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A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) in pregnant women is a rare condition, often remaining undiagnosed due to non-specific clinical symptoms. However, it can lead to life-threatening complications for both the mother and fetus. In vitro fertilization (IVF) is also associated with an increased probability of adverse outcomes compared to the general population. Timely diagnostics and personalized treatment, taking into account the extremely high risk of complications if PHPT and pregnancy result from IVF, require attention of healthcare professionals and formation of a multidisciplinary team.

Background- Primary Hyperparathyroidism (PHPT) has been associated with increased cardiovascular morbidity and early death. Data on the extent and clinical significance of cardiovascular abnormalities in primary hyperparathyroidism (PHPT) are conflicting. The main objective of this study was to evaluate the cardiac function in patients with PHPT without other known risk factors and to analyze the effect of parathyroidectomy. Methodology- In a Prospective Observational Cohort design, sixteen patients with Primary Hyperparathyroidism underwent Two-dimensional echocardiography, Electrocardiography, serum N-terminal pro-brain natriuretic peptide (NT-proBNP, a myocardial damage marker), before and 3 months after successful parathyroidectomy. Result- We observed significant improvement in Left ventricular ejection fraction (p = 0.010) in patients undergoing parathyroid surgery after 3 months postoperatively. There is significant reduction in LVMI (p=0.044) & posterior wall thickness (p=0.007), which are indicators of left ventricular hypertrophy after 3 months of surgery. Conclusion- Patients with PHPT who are symptomatic exhibit significant cardiovascular dysfunction, which improves three months following successful parathyroidectomy. As a part of screening, we should consider routine cardiovascular evaluation in all symptomatic patients of PHPT. Symptomatic PHPT patients should undergo early curative surgery for the reversal of the cardiovascular dysfunction and in asymptomatic PHPT patients also early surgery is recommended for the prevention of end organ damage. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) in paediatric and adolescent age group presents with some unique challenges for clinicians. While the disease in the adult counterparts presents with symptoms which are described quite extensively in literature, children/adolescents have manifestations which are quite different and severe compared to the former. The present case series aimed to highlight the peculiarities of presentation of PHPT in children and adolescents. In this case series, we present experience of 5 cases of PHPT in children and adolescents from our centre. We compared our data with the data already available in literature. We have also described salient presenting features of PHPT in individuals less than 19 years old previously reported in literature and pointed out the specificities of this disease at this age group. PHPT in children and adolescents should be considered as a separate entity compared to that in adults, given its unique features, such as rachitic features, and severity of different presenting phenotypes. Persistence of rachitic features despite vitamin D correction, pancreatitis, bilateral nephrolithiasis and otherwise unexplained psychiatric abnormalities of insidious onset require greater clinical vigilance and serum/urine calcium testing to rule out this uncommon yet possible entity. [ABSTRACT FROM AUTHOR]

Bakground: Vitamin D (Vit D) deficiency is common in patients with hyperparathyroidism, but the importance of replacement before surgery is controversial. It can be predicted that hypocalcemia risk will be higher in patients with high bone turnover. Aim: In this study, the effect of preoperative ALP/Vit D ratio on postoperative hypocalcemia was investigated. Methods: Among the primary hyperparathyroidism cases who were operated between 2015 and 2022, 158 patients with complete data were included in the study. Preoperative laboratory results, radiological images, and pathology reports of the patients were evaluated retrospectively. The cross-sectional value of the ALP/Vit D value predicting hypocalcemia was calculated. The effect of these parameters on postoperative hypocalcemia was investigated. Results: The mean age of our patients was 54 (21–81 years). When factors affecting postoperative hypocalcemia were evaluated by univariable analysis, Vit D deficiency and insufficiency (p < 0.001), ALP (p < 0.001), ALP/Vit D ratio (p < 0.001), and T score (p = 0.026) found to be factors affecting postoperative hypocalcemia. In multivariate analysis, the ALP/Vit D ratio was found to be an independent variable in predicting hypocalcemia. It was found that hypocalcemia was 45 times more common in patients with ALP/Vit D > 6.34 (p < 0.001). ALP/Vit D ratio predicts patients who will develop postoperative hypocalcemia with 87.2% sensitivity and 87.1% specificity. Conclusions: Vit D deficiency increases the risk of postoperative hypocalcemia, but it is not sufficient alone to predict it. The risk increases more in patients with high bone turnover. The preoperative ALP/Vit D ratio is the strongest predictor of postoperative hypocalcemia risk. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism (PHPT) is an endocrinological disease that affects systemic inflammation. This study is aimed to investigate the preoperative and postoperative effect of PHPT on systemic inflammation. A total of 203 patients who were successfully operated for PHPT and 98 healthy controls were included in the study. The blood tests of the patients in the last month preoperatively and in the postoperative 6th month were compared. In addition, preoperative and postoperative tests were compared with the healthy control group. When the preoperative neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic inflammation index (SII) values of the patients who were operated for parathyroid adenoma were compared with the control group (p values were < 0.05, 0.01, 0.19, < 0.05), the NLR, PLR, and SII values were significantly lower in the patient group with parathyroid adenoma than in the control group. When the preoperative and postoperative 6th month NLR, PLR, LMR, and SII values of the patients were compared (p values: 0.026, 0.56, 0.023, 0.016, respectively), there was a significant increase in NLR and SII values after excision, while a significant decrease was observed in the LMR value. When the postoperative 6th month NLR, PLR, LMR, SII values were compared with the healthy control group (p values: 0.22, 0.29, 0.19, 0.29, respectively), no significant difference was observed between all values. We found that the immune system was suppressed in PHPT and this returned to normal levels after a successful surgery. [ABSTRACT FROM AUTHOR]

