Brown Tumor Research Articles

From acute hypercalcaemia to post-parathyroidectomy hungry bone syndrome in a patient with primary hyperparathyroidism-associated brown tumours.

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Tertiary Hyperparathyroidism Presenting as Multifocal Brown Tumors: A Case Report

Brown Tumor (BT) of the bone is a rare manifestation of hyperparathyroidism (HPTH), an unusual reactive bone lesion attributed to disturbed bone remodeling, from long-standing increase in parathyroid hormone level (PTH). Historically, BTs were described with primary HPTH but due to early diagnosis of this entity, and improved survival in patients with end-stage renal disease (ESRD) especially those on renal replacement therapy (RRT), more cases of BT are now described in this population, and less in PHPTH. Thus, it is mostly the consequence of untreated secondary or tertiary HPTH whose major culprits are chronic kidney disease (CKD) and ESRD. The management of brown tumors related to chronic renal failure consists primarily of its prevention through the use of phosphate binders, vitamin D analogues, and calcimimetics with surgical parathyroidectomy reserved as the final resort in refractory cases. Herein, we present the case of a 24-year-old female patient with ESRD on intermittent hemodialysis (IHD) who developed recent onset facial tumefaction. Blood work revealed markedly elevated PTH at more than 5000 pg/ml, upper borderline hypercalcemia, and hyperphosphatemia. Further investigations with chest computed tomography (CT) and Technetium-99m (99mTc)- Sestamibi scan nuclear imaging showed multiple ribs lytic lesions as well as features of extensive BT and parathyroid adenomas. Thereafter, the patient was sent for parathyroidectomy after which the patient developed hungry bone syndrome.

P118 Differentiating between a central giant cell granuloma and brown tumour – a case study

P118 Differentiating between a central giant cell granuloma and brown tumour – a case study

Giant cell tumor of the clivus misdiagnosed as calcifying fibrous tumor

Abstract Introduction/Objective Giant cell tumors of bone (GCTs) are generally benign, locally aggressive lesions accounting for approximately 4% of primary bone tumors. GCTs of the skull are rare and constitute <1% of all reported GCTs as they typically occur in the epiphysis of long bones. Specifically, in the clivus location, these tumors are exceedingly rare with fewer than 10 articles in English literature. The purpose of this report is to describe a case of GCT in this unusual location that was misdiagnosed as giant cell reparative granuloma on biopsy and subsequently calcifying fibrous tumor on resection. Methods/Case Report A 34-year-old male presented with history of headache, visual disturbance, epistaxis, and nausea. MRI demonstrated a large soft tissue mass eroding the clivus. A biopsy was interpreted at an outside institution as giant cell reparative granuloma. The patient was treated with denosumab and subsequently underwent resection of the mass due to worsening symptoms. Post-treatment pathology was interpreted as calcifying fibrous tumor. The patient presented to our institution for further management and outside pathology was reviewed. Histologically, the initial tumor was composed of a bland spindle cell proliferation with admixed osteoclast-type giant cells. In this location, the differential diagnosis includes Brown tumor, giant cell reparative granuloma, and, rarely, GCT. HG34W immunostain was positive in the tumor cells confirming the diagnosis of GCT. The post-therapy specimen showed abundant woven bone formation and a lack of giant cells. Post-denosumab GCT are known to show these features. Follow up imaging showed a slow growing moderately enhancing mass at the resection site. Patient is alive with disease 36 months after initial diagnosis. Results (if a Case Study enter NA) NA Conclusion With rare exceptions, bone tumors frequently follow generalized patterns of involvement. Pathologists need to be aware of these exceptions. Appropriate panel of immunohistochemical stains help clinching the right diagnosis, especially in unusual clinical settings.

