Clinical Diagnosis and Management of Hypercalcemic crisis resulting from Hyperparathyroidism：A 16-Year Experience with 79 Cases

Clinical Diagnosis and Management of Hypercalcemic crisis resulting from Hyperparathyroidism：A 16-Year Experience with 79 Cases | 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 Clinical Diagnosis and Management of Hypercalcemic crisis resulting from Hyperparathyroidism：A 16-Year Experience with 79 Cases Yuqing Qu, Yang Liu, Xianling Wang, Qinghua Guo, Jin Du, Yu Pei, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7859238/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background To analyze a large-sample cohort of hypercalcemic crisis cases caused by hyperparathyroidism, focusing on etiology, clinical manifestations, diagnosis, emergency treatments, and etiological treatments. Methods Patients with hypercalcemic crisis due to hyperparathyroidism admitted in our institution from January 2009 to January 2025 were enrolled. Comprehensive data included demographic characteristics, clinical manifestations, etiological subtypes, imaging examination, emergency treatments, and etiological treatments. Serial assessments of serum parathyroid hormone, calcium, and phosphorus levels were compared pre- and post-emergency treatment. Results A total of 79 patients (39 males, 40 females) were included, with a mean age of (51.51 ± 15.74) years. Primary hyperparathyroidism accounted for 93.67% (74/79), while tertiary hyperparathyroidism accounted for 6.33% (5/79). Clinical manifestations included endocrine symptoms (83.54%, 66/79), gastrointestinal symptoms (74.68%, 59/79), skeletal symptoms (68.35%, 54/79), renal symptoms (59.49%, 47/79), neurological symptoms (56.96%, 45/79), and cardiovascular symptoms (20.25%, 16/79). After the administration of emergency calcium-lowering therapy (hydration, subcutaneous calcitonin, intravenous bisphosphonates, or hemodialysis), 88.61% (70/79) patients got clinical improvement. Surgical parathyroidectomy achieved a 100% improvement rate (36/36 primary hyperparathyroidism; 2/2 tertiary hyperparathyroidism). All three patients (2 primary hyperparathyroidism, 1 tertiary hyperparathyroidism) treated with microwave ablation achieved complete remission. Conclusions Hypercalcemic crisis caused by hyperparathyroidism presents with diverse and nonspecific clinical manifestations. It has challenges for early diagnosis and increasing risks of misdiagnosis. Efficient and thorough calcium-reducing interventions in the emergency context can facilitate a fast alleviation of clinical manifestations. Total parathyroidectomy and microwave ablation can get high cure rates and lead to sustained clinical remission. Hypercalcemic crisis Hyperparathyroidism Parathyroid hormone Primary hyperparathyroidism Tertiary hyperparathyroidism Background Hyperparathyroidism (HPT) is classified into three subtypes: primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), and tertiary hyperparathyroidism (THPT). Both PHPT and THPT can cause hypercalcemia. Hypercalcemic crisis occurs when the total calcium (SCa) level exceeds 14 mg/dL, accompanied by a series of severe clinical symptoms such as kidney failure, acute pancreatitis, and mental changes. Hypercalcemic crisis represents a life-threatening complication of HPT [ 1 ]. Patients with HPT-induced hypercalcemic crisis often exhibit nonspecific and heterogeneous clinical manifestations. As a result, the association between hypercalcemia and its symptoms have always been overlooked or masked by comorbid conditions, leading to misdiagnosis and delayed identification. Definitive etiological treatments, such as parathyroidectomy or microwave ablation, can achieve high cure rates [2]. This study conducted a retrospective analysis of the clinical data from 79 patients with HPT-related hypercalcemic crisis treated in our hospital during a 16-year period. We have delineated the characteristics, diagnostic methodologies, emergency treatments, and outcomes of etiological treatments, to enhance clinicians’ awareness of this endocrine emergency,, improve standardized management, and underscore the necessity of strengthened multidisciplinary collaboration. Methods Patients Cases were identified by searching the First Medical Center of Chinese PLA General Hospital Electronic Health Record (EHR) system. We conducted a retrospective search for all patients within the Department of Endocrinology between January 2009 and January 2025 whose records contained the International Classification of Diseases-10 (ICD-10). A total of 79 patients diagnosed with HPT were enrolled. The diagnostic criteria for hypercalcemic crisis include a SCa level over 14 mg/dL, accompanied by a range of severe clinical manifestations. All patients included were definitively diagnosed with HPT, with albumin-corrected SCa levels above 14 mg/dL with the biochemical profile being the primary criterion for inclusion. Methods The clinical data was analyzed as follows: (1) general information, such as age, gender, and clinical manifestations; (2) laboratory evaluation, including total SCa, serum phosphorus(P), alkaline phosphatase (ALP), serum 25-hydroxyvitamin D, and parathyroid hormone (PTH); (3) imageological examination of the tumor, such as ultrasound, parathyroid computed tomography (CT), parathyroid magnetic resonance imaging (MRI), parathyroid 99mTc methoxy isobutyl isonitrile (99mTc MIBI); (4) misdiagnosed and undiagnosed conditions; (5) emergency and etiological treatments (surgery, radiofrequency ablation, chemotherapy, etc); (6) morphological and immunohistochemical evaluation of tumors; (7) therapeutic outcomes: improvement: post-treatment adjusted total SCa < 14 mg/dL; remission: significant decrease in clinical symptoms and signs; resolved: total SCa < 10 mg/dL, rectified by therapy, with no associated clinical symptoms or signs. This retrospective study was approved by the Medical Ethics Committee of the First Medical Center of Chinese PLA General Hospital. As a retrospective analysis of de-identified patient data from institutional electronic health records, the Ethics Committee waived the need for individual informed consent. Robust data protection measures were enforced, including patient anonymization via unique codes and secure storage on encrypted hospital servers with restricted access.We had complied with the Declaration of Helsinki Ethical Principles for medical research involving human subjects. Statistical Analysis Statistical analyses were performed with IBM SPSS Statistics version 22.0. The quantitative variables were presented as the mean ± standard error and and comparisons were performed using Student’s t-test. Non-quantitative data that deviated from a normal distribution were presented as the median (r) or interquartile range (P25, P75). Levels of statistical significance were set at p < 0.05. Results General Information A total of 79 patients were diagnosed with HPT leading to a hypercalcemic crisis, including 39 men (49.37%) and 40 females (50.63%), with a mean age of 51.51 ± 15.74 years. In this cohort of 79 patients, PHPT was predominant, with a prevalence of 93.67% (74/79), while THPT was observed in only 6.33% (5/79). Among the 79 patients, 83.54% (66/79) presented with endocrine system symptoms, 74.68% (59/79) with digestive symptoms, 68.35% (54/79) with skeletal system symptoms, 59.49% (47/79) with urinary system symptoms, 56.96% (45/79) with nervous system symptoms, and 20.25% (16/79) with cardiovascular system symptoms, respectively. Clinical manifestations Primary hyperparathyroidism In the cohort of 74 individuals experiencing hypercalcemic crisis caused by PHPT, systemic manifestations were observed in the following order of prevalence: endocrine system (83.78%), digestive system (75.68%), urinary system (70.27%), skeletal system (67.57%), neurological system (56.76%), and cardiovascular system (20.27%). The primary clinical manifestations of Endocrine system were xerostomia, polydipsia, polyuria, hyperglycemia, and hypokalemia; Gastrointestinal abnormalities presented as nausea (82.1%), vomiting (64.3%), stomach discomfort (41.1%), and anorexia (33.9%), with 4 instances (7.14%) exhibiting simultaneous cholelithiasis; The presenting symptoms were urinary urgency (76.9%), dysuria (69.2%), renal insufficiency (53.8%), and flank pain (48.1%), worsened by nephrolithiasis in 25 individuals (48.07%); Musculoskeletal consequences comprised osteodynia (88.0%) and osteoporosis (72.0%), with 11 patients (22.00%) indicating a history of pathological fractures; The spectrum of neurological symptoms included headache (71.4%), dizziness (66.7%), lethargy (52.4%), and nonspecific tiredness (92.9%); The presenting symptoms of Cardiovascular system were palpitations (86.7%), chest tightness (73.3%), and dyspnea on exercise (53.3%) (Table 1 A). Tertiary hyperparathyroidism All 5 patients experiencing the hypercalcemic crisis caused by THPT had a history of chronic renal disease. Four patients displayed endocrine symptoms including xerostomia, hyperglycemia, gout, and electrolyte imbalances, alongside skeletal symptoms such as osseous pain and fractures.Three patients displayed gastrointestinal symptoms including anorexia, abdominal distension, diarrhea, nausea, vomiting, and hepatic dysfunction, as well neurological symptoms