Purpose: Baseline renal dysfunction predicts mortality in primary hyperparathyroidism (PHPT). However, it remains controversial whether renal insufficiency in PHPT is due to disease severity alone or other risk factors. This study aimed to explore the association of clinico-biochemical variables with renal dysfunction [estimated glomerular filtration rate (eGFR) < 60 ml/min/m2] in PHPT. Methods: A total of 112 patients of PHPT were selected and divided into following subgroups: renal dysfunction (n = 28) and normal renal function (n = 84). Demographic characteristics, traditional risk factors, phenotypes of PHPT based on target organ involvement, and biochemical parameters were compared between these subgroups. Results: Patient subgroups of PHPT with and without renal dysfunction had similar age, frequency of diabetes, and hypertension. Renal dysfunction was more prevalent in males (p < 0.05). Compared to normal renal function subgroup, individuals with renal dysfunction had higher serum levels of calcium, phosphate, alkaline phosphatase, intact parathormone (all p < 0.05), while having lower hemoglobin levels (p < 0.05) and higher nephrolithiasis rates (p < 0.05). Multiple regression analysis revealed that nephrolithiasis, serum calcium-phosphorous product (CaxP), parathormone levels were positively associated with baseline renal dysfunction (all p < 0.01). A baseline PTH > 456 pg/mL and CaxP > 30.0 mg2/dl2 could discriminate renal dysfunction from normal renal function with sensitivity and specificity of 75% and 74.5% and 92.6% and 74.4%, respectively. Conclusion: Renal dysfunction was associated with presence of nephrolithiasis, elevated serum CaxP and PTH levels in our cohort with predominantly symptomatic PHPT, indicating an association with the underlying disease itself. Serum CaxP may additionally be appraised during risk assessment in PHPT. [ABSTRACT FROM AUTHOR]

Wongel Tena Shale,1 Tolasa Dibisa Jirata,2 Mekbeb Chere Enawgaw,1,3 Ararso Gonfa Metekia,2 Yosef Lemma Kelecha1 1Jimma University College of Public Health and Medical Sciences, Department of Surgery, Jimma University, Jimma, Oromia, Ethiopia; 2Jimma University College of Public Health and Medical Sciences, Department of Orthopedic Surgery, Jimma University, Jimma, Oromia, Ethiopia; 3Jimma University College of Public Health and Medical Sciences, Department of Surgery, Urology Unit, Jimma University, Jimma, Oromia, EthiopiaCorrespondence: Wongel Tena Shale, Jimma, Oromia, Ethiopia, Tel +251911636127 ; +251913862475, Email tenawongel@gmail.comBackground: The endocrine disorder known as hyperparathyroidism (HPT) is characterized by excessive parathyroid hormone (PTH) secretion, and when it is accompanied with hypercalcemia it is called primary HPT (PHPT). PHPT is characterized by the hyper-functioning of one or more parathyroids. The most common form of PHPT is sporadic parathyroid adenoma.Case Presentation: A 33-year-old male presented to our emergency room with the classic presentation of PHPT affecting the skeletal, gastrointestinal, genitourinary, and neurologic systems including, multiple long bone fractures and bilateral nephrolithiasis with preserved renal function. Diagnosis was made by elevated serum PTH and calcium levels, as well as, bone imaging. Neck ultrasound and fine needle aspiration cytology (FNAC) of the neck mass were done to localize the lesion. After pre-operative optimization, bilateral neck exploration and en-bloc resection of the left inferior parathyroid with the left lobe of the thyroid was done. In the post-operative period, he developed persistent hypotension and severe hypocalcemia.Conclusion: Although it is uncommon in the industrialized countries, the traditional PHPT presentation with “Bones, Stones, abdominal groans, and psychic moans” is nevertheless common in impoverished nations like Ethiopia. Surgery is the mainstay of treatment but complications such as hungry bone syndrome can increase the post-operative morbidity following parathyroidectomy.Keywords: primary hyperparathyroidism, PHPT, bones, stones, abdominal groans, psychic overtones, brown tumor, hungry bone syndrome, case report

Objective: Accurate demarcation between multiple endocrine neoplasia, type 1 (MEN1)‐ related primary hyperparathyroidism (MPHPT) and sporadic PHPT (SPHPT) is important to plan the management of primary parathyroid disease and surveillance for other endocrine and nonendocrine tumours. The objective of this study is to compare the clinical, biochemical and radiological features and surgical outcomes in patients with MPHPT versus SPHPT and to identify the predictors of MEN1 syndrome in PHPT. Design, Patients and Measurements: This was an ambispective observationalstudy involving 251 patients with SPHPT and 23 patients with MPHPT evaluated at the endocrine clinic of All India Institute of Medical Sciences, New Delhi, India between January 2015 and December 2021. Results: The prevalence of MEN1 syndrome among patients with PHPT was 8.2% and a genetic mutation was identified by Sanger sequencing in 26.1% of patients with MPHPT. Patients with MPHPT were younger (p <.001), had lower mean serum calcium (p =.01) and alkaline phosphatase (ALP; p =.03) levels and lower bone mineral density (BMD) Z score at lumbar spine (p <.001) and femoral neck (p =.007). The prevalence of renal stones (p =.03) and their complications (p =.006) was significantly higher in MPHPT group. On multivariable analysis, factors predictive of MPHPT were hyperplasia on histopathology [OR 40.1, p <.001], ALP levels within reference range [OR 5.6, p =.02] and lumbar spine BMD [OR 0.39 per unit increase in Z score, p <.001]. Conclusions: Patients with MPHPT have more severe, frequent and early onset of bone and renal involvement despite milder biochemical features. A normal serum ALP, low BMD for age and gender at lumbar spine and histopathology evidence of hyperplasia are predictive factors for MEN1 syndrome in PHPT. [ABSTRACT FROM AUTHOR]