Panoramic Radiographic Evaluation of the Osseous Morphological Changes in Iraqi Patients with Chronic Renal Failure

To make comparative evaluation of gonial cortical bone thickness, antegonial index, gonial angle values and mandibular canal bone resorption, pathologies like ground-glass appearance in jawbones and brown tumor i n Iraqi patients undergoing dialysis due to chronic renal failure and patients from the healthy control group on panoramic .Panoramic radiographs were taken from 40 patients divided into two groups (20 normal and 20 dialysis patients) .Gonial cortical thickness, antegonial index and gonial angle values with the mandibular canal wall resorption were assessed , pathologies such as ground-glass appearance and Brown tumor as “available” or “not available.” Mandibular canal wall resorption (Chi-square:16.52 , P<0.01) was found highly statistically significant difference between the patient and control groups ,resorption detected mainly in right side of male patients .Panoramic radiographs showed decreasing in values of the measuring parametersin patients receiving dialysis treatment due to chronic renal failure compared to the control group.

Pediatric Neuroendocrine Neoplasia of the Parathyroid Glands: Delving into Primary Hyperparathyroidism.

Our objective was to overview the most recent data on primary hyperparathyroidism (PHP) in children and teenagers from a multidisciplinary perspective. Methods: narrative review based on full-length, English-language papers (from PubMed, between January 2020 and July 2023). Results: 48 papers (14 studies of ≥10 subjects/study, and 34 case reports/series of <10 patients/study). Study-sample-based analysis: except for one case-control study, all of the studies were retrospective, representing both multicenter (n = 5) and single-center (n = 7) studies, and cohort sizes varied from small (N = 10 to 19), to medium-sized (N = 23 to 36) and large (N = 63 to 83); in total, the reviewed studies covered 493 individuals with PHP. Case reports/series (n = 34, N = 41): the mean ages studied varied from 10.2 to 14 years in case reports, and the mean age was 17 years in case series. No clear female predominance was identified, unlike that observed in the adult population. Concerning the assessments, there were four major types of endpoints: imaging data collection, such as ultrasound, 99mTc Sestamibi, or dual-phase computed tomography (CT); gene testing/familial syndrome identification; preoperative findings; and exposure to surgical outcome/preoperative drugs, like cinacalcet, over a 2.2-year median (plus two case reports of denosumab used as an off-label calcium-lowering agent). Single-gland cases (representing 85% of sporadic cases and 19% of genetic PHP cases) showed 100% sensitivity for neck ultrasounds, with 98% concordance with 99mTc Sestamibi, as well as a 91% sensitivity for dual-phase CT, with 25% of the lesions being ectopic parathyroids (mostly mediastinal intra-thymic). Case reports included another 9/41 patients with ectopic parathyroid adenomas, 3/41 with parathyroid carcinomas, and 8/41 subjects with brown tumors. Genetic PHP (which has a prevalence of 5-26.9%) mostly involved MEN1, followed by CDC73, CASR, RET, and CDKN1B, as well as one case of VHL. Symptomatic PHP: 70-100% of all cases. Asymptomatic PHP: 60% of genetic PHP cases. Renal involvement: 10.5% of a cohort with genetic PHP, 71% of sporadic PHP cases; 50% (in a cohort with a mean age of 16.7), 29% (in a cohort with a mean age of 15.2); 0% (in infancy) to 50-62% (in teenagers). Bone anomalies: 83% of the children in one study and 62% of those in two other studies. Gastrointestinal issues: 40% of one cohort, but the data are heterogeneous. Cure rate through parathyroidectomy: 97-98%. Recurrent PHP: 2% of sporadic PHP cases and 38% of familial PHP cases. Hungry bone syndrome: maximum rate of 34-40%. Case reports identified another 7/41 subjects with the same post-parathyroidectomy condition; a potential connection with ectopic presentation or brown tumors is suggested, but there are limited data. Minimally invasive thoracoscopic approaches for ectopic tumors seemed safe. The current level of statistical evidence on pediatric PHP qualifies our study- and case-sample-based analysis (n = 48, N = 534) as one of the largest of its kind. Awareness of PHP is the key factor to benefit our young patients.

