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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.)

Parathyroid carcinoma (PCA) is a rare malignancy accounting for approximately 1% of all patients with primary hyperparathyroidism. It is characterised by excessive parathyroid hormone (PTH) production. This manuscript reviews recent advances in the management of parathyroid carcinoma, focusing on molecular insights, diagnostic modalities, surgical innovations, adjuvant therapies, and emerging targeted treatments. Recently published manuscripts (between 2022 and 2023) were obtained from Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica (Embase), Cochrane Central Register of Controlled Trials (CENTRAL), and European Union Drug Regulating Authorities Clinical Trials (EudraCT). These were assessed for their relevance in terms of the diagnosis and management of patients with PCA. This manuscript explores the role of genetic profiling and presents case studies illustrating successful management strategies. The manuscript also discusses the ongoing challenges in the management of parathyroid carcinoma, suggesting future research directions and potential therapeutic avenues., Competing Interests: Declaration of competing interest The authors declare no competing interests in relation to this specific paper. GKD has received research grants from the NIHR, Novo Nordisk UK Foundation and DDM, and honoraria for educational events from Novo Nordisk, Medtronic, and J&J/Ethicon which are not related to this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: Preoperative and intraoperative diagnostic tools influence the surgical management of primary hyperparathyroidism (PHPT), whereby their performance of classification varies considerably for the two common causes of PHPT: solitary adenomas and multiglandular disease. A consensus on the use of such diagnostic tools for optimal perioperative management of all PHPT patients has not been reached., Design: A decision tree model was constructed to estimate and compare the clinical outcomes and the cost-effectiveness of preoperative imaging modalities and intraoperative parathyroid hormone (ioPTH) monitoring criteria in a 21-year time horizon with a 3% discount rate. The robustness of the model was assessed by conducting a one-way sensitivity analysis and probabilistic uncertainty analysis., Setting: The US healthcare system., Population: A hypothetical population consisting of 5000 patients with sporadic, symptomatic or asymptomatic PHPT., Interventions: Preoperative and intraoperative diagnostic modalities for parathyroidectomy., Main Outcome Measures: Costs, quality-adjusted life-years (QALYs), net monetary benefits (NMBs) and clinical outcomes., Results: In the base-case analysis, four-dimensional (4D) CT was the least expensive strategy with US$10 276 and 15.333 QALYs. Ultrasound and 99m Tc-Sestamibi single-photon-emission CT/CT were both dominated strategies while 18 F-fluorocholine positron emission tomography was cost-effective with an NMB of US$416 considering a willingness to pay a threshold of US$95 958. The application of ioPTH monitoring with the Vienna criterion decreased the rate of reoperations from 10.50 to 0.58 per 1000 patients compared to not using ioPTH monitoring. Due to an increased rate of bilateral neck explorations from 257.45 to 347.45 per 1000 patients, it was not cost-effective., Conclusions: 4D-CT is the most cost-effective modality for the preoperative localisation of solitary parathyroid adenomas and multiglandular disease. The use of ioPTH monitoring is not cost-effective, but to minimise clinical complications, the Miami criterion should be applied for suspected solitary adenomas and the Vienna criterion for multiglandular disease., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment., Competing Interests: Disclosure No disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The mainstay of successful treatment for parathyroid carcinoma remains complete surgical excision. Although intraoperative parathyroid hormone (ioPTH) monitoring is a useful adjunct during parathyroidectomy for benign primary hyperparathyroidism, its utility for parathyroid carcinoma remains unclear., Methods: A retrospective review of 796 patients who underwent parathyroidectomy with ioPTH monitoring for primary hyperparathyroidism revealed 13 patients with parathyroid carcinoma on final pathology from two academic institutions. A systematic review yielded 5 additional parathyroid carcinoma patients. Complete excision of malignancy, or operative success (eucalcemia ≥6 mo. after parathyroidectomy); operative failure (persistent hypercalcemia <6 mo. after parathyroidectomy); and perioperative complications were evaluated. Comparison of the >50% ioPTH decrease alone to >50% ioPTH decrease into normal reference range was analyzed using Chi-squared, Kolmogorov-Smirnov, Kruskal-Wallis tests., Results: All 18 parathyroid carcinoma patients achieved a >50% ioPTH decrease, and 14 patients also had a final ioPTH level decrease into normal reference range. 93% of patients who met normal parathyroid hormone reference range had operative success, whereas only two of the four (50%) patients with parathyroid carcinoma with a >50% ioPTH decrease alone demonstrated operative success., Conclusions: Parathyroidectomy guided by a >50% ioPTH decrease into normal reference range may better predict complete excision of malignant tissue in patients with parathyroid carcinoma compared to >50% ioPTH decrease alone. IoPTH monitoring should be used in conjunction with clinical judgment and complete en bloc resection for optimal treatment and success., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Primary hyperparathyroidism can be sporadic or part of a genetic syndrome, such as MEN1 or HPT-JT. Diagnosis of hereditary HPT requires a thorough history and physical. Parathyroidectomy is curative with greater than 95% success. However, some patients have persistent or recurrent disease requiring reoperation. Reoperative parathyroidectomy is technically challenging, and localizing the pathologic gland can difficult. Patients needing reoperation should undergo evaluation by a high-volume surgeon. Care should be taken to obtain all of the preoperative workup and operative note from the initial surgery. Radioguided parathyroidectomy can be safely and effectively performed in patients with hereditary HPT or undergoing reoperative surgery., Competing Interests: Disclosure The authors have no disclosures., (Copyright © 2024 Elsevier Inc. All rights reserved.)

BACKGROUND Benign parathyroid adenoma is a cause of hypercalcemia, which can lead to acute pancreatitis. Patients with acute pancreatitis are at risk for venous thrombosis. This report describes a 34-year-old woman with hypercalcemia due to parathyroid adenoma and acute pancreatitis associated with splenic vein and superior mesenteric vein thrombosis. CASE REPORT A previously healthy 34-year-old woman presented with severe epigastric pain that radiated to the back, associated with vomiting. Her abdominal examination was soft and lax, with epigastric and left upper quadrant tenderness. Pancreatitis with splenic and superior mesenteric veins thrombosis was diagnosed. The diagnosis was confirmed by an elevated serum lipase level and contrast-enhanced computed tomography (CT) of abdomen. Her serum calcium level was elevated. However, further workup revealed elevated parathyroid hormone (PTH) levels and radiological imaging showed parathyroid adenoma. She was diagnosed with hypercalcemia-induced pancreatitis secondary to hyperparathyroidism with intraabdominal venous thrombosis. The patient was initially treated conservatively, and later underwent parathyroidectomy after her condition was stabilized. The patient is currently in good condition, after a 2-year follow-up period. CONCLUSIONS Acute pancreatitis and thrombosis secondary to primary hyperparathyroidism (PHPT) are rare, but can lead to potentially fatal complications, especially in patients without symptoms of PHPT. This report highlights the importance of recognizing that hypercalcemia associated with parathyroid adenoma can result in acute pancreatitis, leading to hypercoagulable states and inflammation of adjacent vessels, including the splenic and mesenteric veins. To the best of our knowledge, this is second case report of acute pancreatitis with intraabdominal venous thrombosis secondary to PHPT.