Context The glial cells missing 2 (GCM2) gene functions as a transcription factor that is essential for parathyroid gland development, and variants in this gene have been associated with 2 parathyroid diseases: isolated hypoparathyroidism in patients with homozygous germline inactivating variants and primary hyperparathyroidism in patients with heterozygous germline activating variants. A recurrent germline activating missense variant of GCM2 , p.Y394S, has been reported in patients with familial primary hyperparathyroidism. Objective To determine whether the GCM2 p.Y394S missense variant causes overactive and enlarged parathyroid glands in a mouse model. Methods CRISPR/Cas9 gene editing technology was used to generate a mouse model with the germline heterozygous Gcm2 variant p.Y392S that corresponds to the human GCM2 p.Y394S variant. Wild-type (Gcm2 +/+) and germline heterozygous (Gcm2 +/Y392S) mice were evaluated for serum biochemistry and parathyroid gland morphology. Results Gcm2 +/Y392S mice did not show any change compared to Gcm2 +/+ mice in serum calcium and parathyroid hormone levels, parathyroid gland histology, cell proliferation, or parathyroid gland size. Conclusion The mouse model of the p.Y392S variant of Gcm2 shows that this variant is tolerated in mice, as it does not increase parathyroid gland cell proliferation and circulating calcium or PTH levels. Further investigation of Gcm2 +/Y392S mice to study the effect of this variant of Gcm2 on early events in parathyroid gland development will be of interest. [ABSTRACT FROM AUTHOR]

Abstract Background As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion’s location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. Case presentation We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient’s symptoms disappeared and serum levels of PTH and calcium normalized. Conclusions SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT.

Minimally invasive parathyroidectomy (MIP) is the standard of care for primary hyperparathyroidism (PHPT). Four dimensional computed tomography(4DCT) and F‐18 Fluorocholine positron emission tomography/computed tomography (FCH PET/CT) localize adenomas accurately to perform MIP. We aimed to conduct a systematic review and metanalysis to evaluate the diagnostic performance of 4DCT and FCH PET/CT scan for quadrant wise localisation in PHPT patients and to do head‐to‐head comparison between these two modalities. Design, Patients and Measurement : After searching through PubMed and EMBASE databases, 46 studies (using histology as a gold standard) of 4DCT and FCH PET/CT were included. Results: Total number of patients included were 1651 and 952 for 4DCT scan (studies n = 26) and FCH PET/CT scan (studies n = 24) respectively. In per patient analysis, FCH PET/CT and 4DCT had pooled sensitivities of 92% (88−94) and 85% (73−92) respectively and in per lesion analysis, 90% (86−93) and 79% (71−84), respectively. In the subgroup with negative conventional imaging/persistent PHPT, FCH PET/CT had comparable sensitivity to 4DCT (84% [74−90] vs. 72% [46−88]). As per patient wise analysis, FCH PET/CT had better detection rates than 4DCT ([92.4 vs. 76.85], odds ratio −3.89 [1.6−9.36] p =.0024) in the subpopulation where both FCH PET/CT and 4DCT were reported. Conclusion: Both 4DCT and FCH PET/CT scan performed well in newly diagnosed patients, patients with persistent disease and in those with inconclusive conventional imaging results. FCH PET/CT scan had a higher pooled sensitivity than 4DCT in detecting patients with PHPT in head to head comparison. [ABSTRACT FROM AUTHOR]

Background: It has been a matter of debate for long time about the existence of two distinct phenotypes of primary hyperparathyroidism (PHPT) predisposed to either renal or skeletal manifestation. Objective: To differentiate characteristics of symptomatic PHPT patients based on the presence of skeletal or renal involvement. Design: Retrospective analysis of data from the Indian PHPT registry. Patients: PHPT patients were divided into four discrete groups: asymptomatic, presenting with renal manifestations alone, skeletal manifestations alone, and both skeletal and renal manifestations. Measurements: Clinical, biochemical, and tumour weight and histopathological characteristics of these groups were compared. Results: Of the 229 eligible patients, 45 were asymptomatic, 62 had renal manifestations, 55 had skeletal manifestations, and 67 had both skeletal and renal manifestations. Patients with both skeletal and renal manifestations had higher serum calcium levels than those with isolated skeletal involvement [12.5 (11.1–13.7) mg/dL, 11.2 (10.6–12.3) mg/dL, respectively; p <.05]. Serum alkaline phosphatase (AP), plasma parathyroid hormone (PTH) levels, and parathyroid tumour weight were significantly higher in patients with isolated skeletal, and both skeletal and renal manifestations, compared to the other two groups. A preoperative PTH and AP level of 300 pg/mL and 152 U/L, predicted the risk of developing skeletal involvement with sensitivity and specificity of 71%, 70%, and 69%, 67%, respectively. Conclusions: We observed distinct skeletal and renal phenotypic subgroups among PHPT patients with characteristic biochemical and hormonal patterns with higher parathyroid disease burden in patients with skeletal complications compared to those with isolated renal manifestation. [ABSTRACT FROM AUTHOR]