Brown Tumor with Multiple Lesions as a Manifestation of Tertiary Hyperparathyroidism: A Case Report and Literature Review

Brown tumor is an uncommon focal lytic bone lesion, which is considered as an end-stage lesion of abnormal bone metabolism, caused by long-standing increased parathyroid hormone levels. It is a rare manifestation of hyperparathyroidism that is classified into three types, of which tertiary is the rarest. It can be found in any part of the skeleton, and in some cases, occurs in multiple bones and can be easily misdiagnosed as a metastatic tumor. Therefore, although uncommon, it should be generally considered as a differential diagnosis with bone malignancy lesions, and particularly in patients with renal failure on long-term hemodialysis. In the present case report, a young patient with end stage renal disease presented with tertiary hyperparathyroidism revealed by multiple brown tumors of the pelvis and mandible. We recall through this observation the importance of clinical context, the complementary roles that different imaging modalities can play in different settings, and the relevance of measuring serum calcium and parathyroid hormone before the diagnosis of osteolytic bone lesions.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report

BackgroundPrimary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor.Case presentationThe proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband’s daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient’s blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father’s first signs of brown tumor were in the right maxilla, while the daughter’s appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland.ConclusionWe report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

SAT210 A Case Of Recurrent Metastatic Parathyroid Cancer Complicated By Multiple Brown Tumors

Abstract Disclosure: A. Elmaaz: None. E. Bustamante: None. M. Batra: None. Introduction: Parathyroid cancer is a rare malignancy with about 25 % incidence of metastasis. Brown tumors are benign bone lesions caused by excessive bone turnover which are rarely associated with parathyroid carcinoma. Here, we present a case of recurrent metastatic parathyroid cancer complicated by multiple brown tumors. Case Presentation: A 63-year-old male presented with back pain, generalized weakness, and significant weight loss. Laboratory findings showed hypercalcemia 14.4 mg/dl, Alkaline phosphatase 253 U/L, and phosphorus 2.3 mg/dl. He was admitted to the hospital for hypercalcemia workup. MRI spine showed a heterogeneous mass arising from the left thyroid lobe and conglomerate lymph node, along with extensive metastatic sclerotic lytic lesions throughout the spine. MRI brain revealed multiple metastatic lesions in the skull base, facial bones, and the right angle of the mandible. Further workup revealed normal PSA, normal serum levels of free lambda and kappa light chains, and normal urine and serum protein electrophoresis. PTH levels, 2435.1 (8.7-77.1) pg/ml, and PTH-rP levels &amp;lt;1.1 pmol/l were noted. Ultrasound-guided FNA of the thyroid mass showed solid growth of malignant parathyroid cells strongly stained for PTH. Biopsy of the body of the T12 vertebra and mandibular lesions showed giant cell lesions of the bone with fibrous dysplasia, consistent with brown tumors. IV hydration, calcitonin, cinacalcet, and IV zoledronic acid started, followed by left hemithyroidectomy and left inferior parathyroidectomy. Surgical pathology was positive for parathyroid carcinoma invading the thyroid gland. His calcium and PTH levels post-surgery significantly improved. A few months later, the patient presented again with hypercalcemia and high levels of PTH. Sestamibi parathyroid scan showed no evidence of parathyroid adenoma. Because of enlarging left neck mass, confirmed by MRI neck, he then underwent excision of the left subcutaneous cervical lesion involving the left sternomastoid muscle. Surgical pathology was consistent with parathyroid carcinoma involving soft tissue. His calcium and PTH levels improved on subsequent follow-up visits. Conclusion: Parathyroid carcinoma is not a common cause of hypercalcemia. Though a rare entity, parathyroid cancer should be considered in the differentials of hypercalcemia and extremely high levels of PTH. Metastasis either locally or remotely should not be overlooked. Brown tumors could mimic bone metastasis and giant cell tumors; therefore, the clinical presentation is important for the diagnosis. Presentation: Saturday, June 17, 2023