Background: Parathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience., Case Presentation: We describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter., Conclusion: Parathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma., (© 2024. The Author(s).)

Background: Multiple endocrine neoplasias (MENs) are a group of hereditary diseases involving multiple endocrine glands, and their prevalence is low. MEN type 1 (MEN1) has diverse clinical manifestations, mainly involving the parathyroid glands, gastrointestinal tract, pancreas and pituitary gland, making it easy to miss the clinical diagnosis., Case Summary: We present the case of a patient in whom MEN1 was detected early. A middle-aged male with recurrent abdominal pain and diarrhea was admitted to the hospital. Blood tests at admission revealed hypercalcemia and hypophosphatemia, and emission computed tomography of the parathyroid glands revealed a hyperfunctioning parathyroid lesion. Gastroscopy findings suggested a duodenal bulge and ulceration. Ultrasound endoscopy revealed a hypoechoic lesion in the duodenal bulb. Further blood tests revealed elevated levels of serum gastrin. Surgery was performed, and pathological analysis of the surgical specimens revealed a parathyroid adenoma after parathyroidectomy and a neuroendocrine tumor after duodenal bulbectomy. The time from onset to the definitive diagnosis of MEN1 was only approximately 1 year., Conclusion: For patients who present with gastrointestinal symptoms accompanied by hypercalcemia and hypophosphatemia, clinicians need to be alert to the possibility of MEN1., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ectopic parathyroid adenomas are an uncommon etiology of primary hyperparathyroidism. We present a case of a patient admitted to the hospital with severe hypercalcemia and elevated parathyroid hormone levels, in whom imaging revealed two distinct parathyroid masses in the prevertebral space, representing a rare and atypical location for parathyroid tissue. This case highlights the importance of considering ectopic parathyroid adenomas as a potential cause of hyperparathyroidism and discusses the diagnostic challenges and management strategies associated with such cases., 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.

Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: In contrast to adults, primary hyperparathyroidism (PHPT) in children and adolescents is a rare endocrine disorder., Methods: A retrospective review of PHPT cases between 2005 and 2022 from a single tertiary university medical center, including clinical signs and symptoms, laboratory findings, radiological evaluation, treatment, and postoperative complications., Results: Ten children (mean age at diagnosis 16.3 ± 1.3 years) were diagnosed with PHPT. All patients were in late pubertal stages without sex predominance and 8 were symptomatic. Mean calcium level was 13.6 ± 2.5 mg/dL, and mean parathyroid hormone levels were 204.8 ± 163.1 pg/mL. Parathyroid adenoma was confirmed by the postsurgical pathology results., Conclusions: PHPT in children and adolescents is often symptomatic and more severe than adults. The main cause is single parathyroid adenoma. Associated hypercalcemic syndromes were not found. Patients were cured after surgical removal of the adenoma without significant postoperative complications and no recurrence during 10.4 ± 5.9 years follow-up., Competing Interests: Disclosure The authors have no conflicts of interest to disclose. No funding was received for this article., (Copyright © 2024 AACE. Published by Elsevier Inc. All rights reserved.)

Purpose: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. However, the diagnosis of PC is still a difficult problem. A model with immunohistochemical (IHC) staining of 5 biomarkers has been reported from limited samples for the differential diagnosis of PC. In the present study, a series of IHC markers was applied in relatively large samples to optimize the diagnostic model for PC., Methods: In this study, 44 patients with PC, 6 patients with atypical parathyroid tumors and 57 patients with parathyroid adenomas were included. IHC staining for parafibromin, Ki-67, galectin-3, protein-encoding gene product 9.5 (PGP9.5), E-cadherin, and enhancer of zeste homolog 2 (EZH2) was performed on formalin-fixed, paraffin-embedded tissue samples. The effects of clinical characteristics, surgical procedure, and IHC staining results of tumor tissues on the diagnosis and prognosis of PC were evaluated retrospectively., Results: A logistic regression model with IHC results of parafibromin, Ki-67, and E-cadherin was created to differentiate PC with an area under the curve of 0.843. Cox proportional hazards analysis showed that negative parafibromin staining (hazard ratio: 3.26, 95% confidence interval: 1.28-8.34, P = 0.013) was related to the recurrence of PC., Conclusion: An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish PC from parathyroid neoplasms. Among the 6 IHC markers and clinical features examined, the risk factor related to PC recurrence was parafibromin staining loss., (© 2024. The Author(s).)

Technetium-99m sestamibi single-photon emission computed tomography/computed tomography ( 99m Tc-sestamibi SPECT/CT) is a mainstay of the pre-operative localization of parathyroid lesions. We report here the case of a 30 year-old woman with a fortuitously discovered 2 cm cervical mass for which a parathyroid origin was originally suspected due to its retro-thyroidal localization and a personal history of nephrolithiasis. Normal serum calcium and parathyroid hormone (PTH) levels excluded primary hyperparathyroidism, raising suspicion of a non-functional parathyroid adenoma, and SPECT/CT imaging showed that the mass was 99m Tc-sestamibi-avid. Fine-needle aspiration (FNA) was performed; cytology was non-diagnostic but the needle washout was negative for thyroglobulin, calcitonin and PTH, arguing against a thyroidal or parathyroidal origin of the mass. Core needle biopsy revealed a schwannoma, ostensibly originating from the recurrent laryngeal nerve; upon surgical resection, it was finally found to arise from the esophageal submucosa. This case illustrates the fact that endocrinologists, radiologists, nuclear medicine, head and neck, and other specialists investigating patients with cervical masses should be aware that schwannomas need to be considered in the differential diagnosis of focal 99m Tc-sestamibi uptake in the neck region., 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 Fiore, Gombert, La Rosa, Dunet, Sykiotis and Gorostidi.)