Background: As an invasive technique, selective venous sampling (SVS) is considered a useful method to identify a lesion's location to increase the success rate of secondary surgery in patients with primary hyperparathyroidism (pHPT) caused by ectopic parathyroid adenomas. Case presentation: We present a case of post-surgical persistent hypercalcemia and elevated parathyroid hormone (PTH) levels in a 44-year-old woman with previously undetected parathyroid adenoma. An SVS was then performed for further localization of the adenoma, as other non-invasive methods showed negative results. After SVS, an ectopic adenoma was suspected in the sheath of the left carotid artery, previously considered as a schwannoma, and was pathologically confirmed after the second operation. Postoperatively, the patient's symptoms disappeared and serum levels of PTH and calcium normalized. Conclusions: SVS can provide precise diagnosis and accurate positioning before re-operation in patients with pHPT. [ABSTRACT FROM AUTHOR]

The continuous cell line of epithelial human parathyroid cells has been proven difficult. Previously, PTH-C1 cell line was only established rat parathyroid tissue cell line known to express the parathyroid hormone-related peptide (Pthrp) gene. The paucity of continuous cell line of human parathyroid cells secreting parathyroid hormone (PTH) has imposed hurdle in in vitro assessment of the mechanisms involved in the control of parathyroid cell function and proliferation. The primary cell cultures of human parathyroid cells were derived from parathyroid adenoma tissue biopsy (n = 5). The cells were subsequently subcultured to maintained primary subclones. Karyotyping analysis was performed to analyze the genotypic identity of derived subclones. The expression of calcium-sensing receptor (CaSR) and intact parathyroid hormone (iPTH) were analyzed using immunocytochemistry and immunofluorescence. In the present study, we have used a defined condition medium to generate the continuous culture of human parathyroid cells derived from patients with parathyroid adenoma due to primary hyperparathyroidism. The subcultured primary subclones were maintained epithelial and polygonal morphology, doubling time of approximately 25 h, displaying a diploid chromosome number, and secretion of PTH. This cell line produces PTH and expresses the calcium-sensing receptor (CaSR) known to be involved in parathyroid function. Altogether these findings indicate the uniqueness of the human parathyroid cell line as an in vitro model for cellular and molecular studies on parathyroid physiopathology. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism is caused by solitary parathyroid adenomas (PTAs) in most cases (⁓85%), and it has been previously reported that PTAs are associated with cardiovascular disease (CVD) and type-2 diabetes (T2D). To understand the molecular basis of PTAs, we have investigated the genetic association amongst PTAs, CVD and T2D through an integrative network-based approach and observed a remarkable resemblance. The current study proposed to compare the PTAs-associated proteins with the overlapping proteins of CVD and T2D to determine the disease relationship. We constructed the protein–protein interaction network by integrating curated and experimentally validated interactions in humans. We found the |$11$| highly clustered modules in the network, which contain a total of |$13$| hub proteins (TP53, ESR1, EGFR, POTEF, MEN1, FLNA, CDKN2B, ACTB, CTNNB1, CAV1, MAPK1, G6PD and CCND1) that commonly co-exist in PTAs, CDV and T2D and reached to network's hierarchically modular organization. Additionally, we implemented a gene-set over-representation analysis over biological processes and pathways that helped to identify disease-associated pathways and prioritize target disease proteins. Moreover, we identified the respective drugs of these hub proteins. We built a bipartite network that helps decipher the drug–target interaction, highlighting the influential roles of these drugs on apparently unrelated targets and pathways. Targeting these hub proteins by using drug combinations or drug-repurposing approaches will improve the clinical conditions in comorbidity, enhance the potency of a few drugs and give a synergistic effect with better outcomes. This network-based analysis opens a new horizon for more personalized treatment and drug-repurposing opportunities to investigate new targets and multi-drug treatment and may be helpful in further analysis of the mechanisms underlying PTA and associated diseases. [ABSTRACT FROM AUTHOR]

Abstract Background The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium.

Background: The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation: Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion: Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium. [ABSTRACT FROM AUTHOR]

Background: Cinacalcet is a calcimimetic drug that has increasingly been used as a bridging therapy for primary hyperparathyroidism (pHPT), especially during the COVID-19 pandemic. The aim of our study was to investigate if preoperative cinacalcet therapy affects intraoperative parathyroid hormone (IOPTH) monitoring during parathyroidectomy, which is an important indicator for the success of surgery. Methods: In this single-center retrospective analysis, we studied the outcomes of 72 patients who underwent surgery for pHPT. We evaluated two groups: those with cinacalcet therapy before operation—the cinacalcet group (CG)—and those without medical therapy preoperatively (non-CG). In order to perform a between-group comparison of time trends, we fit a linear mixed-effects model with PTH as the response variable and predictors PTH levels preoperatively, group (cinacalcet yes/no), time, the group-by-time interaction, and a random intercept (per subject). Results: Our cohort included 51 (71%) women and 21 (29%) men, who were operated upon for pHPT in the period from January 2018 until August 2021. All patients were diagnosed with pHPT and 54% of the cohort were symptomatic for hypercalcemia. Moreover, 30% of the patients were treated with cinacalcet as a bridging therapy preoperatively, and this increased during the COVID-19 pandemic, as 64% of this group were treated in the last two years. Calcium values were significantly different before (p < 0.001) and after (p = 0.0089) surgery, but calcium level change did not differ significantly between the CG and non-CG. Parathyroid hormone (PTH) levels dropped significantly in both groups during 10 min IOPTH monitoring (p < 0.001), but there was no significant difference between the two groups (p = 0.212). Conclusions: In the examined patient cohort, the use of cinacalcet did not affect the value of IOPTH monitoring during surgery for pHPT. [ABSTRACT FROM AUTHOR]