SAT201 A Rare Case Of A Mediastinal Atypical Parathyroid Adenoma Resulting In Severe Hypercalcemia And Brown Tumor

Abstract Disclosure: O.A. Aluko: None. D. Franey: None. R. Quiros: None. W. Burfeind: None. R.E. Amori: None. Introduction: Primary hyperparathyroidism is most often from parathyroid adenomas located usually in close association to the thyroid gland. Ectopic parathyroid glands result in significant variability in the position of the gland, however rarely in the mediastinum. We report a case of a patient with severe hypercalcemia from a large, ectopic mediastinal parathyroid adenoma. Case Report: A 53-year old male with a past medical history of hypercalcemia and nephrolithiasis was sent to the ER for evaluation of hypercalcemia after he was found to have a corrected calcium of 12.5 mg/dl (n8.4 - 10.2 mg/dl) on routine labs. Repeat blood work at presentation confirmed hypercalcemia with a corrected calcium 11.9 mg/dl and elevated ALP of 211 U/l (n 43 - 122 U/L), elevated initial PTH of799 pg/ml (n 18.4 - 80.1 pg/ml), Vit D 32.7 ng/ml (n 30 - 100 ng/ml), and low phosphorus 2.4 mg/dl (n2.7 - 4.5 mg/dl). Calcium slightly improved to 11.7 mg/dl after IV hydration. Chest CT showed a large mediastinal mass compressing trachea and esophagus, suspicious for parathyroid origin, with a smaller left sided lesion suspicious for parathyroid adenoma. CT also showed multiple bone lesions likely brown tumors. He underwent complete robotic resection of the mediastinal mass. Immediately prior to surgery, PTH was 1002.8 pg/ml, and fell to 131.1 pg/ml and 44.1 pg/ml following removal of the mediastinal mass. Adherence of the mass to surrounding structures made resection challenging, resulting in a right vocal cord paralysis. After surgery, he was empirically started on IV calcium and calcitriol for high clinical concern for hungry bone syndrome, both later discontinued as serum calcium remained within normal limits. Pathologic findings reported as highly suspicious, however not definitive for parathyroid carcinoma with no evidence of perineural or lymphovascular invasion. Given rarity, he was referred to a tertiary cancer center where he was diagnosed with Atypical parathyroid Adenoma (APA). He underwent a right pubic biopsy with pathology diagnosis of brown tumor of hyperparathyroidism. He started on cinacalcet 30 mg daily after surgery. There is a future plan for resection of the smaller left sided parathyroid adenoma. Conclusion: This case highlights two rare entities; a mediastinal ectopic parathyroid and atypical parathyroid adenoma. Atypical Parathyroid Adenoma is a not-well defined entity which could mimic a parathyroid carcinoma as seen in our case. The location of the mass in the superior mediastinum is unusual, making it more difficult to diagnose, and could increase risk of complications during resection. Delayed diagnosis of these entities can lead to severe hypercalcemia and skeletal complications infrequently seen in common primary hyperparathyroidism cases. Presentation: Saturday, June 17, 2023

