A Case Report and Literature Review of a Giant Parathyroid Adenoma with Digestive System Symptoms and Brown Tumor

A Case Report and Literature Review of a Giant Parathyroid Adenoma with Digestive System Symptoms and Brown Tumor | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Case Report and Literature Review of a Giant Parathyroid Adenoma with Digestive System Symptoms and Brown Tumor Wen-ting Pan, Zhi-Hong Zhao, Kun Wang, Liang Ou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4330728/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: A parathyroid adenoma stands as the primary cause of primary hyperparathyroidism, and clinically it often presents with symptoms such as elevated blood calcium levels and recurrent kidney stones. Parathyroid adenoma discovered due to symptoms such as nausea and vomiting is relatively rare. Case presentation: A 59-year-old woman was hospitalized due to symptoms of nausea and vomiting. Imaging studies unveiled a solid mass located on the posterior aspect of the left thyroid lobe, potentially of parathyroid origin, along with multiple bone destruction throughout the body. Laboratory tests showed elevated serum total calcium, low potassium, and increased parathyroid hormone levels. The final diagnosis was primary hyperparathyroidism complicated by the brown tumor. Symptomatic treatment, including calcium reduction, fluid replacement, and electrolyte supplementation, was initiated. Subsequently, parathyroid adenoma resection was performed. Postoperatively, the patient developed hungry bone syndrome, which was treated with calcium supplementation, and follow-up showed normalization of blood calcium levels. Conclusions: Unexplained nausea accompanied by electrolyte disturbances should raise suspicion of rare causes such as primary hyperparathyroidism. When there are multiple systemic osteolytic changes, brown tumor should be considered, along with assessment of serum calcium and parathyroid hormone levels for diagnosis. Case report Primary hyperparathyroidism Parathyroid adenoma Brown tumor Hungry bone syndrome Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Primary hyperparathyroidism (PHPT) constitutes an endocrine disorder, with its etiology encompassing parathyroid hyperplasia, adenoma, or carcinoma. Among these, parathyroid adenoma is the most common cause, with the majority (80%-85%) of primary hyperparathyroidism cases being caused by a single parathyroid adenoma [1]. Excessive secretion of parathyroid hormone results in a substantial elevation of serum calcium levels [2]. The primary manifestations encompass symptoms across multiple organs and systems, encompassing the digestive system (nausea, vomiting, ulcers), kidneys (stones, polyuria, impaired renal function), skeletal system (bone pain, cystic fibrous osteitis, osteoporosis, brown tumors), cardiovascular system (arrhythmia, atherosclerosis), and nervous system (depression, dementia, cognitive impairment) [3]. Here, we present a case of parathyroid adenoma accompanied by a brown tumor, diagnosed based on symptoms of vomiting and electrolyte imbalance. This case underscores the significance of considering primary hyperparathyroidism (PHPT) as a potential differential diagnosis when gastrointestinal symptoms manifest, as well as the necessity of measuring serum calcium and parathyroid hormone(PTH) levels prior to diagnosing osteolytic bone lesions. Case presentation A 59-year-old woman was admitted to our hospital due to a month-long history of nausea and vomiting. One month earlier, an endoscopy at an external hospital indicated superficial atrophic gastritis with no other significant abnormalities. Abdominal CT showed multiple soft tissue density shadows with bone destruction in bilateral ribs, T12 thoracic vertebra, and right iliac bone, raising suspicions of metastatic tumor or multiple myeloma; bilateral kidney stones were also observed (Figure 1). Laboratory tests showed: low potassium 2.61 mmol/L（N：3.5-5.3 mmol/L）, high calcium 2.99 mmol/L（N：2.00-2.50 mmol/L）, and low phosphate 0.57 mmol/L（N：0.90-1.34 mmol/L）(Figure 3). Potassium supplementation and calcium reduction treatments were administered at that time. Eighteen days before admission, a follow-up test indicated: high chloride 108.2 mmol/L（N：98-107 mmol/L）, high calcium 3.00 mmol/L, low phosphate 0.75 mmol/L, and normal levels of blood sodium and potassium. Subsequently, the patient presented herself at our hospital. Upon physical examination, the patient exhibited multiple skeletal deformities throughout the body, without abdominal tenderness or rebound tenderness; the neurological examination was regular. The patient had recently lost 10 pounds and had a history of poliomyelitis 50 years ago, hypertension for 30 years, and regular use of amlodipine besylate with well-controlled blood pressure. Three years ago, she had a history of left femur fracture and underwent internal fixation surgery. PET-CT revealed a soft tissue shadow with mild increased FDG metabolism behind and below the left thyroid lobe, suggesting a parathyroid origin (parathyroid adenoma or other); widespread uneven reduction in bone density and multiple bone destructions throughout the skeleton, suggesting fibrous cystic osteitis; bilateral kidney stones; osteoporosis(Figure 4). Further investigation showed a parathyroid hormone level of 827.40 pg/ml（N：12-88 pg/ml）(Figure 2). On the second day of admission to our department, the patient's parathyroid hormone levels further increased, peaking at 1766 pg/ml. Serum amylase levels also rose, peaking at 192 U/L（N：30-110 U/L）, and serum lipase levels increased significantly, peaking at 1216 U/L（N：30-110 U/L）. Serum calcium levels fluctuated and increased, peaking at 2.99 mmol/L, while vitamin D levels were low at 7.62 ng/ml（N：>20 ng/ml）. Thyroid ultrasound revealed a solid mass on the posterior aspect of the left thyroid lobe, likely originating from the parathyroid, approximately 45×28×26mm in size, with a relatively clear boundary and somewhat irregular shape(Figure 5). The diagnosis of a parathyroid tumor was confirmed. Combining this with the PET-CT findings of osteolytic lesions, the comprehensive diagnosis was parathyroid tumor with brown tumor[4]. Before surgery, intravenous potassium chloride was administered to improve the patient's hypokalemia, and intravenous esomeprazole sodium was given for stomach protection; the patient also took potassium citrate granules orally for potassium supplementation. During surgery, exploration unveiled the lesion affixed to the posterior aspect of the lower pole of the left thyroid lobe(Figure 6). Rapid intraoperative pathological examination indicated parathyroid adenoma-like hyperplasia (left parathyroid gland) (Figure 7). The surgery went smoothly, and the intraoperative PTH level was 81.90 pg/ml, significantly lower than preoperative levels. One hour after surgery, follow-up PTH decreased from 81.90 pg/ml to 16.30 pg/ml, with Serum lipase levels at 333 U/L and Serum amylase at 90 U/L. Postoperatively, the patient experienced persistent recurrent hypocalcemia, with serum total calcium levels as low as 1.76 mmol/L, consistent with the presentation of 'hungry bone syndrome'(HBS)[5]. The patient received treatment with oral calcium carbonate chewable tablets (1.5g twice daily), alfacalcidol tablets (0.5 µg daily), and intravenous calcium gluconate. Follow-up tests showed that vitamin D levels remained below average, so the oral dose of alfacalcidol was increased to 1.5 µg daily, leading to gradual improvement in indicators. Postoperatively, the patient's PTH, serum calcium and phosphorus levels, serum amylase, and serum lipase returned to normal, and the degree of bone destruction improved compared to before. Discussion Parathyroid adenoma stands as the most frequent cause of primary hyperparathyroidism. Its clinical manifestations include gastrointestinal symptoms (nausea, vomiting, peptic ulcer), kidney stones, osteoporosis with fractures, and changes in mental state[6]. In this case, the patient presented with unexplained nausea and vomiting upon admission. While PET-CT revealed a soft tissue shadow situated behind and below the left lobe of the thyroid, suggesting the diagnosis of a parathyroid tumor, other possible diagnoses for the patient's nausea and vomiting symptoms should also be considered. These include nausea and vomiting due to visceral pain (acute gastroenteritis, cholecystitis, appendicitis, pancreatitis), nausea and vomiting due to mechanical intestinal obstruction, or endocrine disorders (Primary hyperparathyroidism causing hypercalcemia-induced nausea and vomiting). Among these, clinicians are most likely to suspect a diagnosis of acute gastroenteritis, but the patient reported no consumption of contaminated food and had no abdominal pain. Gastric endoscopy showed superficial atrophic gastritis, and treatment with gastroprotective drugs did not alleviate the symptoms, suggesting that the diagnosis of acute gastroenteritis is less likely. Since the patient had no abdominal tenderness, rebound tenderness, or optimistic Murphy's sign on physical examination and imaging did not reveal gallstones or peritoneal effusion around the appendix, the diagnoses of cholecystitis and appendicitis can be ruled out[7, 8]. In this situation, acute pancreatitis might be the first consideration. Interestingly, the patient's serum amylase and lipase levels were indeed noticeably elevated. Throughout the patient's hospitalization at the specialized facility, serum amylase peaked at 192 U/L, and serum lipase peaked at 1216 U/L, but none exceeded three times the upper limit of normal. Additionally, imaging did not show inflammatory changes in the pancreas, so the criteria for diagnosing pancreatitis were not met [9]. In addition, nausea and vomiting can also be caused by mechanical intestinal obstruction, but this type of vomiting usually consists primarily of gastrointestinal contents and is accompanied by abdominal pain, distension, and cessation of gas and stool passage from the anus [10],imaging showed distended intestinal loops filled with gas, which does not match the patient's symptoms. Finally, based on imaging and the patient's clinical symptoms, it is considered that the nausea and vomiting are caused by primary hyperparathyroidism. It is worth noting that the patient had abnormal elevations in serum amylase and lipase during the course of the illness, although not enough to diagnose pancreatitis. This suggests that there may be a potential mechanism by which the parathyroid adenoma could be causing pancreatic disease. Previous studies have indicated an association between primary hyperparathyroidism and pancreatitis [11]. Recent literature suggests that PHPT causing pancreatitis may involve three mechanisms: First, elevated serum calcium levels due to PHPT accelerate the conversion of pancreatic proenzymes to active enzymes by trypsin, leading to pancreatic self-digestion and pancreatitis[12]. Second, hypercalcemia promotes calcium deposition, leading to pancreatic duct obstruction and the formation of pancreatic stones, resulting in pancreatitis [13]. Third, elevated calcium levels and genetic mutations such as mutations in serine protease inhibitor Kazal type 1 (SPINK1) and cystic fibrosis transmembrane conductance regulator (CFTR) can contribute to the development of pancreatitis [14]. Therefore, the specific mechanism between parathyroid adenoma and the pancreas remains to be further investigated. In clinical diagnosis, in addition to detecting parathyroid tumors through PET-CT, elevated blood calcium is also a key indicator suggesting primary hyperparathyroidism. The premise for assessing the extent of abnormal elevation in blood calcium is to determine the accurate initial blood calcium level by excluding the influence of protein binding, i.e., adjusting the calcium level (corrected calcium (mmol/L) = serum total calcium - (serum albumin - 40 g/L) × 0.02)[15]. When the patient was admitted, the serum total calcium was 2.99 mmol/L, and the albumin was 42.5 g/L（N：40-55 g/L）. The corrected calcium was 2.94 mmol/L（N：2.00-2.50 mmol/L）. The diagnosis was mild hypercalcemia [16]. Next, it is essential to analyze the specific reasons for hypercalcemia, whether it is due to primary hyperparathyroidism, malignancy-related osteolytic hypercalcemia, or a combination of both mechanisms. Hypercalcemia associated with cancer is referred to as hypercalcemia of malignancy (HCM). The onset of hypertrophic cardiomyopathy (HCM) may be associated with elevated levels of parathyroid hormone-related protein (PTHrP), local bone resorption induced by cytokines, production of 1,25-dihydroxyvitamin D by tumors, or ectopic PTH [17]. These mechanisms lead to increased blood calcium levels, increased intestinal calcium absorption, and increased bone resorption, which in turn cause a reduction in parathyroid hormone levels [18]. However, upon reviewing the patient's medical history, there were no signs of systemic malignancies, and imaging did not reveal any apparent tumor lesions. Additionally, the patient exhibited significantly elevated parathyroid hormone levels, suggesting that hypercalcemia was unlikely caused by malignancy. Further investigation into whether the patient's hypercalcemia was caused by parathyroid hormone revealed that upon admission, the patient's blood calcium levels had further increased, and circulating PTH levels had significantly risen. Hypophosphatemia and decreased levels of 25-hydroxyvitamin D are all diagnostic criteria for primary hyperparathyroidism [19], combined with imaging localization of the parathyroid tumor, the diagnosis of the patient's parathyroid tumor was ultimately confirmed. The patient has had poliomyelitis since childhood and reports low physical activity. On physical examination, multiple skeletal deformities were observed throughout the body. Additionally, there is a history of left femoral fracture. CT findings showed multiple soft tissue density shadows accompanied by bone destruction throughout the body, suggesting a diagnosis of metastatic tumor or multiple myeloma. However, other possibilities should also be considered, such as brown tumors, fibrous dysplasia, or ossifying fibromas. Indeed, some cancer metastases can cause widespread bone destruction in patients, but in this case, there were no previous findings of malignancy before admission, and tumor markers were within normal range. This suggests that the diagnosis of metastatic tumor is less likely [18]. The imaging manifestations of fibrous dysplasia, ossifying fibromas, and multiple myeloma differ significantly from the patient's imaging findings. Therefore, these diagnoses can also be excluded [20]. Subsequent PET-CT results showed a mass originating from the parathyroid gland, with multiple areas of bone destruction throughout the body, local thickening and expansion of the bone, suggestive of fibrous cystic osteitis, bilateral kidney stones, and osteoporosis. Combined with laboratory findings of elevated PTH, elevated blood calcium, and decreased blood phosphorus, all of these factors point to a brown tumor caused by primary hyperparathyroidism [21]. Brown tumors result from heightened osteoclast activity triggered by excessive levels of parathyroid hormone. They are closely related to primary hyperparathyroidism, and approximately 3% of patients with primary hyperparathyroidism develop brown tumors [22]. It can usually affect any part of the skeletal system, including the skull (usually the jawbone), cranial bones, clavicles, ribs, pelvic bones, femur, and spine. Clinically, it may present as bone pain, pathological fractures, or urinary stones, or it can be asymptomatic [23]. Three months after surgery, a follow-up CT scan showed improvement in the osteolytic lesions throughout the body compared to before, further confirming the diagnosis of parathyroid adenoma with brown tumors. Parathyroid adenomas are usually very small, typically measuring between 3-5 mm, with an average weight of less than 1g. Parathyroid adenomas that weigh more than 3.5g have a length greater than 2cm and are associated with clinical manifestations of hyperparathyroidism, which are referred to as giant parathyroid adenomas [24]. In this case, the excised specimen measured 3.5 × 3.5 × 2 cm and weighed 10.0 g, meeting the criteria for a giant parathyroid adenoma. The preferred treatment for parathyroid adenoma is usually surgical removal [25]. After surgery, the patient experienced persistent hypocalcemia, with a post-operative serum total calcium level as low as 1.76 mmol/L. For patients who have undergone thyroid or parathyroid surgery and maintain serum calcium levels below 2.1 mmol/L for over four days, hypoparathyroidism (HBS) may be contemplated [5]. HBS mainly manifests as persistent hypocalcemia, which can lead to arrhythmias, seizures, skeletal pain, and even death. Early intervention may be vital to preventing HBS after surgery. Relevant literature indicates that preoperative serum vitamin D levels do not independently predict postoperative hypoparathyroidism (HBS) [26]. After parathyroidectomy, the proportion of patients with vitamin D deficiency who develop post-operative hypocalcemia is higher than in those without vitamin D deficiency, highlighting the importance of high-dose vitamin D supplementation therapy. In this case, the patient did indeed experience hungry bone syndrome and vitamin D deficiency after surgery and was treated with oral calcium carbonate chewable tablets (1.5g twice daily), alfacalcidol tablets (1.5ug once daily), and intravenous calcium gluconate. During an outpatient follow-up one month post-surgery, the patient exhibited normal levels of parathyroid hormone (PTH), serum calcium, vitamin D, and blood cell counts. So far, there have been few reports on the occurrence of pancytopenia after parathyroidectomy. In this case, ten days after surgery, the patient developed pancytopenia with fluctuating leukocyte levels dropping to a peak of 1.6 × 10 9 /L（N：3.5-9.5 × 10 9 /L）, persistent decline in platelet levels to a peak of 84 × 10 9 /L（N：125-350 × 10 9 /L）, and fluctuating reductions in erythrocyte levels to a peak of 2.49 × 10 12 /L（N：3.8-5.1 × 10 12 /L）. Complement immunoglobulin levels, anemia screening, and immunofixation electrophoresis were all inconclusive. According to relevant literature, anemia in PHPT cases usually presents as normocytic normochromic anemia[27]， thrombocytopenia is also a rare manifestation of PHPT[28]. Prior reports indicate that intact parathyroid hormone (PTH) may impede the proliferation of erythroid progenitor cells and the production of erythropoietin, potentially resulting in a decline in red blood cell levels. PTH promotes bone marrow fibrosis, leading to a decrease in hematopoietic factors, which in turn causes thrombocytopenia[29, 30]. However, these conclusions contradict some research reports, so the specific mechanism of pancytopenia after parathyroid adenoma surgery remains unclear and requires further investigation. Conclusion Primary hyperparathyroidism has numerous clinical manifestations, and severe primary hyperparathyroidism can lead to severe hypercalcemia, which can be life-threatening. Early diagnosis and treatment are essential. PET-CT has higher sensitivity than regular CT for diagnosing parathyroid tumors. For patients with primary hyperparathyroidism who have significant systemic bone symptoms, clinicians should include brown tumors in the differential diagnosis. Additionally, the potential endocrine relationship between parathyroid adenoma and pancreatitis, as well as the reason for pancytopenia after parathyroid adenoma surgery, warrants further in-depth research. Declarations Ethics approval and consent to participate Ethics committee：Ethics Committee of Jiangsu University Affiliated Hospital. Committee’s reference number：KY2023K1105. Consent for publication The patient provided written informed consent for the publication of this case report and any accompanying images. A copy of the written consent form is available for review by the series editor of this journal. Availability of data and materials The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding All funding for the report research comes from a project in Zhenjiang City, Zhi-Hong Zhao, Affiliated Hospital of Jiangsu University, with project number: SH2016030. Authors’ contributions PWT conceptualized the manuscript, interpreted the data, and revised the manuscript. OL revised the draft and analyzed specific diagnostic correlations. ZZH performed the diagnosis, surgery, and follow-up for the patient. WK engaged in the case discussion and aided in manuscript revisions. All authors have reviewed and endorsed the final manuscript. Acknowledgment The authors express sincere gratitude to the patients who consented to participate in this study. References Abshirini H, Heidari M, Fahimi A, Ghorbani P, Ghadirzadeh E, Shafiei S: Giant parathyroid adenoma presenting with multiple pathologic fractures: A case report . Clinical Case Reports 2023, 11 (6). Kowalski GJ, Buła G, Żądło D, Gawrychowska A, Gawrychowski J: Primary hyperparathyroidism . Endokrynologia Polska 2020, 71 (3):260-270. Kochman M: Primary hyperparathyroidism: clinical manifestations, diagnosis, and evaluation according to the Fifth International Workshop guidelines . Reumatologia 2023, 61 (4):256-263. Werner J, Grünig H, Loher H, Fischli S, Strobel K, Wicke C: Localization of Brown Tumors With 18F-Fluorocholine PET/CT Imaging in Severe Primary Hyperparathyroidism . Clinical Nuclear Medicine 2023, 48 (8):e387-e389. M NE, Aw N, Ml N: The role of intra-operative parathyroid hormone assay in non-localized adenoma . Pakistan journal of medical sciences 2022, 38 (8):2376-2379. Aygün N, Uludağ M: Surgical Treatment of Primary Hyperparathyroidism: Which Therapy to Whom? Sisli Etfal Hastanesi tip bulteni 2019, 53 (3):201-214. Delungahawatta T, Rao SJ, Wolff M, Haas CJ: Pulmonary Clostridium perfringens: Seeding Beyond the Gastrointestinal Tract . Journal of community hospital internal medicine perspectives 2024, 14 (1):30-34. Khatoon MA, Naeem S, Akmal U, Farid A, Ahmed Khan S: Retrocecal Ascending Appendix Attached to the Hepatic Flexure and Right Intra-abdominal Testis Identified During Open Appendicectomy: A Case Report . Cureus 2024, 16 (4):e57484. Nepali A, Kharga S, Jayan M, Adhikari P, Shah A, Sanker V: Acute pancreatitis secondary to moderate hypertriglyceridemia: A case report . Clin Case Rep 2024, 12 (3):e8582. Chaouch MA, Taieb AH, Jallali M, Chedly E, Gafsi B, Noomen F: Rare case report of intestinal obstruction due to incarcerated small bowel in omental breach . Int J Surg Case Rep 2024, 115 :109245. Bhadada SK, Udawat HP, Bhansali A, Rana SS, Sinha SK, Bhasin DK: Chronic pancreatitis in primary hyperparathyroidism: comparison with alcoholic and idiopathic chronic pancreatitis . Journal of gastroenterology and hepatology 2008, 23 (6):959-964. Haverback BJ, Dyce B, Bundy H, Edmondson HA: Trypsin, trypsinogen and trypsin inhibitor in human pancreatic juice . The American journal of medicine 1960, 29 :421-433. Devgan Y, Mayilvaganan S, Mishra A, Chand G, Agarwal G, Mohindra S, Gupta S, Agarwal A: PHPT with Pancreatitis: Atypical Presentation of PHPT . Indian journal of endocrinology and metabolism 2023, 27 (6):513-518. Mehta G, Rathod VM, Patel T, Solanki D: Atypical Presentation of Primary Hyperparathyroidism as Recurrent Pancreatitis: A Case Report With a Review of the Literature . Cureus 2023, 15 (6):e41140. Qi H, Wang B, Zhu L: Independent associations of serum calcium with or without albumin adjustment and serum phosphorus with nonalcoholic fatty liver disease: results from NHANES 1999-2018 . Frontiers in endocrinology 2024, 15 :1323990. Al Hassan MS, El Ansari W, Issa N, Darweesh A, Abdelaal A: Severe hypercalcemia secondary to parathyroid adenoma: Series of four consecutive cases at a tertiary care hospital in Qatar . International Journal of Surgery Case Reports 2023, 109 . Vasquez L, Cortes T: Hypercalcemia of Malignancy Complicated by Osteonecrosis of the Jaw Treated With Cinacalcet . JCEM case reports 2023, 1 (5):luad105. Carpenter TO: Case 32-2021: A 14-Year-Old Girl with Swelling of the Jaw and Hypercalcemia. Reply . The New England journal of medicine 2022, 386 (3):296. Issa PP, Kandil E, Lee GS: Radiofrequency ablation as a treatment modality for primary hyperparathyroidism: a systematic literature review . Gland surgery 2024, 13 (1):87-99. Ibrahem HM: Gnathic Bones and Hyperparathyroidism: A Review on the Metabolic Bony Changes Affecting the Mandible and Maxilla in case of Hyperparathyroidism . Advances in medicine 2020, 2020 :6836123. Majic Tengg A, Cigrovski Berkovic M, Zajc I, Salaric I, Müller D, Markota I: Expect the unexpected: Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism . World journal of clinical cases 2024, 12 (7):1200-1204. Ergen FB, Ayvaz M, Yildiz AE, Aydingoz U, Gedikoglu G: Brown tumour presenting as a soft-tissue mass . Clinical radiology 2012, 67 (3):286-289. Hoshi M, Takami M, Kajikawa M, Teramura K, Okamoto T, Yanagida I, Matsumura A: A case of multiple skeletal lesions of brown tumors, mimicking carcinoma metastases . Archives of orthopaedic and trauma surgery 2008, 128 (2):149-154. Matías-García B, Mendoza-Moreno F, Díez-Alonso M, Ovejero-Merino E, Vera-Mansilla C, Blázquez-Martín A, Quiroga-Valcárcel A, Jiménez-Martín R, D'Amico R, Lasa-Unzúe I et al : Spontaneous cervical hematoma caused by giant parathyroid adenoma in an elderly patient: A case report . Medicine international 2024, 4 (1):1. Papanikos V, Papadodima E, Bantouna D, Paparodis RD, Livadas S, Angelopoulos N, Karvounis E: Hypercalcemic Crisis Due to a Giant Intrathyroidal Parathyroid Adenoma, with Postsurgical Severe Hypocalcemia and Hungry Bone Syndrome: A Case Report . Clinics and practice 2024, 14 (1):179-187. Salman MA, Rabiee A, Salman AA, Youssef A, Shaaban HE, Ftohy T, Maurice KK, Balamoun H: Role of vitamin D supplements in prevention of hungry bone syndrome after successful parathyroidectomy for primary hyperparathyroidism: A prospective study . Scandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society 2021, 110 (3):329-334. Bhadada SK, Bhansali A, Ahluwalia J, Chanukya GV, Behera A, Dutta P: Anaemia and marrow fibrosis in patients with primary hyperparathyroidism before and after curative parathyroidectomy . Clinical endocrinology 2009, 70 (4):527-532. Bhadada SK, Arya AK, Mukhopadhyay S, Khadgawat R, Sukumar S, Lodha S, Singh DN, Sathya A, Singh P, Bhansali A: Primary hyperparathyroidism: insights from the Indian PHPT registry . Journal of bone and mineral metabolism 2018, 36 (2):238-245. Bhadada SK, Arya AK, Parthan G, Singh P: The resolution of anemia after curative parathyroidectomy is sustained even after a decade . Indian journal of endocrinology and metabolism 2015, 19 (5):691-692. Lotinun S, Sibonga JD, Turner RT: Evidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts . Endocrinology 2005, 146 (9):4074-4081. Additional Declarations No competing interests reported. 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18:10:41","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":40054,"visible":true,"origin":"","legend":"\u003cp\u003eSummary of biochemical investigations at presentation.\u003c/p\u003e","description":"","filename":"Figure3Summaryofbiochemicalinvestigationsatpresentation..png","url":"https://assets-eu.researchsquare.com/files/rs-4330728/v1/1622dbc4548ba01255e5604f.png"},{"id":56196469,"identity":"c1de8d85-2c7d-42fe-8ef8-67869cca31fd","added_by":"auto","created_at":"2024-05-09 18:10:45","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":597537,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT.\u003c/p\u003e","description":"","filename":"Figure4PETCT..png","url":"https://assets-eu.researchsquare.com/files/rs-4330728/v1/244e922ec7c05c155d0e6e2c.png"},{"id":56196428,"identity":"7a97772c-103a-4ed9-85cd-b15ee93192ca","added_by":"auto","created_at":"2024-05-09 18:10:35","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":207327,"visible":true,"origin":"","legend":"\u003cp\u003eNeck ultrasound.\u003c/p\u003e","description":"","filename":"Figure5Neckultrasound..png","url":"https://assets-eu.researchsquare.com/files/rs-4330728/v1/9654fc2fcd123abc6c68fd15.png"},{"id":56196324,"identity":"ac6f823a-23f1-4c98-8269-bb373a07ce55","added_by":"auto","created_at":"2024-05-09 18:09:39","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":1011749,"visible":true,"origin":"","legend":"\u003cp\u003eParathyroid adenoma specimen after excision.\u003c/p\u003e","description":"","filename":"Figure6Parathyroidadenomaspecimenafterexcision..png","url":"https://assets-eu.researchsquare.com/files/rs-4330728/v1/46c8c50c94356214c202eea8.png"},{"id":56196411,"identity":"27ef21cd-e752-49b8-93ba-c99d67a79b30","added_by":"auto","created_at":"2024-05-09 18:10:23","extension":"jpg","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":10468804,"visible":true,"origin":"","legend":"\u003cp\u003eAdenoma of parathyroid gland HE-staining, 20× magnification.\u003c/p\u003e","description":"","filename":"Figure7AdenomaofparathyroidglandHEstaining20magnification..jpg","url":"https://assets-eu.researchsquare.com/files/rs-4330728/v1/294023b9ab7146fe5823c7d4.jpg"},{"id":56427435,"identity":"4c083777-eb66-4f10-b906-cdbd6b344c0e","added_by":"auto","created_at":"2024-05-14 04:54:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":13867177,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4330728/v1/07e8b0ed-633a-4884-8624-99d44709d97e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Case Report and Literature Review of a Giant Parathyroid Adenoma with Digestive System Symptoms and Brown Tumor","fulltext":[{"header":"Background","content":"\u003cp\u003ePrimary hyperparathyroidism (PHPT) constitutes an endocrine disorder, with its etiology encompassing parathyroid hyperplasia, adenoma, or carcinoma. Among these, parathyroid adenoma is the most common cause, with the majority (80%-85%) of primary hyperparathyroidism cases being caused by a single parathyroid adenoma [1]. Excessive secretion of parathyroid hormone results in a substantial elevation of serum calcium levels [2]. The primary manifestations encompass symptoms across multiple organs and systems, encompassing the digestive system (nausea, vomiting, ulcers), kidneys (stones, polyuria, impaired renal function), skeletal system (bone pain, cystic fibrous osteitis, osteoporosis, brown tumors), cardiovascular system (arrhythmia, atherosclerosis), and nervous system (depression, dementia, cognitive impairment) [3]. Here, we present a case of parathyroid adenoma accompanied by a brown tumor, diagnosed based on symptoms of vomiting and electrolyte imbalance. This case underscores the significance of considering primary hyperparathyroidism (PHPT) as a potential differential diagnosis when gastrointestinal symptoms manifest, as well as the necessity of measuring serum calcium and parathyroid hormone(PTH) levels prior to diagnosing osteolytic bone lesions.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 59-year-old woman was admitted to our hospital due to a month-long history of nausea and vomiting. One month earlier, an endoscopy at an external hospital indicated superficial atrophic gastritis with no other significant abnormalities. Abdominal CT showed multiple soft tissue density shadows with bone destruction in bilateral ribs, T12 thoracic vertebra, and right iliac bone, raising suspicions of metastatic tumor or multiple myeloma; bilateral kidney stones were also observed (Figure 1). Laboratory tests showed: low potassium 2.61 mmol/L（N：3.5-5.3 mmol/L）, high calcium 2.99 mmol/L（N：2.00-2.50 mmol/L）, and low phosphate 0.57 mmol/L（N：0.90-1.34 mmol/L）(Figure 3). Potassium supplementation and calcium reduction treatments were administered at that time. Eighteen days before admission, a follow-up test indicated: high chloride 108.2 mmol/L（N：98-107 mmol/L）, high calcium 3.00 mmol/L, low phosphate 0.75 mmol/L, and normal levels of blood sodium and potassium. Subsequently, the patient presented herself at our hospital. Upon physical examination, the patient exhibited multiple skeletal deformities throughout the body, without abdominal tenderness or rebound tenderness; the neurological examination was regular. The patient had recently lost 10 pounds and had a history of poliomyelitis 50 years ago, hypertension for 30 years, and regular use of amlodipine besylate with well-controlled blood pressure. Three years ago, she had a history of left femur fracture and underwent internal fixation surgery. PET-CT revealed a soft tissue shadow with mild increased FDG metabolism behind and below the left thyroid lobe, suggesting a parathyroid origin (parathyroid adenoma or other); widespread uneven reduction in bone density and multiple bone destructions throughout the skeleton, suggesting fibrous cystic osteitis; bilateral kidney stones; osteoporosis(Figure 4). Further investigation showed a parathyroid hormone level of 827.40 pg/ml（N：12-88 pg/ml）(Figure 2). On the second day of admission to our department, the patient\u0026apos;s parathyroid hormone levels further increased, peaking at 1766 pg/ml. Serum amylase levels also rose, peaking at 192 U/L（N：30-110 U/L）, and serum lipase levels increased significantly, peaking at 1216 U/L（N：30-110 U/L）. Serum calcium levels fluctuated and increased, peaking at 2.99 mmol/L, while vitamin D levels were low at 7.62 ng/ml（N：\u0026gt;20 ng/ml）. Thyroid ultrasound revealed a solid mass on the posterior aspect of the left thyroid lobe, likely originating from the parathyroid, approximately 45\u0026times;28\u0026times;26mm in size, with a relatively clear boundary and somewhat irregular shape(Figure 5). The diagnosis of a parathyroid tumor was confirmed. Combining this with the PET-CT findings of osteolytic lesions, the comprehensive diagnosis was parathyroid tumor with brown tumor[4]. Before surgery, intravenous potassium chloride was administered to improve the patient\u0026apos;s hypokalemia, and intravenous esomeprazole sodium was given for stomach protection; the patient also took potassium citrate granules orally for potassium supplementation. During surgery, exploration unveiled the lesion affixed to the posterior aspect of the lower pole of the left thyroid lobe(Figure 6). Rapid intraoperative pathological examination indicated parathyroid adenoma-like hyperplasia (left parathyroid gland) (Figure 7). The surgery went smoothly, and the intraoperative PTH level was 81.90 pg/ml, significantly lower than preoperative levels. One hour after surgery, follow-up PTH decreased from 81.90 pg/ml to 16.30 pg/ml, with Serum lipase levels at 333 U/L and Serum amylase at 90 U/L. Postoperatively, the patient experienced persistent recurrent hypocalcemia, with serum total calcium levels as low as 1.76 mmol/L, consistent with the presentation of \u0026apos;hungry bone syndrome\u0026apos;(HBS)[5]. The patient received treatment with oral calcium carbonate chewable tablets (1.5g twice daily), alfacalcidol tablets (0.5 \u0026micro;g daily), and intravenous calcium gluconate. Follow-up tests showed that vitamin D levels remained below average, so the oral dose of alfacalcidol was increased to 1.5 \u0026micro;g daily, leading to gradual improvement in indicators. Postoperatively, the patient\u0026apos;s PTH, serum calcium and phosphorus levels, serum amylase, and serum lipase returned to normal, and the degree of bone destruction improved compared to before.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eParathyroid adenoma stands as the most frequent cause of primary hyperparathyroidism. Its clinical manifestations include gastrointestinal symptoms (nausea, vomiting, peptic ulcer), kidney stones, osteoporosis with fractures, and changes in mental state[6]. In this case, the patient presented with unexplained nausea and vomiting upon admission. While PET-CT revealed a soft tissue shadow situated behind and below the left lobe of the thyroid, suggesting the diagnosis of a parathyroid tumor, other possible diagnoses for the patient\u0026apos;s nausea and vomiting symptoms should also be considered. These include nausea and vomiting due to visceral pain (acute gastroenteritis, cholecystitis, appendicitis, pancreatitis), nausea and vomiting due to mechanical intestinal obstruction, or endocrine disorders (Primary hyperparathyroidism causing hypercalcemia-induced nausea and vomiting). Among these, clinicians are most likely to suspect a diagnosis of acute gastroenteritis, but the patient reported no consumption of contaminated food and had no abdominal pain. Gastric endoscopy showed superficial atrophic gastritis, and treatment with gastroprotective drugs did not alleviate the symptoms, suggesting that the diagnosis of acute gastroenteritis is less likely. Since the patient had no abdominal tenderness, rebound tenderness, or optimistic Murphy\u0026apos;s sign on physical examination and imaging did not reveal gallstones or peritoneal effusion around the appendix, the diagnoses of cholecystitis and appendicitis can be ruled out[7, 8]. In this situation, acute pancreatitis might be the first consideration. Interestingly, the patient\u0026apos;s serum amylase and lipase levels were indeed noticeably elevated. Throughout the patient\u0026apos;s hospitalization at the specialized facility, serum amylase peaked at 192 U/L, and serum lipase peaked at 1216 U/L, but none exceeded three times the upper limit of normal. Additionally, imaging did not show inflammatory changes in the pancreas, so the criteria for diagnosing pancreatitis were not met\u0026nbsp;[9]. In addition, nausea and vomiting can also be caused by mechanical intestinal obstruction, but this type of vomiting usually consists primarily of gastrointestinal contents and is accompanied by abdominal pain, distension, and cessation of gas and stool passage from the anus\u0026nbsp;[10],imaging showed distended intestinal loops filled with gas, which does not match the patient\u0026apos;s symptoms. Finally, based on imaging and the patient\u0026apos;s clinical symptoms, it is considered that the nausea and vomiting are caused by primary hyperparathyroidism. It is worth noting that the patient had abnormal elevations in serum amylase and lipase during the course of the illness, although not enough to diagnose pancreatitis. This suggests that there may be a potential mechanism by which the parathyroid adenoma could be causing pancreatic disease. Previous studies have indicated an association between primary hyperparathyroidism and pancreatitis\u0026nbsp;[11]. Recent literature suggests that PHPT causing pancreatitis may involve three mechanisms: First, elevated serum calcium levels due to PHPT accelerate the conversion of pancreatic proenzymes to active enzymes by trypsin, leading to pancreatic self-digestion and pancreatitis[12]. Second, hypercalcemia promotes calcium deposition, leading to pancreatic duct obstruction and the formation of pancreatic stones, resulting in pancreatitis\u0026nbsp;[13]. Third, elevated calcium levels and genetic mutations such as mutations in serine protease inhibitor Kazal type 1 (SPINK1) and cystic fibrosis transmembrane conductance regulator (CFTR) can contribute to the development of pancreatitis\u0026nbsp;[14]. Therefore, the specific mechanism between parathyroid adenoma and the pancreas remains to be further investigated.\u003c/p\u003e\n\u003cp\u003eIn clinical diagnosis, in addition to detecting parathyroid tumors through PET-CT, elevated blood calcium is also a key indicator suggesting primary hyperparathyroidism. The premise for assessing the extent of abnormal elevation in blood calcium is to determine the accurate initial blood calcium level by excluding the influence of protein binding, i.e., adjusting the calcium level (corrected calcium (mmol/L) = serum total calcium - (serum albumin - 40 g/L) \u0026times; 0.02)[15]. When the patient was admitted, the serum total calcium was 2.99 mmol/L, and the albumin was 42.5 g/L（N：40-55 g/L）. The corrected calcium was 2.94 mmol/L（N：2.00-2.50 mmol/L）. The diagnosis was mild hypercalcemia [16]. Next, it is essential to analyze the specific reasons for hypercalcemia, whether it is due to primary hyperparathyroidism, malignancy-related osteolytic hypercalcemia, or a combination of both mechanisms. Hypercalcemia associated with cancer is referred to as hypercalcemia of malignancy (HCM). The onset of hypertrophic cardiomyopathy (HCM) may be associated with elevated levels of parathyroid hormone-related protein (PTHrP), local bone resorption induced by cytokines, production of 1,25-dihydroxyvitamin D by tumors, or ectopic PTH [17]. These mechanisms lead to increased blood calcium levels, increased intestinal calcium absorption, and increased bone resorption, which in turn cause a reduction in parathyroid hormone levels [18]. However, upon reviewing the patient\u0026apos;s medical history, there were no signs of systemic malignancies, and imaging did not reveal any apparent tumor lesions. Additionally, the patient exhibited significantly elevated parathyroid hormone levels, suggesting that hypercalcemia was unlikely caused by malignancy. Further investigation into whether the patient\u0026apos;s hypercalcemia was caused by parathyroid hormone revealed that upon admission, the patient\u0026apos;s blood calcium levels had further increased, and circulating PTH levels had significantly risen. Hypophosphatemia and decreased levels of 25-hydroxyvitamin D are all diagnostic criteria for primary hyperparathyroidism [19], combined with imaging localization of the parathyroid tumor, the diagnosis of the patient\u0026apos;s parathyroid tumor was ultimately confirmed.\u003c/p\u003e\n\u003cp\u003eThe patient has had poliomyelitis since childhood and reports low physical activity. On physical examination, multiple skeletal deformities were observed throughout the body. Additionally, there is a history of left femoral fracture. CT findings showed multiple soft tissue density shadows accompanied by bone destruction throughout the body, suggesting a diagnosis of metastatic tumor or multiple myeloma. However, other possibilities should also be considered, such as brown tumors, fibrous dysplasia, or ossifying fibromas. Indeed, some cancer metastases can cause widespread bone destruction in patients, but in this case, there were no previous findings of malignancy before admission, and tumor markers were within normal range. This suggests that the diagnosis of metastatic tumor is less likely [18]. The imaging manifestations of fibrous dysplasia, ossifying fibromas, and multiple myeloma differ significantly from the patient\u0026apos;s imaging findings. Therefore, these diagnoses can also be excluded [20]. Subsequent PET-CT results showed a mass originating from the parathyroid gland, with multiple areas of bone destruction throughout the body, local thickening and expansion of the bone, suggestive of fibrous cystic osteitis, bilateral kidney stones, and osteoporosis. Combined with laboratory findings of elevated PTH, elevated blood calcium, and decreased blood phosphorus, all of these factors point to a brown tumor caused by primary hyperparathyroidism [21]. Brown tumors result from heightened osteoclast activity triggered by excessive levels of parathyroid hormone. They are closely related to primary hyperparathyroidism, and approximately 3% of patients with primary hyperparathyroidism develop brown tumors [22]. It can usually affect any part of the skeletal system, including the skull (usually the jawbone), cranial bones, clavicles, ribs, pelvic bones, femur, and spine. Clinically, it may present as bone pain, pathological fractures, or urinary stones, or it can be asymptomatic [23]. Three months after surgery, a follow-up CT scan showed improvement in the osteolytic lesions throughout the body compared to before, further confirming the diagnosis of parathyroid adenoma with brown tumors.\u003c/p\u003e\n\u003cp\u003eParathyroid adenomas are usually very small, typically measuring between 3-5 mm, with an average weight of less than 1g. Parathyroid adenomas that weigh more than 3.5g have a length greater than 2cm and are associated with clinical manifestations of hyperparathyroidism, which are referred to as giant parathyroid adenomas [24]. In this case, the excised specimen measured 3.5 \u0026times; 3.5 \u0026times; 2 cm and weighed 10.0 g, meeting the criteria for a giant parathyroid adenoma. The preferred treatment for parathyroid adenoma is usually surgical removal [25]. After surgery, the patient experienced persistent hypocalcemia, with a post-operative serum total calcium level as low as 1.76 mmol/L. For patients who have undergone thyroid or parathyroid surgery and maintain serum calcium levels below 2.1 mmol/L for over four days, hypoparathyroidism (HBS) may be contemplated [5]. HBS mainly manifests as persistent hypocalcemia, which can lead to arrhythmias, seizures, skeletal pain, and even death. Early intervention may be vital to preventing HBS after surgery. Relevant literature indicates that preoperative serum vitamin D levels do not independently predict postoperative hypoparathyroidism (HBS) [26]. After parathyroidectomy, the proportion of patients with vitamin D deficiency who develop post-operative hypocalcemia is higher than in those without vitamin D deficiency, highlighting the importance of high-dose vitamin D supplementation therapy. In this case, the patient did indeed experience hungry bone syndrome and vitamin D deficiency after surgery and was treated with oral calcium carbonate chewable tablets (1.5g twice daily), alfacalcidol tablets (1.5ug once daily), and intravenous calcium gluconate. During an outpatient follow-up one month post-surgery, the patient exhibited normal levels of parathyroid hormone (PTH), serum calcium, vitamin D, and blood cell counts.\u003c/p\u003e\n\u003cp\u003eSo far, there have been few reports on the occurrence of pancytopenia after parathyroidectomy. In this case, ten days after surgery, the patient developed pancytopenia with fluctuating leukocyte levels dropping to a peak of 1.6 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L（N：3.5-9.5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L）, persistent decline in platelet levels to a peak of 84 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L（N：125-350 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e/L）, and fluctuating reductions in erythrocyte levels to a peak of 2.49 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L（N：3.8-5.1 \u0026times; 10\u003csup\u003e12\u003c/sup\u003e/L）. Complement immunoglobulin levels, anemia screening, and immunofixation electrophoresis were all inconclusive. According to relevant literature, anemia in PHPT cases usually presents as normocytic normochromic anemia[27]， thrombocytopenia is also a rare manifestation of PHPT[28]. Prior reports indicate that intact parathyroid hormone (PTH) may impede the proliferation of erythroid progenitor cells and the production of erythropoietin, potentially resulting in a decline in red blood cell levels. PTH promotes bone marrow fibrosis, leading to a decrease in hematopoietic factors, which in turn causes thrombocytopenia[29, 30]. However, these conclusions contradict some research reports, so the specific mechanism of pancytopenia after parathyroid adenoma surgery remains unclear and requires further investigation.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePrimary hyperparathyroidism has numerous clinical manifestations, and severe primary hyperparathyroidism can lead to severe hypercalcemia, which can be life-threatening. Early diagnosis and treatment are essential. PET-CT has higher sensitivity than regular CT for diagnosing parathyroid tumors. For patients with primary hyperparathyroidism who have significant systemic bone symptoms, clinicians should include brown tumors in the differential diagnosis. Additionally, the potential endocrine relationship between parathyroid adenoma and pancreatitis, as well as the reason for pancytopenia after parathyroid adenoma surgery, warrants further in-depth research.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics committee：Ethics Committee of Jiangsu University Affiliated Hospital.\u003c/p\u003e\n\u003cp\u003eCommittee\u0026rsquo;s reference number：KY2023K1105.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe patient provided written informed consent for the publication of this case report and any accompanying images. A copy of the written consent form is available for review by the series editor of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll funding for the report research comes from a project in Zhenjiang City, Zhi-Hong Zhao, Affiliated Hospital of Jiangsu University, with project number: SH2016030.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePWT conceptualized the manuscript, interpreted the data, and revised the manuscript. OL revised the draft and analyzed specific diagnostic correlations. ZZH performed the diagnosis, surgery, and follow-up for the patient. WK engaged in the case discussion and aided in manuscript revisions. All authors have reviewed and endorsed the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors express sincere gratitude to the patients who consented to participate in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAbshirini H, Heidari M, Fahimi A, Ghorbani P, Ghadirzadeh E, Shafiei S: \u003cstrong\u003eGiant parathyroid adenoma presenting with multiple pathologic fractures: A case report\u003c/strong\u003e. \u003cem\u003eClinical Case Reports \u003c/em\u003e2023, \u003cstrong\u003e11\u003c/strong\u003e(6).\u003c/li\u003e\n\u003cli\u003eKowalski GJ, Buła G, Żądło D, Gawrychowska A, Gawrychowski J: \u003cstrong\u003ePrimary hyperparathyroidism\u003c/strong\u003e. \u003cem\u003eEndokrynologia Polska \u003c/em\u003e2020, \u003cstrong\u003e71\u003c/strong\u003e(3):260-270.\u003c/li\u003e\n\u003cli\u003eKochman M: \u003cstrong\u003ePrimary hyperparathyroidism: clinical manifestations, diagnosis, and evaluation according to the Fifth International Workshop guidelines\u003c/strong\u003e. \u003cem\u003eReumatologia \u003c/em\u003e2023, \u003cstrong\u003e61\u003c/strong\u003e(4):256-263.\u003c/li\u003e\n\u003cli\u003eWerner J, Gr\u0026uuml;nig H, Loher H, Fischli S, Strobel K, Wicke C: \u003cstrong\u003eLocalization of Brown Tumors With 18F-Fluorocholine PET/CT Imaging in Severe Primary Hyperparathyroidism\u003c/strong\u003e. \u003cem\u003eClinical Nuclear Medicine \u003c/em\u003e2023, \u003cstrong\u003e48\u003c/strong\u003e(8):e387-e389.\u003c/li\u003e\n\u003cli\u003eM NE, Aw N, Ml N: \u003cstrong\u003eThe role of intra-operative parathyroid hormone assay in non-localized adenoma\u003c/strong\u003e. \u003cem\u003ePakistan journal of medical sciences \u003c/em\u003e2022, \u003cstrong\u003e38\u003c/strong\u003e(8):2376-2379.\u003c/li\u003e\n\u003cli\u003eAyg\u0026uuml;n N, Uludağ M: \u003cstrong\u003eSurgical Treatment of Primary Hyperparathyroidism: Which Therapy to Whom?\u003c/strong\u003e \u003cem\u003eSisli Etfal Hastanesi tip bulteni \u003c/em\u003e2019, \u003cstrong\u003e53\u003c/strong\u003e(3):201-214.\u003c/li\u003e\n\u003cli\u003eDelungahawatta T, Rao SJ, Wolff M, Haas CJ: \u003cstrong\u003ePulmonary Clostridium perfringens: Seeding Beyond the Gastrointestinal Tract\u003c/strong\u003e. \u003cem\u003eJournal of community hospital internal medicine perspectives \u003c/em\u003e2024, \u003cstrong\u003e14\u003c/strong\u003e(1):30-34.\u003c/li\u003e\n\u003cli\u003eKhatoon MA, Naeem S, Akmal U, Farid A, Ahmed Khan S: \u003cstrong\u003eRetrocecal Ascending Appendix Attached to the Hepatic Flexure and Right Intra-abdominal Testis Identified During Open Appendicectomy: A Case Report\u003c/strong\u003e. \u003cem\u003eCureus \u003c/em\u003e2024, \u003cstrong\u003e16\u003c/strong\u003e(4):e57484.\u003c/li\u003e\n\u003cli\u003eNepali A, Kharga S, Jayan M, Adhikari P, Shah A, Sanker V: \u003cstrong\u003eAcute pancreatitis secondary to moderate hypertriglyceridemia: A case report\u003c/strong\u003e. \u003cem\u003eClin Case Rep \u003c/em\u003e2024, \u003cstrong\u003e12\u003c/strong\u003e(3):e8582.\u003c/li\u003e\n\u003cli\u003eChaouch MA, Taieb AH, Jallali M, Chedly E, Gafsi B, Noomen F: \u003cstrong\u003eRare case report of intestinal obstruction due to incarcerated small bowel in omental breach\u003c/strong\u003e. \u003cem\u003eInt J Surg Case Rep \u003c/em\u003e2024, \u003cstrong\u003e115\u003c/strong\u003e:109245.\u003c/li\u003e\n\u003cli\u003eBhadada SK, Udawat HP, Bhansali A, Rana SS, Sinha SK, Bhasin DK: \u003cstrong\u003eChronic pancreatitis in primary hyperparathyroidism: comparison with alcoholic and idiopathic chronic pancreatitis\u003c/strong\u003e. \u003cem\u003eJournal of gastroenterology and hepatology \u003c/em\u003e2008, \u003cstrong\u003e23\u003c/strong\u003e(6):959-964.\u003c/li\u003e\n\u003cli\u003eHaverback BJ, Dyce B, Bundy H, Edmondson HA: \u003cstrong\u003eTrypsin, trypsinogen and trypsin inhibitor in human pancreatic juice\u003c/strong\u003e. \u003cem\u003eThe American journal of medicine \u003c/em\u003e1960, \u003cstrong\u003e29\u003c/strong\u003e:421-433.\u003c/li\u003e\n\u003cli\u003eDevgan Y, Mayilvaganan S, Mishra A, Chand G, Agarwal G, Mohindra S, Gupta S, Agarwal A: \u003cstrong\u003ePHPT with Pancreatitis: Atypical Presentation of PHPT\u003c/strong\u003e. \u003cem\u003eIndian journal of endocrinology and metabolism \u003c/em\u003e2023, \u003cstrong\u003e27\u003c/strong\u003e(6):513-518.\u003c/li\u003e\n\u003cli\u003eMehta G, Rathod VM, Patel T, Solanki D: \u003cstrong\u003eAtypical Presentation of Primary Hyperparathyroidism as Recurrent Pancreatitis: A Case Report With a Review of the Literature\u003c/strong\u003e. \u003cem\u003eCureus \u003c/em\u003e2023, \u003cstrong\u003e15\u003c/strong\u003e(6):e41140.\u003c/li\u003e\n\u003cli\u003eQi H, