5 years after surgery [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Another study reported an isolated increase in PTH levels in 23% of 547 patients with PHPT at 12 months after surgery [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. A review of 33 studies revealed that the prevalence of NCePTH was 3\u0026ndash;46% at greater than 6 months after surgery [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Compared with previous studies, our study defined NCePTH as an elevated PTH level during the last follow-up at least 6 months after surgery, and different studies had different inclusion and exclusion criteria, which led to different prevalences.\u003c/p\u003e\u003cp\u003eThe increasing number of patients with NCePTH raises clinical questions about the etiology of NCePTH and whether it can be used to predict the relationships among clinicopathological factors. Previous studies have shown that high preoperative PTH levels [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], vitamin D deficiency [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], impaired renal function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], severe bone disease [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and larger adenomas [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] are potential risk factors for NCePTH. Our data revealed that high PTH levels preoperatively and on the first day after surgery were correlated with an increased risk of NCePTH. These results are consistent with those of previous reports. For example, Bergenflz et al demonstrated that the preoperative PTH level correlated with the postoperative PTH level at one year (r\u0026thinsp;=\u0026thinsp;0.36; p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In one cohort of 407 patients who underwent parathyroidectomy for PHPT, the presurgical PTH level was significantly greater (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) in those with NCePTH (156.5 pg/mL) than in those with a presurgical level of 102.5 pg/mL in whom the PTH level normalized [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. A retrospective analysis revealed that, in 1037 patients with PHPT, NCePTH was linked to greater preoperative PTH levels at 6 months [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Our data also revealed that the preoperative PTH level in the NCePTH group was greater than that in the cured group (228 pg/mL vs. 150 pg/mL, p\u0026thinsp;=\u0026thinsp;0.039). Mandal et al reported that the PTH levels on the first day of the operation were significantly greater (20\u0026thinsp;\u0026plusmn;\u0026thinsp;6 vs. 10\u0026thinsp;\u0026plusmn;\u0026thinsp;2 pg/mL) in 12% of the 78 patients with NCePTH (27). Our study also revealed that the PTH levels on the first day after surgery in the NCePTH group (23.5 vs. 9.7 pg/mL, p\u0026thinsp;=\u0026thinsp;0.000) were greater than those in the cured group. The etiology of NCePTH remains uncertain, but it is likely multifactorial. Some studies speculate that the impaired responsiveness of PTH may be due to PTH receptor downregulation in patients with higher preoperative PTH concentrations. When PTH levels decrease immediately after successful parathyroidectomy, patients may have an altered set point for PTH release for calcium homeostasis, resulting in parathyroid hormone resistance (higher PTH release) and/or decreased sensitivity of the calcium-sensing receptor.\u003c/p\u003e\u003cp\u003eAnother potential mechanism for NCePTH is vitamin D deficiency. Some studies have shown that patients with vitamin D deficiency are more likely to exhibit NCePTH [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Beyer et al reported that a significantly lower incidence of NCePTH was observed when patients were treated postoperatively with calcitriol [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Another retrospective analysis revealed that uncontrolled calcium supplementation in patients with NCePTH may lead to normalization of PTH in some patients [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our study revealed that 25-hydroxyvitamin D levels were lower (37.4 nmol/L vs. 40.2 nmol/L) in the NCePTH group than in the control group, but this difference was not significant. These inconsistencies with the literature may be due to the incomplete 25-hydroxyvitamin D data in our study and the nonroutine measurement of vitamin D levels after surgery. Our study revealed no evidence for associations of older age, BMI, impaired renal function, severe bone disease, or larger adenomas with NCePTH.