SAT249 Femur Lysis Calcium Crisis

Abstract Disclosure: G. Gupta: None. S. Idriss: None. N. Barua: None. J. Hodge: None. I. Jamal: None. Introduction: Primary hyperparathyroidism usually presents with symptoms of bone pain, fatigue, polyuria, constipation, and nephrolithiasis. Here we describe a 27-year-old female with a femoral neck fracture and found to have a parathyroid mass. Case: 27 y/o female with autism spectrum, presented to the ED for evaluation of a mechanical fall and was found to have a left femur and pubic ramus fracture. On arrival she was vitally stable, labs were significant for parathyroid hormone-related hypercalcemia corrected Ca 14.8 mg/dL, PTH 911 peaked to 2884 pg/mL, vit D level of 12.7 ng/mL, phosphorus of 2.3 mg/dL. Trauma workup revealed numerous osseous lytic lesions lower extremities. Review of system was negative except for localized pain at fracture site. Family history negative for hypercalcemia or hyperparathyroidism. She was managed with IV fluids, IV Zoledronic Acid 4 mg, SC calcitonin 240 units, and 50K IU D3. During hospitalization, she needed re-dozing with Zoledronic acid and Cinacalcet due to recurrence of significant hypercalcemia, warranting further imaging. CT neck showed mandibular and maxillary bone lesions raising suspicion of hyperparathyroidism jaw tumor syndrome (HPT-JT) vs brown tumors, 3.1 cm lobular mass inferior to the right thyroid lobe suspicious for large parathyroid adenoma vs carcinoma, and other multiple enlarged parathyroids. She underwent left femur cephalomedullary nailing and prophylactic nailing for the impending right femur fracture. Bone pathology showed fragmented bone, adipose, and skeletal muscle with fibrinous debris. She underwent subtotal parathyroidectomy (4-1/2 glands) and intraoperative PTH level declined from 1537 to 75 pg/mL 15 minutes after removal. Pathology showed tissue consistent with multi glandular parathyroid disease without evidence of malignancy. Postop her course was complicated with hungry bone syndrome requiring a few weeks on IV calcium. Discussion: Pathologic conditions in primary hyperparathyroidism include single adenomas (80-90% of the time), multiglandular hyperplasia multiple-gland (three or more glands) accounting for approximately 6%, and parathyroid carcinomas account for 1-2% of cases. Other conditions as with primary hyperparathyroidism include Familial hyperparathyroidism such as MEN 1 &amp; 2A, Familial isolated hyperparathyroidism, and Familial HPT-JT syndrome, previously termed familial cystic parathyroid adenomatosis. Interestingly our pt had multiglandular hyperplasia which is a less common cause, she also demonstrated jaw lesions but didn’t fulfill the criteria for HPT-JT. Conclusion: Our patient had an unusual presentation of large bone fracture and multiple lytic lesions likely representing a brown tumor of the bone due to primary hyperparathyroidism. Most patients with lytic lesions have malignancy, however, endocrine pathologies should also be considered. Presentation: Saturday, June 17, 2023

SAT181 Clinical Profile And Treatment Outcomes Of Patients With Sporadic And Multiple Endocrine Neoplasia Syndrome-related Primary Hyperparathyroidism

