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This study aimed to evaluate the prevalence and risk of malignant neoplasm in primary hyperparathyroidism (PHPT) patients. Potentially eligible studies were retrieved from PubMed and Embase databases from inception to November 2023 using search strategy consisting of terms for "Primary hyperparathyroidism" and "Malignant neoplasm". Eligible study must report prevalence of malignant neoplasm among patients with PHPT or compare the risk of malignant neoplasm between patients with PHPT and comparators. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method.A total of 11,926 articles were identified. After two rounds of systematic review, 50 studies were included. The meta-analysis revealed that pooled prevalence rates of overall cancer was 0.19 (95%CI: 0.13-0.25; I 2 94%). The two most prevalent types of malignancy among patients with PHPT ware papillary thyroid cancer (pooled prevalence: 0.07; 95%CI: 0.06-0.08; I 2 85%) and breast cancer (pooled prevalence: 0.05; 95%CI: 0.03-0.07; I 2 87%). Subgroup analysis of studies focusing on patients undergoing parathyroidectomy reported a fourfold higher prevalence of papillary thyroid cancer than the remaining studies (0.08 versus 0.02). The meta-analysis of cohort studies found a significant association between PHPT and overall cancer with the pooled risk ratio of 1.28 (95%CI: 1.23-1.33; I 2 66.9%).We found that the pooled prevalence of malignant neoplasm in PHPT was 19%, with papillary thyroid cancer and breast cancer being the most prevalent types. The meta-analysis of cohort studies showed that patient with PHPT carried an approximately 28% increased risk of malignancy., (© 2024. The Author(s).)

Introduction: Primary hyperparathyroidism (PHPT) is a common endocrine disease with a variable presentation. There is a recent increase in the number of asymptomatic cases due to the use of multichannel automated analyzers., (This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: There has been a notable shift towards the diagnosis of less severe and asymptomatic primary hyperparathyroidism (PHPT) in developed countries. However, there is a paucity of recent data from sub-Saharan Africa (SSA), and also, no reported data from SSA on the utility of intra-operative parathyroid hormone (IO-PTH) monitoring. In an earlier study from Inkosi Albert Luthuli Central Hospital (IALCH), Durban, South Africa (2003-2009), majority of patients (92.9%) had symptomatic disease. The aim of this study was to evaluate the clinical profile and management outcomes of patients presenting with PHPT at IALCH., Methods: A retrospective chart review of patients with PHPT attending the Endocrinology clinic at IALCH between July 2009 and December 2021. Clinical presentation, laboratory results, radiologic findings, surgical notes and histology were recorded., Results: Analysis included 110 patients (87% female) with PHPT. Median age at presentation was 57 (44; 67.5) years. Symptomatic disease was present in 62.7% (n:69); 20.9% (n:23) had a history of nephrolithiasis and 7.3% (n:8) presented with previous fragility fractures. Mean serum calcium was 2.87 ± 0.34 mmol/l; median serum-PTH was 23.3 (15.59; 45.38) pmol/l, alkaline phosphatase 117.5 (89; 145.5) U/l and 25-hydroxyvitamin-D 42.9 (33.26; 62.92) nmol/l. Sestamibi scan (n:106 patients) identified an adenoma in 83.02%. Parathyroidectomy was performed on 84 patients with a cure rate of 95.2%. Reasons for conservative management (n:26) included: no current surgical indication (n:7), refusal (n:5) or deferral of surgery (n:5), loss to follow-up (n:5) and assessed as high anaesthetic risk (n:4). IO-PTH measurements performed on 28 patients indicated surgical success in 100%, based on Miami criteria. Histology confirmed adenoma in 88.1%, hyperplasia in 7.1% and carcinoma in 4.8%. Post-operative hypocalcaemia developed in 30 patients (35.7%), of whom, 14 developed hungry bone syndrome (HBS). In multivariate analysis, significant risk factors associated with HBS included male sex (OR 7.01; 95% CI 1.28, 38.39; p 0.025) and elevated pre-operative PTH (OR 1.01; 95% CI 1.00, 1.02; p 0.008)., Conclusions: The proportion of asymptomatic PHPT has increased at this centre over the past decade but symptomatic disease remains the dominant presentation. Parathyroidectomy is curative in the majority of patients. IO-PTH monitoring is valuable in ensuring successful surgery., (© 2024. The Author(s).)

Objective: Apart from renal stones, primary hyperparathyroidism (PHPT) has been linked to the occurrence of gallstone disease (GSD). Nevertheless, the association is not consistent across all studies. The present systematic review and meta-analysis aims to collate the hitherto available evidence and provide a pooled estimate of the association between GSD and PHPT., Methods: PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched from inception till May 10, 2023 for observational studies reporting the prevalence of GSD (in terms of absolute numbers) in patients with PHPT. The pooled prevalence of GSD and odds ratio with 95% CI of the occurrence of GSD in patients with PHPT as compared to age- and sex-matched controls were calculated. Subgroup analysis was performed based on patient ethnicity (Indian/Caucasian). Statistical analysis was carried out using R version 4.2.2. Random-effects model with Hartung-Knapp adjustment was used for analyses., Results: A total of 7 observational studies were included, pooling data from 15 949 patients with PHPT. The pooled prevalence of GSD in patients with PHPT was 16% (95% CI: 7%, 25%, I 2  = 99%), being 13% (95% CI: 0%, 66%, I 2  = 76%) in Indians, and 17% (95% CI: 4%, 31%, I 2  = 99%) in Caucasians. Data consolidated from 3 studies showed that the pooled odds ratio of occurrence of GSD in patients with PHPT compared to controls was 1.77 (95% CI: 1.60, 1.97, P < .001, I 2  = 0%)., Conclusions: GSD is more prevalent in patients with PHPT than in the general population. Thus, PHPT may be considered an additional risk factor for GSD., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2023 AACE. Published by Elsevier Inc. All rights reserved.)

Primary hyperthyroidism (PHPT) is a relatively uncommon disease and leads to increased calcium levels. Ionized calcium, known as clotting Factor IV, may lead to overt coagulation cascade activation, increasing the risk of venous thromboembolism (VTE). National Inpatient Sample Database was used to sample individuals with primary hyperparathyroidism, and baseline demographics and comorbidities were collected using ICD-10 codes. Patients with missing data and age less than 18 were excluded. Moreover, patients with other types of hyperparathyroidism and risk factors for VTE, such as malignancy, thrombophilia, chronic kidney and liver disease, fractures, trauma, oral contraceptive/steroid use, and organ transplant, were excluded. Greedy propensity matching using R was performed to match patients with and without primary hyperparathyroidism on age, race, gender, and 10 other comorbidities, including chronic deep venous thromboembolism. Univariate analysis pre- and post-match were performed. Binary logistic regression was performed after matching to assess whether primary hyperparathyroidism was an independent risk factor for acute VTE. A p-value of  < 0.05 was considered statistically significant. Out of 460,529 patients included in the study, 1114 (6.5%) had PHPT. Baseline comorbidities were more common in the PHPT group. On univariate analysis, patients with PHPT were more likely to have acute VTE (2.5% vs. 1.4%; p < 0.001). After 1:1 matching, PHPT patients were twice as likely to have Acute VTE. (OR: 2.1 [1.08-4.1]; p < 0.025). These findings suggest an association between PHPT and VTE, which should be further investigated to prevent the increasing incidence of VTE and its recurrence., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered., Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations., Results: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations., Conclusion: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Protein-truncating germline pathogenic variants in the N- and C-terminal exons (2, 9, and 10) of the MEN1 gene may be associated with aggressive pancreatic neuroendocrine tumors. However, the impact of these variants on parathyroid disease is poorly understood. We sought to investigate the effects of genotype and surgical approach on clinical phenotype and postoperative outcomes in patients with multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism., Methods: We identified patients with MEN1 evaluated at our institution from 1985 to 2020 and stratified them by genotype, (truncating variants in exons 2, 9, or 10, or other variants), and index surgical approach, (less-than-subtotal parathyroidectomy [

Background: The aim of this study was to analyze the prevalence of primary and secondary hyperparathyroidism in patients with primary aldosteronism (PA), and its implication on cardiovascular and metabolic outcomes., Methods: A retrospective study of patients with PA (exposed cohort, N.=44) and all hypertensive (EH) patients with adrenal lesions without PA nor other adrenal hypersecretion (non-exposed cohort, N.=41) on follow-up at our center between 2016 and 2020., Results: The mean age of patients with PA and EH was 55.1±14.13 and 66.3±10.93 (P<0.001), and 50% of PA and 39.0% of EH were women (P=0.309). At diagnosis, the prevalence of primary hyperparathyroidism in PA was of 18.2%, and all were normocalcemic hyperparathyroidism cases. Globally, no differences were found in the prevalence of primary hyperparathyroidism compared to EH (18.2% vs. 29.3%, P=0.229), but hypercalcemic primary hyperparathyroidism was significantly more prevalent in EH patients than in PA (22.0% vs. 0%, P=0.001). There were 47.7% (N.=21) cases of secondary hyperparathyroidism in patients with PA (4 due to chronic kidney disease (CKD) and vitamin D deficiency, and 17 due to vitamin D deficiency alone). The cardiometabolic profile of patients with PA and hyperparathyroidism (N.=29) was similar to of those patients without hyperparathyroidism (N.=15) at diagnosis and after a median follow-up of 3.6 years (interquartile range 1.1-5.9)., Conclusions: Although primary and secondary hyperparathyroidism are common in patients with PA, their prevalence was similar than the observed in EH patients. Primary hyperparathyroidism is usually mild in PA, appearing as normocalcemic forms. No negative implications of the hyperparathyroidism in the cardiometabolic profile of PA were observed.