such as mental agitation, exhaustion, insomnia, and confusion. One patient exhibited cardiovascular symptoms including chest tightness, dyspnea, and heart failure (Table 1 A). Laboratory and Imaging Ivestigations Primary hyperparathyroidism The average albumin-corrected SCa level in 74 patients with PHPT was 14.08 ± 2.68 mg/dL (normal range 8.36–10.16 mg/dL). Additionally, the mean serum phosphorus level was 0.86 ± 0.37 mmol/L (normal range 0.89–1.6 mmol/L) and the mean 25-OH vitamin D3 level was 11.62 ± 6.95 ng/ml (normal range 20–30 ng/ml). Meanwhile, the median (interquartile spacing) of PTH was 534.50 (256.50, 1160.75) pg/ml (normal range 15–65 pg/ml) and the median (interquartile spacing) of ALP was 113.00 (89.90, 339.80) U/L (normal range 0-130 U/L) (Table 1 A). Ultrasonography was conducted in 87.84% (65/74) of cases, with a positive rate of 60.00% (39/65); CT was utilized in 60.81% (45/74) of cases, with a positive rate of 82.22% (37/45); MRI was employed in 13.51% (10/74) of cases, with a positive rate of 90.00% (9/10); 99mTc MIBI was administered in 79.72% (59/74) of cases, with a positive rate of 84.74% (50/59). Tertiary hyperparathyroidism The average total SCa level at the diagnosis of hypercalcemic crisis in 5 patients with THPT was 15.76 ± 1.8 mg/dL (normal range 8.36–10.16 mg/dL), while the average albumin-corrected SCa level was 16.60 ± 1.8 mg/dL (normal range 8.36–10.16 mg/dL). The mean serum phosphorus level was 0.87 ± 0.04 mmol/L (normal range 0.89–1.6 mmol/L) and the mean 25-OH vitamin D3 level was 15.00 ± 3.96 ng/ml (normal range 20–30 ng/ml). Meanwhile, the median (interquartile spacing) of PTH was 741.30 (440.35, 1373.50) pg/ml (normal range 15–65 pg/ml) and the median (interquartile spacing) of ALP was 204.40 (130.10, 224.10) U/L (normal range 0-130 U/L) (Table 1 A). Four patients underwent ultrasonography, with a 100% positivity rate (4/4). Three patients underwent 99mTc MIBI, also with a 100% positivity rate (3/3). Only one patient underwent MRI, which was reported as positive. None of the five patients underwent CT scanning owing to renal insufficiency. Diagnosis Misdiagnosis occurred in 6.32% (5/79) of the patients, which included one instance of unstable angina pectoris misdiagnosed in the cardiology department due to cardiovascular symptoms; One case was mistakenly categorized as brucellosis in the pain department due to a multitude of nonspecific systoms, and three cases were overlooked due to insufficient attention to the SCa profile at the initial consultation. This study demonstrated that the rapid identification of hypercalcemic crisis (0.9 ± 0.2 days to diagnosis ) and thorough analysis of clinical data led to a definitive etiology in 100% (79/79) of cases (4.0 ± 0.2 days to etiological clarity) through history taking, physical examination, clinical presentation, and qualitative diagnostic methods (biochemical tests including SCa, serum phosphorus, ALP, PTH, and 25-OH vitamin D3 and various locoregional diagnostic techniques). Emergency treatment and regression Emergency treatments were promptly executed following the confirmation of the diagnosis. The implementation of emergency calcium-lowering treatment via hydration (4,000 ml of water daily) or intravenous saline (4,000ml) accounted for 88.61% (70/79) of cases, with PHPT patients comprising 89.19% (66/74) and THPT patients 80.00% (4/5). Bisphosphonate therapy accounted for 64.56% (51/79), with PHPT 66.22% (49/74) and THPT 40% (2/5). Intravenous zoledronic acid was administered in 88.24% (45/51) of patients, while other bisphosphonate agents were administered in 11.76% (6/51) patients. Diuretic treatment, exclusively utilizing intravenous furosemide, accounted for 31.65% (25/79), with PHPT at 31.08% (23/74) and THPT at 40% (2/5). Subcutaneous calcitonin treatment, accounted for 30.38% (24/79), with PHPT at 28.38% (21/74) and THPT at 60.00% (3/5). Glucocorticoid treatment comprised 15.19% (12/79) of the cohort, with 14.86% (11/74) among PHPT patients and 20.00% (1/5) among THPT patients. Only four patients underwent haemodialysis for severe hypercalcemia, comprising three with PHPT and one with THPT (Table 1 B). The average albumin-corrected SCa level decreased from 14.12 ± 2.92 mg/dL to 11.08 ± 1.40 mg/dL (normal range 8.36–10.16 mg/dL) in 79 individuals after emergency treatments. After the immediate interventions, the average albumin-corrected SCa levels significantly decreased, with an improvement rate of 88.61% (70/79) and a complete remission rate of clinical symptoms at 100% (79/79). Etiological treatment and regression Hypercalcemic crisis caused by PHPT Thirty-six patients of PHPT underwent surgery at our center, with postoperative pathology confirming the presence of parathyroid adenoma. The median serum PTH levels (interquartile range) decreased from 508.20 (235.85, 1244.25) pg/ml preoperatively to 14.30 (10.42, 33.56) pg/ml postoperatively (normal range 15–65 pg/ml). The mean albumin-corrected SCa level declined from 14 ± 2.6 mg/dL to 11.52 ± 1.0 mg/dL(Table 1 B). The surgical improvement rate was 100% (36 out of 36), and the cure rate was 88.89% (32 out of 36). Two patients with pathology consistent with parathyroid adenoma, confirmed by puncture biopsy, underwent microwave ablation at our center. Subsequent measurements of serum PTH and albumin-corrected SCa levels shown considerable reductions, achieving a 100% improvement rate. The remaining patients with PHPT were not enrolled in the analysis since they returned to their hometowns for additional surgical treatment, for which no data were accessible. Hypercalcemic crisis caused by THPT Two of the five patients with THPT underwent surgery at our center, and postoperative pathology confirmed the diagnosis of parathyroid adenomatous hyperplasia. The mean postoperative serum PTH decreased from 741.30 (440.35, 1373.50) pg/ml to 10.18 (5.69, 23.73) pg/ml (normal range 15–65 pg/ml), meanwhile the mean post albumin-corrected SCa declined from 15.28 to 9.52 mg/dL. One patient underwent microwave ablation, resulting in a postoperative reduction of serum PTH from 1015.00 pg/ml preoperatively to 37.28 pg/ml postoperatively, and a reduction in albumin-corrected SCa from 15.24 to 10.04 mg/dL. All five patients got long-term remission of their clinical manifestations by allopathic interventions, including surgery, microwave ablation, and pharmacotherapy. Discussion Hyperparathyroidism is a metabolic condition caused by the excessive synthesis of PTH, characterized by hypercalcemia, hypophosphatemia, and dysfunction of target organs. PHPT encompasses a range of clinical symptoms caused by the autonomous production of excessive PTH, leading to hypercalcemia, enhancedrenal calcium reabsorption, and increased urine phosphorus excretion [ 3 ]. SHPT is the compensatory activation of parathyroid tissue due to hypocalcemia, resulting in hyperplasia and hypertrophy of the parathyroid glands, which causes excessive production of PTH. THPT results from prolonged and uncontrolled SHPT, wherein the parathyroid glands transition from compensatory hyperplasia to autonomous production of PTH [ 4 ]. Both PHPT and THPT can lead to hypercalcemia, and a hypercalcemic crisis may occur if the SCa level exceeds 14 mg/dL alongside a constellation of severe clinical manifestations. The hypercalcemic crisis is a severe consequence of hyperparathyroidism and constitutes a life-threatening endocrine emergency. Our study demonstrates that primary hyperparathyroidism (PHPT) is the most frequent etiology of hypercalcemic crisis among hyperparathyroidism cases in China, where such reports are scarce. Specifically, PHPT constituted 93.67% (74/79) of cases, whereas tertiary hyperparathyroidism (THPT) represented only 6.33% (5/79). In PHPT, the parathyroid glands produce excessive PTH, which binds to PTH receptors in bone and kidney, promoting bone resorption, resulting in calcium release into the bloodstream, increasing renal tubular calcium reabsorption, and stimulating the synthesis of 1,25-dihydroxyvitamin D3, thereby enhancing intestinal calcium absorption. Enhanced intestinal calcium absorption can induce a hypercalcemic crisis. The pathogenesis of THPT arises from the sustained stimulation of long-term SHPT (e.g., chronic kidney disease or vitamin D deficiency), resulting in the transition of the parathyroid glands from compensatory hyperplasia to autonomous secretion, ultimately resulting in persistent hypercalcemia and multisystem damage [ 5 ]. The clinical manifestations of hypercalcemic crisis are intricate and diverse, resulting in misdiagnosis with other conditions. Hypercalcemic crisis, a severe complication of HPT, has always been overlooked and misdiagnosed. Thus, early identification of its signs and symptoms is essential. The occurrence and intensity of clinical symptoms of hypercalcaemia are proportional to the degree of SCa elevation and the patient's capacity to endure elevated SCa levels. Appropriate extracellular fluid calcium concentrations are essential for the regular functioning of various systems. Hence, hypercalcemic crisis may result in inattention, ataxia, and even coma. The cardiovascular system symptoms exhibit hypertension, bradycardia, arrhythmia, and Q-T interval shortening. Gastrointestinal signs include anorexia, nausea, vomiting, and