Abstract Disclosure: U.E. Mathew: None. V.P. Jyotsna: None. A.S. Upadhyay: None. A. Goyal: None. D. Kandaswamy: None. C. Bal: None. A. Sharma: None. C.K. Sharma: None. S. Aggarwal: None. N. Tandon: None. Primary hyperparathyroidism (PHPT) is the most frequent endocrine disorder in MEN-1. The MEN-1 related PHPT (MPHPT) differs from sporadic (SPHPT) in many aspects. The distinction between them is very important at the point of diagnosis as it enables planning on treatment and subsequent surveillance for other endocrine tumours. Objective: The aim of study was to compare the clinical, biochemical, radiological features and surgical outcome in patients with MPHPT versus SPHPT and to identify the predictors of MEN-1 among apparently sporadic hyperparathyroidism. Design: Ambispective cross-sectional study from 2015-2021. Participants: 251 subjects with SPHPT and 23 subjects with MPHPT. Setting: The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Results: The classical symptoms of hyperparathyroidism (80.5% vs 47.8%, p&amp;lt;0.001), mean serum calcium (12.7 vs 11.8 mg/dl, p=0.01) and alkaline phosphatase (ALP) levels (p=0.03) were significantly seen higher in SPHPT than MPHPT. MEN-1 patients showed low bone mineral density (BMD) at lumbar spine (-1.52±1.44 vs -2.6±1.25, p=0.001) and femoral neck (1.13±1.37 vs-1.81±1.01, p=0.002) and higher prevalence of complicated nephrolithiasis (34.5 % vs 56.5%, p=0.03) for the age. BMD at their lumbar spine showed an inverse correlation with serum PTH (r=-0.51, p=0.01). Whereas the typical radiological features of hyperparathyroidism and severe skeletal manifestations including brown tumours and fractures were observed less in MEN-1 (44.8% vs 21.7% vs, p=0.02). The overall remission rate was 98.6% in SPHPT and 90% in MPHPT on long term follow up.Despite milder biochemical features, the frequency of hungry bone syndrome was not different from SPHPT (11.6% vs 15.8%, p=0.32). The transient and permanent hypoparathyroidism were more common in MPHPT group (24.4% vs 50%, p=0.01: 0.4% vs 15%, p=0.002).The factors strongly predictive of MEN-1 in multivariate analysis were ALP within the normal range (OR 4.2(95% CI 1.1-16.9), p=0.038), lower lumbar spine BMD (OR 0.47 (95% CI (0.28-0.76), p=0.003) and hyperplastic parathyroid gland on histopathology (OR 37.1(95% CI (9.9-138.6), p&amp;lt;0.001). The multivariate predictive model showed an excellent discrimination between two classes with area under curve in ROC was 0.91. Conclusions: MEN-1 associated PHPT have severe bone and renal involvement despite milder biochemical features, even in Indian settings, where there is a higher frequency of severe symptomatic sporadic hyperparathyroidism. MEN-1 should be suspected when, a discordant finding of severe degree of bone demineralisation at lumbar spine and in normal range of ALP, has observed among apparently SPHPT. Our model can assist in deciding on screening for MEN-1 as the family history and multiglandular involvement may be absent at the presentation, and delay in development of other endocrine tumours. Presentation: Saturday, June 17, 2023

Brown tumor of multiple facial bones associated with tertiary hyperparathyroidism in a patient on maintenance hemodialysis

A brown tumor is a non-cancerous bone lesion that develops due to excessive parathyroid hormone (PTH) levels and can result in bone resorption, ultimately contributing to skeletal deformities. We describe one rare case of a patient on Hemodialysis who develops a brown tumor of multiple facial bones due to Tertiary Hyperparathyroidism.

Gene Polymorphism Influencing Persistent Bone Resorption in Brown Tumor: A Case Series with Possible Pathogenesis and Potential Therapeutic Approach.

Brown tumor represents a terminal stage of bone remodeling process due to an imbalance between osteoclastic and osteoblastic activity. It represents a reparative cellular process, rather than a neoplastic process mostly associated with primary or secondary hyperparathyroidism. Although parathyroidectomy is the first treatment of choice for brown tumors, several cases don't resolve even after normalization of parathyroid hormone levels which leads to surgical intervention. Therefore, to avoid multiple bone surgeries in the same patient, it is crucial to have a conservative approach like targeted therapy which could block certain molecules involved in bone resorption. In this string, we have recognized and quantified three molecules namely sclerostin, MCP-1 and CD73 in brown tumors and correlated their expression with bone resorption pathogenesis and potential therapeutic approach.

The evolution of primary hyperparathyroidism publications and global productivity from past to present: A bibliometric analysis during 1980 to 2022.

