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Most of the primary hyperparathyroidism is due to adenomas in the parathyroid glands. Hypercalcemia is more common in primary hyperparathyroidism. Hyperparathyroidism may be asymptomatic and detected incidentally as part of a routine serological evaluation. Oral health care providers should recognize distinct changes in the jawbone associated with primary and secondary hyperparathyroidism., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Parathyroidectomy has been shown to reduce cardiovascular risk factors in some studies, although findings on these parameters remain inconsistent., Objectives: This study aimed to evaluate inflammatory and cardiovascular risk markers in patients with Primary Hyperparathyroidism (PHPT) before and one month after successful parathyroidectomy (PTX)., Methods: We retrospectively analyzed PHPT patients who visited the outpatient clinic between 2015 and 2020. Patient demographics, hemogram data, calcium, parathormone (PTH), vitamin D, high-density lipoprotein (HDL), mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-HDL ratio (MHR) were recorded and compared pre- and postoperatively., Results: The analysis revealed significant postoperative increases in platelet, MPV, HDL, PLR, and vitamin D levels (p = 0.001, p = 0.001, p = 0.001, p = 0.024, p = 0.001, respectively). Conversely, PTH, calcium, NLR, and MHR levels significantly decreased (p = 0.001, p = 0.001, p = 0.011, p = 0.019, respective-ly). Correlation analysis demonstrated a negative association between postoperative PTH and vitamin D (p = 0.010, r = -0.292**) and a positive association between postoperative PTH and both calcium (p = 0.008, r = 0.309**) and NLR (p = 0.046, r = 0.227**). Multivariable regression analysis demonstrated that postoperative PTH levels were significantly associated with calcium (B = 39.82, Beta = 0.321, p = 0.0469), NLR (B = 110.02, Beta = 0.428, p = 0.0384), baseline comorbidity scores (B = -30.54, Beta = -0.287, p = 0.0361), and preoperative inflammation levels (B = 25.69, Beta = 0.311, p = 0.0386)., Conclusion: Our findings highlight a potential link between PHPT and inflammatory-cardiovascular risk, with parathyroidectomy exerting a beneficial effect within the first month post-surgery. The study also suggests that these risk factors may be modifiable with timely surgical intervention., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the decision of Health Sciences University Adana City Hospital Local Ethics Committee (2020/10, 29/01/2020). The Declaration of Helsinki protocol was followed in the research protocol. All procedures involving human participants in this study were conducted in compliance with the ethical standards set by the institutional research committee and in alignment with the 1964 Helsinki Declaration and its subsequent amendments or similar ethical standards. Participants were recruited only after providing written informed consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Primary hyperparathyroidism (PHPT) is characterized by inappropriate secretion of parathyroid hormone, causing hypercalcemia and hypercalciuria, leading to renal stone diseases and nephrocalcinosis. The frequency, risk factors, and curative effect on nephrocalcinosis in post-parathyroidectomy have not been identified yet. Therefore, the present study evaluated the clinico-biochemical, radiological parameters and curative effect on nephrocalcinosis. A total of 583 PHPT patients were analysed in four groups viz. Group 1 (PHPT with nephrocalcinosis-98; 16.8%); Group 2 (PHPT with nephrolithiasis-227; 38.9%); Group 3 (PHPT with both nephrolithiasis and nephrocalcinosis-59; 10.1%); and Group 4 (PHPT without renal diseases-199, 34.1%). In the sub-group analysis, younger age (p ≤ 0.05), male gender (p ≤ 0.05), and hematuria (p ≤ 0.005) were significant in Group 1 vs. Group 4. Dysuria and low eGFR were significant in Group 1 vs. Group 2 (p ≤ 0.0005; p ≤ 0.05) and Group 1 vs. Group 4 (p ≤ 0.0005; p ≤ 0.0005). Polyuria (p ≤ 0.05; p ≤ 0.05, p ≤ 0.005), and gravluria (p ≤ 0.05; p ≤ 0.0005, p ≤ 0.005) were frequent in Group 1 vs. other groups. A significant difference was observed in S.Ca and, 24-hrs U.Ca in Group 1 vs. Group 2 {(12.2 (10.8-13.4) vs. 11.2 (10.7-12.4), p ≤ 0.05; 301 (189.5-465) vs. 180 (92.5-323.1), p ≤ 0.05} and Group 1 vs. Group 4 {(12.2 (10.8-13.4) vs. 11.4 (10.7-12.5), p ≤ 0.05 ; 301 (189.5-465) vs. 213 (110-360), p ≤ 0.0005}. Multivariate logistic regression showed gravluria [aOR = 9.2, p = 0.0001], S.Ca (aOR = 1.30, p = 0.003) and, 24-hrs U.Ca (aOR = 1.02, p = 0.042) to be independent predictors of nephrocalcinosis. Pre and post-operative assessment revealed decreased S. Ca levels [(11.9 ± 1.9) vs. (10.5 ± 1.0) mg/dL; p = 0.04] and complete radiological resolution (10.4%) in PHPT with nephrocalcinosis. Therefore, serum calcium, 24-hrs Urinary calcium, and gravluria were independent predictors of nephrocalcinosis with 10.4% showing complete radiological resolution post-operatively., Competing Interests: Declarations. Ethical approval: Institutes Ethics Committee of Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh has approved the study protocol. Consent for Patient: Obtained from each patient recruited in a study. Conflict of interest: The authors declare that they have no conflicts of interest., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Purpose: Data on the polar vessel sign (enlarged feeding vessel terminating in parathyroid lesions) on four-dimensional computed tomography (4D-CT) is limited. We performed a retrospective analysis to determine the prevalence, predictors, and adjunctive utility of polar vessel sign in pre-operative 4D-CT of patients with primary hyperparathyroidism (PHPT)., Methods: One radiologist blinded to the patients' details reported the 4D-CT of eighty-four operated patients with histopathology-proven single-gland PHPT. Two protocols were used to obtain arterial-phase images: timed via bolus tracking (n = 41) or fixed at 20 s after contrast injection (n = 43)., Results: Seventy-one patients were symptomatic for PHPT, with median serum calcium 12.1 mg/dL. On the arterial phase of 4D-CT, 88.1% of lesions had the polar vessel sign, including 7/9 asymptomatic patients, 6/6 parathyroid carcinomas, and 3/4 ectopic(1:mediastinum, 2:thyro-thymic ligament). Predictors of polar vessel sign were maximum lesion dimension (2.2 vs. 1.4 cm; P = 0.03), solid-cystic CT morphology (47.3% vs. none; P = 0.004), and bolus tracking-timed arterial phase (55.4% vs. none; P = 0.001). Of these, bolus tracking improved the polar vessel's visualization (100% vs. 76.7%; P = 0.001) independent of lesion dimension and solid-cystic morphology. The latter two predicted polar vessel sign in images obtained at a fixed interval (20 s). A significantly lower proportion of bolus tracking-timed scans had lesion percentage arterial enhancement (PAE) < 128.9% (2/41 vs. 9/43; P = 0.04). Even with suboptimal PAE, the polar vessel helped identify 9/11 lesions., Conclusion: The polar vessel sign demonstrated an additive role to PAE during CT reporting. Bolus tracking is valuable in optimizing vessel and tumor arterial enhancement and is easily incorporated into parathyroid 4D-CT protocol., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests. Ethics approval: The research was performed in accordance with the Declaration of Helsinki. The study was approved by the Institutional Ethics Committee [project number EC/OA-106/2023]. Informed consent: Informed consent was waived by Institutional Ethics Committee as this was a retrospective record study., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Primary hyperparathyroidism (PHPT) patients commonly report weakness and fatigue, though the underlying mechanisms are uncertain. Our purpose is to determine whether CT-derived muscle and adipose tissue metrics are associated with weakness and fatigue in PHPT patients., Methods: For this retrospective study, cross-sectional muscle and adipose tissue metrics were derived from CTs in PHPT patients undergoing preoperative imaging within 1 year of parathyroid surgery. Skeletal muscle index (SMI) and visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) ratio were calculated based on a single CT image at the level of the L3 vertebra. Established sex-specific SMI thresholds were used to define sarcopenia. Demographic and clinical data were collected from the electronic health record. When available, postoperative CT images were analyzed to assess for changes in body composition pre- and post-parathyroidectomy., Results: The cohort comprised 53 PHPT patients (38 females, 15 males, mean age 61.4 years), of whom 24 (45%) reported weakness, 43 (81%) reported fatigue, and 31 (58%) met CT-based criteria for sarcopenia. Lower SMI was significantly associated with preoperative weakness in females but not males. For both weakness and fatigue, VAT/SAT ratios were higher in symptomatic females and lower in symptomatic males than their asymptomatic counterparts, though these differences were not statistically significant. In patients with postoperative CTs (n = 23), no significant changes in CT metrics were observed after parathyroidectomy., Discussion: In females but not males with PHPT, subjective preoperative weakness was significantly associated with lower SMI. Effects of parathyroid hormone on skeletal muscle and visceral adiposity may differ by sex., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: 4D-CT has garnered attention as complementary imaging for patients with primary hyperparathyroidism (pHPT). Herein we evaluated a diagnostic strategy using [ 18 F]Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT), followed by 4D-CT integrated into PET/4D-CT after negative/inconclusive PET/CT results in a single-center retrospective cohort of 166 pHPT patients who underwent parathyroidectomy after [ 18 F]Fluorocholine PET/4D-CT., Methods: PET/CT and 4D-CT images were interpreted by three nuclear medicine physicians and one expert radiologist. Pathological findings were documented, and concordance rates were assessed. PET/CT results were categorized as positive/negative, with positive cases rated on a 3-level certitude scale: low, moderate, high. Inconclusive cases included low/moderate positivity. The added value of PET/4D-CT was assessed for negative/inconclusive cases through joint reading., Results: PET/CT lesion-based analysis showed almost perfect interobserver concordance (Cohen's kappa >.8). Across the cohort, PET/CT had a sensitivity of 83%, specificity of 97%, PPV of 90% and NPV of 94%. For 4D-CT, these values were sensitivity: 53%, specificity: 84%, PPV: 56% and NPV: 82%. PET/CT was significantly more accurate than 4D-CT. Among 44 patients with negative/inconclusive results, PET/CT had sensitivity: 60%, specificity: 91%, PPV: 71% and NPV: 86%. In the same patients, sensitivity and specificity of the sequential diagnostic algorithm increased to 80% and 97%, showing significantly better global accuracy (92% vs. 83%) than standard PET/CT., Conclusions: We support a personalized imaging algorithm for pHPT, placing [ 18 F]Fluorocholine PET/CT at the forefront, followed by 4D-CT integrated into PET/4D-CT in the same imaging session for negative/inconclusive results. When PET/CT results are clearly positive, the additional sensitivity benefit of 4D-CT is minimal., (© 2024 The Author(s). European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Primary hyperparathyroidism (pHPT) is marked by mineral imbalances, often leading to nephrolithiasis and osteoporosis. While imaging remains the cornerstone for stone detection, there is growing interest in biochemical markers that could enhance diagnostic accuracy. This study investigates the calcium-to-magnesium (Ca/Mg) ratio as a novel biomarker for nephrolithiasis, comparing its utility to traditional 24-h urinary calcium excretion and exploring its broader clinical implications. In this retrospective study of 367 pHPT patients, clinical, biochemical, and bone mineral density (BMD) data were analyzed. Nephrolithiasis was diagnosed via imaging, and the diagnostic performance of the Ca/Mg ratio and urinary calcium excretion was assessed through receiver operating characteristic analysis. Multivariable regression was employed to identify predictors of kidney stones. The Ca/Mg ratio, with an optimal cutoff of 6.35, demonstrated superior specificity (78%) compared to 24-h urinary calcium excretion (44%) while maintaining comparable sensitivity (71% vs. 78%). Elevated Ca/Mg ratios strongly correlated with nephrolithiasis, independent of other demographic factors. Hypomagnesemia was linked to a higher prevalence of kidney stones, reduced BMD, and increased serum calcium and creatinine levels, emphasizing its impact on skeletal and renal health. The Ca/Mg ratio emerges as a promising, non-invasive biomarker for nephrolithiasis in pHPT, outperforming traditional urinary calcium measures. It reflects underlying mineral imbalances and offers a practical tool for risk stratification and clinical decision-making. These findings underscore the need for further research into magnesium-targeted interventions, which may transform the management of pHPT-related complications., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical Statement: The study was planned retrospectively, and research permission was obtained from Bursa City Hospital’s scientific research ethics committee with protocol number 2024-11/4., (© 2025. The Author(s).)