Context: Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia, yet long-term (5- and 10-year) recurrence rates after curative surgery have been unclear., Objective: To perform the first systematic review and meta-analysis investigating the long-term recurrence rates of sporadic PHPT after successful parathyroidectomy., Methods: A comprehensive search of multiple databases (including PubMed, EMBASE, Cochrane, EBSCO-CINHAL, EMBASE, Ovid, Scopus, and Google Scholar) was performed from each database's inception to January 18, 2023. Observational studies reporting at least 5 years of follow-up data after surgical resection were included. Two reviewers independently screened articles for relevance. Of 5769 articles initially identified, 242 were examined in full-text review and 34 were deemed eligible for inclusion. Two authors independently performed data extraction and study appraisal, using the National Institutes of Health study quality assessment tools., Results: Of 30 658 participants, 350 patients (1.1%) experienced recurrence after resection. A meta-analysis of proportions was performed to obtain the pooled recurrence rates. The pooled estimate for overall recurrence rate was 1.56% (95% CI 0.96-2.28%; I2 = 91%). The pooled estimates for 5- and 10-year recurrence rate after resection were 0.23% (0.04-0.53%, 19 studies; I2 = 66%) and 1.03% (0.45-1.80%, 14 studies; I2 = 89%), respectively. Sensitivity analyses did not find a statistically significant difference when adjusting for study size, diagnosis, or surgical approach., Conclusion: Approximately 1.56% of sporadic PHPT patients eventually develop recurrence following parathyroidectomy. The initial diagnosis and procedure type does not influence recurrence rates. Consistent long-term follow-up is warranted to help identify recurrent disease., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Cardiovascular diseases (CVD) and metabolic disorders (MD) have retained leading positions in the structure of morbidity and mortality for many years. Primary hyperparathyroidism (PHPT) is also associated with a greater incidence of CVD and MD. The aim of the present study was to describe the prevalence and structure of CVD and MD in hospitalized patients with PHPT and to search for possible associations between these pathologies., Methods: 838 patients with a verified PHPT were included in the study. The studied cohort was divided into 2 groups according to their age at the time of admission: patients aged 18 to 49 years (group A, n = 150); patients aged 50 years and older (group B, n = 688)., Results: There were no significant differences between two groups in parameters of calcium-phosphorus metabolism. Obesity was diagnosed in 24.2% of patients in group A and in 35.9% in group B. Type 2 diabetes mellitus was more common in older patients (14.4% in group B vs. 2.6% in group A). Arterial hypertension, ischemic heart disease, chronic heart failure and brachiocephalic arteries atherosclerosis were more frequent in older patients, occurring in 79.1%, 10.8%, 8.4%, and 84% of cases respectively. The cutoff points that increased the risk of CVD detection turned out to be age above 56 years, eGFR below 92 ml/min/1.73m2, BMI above 28.3 kg/m2., Discussion: The present study demonstrated a high incidence of some CVD, as well as disorders of lipid, carbohydrate and purine metabolism in patients with PHPT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dobreva, Gorbacheva, Bibik, Eremkina, Elfimova, Salimkhanov, Kovaleva, Maganeva and Mokrysheva.)

Context: Primary hyperparathyroidism (PHPT) is associated with increased risk of morbidity and death, and vitamin D levels are a potentially confounding variable., Objective: The aim of this study was to assess morbidity and mortality associated with primary hyperparathyroidism (PHPT)., Methods: In this population-based retrospective matched cohort study, data linkage of biochemistry, hospital admissions, prescribing, imaging, pathology, and deaths was used to identify patients across the region of Tayside, Scotland, who had PHPT from 1997 to 2019. Cox proportional hazards models and hazards ratios (HR) were used to explore the relationship between exposure to PHPT and several clinical outcomes. Comparisons were made with an age- and gender-matched cohort., Results: In 11 616 people with PHPT (66.8% female), with a mean follow-up period of 8.8 years, there was an adjusted HR of death of 2.05 (95% CI, 1.97-2.13) for those exposed to PHPT. There was also an increased risk of cardiovascular disease (HR = 1.34; 95% CI, 1.24-1.45), cerebrovascular disease (HR = 1.29; 95% CI, 1.15-1.45), diabetes (HR = 1.39; 95% CI, 1.26-1.54), renal stones (HR = 3.02; 95% CI, 2.19-4.17) and osteoporosis (HR = 1.31; 95% CI, 1.16-1.49). Following adjustment for serum vitamin D concentrations (n = 2748), increased risks for death, diabetes, renal stones, and osteoporosis persisted, but not for cardiovascular or cerebrovascular disease., Conclusion: In a large population-based study, PHPT was associated with death, diabetes, renal stones, and osteoporosis, independent of serum vitamin D concentration., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Introduction: Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation., Materials and Methods: The cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/)., Results: The median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in MEN1 , CDC73 , RET genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol., Conclusion: The detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mokrysheva, Eremkina, Elfimova, Kovaleva, Miliutina, Bibik, Gorbacheva, Dobreva, Maganeva, Krupinova, Salimkhanov, Aboishava, Karaseva, Melnichenko and Dedov.)

Purpose: Previous studies have pointed to the role of parathormone (PTH) in the development of simple renal cysts. However, there is insufficient evidence related to simple renal cysts in primary hyperparathyroidism (PHPT). Therefore, this study aimed to evaluate the prevalence and risk factors associated with renal cysts in PHPT patients., Methods: In this retrospective study, we included 235 patients treated surgically for PHPT and 147 control subjects. The clinical and physical examination findings, laboratory test results, and neck and urinary system ultrasonography examination findings were evaluated. Postoperative parathyroid adenoma volume and weight were also recorded., Results: Simple renal cysts were found in 53 PHPT patients (22.6%) and in 15 control subjects (10.2%) (p = 0.002). Kidney stones were found in 33 PHPT patients (14%) and in only seven control subjects (4.8%) (p = 0.004). The presence of PHPT and high PTH levels independently supported the development of a simple renal cyst. Advanced age was determined as a risk factor for the development of simple renal cysts, and the presence of kidney stones was an independent predictor of simple renal cysts in PHPT patients. There was no relationship between the presence of simple renal cysts and the volume and weight of parathyroid adenoma., Conclusion: A diagnosis of PHPT, high PTH levels, advanced age, and kidney stones are independent risk factors for simple renal cysts in PHPT patients. These patients should be evaluated regularly for complications of renal cysts and nephrolithiasis., (© 2022. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Introduction: Quality of life (QoL) in patients with primary hyperparathyroidism (PHPT) can be negatively affected by the disease, and it is important to identify risk factors. The objectives of the present study were to analyze QoL, mood and quality of sleep in patients with PHPT and to determine the impact of socio-personal and clinical variables., Patients and Method: The study group included patients diagnosed with PHPT, and the control group was taken from general population, paired by age and gender. QoL was analyzed using the SF-36 and the PHPQoL questionnaires. The Beck-II and Pittsburg questionnaires were used to assess depression and sleep quality. Socio-personal and clinical variables were analyzed. Statistical analysis on SPSS software v.28 used the Student t-test, ANOVA, Pearson's rank correlation, Mann-Whitney test, Kruskal-Wallis test and Spearman's rank correlation. A multiple linear regression model of the QoL was constructed., Results: Sixty-five patients with PHPT were analyzed. A greater negative effect on QoL, mood and sleep quality were observed in patients with PHPT than in controls (P<0.05), with a good correlation between the various questionnaires. Several socio-personal variables had an effect on QoL and mood (P<0.05). QoL in patients with PHPT was affected by educational level, having offspring, and psychological symptoms (P<0.05)., Conclusions: Patients with PHPT had poorer QoL and greater neurocognitive disorder than the general population. Socio-personal profile should be taken into account in the clinical assessment of these patients, together with psychological symptoms., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Normocalcaemic primary hyperparathyroidism (NPHPT) is often under-recognised in clinical practice., Aim: To determine the prevalence and clinical significance of NPHPT in an unselected sample in an acute hospital setting., Methods: Patients aged >18 years who had measurement of an elevated serum parathyroid hormone (PTH ≥ 7 pmol/L) during 12 months from 1 January 2017 to 31 December 2017 were retrospectively studied. NPHPT was defined by the presence of elevated serum PTH with normal albumin-corrected serum calcium on two or more occasions after excluding secondary causes. Patients were followed up for 2 years. Relevant data were collected by review of electronic medical records., Results: Of the 2593 patients who had PTH measured during the study period, 1278 had serum PTH ≥ 7 pmol/L. Hypercalcaemic primary hyperparathyroidism (PHPT) was diagnosed in 174 patients. Secondary causes for elevated serum PTH were identified in 993 patients: 815 (chronic kidney disease - estimated glomerular filtration rate < 60 mL/min/1.73 m 2 or renal transplant), 98 (vitamin D deficiency - 25(OH)D < 50 nmol/L), 28 (gastric bypass surgery), 38 (medications), 13 (malabsorption or post-thyroidectomy) and 1 (hypercalciuria). Data were incomplete for 80 patients. The prevalence of NPHPT with and without the exclusion of hypercalciuria was 0.19% (5) and 0.39% (10) respectively. The prevalence of nephrolithiasis in NPHPT was higher than PHPT (100% vs 15% among five patients (P < 0.001) and 50% vs 15% among 10 patients (P = 0.014)). The prevalence of osteoporosis was not significantly different between NPHPT and PHPT (20% vs 45% among five patients (P = 0.389) and 30% vs 45% among 10 patients (P = 0.518))., Conclusion: These findings give further credence to the diagnosis of NPHPT as a clinical entity. Nephrolithiasis may be a greater problem than osteoporosis in NPHPT compared with PHPT. This needs prospective evaluation., (© 2021 Royal Australasian College of Physicians.)