Rationale: Primary hyperparathyroidism, though relatively prevalent among endocrine disorders, affecting 1% of the general population, often presents diagnostic challenges. Given its potential to precipitate severe complications including nephrolithiasis and fractures, timely diagnosis, and effective management are crucial., Patient Concerns: A 38-year-old woman with hypercalcemia was referred to the Department of Nuclear Medicine for a Tc-99m MIBI scan., Diagnoses: Tc-99m MIBI scan showed focal increased uptake in the left thyroid gland area, initially suggesting a parathyroid adenoma. Further examination using SPECT/CT revealed a nodular lesion within the left thyroid gland showing high Tc-99m MIBI uptake., Interventions: Left thyroid lumpectomy confirmed the lesion as follicular thyroid carcinoma. On the second Tc-99m MIBI scan conducted after total thyroidectomy, a parathyroid adenoma was eventually detected in the right lower area, enabling the subsequent appropriate treatment, a right lower parathyroidectomy., Outcomes: Thirteen days after the parathyroidectomy, serum levels of total calcium and parathyroid hormone returned to normal. Furthermore, bone mineral density evaluated using DEXA remained within the expected range for her age even after 14 months., Lessons: When interpreting the Tc-99m MIBI scan, it is essential to keep in mind that various tumors rich in mitochondria, such as thyroid carcinoma, could show a high uptake of Tc-99m MIBI., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Competing Interests: Les auteurs déclarent n’avoir aucun lien d’intérêts.

Background: Recognizing the parathyroid gland and distinguishing the parathyroid from thyroid lesions in fine needle aspiration (FNA) is challenging. This study aimed to identify cytomorphologic features suggestive of parathyroid origin and to assess the utility of cytopathology in conjunction with ancillary tests in the identification of parathyroid glands., Materials and Methods: Ultrasound (US) guided FNA of parathyroid gland and lesions in 81 patients were reviewed concerning clinical history and correlated to histopathologic findings in available cases. FNA smears were evaluated for cellularity, architectural patterns, cellular and nuclear features, and background of the smears. In 78 cases, FNA was supplemented by a measurement of parathormone (PTH) levels in the needle washout fluid (FNA-PTH assay) and/or GATA3/PTH/chromogranin-A immunostainings., Results: Sixty-four cases were diagnosed cytologically as parathyroid lesions in conjunction with FNA-PTH assay and/or immunocytochemical examinations. In an additional nine cases, a diagnosis of parathyroid lesions was rendered after repeated FNA with FNA-PTH assay. The histolopathologic diagnosis of surgically excised cases (n = 75) included parathyroid adenoma (60 cases), atypical parathyroid adenoma (4 cases), parathyroid hyperplasia (10 cases), and parathyroid carcinoma (1 case). Major cytological findings of parathyroid tissue included high cellularity, scattered naked nuclei, cribriform and three-dimensional clusters, stippled chromatin, and oxyphilic cytoplasm while papillary pattern or colloid-like material was identified in three cases respectively. No nuclear grooves or inclusions were seen in any case., Conclusions: High cellularity scattered naked nuclei, cribriform and three-dimensional patterns, stippled chromatin and oxyphilic cytoplasm are cytomorphologic features that favour parathyroid origin. A combination of these features with FNA-PTH assay and/or GATA3, PTH, and chromogranin-A immunostainings on cytologic specimens aid in the identification of parathyroid glands and the distinguishing of parathyroid from thyroid lesions., (© 2024 John Wiley & Sons Ltd.)

This is a case of primary hyperparathyroidism in a female teenager with multiple fractures and severe bone manifestations. The histopathology revealed atypical parathyroid adenoma, an exceedingly rare form of hyperparathyroidism; its main differential diagnosis is parathyroid carcinoma, as it shares both clinical and histological characteristics with it, in addition to its still uncertain malignant potential., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives : Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by excessive production of parathyroid hormone (PTH) leading to elevated calcium levels. Diagnosis is primarily based on biochemical evaluation, and surgery is the curative treatment. Imaging techniques like ultrasound and Tc-99m Sestamibi scintigraphy are used for localization, but selective Internal Jugular Venous (SVS) becomes valuable in cases of inconclusive or conflicting results. This study evaluated the diagnostic efficacy of SVS for localizing parathyroid adenomas in cases where non-invasive radiological diagnostic methods yielded inconclusive results or negative findings despite clinical symptoms suggestive of pHPT. Materials and Methods : In this retrospective study, a total of 28 patients diagnosed with pHPT underwent SVS at a tertiary center known for receiving referrals from 2017 to 2022. The diagnoses were confirmed through biochemical analysis. The SVS results in 22 patients were compared with non-invasive imaging methods, including ultrasound, scintigraphy, and computed tomography with/without contrast material. SVS was indicated when at least two non-invasive diagnostic procedures failed to clearly localize the parathyroid glands or provided ambiguous results. Results : SVS demonstrated higher sensitivity for localizing parathyroid adenomas compared to non-invasive imaging methods, accurately lateralizing the adenoma in 68.18% of cases. Among the SVS findings, 31.8% of patients had negative results, with 9.1% not having clinically proven parathyroid adenoma, while 22.7% had false negative SVS findings but were later confirmed to have adenoma during surgery. Ultrasound correctly identified the location in 45.45% of cases, CT in 27.27%, and scintigraphy in 40.9%. Conclusions : SVS is a valuable diagnostic tool for accurately localizing parathyroid adenomas in patients with inconclusive non-invasive imaging results. It aids in targeted surgical interventions, contributing to improved management and treatment outcomes in primary hyperparathyroidism.

Purpose: The purpose of this investigation is to understand the accuracy of machine learning techniques to detect biopsy-proven adenomas from similar appearing lymph nodes and factors that influence accuracy by comparing support vector machine (SVM) and bidirectional Long short-term memory (Bi-LSTM) analyses. This will provide greater insight into how these tools could integrate multidimensional data and aid the detection of parathyroid adenomas consistently and accurately., Methods: Ninety-nine patients were identified; 93 4D-CTs of patients with pathology-proven parathyroid adenomas were reviewed; 94 parathyroid adenomas and 112 lymph nodes were analyzed. A 2D slice through the lesions in each phase was used to perform sequence classification with ResNet50 as the pre-trained network to construct the Bi-LSTM model, and the mean enhancement curves were used to form an SVM model. The model characteristics and accuracy were calculated for the training and validation data sets., Results: On the training data, the area under the curve (AUC) of the Bi-LSTM was 0.99, while the SVM was 0.95 and statistically significant on the DeLong test. The overall accuracy of the Bi-LSTM on the validation data set was 92 %, while the SVM was 88 %. The accuracy for parathyroid adenomas specifically was 93 % for the Bi-LSTM and 83 % for the SVM model., Conclusion: Enhancement characteristics are a distinguishing feature that accurately identifies parathyroid adenomas alone. The Bi-LSTM performs statistically better in identifying parathyroid adenomas than the SVM analysis when using both morphologic and enhancement information to distinguish between parathyroid adenomas and lymph nodes., Summary Statement: The Bi-LSTM more accurately identifies parathyroid adenomas than the SVM analysis, which uses both morphologic and enhancement information to distinguish between parathyroid adenomas and lymph nodes, performs statistically better., Competing Interests: Declaration of competing interest No conflict of interest of any of the authors., (Published by Elsevier Inc.)

A total of 1 out of 10 patients with primary hyperparathyroidism (PHP) presents an underlying genetic form, such as multiple endocrine neoplasia types 1, 2A, etc., as well as hyperparathyroidism-jaw tumour syndrome (HJT). We aimed to summarise the recent data, thus raising more awareness regarding HJT, from the clinical perspective of PHP in association with the challenges and pitfalls of CDC73 genetic testing and parafibromin staining. This narrative review included a sample-focused analysis from the past decade according to a PubMed search. We identified 17 original human studies (≥4 patients per article). The mean age at disease onset was between 20.8 and 39.5 years, while the largest study found that 71% of patients had HJT recognised before the age of 30. Males and females seemed to be equally affected, in contrast with sporadic PHP. PHP represented the central manifestation of HJT, occurring as the first manifestation in up to 85% of HJT cases. A biochemistry panel found a mean serum calcium level above the level of 12 mg/dL in PHP. PTH was elevated in HJT as well, with average values of at least 236.6 pg/mL. The most frequent pathological type in PHP was a parathyroid adenoma, but the incidence of a parathyroid carcinoma was much higher than in non-HJT cases (15% of all parathyroid tumours), with the diagnosis being established between the age of 15 and 37.5. In some families up to 85% of carriers suffered from a parathyroid carcinoma thus indicating that certain CDC73 pathogenic variants may harbour a higher risk. An important issue in HJT was represented by the parafibromin profile in the parathyroid tumours since in HJT both parathyroid adenomas and carcinomas might display a deficient immunoreactivity. Another frequent manifestation in HJT was ossifying fibromas of the jaw (affecting 5.4% to 50% of patients; the largest study found a prevalence of 15.4%). HJT was associated with a wide variety of kidney lesion (mostly: kidney cysts, with a prevalence of up to 75%, and renal tumours involved in 19% of patients). The risk of uterine lesions seemed increased in HJT, especially with concern to leiomyomas, adenofibromas, and adenomyosis. The underlying pathogenic mechanisms and the involvement of CDC73 pathogenic variants and parafibromin expression are yet to be explored. Currently, the heterogeneous expression of parafibromin status and, the wide spectrum of CDC73 mutations including the variety of clinical presentations in HJT, make it difficult to predict the phenotype based on the genotype. The central role of HJT-PHP is, however, the main clinical element, while the elevated risk of parathyroid carcinoma requires a special awareness.

We present successful surgical treatment of a patient with chronic kidney disease (CKD) and hyperparathyroidism undergoing renal replacement therapy. At baseline, parathyroidectomy via cervical access was performed for parathyroid adenomas. After 6 years, clinical and laboratory relapse of disease required thoracoscopic resection of atypically located anterior mediastinal adenoma. This case demonstrates that this disease is one of the most difficult in modern medicine requiring a special approach in diagnosis and treatment. Patients with CKD and hyperparathyroidism need for follow-up, control of total and ionized serum calcium, inorganic phosphorus and parathormone, osteodensitometry, ultrasound and scintigraphy of thyroid and parathyroid glands, and, if necessary, CT or MRI of the neck and chest organs.

Primary hyperparathyroidism (PHPT) is characterized by elevated levels of calcium and parathyroid hormone (PTH). However, the interpretation of diagnostic tests, such as serum calcium and PTH levels, is complex in pregnant women. The aim of this report is to present a case of PHTP in a pregnant adolescent, with a special emphasis on an uncommon complication, as well as diagnostic and treatment strategies. A 17-year-old pregnant female presented with hyperemesis gravidarum and neurological symptoms, leading to the diagnosis of cerebral venous thrombosis. Further investigations revealed hypercalcemia and persistently elevated PTH levels, consistent with PHPT. After localization studies, the patient underwent an emergency parathyroidectomy with a diagnosis of parathyroid adenoma. During follow-up, intrauterine growth restriction and severe preeclampsia developed, necessitating an emergency cesarean section. Both the mother and neonate had favorable outcomes. PHPT is an infrequent condition in the pregnant population, and its diagnosis can be challenging due to the overlap of symptoms with normal physiological changes during pregnancy. The occurrence of uncommon complications, such as thrombotic phenomena, highlights the need for a comprehensive approach to ensure early detection and management. In most cases, parathyroidectomy is the treatment of choice.

Differential diagnosis of atypical parathyroid tumors (APT) and parathyroid carcinomas (PC) is important in determining further management and prognosis. Morphologic diagnosis is sometimes difficult, in which case it is supplemented by immunohistochemical (IHC) examination., Objective: Studying the role of IHC analysis in the differential diagnosis of APT and PC., Material and Methods: The study included 44 patients with morphologic diagnosis of the APT established after surgical treatment for primary hyperparathyroidism on the basis of Endocrinology Research Centre during 2018-2023. All cases underwent IHC examination with evaluation of CD31/CD34 and parathormone (PTH) expression for identification of vascular invasion, Ki-67, parafibromin., Results: According to the results of IHC analysis in 8/44 patients (18.2%) the diagnosis of APT was revised in favor of the PC: in 7 of them vascular invasion was detected; in 1 patient the additional series of slices in the surrounding fatty tissue revealed foci of tumor growth, confirmed by positive reaction with antibodies to PTH. According to IHC results, the material was divided into 2 groups: APT and PC. There were no differences in clinical and morphological characteristics, Ki-67% level and parafibromin expression between the groups., Conclusion: Assessment of clinical and laboratory-instrumental data at the preoperative stage does not allow differentiating APT from PC. In case of APT diagnosis and detection of suspicious morphological features, it is necessary to perform IHC examination to exclude PC.

Primary hyperparathyroidism (PHPT) is rare in pregnancy. This condition is challenging to diagnose and manage due to the limited diagnostic and therapeutic options that are safe during pregnancy. If not diagnosed and managed in a timely manner, serious maternal and foetal complications may occur. We report two cases, one with surgical intervention and one without, to show the importance of timely surgical intervention and discuss the challenges in the management of PHPT in pregnancy., Competing Interests: The authors declared no conflict of interest., (© 2024 Journal of the ASEAN Federation of Endocrine Societies.)