The aim of this study was to perform a descriptive analysis of scientific articles about primary hyperparathyroidism (PHPT) using bibliometric approaches. By analyzing the links between the various research components (authors, journals, institutions, countries) of the academic outputs, it was aimed to summarize the intellectual structure of PHPT, identify recent research trends, and determine the global productivity. Three thousand nine hundred fifty-four articles on PHPT published between 1980 and 2022 were pulled from the Web of Science database and analyzed using bibliometric approaches. Bibliometric network visualization maps were used to identify trending topics, citation analysis, and international collaborations. Spearman correlation coefficient was used for correlation analysis. The 3 most prolific authors are Bilezikian JP. (n = 87), Silverberg SJ. (n = 72) and Akerstrom G. (n = 57). The top 3 most productive institutions were Columbia University (n = 133), Udice French Research Universities (n = 127) and Uppsala University (n = 98). The top 3 most productive journals were Surgery (n = 216), Journal of Clinical Endocrinology and Metabolism (n = 201) and World Journal of Surgery (n = 148). The top 3 contributing countries to the PHPT literature were United States of America (n = 1062, 26.8%), Italy (346, 8.7%) and United Kingdom (274, 6.9%). The most studied topics from past to present are parathyroidectomy, hypercalcemia, parathyroid hormone/adenoma/glands, calcium/calcimimetics, scintigraphy/sestamibi, bone mineral density, ultrasound, vitamin D, osteoporosis, minimally invasive parathyroidectomy, brown tumor, nephrocalcinosis/nephrolithiasis, multiple endocrine neoplasia type 1, normocalcemia, pregnancy, imaging/preoperative imaging, parathyroid cancer/carcinoma, asymptomatic primary hyperparathyroidism, and cinacalcet. The trending topics in recent years were normocalcemic primary hyperparathyroidism, trabecular bone score, children, CDC73, microwave ablation, radiofrequency ablation, denosumab, cinacalcet, preoperative imaging, imaging, diagnosis, CT, PET, PET/CT, 4D/CT, SPECT/CT, F-18-fluorocholine, quality of life, fractures, and metabolic syndrome. We can say that there will be an increasing research trend on PHPT in the coming years. In addition to the Western countries such as the United States and European countries with large economies, Japan and Turkey were also identified as leading countries in the development of the PHPT literature. This study provides significant information about the intellectual structure and global productivity of PHPT to clinicians and other researchers interested on PHPT.

Multiple Bone Cysts Caused by Hyperparathyroidism: A Case Report and Review of the Literature.

Brown tumor, a skeletal complication of severe hyperparathyroidism, comprises reparative granulation tissue and proliferating fibrous tissue with hemosiderin deposition. Multiple brown tumors are extremely rare complications of primary hyperparathyroidism. A 41-year-old woman presented with pain in the left knee. Radiography showed multiple cystic lesions in both femurs and the left proximal tibia, and additional radiography showed multiple cystic lesions in the left humerus and ulna. Magnetic resonance imaging (MRI) revealed multiple cystic lesions in the bilateral femurs, left proximal tibia, and ilium. Laboratory tests revealed hypercalcemia (albumin-corrected calcium level, 13.9 mg/dl), hypophosphatemia (phosphate level, 1.6 mg/dl), elevated level of alkaline phosphatase level (614 U/l), and markedly elevated parathyroid hormone (PTH) level (1,070 pg/ml; normal range=10-65 ng/l). 99mTc-hexakis-2-methoxyisobutyl-isonitrile scintigraphy revealed tracer accumulation in the left upper parathyroid gland, which was consistent with parathyroid tumor. Although resection of the parathyroid tumor was planned, the patient developed parathyroid apoplexy before tumor excision. After the parathyroid apoplexy, serum calcium and PTH levels temporarily normalized. Resurgence of the PTH level was observed 2 years after the diagnosis, and the patient underwent left upper parathyroidectomy. One year after the tumor excision, the patient had no symptoms, and MRI showed shrinkage of the cystic bone lesions. This report emphasizes the importance of considering hyperparathy-roidism as a differential diagnosis for patients with multiple bone lesions.

Brownish limb tumor as a presentation of primary hyperparathyroidism

43-year-old male, with tumor in the anterior region of the right lower limb (figure 1) and biopsy compatible with brown tumor. He presented total serum calcium 12.3 mg/dl and 13 mg/dl (NR: 8.3-10.3), parathormone (PTH) 1057 pg/ml (NR 15-65). With the diagnosis of primary hyperparathyroidism, a 99mTc-MIBI parathyroid scintigraphy with SPECT was requested, which showed hyperfunctioning parathyroid tissue in the projection of the left inferior parathyroid gland. Hand radiographs showed a lytic lesion in punch in the distal phalanx of the first finger of the left hand (figure 2); in the clavicle radiograph: lytic lesion of 10 mm x 8 mm in the right clavicle, no alterations were evidenced in the skull radiograph.