Context: Primary hyperparathyroidism (PHPT) is an endocrine disorder that is treated surgically, and some correlation between the size of the responsible lesion and preoperative clinical data is assumed., Objective: The purpose of this study was to predict tumor volume of the lesion responsible for PHPT from preoperative clinical data., Methods: Participants comprised patients with surgically treated PHPT who underwent initial surgery in our department between January 2000 and December 2021. The volume of parathyroid gland removed was used as the primary outcome and associations with preoperative clinical data were assessed by multivariable analysis., Results: A positive correlation was identified between parathyroid tumor volume and both preoperative intact parathyroid hormone (PTH) (Spearman's r = 0.503) and calcium values (Spearman's r = 0.338). Data for intact PTH value and tumor volume were logarithmically transformed (ln-PTH = log-transformed intact PTH value; ln-volume = log-transformed tumor volume). Multiple regression analysis revealed male sex, ln-PTH and calcium values as significant predictors of ln-volume, with standardized regression coefficients of 0.213 (95% CI 0.103-0.323), 0.5018 (95% CI 0.4442-0559), and 0.322 (95% CI 0.0339-0.149), respectively. The adjusted R2 for this model is 0.320., Conclusion: Preoperative serum intact PTH value is associated with tumor volume of the lesion responsible for PHPT. A rough estimation of the tumor size would provide responsible physicians with opportunities to add further imaging tests or plan appropriate surgical strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Multiple endocrine neoplasia type 1 (MEN1) syndrome is an autosomal dominant disorder caused by a germline pathogenic variant in the MEN1 tumor suppressor gene. Patients with MEN1 have a high risk for primary hyperparathyroidism (PHPT) with a penetrance of nearly 100%, pituitary adenomas (PitAd) in 40% of patients, and neuroendocrine neoplasms (NEN) of the pancreas (40% of patients), duodenum, lung, and thymus. Increased MEN1-related mortality is mainly related to duodenal-pancreatic and thymic NEN. Management of PHPT differs from that of patients with sporadic disease, as the surgical approach in MEN1-related PHPT includes near-total or total parathyroidectomy because of multigland hyperplasia in most patients and the consequent high risk of recurrence. NEN management also differs from patients with sporadic disease due to multiple synchronous and metasynchronous neoplasms. In addition, the lifelong risk of developing NEN requires special considerations to avoid excessive surgeries and to minimize damage to the patient's function and well-being. This progress report will outline current insights into surveillance and management of the major clinical manifestation of MEN1 syndrome in children and adults with MEN1 diagnosis. In addition, we will discuss MEN1-like clinical presentation with negative MEN1-genetic workup and future clinical and research directions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Primary hyperparathyroidism (PHPT) is more prevalent in populations with obesity. Obesity-related vitamin D deficiency may affect rates of multigland parathyroid disease, but this relationship is less clear. We aimed to assess the relationship between obesity and the rate of multigland disease in patients with PHPT., Methods: Patients who underwent parathyroidectomy from 2015 to 2021 for sporadic PHPT at a tertiary center were retrospectively analyzed. The primary outcome was rates of single-gland versus four-gland parathyroid hyperplasia in relation to obesity. Secondary outcomes included analysis of serum biochemistries [parathyroid hormone (PTH), calcium, 25(OH) vitamin D (25OHD)] before and 6 mo postoperatively based on obesity classification: no obesity (body mass index [BMI] <30 kg/m 2 ), Class 1 (BMI 30-34.9 kg/m 2 ), Class 2 (BMI 35-39.9 kg/m 2 ), Class 3 (BMI ≥40 kg/m 2 ). Statistical analysis was performed using Chi-square, Mann-Whitney U, and Kruskal-Wallis tests where applicable., Results: Of 2634 patients who underwent parathyroidectomy, a total of 1173 had obesity. Obesity did not confer any differences in the proportion of four-gland versus single-gland hyperplasia (25 versus 26%, P = 0.79). Compared to patients without obesity, preoperative PTH levels were higher in patients with Class 2 [86 (interquartile range [IQR] 66-118) versus 95 (IQR 70-137) pg/mL, P = 0.001] and Class 3 [86 (IQR 66-118) versus 104 (76-150) pg/mL, P < 0.001] obesity. Conversely, 25OHD before surgery was lower across obesity subclasses [no obesity: 36.0 (25.3-49.3), Class 1: 32.5 (24.0-46.0), Class 2: 32.9 (22.0-44.6), Class 3: 31.7 (20.4-45.0) ng/mL, P < 0.001]. Postoperative PTH and 25OHD improved in all cohorts. No calcium-related differences were found among patients based on obesity classification., Conclusions: Obesity is not associated with an increased rate of four-gland hyperplasia in patients with PHPT, and therefore should not alter surgical management. The levels of 25OHD in patients with obesity should be monitored for vitamin deficiency preoperatively and postoperatively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Primary hyperparathyroidism (pHPT) in children is uncommon, resulting in a paucity of data describing the disease process in this population. Herein, in an effort to bridge the information gap, we review our experience with pHPT in adolescent patients under 20 y of age at a specialized tertiary referral center., Methods: A retrospective chart review included all adolescent patients with pHPT, who underwent surgery at our institution between 2004 and 2023. Presenting symptoms, biochemical workup, intraoperative findings, and outcomes were collected and analyzed., Results: Forty-nine adolescent patients were included, with 45% (n = 22) being male. The median age at diagnosis was 16.6 y (14.1-20). On presentation, 71% (n = 35) were symptomatic, most commonly nephrolithiasis (35%, n = 17). The median preoperative calcium and parathyroid hormone were 12 mg/dL (11.3-12.6) and 128pg/mL (105-170.5), respectively. Focused parathyroidectomy was performed in 61% (n = 30) and four-gland exploration in 39% (n = 19) of patients. Eighty-six percent were found to have a single adenoma and 14% had multigland disease. Preoperative localization with ultrasound and Sestamibi had a sensitivity of 57% and 59%, respectively. When combining both imaging modalities, sensitivity increased to 78% (positive predictive value 91%). There were no surgical complications. At the median follow-up of 61.0 mo, 4% of patients were found to have recurrent pHPT. Younger age (OR 0.64, P = 0.038) and sporadic disease (OR 0.04, P = 0.050) had less likelihood of recurrence., Conclusions: Most adolescent patients with pHPT present with symptoms and have single gland disease. Adolescent pHPT should be treated like adult pHPT, utilizing intraoperative PTH and two preoperative imaging modalities., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Normocalcemic Primary Hyperparathyroidism (NPHPT) is a complex syndrome that causes excess secretion of parathyroid hormone (PTH) from the parathyroid glands. PTH in bone activates the function of osteoclasts, to increase bone resorption and thus increase plasma calcium levels. Given that periodontitis generates osteolytic lesions and has a high prevalence in adults, both pathologies could share etiopathogenic mechanisms, although no studies have been found to date that have investigated this. Therefore, the aim of the study was to evaluate the bone density, periodontal status and biochemistry variables to determinate if there is a relationship between both pathologies., Material and Methods: A case-control study was carried out with 86 cases (NPHPT) and 87 controls. Bone density was evaluated through computed tomography, measured in Hounsfield units, in seven Regions of Interest. Periodontal status and biochemical variables, such as marker hormones of bone metabolism (25 OH vitamin D and PTH), were analyzed. A Student's t test, bivariate correlations were performed and the OR was calculated., Results: NPHPT patients are more susceptible to changes in the pattern of bone remodeling due to elevated serum levels of PTH and a decrease in 25OH vitamin D under conditions of normocalcemia. The 58.9% of cases group had periodontitis Stage IV, 27% Stage III, 9.45% Stage II and 8.1% with Stage I. Control group showed a 32% periodontitis Stage IV, 39% Stage III, 8.82% have Stage II and 16.2% Stage I., Conclusions: There was an association between NPHPT and periodontitis, with patients with NPHPT showing a 1.78 (OR) greater probability of suffering from periodontitis. Our biochemical results showed that the increase in PTH and the decrease in 25OH VIT-D were associated with loss of bone density and these patients presented advanced periodontitis.