Purpose: Primary hyperparathyroidism (PHPT) is a common endocrine disorder with increasing incidence, while epidemiologic data in Asian population has been lacking. Therefore, we aimed to identify the incidence, prognosis, and prognostic factors of PHPT patients who underwent parathyroidectomy in Korea., Methods: In this retrospective nationwide cohort, patients with PHPT were defined as those with diagnostic codes of PHPT and procedural codes for parathyroidectomy, excluding chronic renal failure or secondary hyperparathyroidism based on National Health Insurance Services database in Korea in 2002-2018. Main primary outcomes were all-cause mortality, cardiovascular, and cerebrovascular events., Results: A total of 5561 patients were diagnosed with PHPT and had parathyroidectomy. The mean age was 54.5 years, and 71.8% were women. The age-standardized incidence was 10.1/100,000 person-year in 2018, rising from 1.7/100,000 person-year in 2002. During a mean of 5.9 years, history of cardiovascular disease, mood disorder, and genitourinary stone had increased risks of mortality with hazard ratios (HRs) of 1.59 (95% confidence interval [CI] 1.10-2.29), 1.43 (CI 1.14-1.80), and 1.40 (CI 1.09-1.80), respectively. History of hypertension, cerebrovascular disease, diabetes mellitus, and mood disorder were risk factors for cardiovascular events with HRs of 1.42 (CI 1.22-1.66), 1.29 (CI 1.05-1.58), 1.22 (CI 1.07-1.40), and 1.14 (CI 1.00-1.29), respectively. Mood disorder was a significant risk factor for cerebrovascular events (HR 1.30, CI 1.11-1.52)., Conclusion: The incidence of PHPT patients who underwent parathyroidectomy has been rising in Korea as reported in other countries. Patients with complications, especially mood disorder, had increased cardiovascular and cerebrovascular events and mortality risks., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Despite access to routine laboratory evaluation, primary hyperparathyroidism (PHP) remains underdiagnosed and undertreated., Objective: To determine the consequences associated with missed diagnoses and prolonged time to diagnosis and treatment of PHP., Design, Setting, and Participants: This is a retrospective cohort study of patients older than 40 years with 2 instances of hypercalcemia during 2010 to 2020 and 3 years of follow-up. Patients were recruited from 63 health care organizations in the TriNetX Research Network. Data analysis was performed from January 2010 to September 2020., Exposures: Elevated serum calcium., Main Outcomes and Measures: Existing symptoms and diagnoses associated with PHP (osteoporosis, fractures, urolithiasis, major depressive disorder, anxiety, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, constipation, insomnia, polyuria, weakness, abdominal pain, headache, nausea, amnesia, and gallstones) compared in patients deemed high-risk and without a diagnosis and matched controls, and those who experienced times from documented hypercalcemia to diagnosis and diagnosis to treatment within or beyond 1 year., Results: There were 135 034 patients analyzed (96 554 women [72%]; 28 892 Black patients [21%] and 88 010 White patients [65%]; 3608 Hispanic patients [3%] and 98 279 non-Hispanic patients [73%]; mean [SD] age, 63 [10] years). Two groups without a documented diagnosis of PHP were identified as high risk: 20 176 patients (14.9%) with parathyroid hormone greater than or equal to 50 pg/mL and 24 905 patients (18.4%) with no parathyroid hormone level obtained or recorded explanation for hypercalcemia. High-risk patients experienced significantly increased rates of all associated symptoms and diagnoses compared with matched controls. Just 9.7% of those with hypercalcemia (13 136 patients) had a diagnosis of PHP. Compared with individuals who received a diagnosis within 1 year of hypercalcemia, those whose workup exceeded 1 year had significantly increased rates of major depressive disorder, anxiety, hypertension, gastroesophageal reflux disease, malaise or fatigue, joint pain or myalgias, polyuria, weakness, abdominal pain, and headache at 3 years. The rate of osteoporosis increased from 17.1% (628 patients) to 25.4% (935 patients) over the study period in the group with delayed diagnosis. Among those with a diagnosis, 5280 patients (40.2%) underwent parathyroidectomy. Surgery beyond 1 year of diagnosis was associated with significantly increased rates of osteoporosis and hypertension at 3 years after diagnosis compared with those treated within 1 year., Conclusions and Relevance: Many patients were at high risk for PHP without a documented diagnosis. Complications in these patients, as well as those who received a diagnosis after prolonged workup or time to treatment, resulted in patient harm. System-level interventions are necessary to ensure proper diagnosis and prompt treatment of PHP.

Context: A hypothesis-free genetic association analysis has not been reported for patients with primary hyperparathyroidism (PHPT)., Objective: We aimed to investigate genetic associations with PHPT using both genome-wide association study (GWAS) and candidate gene approaches., Methods: A cross-sectional study was conducted among patients of European White ethnicity recruited in Tayside (Scotland, UK). Electronic medical records were used to identify PHPT cases and controls, and linked to genetic biobank data. Genetic associations were performed by logistic regression models and odds ratios (ORs). The combined effect of the genotypes was researched by genetic risk score (GRS) analysis., Results: We identified 15 622 individuals for the GWAS that yielded 34 top single-nucleotide variations (formerly single-nucleotide polymorphisms), and LPAR3-rs147672681 reached genome-wide statistical significance (P = 1.2e-08). Using a more restricted PHPT definition, 8722 individuals with data on the GWAS-identified loci were found. Age- and sex-adjusted ORs for the effect alleles of SOX9-rs11656269, SLITRK5-rs185436526, and BCDIN3D-AS1-rs2045094 showed statistically significant increased risks (P < 1.5e-03). GRS analysis of 5482 individuals showed an OR of 2.51 (P = 1.6e-04), 3.78 (P = 4.0e-08), and 7.71 (P = 5.3e-17) for the second, third, and fourth quartiles, respectively, compared to the first, and there was a statistically significant linear trend across quartiles (P < 1.0e-04). Results were similar when stratifying by sex., Conclusion: Using genetic loci discovered in a GWAS of PHPT carried out in a Scottish population, this study suggests new evidence for the involvement of genetic variants at SOX9, SLITRK5, LPAR3, and BCDIN3D-AS1. It also suggests that male and female carriers of greater numbers of PHPT-risk alleles both have a statistically significant increased risk of PHPT., Competing Interests: Conflict of Interest: The authors declare that there are no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