Síndrome de Sagliker: una nueva entidad, un problema antiguo.

Introduction: Sagliker syndrome, described by Dr. Yahya Sagliker in 2004, constitutes the most advanced state of secondary hyperparathyroidism in chronic kidney disease. Deforming and disabling clinical syndrome that reduces the quality of life and adds psychological disorders to the patient with chronic kidney disease. This study aims to report on a series of eight cases in Mexico and warn about the correct management and follow-up of secondary hyperparathyroidism. Cases: 8 cases are presented with ages between 17 and 35 years, serum parathyroid hormone levels between 1583 and 4715 pg/ml, and alkaline phosphatase levels between 146 and 2065 IU/L. All cases with brown tumors in the maxilla and mandible characteristic of Sagliker syndrome. Evolution: All patients were ingesting calcium and vitamin D analogs at diagnosis or in the last three months. Conclusion: Sagliker syndrome is the most severe and chronic complication of secondary hyperparathyroidism and chronic kidney disease. The significant bone involvement of this syndrome generates a disabling facial and prolonged bone deformity that impacts morbidity, mortality, and mental health. Concomitant with bone alterations, vascular and cardiac calcifications add a crucial cardiovascular risk, so any surgery constitutes a high risk.

Brown Tumour in Chronic Kidney Disease: Revisiting an Old Disease with a New Perspective.

Osteitis fibrosa cystica (OFC) and Brown Tumours are two related but distinct types of bone lesions that result from the overactivity of osteoclasts and are most often associated with chronic kidney disease (CKD). Despite their potential consequences, these conditions are poorly understood because of their rare prevalence and variability in their clinical manifestation. Canonically, OFC and Brown Tumours are caused by secondary hyperparathyroidism in CKD. Recent literature showed that multiple factors, such as hyperactivation of the renin-angiotensin-aldosterone system and chronic inflammation, may also contribute to the occurrence of these diseases through osteoclast activation. Moreover, hotspot KRAS mutations were identified in these lesions, placing them in the spectrum of RAS-MAPK-driven neoplasms, which were until recently thought to be reactive lesions. Some risk factors contributed to the occurrence of OFC and Brown Tumours, such as age, gender, comorbidities, and certain medications. The diagnosis of OFC and Brown Tumours includes clinical symptoms involving chronic bone pain and laboratory findings of hyperparathyroidism. In radiological imaging, the X-ray and Computed tomography (CT) scan could show lytic or multi-lobular cystic alterations. Histologically, both lesions are characterized by clustered osteoclasts in a fibrotic hemorrhagic background. Based on the latest understanding of the mechanism of OFC, this review elaborates on the manifestation, diagnosis, and available therapies that can be leveraged to prevent the occurrence of OFC and Brown Tumours.

Brown tumors revealing primary hyperparathyroidism: It still exists

Hyperparathyroidism is a frequent endocrinopathy, often diagnosed at the stage of subclinical hypercalcemia by systematic calcium measurement and the advent of new parathyroid hormone measurement techniques. Brown tumors represent a late-onset, locally aggressive but potentially benign non-metastatic bone complication secondary to an abnormality of bone metabolism within the context of hyperparathyroidism. It is usually a late complication, rarely revealing. We report 2 clinical cases of primary hyperparathyroidism revealed by a brown tumor, complicated in one case by a pathological fracture. The aim of our work is to underline the importance of looking for hyperparathyroidism in every lytic lesion, given the insidious nature of this endocrinopathy, thus preventing pathological fractures and improving functional quality of life.