Background: Primary hyperparathyroidism predominately affects women who are postmenopausal and causes complications, including fragility fractures. Its treatment is parathyroidectomy, which is associated with low complication and >95% cure rates. Considering fractures are associated with premature death, we aimed to determine whether the surgical management of individuals with biochemical diagnosis of primary hyperparathyroidism was associated with a reduction in fracture risk., Methods: In this population-based cohort study, we used administrative health databases to identify adults ≥18 year old who were biochemically diagnosed with primary hyperparathyroidism between 2007 and 2016 in Ontario. Patients were included if their calcium was ≥2.6 mmol/L (≥10.42 mg/dL) with a concurrent parathyroid hormone of ≥2.2 pmol/L (≥20.75 pg/mL). We followed patients and compared the incidence of fractures between those with and without parathyroidectomy. To control for potential confounding, we used inverse probability of treatment weighting to estimate the average treatment effect in the treated. Fine-Gray competing risk regression models were used to determine the association between surgery and time to fracture., Results: In a cohort of 28,059 with a biochemical diagnosis of primary hyperparathyroidism, the mean age (standard deviation) was 65 years (14.2 years), and 75% (n = 21,139) were female. Only 12.6% (n = 3,523) underwent parathyroidectomy. Weighted fracture cumulative incidence at 12 years postdiagnosis was 10.17% (n = 182) in surgical patients and 14.04% (n = 2,004) in nonsurgical patients. Parathyroidectomy prevented 1 fracture for every 26 surgeries performed (weighted risk difference, 3.87%, 95% confidence interval, 0.96%-6.62%) and reduced the hazard of fracture by 22% (weighted hazard ratio, 0.78; 95% confidence interval, 0.64-0.95)., Conclusion: In a large, publicly funded health system, parathyroidectomy significantly reduced the short- and long-term risk of fragility fractures in patients with primary hyperparathyroidism., Competing Interests: Conflict of Interest/Disclosure The authors have no conflicts of interests or disclosures to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Objectives: To assess the feasibility of performing selective parathyroidectomy without intraoperative parathyroid hormone (PTHio) determination when first-line preoperative localization tests (ultrasonography and [ 99m Tc]Tc-MIBI) are negative and/or discordant, and second-line [ 18 F]F-Colina PET-CT, is positive., Materials and Methods: Retrospective cohort study, including patients with negative or discordant ultrasound and MIBI scans and positive [ 18 F]F-Colina PET-CT, who underwent selective parathyroidectomy between 2019 and 2022. Groups were compared based on PTHio determination. Study variables were: gender, mean age, biochemical cure assessed by PTH value (pg/mL) and corrected calcium by albumin (mg/dL) at 6 months post-surgery follow-up, and histopathological analysis., Results: The final sample included 42 patients. At 6 months post-surgery, in the PTHio group (20 patients), PTH values were 64.50 pg/mL and calcium 9.30 pg/mL, with 19 adenomas and 1 hyperplasia found. In the non-PTHio group (22 patients), PTH values were 61 pg/mL and calcium 9.37 pg/mL, with 22 adenomas found. No statistically significant differences were found between both groups., Conclusions: Based on the results obtained in our patient cohort, selective parathyroidectomy could be considered with negative or discordant first-line tests and positive [ 18 F]F-Colina PET-CT, without intraoperative PTH determination., (Copyright © 2024 Sociedad Española de Medicina Nuclear e Imagen Molecular. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Multiglandular parathyroid disease, which is particularly frequent in patients with mild primary hyperparathyroidism, is a surgical challenge requiring bilateral cervicotomy with 4-gland exploration. Near-infrared autofluorescence of the parathyroid is increasingly used to prevent hypocalcemia after total thyroidectomy. However, its utility in decreasing operating time and aiding parathyroid identification during bilateral 4-gland exploration remains debated., Methods: In our prospective trial, we enrolled consecutive patients with sporadic mild primary hyperparathyroidism (serum calcium <2.85 mmol/L with elevated or nonadapted serum parathyroid hormone levels). With randomization, we assigned patients to classic parathyroidectomy or parathyroidectomy with near-infrared autofluorescence using the Fluobeam 800 device (near-infrared autofluorescence group). All procedures involved planned bilateral neck exploration conducted by 2 experienced surgeons. The primary outcome was mean operating time. Secondary outcomes included the number of visualized and excised glands, complication rates, and cure rates., Results: In total, 132 patients were included (66 per group). Mean age was 64.0 ± 12.0 years, with 85.6% female. Mean preoperative serum calcium level was 2.63 ± 0.11 mmol/L, and median serum PTH level 86.1 [65.6-109.8] pg/mL. The mean operating time did not significantly differ between the classic parathyroidectomy and near-infrared autofluorescence groups (46.9 ± 15.3 minutes and 51.2 ± 22.9 minutes, respectively, P = .21). The use of near-infrared autofluorescence did not significantly modify the number of identified or resected glands nor the rate of complications. Cure rates were similar between groups (92.2% and 94.8%; P = .72)., Conclusion: In this study, near-infrared autofluorescence, in the hands of experienced surgeons, did not reduce operating time for parathyroidectomy during bilateral neck exploration in mild primary hyperparathyroidism. Although not increasing operating time, further evaluation is needed, particularly regarding its role in the surgeon's training., Competing Interests: Conflict of Interest/Disclosure The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The success of parathyroidectomy in primary hyperparathyroidism depends on the intraoperative differentiation of diseased from normal glands. Deep learning can potentially be applied to digitalize this subjective interpretation process that relies heavily on surgeon expertise. In this study, we aimed to investigate whether diseased vs normal parathyroid glands have different near-infrared autofluorescence (NIRAF) signatures and whether related deep learning models can predict normal vs diseased parathyroid glands based on intraoperative in vivo images., Study Design: This prospective study included patients who underwent parathyroidectomy for primary hyperparathyroidism or thyroidectomy using intraoperative NIRAF imaging at a single tertiary referral center from November 2019 to March 2024. Autofluorescence intensity and heterogeneity index of normal vs diseased parathyroid glands were compared, and a deep learning model was developed., Results: NIRAF images of a total of 1,506 normal and 597 diseased parathyroid glands from 797 patients were analyzed. Normal vs diseased glands exhibited a higher median normalized NIRAF intensity (2.68 [2.19 to 3.23] vs 2.09 [1.68 to 2.56] pixels, p < 0.0001) and lower heterogeneity index (0.11 [0.08 to 0.15] vs 0.18 [0.13 to 0.23], p < 0.0001). On receiver operating characteristics analysis, optimal thresholds to predict a diseased gland were 2.22 in pixel intensity and 0.14 in heterogeneity index. On deep learning, precision and recall of the model were 83.3% each, and area under the precision-recall curve was 0.908., Conclusions: Normal and diseased parathyroid glands in primary hyperparathyroidism have different intraoperative NIRAF patterns that could be quantified with intensity and heterogeneity analyses. Visual deep learning models relying on these NIRAF signatures could be built to assist surgeons in differentiating normal from diseased parathyroid glands., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Currently, parathyroidectomy is the standard treatment for Primary Hyperparathyroidism (PHPT). Surgical treatment is often effective, although not free of complications and relapses. Minimally invasive techniques, such as Microwave Ablation (MWA) and Radiofrequency Ablation (RFA), are an alternative to surgery in selected patients. We have, herein, reported on the successful use of RFA in a patient with post-surgical persistent hyperparathyroidism., Case Presentation: A 54-year-old woman was referred to our Center for mild hypercalcemia with exams revealing Primary Hyperparathyroidism (PHPT). Neck ultrasound and Technetium- 99 Methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy scanning revealed a suspicious right parathyroid hyperplasia/adenoma. She underwent parathyroidectomy and histological examination showed a parathyroid nodular hyperplasia. During the follow-up, she suffered from persistent hyperparathyroidism due to a left parathyroid hyperplasia. Thus she was treated with RFA. Blood tests after the procedure showed the remission of the disease 7 months post-treatment., Conclusion: A minimally invasive technique for PHPT may represent a valid alternative to surgery, especially in patients with an elevated surgery-related risk. More studies are necessary to investigate the benefit of RFA as a first-line treatment in PHPT., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Normohormonal primary hyperparathyroidism is characterized by hypercalcemia and inappropriately normal parathyroid hormone levels. We previously reported that intraoperative parathyroid hormone decline of 50-70% for normohormonal and 75-88% for classic primary hyperparathyroidism during parathyroidectomy was predictive of (1) cure and (2) avoidance of hypocalcemia in a single-institution study (derivation cohort). We sought to externally validate these findings., Methods: We performed a multi-institutional retrospective cohort study of patients undergoing parathyroidectomy for primary hyperparathyroidism from 2002 to 2019 (validation cohort). Primary outcomes were biochemical cure (calcium <10.3 mg/dL) and postoperative hypocalcemia (≤8.8 mg/dL) ≥6 months postoperatively. Test characteristics of the previously derived thresholds were evaluated in this cohort., Results: A total of 163 (16%) of 1,037 patients had normohormonal primary hyperparathyroidism. Cure rates were similar for normohormonal and classic primary hyperparathyroidism (94% vs 92%, P = .41). In patients who were cured, the median intraoperative parathyroid hormone decrease was lower in normohormonal compared with classic primary hyperparathyroidism (56.8 vs 73.3%, P < .0001). Rates of hypocalcemia were similar for normohormonal and classic primary hyperparathyroidism (14.6% vs 11.9%, P = .44), but increasing percent intraoperative parathyroid hormone decrease beyond 65% disproportionately correlated with hypocalcemia in patients with normohormonal primary hyperparathyroidism. When intraoperative parathyroid hormone thresholds from the derivation cohort were applied, positive predictive values for cure were 97% and 94% for normohormonal and classic primary hyperparathyroidism, respectively; negative predictive values for hypocalcemia were 89% for both groups. For both cohorts combined, a minimal intraoperative parathyroid hormone of 50% provided similar cure rates between groups (95.4% vs 93.8%, P = .42), whereas intraoperative parathyroid hormone exceeding 65% correlated with a greater risk of hypocalcemia in normohormonal compared with classic primary hyperparathyroidism (13.4% vs 6.9%, P = .02)., Conclusion: This multi-institutional study externally validated that intraoperative parathyroid hormone decrease of 50-65% predicts cure and hypocalcemia in patients with normohormonal primary hyperparathyroidism., Competing Interests: Conflicts of Interest/Disclosure The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Primary hyperparathyroidism (PHPT) is accompanied by a decreased 25-hydroxyvitamin D (25OHD) and vitamin D binding protein (DBP). High parathyroid hormone (PTH) is associated with elevated interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), yet the effect of parathyroidectomy (PTX) on DBP and cytokines is not clear. This study aims to prospectively evaluate the effect of PTX on inflammatory profiles, total and free 25OHD, and DBP in patients with PHPT., Methods: Newly diagnosed patients with PHPT were recruited for the study (n = 70). Twenty-eight patients returned after PTX, 3 months later. Biochemical markers were measured before and after PTX. A group of age and body mass index-matched healthy subjects were included as controls (n = 70)., Results: Before PTX, patients had lower serum DBP (37.5 ± 6.0 vs 41.5 ± 6.1 mg/dL, P < .001) and total 25OHD (30.1 ± 9.5 vs 33.3 ± 7.9 ng/mL, P < .05) but similar free 25OHD when compared to controls. Serum IL-6, C-reactive protein, and MCP-1 were higher in patients with PHPT (P < .05), whereas interleukin-10 was similar to that in controls. PTX increased total and free 25OHD and DBP (P < .001) and decreased serum IL-6 and MCP-1 (P < .05), but not C-reactive protein and interleukin-10. Multiple regression analysis indicated that the preoperative PTH explained a significant portion of the variance of IL-6 and MCP-1 (P < .05)., Conclusion: These findings suggest that PTH may upregulate the production of MCP-1 and IL-6 and downregulate circulating DBP in patients with PHPT that are normalized by PTX. The exact mechanism of IL-6 and MCP-1 on DBP, vitamin D metabolites, and clinical outcomes in patients with PHPT is an area requiring further study., Competing Interests: Disclosure X.W. is an Editorial Board Member of Endocrine Practice and he was not involved in the editorial review or the decision to publish this article. The other authors have no conflicts of interest to disclose., (Published by Elsevier Inc.)

Introduction: Primary hyperparathyroidism (PHPT) increases the risk of osteoporosis and fractures. Despite American Association of Endocrine Surgeons guidelines that recommend bone mineral density (BMD) assessment via dual-energy x-ray absorptiometry (DEXA) for PHPT patients, adherence to these guidelines remains suboptimal., Methods: We performed a retrospective review of preoperative and postoperative DEXA scan practices among PHPT patients at a single academic medical center between 2000 and 2018. Patient data, including demographics and history of bone pathology, was analyzed to identify factors influencing adherence to BMD assessment guidelines., Results: Of the 3384 PHPT patients evaluated for surgery, only 45.4% (n = 1535) underwent preoperative DEXA scan. Women were significantly more likely to undergo preoperative DEXA than men (49.9% versus 29.0%, P < 0.001). Female sex, age ≥65 y, and a history of bone pain or fractures were significant positive predictors of preoperative DEXA scan. Of patients with 2-y follow-up who did not receive a preoperative DEXA (n = 145), only 13.8% (n = 20) received a postoperative DEXA., Conclusions: This study highlights gaps in the adherence to national guidelines for DEXA screening among PHPT patients. This underscreening may contribute to increased morbidity due to unidentified osteoporosis. Efforts must be made to improve clinical practice and bring it into line with best practice as recommended by national guidelines., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: In patients with Primary Hyperparathyroidism (PHPT) vitamin D deficiency has been associated with more severe presentations. Our aim was to investigate the effects of Vitamin D supplementation on mineral homeostasis and related hormones in individuals with and without PHPT., Methods: Individuals with and without PHPT (CTRL) received 14,000 IU/week of oral vitamin D 3 for 12 weeks. At baseline and endpoint, blood samples were collected to measure 1,25(OH) 2 vitamin D (1,25(OH) 2 D), intact Fibroblast Growth Factor 23 (FGF23), 25OHD, Parathormone, and other biochemical markers. The 1,25(OH) 2 D measurement was performed using liquid chromatography and mass spectrometry (LC-MS/MS)., Results: 70 PHPT patients and 75 CTRL were included, and 55 PHPT and 64 CTRL completed the 12-week protocol. After the intervention, there were significant increases in the FGF23 levels (PHPT: 47.9 ± 27.1 to 76.3 ± 33.3; CTRL: 40.5 ± 13.9 to 59.8 ± 19.8 pg/mL, p < 0.001), and significant decreases in 1,25(OH) 2 D levels (PHPT: 94.8 ± 34.6 to 68.9 ± 25.3; CTRL: 68.7 ± 23.5 to 56.4 ± 20.7 pg/mL, p < 0.001). The reduction of 1,25(OH) 2 D was inversely associated with the increase of FGF23 in both the PHPT (r = -0.302, p = 0.028) and CTRL (r = -0.278, p = 0.027). No changes in plasmatic or uninary calcium concentrations were observed in both groups., Conclusion: The weekly administration of 14,000 IU of Vitamin D3 was safe and efficient to increase in 25OHD levels in both groups. However, a paradoxical decrease in 1,25(OH) 2 D levels measured by LC-MS/MS was associated with a significant increase in FGF23 levels in both groups. This phenomenon might represent a defense against hypercalcemia after vitamin D supplementation and paves the way for new studies in this regard., Competing Interests: Declarations. Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest. Research involving human participants and/or animals: The study was approved by the Ethics and Research Committee of the Federal University of São Paulo (registration number 89044117.9.0000.5505). Informed consent: All participants signed an Informed Consent Form., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Purpose: Parathyroid imaging with dual-phase technetium-99m methoxyisobutrylizonitrile (Tc-99m MIBI) scintigraphy serves as an important prerequisite for the identification of hyperfunctioning parathyroid gland(s) in patients with primary hyperparathyroidism (PHPT) for a successful targeted parathyroidectomy. This study aimed to evaluate the clinical value of additional lateral imaging and single-photon emission computed tomography/computed tomography (SPECT/CT) versus conventional planar imaging for locating parathyroid pathologies in patients with PHPT., Materials and Methods: A retrospective review was performed on 105 patients who underwent dual-phase Tc-99m MIBI scintigraphy and were surgically treated by parathyroidectomy. Dual-phase Tc-99m-MIBI planar scintigraphy with additional lateral pinhole views and SPECT/CT imaging was performed on a routine basis, as per departmental protocol. Comparison study between imaging modalities was done by patient-based analysis and scintigraphy results were compared with the clinical findings, biochemical markers, and histopathological findings., Results: Sensitivity and specificity for anterior planar dual-phase Tc-99m MIBI scintigraphy were 78.8 and 80%, respectively. In comparison, lateral pinhole scan and SPECT/CT alone were found to have sensitivities of 85.9 and 90.9%, respectively, with the same specificity. Sensitivity decreased in patients with normocalcaemia and multiglandular disease. The mean adenoma weight and size for true-positive studies were significantly higher than those for false-negative or false-positive studies., Conclusion: SPECT/CT provided the highest diagnostic accuracy for preoperative identification of parathyroid lesions in PHPT patients. Lateral pinhole imaging offers comparable sensitivity and aids in adenoma localisation when SPECT/CT is unavailable., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A 51-year-old female patient with diabetes mellitus and hypertension, exhibiting poor control of blood sugar and blood pressure, was unexpectedly found to have multiple large adrenal nodules, excessive cortisol secretion, and adrenocorticotropic hormone inhibition. Cortisol levels remained unresponsive to both low-dose and high-dose dexamethasone tests, leading to a diagnosis of primary bilateral macronodular adrenal hyperplasia. Concurrently, elevated blood calcium and parathyroid hormone levels, along with 99mTc-methoxyisobutyl isonitrile (99mTc-MIBI) imaging revealing increased 99mTc-MIBI uptake in the right inferior parathyroid gland, suggest the consideration of primary hyperparathyroidism. This case is presented in light of the uncommon clinical coexistence of primary bilateral macronodular adrenal hyperplasia and primary hyperparathyroidism., 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 © 2024 Zhong, Zhang, Li, Chen, Tong, Xia and Wei.)

Background: Surgery is the preferred treatment for primary hyperparathyroidism. Minimally invasive parathyroidectomy is only feasible with accurate preoperative localisation. Virtual 3D anatomical models can be constructed from patient-specific CT scans using segmentation software., Methods: We aimed to create virtual 3D models from 4D-CT scans of parathyroid tumours using segmentation technology. We designed a small pilot study to assess the utility of 3D models within surgical practice. We assessed surgeon, trainee and patients' opinion and satisfaction with the models. The NASA TLX survey was the primary data collection tool., Results: Creation of novel 3D models was achieved, these featured a 360-degree axis of rotation and transparency mode to assist in surgical planning. Models were used intraoperatively with the HoloLens 2 headset to locate parathyroid tumours real time before surgery. Total mean workloads for surgery planning when averaged revealed a decrease workload (39.45 vs 27.45) points with adjunctive use of models (p=0.002). Mental demand showed the greatest decrease in mean workload out of all the 6 subscales tested for in the NASA TLX (210.3 vs 136.7) points. Patient satisfaction score was statistically significant for the difference before and after seeing the 3D model regarding anatomical location (p=≤0.001)., Conclusion: In this work, we developed patient-specific virtual 3D anatomical models of parathyroid tumours for use in surgery using novel techniques, previously never applied to parathyroidectomy. Our initial success in model construction and subsequent opinion of surgeons, trainees and patients contributes to the developing body of literature in favour of virtual modelling for parathyroidectomy., 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 © 2024 Haq, Ahmed, Abdelsalam, Chegini, Kurzawinski, Morley, McGurk and Abdel-Aziz.)

Purpose: Cardiometabolic disorders are non-classical complications of hypercalcemic primary hyperparathyroidism (HC-PHPT), but whether this risk connotes normocalcemic PHPT (NC-PHPT) remains to be elucidated. We investigated cardiometabolic alterations in both forms of PHPT, looking for their association with indices of disease activity., Methods: Patients with HC-PHPT (n = 17), NC-PHPT (n = 17), and controls (n = 34) matched for age, sex, and BMI were assessed for glucose, lipid, blood pressure alterations, and history of cardiovascular events to perform a case-control study at an ambulatory referral center for Bone Metabolism Diseases., Results: NC-PHPT, in comparison to controls, showed similar glucose (mean ± SD, 88 ± 11 vs 95 ± 22 mg/dl), total cholesterol (199 ± 25 vs 207 ± 36 mg/dl), and systolic blood pressure levels (SBP, 132 ± 23 vs 132 ± 19 mmHg), together with a comparable frequency of glucose alterations (6% vs 9%), lipid disorders (41% vs 50%) and hypertension (53% vs 59%, p = NS for all comparisons). Conversely, all these abnormalities were more prevalent in HC-PHPT vs controls (p < 0.05). When compared to NC-PHPT, HC-PHPT showed higher glucose (113 ± 31 mg/dl), total cholesterol (238 ± 43 mg/dl), and SBP levels (147 ± 15 mmHg) as well as an increased frequency of glucose (41%) and lipid alterations (77%) and a higher number of cardiovascular events (18% vs 0%, p < 0.05 for all comparisons). Among indices of PHPT activity, calcium levels displayed a significant correlation with glucose (R = 0.46) and SBP values (R = 0.60, p < 0.05)., Conclusion: NC-PHPT is not associated with cardiovascular alterations. The predominant pathogenetic role of hypercalcemia in the development of cardiometabolic disorders could account for the absence of such alterations in NC-PHPT., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethics approval All procedures performed in the study were in accordance with the ethical standards of the institutional and/or national research committee (Comitato Etico Interaziendale A.O.U. Città della Salute e della Scienza di Torino—A.O. Ordine Mauriziano—A.S.L. Città di Torino) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

Patients with primary hyperparathyroidism (PHPT) frequently report symptoms that are associated with the disease and impact on their quality of life (QoL). While parathyroidectomy corrects calcium and PTH levels, its impact on improving patients' QoL is not clear. In this single centre prospective study, we aimed to assess the impact of a parathyroidectomy on PHPT patients' pre and post parathyroidectomy QoL over a period of three years and nine months. PHPT patients, undergoing parathyroidectomy, voluntarily completed a modified Pasieka Parathyroidectomy Assessment Score (PAS), a tool correlating 13 PHPT symptoms to QoL. Sixty patients with PHPT (mean age 64 years, female to male 4:1) were included in the study. Pre parathyroidectomy, the most common symptoms were: feeling tired easily (n = 58); being forgetful (n = 51); pain in the joints (n = 49); feeling irritable (n = 48) bone pain (n = 45); feeling weak (n = 45); mood swings (n = 42); and being thirsty (n = 42). Parathyroidectomy reduced severity of mean total PAS by 44%, improving from 509 to 284 (p < 0.01). A total of 77% (n = 46) of patients experienced some improvement of PAS. The five most severe symptoms (highest reported individual PAS) showed a significant reduction post parathyroidectomy (p < 0.01): feeling tired easily (mean PAS 65 vs 38); pain in the joints (52 vs 31); being thirsty (46 vs 22); being forgetful (45 vs 28); and bone pain (45 vs 27). Patients with PHPT demonstrated impaired QoL as evidenced by the PAS, and assessing this is valuable in treatment planning. Parathyroidectomy impacts the symptoms that most affect QoL and significantly improves overall QoL in these patients., Competing Interests: Conflict of interest We have no conflicts of interest., (Copyright © 2024 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Retrospective studies are conflicting regarding the risk of primary hyperparathyroidism after radioactive iodine treatment. We hypothesized that primary hyperparathyroidism rates are greater after radioactive iodine than after thyroidectomy and that patients with hypercalcemia after treatment for Graves' disease are not adequately evaluated for primary hyperparathyroidism, contributing to underdiagnosis of radioactive iodine-associated primary hyperparathyroidism., Methods: This retrospective review considers patients undergoing radioactive iodine or thyroidectomy for Graves' disease at a tertiary referral center between January 1, 2000, and January 31, 2022. Patients were identified using a hospital-based cohort discovery tool; exclusions included history of head/neck radiation, primary hyperparathyroidism/parathyroidectomy, renal dysfunction diagnoses, or treatment with both radioactive iodine and thyroidectomy. Patients with an elevated calcium (>10.2 mg/dL) level measured after treatment were classified as "incomplete workup" (no parathyroid hormone), "likely primary hyperparathyroidism" (parathyroid hormone >40 pg/dL), or "unlikely primary hyperparathyroidism" (parathyroid hormone <40 pg/dL)., Results: Of 900 patients, 468 (52%) had been treated with radioactive iodine and 432 (48%) with thyroidectomy. At a median follow-up of 9.39 years (interquartile range, 5.12-13.25), 25% (n = 224) of patients did not have a serum calcium measured and 52 (8%, n = 676) patients had an elevated calcium level. Hypercalcemia was more common after radioactive iodine (10%) than thyroidectomy (6%, P = .061). Of patients with hypercalcemia, 33 (63%) were "incomplete workup," 5 (10%) were "likely primary hyperparathyroidism," and 14 (27%) were "unlikely primary hyperparathyroidism." There was no difference in primary hyperparathyroidism workup rates between patients treated with radioactive iodine (n = 23) and thyroidectomy (n = 10, P = .389)., Conclusions: Patients treated with radioactive iodine for Graves' disease may experience an elevated rate of hypercalcemia, but the majority are not adequately evaluated for primary hyperparathyroidism. Patients with a history of radioactive iodine should undergo regular calcium screening and, if elevated, appropriate workup for primary hyperparathyroidism., Competing Interests: Conflict of Interest/Disclosure The authors have no relevant financial disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with neuropsychiatric symptoms. Although parathyroidectomy has been associated with improvement of preexisting depression among adults with PHPT, the effect of parathyroidectomy on the development of new depression is unknown., Objective: To determine the effect of early parathyroidectomy on the incidence of new depression among adults with PHPT compared with nonoperative management., Design, Setting, and Participants: Analyzed data included observational national Veterans Affairs data from adults with a new diagnosis of PHPT from 2000 through 2019 using target trial emulation with cloning, a biostatistical method that uses observational data to emulate a randomized clinical trial. New depression rates were compared between those treated with early parathyroidectomy vs nonoperative management using an extended Cox model with time-varying inverse probability censoring weighting, adjusted for patient demographics, comorbidities, and depression risk factors. Eligible adults with a new biochemical diagnosis of PHPT, excluding those with past depression diagnoses, residing in an assisted living/nursing facility, or with Charlson Comorbidity Index score higher than 4 were included. These data were analyzed January 4, 2023, through June 15, 2023., Exposure: Early parathyroidectomy (within 1 year of PHPT diagnosis) vs nonoperative management., Main Outcome: New depression, including among subgroups according to patient age (65 years or older; younger than 65 years) and baseline serum calcium (11.3 mg/dL or higher; less than 11.3 mg/dL)., Results: The study team identified 40 231 adults with PHPT and no history of depression of whom 35896 were male (89%) and the mean (SD) age was 67 (11.3) years. A total of 3294 patients underwent early parathyroidectomy (8.2%). The weighted cumulative incidence of depression was 11% at 5 years and 18% at 10 years among patients who underwent parathyroidectomy, compared with 9% and 18%, respectively, among nonoperative patients. Those treated with early parathyroidectomy experienced no difference in the adjusted rate of new depression compared with nonoperative management (hazard ratio, 1.05; 95% CI, 0.94-1.17). There was also no estimated effect of early parathyroidectomy on new depression in subgroup analyses based on patient age or serum calcium., Conclusions: In this study, there was no difference in the incidence of new depression among adults with PHPT treated with early parathyroidectomy vs nonoperative management, which is relevant to preoperative discussions about the benefits and risks of operative treatment.

Purpose: To evaluate the potential benefit of adding a low frequency vascular probe to the conventional pre-operative ultrasound examination of patients with primary hyperparathyroidism., Methods: A prospective cohort of 136 patients with primary hyperparathyroidism underwent a conventional ultrasound examination of the neck with a high frequency ( > 10 MHz) linear ultrasound probe, followed by an add-on examination with a low frequency vascular probe. For each ultrasound probe, and for every potential parathyroid lesion, the presence of a feeding vessel, a polar placement of the feeding vessel, and the presence of a vascular arch was recorded., Results: A total of 146 ultrasound lesions were evaluated for vascularity by each probe. For both ultrasound probes, the odds of a hyperfunctioning parathyroid gland being correctly identified increased with the number of visible vascular features. The vascular probe identified a significantly higher number of vascular features among ultrasound true positive glands compared with the conventional probe (p < 0.0001). Among histopathologically verified pathological parathyroid glands, the vascular probe identified 20% more feeding vessels, 27% more polar placements of the feeding vessel, and 65% more vascular arches than the high frequency probe. However, the diagnostic confidence score for true positive glands did not differ significantly between the probes (p = 0.11)., Conclusion: The addition of a low frequency vascular probe increases the number of visible vascular features in hyperfunctioning parathyroid glands, which facilitates their preoperative detection. Whether or not this can increase the diagnostic confidence of ultrasound examiners has yet to be substantiated., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethics approval The study was carried out in accordance with the ethical principles of the 1964 Declaration of Helsinki and its later amendments. The study is registered at ClinicalTrials.gov (NCT04305561) and has been approved by the Regional Committees on Health Research Ethics for Southern Denmark (project ID S-20190077). Consent to participate Written informed consent was obtained from all participants in this study., (© 2024. The Author(s).)

Background/objective: Primary hyperparathyroidism (PHPT) may be asymptomatic or present with renal calculi, secondary osteoporosis, fractures and neuropsychiatric manifestations. Posterior reversible encephalopathy syndrome (PRES) and parkinsonism are atypical manifestations that may be rarely associated with PHPT. We report two patients who presented with the conditions mentioned above., Case Report: The first patient involved a 38-year-old woman who presented with diminution of vision, seizures, altered behavior and hypertension over eight months. An MRI of the brain done had shown vasogenic edema involving the parieto-occipital regions, suggestive of PRES. A metabolic screen revealed PTH-dependent hypercalcemia that was localized to the left inferior parathyroid gland. Following focused parathyroidectomy, there was improvement in sensorium, vision and normalization of blood pressure. The second patient was of a 74-year-old man who presented with progressive extrapyramidal symptoms of gait abnormalities and rigidity since the past eight months. He was initiated on Selegeline and Levodopa for the same purpose, and subsequently reported minimal improvement in symptoms. Investigations revealed PHPT associated with a right inferior parathyroid adenoma. Within two weeks following surgery, there was an improvement in rigidity and gait and he was able to ambulate without support., Discussion: PRES has been reported to occur in the context of preeclampsia, hypertension, infection, sepsis and autoimmune conditions. PRES associated with hypercalcemia is rarely reported. While extra-pyramidally related manifestations are described in hypoparathyroidism, PHPT related parkinsonism is not commonly encountered. Identifying the underlying aetiology and initiation of corrective measures may lead to amelioration of patient symptomatology., Conclusion: The occurrence of PRES and parkinsonism is rare in primary hyperparathyroidism; the two patients described above highlight the importance of screening for hypercalcemia in the setting of neurological manifestations., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Ethical disclosure Informed consent was taken from the patient. The authors declare that no patient data appears in the article., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: There is relatively scarce data regarding the association between primary hyperparathyroidism (PHPT) and incident diabetes in large population-based longitudinal studies. We aimed to evaluate the risk of incident diabetes in individuals with and without PHPT and investigate the association between serum calcium concentrations and the risk of incident diabetes in patients with PHPT., Methods: We included 2749 PHPT patients and 13,745 age, sex and index year matched non-PHPT individuals during 2000-2019. We used Cox regression models to compare the risk of incident diabetes in individuals with and without PHPT, and the risk of incident diabetes in PHPT patients with serum calcium concentration above and below the median value. The association between serum calcium concentrations and the risk of incident diabetes was examined by restricted cubic spline analyses in patients with PHPT., Results: During a median follow-up time of 5.17 years (IQR 2.17, 9.58), 433 patients (15.75%) with PHPT and 2110 individuals (15.35%) without PHPT developed diabetes, respectively. Patients with PHPT had a higher incidence rate of diabetes compared to non-PHPT individuals (27.60 [95% CI 25.00, 30.30] vs. 23.90 [95% CI 22.80, 24.90] per 1000 person-years, log-rank test p = .007]. Crude Cox regression model showed PHPT was associated with a 15% higher risk of incident diabetes (HR 1.15, 95%CI 1.04, 1.28). In patients with PHPT, a 44% higher risk of incident diabetes was found in patients with serum calcium concentrations above the median value (2.63 mmol/L), compared to those below the median value (HR 1.44, 95%CI 1.08, 1.90). Restricted cubic spline analyses confirmed a positive linear association between serum calcium concentrations and the risk of incident diabetes in those with PHPT (p-value for nonlinear = .751) CONCLUSIONS: Patients with PHPT had a higher risk of incident diabetes compared to non-PHPT individuals. A positive linear association was found between serum calcium concentrations and the risk of incident diabetes in patients with PHPT., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

Background: Primary hyperparathyroidism (PHPT) is a treatable cause of nephrolithiasis. However, PHPT is not consistently evaluated in nephrolithiasis patients. Symptoms of parathyroid disease were explored in relation to evaluation of PHPT in nephrolithiasis patients., Methods: Patients with nephrolithiasis on imaging between 2017 and 2021 were identified. Measurement of serum calcium levels after nephrolithiasis diagnosis was determined. Patients with hypercalcemia (≥ 10.2 ​mg/dL) were identified. Characteristics associated with parathyroid hormone (PTH) evaluation and specialist referral were assessed., Results: Of 2264 nephrolithiasis patients with calcium levels measured, 383 (17.1 ​%) had hypercalcemia. Of those, 107 (27.9 ​%) had PTH levels drawn. PTH was more often assessed in patients with higher median calcium levels, recurrent nephrolithiasis, depression, and osteopenia/osteoporosis. PTH was elevated (>64 ​pg/mL) or non-suppressed (40-64 ​pg/mL) in 68 (63.6 ​%) patients. Of those, 31 (45.6 ​%) were referred to a parathyroid specialist. Referred patients had higher PTH and calcium levels than those without referral, and higher rates of osteopenia/osteoporosis., Conclusions: PTH evaluation in hypercalcemic nephrolithiasis patients was low. The majority of patients evaluated had elevated or non-suppressed PTH levels, but only a fraction were referred to a specialist., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships, with respect to employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, research grants or other funding, that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Denosumab is a completely human monoclonal high-affinity antibody that binds to the nuclear factor kappa-B ligand (RANKL) and is widely used to treat osteoporosis. Furthermore, it can potentially lower serum calcium levels by inhibiting osteoclast activation and preventing bone calcium from being released into the blood. This review aimed to provide evidence of the efficacy and safety of denosumab in treating hypercalcemia in primary hyperparathyroidism (PHPT). PubMed and the Cochrane Library were searched for published studies that described denosumab for hypercalcemia management in PHPT. Data were extracted by two independent investigators and analyzed using SPSS 23. The risk of bias was assessed by NIH Quality Assessment Tool. In total, 161 patients with PHPT from 18 studies were included in this review. The average age was 61 (47-72) years and the highest serum calcium was 3.76 (3.11-4.20) mmol/l. We found that denosumab can effectively reduce the serum calcium level by a median reduction of 0.5 mmol/l within 3 days. Significant reduction was maintained for 14 days. The serum calcium-lowering effect weakened after one month. In conclusion, denosumab has a potential clinical value in treating hypercalcemia in patients with PHPT., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background: Primary hyperparathyroidism (pHPT) is the third most common endocrine system disorder. Parathyroidectomy (PTx) is the gold standard of care in symptomatic patients. Patients who are not surgical candidates may benefit from percutaneous ethanol ablation, which is a minimally invasive procedure. This study aims to evaluate the effectiveness and safety of PTx vs. PEA., Method: A single-centered randomized, not-blinded parallel clinical trial in consecutive patients with pHPT treated with percutaneous alcohol ablation (PEA) between January 2020 and November 2021. Patients with a confirmed solitary parathyroid adenoma and a biochemically verified pHPT were randomly enrolled in the PTx or PEA groups. Complications and lab data were evaluated 24 h, 2 weeks, 3 months, and 6 months following interventions. Effectiveness was defined as complete response (normal calcium and PTH), partial response (reduced but not normalized PTH with normal serum calcium), or disease persistence (elevated calcium and PTH). SPSS 22.0 was used for statistical analysis., Result: The final sample comprised 68 patients in each group which 113 of whom were female (83.0%). Complete response was observed in 91.1% (n = 62) of the PEA group and 98.5% (n = 67) of the PTx group. According to repeated-measures analysis, Calcium, PTH, Phosphorus, and Alkaline phosphatase fell significantly and continuously in each intervention group, except for the persistent patients. According to ROC analysis, a cutoff of > 425.5 mm3 for the adenoma volume and > 13.5 mm for its largest diameter showed a sensitivity = 75% and specificity = 69% for partial response in the PEA group (AUC = 0.81 and 0.84, respectively). PTx group experienced statistically significant higher pain according to the Visual Analogue Scale (VAS score) (p < 0.001)., Conclusion: PTH, serum-adjusted Calcium, and adenoma size and volume were all significantly reduced by PTx and PEA, with no significant difference between them. PEA is an effective alternative to PTx, particularly in adenomas with a volume of less than 425.5 mm3 and a maximum diameter of 13.5 mm., Trial Registration Number: IRCT20210204050241N1 (04/26/2021)., Competing Interests: Declarations. Ethics approval and consent to participate: This trial was accepted by the ethics committee of the Isfahan University of Medical Sciences, with the ethical code: IR.MUI.MED.1400.003 and registration in the clinical trials databases with the IRCT20210204050241N1 code. Written informed consent was obtained from all participants before enrollment. Consent for publication: Not Applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: There has been a shift in recent years toward same-day parathyroidectomies due to the decrease in mutual costs with few significant differences in postoperative morbidity or mortality. We sought to determine if demographics, preoperative patient risk factors, or comorbidities were associated with a patient's likelihood of having same-day or inpatient surgery., Materials and Methods: A prospective database of parathyroid operations from 2001 to 2022 (n = 2948 patients) was reviewed for surgeries completed for primary hyperparathyroidism. Patients were categorized as same-day or inpatient surgery; demographics, risk factors, and co-morbidities were examined and differences across practice patterns during the 21-year period were studied and also analyzed in a subset of patients from 2013 to 2022., Results: In a recent subset of patients from 2013 to 2022, patients having inpatient surgery were more likely to be Black and use anticoagulation or antiplatelet therapy. Multivariable regression confirmed increased odds of aging and black patients requiring inpatient parathyroidectomy. Compared to 2001-2003, there was a significantly increased proportion of patients undergoing same-day surgery; compared to 2010-2012, there was a similar proportion of patients undergoing outpatient surgery between 2013 and 2018, and there was an increased proportion from 2019 through 2022., Conclusion: Same-day parathyroidectomies have been shown to be safe and has become the typical practice for high-volume parathyroid surgeons over the last decade. Complications such as postoperative hematoma or hypocalcemia were previously shown to be incompletely mitigated by increased LOS or inpatient surgery, although demographics are considered to increase the odds of inpatient parathyroidectomy., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Minimally invasive parathyroidectomy is the treatment of choice in patients with primary hyperparathyroidism (PHP), but it needs a reliable preoperative localization method to detect hyperfunctioning parathyroid tissue. Higher sensitivity and lower radiation exposure was demonstrated for [ 18 F]fluorocholine PET/CT (FCh-PET/CT) in comparison to [ 99m Tc]sestamibi (MIBI) scintigraphy. However, data of its efficiency in resource use and patient outcomes is lacking. The aim of our study was to determine the resource efficiency and patient outcomes of FCh-PET/CT in comparison to conventional MIBI scintigraphy., Patients and Methods: A group of 234 patients who underwent surgery after MIBI scintigraphy was compared to a group of 163 patients who underwent surgery after FCh-PET/CT. The whole working process from the implementation of imaging to the completion of surgical treatment was analyzed. The economic burden was expressed in the time needed for the required procedures., Results: The time needed to perform imaging was reduced by 83% after FCh-PET/CT in comparison to MIBI scintigraphy. The time needed to perform surgery was reduced by 41% when intraoperative parathyroid hormone monitoring was not used. There was no significant difference in the time of surgery between FCh-PET/CT and MIBI scintigraphy., Conclusions: FCh-PET/CT reduces the time of imaging, the time of surgery and potentially reduces the number of reoperations for persistent disease., (© 2024 Sebastijan Rep et al., published by Sciendo.)

A man in his late 30s with gait difficulty, dysarthria, impaired consciousness and polyuria was diagnosed with left thalamic infarction. Hypercalcaemia (3.52 mmol/L (2.15-2.52)), high intact-parathyroid hormone (i-PTH) levels (88.8 pmol/L (1.1-6.9)) and high D-dimer levels (14.7 mg/L (<1.0)) were identified, followed by a positive microbubble test on transesophageal echocardiogram, suggesting high-risk patent foramen ovale (PFO) for ischaemic stroke. Paradoxical cerebral embolism via PFO, complicated by a hypercoagulable state and hypercalcemic dehydration, was considered. Polyglandular parathyroid hyperplasia, plus radiolucent mandibular tumours, suggested multiple endocrine neoplasia type 1 (MEN1) or hyperparathyroidism-jaw tumour syndrome. Genetic testing confirmed MEN1. Treatment was 24 mg of oral evocalcet and total parathyroidectomy with forearm autotransplantation, resulting in improved serum calcium and i-PTH levels. Finally, he underwent transcatheter PFO closure. We emphasise careful, etiological pursuit in young-onset stroke and the usefulness of genetic testing in differentiating hyperparathyroidism associated with mandibular tumours., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: As a rare cause of femoral neck fracture, usually, hyperparathyroidism is missed diagnosed by orthopedist. Patient can present with various disappearance of clinical manifestations. Primary hyperparathyroidism in senile male population is commonly an asymptomatic disorder discovered incidentally through routine lab testing. Here, this study reports a case of femoral neck fracture in a senile patient with primary hyperparathyroidism., Patients Concerns: A 70-year-old male patient with a known right femoral neck fracture associated with primary hyperparathyroidism., Diagnoses: A neck ultrasound (US) and computed tomography revealed a solid mass below the right lobe of the thyroid. X-ray plain and computed tomography confirmed right femoral neck fracture and multiple bone lesions. The routine lab testing showed hypercalcemia and hyperkalemia., Interventions: Before undergoing total hip arthroplasty surgery, patient was temporarily treated with hydration, diuretics, and calcitonin. Besides, the patient underwent parathyroidectomy of the enlarged parathyroid gland. Oral calcium preparations were routinely used for prevention of hypocalcemia., Outcomes: After completing all surgery, the patient was discharged without any complications including hypercalcemia and hyperkalemia., Lessons: Femoral neck fracture associated with primary hyperparathyroidism is a rare presentation. This case highlights that hypercalcemia and multiple osteopathy should be considered in the differential diagnosis in patients with pathological fracture caused by micro-traumatic injury., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Context: Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with an impact on fracture incidence and bone mineral density after surgery have not been firmly established., Objective: To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT)., Design: Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register., Setting: Tertiary referral center., Patients or Other Participants: Seven hundred nine patients with successful parathyroidectomy for pHPT and 2112 controls matched on sex, age, and municipality were included in the study., Main Outcome Measures: Fracture incidence, absolute change, and ≥2.77% increase in bone mineral density of femoral neck, L2-L4, and distal third of radius at 1-year follow-up., Results: Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (incidence rate ratio for the highest tertile 220- mg/d 0.29, 95% confidence interval 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin, and adenoma weight were all associated with bone mineral density recovery after surgery., Conclusion: Twenty-four-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Current evidence of cardiovascular (CV) risk in primary hyperparathyroidism (PHPT) is still inconsistent., Objective: To prospectively investigate changes of early atherosclerosis in patients with PHPT undergoing parathyroidectomy (PTx) or conservative management, according to consensus criteria., Methods: Biochemical parameters of PHPT, CV risk factors (systolic and diastolic blood pressure, cholesterol [total, high-density, and low-density], triglyceride, HbA1c, HOMA-IR), and carotid intima-media thickness (IMT) and plaque were assessed in 52 consecutive postmenopausal PHPT patients both at baseline and ≥ 24 months after surgery (PTx, n = 22) or conservative management (non-PTx, n = 30)., Results: At baseline, PTx and non-PTx showed comparable age, BMI, renal function, and 25(OH)D levels, and did not differ for CV risk factors, IMT and plaques, or for prevalence of smoking, diabetes mellitus, or antihypertensive or statin therapy, while all parameters characterizing PHPT differed. Follow-up duration in PTx was longer than in non-PTx (P = .004). Parameters characterizing PHPT significantly improved ≥ 24 months after surgery, whereas in non-PTx serum phosphate slightly decreased and parathyroid hormone increased. Systolic and diastolic blood pressure increased at follow-up in both groups, while other CV risk factors did not significantly vary. In PTx, IMT did not significantly vary after surgery (0.85 ± 0.14 to 0.89 ± 0.22 mm, P = .366), whereas it significantly increased in non-PTx (0.80 ± 0.18 to 0.93 ± 0.23 mm, P = .008), even adjusting for blood pressure. Plaque prevalence and incidence did not significantly differ in the 2 groups., Conclusion: Our results suggest that in postmenopausal patients with PHPT, subclinical atherosclerosis could be halted by PTx, whereas it worsens over time in nonoperated patients with milder disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Primary hyperparathyroidism is an endocrine disease and a common cause of nonmalignant hypercalcemia, often discovered incidentally in asymptomatic patients. The case reported herein illustrates that significant hormonal imbalances can present with unexpectedly mild clinical manifestations., Case Presentation: We describe a 47-year-old Caucasian male with two episodes of kidney stones and otherwise no symptoms of severe hypercalcemia. In our case, fasting emerged as a potential risk factor for the development of renal stones. The diagnosis was primary hyperparathyroidism. The intervention consisted of preoperative fluids and cinacalcet while awaiting surgery. Despite initial stability, the patient experienced a subsequent increase in ionized calcium and parathyroid hormone levels, becoming symptomatic with fatigue, tremors, and heart palpitations. This progression led to a diagnosis of a hypercalcemic crisis, and the plan was accelerated. An acute parathyroid scintigraphy and an ultrasound was performed and revealed a giant intrathoracic parathyroid adenoma. After surgical removal of the adenoma, he developed hungry bones and biochemical remission. The patient has received three extracorporeal shock wave lithotripsy treatments for a stone in the upper left kidney, but as of a computed tomography scan on 9 February 2024, the stone remains unchanged. Owing to the stone's resistance to extracorporeal shock wave lithotripsy and the absence of symptoms, no further treatment is planned. Endoscopic laser treatment (retrograde intrarenal surgery) is an option, but for now, the situation will be monitored., Conclusion: This case report underscores that extremely elevated levels of calcium and parathyroid hormone along with a rare giant parathyroid adenoma may not necessarily present with symptoms indicative of a calcium crisis. Additionally, management of such rare giant parathyroid adenomas requires careful monitoring and a tailored approach to address potential postsurgical complications such as hungry bone syndrome., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval was not required for this case report as it pertains to a single patient´s treatment and outcome, and no experimental procedures were involved. The patient provided informed consent for the treatment and the publication of their case details. All patient information has been anonymized to protect privacy. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests All authors state that they have no competing interests, (© 2024. The Author(s).)

The main diagnostic dilemma in normocalcemic hyperparathyroidism is differentiating this condition from secondary hyperparathyroidism and other causes of elevated parathyroid hormone (PTH) levels in eucalcemic patients, including potential assay interferences. Despite the analytical sensitivity of immunoassays, they may lack adequate accuracy due to several analytical interferences, such as the presence of heterophilic antibodies. Immunoassays for PTH measurement use the immunometric "sandwich" technique, and only a few cases of interference with this assay have been reported to date. We describe herein two patients in whom PTH immunoassay interference was demonstrated. Both patients presented high serum PTH levels, measured using a second-generation Roche electrochemiluminescence assay (ECLIA; Elecsys Roche, Germany), and normocalcemia. When immunoassay interference was suspected, PTH measurements were repeated using a different analytical platform, the 1-84 PTH third-generation Roche Elecsys ECLIA, resulting in normal levels. We subsequently performed serial dilutions using normal mouse serum with the second-generation ECLIA and found no linearity, indicating the presence of interference in both patients. Immunoassay interference may lead to misinterpretation of a patient's results by the laboratory and incorrect treatment planning by the attending physician. Despite its rarity, the presence of interferences in the PTH immunoassay resulting in falsely high PTH levels should be considered when the laboratory result does not match the patient's clinical presentation, thus preventing erroneous diagnoses and unnecessary therapeutic procedures., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Objective: This study analyzed systemic inflammatory changes reflected by hematologic and biochemical indices in patients with hyperparathyroidism (PHPT) after parathyroidectomy., Materials and Methods: Retrospective study of 70 patients who underwent curative parathyroidectomy for PHPT treatment. Data on clinical presentation, biochemical assays, imaging studies, and postoperative outcomes were collected. Systemic inflammation was quantified using different indices, including the triglyceride-glucose (TyG) index, Fibrosis-4 (FIB-4) score, systemic immune-inflammation index (SII), monocyte-to-high-density lipoprotein cholesterol ratio (MHR), platelet-to-lymphocyte ratio (PLR), and platelet distribution width (PDW)., Results: Significant pre-surgical to post-surgical decreases were observed in serum levels of mean normalized calcium (11 ± 0.65 mg/dL and 9.1 ± 0.42 mg/dL, respectively, p = 0.001) and parathyroid hormone (PTH) (235.5 ± 132.9 and 78.1 ± 60.5 ng/L, respectively, p = 0.001). The inflammatory indices changed substantially, with decreases in SII (from 564.8 ± 257.5 to 516.6 ± 201.1, p = 0.001) and PLR (from 143.0 ± 46.2 to 133.6 ± 38.6, p = 0.001). Additionally, PDW decreased from 52.8 ± 8.2% to 47.5 ± 9.3% (p = 0.001) and MHR increased from 7.19 ± 3.06 to 7.81 ± 3.13 (p = 0.001). No significant changes occurred in other inflammatory markers, including the TyG index (p = 0.431) and FIB-4 score (p = 0.401). Logistic regression analysis identified PDW (odds ratio [OR] 0.920, 95% confidence interval [CI] 0.879-0.963, p = 0.001) and PLR (OR 0.991, 95% CI 0.983-1, p = 0.042) as significant predictors of inflammation., Conclusions: Successful parathyroidectomy in patients with PHPT reduces systemic inflammation, as evidenced by decreased PDW and PLR. Our results indicate the importance of integrating PDW and PLR in the postoperative assessment of PHPT for monitoring inflammatory activity., Competing Interests: Disclosure: no potential conflict of interest relevant to this article was reported.

Importance: The success of parathyroidectomy depends on accurate intraoperative localization and identification of all diseased glands in parathyroid exploration based on surgeon expertise to prevent persistent hyperparathyroidism. Near-infrared autofluorescence (NIRAF) imaging has recently emerged as a promising adjunctive intraoperative tool for localizing parathyroid glands; however, its potential utility in the assessment of parathyroid glands has yet to be established., Objective: To analyze the differences in NIRAF signatures of parathyroid glands in single vs multiple glands in primary hyperparathyroidism (pHPT)., Design, Setting, and Participants: This prospective diagnostic study analyzed in vivo NIRAF images of parathyroid glands obtained during parathyroidectomies between November 18, 2019, and December 31, 2023, at a single tertiary referral center. Pixel intensities of the images were measured using third-party software. Patients who underwent parathyroidectomy for sporadic pHPT using a second-generation NIRAF imaging device were included. Patients with multiple endocrine neoplasm disorders were excluded. In vivo NIRAF images obtained during the procedures were analyzed., Exposure: Near-infrared autofluorescence imaging during parathyroidectomy., Main Outcomes and Measures: The primary outcomes were the autofluorescence intensity and heterogeneity of single adenomas and multigland disease (ie, double adenomas and 3- or 4-gland hyperplasia) in sporadic pHPT. Normalized autofluorescence intensity was calculated by dividing the mean pixel intensity of the parathyroid gland by the background tissue. A heterogeneity index was calculated by dividing the standard deviation by the mean pixel intensity of the gland. The secondary outcome was the visibility of each parathyroid gland on NIRAF imaging before it became apparent to the naked eye during exploration., Results: A total of 1287 in vivo NIRAF images obtained from 377 patients (median [IQR] age, 66 [56-73] years; 299 female [79.3%]) were analyzed. Of all patients, 230 (61.0%) had a single adenoma, 91 (24.1%) had double adenomas, and 56 (14.9%) had 3- or 4-gland hyperplasia. A mean (SD) of 3.4 (1.1) parathyroid glands were identified in the procedures. A comparison of 581 diseased glands (45.1%) and 706 normal glands (54.9%) showed a lower median normalized autofluorescence intensity of 2.09 (95% CI, 1.07-4.01) vs 2.66 (95% CI, 1.43-4.20; effect size = 0.36) and higher heterogeneity index of 0.18 (95% CI, 0.07-0.41) vs 0.11 (95% CI, 0.01-0.27; effect size = 0.45), respectively. Of diseased glands, single adenomas (233 [40.1%]) vs double adenomas (187 [32.2%]) and 3- or 4-gland hyperplasia (161 [27.7%]) had a lower median autofluorescence intensity of 1.92 (95% CI, 1.02-4.44) vs 2.22 (95% CI, 1.10-3.97; effect size = 0.21), respectively. On receiver operating characteristic analysis, the optimal autofluorescence intensity threshold to differentiate between single adenomas vs multigland disease was 2.14, with a sensitivity of 64.4%, specificity of 58.1%, and area under the curve of 0.626., Conclusions and Relevance: These findings suggest that parathyroid glands in single- vs multigland disease may exhibit different autofluorescence characteristics. Although the effect size was modest, the differences identified should be kept in mind when assessing the parathyroid glands during surgical exploration.