Background: Spontaneous or fine-needle aspiration biopsy (FNAB)-induced remission of primary hyperparathyroidism (PHPT) is an extremely rare and generally transient phenomenon. Methods: A 40-year-old woman with a history of recurrent kidney stones was diagnosed with PHPT (serum calcium, 14.2 mg/dL; parathyroid hormone [PTH], 380 pg/mL). Ultrasonography and scintigraphy findings were consistent with a left enlarged parathyroid. Ultrasound-guided-FNAB cytology of the lesion did not confirm a parathyroid nature. However, levels of PTH within the needle-washing fluid were elevated. Results: After few days, there was evidence of biochemical remission of the hypercalcemia (calcium, 8.1 mg/dL), and at subsequent follow-up visits, the enlarged parathyroid showed progressive shrinkage with eucalcemia and normalized PTH levels throughout 12 months of follow-up. Conclusions: Rarely, remission of PHPT may occur after ultrasound-guided-FNAB performed on a hyperfunctioning parathyroid lesion.

Hyperparathyroidism-Jaw Tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the most deleterious SNPs mutations on CDC73 gene and to predict their influence on the functional and structural levels using different bioinformatics tools. Method: Computational analysis using twelve different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, P-Mut, I-Mutant ,Project Hope, Chimera, COSMIC and dbSNP Short Genetic Variations were used to identify the impact of mutations in CDC73 gene that might be causing jaw tumor. Results: From (733) SNPs identified in the CDC73 gene we found that only Eleven SNPs (G49C, L63P, L64P, D90H, R222G, W231R, P360S, R441C, R441H, R504S and R504H) has deleterious effect on the function and structure of protein and expected to cause the syndrome. Conclusion: Eleven substantial genetic/molecular aberrations in CDC73 gene identified that could serve as diagnostic markers for hyperparathyroidism-jaw tumor (HPT-JT).

A 51-year-old woman with a history of primary hyperparathyroidism (PHPT) with prior parathyroidectomy, osteoporosis, and learning disability was referred for hypercalcemia discovered after a fall. Family history was negative for PHPT, pituitary, enteropancreatic neuroendocrine, or jaw tumors. Dysmorphic facies, multiple cutaneous melanocytic nevi, café au lait macules, long fingers, and scoliosis were observed. Laboratory evaluation showed an elevated parathyroid hormone (PTH) level, hypercalcemia, and hypophosphatemia, all consistent with PHPT. Preoperative imaging revealed a right inferior candidate parathyroid lesion. The patient underwent right inferior parathyroidectomy with normalization of PTH, calcium, and phosphorus. Genetic testing showed a likely pathogenic de novo heterozygous germline missense variant p.R764W in the ZFX gene that encodes a zinc-finger transcription factor previously shown to harbor somatic missense variants in a subset of sporadic parathyroid tumors. Germline variants in ZFX have been reported in patients with an X-linked intellectual disability syndrome with an increased risk for congenital anomalies and PHPT. Further research may determine if genetic testing for ZFX could be of potential benefit for patients with PHPT and developmental anomalies, even in the absence of a family history of parathyroid disease., (Published by Oxford University Press on behalf of the Endocrine Society 2024.)

Context: Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or distant metastasis, leading to uncertainty regarding its malignant potential., Objective: To characterize the molecular landscape and deregulated pathways in APT., Methods: Whole exome sequencing (WES) was conducted on 16 APTs. DNA from tumors and matched peripheral blood underwent WES using Illumina HiSeq3000., Results: A total of 192 nonsynonymous variants were identified. The median number of protein-altering mutations was 9. The most frequently mutated genes included BCOR, CLMN, EZH1, JAM2, KRTAP13-3, MUC16, MUC19, and OR1S1. Seventeen mutated genes belong to the Cancer Gene Census list. The most consistent hub genes identified through STRING network analysis were ATM, COL4A5, EZH2, MED12, MEN1, MTOR, PI3, PIK3CA, PIK3CB, and UBR5. Deregulated pathways included the PI3 K/AKT/mTOR pathway, Wnt signaling, and extracellular matrix organization. Variants in genes such as MEN1, CDC73, EZH2, PIK3CA, and MTOR, previously reported as established or putative/candidate driver genes in benign adenoma (PA) and/or PC, were also identified in APT., Conclusions: APT does not appear to have a specific molecular signature but shares genomic alterations with both PA and PC. The incidence of CDC73 mutations is low, and it remains unclear whether these mutations are associated with a higher risk of recurrence. Our study confirms that PI3 K/AKT/mTOR and Wnt signaling represents the pivotal pathways in parathyroid tumorigenesis and also revealed mutations in key epigenetic modifier genes (BCOR, KDM2A, MBD4, and EZH2) involved in chromatin remodeling, DNA, and histone methylation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.)