In this narrative review, we present data gathered over four decades (1980-2020) on the epidemiology, pathophysiology and genetics of primary hyperparathyroidism (PHPT). PHPT is typically a disease of postmenopausal women, but its prevalence and incidence vary globally and depend on a number of factors, the most important being the availability to measure serum calcium and parathyroid hormone levels for screening. In the Western world, the change in presentation to asymptomatic PHPT is likely to occur, over time also, in Eastern regions. The selection of the population to be screened will, of course, affect the epidemiological data (ie, general practice as opposed to tertiary center). Parathyroid hormone has a pivotal role in regulating calcium homeostasis; small changes in extracellular Ca++ concentrations are detected by parathyroid cells, which express calcium-sensing receptors (CaSRs). Clonally dysregulated overgrowth of one or more parathyroid glands together with reduced expression of CaSRs is the most important pathophysiologic basis of PHPT. The spectrum of skeletal disease reflects different degrees of dysregulated bone remodeling. Intestinal calcium hyperabsorption together with increased bone resorption lead to increased filtered load of calcium that, in addition to other metabolic factors, predispose to the appearance of calcium-containing kidney stones. A genetic basis of PHPT can be identified in about 10% of all cases. These may occur as a part of multiple endocrine neoplasia syndromes (MEN1-MEN4), or the hyperparathyroidism jaw-tumor syndrome, or it may be caused by nonsyndromic isolated endocrinopathy, such as familial isolated PHPT and neonatal severe hyperparathyroidism. DNA testing may have value in: confirming the clinical diagnosis in a proband; eg, by distinguishing PHPT from familial hypocalciuric hypercalcemia (FHH). Mutation-specific carrier testing can be performed on a proband's relatives and identify where the proband is a mutation carrier, ruling out phenocopies that may confound the diagnosis; and potentially prevention via prenatal/preimplantation diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Objective: The indication of surgery in primary hyperparathyroidism has been controversial, as many patients experience mild disease. The primary aim was to evaluate fracture incidence in a contemporary population-based cohort of patients having surgery for primary hyperparathyroidism. The secondary aim was to investigate whether preoperative serum calcium, adenoma weight or multiglandular disease influence fracture incidence., Design: A retrospective cohort study with population controls. Primary outcomes, defined by discharge diagnoses and prescriptions, were any fracture and fragility fracture, secondary outcomes were multiple fractures anytime and osteoporosis. Subjects were followed 10 years pre- and up to 10 years postoperatively (or 31 December 2015). Multiple events per subject were allowed. Fracture incidence rate ratios (IRRs) for patients pre- and postoperatively were tabulated and evaluated with mixed-effects Poisson regression. Secondary outcomes were evaluated using conditional logistic regression., Patients: A Swedish nationwide cohort of patients having surgery for primary hyperparathyroidism (n = 5009) from the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery between 2003 and 2013 was matched with population controls (n = 14,983). Data were cross-linked with Statistics Sweden and the National Board of Health and Welfare., Measurements: Preoperative serum calcium and adenoma weight at pathological examination., Results: Patients had an increased incidence rate of any fracture preoperatively, IRR 1.27 (95% confidence interval: 1.11-1.46), highest in the last year before surgery. Fracture incidence was not increased postoperatively. Serum calcium, adenoma weight and multiglandular disease were not associated with fracture incidence., Conclusions: Fracture incidence is higher in patients with primary hyperparathyroidism but is normalized after surgery., (© 2022 The Authors. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background & Aims: Primary hyperparathyroidism(PHPT) has been evolving into a milder asymptomatic disease. No study has assessed the association between famine exposure and such a shift. We aim to explore the effects of China's Great Famine exposure on the changing pattern of PHPT phenotypes., Methods: 750 PHPT patients diagnosed from 2000 to 2019 were studied. The clinical presentations were compared between them in recent 10 years (2010-2019) and previous 10 years (2000-2009). Participants were then categorized into fetal, childhood, adolescent, adult exposure, and unexposed groups. Logistic regression was used to estimate the odds ratios (ORs) and confidence intervals (CIs) of famine exposure as factors contributing to the changes in the clinical presentations of PHPT., Results: Serum levels of PTH, albumin-corrected Ca, tumor size, eGFR, BMDs (all P<0.001), and clinical symptoms became milder in recent 10 years. Famine exposure (72.6% vs 58.4%, P<0.001), especially the adult exposure (18.8% vs 4.1%, P<0.001)was significant less in recent 10 years. The ORs (95%CIs) of having upper 3 rd tertile PTH were 2.79(1.34,5.8), 2.07(1.04,4.11), 3.10(1.15,8.38) and 8.85(2.56,30.56) for patients with fetal, childhood, adolescent and adult famine exposure, respectively. The ORs (95%CIs) of upper 3 rd tertile albumin-corrected Ca and upper 3 rd tertile of tumor size was 4.78(1.39, 16.38) and 4.07(1.12,14.84) for participants with adult famine exposure, respectively. All these associations were independent of age, sex, disease duration and other confounders., Conclusions: The clinical manifestations of PHPT in China continue to be milder. Exposure to famine is associated with PHPT. Less famine exposure might be responsible for the mile form of PHPT in recent years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Yang, Zhu, He, Zhao, Zhou, Su, Zhao, Sun, Tao and Liu.)

Context: Primary hyperparathyroidism (PHPT) is associated with an increased risk of kidney stones. Few studies account for PHPT severity or stone risk when comparing stone events after parathyroidectomy vs nonoperative management., Objective: Compare the incidence of kidney stone events in PHPT patients treated with parathyroidectomy vs nonoperative management., Design: Longitudinal cohort study with propensity score inverse probability weighting and multivariable Cox proportional hazards regression., Setting: Veterans Health Administration integrated health care system., Patients: A total of 44 978 patients with > 2 years follow-up after PHPT diagnosis (2000-2018); 5244 patients (11.7%) were treated with parathyroidectomy., Main Outcomes Measure: Clinically significant kidney stone event., Results: The cohort had a mean age of 66.0 years, was 87.8% male, and 66.4% White. Patients treated with parathyroidectomy had higher mean serum calcium (11.2 vs 10.8mg/dL) and were more likely to have a history of kidney stone events. Among patients with baseline history of kidney stones, the unadjusted incidence of ≥ 1 kidney stone event was 30.5% in patients managed with parathyroidectomy (mean follow-up, 5.6 years) compared with 18.0% in those managed nonoperatively (mean follow-up, 5.0 years). Patients treated with parathyroidectomy had a higher adjusted hazard of recurrent kidney stone events (hazard ratio [HR], 1.98; 95% CI, 1.56-2.51); however, this association declined over time (parathyroidectomy × time: HR, 0.80; 95% CI, 0.73-0.87)., Conclusion: In this predominantly male cohort with PHPT, patients treated with parathyroidectomy continued to be at higher risk of kidney stone events in the immediate years after treatment than patients managed nonoperatively, although the adjusted risk of stone events declined with time, suggesting a benefit to surgical treatment., (Published by Oxford University Press on behalf of the Endocrine Society 2022.)

Purpose: Primary hyperparathyroidism (PHPT) is a common cause of hypercalcemia and remains understudied within the Arabian population. The present study, the largest of its kind within the Gulf Cooperation Council (GCC) countries, aims to determine the demographics and clinical presentation of PHPT in Saudi Arabia., Methods: In this multi-center retrospective study involving three tertiary hospitals in different geographic locations of Saudi Arabia namely, Riyadh, Al Ahsa and Jeddah, a total of 205 out of 243 confirmed PHPT cases aged 16 to 93 years old were included (N = 96 from Riyadh; N = 59 from Al Ahsa and N = 50 from Jeddah). Demographics, clinical manifestations and surgical outcomes were recorded as well as laboratory and radiologic investigations including serum parathyroid hormone (PTH), 25(OH)D, adjusted calcium, estimated glomerular filtration rate (eGFR) and nuclear scan outcome., Results: PHPT cases appeared to increase over time when compared to other local studies published so far, with 12.8 cases per 100,000 hospital population. Females outnumber males (3:1) with 86% seen as out-patients. The average age was 59.8 ± 15.5 years. Abnormal PTH scan was seen in 171 patients (83.4%). Kidney stones was the most common renal manifestation (32 cases, 15.6%) and osteoporosis was the most common skeletal manifestation (67 cases, 32.7%). Al Ahsa had the highest prevalence of multiple comorbidities at 54% and the highest prevalence of obesity as a single comorbidity (17%) compared to other regions (p < 0.05). Jeddah recorded the highest prevalence of osteoporosis with bone and joint pains (30%) (p < 0.05)., Conclusion: Comparison of present data with previous local studies suggest an increasing trend in PHPT cases in Saudi Arabia. Regional variations in the clinical presentation of PHPT were observed and warrant further investigation., (© 2022. The Author(s).)