Objective: To develop evidence-based recommendations to guide the surgical management and postoperative follow-up of adults with primary hyperparathyroidism., Methods: Representatives from relevant Australian and New Zealand Societies used a systematic approach for adaptation of guidelines (ADAPTE) to derive an evidence-informed position statement addressing eight key questions., Results: Diagnostic imaging does not determine suitability for surgery but can guide the planning of surgery in suitable candidates. First-line imaging includes ultrasound and either parathyroid 4DCT or scintigraphy, depending on local availability and expertise. Minimally invasive parathyroidectomy is appropriate in most patients with concordant imaging. Bilateral neck exploration should be considered in those with discordant/negative imaging findings, multi-gland disease and genetic/familial risk factors. Parathyroid surgery, especially re-operative surgery, has better outcomes in the hands of higher volume surgeons. Neuromonitoring is generally not required for initial surgery but should be considered for re-operative surgery. Following parathyroidectomy, calcium and parathyroid hormone levels should be re-checked in the first 24 h and repeated early if there are risk factors for hypocalcaemia. Eucalcaemia at 6 months is consistent with surgical cure; parathyroid hormone levels do not need to be re-checked in the absence of other clinical indications. Longer-term surveillance of skeletal health is recommended., Conclusions: This position statement provides up-to-date guidance on evidence-based best practice surgical and postoperative management of adults with primary hyperparathyroidism., (© 2021 John Wiley & Sons Ltd.)

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, predominantly caused by a single parathyroid adenoma that is responsible for the excessive secretion of parathyroid hormone (PTH)-the hallmark of disease. Excess of this hormone causes remarkable changes in bone metabolism, including an increased level of bone remodeling with a predominance of bone resorption. Those changes lead to deterioration of bone structure and density, especially in cortical bone. The main treatment for PHPT is surgical removal of the adenoma, which normalizes PTH levels and terminates the progression of bone disease and leads to its regeneration. However, because not all the patients are suitable candidates for surgery, alternative therapies are needed. Current non-surgical treatments targeting bone disease secondary to PHPT include bisphosphonates and denosumab. Those antiresorptives prevent further bone loss, but they lack the ability to regenerate already degraded bone. There is ongoing research to find targeted drugs capable of halting resorption alongside stimulating bone formation. This review presents the advancements in understanding the molecular mechanisms responsible for bone disease in PHPT and assesses the efficacy of new potential therapeutic approaches (e.g., allosteric inhibitors of the PTH receptor, V-ATPase, or cathepsin inhibitors) aimed at mitigating bone loss and enhancing bone regeneration in affected patients.

Purpose: The current primary hyperparathyroidism (PHPT) presents as a mild disease. We explored skeletal phenotypes in postmenopausal women affected by PHPT, focusing on fracture prevalence., Methods: PHPT women were retrospectively evaluated at four Italian centers for osteoporosis management (two centers in Milan, n = 244; Cuneo, n = 128; Pisa, n = 131). Data collected from clinical records were analyzed by hierarchical clusterization., Results: Considering the whole PHPT series [ n = 503, aged 67.0 (61.0-74.0) years], 90% had low bone mineral density (BMD) and approximately 30% reported at least one fracture. Vertebral fractures were associated with older age and lower hypophosphatemia, while women with appendicular fractures were younger with less severe hypophosphatemia. Fractures were predicted by lumbar T -score. By using a clustering approach, we identified four different skeletal phenotypes (cluster, C): C1 ( n = 53) and C2 ( n = 172) included women with lumbar and femur neck osteopenia, with low prevalence of fractures (11.3%). Osteoporotic PHPT women were grouped into C3 ( n = 142) and C4 ( n = 136); all women in C4 experienced fractures, were older, and were more frequently affected with cardiovascular diseases. In contrast, women included in C3 never experienced fractures and had a lower body mass index (BMI), though they were characterized by severe reduction in BMD at both lumbar and femur sites. Ionized and total calcium, phosphate, 25hydroxyvitamin D levels, kidney function, and stone prevalence (range, 26.4%-29.0%) were similar among clusters C1, C2, and C4, while unfractured women in C3 showed slightly higher ionized hypercalcemia, lower hypophosphatemia, and higher hypercalciuria with a trend to more frequently develop kidney stones (38.7%) than women in the remaining clusters., Conclusions: Skeletal involvement in women with PHPT presented heterogeneous phenotypes with different prevalence of fractures. Fractures were not related to PHPT severity, suggesting that other factors besides PHPT, such as age, BMI, and lumbar and femur BMD, should be considered in the evaluation of bone involvement in postmenopausal women 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Corbetta, Gianotti, Castellano, Carrara, Raineri, Munari, Guabello, Cairoli, Chiodini, Giovanelli, Pierotti, Dinoi, Della Valentina and Cetani.)

Background: Brown tumors are rare bone manifestations of primary hyperparathyroidism (PHPT) that may occur at different sites either as single or multiple lesions and they can easily be mistaken for malignant lesions. Neither bone site nor morphological or functional imaging are useful to drive the differential diagnosis and biopsy is often the only conclusive procedure., Case Description: We report the case of a 53 years-old man referred to our outpatient clinic for severe symptomatic PHPT complicated by nephrolithiasis and osteoporosis. Neck ultrasound and computed tomography (CT) scan showed a large irregular lesion posterior to the lower pole of the right thyroid lobe consistent with an enlarged parathyroid gland. Moreover, two bone lytic lesions were described at the left scapula and the contiguous 7 th rib that showed an increased uptake at total bone scintigraphy. Given the clinical and biochemical picture, the features of the parathyroid lesion and the presence of bone lytic lesions, the suspicion of metastatic parathyroid carcinoma (PC) was raised. However, a CT-guided biopsy performed on the left scapula revealed a brown tumor. The patient underwent en-bloc resection of the right inferior parathyroid grand with the ipsilateral thyroid gland lobe. Histopathology confirmed the diagnosis of PC. Post-surgical biochemical evaluations showed that the patient was cured. A repeated total body CT scan revealed an osteoblastic appearance of the bone lesions ascribed to the partial regression of the brown tumors following surgery., Conclusions: The implication of a diagnosis of brown tumor or bone metastasis is widely different; in fact, the first tends to regress with the surgical treatment of PHPT, whereas the latter has limited cure option and negatively affects the prognosis of patients. Therefore, although brown tumors are extremely rarer than in the past, they must always be taken into consideration in the presence of bone lesions, even in cases of high suspicion of malignancy, to avoid unnecessary and harmful surgical interventions., 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 © 2024 Dinoi, Prete, Sardella, Pierotti, Della Valentina, Dal Lago, Borsari, Pardi, Caligo, Michelucci, Torregrossa, Rossi and Cetani.)

Primary hyperparathyroidism (PHPT) due to ectopic parathyroid adenoma is a rare case of hypercalcemia in the pediatric population. Herein, a rare case of PHPT due to ectopic intrathymic parathyroid adenoma was described in an asymptomatic 15-year-old girl who had incidental diagnosis based on laboratory abnormalities but experienced a 3-month postoperative course of persistently elevated parathyroid hormone (PTH) and hypercalcemia following the initial unsuccessful parathyroidectomy operation carried out in a non-parathyroid expert center. The curative surgical treatment was accomplished only after the patient was reoperated with video-assisted thoracoscopic surgery (VATS) thymectomy by the surgeon experienced in parathyroid surgery with implementation of the combined imaging modalities for accurate localization of ectopic adenoma including 99mTc sestamibi (MIBI) plus neck and thoracic computed tomography (CT) and the appropriate surgical strategies including intraoperative intact PTH monitoring and frozen section diagnosis. Before the reoperation (VATS thymectomy), laboratory findings showed elevated PTH (1,171 ng/L; reference range: 21.80 ng/L-87.5 ng/L) and hypercalcemia (13.4 mg/dL; reference range: 8.4 mg/dL-10.2 mg/dL). The preoperative PTH levels were 94 ng/L at 5 min after thymectomy and 78 ng/L at 10 min. The PTH and calcium levels were 54.3 ng/L and 8.47 mg/dL, respectively, on postoperative day 1 and were 34.2 ng/L and 8.1 mg/dL on postoperative day 2. The patient was discharged on postoperative day 2 without any complications. In conclusion, our findings indicate the likelihood of isolated primary hyperparathyroidism to be incidentally diagnosed based solely on laboratory abnormalities with no specific clinical manifestations in the pediatric age. In addition, using combined imaging modalities (such as MIBI and CT) in accurate localization of ectopic parathyroid adenoma and implementation of surgery by experienced surgeons along with intraoperative intact PTH monitoring and frozen section diagnosis seem crucial to ensure the curative surgical treatment., Competing Interests: The author declares 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 © 2024 Gurluler.)

Objective: To summarize and analyze the diagnostic and therapeutic characteristics of asymptomatic primary hyperparathyroidism (aPHPT). Methods: A retrospective analysis was conducted on the clinical data of 103 patients with aPHPT admitted to the Chinese PLA General Hospital from January 2012 to September 2023. The clinical characteristics, treatment modes, and prognoses of the patients were analyzed. GraphPad Prism 8.0 software was used for statistical analysis. Results: Among the 103 cases, there were 37 males and 66 females, aged from 25 to 78 years, with an average age of (53.81±11.34) years. Ninety-eight cases (95.15%) visited due to abnormal findings during physical examination and 5 cases (4.85%) due to hypertension, diabetes or other diseases. All patients underwent minimally invasive parathyroidectomy with small incision, with 96 cases (93.20%) pathologically diagnosed as adenomas and 7 cases as hyperplasia (6.80%). Postoperative mean serum calcium, parathyroid hormone (PTH) and alkaline phosphatase (ALP) levels were respectively significantly lower than preoperative levels, while postoperative serum phosphorus level was significantly higher than preoperative level ( P <0.05). The mean lesion volume was (3.32±6.72)cm 3 (range 0.05-49.50 cm 3 ). Patients with different lesion volumes had significant differences in preoperative serum calcium, PTH and ALP levels. Lesion volume was positively correlated to preoperative serum calcium(ρ=0.36, P <0.01), PTH(ρ=0.50, P <0.01) and ALP(ρ=0.39, P <0.01). Among 103 patients, 94 cases were followed up (91.26%), 9 cases were lost (8.74%), and the mean follow-up period was (60.15±29.23) months. The followed-up patients were alive and had no recurrence of lesions or complications, and their blood calcium levels were normal. Conclusion: aPHPT can be preliminarily diagnosed through blood biochemistry and imaging examination, and minimally invasive surgery can offer good prognosis without serious complications.