\u003c/p\u003e\u003cp\u003eThis study has certain limitations. First, this was a single-center retrospective study, and some clinicopathological variables, such as 25-hydroxyvitamin D, BMI and bone density measurements, as well as the weight of parathyroid lesions, were incomplete, which may have influenced the statistical analysis and made it difficult to fully rule out secondary hyperparathyroidism. Second, some patients returned to their primary care providers after successful parathyroidectomy and returned to our tertiary referral center because of abnormal laboratory values. This could lead to some patients being lost to follow-up and bias in the incidence rate of NCePTH. Finally, the follow-up period was relatively short, and other possible causes of elevated PTH levels, such as vitamin D status or renal function, were not assessed throughout the follow-up period. Further multicenter, controlled prospective studies with larger samples are needed to address the limitations of our study.\u003c/p\u003e\u003cp\u003eIn conclusion, in this large retrospective series, the incidence rate of NCePTH after successful parathyroidectomy in patients with PHPT was 9.9%. A preoperative PTH concentration\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL and a PTH concentration\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL on the first day after surgery were identified as risk factors for NCePTH after parathyroidectomy. Our data highlight the importance of clinicopathological factors in the prediction of postoperative NCePTH and help the endocrine community refine surveillance strategies for these patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNCePTH \u0026nbsp;Normocalcemia with elevated parathyroid hormone levels\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePHPT \u0026nbsp; primary hyperparathyroidism \u0026nbsp; \u0026nbsp;PTHparathyroid hormone\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI \u0026nbsp;body mass index \u0026nbsp; \u0026nbsp; \u0026nbsp;AITD \u0026nbsp;autoimmune thyroid disease\u003c/p\u003e\n\u003cp\u003eSPECT/CT \u0026nbsp;single photon emission computed tomography/computed tomography\u003c/p\u003e\n\u003cp\u003eSGD \u0026nbsp;single gland disease \u0026nbsp; MGD \u0026nbsp; multigland disease\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization and manuscript writing: Jun Yang, Zhuo He, Xinhui Su. Data collection and organization: Pingping Zhou, Xili Lu, Wanwen Weng, MD, Haohao Wang. Data analysis and statistics: Cheng Ding. Critical revision of the manuscript: Jun Yang, Zhuo He, Xinhui Su. Approval of the final version of the manuscript on behalf of all the authors: Xinhui Su.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe authors thank Weiyi Wang, BA and Shuangzhi Lv, BA, for their follow-up assistance.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no completing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was carried out in accordance with the Helsinki Declaration and approved by the Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (IIT-20241294A).\u0026nbsp;Because this study was retrospective, the requirement of informed consent was waived. It was performed in accordance with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp; \u0026nbsp;Not applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWalker MD, Silverberg SJ. Primary hyperparathyroidism. Nat Rev Endocrinol. 2018;14(2):115\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYeh MW, Ituarte PH, Zhou HC, Nishimoto S, Liu IL, Harari A, et al. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. J Clin Endocrinol Metab. 2013;98(3):1122\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBilezikian JP, Cusano NE, Khan AA, Liu JM, Marcocci C, Bandeira F. Primary hyperparathyroidism. Nat Rev Dis Primers. 2016;2(1):16033.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBilezikian JP, Brandi ML, Eastell R, Silverberg SJ, Udelsman R, Marcocci C et al. Guidelines for the management of asymptomatic primary hyperparathyroidism: summary statement from the Fourth International Workshop. J Clin Endocrinol Metab. 2014;99(10):3561\u0026ndash;3569.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eUdelsman R, Lin Z, Donovan P. The superiority of minimally invasive parathyroidectomy based on 1650 consecutive patients with primary hyperparathyroidism. Ann Surg. 2011;253:585\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede la Plaza Llamas R, Ramia A\u0026acute; ngel JM, Arteaga Peralta V, Garc\u0026acute;ıa Amador C, Lo\u0026acute; pez Marcano AJ, et al. Elevated parathyroid hormone levels after successful parathyroidectomy for primary hyperparathyroidism: a clinical review. Eur Arch Otorhinolaryngol. 2018;275(3):659\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoldfarb M, Gondek S, Irvin GL III, Lew JI. Normocalcemic parathormone elevation after successful parathyroidectomy: long-term analysis of parathormone variations over 10 years. Surgery. 2011;150:1076\u0026ndash;82.