The diagnosis of pathological conditions of the parathyroid glands is the answer to clinically more frequently detected hypercalcemic conditions, including MEN syndromes. In routine biopsy practice, enlarged bodies are also a differential diagnosis for the diagnosis of thyroid nodules. In the chapter of parathyroid tumors, the 5th edition of the WHO classification brings changes influenced similarly to other endocrine organs by the increase in genetic information. At the terminological level, the concept of hyperplasia has been narrowed down to secondary hyperplasia, most of the previously primary hyperplasias are referred to as multiglandular parathyroid disease due to evidence of multiglandular clonal proliferations. The term atypical parathyroid tumor replacing atypical adenoma is newly introduced - the uncertain biological behaviour is emphasized. The basic examination includes parafibromin immunohis- tochemistry, the deficiency of parafibromin being an indicator of an inactivating CDC73 mutation and an increased risk of familial forms, or MEN. Methodologically, refinements are introduced in the quantification of mitotic activity per 10 mm2. Oncocytic subtypes have an arbitrarily declared threshold of more than 75% oncocytes. The definition of lipoadenoma (multiplication of both components, more than 50% of adipose tissue in the tumor) is similarly specified. The diagnosis of cancer remains histopathological with unequivocal evidence of invasion, or microscopically verified metastasis.

Parathyroid carcinoma (PC) is usually associated with severe symptomatic primary hyperparathyroidism (PHPT) and accounts for less than 1% of all cases of PHPT and approximately 0.005% of all cancers. PC most commonly occurs as a sporadic disease and somatic CDC73 mutations can be detected in up to 80% of cases. Approximately 30% of patients harbor a germline mutation of the CDC73 gene. Preoperative diagnosis of PC is difficult because no disease-specific markers are available, and PC should be suspected in patients with severe hypercalcemia and end-organ complications. The diagnosis is based on the evidence of invasive tumor growth at histology and/or metastases. En bloc resection of the tumor, together with the ipsilateral thyroid lobe and adjacent structures, should be performed by an experienced surgeon when PC is suspected. This surgical approach reduces the risk of recurrence and metastasis and offers the highest chance of cure. Nonetheless, PC has a recurrence rate of 40% to 60% and, if feasible, multiple surgical procedures should be performed. When surgery is no longer an option, medical treatment is aimed to reduce hypercalcemia and target organ complications. Targeted agents have been effectively used in a few cases. We describe herein a patient with severe PHPT due to PC and provide a systematic diagnostic and treatment approach. A thorough review of the medical history, a typical clinical and biochemical phenotype and, in some cases, the revision of the histological examination provide the clues for the diagnosis of PC., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Non functional parathyroid carcinoma (PC) is one of the rarest malignant neoplasms. Due to the lack of symptoms and laboratory findings, it is mostly diagnosed in late AQ2 stages, when local invasion and dissemination are already present. However, our case is an exception, because it was detected in early stage, with no local invasion present. We present a case of the smallest non-functional PC yet reported and review of the literature., Case Presentation: A 47-year-old woman was admitted to outpatient Clinic where fine-needle aspiration biopsy (FNAB) of bilateral thyroid nodules (slide 1) and central neck mass (slide 2), which was suspected to be an enlarged lymphatic nodule or parathyroid gland was performed. Results came back as Bethesda I-colloid (slide 1), and Bethesda IV (slide 2), stating that it is hard to distinguish thyroid gland oxyphil lesions from parathyroid cells. Total thyroidectomy was performed as well as excision of the left central neck mass, without any involvement of surrounding structures. Pathological examination revealed bilateral thyroid follicular nodular disease, papillary microcarcinoma, and parathyroid carcinoma with vascular and capsular invasion, measuring 10 × 8 × 7 mm. The immunohistochemical profile included positive PTH, Chromogranin A, and negative TTF1., Conclusion: Non-functional PC is usually diagnosed in advanced stages, already involving adjacent structures; however, this case presents a rare example. It is important not to exclude PC as a differential diagnosis in the absence of elevated Ca and PTH serum levels. Follow-up will be difficult, since there are no prognostic parameters to rely on., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Competing interests: None declared.

Objective: The cytomorphological features of parathyroid tissue (PTT) may overlap with those of thyroid lesions, thus posing a diagnostic challenge. In this retrospective study, we reviewed our institutional experience in using parathyroid hormone (PTH) immunocytochemistry (ICC) to substantiate the diagnosis of PTT on fine needle aspiration (FNA)., Methods: Our pathology database was searched for FNA cases in which PTH ICC was performed between 1 January 2015 and 31 March 2022. PTH ICC was performed on a ThinPrep slide in cases with a clinical suspicion of PTT or with cytomorphological features raising the possibility of PTT. Patients' clinicopathological characteristics, PTH ICC results, cytological diagnoses, and surgical follow-ups, if available, were reviewed and analysed., Results: The study cohort included 103 cases clinically designated as thyroid (n = 85, 82.5%), parathyroid (n = 11, 10.7%) and neck soft tissue (n = 7, 6.8%). PTH immunostaining was negative, positive, and indeterminate in 53 (51.5%), 27 (26.2%), and 23 (22.3%) cases, respectively. Surgical follow-up was available in 27 (26.2%) cases, including 17 thyroid lesions and 10 PTT cases. All positive PTH cases were confirmed to be PTT, while all but one of the negative PTH cases were non-PTT on follow-up. The calculated sensitivity, specificity, positive and negative predictive values were 85.7%, 100%, 100% and 93.3%, respectively., Conclusion: Our study demonstrates that PTH ICC performed on additional ThinPrep slides is a valuable adjunct test in FNA samples with a differential diagnosis of PTT vs non-PTT. Low cellularity may be a limiting factor in the accurate assessment of PTH by ICC., (© 2023 John Wiley & Sons Ltd.)