Background: Primary hyperparathyroidism (PHPT) is often accompanied by neuropsychiatric symptoms. This study aimed to map out psychiatric comorbidity as reflected by medical treatment for psychiatric symptoms., Methods: A retrospective case-control analysis and a prospective cohort analysis of psychotropic drug utilization before and after PTX. A total of 8279 PHPT patients treated with parathyroidectomy in Sweden between July 1, 2008 and December 31, 2017 compared to a matched control cohort from the total population (n = 82,790). Information on filled prescriptions was collected from the Swedish Prescribed Drug Register (SDR). Socioeconomic data and diagnoses were added by linkage to national patient and population registers. Regression analyses were used to calculate relative drug utilization (OR) within 3 years prior to PTX and relative incidence of drug treatment (RR) within 3 years postoperatively., Results: Utilization of antidepressant, anxiolytic and sleep medication was more comprehensive in PHPT patients compared with the controls prior to PTX. The most common were benzodiazepines [OR 1.40 (95% CI: 1.31-1.50)] and selective serotonin reuptake inhibitors [SSRI; OR 1.38 (95% CI: 1.30-1.47)]. Postoperatively, the excess prescription rate for anxiolytic benzodiazepines decreased within three years from a 30 to 19% excess and for benzodiazepines for sleep from 31 to 14%. No corresponding decrease in excess prescription rate was observed for SSRI., Conclusion: PHPT is associated with increased utilization of antidepressive medications and benzodiazepines before PTX. This study implies that psychiatric symptoms should be considered in PHPT patients and continuous medication should be reevaluated after PTX., (© 2022. The Author(s).)

Importance: Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials., Objective: To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes., Design, Setting, and Participants: This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022., Main Outcomes and Measures: The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs)., Results: A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65)., Conclusions and Relevance: Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.

Context: Primary hyperparathyroidism (PHPT) is associated with subclinical cardiovascular disease, but data regarding cardiac conduction abnormalities are limited., Objective and Design: Retrospective cross-sectional comparison of cardiac conduction in patients with PHPT or thyroid disease (TD)., Participants and Setting: Patients ≥40 years old who underwent parathyroidectomy or thyroidectomy at a single tertiary institution from 2013 to 2018., Methods and Outcomes: Demographics and preoperative electrocardiogram (EKG) parameters were compared using the Mann-Whitney U, chi-square test, and linear regression., Results: A total of 1242 patients were included: 49.8% PHPT (n = 619) and 50.2% TD (n = 623). Median age was 60.5 years [interquartile range (IQR) 53.6-67.9]. Compared to controls, PHPT patients had higher median serum calcium [10.7 mg/dL (IQR 10.4-11.1) vs 9.5 mg/dL (IQR 9.3-9.8), P < 0.001] as expected, as well as, a higher prevalence of hyperlipidemia (49% vs 36%, P < 0.001) and hypertension (50.1% vs 42.2%, P < 0.01). Based on EKG, there was no difference in PR interval or the prevalence of arrhythmia, atrioventricular block, ST segment/T wave changes, premature ventricular complexes, right bundle branch block, or left bundle branch block after adjusting for covariates. The PHPT group had a lower mean corrected QT interval (414 ± 24) ms vs 422 ± 24 ms, P < 0.01), adjusted for covariates. Serum calcium predicted QTc independently of age, sex, and other covariates., Conclusions: In the largest study to date, PHPT patients had shorter QTc intervals compared to TD controls but no increased prevalence of arrhythmia based on preoperative EKG., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Primary hyperparathyroidism (HPT) is commonly underdiagnosed and undertreated. Joint pain is a nonspecific symptom associated with osteoarthritis or primary HPT. We hypothesize that patients treated for osteoarthritis are underdiagnosed with primary HPT., Methods: Adult patients diagnosed with hip/knee osteoarthritis at the Medical College of Wisconsin from January 2000 to October 2020 were queried. Patients with a calcium level drawn within 1 year of diagnosis of osteoarthritis were included. Patients who had undergone prior parathyroidectomy were excluded. Patients were stratified by serum calcium level, HPT diagnosis, and PTH level. Arthroplasty rates were compared between groups., Results: Of 54,788 patients, 9,967 patients (18.2%) had a high serum calcium level, of whom 1,089 (10.9%) had a diagnosis of HPT. Only 76 (7.0%) patients with HPT underwent parathyroidectomy, 208 (19.1%) underwent knee/hip arthroplasty, and 14 (1.3%) underwent both. Arthroplasty was performed in 1,793 patients without evaluation and/or definitive treatment for HPT. There were higher rates of arthroplasty performed in patients with a high serum calcium level compared with those without (21.2% vs 17.4%, P < .001)., Conclusion: Patients with high serum calcium levels were more likely to undergo arthroplasty than those with normocalcemia. Hypercalcemia in the setting of hip or knee osteoarthritis should prompt a full evaluation for primary HPT., (Published by Elsevier Inc.)

Background & Objectives: Primary hyperparathyroidism (PHPT) is a common endocrine disorder caused by the elevated secretion of the parathormone (PTH). The aim of this study was to evaluate the haematological manifestations of PHPT in patients with normal renal functions who were treated surgically for parathyroid adenomas., Methods: In this retrospective cross-sectional study, 134 patients with normal renal functions who underwent parathyroidectomies for PHPT were included. The haematological manifestations were evaluated in the total study cohort and in the two groups of different calcium (Ca) levels (Group 1 ≤11.2 mg/dl and Group 2 >11.2 mg/dl)., Results: The overall prevalence of anaemia, leucopenia and thrombocytopenia was 20.1, 6.7 and 6.0 per cent, respectively. Normocytic anaemia was present in 19 (14.2%) patients. There were no significant differences in the prevalence of anaemia, leucopenia and thrombocytopenia between the two groups. There were no correlations between the PTH levels and the leukocyte, haemoglobin or platelet values. Six to 12 months after the parathyroidectomy (PTX), 35.7 per cent of the patients with anaemia, 85.7 per cent of the patients with leucopenia and 100 per cent of the patients with thrombocytopenia had recovered., Interpretation & Conclusions: In the present study, anaemia was seen with a variable frequency in PHPT, but there was no relationship between anaemia and high PTH or Ca levels. The development of anaemia can be seen regardless of the PTH levels in PHPT patients with normal renal functions. High-resolution rates after PTX indicate a possible association between PHPT and thrombocytopenia or leucopenia, although their prevalence is low in PHPT.

Objective: To describe the prevalence and compare the clinicobiochemical profile of patients with primary hyperparathyroidism (PHPT) with and without type 2 diabetes mellitus (T2DM)., Methods: We conducted a retrospective observational study wherein the details of patients with PHPT with T2DM (PHPT-T2DM) and without T2DM were retrieved from the Indian PHPT Registry (www.indianphptregistry.com) between 2005 and 2019. We compared the clinical, biochemical, and postoperative findings of patients with PHPT-T2DM with age-, sex-, and body mass index-matched patients with PHPT without T2DM (in 1:2 ratio)., Results: Of the 464 patients with PHPT, 54 (11.6%) had T2DM. We observed an increase in the prevalence of PHPT-T2DM cases over time; only 7 (7.1%) of the total patients with PHPT had T2DM between 2005 and 2009 that increased to 31 (12.8%) in the last half decade (2015-2019). Patients with PHPT-T2DM had a significantly lower prevalence of nephrolithiasis (18.5% vs 36.1%, respectively; P = .03) and a higher prevalence of pancreatitis (22.2% vs 5.6%, respectively; P = .007) than those without T2DM. Furthermore, intact parathyroid hormone (203 pg/mL [139.8-437.3 pg/mL] vs 285 pg/mL [166-692 pg/mL], respectively; P = .04) and serum creatinine (0.90 mg/dL [0.67-1.25 mg/dL] vs 1.10 mg/dL [0.73-1.68 mg/dL], respectively; P = .03) levels were significantly lower in patients with PHPT-T2DM than those without T2DM. Also, tumor weight tended to be lower in patients with PHPT-T2DM than in the non-T2DM counterparts (1.05 g [0.5-2.93 g] vs 2.16 g [0.81-7.0 g], respectively; P = .06)., Conclusion: The prevalence of T2DM in Asian Indians with PHPT is 11.6%. Patients with PHPT-T2DM are characterized by a higher prevalence of pancreatitis, a lower prevalence of nephrolithiasis, and lower levels of intact parathyroid hormone/creatinine. Part of the clinical picture can possibly be explained by early detection of PHPT in patients with T2DM consequent to more frequent screening., (Copyright © 2021. Published by Elsevier Inc.)