Introduction Primary hyperparathyroidism (PHPT) has undergone a considerable change from being symptomatic to asymptomatic. This is the first large study from North India to study the clinical and biochemical features and surgical outcomes in the present era. Study design This is a cross-sectional study that was conducted in the Department of Endocrinology (SKIMS) from February 2021 to December 2022, in which 103 patients diagnosed with PHPT were included. Evaluation included measurement of total calcium, phosphorus, alkaline phosphate, intact parathyroid hormone, 25-hydroxy vitamin, 24-hour urinary calcium, radiological survey of hands and skull, Dual Energy X-ray absorptiometry, and ultrasonography (USG) of the abdomen. USG neck and technetium-99m sestamibi scans were used for preoperative localization; however, in cases of discordance between these investigations or suspicions of multi-glandular disease, four-dimensional computerized tomography of the neck was used. Patients were subjected to surgery according to the guidelines and monitored post-surgery for complications like hypocalcemia and hungry bone syndrome and to document the cure. Results The mean age of patients was 42.8±14.73 years, with a female-to-male ratio of 4.4:1. The mean eGFR of patients was 99.1±30.87 ml/min, with 55 (53.4%) of them having renal disease. Osteoporosis and fractures were present in 41 (39.8%) and 5 (4.8%) patients, respectively. Cholelithiasis and pancreatitis were present in 25 (24.3%) and 5 (4.9%) patients, respectively. Hypertension (HTN) and diabetes mellitus (DM) were the commonest comorbidities, which were present in 34 (33.1%) and 15 (14.5%) patients, respectively. Mean preoperative levels of calcium, phosphorus (PO4), alkaline phosphate (ALP), intact parathyroid hormone (iPTH), 25(OH)vitamin D, and 24-hour urinary calcium were 12.1 mg/dl, 2.35 mg/dl, 210.2 U/L, 332.9 pg/ml, 25.7 ng/ml, and 452.1 mg/day, respectively. The most common type was right inferior parathyroid adenoma, present in 45 cases (43.7%), followed by left inferior parathyroid adenoma in 31 cases (30.1%). A total of 75 patients (72.8%) underwent minimally invasive parathyroidectomy, with 68 patients (90.7%) achieving a biochemical cure. The mean adenoma weight was 3.19±2.25 g. There was no statistically significant correlation (r) between preoperative biochemical parameters and adenoma weight. Conclusion Despite improvements in imaging and the easy availability of immunoassays for early diagnosis, renal disease continued to be the most common presentation, followed by skeletal involvement in our population. In developing countries like India, any patient presenting with nephrolithiasis or nephrocalcinosis, low bone mass, or fragility fractures should be evaluated for PHPT., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Misgar et al.)

Objective: Primary Hyperparathyroidism (PHPT) is a common disease, frequently diagnosed in post-menopausal women, among whom Osteoporosis (OP) is a common finding. To date, no study has specifically evaluated the asymptomatic PHPT (aPHPT) patients without OP, in particular post-menopausal women who are exposed to an increased risk of developing OP., Design: This study involved a retrospective cross-sectional evaluation., Patients: From our database of 500 consecutive patients diagnosed with PHPT, 178 postmenopausal aPHPT were retrieved., Results: The clinical, biochemical, and imaging data of the 85 patients without OP were not different from those of the 93 with OP, except for bone alkaline phosphatase (significantly higher in the latter group). Among these 85 patients without OP, the 45 patients meeting surgical criteria for parathyroidectomy had significantly higher values of serum PTH (240 vs. 99 ng/L, p =0.03) and calcium (total, 11.2 ± 0.7 vs. 10.6 ± 0.4 mg/dL, p <0.001; ionized, 1.45 ± 0.12 vs. 1.36 ± 0.8 mmol/L, p =0.044) and lower values of serum phosphate (2.57 ± 0.7 vs. 2.94 ± 0.5 mg/dL, p =0.009) and eGFR (68.5 ± 23.8 vs 80.8 ± 14.4 mL/min/1.73 m2, p =0.006) than the 40 aPHPT patients not meeting surgical criteria, without any difference in densitometric data and calculated fracture risk., Conclusion: In our series, post-menopausal aPHPT patients without OP accounted for almost a sixth of the whole PHPT series. About half of these patients did not meet surgical criteria, but their T scores and 10-year fracture risk calculated by FRAX were not significantly different from post-menopausal aPHPT without OP meeting surgical criteria., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To determine the significance and impact of additional chloride testing as part of a diagnostic laboratory test battery for borderline primary hyperparathyroidism (pHPT). Study Design: Retrospective database review of parathyroidectomy patients. Setting: A tertiary care, academic health sciences center. Subjects and Methods: Patients referred to a head and neck endocrine clinic for evaluation and treatment for pHPT. Results: After exclusions, there were a total of 226 patients who underwent parathyroidectomy for primary hyperparathyroidism with the requisite preoperative and postoperative labs. Seventy-seven additional patients who had a thyroid operation for a nonmalignant cause were included as controls. Of the 303 total patients, 166 had normal calcium levels (<10.4 mg/dL), and 54 (32.5%) also exhibited hyperchloremia (>106 mmol/L). Of the 47 patients with normal calcium and parathyroid hormone (PTH) levels (<88 pg/mL), 6 (12.8%) had hyperchloremia, and of the 118 patients with normocalcemic pHPT, 48 (40.7%) were hyperchloremic. The area under the curve for the Cl:PO4 was 0.712. When using a cutoff of 33, the reported sensitivity and specificity of the curve were 58.4% and 28.6%, respectively. Conclusion: The Cl:PO4 ratio was a moderately sensitive test for the diagnosis of the borderline variants of primary hyperparathyroidism. The Ca:PO4 ratio was superior to the Cl:PO4 ratio. Our data also showed the superiority of preoperative calcium and ionized calcium over PTH when predicting the presence of pHPT. [ABSTRACT FROM AUTHOR]