The operative procedure in the surgical treatment of parathyroid carcinoma differs from that of benign hyperparathyroidism. However, preoperative differentiation is often difficult. This study elucidated how clinicians diagnose parathyroid carcinoma and the relationship between preoperative diagnosis and the operative course. Using a retrospective chart review, twenty cases of parathyroid carcinoma from nine participating centers were examined. In 11 cases with preoperative suspicion of malignancy, at least one of these three features was found: elevated serum calcium level (>14 mg/dL), palpable mass, and irregular margin on ultrasonography. Although an intact parathyroid hormone (iPTH) threshold to suspect malignancy has not been established, six cases showed marked iPTH elevation exceeding 8.0 times the upper limit of normal. One case was excluded from analysis due to hemodialysis. Compared with the four cases that showed calcium elevation, the iPTH threshold might represent better sensitivity. Among 9 cases of benign preoperative diagnosis, six cases were performed with pericapsular resection. In three cases where malignancy was suspected in the middle of the operation, the recommended en bloc resection with ipsilateral thyroid lobectomy was not performed but a parathyroidectomy with surrounding soft tissue. In contrast, 10 preoperatively suspected cases underwent en bloc resection, and one case underwent pericapsular resection followed by supplementary ipsilateral hemithyroidectomy due to the uncertain pre- and intraoperative findings to determine the diagnosis. In conclusion, the surgical procedure for parathyroid carcinoma strongly depends on the preoperative diagnosis. The presence of excessive iPTH levels might contribute to improved preoperative diagnostic sensitivity for parathyroid carcinoma.

Background: Parathyroid carcinoma (PC) is an exceedingly rare, slow-growing but progressive endocrine malignancy that represents a diagnostic and therapeutic challenge. Vertebral metastasis of PC is remarkable, with only 3 prior cases of spinal metastasis reported in the literature., Case Description: A 62-year-old woman presented with 1 week of neck pain radiating down her right arm. Cervical x-ray revealed a lytic lesion of the C4 vertebral body. Lab work revealed hypercalcemia with an elevated parathyroid hormone level. Computed tomography and magnetic resonance imaging revealed frank destruction of the C4 vertebral body and pedicles by PC. She was treated with corpectomy, mass excision, anterior cervical discectomy and fusion, postoperative radiotherapy, and nonspecific inhibitors of active tumor pathways. Her symptoms resolved postoperatively, and she has remained negative for reoccurrence at 15-month follow-up., Conclusions: To the authors' knowledge, we report the first described cervical spine metastasis of PC. Additionally, we review the treatment of this rare neoplasm in an extremely rare location in the age of tumor sequencing and morphoproteomic analysis.

Primary hyperparathyroidism caused by parathyroid carcinoma is extremely rare. Clinically, it is very challenging to differentiate between parathyroid carcinoma and adenoma. The correct diagnosis is made based on the histopathology of the resection specimen. This case report presents a woman in her 40s with body aches, knee joint pain, and fatigue, along with chronic kidney disease. Ultrasonography revealed a large hyperechoic lesion in the left parathyroid gland. Serum calcium, parathyroid hormone, urea, and creatinine levels were increased. The inferior parathyroid gland was surgically removed, and histopathological evaluation confirmed a diagnosis of parathyroid carcinoma. Unfortunately, many patients do not undergo complete resection due to a lack of a correct diagnosis during the initial surgery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent data suggest an increase in the overall incidence of parathyroid disorders, with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be nonspecific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT that may be associated with extraparathyroidal manifestations, requiring active surveillance for these manifestations as seen in multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multiglandular disease, recurrent PHPT, young onset PHPT (age ≤40 years), and those with a family history of parathyroid tumors. However, the underlying genetic cause for the majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for parathyroidectomy and has implications for the family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of sporadic parathyroid tumors. But the genetic cause in approximately half of the sporadic parathyroid tumors remains unknown. Furthermore, there is no systemic therapy for parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid tumors will allow us to identify biomarkers for diagnosis and novel targets for therapy., (Published by Oxford University Press on behalf of the Endocrine Society 2023.)

Introduction: Primary hyperparathyroidism (PHPT) caused by parathyroid tumours is mostly sporadic, with a genetic cause identified in 5-10% of cases. Familial parathyroid tumours can be included in complex syndromes, such as multiple endocrine neoplasia (MEN) type 1, 2A and 4 or hyperparathyroidism-jaw tumour syndrome (HPT-JT)., Objective: Characterisation of the familial parathyroid tumours followed-up at our centre and comparison of the different clinicopathological manifestations between the syndromes., Methods: Retrospective analysis of 48 patients with familial parathyroid tumours harbouring RET (n = 11), CDC73 (n = 20) and MEN1 (n = 17) germline mutations was performed., Results: Cases of PHPT in MEN2A syndrome presented with lower serum PTH (sPTH) and serum calcium (sCa) levels at diagnosis (sPTH = 108.0 (IQR 53.3) pg/mL, sCa = 10.6 ± 1.1 mg/dL) than MEN1 (sPTH = 196.9 (IQR 210.5) pg/mL, sCa = 11.7 ± 1.2 mg/dL) (p = 0.01, p = 0.03, respectively) or HPT-JT cases (sPTH = 383.5 (IQR 775.8) pg/mL, sCa = 12.9 ± 1.8 mg/dL) (p = 0.01; p < 0.001, respectively). There was a statistical difference in sCa levels between MEN1 and HPT-JT (p = 0.02), but not between sPTH (p = 0.07). The predominant first manifestation of the syndrome in MEN1 was gastroenteropancreatic neuroendocrine tumour (GEP-NET) in 47.1% of the cases, in MEN2A was medullary thyroid cancer (90.9%) and in HPT-JT was PHPT in 85% patients. In MEN1 syndrome, the number of affected parathyroid glands was significantly higher than in MEN2A (p < 0.001) and HPT-JT (p = 0.01)., Conclusion: The first manifestation of the syndrome in MEN1 cases was GEP-NET and not PHPT. Although presenting at similar ages, patients with MEN2A exhibit less severe biochemical and clinical PHPT at diagnosis than the other familial syndromes., (© 2023. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Rationale: Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine neoplasia 1 syndrome (MEN-1). As its main pathogenic factor involves genetic mutations, it can cause a variety of different clinical symptoms. However, cases with negative genetic testing results and multiple nonfunctional malignant neuroendocrine tumors (NETs) with metastasis are relatively rare., Patient Concerns: A 33-year-old man was admitted to the hospital for hyperparathyroidism. Imaging examination revealed multiple nodules in the parathyroid gland, pancreas, thymus, and adrenal gland, and multiple metastases to the lung, liver, thoracolumbar, as well as mediastinal lymph nodes., Diagnoses: After multidisciplinary consultation, this patient was diagnosed with MEN-1 syndrome with various original tumors and multiple systemic metastases., Interventions: The patient underwent parathyroid tumor resection and metastasis biopsy., Outcomes: The patient received denosumab and sorafenib treatment., Lessons: As an autosomal dominant hereditary disease, MEN-1 patients present with parathyroid hyperplasia, pancreatic and intestinal tumors, pituitary tumors, and so on, which are caused by genetic mutations. These patients would have hyperparathyroidism, hypoglycemia, gastric ulcer, and gastrointestinal diseases. However, some patients with MEN-1 syndrome cannot be diagnosed by genetic testing and simultaneously present with multiple nonfunctional NETs with systemic metastasis. This increases the difficulty of diagnosis and the subsequent treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Parathyroid cancer (PTC) is an extremely rare malignancy with an incidence of 5.7 per 10 million people. The exact preoperative or intraoperative diagnosis is difficult, but of paramount importance, because resection with negative margins is the only effective treatment., Case Report: A 46-years-old female was referred from another hospital with a diagnosis of "hyper-functioning thyroid nodule", based on the ultrasound showing a lesion of the right thyroid lobe and elevated FT4. At the admission, she had severe pain in the right inguinal area, fatigue, muscle weakness, and excessive diuresis. The blood assay demonstrated serum calcium of 4.02 mmol/l, parathyroid hormone of 1433.2 pg/ml, FT4 of 17.49 pmol/l, creatinine of 296 μmol/l. CT showed a tumor of the right thyroid lobe with a size of 2.5. A right lobectomy was performed. Right parathyroid glands were not found. Because of the constellation for hyperparathyroidism and suspicion of parathyroid malignancy ipsilateral and central lymph node dissection and partial removal of the right sternothyroid muscle were performed, which correlated with a significant intraoperative drop in the parathyroid hormone. Three months later, a re-resection was performed because of SPECT-CT evidence for residual parathyroid tissue., Conclusion: The timely diagnosis of PTC is a prerequisite for a good outcome. The best preoperative indicators are serum parathyroid hormone > 4 times above the upper limit, serum calcium > 14 mg/dL, a palpable neck mass, and a local invasion found intraoperatively. The only curative treatment is the complete removal of the tumor with a negative margin., Key Words: Delayed diagnosis, Hyperparathyroidism, Parathyroid cancer, Surgery.