Background: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized., Methods: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age., Results: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel., Conclusion: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Preventing cervical reoperations is important-especially after parathyroidectomy. We sought to examine early predictors of recurrence of primary hyperparathyroidism after surgical cure., Methods: Adult patients with sporadic primary hyperparathyroidism treated with parathyroidectomy between September 1, 1997, and September 1, 2019, with confirmed eucalcemia at 6 months postoperatively were identified. Recurrence was defined as hypercalcemia (>10.2 mg/dL) with an elevated or nonsuppressed parathyroid hormone level on subsequent follow-up., Results: Parathyroidectomy was performed in 522 patients (median age, 62.1 years, 77% female) with the majority undergoing planned minimally invasive parathyroidectomy (85.4%, n = 446). After a median follow-up of 30.9 months, 13 patients (2.5%) recurred (median time to recurrence 50.2 months, interquartile range 27.9-66.5), all of whom underwent planned minimally invasive parathyroidectomy (n = 13/446, 2.9%). Recurrence was more common in those with higher (but still normal) 6-month calcium (10.1 vs 9.3 mg/dL, P < .001) or parathyroid hormone values (64 vs 46 pg/mL, P < .01). Multivariate analysis revealed that age >66.5 years, calcium ≥9.8mg/dL and parathyroid hormone ≥80 pg/mL at 6 months were associated with increased risk of recurrence. In addition, the presence of at least 1 preoperative imaging study that conflicted with intraoperative findings among minimally invasive parathyroidectomy patients (n = 446) was associated with increased risk of recurrence (hazard ratio 4.93, 95% confidence interval 1.25-16.53, P = .016)., Conclusion: Recurrence of sporadic primary hyperparathyroidism after initial surgical cure in the era of minimally invasive parathyroidectomy is 2.5%. Identification of those at risk for recurrence using 6-month serum calcium ≥9.8 mg/dL, parathyroid hormone ≥80 pg/mL, and/or potentially conflicting localization studies may inform surveillance strategies., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Primary hyperparathyroidism (pHPT) caused by a single benign parathyroid adenoma is a common endocrine disorder that is affected by regional differences. Living in different geographical regions reveals differences in the laboratory results and pathological findings, but studies on this subject are not sufficient. The article focuses on biochemical and pathological effects of geographical differences in parathyroid adenoma. In addition, the present study seeks to elaborate on treatment methods and effectiveness of screening in geographical area of Bulgaria and Turkey., Method: In this prospective study, 159 patients were included from 16 centres. Demographic characteristics, symptoms, biochemical markers and pathologic characteristics were analysed and compared between 8 different regions., Results: Patients from Turkish Black Sea had the highest median serum calcium (Ca) level, whereas patients from Eastern Turkey had the lowest median serum phosphorus (P) level. On the other hand, there was no significant difference between Ca, parathormone (PTH) and P levels according to regions. Patients from Eastern Turkey had the highest adenoma weight, while patients from Bulgaria had the lowest adenoma weight. The weight of adenoma showed statistically significant differences between regions (p < 0.001). There was a correlation between adenoma weight and serum PTH level (p = 0.05) and Ca level (p = 0.035)., Conclusion: This study has provided a deeper insight into the effect of the regional differences upon clinicopathological changing and biochemical values of pHTP patients with adenoma. Awareness of regional differences will assist in biochemical screening and treatment of this patient group., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests. Availability of data and material (data transparency):, (Copyright © 2021. Published by Elsevier Taiwan LLC.)

Background: The incidence of adverse perioperative cardiac complications after parathyroidectomy has not been well described. This study aimed to evaluate the incidence of perioperative chest pain and cardiac complications after parathyroidectomy and to evaluate risk factors that may identify patients who are more likely to benefit from a cardiac workup., Methods: We performed a retrospective study of all patients undergoing parathyroidectomy for primary hyperparathyroidism by a single endocrine surgeon at a tertiary endocrine centre between 2011 and 2018. Patient demographics, clinicopathologic variables, operative and postoperative details (reported chest pain, performance of a cardiac workup and new postoperative cardiac diagnosis) were reviewed. Patients with chest pain were compared to those without chest pain using the Fisher exact test and Student t test., Results: Fourteen of 295 patients (4.7%) reported chest pain in the immediate postoperative period. Most patients were investigated with a 12-lead electrocardiogram and troponin ( n = 12/14), yet none were diagnosed with a cardiac event. When comparing patients with and without chest pain, there was no significant difference in age, gender, body mass index, presence of cardiovascular risk factors, American Society of Anesthesiologists score or length of surgery., Conclusion: Postoperative chest pain after parathyroidectomy is not an uncommon event and leads to a cardiac workup in most cases; however, the risk of significant postoperative cardiac events is minimal. In the "choosing wisely" era, one should evaluate each patient's pretest probability of such events and avoid extensive workup in low-risk patients to avoid unnecessary costs to the health care system., Competing Interests: Competing interests: None declared., (© 2021 CMA Joule Inc. or its licensors.)

Secondary hyperparathyroidism (SHPT) is characterized by excessive serum parathyroid hormone levels in response to decreasing kidney function, and tertiary hyperparathyroidism (THPT) is often the result of a long-standing SHPT. To date, several genes have been associated with the pathogenesis of primary hyperparathyroidism (PHPT). However, the molecular genetic mechanisms of uremic hyperparathyroidism (HPT) remain uncharacterized. To elucidate the differences in genetic alterations between PHPT and SHPT/THPT, the targeted next-generation sequencing of genes associated with HPT was performed using DNA extracted from parathyroid tissues. As a result, 26 variants in 19 PHPT or SHPT/THPT appeared as candidate pathogenic mutations, which corresponded to 9 (35%) nonsense, 8 (31%) frameshift, 6 (23%) missense, and 3 (11%) splice site mutations. The MEN1 (23%, 6/26), ASXL3 (15%, 4/26), EZH2 (12%, 3/26), and MTOR (8%, 2/26) genes were frequently mutated. Sixteen of 25 patients with PHPT (64%) had one or more mutations, whereas 3 (21%) of 21 patients with SHPT/THPT had only 1 mutation (p = 0.001). Sixteen of 28 patients (57%) with parathyroid adenoma (PA) had one or more mutations, whereas 3 of 18 patients (17%) with parathyroid hyperplasia (PH) had just one mutation (p = 0.003). Known driver mutations associated with parathyroid tumorigenesis such as CCND1/PRAD1, CDC73/HRPT2, and MEN1 were identified only in PA (44%, 7/16 with mutations). Our results suggest that molecular genetic abnormalities in SHPT/THPT are distinct from those in PHPT. These findings may help in analyzing the molecular pathogenesis underlying uremic HPT development., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Primary hyperparathyroidism is a common endocrine disorder. It used to present as a highly symptomatic disease before the advent of the multichannel autoanalyzer, now usually presenting as mild asymptomatic hypercalcemia. A newer presentation has been increasingly identified in the past two decades, normocalcemic primary hyperparathyroidism, presenting with elevated parathyroid hormone concentrations and consistently normal serum calcium. These patients are usually symptomatic, with parathyroid hormone levels measured in the evaluation for kidney stones or osteoporosis. It is important to exclude causes of secondary hyperparathyroidism. This review will focus on the evaluation and management of elevated parathyroid hormone levels in normocalcemic patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The combination of primary hyperparathyroidism (PHPT) with anemia was first described in 1931. It remains unclear whether PHPT is the direct cause of anemia, or it develops due to PHPT's complications. The frequency of PHPT--associated anemia in the Russian population is unknown., Aim: To assess the prevalence of anemia in patients with PHPT admitted to the Department of Parathyroid Glands Pathology in the Endocrinology Research Centre from January 2017 to August 2020., Materials and Methods: The study included patients with PHPT over 18 years old. A single-center observational one-stage one-sample uncontrolled study was carried out. We analyzed laboratory and instrumental data obtained during inpatient examination in accordance with the standards of medical care. Statistical analysis was performed using Statistica 13 (StatSoft, USA) and SPSS (IBM, USA) software packages., Results: The study included 327 patients with PHPT, 28 (9%) men and 299 (91%) women. The median age was 59 years [51; 66]. 26 patients (8%) with anemia were identified. Statistically significant differences between patients with and without anemia were found only in the GFR. Comparison of patients with and without anemia didn't reveal any significant differences in the incidence of PHPT's complications.Significant differences in serum hemoglobin concentration and average hemoglobin concentration in erythrocytes were revealed between patients with and without vertebrae fractures. In the group of patients without compression fractures these parameters were higher.In the subgroup of patients with total calcium concentration above 3 mmol/L and PTH above 3 normal values, the incidence of anemia reached 21% (95% CI: 10%; 35%). Within this group we revealed tendencies to higher levels of PTH, ionized calcium and osteocalcin in patients with anemia., Conclusion: In general, there was no correlation between hypercalcemia, the degree of PTH elevation and the presence of anemia in patients with PHPT. However, in the subgroup of patients with severe hypercalcemia, there was a relationship between the concentration of PTH, ionized calcium and the presence of anemia. In patients with PHPT and vertebral fractures, significantly lower concentrations of blood hemoglobin and hemoglobin in erythrocytes were observed.

Objective: To describe the details of widely invasive parathyroid carcinoma (WIPC) patients admitted in the Endocrinology department of our institute during the last 22 years and to compare their clinical, biochemical, and hormonal profile with minimally invasive parathyroid carcinoma (MIPC) and sporadic parathyroid adenoma patients., Methods: This is a retrospective analysis of data from the Indian primary hyperparathyroidism registry., Results: Of the 547 primary hyperparathyroidism patients in the registry, 5 (2 men and 3 women) had WIPC (0.9%) and 7 (1 man and 6 women) had MIPC (1.3%), with median ages of 45 (interquartile range, 41-51) years and 47 (interquartile range, 28-48) years, respectively. Among the patients with WIPC, renal manifestations were present in 5 patients, skeletal manifestations in 4 patients, and palpable neck masses in 4 patients. Three patients had distant metastases and 2 had cervical lymph node involvement. All 5 patients had surgical resection of their cancers, with persistent disease in 4 patients, but all patients died within 2 years after surgery. One patient with MIPC had a palpable parathyroid nodule; none had lymph nodal or distant metastases. None of the patients with MIPC died during the median follow-up of 18 (interquartile range, 12-18) months. Patients with WIPC had significantly higher serum calcium level compared with sporadic parathyroid adenoma patients with skeletal and renal manifestations., Conclusion: Accurate histopathologic classification of parathyroid carcinoma is important as WIPC is associated with a more aggressive clinical course and a higher risk of mortality than MIPC., (Copyright © 2021 AACE. Published by Elsevier Inc. All rights reserved.)

Objective: Patients with primary hyperparathyroidism (PHPT) are at increased risk of kidney stones. Guidelines recommend parathyroidectomy in patients with PHPT with a history of stone disease. This study aimed to compare the 5-year incidence of clinically significant kidney stone events in patients with PHPT treated with parathyroidectomy versus nonoperative management., Methods: We performed a longitudinal cohort study of patients with PHPT in a national commercial insurance claims database (2006-2019). Propensity score inverse probability weighting-adjusted multivariable regression models were calculated., Results: We identified 7623 patients aged ≥35 years old with continuous enrollment >1 year before and >5 years after PHPT diagnosis. A total of 2933 patients (38.5%) were treated with parathyroidectomy. The cohort had a mean age of 66.5 years, 5953 (78.1%) were female, and 5520 (72.4%) were White. Over 5 years, the unadjusted incidence of ≥1 kidney stone event was higher in patients who were managed with parathyroidectomy compared with those who were managed nonoperatively overall (5.4% vs 4.1%, respectively) and among those with a history of kidney stones at PHPT diagnosis (17.9% vs 16.4%, respectively). On multivariable analysis, parathyroidectomy was associated with no statistically significant difference in the odds of a 5-year kidney stone event among patients with a history of kidney stones (odds ratio, 1.03; 95% CI, 0.71-1.50) or those without a history of kidney stones (odds ratio, 1.16; 95% CI, 0.84-1.60)., Conclusion: Based on this claim analysis, there was no difference in the odds of 5-year kidney stone events in patients with PHPT who were treated with parathyroidectomy versus nonoperative management. Time horizon for benefit should be considered when making treatment decisions for PHPT based on the risk of kidney stone events., (Published by Elsevier Inc.)

Background: Primary hyperparathyroidism (PHPT) caused by double adenoma may carry a higher risk of failure to cure. We compared outcomes in single adenoma (SA), double adenoma (DA) and four-gland hyperplasia (HP)., Methods: Patients undergoing initial parathyroidectomy for PHPT were categorized by diagnosis. The primary outcome was persistent/recurrent disease postoperatively., Results: Of 3408 patients, 81.3% had SA, 9.5% had DA, and 9.3% had HP. Rates of persistence/recurrence were 2.9%, 5.3%, and 4.5% in SA, DA, and HP, respectively (p = 0.281). Patients with persistence/recurrence had higher preoperative calcium (11.0 vs 10.7 mg/dl, p = 0.028) and PTH (96 vs 77 pg/ml, p = 0.015), and lower rates of IOPTH normalization (77% vs 96%, p < 0.001). On multivariable analysis, DA was associated with increased risk of persistent/recurrent disease (OR 3.0, p = 0.017)., Conclusions: Most patients with DA are cured with removal of two glands, but approximately 5% experience disease persistence/recurrence. Low-normal final IOPTH was associated with lower risk of persistent/recurrent disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/aim: Primary hyperparathyroidism (PHPT) is a disease that is diagnosed more frequently and generally in the asymptomatic period, with widely available biochemical tests. Evidence suggesting an association between PHPT and malignancy risk is increasing. Clarification of this association will be useful in PHPT for malignancy screening and management of patients with PHPT. In this study, we aimed to investigate the frequency of cancer in PHPT patients., Materials and Methods: A total of 775 PHPT patients were included in the retrospective study. Demographic, clinical and laboratory data of the patients were evaluated retrospectively., Results: Malignancy was detected in 128 (16.50%) of 775 PHPT patients (female/male: 625/150). The mean age at diagnosis of PHPT was 57.99 ± 10.86 years, and the mean age at diagnosis of malignancy was 57.46 ± 11.17 years. Of the 128 patients with malignancy, 53 (41.40%) were diagnosed in the same year as PHPT. In terms of malignancy types, 51 (6.50%) of 775 PHPT patients had thyroid cancer. Thyroid cancer was followed by breast cancer (2.30%) and stomach cancer (1%) in order of frequency., Conclusion: We think that PHPT patients should be examined more carefully in terms of cancer risk, especially thyroid cancer. More comprehensive studies are needed to clarify the relationship between PHPT and cancer., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: The occurrence of hypomagnesemia in patients with primary hyperparathyroidism (PHPT) has been noted previously; however, the association of hypomagnesemia and severity of primary hyperparathyroidism remains unknown. The present study aimed to evaluate the association of hypomagnesemia with biochemical and clinical manifestations in patients with PHPT., Methods: This was a retrospective study conducted at a tertiary hospital. We obtained data from 307 patients with PHPT from January 2010 through August 2020. Data on demographics, history, laboratory findings, bone densitometry findings, and clinical presentation and complications were collected and were compared in normal magnesium group vs hypomagnesemia group., Results: Among the 307 patients with PHPT included in our study, 77 patients (33/102 [32.4%] males and 44/205 [21.5%] females) had hypomagnesemia. Mean hemoglobin levels in the hypomagnesemia group were significantly lower than those in the normal magnesium group in both males and females. In contrast, patients with hypomagnesemia had a higher mean serum calcium and parathyroid hormone than individuals with normal magnesium. The typical symptoms of PHPT, such as nephrolithiasis, bone pain/fractures, polyuria, or polydipsia, were more common in the hypomagnesemia group. In addition, patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis. Even after adjusting for potential confounders, including age, sex, body mass index, estimated glomerular filtration rate, and parathyroid hormone levels, these associations remained essentially unchanged., Conclusion: Biochemical and clinical evidence indicates that patients with PHPT with hypomagnesemia have more severe hyperparathyroidism than those without hypomagnesemia. In addition, PHPT patients with hypomagnesemia had a higher prevalence of osteoporosis, anemia, and hypercalcemic crisis., (© 2021. The Author(s).)