constipation. Manifestations of the urinary system include polyuria, renal calculi, renal calcification, decreased glomerular filtration rate, and hyperchloremic acidosis [ 6 ]. This study revealed that the clinical manifestations of patients experiencing a hypercalcemic crisis predominantly affected the endocrine, digestive, urinary, skeletal, and neurological systems, with incidences above 50%. This complexity and variability in symptoms hindered early identification of the condition. Hypercalcemic crisis has always been frequently misdiagnosed as chronic gastritis and urinary calculi[ 7 , 8 ]. Clinicians encountering patients with suggestive symptoms should prioritize SCa testing. This practice facilitates early detection of hypercalcemic crisis and reduces the likelihood of diagnostic delays or errors. The diagnosis of hypercalcemic crisis caused by HPT primarily relies on clinical manifestations and laboratory evaluations. A definitive diagnosis is established when SCa levels exceed 14 mg/dL, in conjunction with elevated PTH levels and a range of severe clinical symptoms. Hypercalcemic crisis is a perilous situation; urgent calcium reduction is essential. Clinical interventions to reduce SCa mostly encompass hydration treatment, diuretics to enhance calcium excretion, and bisphosphonates to suppress osteoclast activity [ 7 ]. Hydration is the essential component of treatment, resolving dehydration by rapid volume expansion, diluting SCa levels, and enhancing urinary calcium excretion. The preferred intravenous fluid is 0.9% saline, administered at an infusion rate of 200–300 ml/h, totaling 3–6 liters daily. Continuous monitoring of serum electrolytes and electrocardiograms is essential during hydration therapy to prevent electrolyte imbalances or volume overload. Diuretics (e.g. furosemide 20–40 mg intravenously every 4–6 hours) may be used in conjunction with sufficient hydration; however, thiazide diuretics are contraindicated due to their propensity to elevate calcium levels. Bisphosphonates exhibit a delayed onset and prolonged duration of action, and frequently used in conjunction with calcitonin to manage hypercalcemic crisis. Bisphosphonates reduce serum calcium levels by inhibiting osteoclast-mediated bone resorption. Zoledronic acid (4 mg intravenously over a minimum of 15 minutes) or pamidronate (60–90 mg intravenously over a minimum of 2 hours) can get a calcitonin-lowering effect within the first 24–48 hours of administration, with effects persisting for several weeks [ 9 ]. Calcitonin is employed for short-term transitional treatment by reducing SCa levels through the twin mechanisms of decreasing osteoclast-mediated bone resorption and enhancing renal excretion. Glucocorticoids diminish SCa levels via suppressing the production of 1,25-dihydroxyvitamin D and decreasing the release of inflammatory mediators[ 10 ]. Haemodialysis is not the primary treatment for hypercalcemic crisis; it can be performed when SCa levels are significantly high and pose a life-threatening risk [ 11 ]. This study reports an improvement rate of 88.61% (70/79) in patients following the aforementioned emergency calcium-lowering medication. Prompt and effective calcium-lowering interventions can not only save patient's life but also provide an opportunity for further etiological therapy. Medical treatment with cinacalcet or surgical treatment with parathyroidectomy (PTX) are both viable options for addressing tertiary hyperparathyroidism [ 12 ]. Cinacalcet is a calcimimetic drug that suppresses the production of PTH by enhancing the sensitivity of the calcium-sensing receptors of the parathyroid gland to calcium [ 13 , 14 ]. It is important to note that the timeframe of this study predates the widespread clinical use of calcimimetics, such as cinacalcet, for the management of THPT in our region. In addition, the number of cases of THPT in this study was relatively small. Consequently, none of the patients in our cohort received this class of medication. Surgical excision is the most efficacious treatment for PHPT and THPT[ 15 ]. Microwave ablation, with precise preoperative localization, is also an effective therapy. In China, 99mTc MIBI, ultrasonography, and CT are the primary imageological examination for preoperative localization; the sensitivity of parathyroid 99mTc MIBI for localizing parathyroid lesions was 82% to 100% internationally, with a sensitivity of 91.4% [ 3 , 4 , 16 ]. The positive rate of 99mTc MIBI in our study was 85.43% (53/62), consistent with national and worldwide data, indicating that it exhibits greater sensitivity. The ultrasound positive rate was 62.32% (43/69), while the CT positive rate was 82.22% (37/45), indicating that the combination of 99mTc MIBI with ultrasound and CT considerably enhances the detection rate of tumors, particularly for ectopic adenomas or tiny adenomas. The results of our study are generally in accordance with other centers in China. Following precise localization by imaging assessment, 38 patients underwent surgical intervention, resulting in improvements for all. And 34 patients got complete recovery. Microwave ablation has several advantages: straightforward operational procedure, little trauma, thorough tumor deactivation, and few complications [ 16 ]. Three patients underwent microwave ablation therapy. Subsequently, their serum PTH and SCa levels returned to normal, resulting in complete recovery in all patients. Our study has several limitations. It was a retrospective analysis of a single surgeon’s experience at a single tertiary care institution and as a result, the findings may not be generalizable to other institutions. Some of our patients were lost to follow-up and excluded from definitive treatment analysis. This introduces a major bias and likely overestimates surgical outcomes. A notable aspect of our study is the absence of experience with cinacalcet or other calcimimetics in our cohort. Conclutions Based on a retrospective analysis of a larger cohort of hyperparathyroidism patients in our clinical center, the incidence of hypercalcemic crisis was much higher in PHPT patients than THPT patients. The clinical symptoms of patients with a hypercalcemic crisis are intricate and diverse, which can easily result in overlook or misdiagnoses. Prompt and efficient emergency interventions for reducing calcium levels, including hydration, calcitonin, bisphosphonates, and haemodialysis, are essential precondition. Surgical procedures and microwave ablation are radical therapies that can get a high cure rate and alleviate clinical symptoms. Abbreviations HPT:Hyperparathyroidism; PHPT: primary hyperparathyroidism; THPT: tertiary hyperparathyroidism; SCa: serum calcium; P:phosphorus; ALP: alkaline phosphatase; PTH:parathyroid hormone; CT:computed tomography; MRI: magnetic resonance imaging; 99mTc MIBI: 99mTc methoxy isobutyl isonitrile. Declarations Acknowledgments Thanks for the approval of the First Medical Center of Chinese PLA General Hospital. Authors’ contributions Design of this study, and reviewed and edited this article: XW; Conceived and designed the experiments: YL and YQ; Constructed figure and table: YQ; Analyzed the data:YL; Wrote and translated: YQ. All authors contributed to the article and approved the submitted version. Funding No funding was received to assist with the preparation of this manuscript. Data Availability Data sharing is not applicable to this article as no datasets were generated or analysed during the current study. Clinical trial number Not applicable. Ethics approval and consent to participate This retrospective study was approved by the Medical Ethics Committee of the First Medical Center of Chinese PLA General Hospital. As a retrospective analysis of de-identified patient data from institutional electronic health records, the Ethics Committee waived the need for individual informed consent. Robust data protection measures were enforced, including patient anonymization via unique codes and secure storage on encrypted hospital servers with restricted access. We had complied with the Declaration of Helsinki Ethical Principles for medical research involving human subjects. Consent for publication This manuscript does not report personal data such as individual details, images or videos; therefore, consent for publication is not applicable Competing interests The authors declare that they have no competing interests. Author details 1 Department of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China 2 Department of Endocrinology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China 3 Department of Endocrinology, Shexian Hospital, Handan 056400, Hebei Province,China References Jiajue RZ, Wang JJ, Jiang Y, Li M, Xia WB, Xing XP, Wang O. Primary hyperparathyroidism-hypercalcemia crisis-severe renal failure. Chinese Journal Osteoporosis and Bone Mineral Research. 2022; 15(6): 661-664.https://doi.org/10.3969/j.issn.1674-2591.2022.06.0072.Bedini I, Begnis GS, Poenitz F, et al. Hypercalcemic crisis as a presentation of primary hyperparathyroidism.Medicina (B Aires). 2023;83(5):804-807. 