In this article, we discuss difficulties in parathyroid localization modalities in diagnosis of primary hyperparathyroidism. Most often, superior parathyroid glands are located on the posteromedial surface of the right and left lobes of the thyroid gland, however, they also could be found at the carotid bifurcation, behind pharynx and esophagus, as well as inside thyroid gland. Location of the inferior parathyroid glands is more variable: on the side or back surface, or below the lower pole of the thyroid gland, as well as in thymus, posterior or anterior mediastinum, or inside thyroid. Localization modalities of primary hyperparathyroidism are based on neck ultrasonography, scintigraphy with sestamibi, computed tomography of neck and mediastinum. In cases with combination of multinodal goitre and an intrathyroid location of the parathyroid gland, there might be additional difficulties in verification of various patterns (thyroid nodules or parathyroid glands). In this article, we present two clinical cases of intrathyroid location of parathyroid glands. The algorithm of parathyroid adenoma localization is shown. Determination of PTH level in washing liquid after fine-needle aspiration biopsy from necessary punctures of the nodule formations, which can be either intrathyroid parathyroid glands or thyroid nodules, can also help to avoid diagnostic mistakes.

• Ectopic parathyroid adenomas located deeper in the mediastinum remain a surgical challenge. • Their incidence reaches up to 20% of the general population and they tend to constitute a severe cause of failed primary surgery for PHPT. • Such aberrations seem to be more common than described in the literature and there are possible anatomic aberrations that have not been described yet. • Preoperative detection of the mediastinal parathyroid adenoma and detailed exposure of the operative field are essential for a safe mid-sternal thoracotomy. Ectopic parathyroid glands occur in 6–16% of cases of PHPT and they constitute a potential cause of failed primary surgical therapy. In particular, aberrant adenomas located deeper in the mediastinum, as in the presented case, remain a severe challenge for the surgeons. A 54-year-old Caucasian female proceeded to our institution with signs and symptoms of PHPT. Imaging studies performed identified a large mass localized in the lower anterior mediastinum, on the left of the median line. A mid-sternal thoracotomy was performed and the aberrant adenoma was finally detected anterior to the pericardium and the left pericardiophrenic vessels and the left phrenic nerve. The operation was uneventful. A meticulous review of the literature was conducted as well. Single parathyroid adenomas are the key culprits of PHPT. Anatomic aberrations of the location of the parathyroid glands and their adenomas are more common than described in the literature and there are possible anatomic aberrations that have not been described yet. All these anatomic variations constitute major risk-factors of thoracic bleeding and of nerve injury. Detailed preoperative detection in addition to meticulous exposure of the operative field are fundamental in order to perform a safe adenoma excision without harmful impacts to the patient. [ABSTRACT FROM AUTHOR]

The presentation of primary hyperparathyroidism (PHPT) in most Western countries has evolved from the classic description of 'stones, bones, and groans' to becoming increasingly asymptomatic as a result of more frequent serum calcium screening. However, many developing countries are still reporting predominantly symptomatic PHPT with the classic complications of skeletal disease and nephrolithiasis still being quite common. Furthermore, the exact prevalence of PHPT in children is not known but it is thought to be uncommon and the clinical presentation and outcomes in this subgroup of patients are not well described in the literature. Two cases of PHPT occurring in adolescent boys are reported. Both cases initially presented with chronic bone pain involving the lower limbs and had a long delay before the diagnosis of PHPT was confirmed. They developed progressive deformities of the lower limbs, which resembled rickets clinically. Radiological features were also suggestive of rickets. However, biochemistry confirmed parathyroid hormone mediated hypercalcaemia in both cases and after parathyroid surgery a parathyroid adenoma was confirmed histologically as the aetiology of hypercalcaemia. Therefore, PHPT occurring in adolescence may have a clinical presentation almost identical to that of rickets. All patients presenting with skeletal deformities including a rickets phenotype must have serum calcium and phosphate levels measured as part of the diagnostic workup. [ABSTRACT FROM AUTHOR]

Abstract Background Nephrolithiasis is a classic, treatable manifestation of primary hyperparathyroidism (PHPT). We examined predictors of kidney stone formation in PHPT patients and determined how efficiently the diagnosis of PHPT is made in patients whose initial presentation is with stones. Materials and methods We performed a retrospective analysis of surgically treated PHPT patients, comparing 247 patients who were kidney stone formers and 1047 patients with no kidney stones. We also analyzed 51 stone-forming patients whose stone evaluation and treatment were completed within our health system before PHPT diagnosis. Results Stone-forming patients had higher 24-h urinary calcium (342 versus 304 mg/d, P = 0.005), higher alkaline phosphatase (92 versus 85 IU/L, P = 0.012), and were more likely to be normocalcemic (26.6% versus 16.9%, P = 0.001). Surprisingly, 47.3% of stone formers had normal urinary calcium levels (<300 mg/d). Of the 51 stone-forming patients treated at our institution, serum calcium was measured within 6 mo of stone diagnosis in 37 (72.5%) patients. Only 16 (31.4%) of these patients had elevated calcium levels, and only 10 (62.5%) of these 16 had a serum parathyroid hormone ordered within the following 3 mo. These patients had a significantly shorter time from their first stone to surgical treatment compared to other patients (median 8.5 versus 49.1 mo, P = 0.001). Conclusions Elevated serum and urinary calcium levels are not evaluated in the majority of PHPT patients presenting with kidney stones. In nephrolithiasis patients, provider consideration of PHPT with prompt serum calcium and parathyroid hormone evaluation significantly reduces time to treatment. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to demonstrate the high number of kidney stones in primary hyperparathyroidism (PHPT) and the low number of in fact 'asymptomatic' patients. Methods: Forty patients with PHPT (28 female, 12 male; median age 58 (range 33-80) years; interquartile range 17 years [51-68]) without known symptoms of kidney stones prospectively underwent multidetector computed tomography (MDCT) and ultrasound (US) examinations of the urinary tract prior to parathyroid surgery. Images were evaluated for the presence and absence of stones, as well as for the number of stones and sizes in the long axis. The MDCT and US examinations were interpreted by two experienced radiologists who were blinded to all clinical and biochemical data. Statistical analysis was performed using the Wilcoxon signed-rank test. Results: US revealed a total of 4 kidney stones in 4 (10 %) of 40 patients (median size 6.5 mm, interquartile range 11.5 mm). MDCT showed a total of 41 stones (median size was 3 mm, interquartile range 2.25 mm) in 15 (38 %) of 40 patients. The number of kidney stones detected with MDCT was significantly higher compared to US ( p = 0.00124). Conclusions: MDCT is a highly sensitive method for the detection of 'silent' kidney stones in patients with PHPT. By widely applying this method, the number of asymptomatic courses of PHPT may be substantially reduced. MDCT should be used primarily to detect kidney stones in PHPT and to exclude asymptomatic PHPT. [ABSTRACT FROM AUTHOR]

Objective: The long-term renal consequences of curative parathyroidectomy (PTX) in symptomatic primary hyperparathyroidism (sPHPT) are not well characterized. We aimed to assess renal glomerular and tubular functions in an sPHPT cohort at ≥1 year's follow-up., Design: Retrospective-prospective study., Methods: sPHPT patients with preoperative eGFR ≥60mL/min/1.73m 2 and in remission (normocalcemic) for ≥1 year after PTX underwent clinical and biochemical assessment (calcium profile, renal parameters). Ammonium chloride and bicarbonate loading tests were performed in patients with renal tubular dysfunction (RTD)., Results: Forty-eight patients (31 females) with median plasma PTH 1,029 (338-1604) pg/mL and mean eGFR 109.2±26.0mL/min/1.73m 2 at diagnosis were evaluated at 5.62±3.66 years after curative PTX. At follow-up, eGFR was <60mL/min/m 2 in 5 patients (10.4%). Patients with >10% drop in eGFR (n=31) had significantly higher pre-PTX plasma PTH (1,137 vs. 687pg/mL), and longer time to post-PTX evaluation (6.8 vs. 3.4 years). RTD was seen in 11 patients (22.9%): urinary low molecular weight proteinuria (14.6%), distal renal tubular acidosis (12.5%), hypophosphatemia (8.3%), and hypokalemia (8.3%); RTD was associated with significantly lower post-PTX eGFR (72.7 vs. 95.4mL/min/m 2 ). Five of the 7 RTD patients undergoing loading test had impaired urinary acidification, whereas none had impaired bicarbonate resorption., Conclusions: Reduction in eGFR and subclinical RTD were prevalent at long-term follow-up in the present Asian-Indian cohort with cured sPHPT. Further studies are warranted to understand the clinical implications of these various renal abnormalities., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Primary hyperparathyroidism (HPT) is the most common endocrinopathy in Multiple Endocrine Neoplasia type 1 (MEN1) syndrome. Supernumerary and/or ectopic parathyroid glands, potentially causes of persistent or recurrent HPT after surgery, have been previously described. However, this is the first ever described case of ectopic parathyroid gland localized in the aortopulmunary window causing HPT in MEN1. After a consistent concordant pre-operative imaging assessment the patient, a 16 years old male affected by a severe hypercalcemia, underwent surgery. The parathyroid was found very deeply near the tracheal bifurcation, hidden by the aortic arch itself and for this reason not visible at the beginning of the dissection but only after being identified by palpation for its typical consistence. The intraoperative PTH decreased at normal level 10 min after removal of the ectopic gland. The patient remained with normal value of calcemia and PTH during the 10 months of follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The incidence of recurrent primary hyperparathyroidism (PHPT) had been reported to be between 1% and 10%. The purpose of this study was to examine if patients with multigland disease have a different recurrence rate. Methodology: A retrospective analysis of a prospectively collected database was performed on patients with PHPT who underwent parathyroidectomy at one institution between 2001 and 2013. Patients who underwent initial parathyroidectomy with at least 6 mo of follow-up were included and were divided into three groups according to operative notes: single adenoma (SA), double adenoma (DA), and hyperplasia (HP). An elevated postoperative serum calcium level within 6 mo of surgery was defined as a persistent disease, whereas an elevated calcium after 6 mo was defined as a recurrence. Results: In total, 1402 patients met inclusion criteria, and the success rate of parathyroidectomy was 98.4%. The mean age was 60 ± 14 y and 78.5% were female. Among them, 1097 patients (78%) had SA, 124 patients (9%) had DA, and 181 patients had HP (13%). The rate of persistent PHPT was higher among patients with DA (4%) versus SA (1.3%) and HP (2.2%) (P = 0.0049). Moreover, the recurrence rate was higher among patients with DA (7.3%) versus SA (1.7%) and HP (4.4%) (P = 0.0005) with identical median follow-up time. The median of the follow-up was 11 mo for patients with SA, 12.5 for patients with DA, and 12 for patients with HP (P = 0.1603). Conclusions: Recurrent and persistent PHPT occur more frequently in patients with DA. These data suggest that DA in some cases could represent asymmetric or asynchronous hyperplasia. Therefore, patients with DA may warrant more rigorous intraoperative scrutiny and more vigilant monitoring after parathyroidectomy. [Copyright &y& Elsevier]