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNing L, Sippel R, Schaefer S, Chen H. What is the clinical significance of an elevated parathyroid hormone level after curative surgery for primary hyperparathyroidism? Ann Surg. 2009;249:469\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSolorzano CC, Mendez W, Lew JI, Rodgers SE, Montano R, Carneiro-Pla DM, et al. Long-term outcome of patients with elevated parathyroid hormone levels after successful parathyroidectomy for sporadic primary hyperparathyroidism. Arch Surg. 2008;143:659\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLang BH, Wong IY, Wong KP, Lo C. Eucalcemic parathyroid hormone elevation after parathyroidectomy for primary sporadic hyperparathyroidism: risk factors, trend, and outcome. Ann Surg Oncol. 2012;1:584\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang TS, Ostrower ST, Heller KS. Persistently elevated parathyroid hormone levels after parathyroid surgery. Surgery. 2005;138:1130\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarty SE, Roberts MM, Virji MA, Haywood L, Yim JH. Elevated serum parathormone level after concise parathyroidectomy for primary sporadic hyperparathyroidism. Surgery. 2002;132(6):1086\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDenizot A, Pucini M, Chagnaud C, Botti G, Henry JF. Normocalcemia with elevated parathyroid hormone levels after surgical treatment of primary hyperparathyroidism. Am J Surg. 2001;182(1):15\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWesterdahl J, Valdemarsson S, Lindblom P, Bergenfelz A. Postoperative elevated serum levels of intact parathyroid hormone after surgery for parathyroid adenoma: sign of bone remineralization and decreased calcium absorption. World J Surg. 2000;24(11):1323\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeyer TD, Solorzano CC, Prinz RA, Babu A, Nilubol N, Patel S. Oral vitamin D supplementation reduces the incidence of eucalcemic PTH elevation after surgery for primary hyperparathyroidism. Surgery. 2007;141(6):777\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNordenstr\u0026ouml;m E, Westerdahl J, Bergenfelz A. Long-term follow-up of patients with elevated PTH levels following successful exploration for primary hyperparathyroidism. World J Surg. 2004;28(6):570\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLavryk OA, Siperstein AE. Pattern of calcium and parathyroid hormone normalization at 12-months follow-up after parathyroid operation. Surgery. 2017;161(4):1139\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eYamashita H, Noguchi S, Moriyama T, Takamatsu Y, Sadanaga K, Uchino S, et al. Reelevation of parathyroid hormone level after parathyroidectomy in patients with primary hyperparathyroidism: Importance of decreased renal parathyroid hormone sensitivity. Surgery. 2005;137:419\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMittendorf EA, McHenry CR. Persistent parathyroid hormone elevation following curative parathyroidectomy for primary hyperparathyroidism. Arch Otolaryngol Head Neck Surg. 2002;128:275\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStewart ZA, Blackford A, Somervell H, Friedman K, Garrett-Mayer E, Dackiw AP, et al. 25-hydroxyvitamin D deffciency is a risk factor for symptoms of postoperative hypocalcemia and secondary hyperparathyroidism after minimally invasive parathyroidectomy. Surgery. 2005;138:1018\u0026ndash;25.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDhillon KS, Cohan P, Darwin C, Van Herle A, Chopra IJ. Elevated serum parathyroid hormone concentration in eucalcemic patients after parathyroidectomy for primary hyperparathyroidism and its relationship to vitamin D profile. Metabolism. 2004;53:1101\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBergenfelz A, Valdemarsson S, Tibblin S. Persistent elevated serum levels of intact parathyroid hormone after operation for sporadic parathyroid adenoma: Evidence of detrimental effects of severe parathyroid disease. Surgery. 1996;119:624\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeyer TD, Chen EL, Nilubol N, Prinz RA, Solorzano CC. Short-term outcomes of parathyroidectomy in patients with or without 25-hydroxy vitamin D insufffciency. J Surg Res. 2007;143:145\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNordenstr\u0026ouml;m E, Westerdahl J, Isaksson A, Lindblom P, Bergenfelz A. Patients with elevated serum parathyroid hormone levels after parathyroidectomy: Showing signs of decreased peripheral parathyroid hormone sensitivity. World J Surg. 2003;27:212\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCaldwell M, Laux J, Clark M, Kim L, Rubin J. Persistently Elevated PTH After Parathyroidectomy at One Year: Experience in a Tertiary Referral Center. J Clin Endocrinol Metab. 