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., (© 2023. The Author(s).)

Background: To investigate the characteristics of reticular fibre structure (RFS) in parathyroid adenoma (PTA), atypical parathyroid tumour (APT), and parathyroid carcinoma (PTC), and to assess its value as a diagnostic indicator., Methods: Clinical data and pathological specimens of patients with PTA, APT or PTC were collected. Reticular fibre staining was performed to observe the characteristics of RFS. This study evaluated the incidence of RFS destruction in parathyroid tumours, compared RFS destruction between primary PTC and recurrent and metastatic PTC, and explored the association between RFS destruction and clinicopathological features of APT and primary PTC., Results: Reticular fibre staining was performed in 50 patients with PTA, 25 patients with APT, and 36 patients with PTC. In PTA cases, a delicate RFS was observed. In both the APT and PTC groups, incomplete RFS areas were observed. The incidence of RFS destruction was different among the PTA, APT, and PTC groups (P < 0.001, χ 2 -test), at 0% (0/50), 44% (11/25), and 86% (31/36), respectively. When differentiating PTC from APT, the sensitivity and specificity of RFS destruction were 81% and 56%, respectively. The incidence of RFS destruction was 73% (8/11) in the primary PTC group and 92% (23/25) in the recurrent and metastatic PTC groups. In both the APT group and primary PTC group, no correlation was found between RFS destruction and clinicopathological features., Conclusion: RFS destruction may indicate that parathyroid tumours have unfavourable biological behaviours.Reticular fibre staining may be a valuable tool for improving the diagnostic accuracy in parathyroid tumours., (© 2023. The Author(s).)

Primary hyperparathyroidism (pHPT) is a frequent endocrine disease, the incidence of which is clearly increasing. In addition to the classical symptoms of bone pain, osteoporosis and renal calculi, nonspecific complaints, such as listlessness and exhaustion, anxiety states and depressive symptoms also often occur. The diagnosis is simple and is carried out by determination of calcium and parathormone (PTH) serum levels. The majority of parathyroid adenomas can be localized by ultrasound and Tc-99m-MIBI scintigraphy. The indications for surgery can normally already be identified by the laboratory biochemical detection. Surgery is the only curative treatment of pHPT and is normally successful. In addition to bilateral exploration, a focused parathyroidectomy can be planned. The success of surgery can be intraoperatively documented by the determination of intraoperative Quick PTH (IOPTH)., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Primary hyperparathyroidism (pHPT) is now diagnosed much earlier and is often asymptomatic. Biochemically mild pHPT is characterized by small parathyroid adenomas (NSDA) and the results of localization diagnostics as well as surgical treatment are poorer. The frequency of redo surgery is 3-14% in large registries. The planning of a reoperation is no different from the basic principles for the first intervention. Diagnosis and differential diagnoses must be checked. This is followed by a review of the first operation and the associated histology as well as imaging and the course of parathyroid hormone (PTH) values. The next step is to check whether the reoperation is necessary. Most patients still have comprehensible indications that correspond to the guidelines and also ex-post. In contrast to the first intervention, there is always a need to attempt to localize the NSDA. The first procedure is a surgically performed ultrasound. Other localization options are MIBI-SPECT scintigraphy, 4D-CT and FEC-PET-CT, with the latter having the highest sensitivity. There is a clear relationship between higher case numbers and better surgical outcomes. Personal experience is decisive and in terms of predicting success this is even more important than the results of localization procedures. The goal of maximizing the outcome and minimizing morbidity justifies what is from the perspective of those affected probably the most important requirement for the future: no redo surgery for HPT outside of a high-volume center., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

A clinical diagnosis of multiple endocrine neoplasia type 1 (MEN1) syndrome is usually confirmed with genetic testing in the germline. It is expected that menin protein expression is lost in MEN1-related tumors. Therefore, we investigated the potential of menin immunohistochemistry in parathyroid adenomas as an additional tool in the recognition and genetic diagnosis of MEN1 syndrome. Local pathology archives were searched for parathyroid tumors from patients with MEN1 syndrome and without MEN1, including sporadic, patients with multiple endocrine neoplasia type 2A and hyperparathyroidism-jaw parathyroid tumors. Menin immunohistochemistry was performed and its use to identify MEN1-related tumors was assessed. Twenty-nine parathyroid tumors from 16 patients with MEN1 and 61 patients with parathyroid tumors from 32 non-MEN1 were evaluated. Immunohistochemical nuclear menin loss in one or more tumors was found in 100% of patients with MEN1 and 9% of patients with non-MEN1. In patients with multiple tumors, menin loss in at least one tumor was seen in 100% of 8 patients with MEN1 and 21% of patients with 14 non-MEN1. Using a cutoff of at least 2 tumors showing menin loss per patient, the positive and negative predictive values for the diagnosis MEN1 were both 100%. The practical and additional value of menin immunohistochemistry in clinical genetic MEN1 diagnosis is further illustrated by menin immunohistochemistry in 2 cases with a germline variant of unknown significance in the MEN1 gene. Menin immunohistochemistry is useful in the recognition of MEN1 syndrome as well as in the clinical genetic analysis of patients with inconclusive MEN1 germline testing., Competing Interests: Conflicts of Interest and Source of Funding: A.V.D.V. is supported by a research grant from the Dutch Cancer Society (KWF). For the remaining authors, none were declared., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