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E tiolog y Number of cases Proportion of Clinical manifestations （ n, % ） Laboratory Digestive system skeletal system Neurological system Urinary system cardiovascular systems SCa （ mg/dL ） albumin-corrected SCa （ mg/dL ） P （ mmol/L ） 25-OH vitamin D3 （ ng/ml ） ALP （ U/L ）（ P25,P75 ） PTH (pg/ml) （ P25,P75 ） PHPT 74 56, 75.68 50, 67.57 42, 56.76 52, 70.27 15, 20.27 14.52±2.32 14.08±2.68 0.86±0.37 11.62±6.95 113.00 （89.90，339.80） 534.50 （256.50，1160.75） THPT 5 3, 60 4, 80 3, 60 5, 100 1, 20 15.76±1.8 16.6±1.92 0.87±0.04 15.00±3.96 204.40 （130.10，224.10） 741.30 （440.35，1373.50） Normal range 8.36 - 10.16 8.36 - 10.16 0.89-1.6 20-32 0-130 15-65 Table 1 B Treatment plans, and outcomes of patients with hypercalcaemia crisis due to hyperparathyroidism. E tiolog y Number of cases Proportion of treatments （ n,% ） Laboratory after treatment hydration Diuretic calcitonin Bisphosphonate Glucocorticoids Haemodialysis surgery microwave ablation albumin-corrected SCa （ mg/dL ） P （ mmol/L ） PTH (pg/ml) （ P25,P75 ） PHPT 74 66, 89.19 23, 31.08 21, 28.38 49,66.22 11,14.86 3, 4.05 36, 48.65 2, 2.70 11.52±1.0 0.79±0.24 15.22（11.63，34.18） THPT 5 4, 80 2, 40 3, 60 2, 40 1, 20 1, 20 2, 40 1, 20 9.84±0.44 0.87±0.89 10.18（5.69，23.73） Normal range 8.36 - 10.16 0.89-1.6 15-65 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 16 Jan, 2026 Reviews received at journal 15 Jan, 2026 Reviewers agreed at journal 15 Jan, 2026 Reviewers agreed at journal 13 Jan, 2026 Reviews received at journal 23 Dec, 2025 Reviewers agreed at journal 17 Dec, 2025 Reviewers agreed at journal 18 Nov, 2025 Reviewers invited by journal 11 Nov, 2025 Editor invited by journal 24 Oct, 2025 Editor assigned by journal 17 Oct, 2025 Submission checks completed at journal 17 Oct, 2025 First submitted to journal 14 Oct, 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. 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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-7859238","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":547043649,"identity":"4dcc0dd3-3899-4d3f-8a7c-2ddcbb90d0ac","order_by":0,"name":"Yuqing Qu","email":"","orcid":"","institution":"the first medical center of PLA general hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuqing","middleName":"","lastName":"Qu","suffix":""},{"id":547043650,"identity":"25df8797-3805-4e7a-a0d2-8c9bcb7f4aa8","order_by":1,"name":"Yang Liu","email":"","orcid":"","institution":"the first medical center of PLA general 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10:02:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":856578,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7859238/v1/ea9f9a15-bece-4d2b-8004-18d8349bb60e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Diagnosis and Management of Hypercalcemic crisis resulting from Hyperparathyroidism：A 16-Year Experience with 79 Cases","fulltext":[{"header":"Background","content":"\u003cp\u003eHyperparathyroidism (HPT) is classified into three subtypes: primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), and tertiary hyperparathyroidism (THPT). Both PHPT and THPT can cause hypercalcemia. Hypercalcemic crisis occurs when the total calcium (SCa) level exceeds 14 mg/dL, accompanied by a series of severe clinical symptoms such as kidney failure, acute pancreatitis, and mental changes. Hypercalcemic crisis represents a life-threatening complication of HPT [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Patients with HPT-induced hypercalcemic crisis often exhibit nonspecific and heterogeneous clinical manifestations. As a result, the association between hypercalcemia and its symptoms have always been overlooked or masked by comorbid conditions, leading to misdiagnosis and delayed identification. Definitive etiological treatments, such as parathyroidectomy or microwave ablation, can achieve high cure rates [2]. This study conducted a retrospective analysis of the clinical data from 79 patients with HPT-related hypercalcemic crisis treated in our hospital during a 16-year period. We have delineated the characteristics, diagnostic methodologies, emergency treatments, and outcomes of etiological treatments, to enhance clinicians\u0026rsquo; awareness of this endocrine emergency,, improve standardized management, and underscore the necessity of strengthened multidisciplinary collaboration.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatients\u003c/h2\u003e\u003cp\u003eCases were identified by searching the First Medical Center of Chinese PLA General Hospital Electronic Health Record (EHR) system. We conducted a retrospective search for all patients within the Department of Endocrinology between January 2009 and January 2025 whose records contained the International Classification of Diseases-10 (ICD-10). A total of 79 patients diagnosed with HPT were enrolled. The diagnostic criteria for hypercalcemic crisis include a SCa level over 14 mg/dL, accompanied by a range of severe clinical manifestations. All patients included were definitively diagnosed with HPT, with albumin-corrected SCa levels above 14 mg/dL with the biochemical profile being the primary criterion for inclusion.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMethods\u003c/h3\u003e\n\u003cp\u003eThe clinical data was analyzed as follows: (1) general information, such as age, gender, and clinical manifestations; (2) laboratory evaluation, including total SCa, serum phosphorus(P), alkaline phosphatase (ALP), serum 25-hydroxyvitamin D, and parathyroid hormone (PTH); (3) imageological examination of the tumor, such as ultrasound, parathyroid computed tomography (CT), parathyroid magnetic resonance imaging (MRI), parathyroid 99mTc methoxy isobutyl isonitrile (99mTc MIBI); (4) misdiagnosed and undiagnosed conditions; (5) emergency and etiological treatments (surgery, radiofrequency ablation, chemotherapy, etc); (6) morphological and immunohistochemical evaluation of tumors; (7) therapeutic outcomes: improvement: post-treatment adjusted total SCa\u0026thinsp;\u0026lt;\u0026thinsp;14 mg/dL; remission: significant decrease in clinical symptoms and signs; resolved: total SCa\u0026thinsp;\u0026lt;\u0026thinsp;10 mg/dL, rectified by therapy, with no associated clinical symptoms or signs.\u003c/p\u003e\u003cp\u003e This retrospective study was approved by the Medical Ethics Committee of the First Medical Center of Chinese PLA General Hospital. As a retrospective analysis of de-identified patient data from institutional electronic health records, the Ethics Committee waived the need for individual informed consent. Robust data protection measures were enforced, including patient anonymization via unique codes and secure storage on encrypted hospital servers with restricted access.We had complied with the Declaration of Helsinki Ethical Principles for medical research involving human subjects.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed with IBM SPSS Statistics version 22.0. The quantitative variables were presented as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard error and and comparisons were performed using Student\u0026rsquo;s t-test. Non-quantitative data that deviated from a normal distribution were presented as the median (r) or interquartile range (P25, P75). Levels of statistical significance were set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eGeneral Information\u003c/h2\u003e\u003cp\u003eA total of 79 patients were diagnosed with HPT leading to a hypercalcemic crisis, including 39 men (49.37%) and 40 females (50.63%), with a mean age of 51.51\u0026thinsp;\u0026plusmn;\u0026thinsp;15.74 years. In this cohort of 79 patients, PHPT was predominant, with a prevalence of 93.67% (74/79), while THPT was observed in only 6.33% (5/79). Among the 79 patients, 83.54% (66/79) presented with endocrine system symptoms, 74.68% (59/79) with digestive symptoms, 68.35% (54/79) with skeletal system symptoms, 59.49% (47/79) with urinary system symptoms, 56.96% (45/79) with nervous system symptoms, and 20.25% (16/79) with cardiovascular system symptoms, respectively.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eClinical manifestations\u003c/h2\u003e\u003cp\u003e\u003cb\u003ePrimary hyperparathyroidism\u003c/b\u003e In the cohort of 74 individuals experiencing hypercalcemic crisis caused by PHPT, systemic manifestations were observed in the following order of prevalence: endocrine system (83.78%), digestive system (75.68%), urinary system (70.27%), skeletal system (67.57%), neurological system (56.76%), and cardiovascular system (20.27%). The primary clinical manifestations of Endocrine system were xerostomia, polydipsia, polyuria, hyperglycemia, and hypokalemia; Gastrointestinal abnormalities presented as nausea (82.1%), vomiting (64.3%), stomach discomfort (41.1%), and anorexia (33.9%), with 4 instances (7.14%) exhibiting simultaneous cholelithiasis; The presenting symptoms were urinary urgency (76.9%), dysuria (69.2%), renal insufficiency (53.8%), and flank pain (48.1%), worsened by nephrolithiasis in 25 individuals (48.07%); Musculoskeletal consequences comprised osteodynia (88.0%) and osteoporosis (72.0%), with 11 patients (22.00%) indicating a history of pathological fractures; The spectrum of neurological symptoms included headache (71.4%), dizziness (66.7%), lethargy (52.4%), and nonspecific tiredness (92.9%); The presenting symptoms of Cardiovascular system were palpitations (86.7%), chest tightness (73.3%), and dyspnea on exercise (53.3%) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e\u003cp\u003e\u003cb\u003eTertiary hyperparathyroidism\u003c/b\u003e All 5 patients experiencing the hypercalcemic crisis caused by THPT had a history of chronic renal disease. Four patients displayed endocrine symptoms including xerostomia, hyperglycemia, gout, and electrolyte imbalances, alongside skeletal symptoms such as osseous pain and fractures.Three patients displayed gastrointestinal symptoms including anorexia, abdominal distension, diarrhea, nausea, vomiting, and hepatic dysfunction, as well neurological symptoms such as mental agitation, exhaustion, insomnia, and confusion. One patient exhibited cardiovascular symptoms including chest tightness, dyspnea, and heart failure (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLaboratory and Imaging Ivestigations\u003c/h3\u003e\n\u003cp\u003e\u003cb\u003ePrimary hyperparathyroidism\u003c/b\u003e The average albumin-corrected SCa level in 74 patients with PHPT was 14.08\u0026thinsp;\u0026plusmn;\u0026thinsp;2.68 mg/dL (normal range 8.36\u0026ndash;10.16 mg/dL). Additionally, the mean serum phosphorus level was 0.86\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37 mmol/L (normal range 0.89\u0026ndash;1.6 mmol/L) and the mean 25-OH vitamin D3 level was 11.62\u0026thinsp;\u0026plusmn;\u0026thinsp;6.95 ng/ml (normal range 20\u0026ndash;30 ng/ml). Meanwhile, the median (interquartile spacing) of PTH was 534.50 (256.50, 1160.75) pg/ml (normal range 15\u0026ndash;65 pg/ml) and the median (interquartile spacing) of ALP was 113.00 (89.90, 339.80) U/L (normal range 0-130 U/L) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Ultrasonography was conducted in 87.84% (65/74) of cases, with a positive rate of 60.00% (39/65); CT was utilized in 60.81% (45/74) of cases, with a positive rate of 82.22% (37/45); MRI was employed in 13.51% (10/74) of cases, with a positive rate of 90.00% (9/10); 99mTc MIBI was administered in 79.72% (59/74) of cases, with a positive rate of 84.74% (50/59).\u003c/p\u003e\u003cp\u003e\u003cb\u003eTertiary hyperparathyroidism\u003c/b\u003e The average total SCa level at the diagnosis of hypercalcemic crisis in 5 patients with THPT was 15.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 mg/dL (normal range 8.36\u0026ndash;10.16 mg/dL), while the average albumin-corrected SCa level was 16.60\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8 mg/dL (normal range 8.36\u0026ndash;10.16 mg/dL). The mean serum phosphorus level was 0.87\u0026thinsp;\u0026plusmn;\u0026thinsp;0.04 mmol/L (normal range 0.89\u0026ndash;1.6 mmol/L) and the mean 25-OH vitamin D3 level was 15.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.96 ng/ml (normal range 20\u0026ndash;30 ng/ml). Meanwhile, the median (interquartile spacing) of PTH was 741.30 (440.35, 1373.50) pg/ml (normal range 15\u0026ndash;65 pg/ml) and the median (interquartile spacing) of ALP was 204.40 (130.10, 224.10) U/L (normal range 0-130 U/L) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA). Four patients underwent ultrasonography, with a 100% positivity rate (4/4). Three patients underwent 99mTc MIBI, also with a 100% positivity rate (3/3). Only one patient underwent MRI, which was reported as positive. None of the five patients underwent CT scanning owing to renal insufficiency.\u003c/p\u003e\n\u003ch3\u003eDiagnosis\u003c/h3\u003e\n\u003cp\u003eMisdiagnosis occurred in 6.32% (5/79) of the patients, which included one instance of unstable angina pectoris misdiagnosed in the cardiology department due to cardiovascular symptoms; One case was mistakenly categorized as brucellosis in the pain department due to a multitude of nonspecific systoms, and three cases were overlooked due to insufficient attention to the SCa profile at the initial consultation. This study demonstrated that the rapid identification of hypercalcemic crisis (0.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 days to diagnosis ) and thorough analysis of clinical data led to a definitive etiology in 100% (79/79) of cases (4.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.2 days to etiological clarity) through history taking, physical examination, clinical presentation, and qualitative diagnostic methods (biochemical tests including SCa, serum phosphorus, ALP, PTH, and 25-OH vitamin D3 and various locoregional diagnostic techniques).\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eEmergency treatment and regression\u003c/h2\u003e\u003cp\u003eEmergency treatments were promptly executed following the confirmation of the diagnosis. The implementation of emergency calcium-lowering treatment via hydration (4,000 ml of water daily) or intravenous saline (4,000ml) accounted for 88.61% (70/79) of cases, with PHPT patients comprising 89.19% (66/74) and THPT patients 80.00% (4/5). Bisphosphonate therapy accounted for 64.56% (51/79), with PHPT 66.22% (49/74) and THPT 40% (2/5). Intravenous zoledronic acid was administered in 88.24% (45/51) of patients, while other bisphosphonate agents were administered in 11.76% (6/51) patients. Diuretic treatment, exclusively utilizing intravenous furosemide, accounted for 31.65% (25/79), with PHPT at 31.08% (23/74) and THPT at 40% (2/5). Subcutaneous calcitonin treatment, accounted for 30.38% (24/79), with PHPT at 28.38% (21/74) and THPT at 60.00% (3/5). Glucocorticoid treatment comprised 15.19% (12/79) of the cohort, with 14.86% (11/74) among PHPT patients and 20.00% (1/5) among THPT patients. Only four patients underwent haemodialysis for severe hypercalcemia, comprising three with PHPT and one with THPT (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The average albumin-corrected SCa level decreased from 14.12\u0026thinsp;\u0026plusmn;\u0026thinsp;2.92 mg/dL to 11.08\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40 mg/dL (normal range 8.36\u0026ndash;10.16 mg/dL) in 79 individuals after emergency treatments. After the immediate interventions, the average albumin-corrected SCa levels significantly decreased, with an improvement rate of 88.61% (70/79) and a complete remission rate of clinical symptoms at 100% (79/79).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eEtiological treatment and regression\u003c/h2\u003e\u003cp\u003e\u003cb\u003eHypercalcemic crisis caused by PHPT\u003c/b\u003e Thirty-six patients of PHPT underwent surgery at our center, with postoperative pathology confirming the presence of parathyroid adenoma. The median serum PTH levels (interquartile range) decreased from 508.20 (235.85, 1244.25) pg/ml preoperatively to 14.30 (10.42, 33.56) pg/ml postoperatively (normal range 15\u0026ndash;65 pg/ml). The mean albumin-corrected SCa level declined from 14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6 mg/dL to 11.52\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0 mg/dL(Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB). The surgical improvement rate was 100% (36 out of 36), and the cure rate was 88.89% (32 out of 36). Two patients with pathology consistent with parathyroid adenoma, confirmed by puncture biopsy, underwent microwave ablation at our center. Subsequent measurements of serum PTH and albumin-corrected SCa levels shown considerable reductions, achieving a 100% improvement rate. The remaining patients with PHPT were not enrolled in the analysis since they returned to their hometowns for additional surgical treatment, for which no data were accessible.\u003c/p\u003e\u003cp\u003e\u003cb\u003eHypercalcemic crisis caused by THPT\u003c/b\u003e Two of the five patients with THPT underwent surgery at our center, and postoperative pathology confirmed the diagnosis of parathyroid adenomatous hyperplasia. The mean postoperative serum PTH decreased from 741.30 (440.35, 1373.50) pg/ml to 10.18 (5.69, 23.73) pg/ml (normal range 15\u0026ndash;65 pg/ml), meanwhile the mean post albumin-corrected SCa declined from 15.28 to 9.52 mg/dL. One patient underwent microwave ablation, resulting in a postoperative reduction of serum PTH from 1015.00 pg/ml preoperatively to 37.28 pg/ml postoperatively, and a reduction in albumin-corrected SCa from 15.24 to 10.04 mg/dL. All five patients got long-term remission of their clinical manifestations by allopathic interventions, including surgery, microwave ablation, and pharmacotherapy.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eHyperparathyroidism is a metabolic condition caused by the excessive synthesis of PTH, characterized by hypercalcemia, hypophosphatemia, and dysfunction of target organs. PHPT encompasses a range of clinical symptoms caused by the autonomous production of excessive PTH, leading to hypercalcemia, enhancedrenal calcium reabsorption, and increased urine phosphorus excretion [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. SHPT is the compensatory activation of parathyroid tissue due to hypocalcemia, resulting in hyperplasia and hypertrophy of the parathyroid glands, which causes excessive production of PTH. THPT results from prolonged and uncontrolled SHPT, wherein the parathyroid glands transition from compensatory hyperplasia to autonomous production of PTH [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Both PHPT and THPT can lead to hypercalcemia, and a hypercalcemic crisis may occur if the SCa level exceeds 14 mg/dL alongside a constellation of severe clinical manifestations. The hypercalcemic crisis is a severe consequence of hyperparathyroidism and constitutes a life-threatening endocrine emergency. Our study demonstrates that primary hyperparathyroidism (PHPT) is the most frequent etiology of hypercalcemic crisis among hyperparathyroidism cases in China, where such reports are scarce. Specifically, PHPT constituted 93.67% (74/79) of cases, whereas tertiary hyperparathyroidism (THPT) represented only 6.33% (5/79).\u003c/p\u003e\u003cp\u003eIn PHPT, the parathyroid glands produce excessive PTH, which binds to PTH receptors in bone and kidney, promoting bone resorption, resulting in calcium release into the bloodstream, increasing renal tubular calcium reabsorption, and stimulating the synthesis of 1,25-dihydroxyvitamin D3, thereby enhancing intestinal calcium absorption. Enhanced intestinal calcium absorption can induce a hypercalcemic crisis. The pathogenesis of THPT arises from the sustained stimulation of long-term SHPT (e.g., chronic kidney disease or vitamin D deficiency), resulting in the transition of the parathyroid glands from compensatory hyperplasia to autonomous secretion, ultimately resulting in persistent hypercalcemia and multisystem damage [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe clinical manifestations of hypercalcemic crisis are intricate and diverse, resulting in misdiagnosis with other conditions. Hypercalcemic crisis, a severe complication of HPT, has always been overlooked and misdiagnosed. Thus, early identification of its signs and symptoms is essential. The occurrence and intensity of clinical symptoms of hypercalcaemia are proportional to the degree of SCa elevation and the patient's capacity to endure elevated SCa levels. Appropriate extracellular fluid calcium concentrations are essential for the regular functioning of various systems. Hence, hypercalcemic crisis may result in inattention, ataxia, and even coma. The cardiovascular system symptoms exhibit hypertension, bradycardia, arrhythmia, and Q-T interval shortening. Gastrointestinal signs include anorexia, nausea, vomiting, and constipation. Manifestations of the urinary system include polyuria, renal calculi, renal calcification, decreased glomerular filtration rate, and hyperchloremic acidosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This study revealed that the clinical manifestations of patients experiencing a hypercalcemic crisis predominantly affected the endocrine, digestive, urinary, skeletal, and neurological systems, with incidences above 50%. This complexity and variability in symptoms hindered early identification of the condition. Hypercalcemic crisis has always been frequently misdiagnosed as chronic gastritis and urinary calculi[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Clinicians encountering patients with suggestive symptoms should prioritize SCa testing. This practice facilitates early detection of hypercalcemic crisis and reduces the likelihood of diagnostic delays or errors.\u003c/p\u003e\u003cp\u003eThe diagnosis of hypercalcemic crisis caused by HPT primarily relies on clinical manifestations and laboratory evaluations. A definitive diagnosis is established when SCa levels exceed 14 mg/dL, in conjunction with elevated PTH levels and a range of severe clinical symptoms. Hypercalcemic crisis is a perilous situation; urgent calcium reduction is essential. Clinical interventions to reduce SCa mostly encompass hydration treatment, diuretics to enhance calcium excretion, and bisphosphonates to suppress osteoclast activity [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Hydration is the essential component of treatment, resolving dehydration by rapid volume expansion, diluting SCa levels, and enhancing urinary calcium excretion. The preferred intravenous fluid is 0.9% saline, administered at an infusion rate of 200\u0026ndash;300 ml/h, totaling 3\u0026ndash;6 liters daily. Continuous monitoring of serum electrolytes and electrocardiograms is essential during hydration therapy to prevent electrolyte imbalances or volume overload. Diuretics (e.g. furosemide 20\u0026ndash;40 mg intravenously every 4\u0026ndash;6 hours) may be used in conjunction with sufficient hydration; however, thiazide diuretics are contraindicated due to their propensity to elevate calcium levels. Bisphosphonates exhibit a delayed onset and prolonged duration of action, and frequently used in conjunction with calcitonin to manage hypercalcemic crisis. Bisphosphonates reduce serum calcium levels by inhibiting osteoclast-mediated bone resorption. Zoledronic acid (4 mg intravenously over a minimum of 15 minutes) or pamidronate (60\u0026ndash;90 mg intravenously over a minimum of 2 hours) can get a calcitonin-lowering effect within the first 24\u0026ndash;48 hours of administration, with effects persisting for several weeks [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Calcitonin is employed for short-term transitional treatment by reducing SCa levels through the twin mechanisms of decreasing osteoclast-mediated bone resorption and enhancing renal excretion. Glucocorticoids diminish SCa levels via suppressing the production of 1,25-dihydroxyvitamin D and decreasing the release of inflammatory mediators[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Haemodialysis is not the primary treatment for hypercalcemic crisis; it can be performed when SCa levels are significantly high and pose a life-threatening risk [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This study reports an improvement rate of 88.61% (70/79) in patients following the aforementioned emergency calcium-lowering medication. Prompt and effective calcium-lowering interventions can not only save patient's life but also provide an opportunity for further etiological therapy.\u003c/p\u003e\u003cp\u003eMedical treatment with cinacalcet or surgical treatment with parathyroidectomy (PTX) are both viable options for addressing tertiary hyperparathyroidism [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Cinacalcet is a calcimimetic drug that suppresses the production of PTH by enhancing the sensitivity of the calcium-sensing receptors of the parathyroid gland to calcium [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. It is important to note that the timeframe of this study predates the widespread clinical use of calcimimetics, such as cinacalcet, for the management of THPT in our region. In addition, the number of cases of THPT in this study was relatively small. Consequently, none of the patients in our cohort received this class of medication. Surgical excision is the most efficacious treatment for PHPT and THPT[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Microwave ablation, with precise preoperative localization, is also an effective therapy. In China, 99mTc MIBI, ultrasonography, and CT are the primary imageological examination for preoperative localization; the sensitivity of parathyroid 99mTc MIBI for localizing parathyroid lesions was 82% to 100% internationally, with a sensitivity of 91.4% [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. The positive rate of 99mTc MIBI in our study was 85.43% (53/62), consistent with national and worldwide data, indicating that it exhibits greater sensitivity. The ultrasound positive rate was 62.32% (43/69), while the CT positive rate was 82.22% (37/45), indicating that the combination of 99mTc MIBI with ultrasound and CT considerably enhances the detection rate of tumors, particularly for ectopic adenomas or tiny adenomas. The results of our study are generally in accordance with other centers in China. Following precise localization by imaging assessment, 38 patients underwent surgical intervention, resulting in improvements for all. And 34 patients got complete recovery. Microwave ablation has several advantages: straightforward operational procedure, little trauma, thorough tumor deactivation, and few complications [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Three patients underwent microwave ablation therapy. Subsequently, their serum PTH and SCa levels returned to normal, resulting in complete recovery in all patients.\u003c/p\u003e\u003cp\u003eOur study has several limitations. It was a retrospective analysis of a single surgeon\u0026rsquo;s experience at a single tertiary care institution and as a result, the findings may not be generalizable to other institutions. Some of our patients were lost to follow-up and excluded from definitive treatment analysis. This introduces a major bias and likely overestimates surgical outcomes. A notable aspect of our study is the absence of experience with cinacalcet or other calcimimetics in our cohort.\u003c/p\u003e"},{"header":"Conclutions","content":"\u003cp\u003eBased on a retrospective analysis of a larger cohort of hyperparathyroidism patients in our clinical center, the incidence of hypercalcemic crisis was much higher in PHPT patients than THPT patients. The clinical symptoms of patients with a hypercalcemic crisis are intricate and diverse, which can easily result in overlook or misdiagnoses. Prompt and efficient emergency interventions for reducing calcium levels, including hydration, calcitonin, bisphosphonates, and haemodialysis, are essential precondition. Surgical procedures and microwave ablation are radical therapies that can get a high cure rate and alleviate clinical symptoms.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHPT:Hyperparathyroidism; PHPT: primary hyperparathyroidism; THPT: tertiary hyperparathyroidism; SCa: serum calcium; P:phosphorus; ALP: alkaline phosphatase; PTH:parathyroid hormone; CT:computed tomography; MRI: magnetic resonance imaging; 99mTc MIBI: 99mTc methoxy isobutyl isonitrile.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003eThanks for the approval of the First Medical Center of Chinese PLA General Hospital.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eDesign of this study, and reviewed and edited this article: XW; Conceived and designed the experiments: YL and YQ; Constructed figure and table: YQ; Analyzed the data:YL; Wrote and translated: YQ. All authors contributed to the article and approved the submitted version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003eNo funding was received to assist with the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003eData sharing is not applicable to this article as no datasets were generated or analysed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective study was approved by the Medical Ethics Committee of the First Medical Center of Chinese PLA General Hospital. As a retrospective analysis of de-identified patient data from institutional electronic health records, the Ethics Committee waived the need for individual informed consent. Robust data protection measures were enforced, including patient anonymization via unique codes and secure storage on encrypted hospital servers with restricted access. We had complied with the Declaration of Helsinki Ethical Principles for medical research involving human subjects.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis manuscript does not report personal data such as individual details, images or videos; therefore, consent for publication is not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Endocrinology, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e2\u0026nbsp;\u003c/sup\u003eDepartment of Endocrinology, Yantai Yuhuangding Hospital, Yantai 264000, Shandong Province, China\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e3\u0026nbsp;\u003c/sup\u003eDepartment of Endocrinology, Shexian Hospital, Handan 056400, Hebei Province,China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eJiajue RZ, Wang JJ, Jiang Y, Li M, Xia WB, Xing XP, Wang O. Primary hyperparathyroidism-hypercalcemia crisis-severe renal failure. Chinese Journal Osteoporosis and Bone Mineral Research. 2022; 15(6): 661-664.https://doi.org/10.3969/j.issn.1674-2591.2022.06.0072.Bedini I, Begnis GS, Poenitz F, et al. Hypercalcemic crisis as a presentation of primary hyperparathyroidism.Medicina (B Aires). 2023;83(5):804-807.\u003c/li\u003e\n\u003cli\u003eKong LQ, Qu XQ, Mu LY, Li F, Li HY, Ren GS, Wu KN. All-round and full-cycle management of primary hyperparathyroidism.Chinese Journal Endocrinology Surgery. 2024; 18(1): 17-20.https://doi.org/10.3760/cma.j.cn.115807-20240110-00010\u003c/li\u003e\n\u003cli\u003eZhang LX, Zhang B, Liu XY, Wang ZM, Qi P, Zhang TY, Zhang Q. Advances in the treatment of secondary and tertiary hyperparathyroidism.Frontiers in Endocrinology. 2022);12:1-8. https://doi.org/10.3389/fendo.2022.1059828\u003c/li\u003e\n\u003cli\u003ePalumbo VD, Damiano G, Messina M, Fazzotta S, Lo Monte G, Lo Monte AI. Tertiary hyperparathyroidism: a review.Clinical Terapeutica. 2021; 172 (3): 241-246. https://doi.org/10.7417/CT.2021.2322\u003c/li\u003e\n\u003cli\u003eOmotosho YB, Zahra F. Resistant Hypercalcemia. Treasure Island: Stat-Pearls, 2023.\u003c/li\u003e\n\u003cli\u003eM.D.Walker,E.Shane. Hypercalcemia:A Review.The Journal of the American Medical Association. 2022); 328(16):1624-1636.https://doi.org/10.1001/jama.2022.18331\u003c/li\u003e\n\u003cli\u003eQu YQ, Liu Y, Wang XL, Guo QH, Du J, Pei Y, Ba JM, Gu WJ, Dou JT, Lv ZH, Mu YM. Clinical Characteristics and Management of hypercalcemia crisis in 155 patients: a single center retrospective study. International Journal of Endocrinology. 2024; 1-7. https://doi.org/10.1155/2024/4689745\u003c/li\u003e\n\u003cli\u003eMuntaser A, Thelen A, R Sehgal A, R McHenry C. Hyperparathyroid crisis: Characteristics and outcomes. American journal of surgery. 2023; 225(3):477-480. https://doi.org/10.1016/j.amjsurg.2022.10.028\u003c/li\u003e\n\u003cli\u003eVarma TH, Sahitya DSK, Dusad S, Agarwal A, Dayal D. Oral prednisolone for management of persistent hypercalcemia fterhypercalcemic crisis in the Williams-Beuren syndrome. Pediatric endocrinology,diabetes, and metabolism. 2018; 24 (2) : 106-109. https://doi.org/10.18544/PEDM-24.02.0109\u003c/li\u003e\n\u003cli\u003eBui-Thi HD, Le-Phuong T, Tran-Viet T, Nguyen-Huu P. Successful management of hypercalcemic crisis by continuous renal replacement therapy with regional citrate anticoagulation and surgery: a case report. Therapeutic Advances in Endocrinology and Metabolism. 2025; 16:1-7. https://doi.org/10.1177/20420188251323953\u003c/li\u003e\n\u003cli\u003eDouthat WG, Chiurchiu CR, Massari PU. New options for the management of hyperparathyroidism after renal transplantation. World J Transplant. 2012;2:41\u0026ndash;45. https://doi.org/10.5500/wjt.v2.i3.41\u003c/li\u003e\n\u003cli\u003eBrown EM. Clinical utility of calcimimetics targeting the extracellular calcium-sensing receptor (CaSR). Biochem Pharmacol. 2010;80:297\u0026ndash;307.https://doi.org/10.10.1016/j.bcp.2010.04.002\u003c/li\u003e\n\u003cli\u003eJung SY, Kim H, Kwon H, et al. Parathyroidectomy versus cinacalcet in the treatment of tertiary hyperparathyroidism after kidney transplantation: a retrospective study. Kidney Res Clin Pract. 2022;41(4):473-481.https://doi.org/10.23876/j.krcp.21.210\u003c/li\u003e\n\u003cli\u003eZhang WJ, Ren HL, Liao QX, Wu J. Cost‑Effectiveness and Clinical Outcomes of Secondary Hyperparathyroidism Treatments in Patients with Chronic Kidney Disease. Calcified Tissue International. 2024; 114:368\u0026ndash;376. https://doi.org/10.1007/s00223-024-01187-3\u003c/li\u003e\n\u003cli\u003eXu W, Li SH, Cheng F, Gong LF, Tang WG, Lu JK, Li Y, Wang ZX. Microwave ablation versus radiofrequency ablation for patients with primary and secondary hyperparathyroidism: a meta-analysis.International urology and nephrology. 2023; 55(9): 2237-2247.https://doi.org/10.1007/s11255-023-03543-y\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 A \u0026nbsp; \u0026nbsp;Clinical manifestations distribution, biochemical test results of patients with hypercalcaemia crisis due to hyperparathyroidism.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1085\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003etiolog\u003c/strong\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of cases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"5\" style=\"width: 362px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProportion of Clinical manifestations\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en, %\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"6\" style=\"width: 601px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDigestive system\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eskeletal system\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNeurological system\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUrinary system\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecardiovascular systems\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCa\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003emg/dL\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ealbumin-corrected SCa\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003emg/dL\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003emmol/L\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e25-OH vitamin D3\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eng/ml\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eALP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eU/L\u003c/strong\u003e\u003cstrong\u003e）（\u003c/strong\u003e\u003cstrong\u003eP25,P75\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTH\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(pg/ml)\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eP25,P75\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003ePHPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e56, 75.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e50, 67.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e42, 56.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e52, 70.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e15, 20.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e14.52\u0026plusmn;2.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e14.08\u0026plusmn;2.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.86\u0026plusmn;0.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e11.62\u0026plusmn;6.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e113.00\u003c/p\u003e\n \u003cp\u003e（89.90，339.80）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e534.50\u003c/p\u003e\n \u003cp\u003e（256.50，1160.75）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eTHPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e3, 60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e4, 80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e3, 60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e5, 100\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e1, 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e15.76\u0026plusmn;1.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e16.6\u0026plusmn;1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.87\u0026plusmn;0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e15.00\u0026plusmn;3.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e204.40\u003c/p\u003e\n \u003cp\u003e（130.10，224.10）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e741.30\u003c/p\u003e\n \u003cp\u003e（440.35，1373.50）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003eNormal range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 82px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 59px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e8.36 - 10.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 134px;\"\u003e\n \u003cp\u003e8.36 - 10.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.89-1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e20-32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 109px;\"\u003e\n \u003cp\u003e0-130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 131px;\"\u003e\n \u003cp\u003e15-65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eTable 1 B \u0026nbsp; \u0026nbsp;Treatment plans, and outcomes of patients with hypercalcaemia crisis due to hyperparathyroidism.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"1102\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eE\u003c/strong\u003e\u003cstrong\u003etiolog\u003c/strong\u003e\u003cstrong\u003ey\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of cases\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"8\" style=\"width: 644px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eProportion of treatments\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003en,%\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"3\" style=\"width: 324px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLaboratory after treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ehydration\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDiuretic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ecalcitonin\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eBisphosphonate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGlucocorticoids\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHaemodialysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u003cstrong\u003esurgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cstrong\u003emicrowave ablation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ealbumin-corrected SCa\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003emg/dL\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003emmol/L\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePTH\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(pg/ml)\u003c/strong\u003e\u003cstrong\u003e（\u003c/strong\u003e\u003cstrong\u003eP25,P75\u003c/strong\u003e\u003cstrong\u003e）\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003ePHPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e66, 89.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e23, 31.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e21, 28.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e49,66.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e11,14.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e3, 4.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e36, 48.65\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e2, 2.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e11.52\u0026plusmn;1.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e0.79\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e15.22（11.63，34.18）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eTHPT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e4, 80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e2, 40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e3, 60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e2, 40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e1, 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e1, 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e2, 40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1, 20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e9.84\u0026plusmn;0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e0.87\u0026plusmn;0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e10.18（5.69，23.73）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003eNormal range\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 69px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 99px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 98px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 61px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 138px;\"\u003e\n \u003cp\u003e8.36 - 10.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 75px;\"\u003e\n \u003cp\u003e0.89-1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 111px;\"\u003e\n \u003cp\u003e15-65\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Hypercalcemic crisis, Hyperparathyroidism, Parathyroid hormone, Primary hyperparathyroidism, Tertiary hyperparathyroidism","lastPublishedDoi":"10.21203/rs.3.rs-7859238/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7859238/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eTo analyze a large-sample cohort of hypercalcemic crisis cases caused by hyperparathyroidism, focusing on etiology, clinical manifestations, diagnosis, emergency treatments, and etiological treatments.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003ePatients with hypercalcemic crisis due to hyperparathyroidism admitted in our institution from January 2009 to January 2025 were enrolled. Comprehensive data included demographic characteristics, clinical manifestations, etiological subtypes, imaging examination, emergency treatments, and etiological treatments. Serial assessments of serum parathyroid hormone, calcium, and phosphorus levels were compared pre- and post-emergency treatment.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 79 patients (39 males, 40 females) were included, with a mean age of (51.51\u0026thinsp;\u0026plusmn;\u0026thinsp;15.74) years. Primary hyperparathyroidism accounted for 93.67% (74/79), while tertiary hyperparathyroidism accounted for 6.33% (5/79). Clinical manifestations included endocrine symptoms (83.54%, 66/79), gastrointestinal symptoms (74.68%, 59/79), skeletal symptoms (68.35%, 54/79), renal symptoms (59.49%, 47/79), neurological symptoms (56.96%, 45/79), and cardiovascular symptoms (20.25%, 16/79). After the administration of emergency calcium-lowering therapy (hydration, subcutaneous calcitonin, intravenous bisphosphonates, or hemodialysis), 88.61% (70/79) patients got clinical improvement. Surgical parathyroidectomy achieved a 100% improvement rate (36/36 primary hyperparathyroidism; 2/2 tertiary hyperparathyroidism). All three patients (2 primary hyperparathyroidism, 1 tertiary hyperparathyroidism) treated with microwave ablation achieved complete remission.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eHypercalcemic crisis caused by hyperparathyroidism presents with diverse and nonspecific clinical manifestations. It has challenges for early diagnosis and increasing risks of misdiagnosis. Efficient and thorough calcium-reducing interventions in the emergency context can facilitate a fast alleviation of clinical manifestations. Total parathyroidectomy and microwave ablation can get high cure rates and lead to sustained clinical remission.\u003c/p\u003e","manuscriptTitle":"Clinical Diagnosis and Management of Hypercalcemic crisis resulting from Hyperparathyroidism：A 16-Year Experience with 79 Cases","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-20 18:09:58","doi":"10.21203/rs.3.rs-7859238/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-01-16T08:08:18+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-01-15T10:23:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"46656400833427006737436982563622372291","date":"2026-01-15T05:20:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"54263337585982335841964214840039445540","date":"2026-01-13T13:18:00+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-23T10:06:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"82873666193290801096661055147858231262","date":"2025-12-17T09:58:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"275236666484748709464182437278931140077","date":"2025-11-18T14:45:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-11T11:19:02+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-24T09:33:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-17T23:46:30+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-17T23:45:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-10-14T13:34:30+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":"ab3d07aa-ac3a-40f4-8a87-0c091916de8e","owner":[],"postedDate":"November 20th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-20T12:23:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-20 18:09:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7859238","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7859238","identity":"rs-7859238","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}