2019;104(10):4473\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCarsello CB, Yen TW, Wang TS. Persistent elevation in serum parathyroid hormone levels in normocalcemic patients after parathyroidectomy: does it matter? Surgery. 2012;152(4):575\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMandal AK, Udelsman R. Secondary hyperparathyroidism is an expected consequence of parathyroidectomy for primary hyperparathyroidism: a prospective study. Surgery. 1998;124(6):1021\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"normocalcemic, elevated parathyroid hormone, parathyroidectomy, primary hyperparathyroidism, risk factors","lastPublishedDoi":"10.21203/rs.3.rs-7022277/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7022277/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eNormocalcemia with elevated parathyroid hormone levels (NCePTH) after successful parathyroidectomy in patients with primary hyperparathyroidism (PHPT) has drawn attention during the postoperative period and remain a clinical conundrum.\u003c/p\u003e\u003ch2\u003ePatients and methods:\u003c/h2\u003e\u003cp\u003eWe retrospectively studied 539 consecutive patients with PHPT who underwent parathyroid surgery from August 2017 to December 2023.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe mean age of the patients was 53.3 years, and 66.3% of the patients were female. After a median follow-up of 12 months, 9.9% of the patients were diagnosed with NCePTH. Compared with patients who were cured after surgery, those with NCePTH had high preoperative serum PTH levels (median [quartile], 228 pg/mL [126, 387] vs. 150 pg/mL [108.65, 251.5], p\u0026thinsp;=\u0026thinsp;0.039) and PTH levels on the first postoperative day (median [quartile], 23.5 pg/mL [8.1, 35.6] vs. 9.7 pg/mL [4, 21.15], p\u0026thinsp;=\u0026thinsp;0.000). Patients with NCePTH after surgery did not differ from those with normal PTH levels in terms of sex, age, body mass index, history of thyroid/parathyroid surgery, calcium, phosphorus, and creatinine levels and parathyroid lesion size. According to the multivariable analysis, a preoperative PTH concentration\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL (odds ratio [OR], 8.78; p\u0026thinsp;=\u0026thinsp;0.003) and PTH concentration\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL (odds ratio [OR], 12.47; p\u0026thinsp;=\u0026thinsp;0.0004) on the first day after surgery remained risk factors for NCePTH.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThe incidence rate of NCePTH after successful parathyroidectomy in patients with PHPT was 9.9%. A preoperative PTH concentration\u0026thinsp;\u0026ge;\u0026thinsp;191 pg/mL and a PTH concentration\u0026thinsp;\u0026ge;\u0026thinsp;16.4 pg/mL on the first day after surgery were identified as risk factors for NCePTH after parathyroidectomy.\u003c/p\u003e","manuscriptTitle":"Elevated parathyroid hormone levels in normocalcemic patients after parathyroidectomy for primary hyperparathyroidism: What risk factors should be considered?","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 05:47:13","doi":"10.21203/rs.3.rs-7022277/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-23T12:52:26+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"268477588444100926368507435962782138083","date":"2025-09-21T12:06:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-21T01:49:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117089940234619211337014862007904728560","date":"2025-09-12T13:46:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-08T16:39:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"230062536757738578028520690458579512829","date":"2025-09-06T08:36:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310393862656697450628532921964818904","date":"2025-08-29T00:04:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-06T14:47:52+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-07-03T09:31:30+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-03T05:54:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-03T05:49:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-07-01T16:18:29+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"637b5d59-eb40-4448-b7ca-585aec52577a","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-09T16:07:59+00:00","versionOfRecord":{"articleIdentity":"rs-7022277","link":"https://doi.org/10.1186/s12902-026-02228-8","journal":{"identity":"bmc-endocrine-disorders","isVorOnly":false,"title":"BMC Endocrine Disorders"},"publishedOn":"2026-03-07 15:57:42","publishedOnDateReadable":"March 7th, 2026"},"versionCreatedAt":"2025-07-14 05:47:13","video":"","vorDoi":"10.1186/s12902-026-02228-8","vorDoiUrl":"https://doi.org/10.1186/s12902-026-02228-8","workflowStages":[]},"version":"v1","identity":"rs-7022277","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7022277","identity":"rs-7022277","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}