BACKGROUND Parathyroid carcinoma represents about 0.005% of all malignancies and accounts for less than 1% of primary hyperparathyroidism cases. Precise preoperative diagnosis of parathyroid carcinoma is challenging, and it is usually diagnosed postoperatively by histological examination. Early suspicion of parathyroid carcinoma can lead to a more extensive surgical approach to reduce the risk of carcinoma recurrence. CASE REPORT The first case involves a 58-year-old woman who presented with severe back pain. An incidental finding on cervical magnetic resonance imaging of a soft-tissue-density mass at the right para-tracheal zone. The large size and the noticeable mass effect pushing the trachea and esophagus to the left side suggested the need for further investigations to rule out malignancy. Initially, it was thought to be a thyroid nodule investigated by fine-needle aspiration that revealed follicular thyroid cancer. After a histopathological examination, it was determined to be a parathyroid carcinoma. The second case involved a 30-year-old woman with a lower-limb tingling sensation. The significantly enlarged mass seen during thyroid ultrasound warranted surgical excision and histopathological analysis to rule out malignancy. Excision of what was considered a parathyroid adenoma revealed a histopathological finding of carcinoma, prompting a hemithyroidectomy. Both patients had high calcium and parathyroid hormone levels preoperatively. CONCLUSIONS Preoperative high calcium, intact parathyroid hormone, creatinine, and alkaline phosphatase, in addition to the lymphocyte-to-monocyte ratio and tumor diameter, are suggested to be predictive of parathyroid carcinoma diagnosis and should be carefully analyzed in all patients presenting with primary hyperparathyroidism.

Background: Parathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (PHPT) and particularly rare in the mediastinum. Herein, we present a case of mediastinal PC and conduct a related literature review., Case Presentation: We described a case of a 50-year-old female patient with PHPT due to mediastinal PC. She was initially admitted to a local hospital in her hometown with hypercalcemia and high blood concentrations of PTH (parathyroid hormone). The patient underwent neck parathyroidectomy and pathological examination suggested parathyroid adenoma. Although the overproduction of serum calcium and PTH declined after the surgery, calcium and PTH increased again one month later, so the patient was transferred to our hospital. A 99 m Tc-sestamibi scan revealed an ectopic finding in the mediastinum, which was also indicated on the CT image. After removing the mediastinal mass, the metabolism of calcium and PTH quickly reverted to normal and the pathologic features of the mass were consistent with PC. By reviewing the related literature, we noticed that only scattered reports were published before 1982, and those were not included in the present review due to their differences with current radiological examination and treatment methods. After excluding outdated studies, we summarized and analyzed 20 reports of isolated mediastinal PC and concluded that. Parathyroidectomy remains the only curative treatment for the disease. Furthermore, the success of treatment directly depends on accurate preoperative localization., Conclusion: With this study, we emphasize the importance of accurate preoperative diagnosis of mediastinal PC and improve clinicians' understanding of the disease., (© 2023. The Author(s).)

Purpose: This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on for primary hyperparathyroidism (PHPT) with uniglandular parathyroid adenomas in other localizations., Methods: The data of PHPT patients who underwent parathyroidectomy in our institution were assessed retrospectively. Abnormal gland localization was confirmed by operative and pathology reports as well as normocalcemia that lasted for at least 6 months postoperatively. The relationships of biochemical and clinical findings of patients with confirmed adenoma localizations were analyzed. In order to determine independent factors that can predict EPAs, binary logistic regression was used., Results: Among 421 patients (83.4% female, mean age 49 ± 13.2 years) enrolled in the study, the most common adenoma localization was the lower left parathyroid gland (36.1%; p < 0.001). Parathyroid adenomas were more common in lower localizations compared to upper localizations and were smaller in size (p < 0.001 and p = 0.004, respectively). In univariate analysis, serum intact parathyroid hormone and calcium levels were found to be higher (p = 0.004 and p = 0.002, respectively), moderate/severe hypercalcemia was more common (p = 0.024), phosphorus levels were lower (p = 0.04), and postoperative transient hypocalcemia was more common (p = 0.013) in cases of EPAs than other localizations. There was no significant difference in adenoma size between EPAs and other classical localizations. In multivariate analysis, only a high serum calcium level was an independent predictor of EPAs (OR 2.017, 95% CI 1.142-3.564, p = 0.016). Receiver-operating characteristic curve analysis yielded an optimal cutoff value of 12.25 mg/dL for serum calcium (88% sensitivity, 63% specificity, and area under the curve: 0.861)., Conclusion: EPAs can cause a more biochemically distinct PHPT picture compared to parathyroid adenomas in classical localizations. A high calcium level at diagnosis may be a clinical predictor for EPAs and may affect the clinical approach and imaging technique choices. Due to the increased risk of transient hypocalcemia in patients with EPAs, caution should be exercised in postoperative follow-up. Furthermore, in the event of negative preoperative imaging, starting the parathyroid exploration from the lower left region may be a good option for the surgeon., (© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

A man in his 50s was referred with profound, symptomatic hypercalcaemia. He was diagnosed with primary hyperparathyroidism, confirmed on 99m Tc-sestamibi scan. He was treated for the hypercalcaemia and referred to ear, nose and throat (ENT) surgeons for parathyroidectomy, which was delayed due to the COVID-19 pandemic. In the ensuing 18 months, he had five hospital admissions with severe hypercalcaemia requiring intravenous fluids and bisphosphonate infusions. During the last admission, hypercalcaemia was resistant to maximal medical management. Emergency parathyroidectomy was planned, but delayed due to intervening COVID-19 infection. Due to persistent severe hypercalcaemia (serum calcium: 4.23 mmol/L), he was commenced on intravenous steroids, following which serum calcium normalised. Subsequently, he underwent emergency parathyroidectomy, which normalised his serum parathyroid and calcium levels. On histopathological examination, a diagnosis of parathyroid carcinoma was made. On follow-up, patient remained well and normocalcaemic. In patients with primary hyperparathyroidism unresponsive to standard therapy, but responsive to steroids, underlying parathyroid malignancy should be considered., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)