Background: Hyperparathyroidism (HPT) occurs in about 1% of the general population. Previous studies have suggested that the incidence is higher in those patients with thyroid disease who are undergoing thyroid surgery. The study purpose was to examine the incidence of concomitant HPT in patients already undergoing a thyroid procedure and to identify risk factors., Materials and Methods: A prospective database of all patients who had thyroidectomy by the endocrine surgery team was reviewed between August 2012 and April 2020. Per institutional protocol, all patients having thyroid surgery were screened for concomitant hyperparathyroidism. ANOVA/T-Test and Chi-square were conducted to compare those with and without hyperparathyroidism., Results: The median age was 43 and 79% were female. Of the 481 patients undergoing thyroidectomy, 31 (6%) had HPT. The mean preoperative calcium and parathyroid hormone levels were 10 ± 0 mg/dL and 67 ± 5 pg/mL, respectively. When comparing the groups, patients with concomitant HPT were older (53 ± 4 versus 42 ± 1 y, P = 0.005). African American race was a significant risk factor for concomitant HPT. While African Americans represented only 29% of those undergoing surgery, 58% of those with concomitant HPT were African American (P = 0.007)., Conclusion: In patients having thyroid surgery, concomitant HPT was present in 6% of the population, higher than estimated general population prevalence. While we understand that primary HPT incidence increases with age, to our knowledge, this is the first report to document that African Americans are at a higher risk for concomitant HPT with thyroid disease. Thus, routine screening for hyperparathyroidism in patients undergoing thyroid surgery, especially in vulnerable populations, such as the older and African American population, is beneficial., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To present the data on primary hyperparathyroidism (PHPT) in pregnancy from India obtained from a large database maintained over 15 years., Methods: We retrieved data of all women with gestational PHPT from the Indian PHPT registry between July 2005 and January 2020, and compared their clinical, biochemical, and other characteristics with age-matched non-pregnant women with PHPT., Results: Out of 386 women, eight had gestational PHPT (2.1%). The common presenting manifestations were acute pancreatitis (50%) and renal stone disease (50%); two were asymptomatic. Five women (62.5%) had a history of prior miscarriages. Seven patients (88%) had preeclampsia during the present gestation. Serum calcium and intact parathyroid hormone (iPTH) were not statistically different from the age-matched non-pregnant PHPT group. Six patients with mild-to-moderate hypercalcemia were medically managed with hydration with/without cinacalcet while one patient underwent percutaneous ethanol ablation of the parathyroid adenoma; none underwent surgery during pregnancy. Mean serum calcium maintained from treatment initiation till delivery was 10.5 ± 0.4 mg/dl. One patient had spontaneous preterm delivery at 36 weeks; the remaining patients had normal vaginal delivery at term. None had severe preeclampsia/eclampsia. Fetal outcomes included low birth weight in three newborns (37.5%); two of them had hypocalcemic seizures., Conclusion: The prevalence of gestational PHPT was 2.1% in this largest Indian PHPT cohort, which is higher than that reported from the West (< 1%). Gestational PHPT can lead to preeclampsia and miscarriage. Pregnant PHPT patients with mild-to-moderate hypercalcemia can be managed with hydration/cinacalcet; however, long-term safety data and large-scale randomized controlled trials are required.

Objective: Primary hyperparathyroidism (PHPT) is a common endocrine disorder in women which becomes more prevalent after menopause. In this study, we compared the demographic, clinical, and biochemical variables between premenopausal (pre-M) and postmenopausal (post-M) women with PHPT., Methods: A retrospective analysis (from 2005 to 2019) of enrolled women PHPT patients from an online Indian PHPT registry., Results: Of the women with PHPT, 232 and 122 were pre-M and post-M, respectively. The number of post-M PHPT cases registered had a 3.3-fold increase in 2015-2019 from 2005-2009 compared with only a 2.5-fold increase in pre-M cases in the same duration. The majority were symptomatic (90%), although pre-M had a higher proportion of symptomatic than post-M (92% vs 85%; P = .04). Pre-M women showed more prevalence of osteitis fibrosa cystica than post-M women (28% vs 13%; P = .03), although hypertension and gallstone disease were seen more frequently in post-M PHPT women. Pre-M women had a significantly higher median PTH (403 vs 246 pg/mL; P = .02) and median alkaline phosphatase (202 vs 145 pg/mL; P = .02) than post-M women, and vitamin D deficiency was more common in pre-M women (58% vs 45%; P = .03). Gland localization, tumor weight, and disease cure rates did not differ according to menopausal status., Conclusion: PHPT was more prevalent in pre-M women, although the number of post-M cases had significantly increased in the last 10 years. Pre-M women had generally more severe clinical and biochemical variables than post-M PHPT women., (Copyright © 2020 American Association of Clinical Endocrinologists. All rights reserved.)

Acute pancreatitis as an initial manifestation of primary hyperparathyroidism (PHPT) is a rare occurrence and timely diagnosis of PHPT is crucial in preventing repeat attack of pancreatitis. The study aimed at evaluating the clinico-radiological profile of patients admitted with acute pancreatitis as the index presentation of PHPT and to determine the factors associated with development of severe pancreatitis. This series included retrospective analysis of medical records of 30 patients admitted with acute pancreatitis as initial manifestation of PHPT. Additionally, we analyzed the data of another 30 patients admitted with PHPT but without any evidence of pancreatitis, to serve as control group. The mean age of the subjects was 44.9±13.9 years with male to female ratio of 1.30. The mean serum calcium level was 12.24±2.79 mg/dl and five (16.6%) patients had normocalcemia at time of presentation. Presence of nephrolithiasis was significantly associated with severe pancreatitis. One patient had refractory hypercalcemia associated with renal failure and was successfully managed with denosumab. Patients with PHPT associated with acute pancreatitis had significantly higher calcium levels and lower frequency of skeletal involvement as compared to PHPT patients without pancreatitis. PHPT masquerading as acute pancreatitis is rare and high index of suspicion is required to diagnose this condition especially in the presence of normocalcemia at presentation. Patients with PHPT associated pancreatitis had male preponderance, higher calcium levels, and lower frequency of skeletal involvement as compared to PHPT patients without pancreatitis., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

An increased risk of fractures in primary hyperparathyroidism (PHPT) has been reported in a number of relatively small studies. Performing a systematic literature search, we identified available studies and calculated common estimates by pooling results from the individual studies in a meta-analysis. Searching EMBASE and PubMed, we identified published studies reporting the risk of fractures in PHPT compared to a control group. We calculated odds ratio (OR) with 95% confidence interval (CI). A total of 804 studies were identified of which 12 studies were included. Risk of any fracture was increased compared to controls (OR 2.01; 95% CI, 1.61-2.50; I 2 46%, 5 studies). Analysis of fracture risk at specific sites showed an increased risk of fracture at the forearm (OR 2.36; 95% CI, 1.64-3.38; I 2 0%, 4 studies) and spine (OR 3.00; 95% CI, 1.41, 6.37, I 2 88%, 9 studies). Risk estimate for hip fractures was non-significantly increased (OR 1.27; 95% CI, 0.97-1.66; I 2 0%, 3 studies). Risk of vertebral fractures (VFx) was also increased if analyses were restricted to only studies with a healthy control group (OR 5.76; 95% CI, 3.86-8.60; I 2 29%, 6 studies), studies including patients with mild PHPT (OR 4.22; 95% CI, 2.20-8.12; I 2 57%, 4 studies) or studies including postmenopausal women (OR 8.07; 95% CI, 4.79-13.59; I 2 0%, 3 studies). PHPT is associated with an increased risk of fractures. Although a number of studies are limited-it seems that the risk is increased across different skeletal sites including patients with mild PHPT and postmenopausal women.

Context: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality., Objective: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX., Methods: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022)., Conclusion: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: The prevalence of asymptomatic primary hyperparathyroidism (PHPT) in China is lower than that in European and American countries and the study about the characteristics of asymptomatic PHPT was rare in China. This study aims to explore the characteristics of asymptomatic PHPT., Methods: Clinical data of 150 patients with PHPT confirmed by operation and pathological examination were retrospectively analyzed. The patients were assigned into a symptomatic PHPT group ( n =124) and an asymptomatic PHPT group ( n =26)., Results: The proportion of adenomas was higher than that of adenocarcinoma in the asymptomatic PHPT group. The proportion of the first diagnosis due to hypercalcemia found via biochemical examination in the asymptomatic PHPT group was higher than that in the symptomatic PHPT group (76.92% vs 25.81%, P <0.001). The duration was shorter in the asymptomatic PHPT patients than that in the symptomatic PHPT patients (median 12 months vs 24 months, P =0.004). The serum calcium, the albumin-corrected serum calcium, and parathyroid hormone (PTH) were lower in the asymptomatic PHPT patients than those in the symptomatic PHPT ( P =0.003, P =0.006, and P =0.042, respectively). The serum 1,25-dihydroxyvitamin D 3 was higher ( P <0.001), the diameter was shorter ( P =0.028), and the bone mineral densities (BMD) of L 2~4 and femoral neck were higher in the asymptomatic PHPT patients than those in the symptomatic PHPT patients (both P <0.001)., Conclusions: Only a minority of PHPT patients are asymptomatic. Compared with the symptomatic PHPT patients, the primary cause of diagnosis is hypercalcemia, the duration of diagnosis and the diameter of parathyroid gland are shorter, the levels of serum calcium, and PTH are lower, the proportion of adenomas, vitamin D, and the BMD of L 2-4 and femoral neck are higher, and the pathological type is benign in the asymptomatic PHPT patients.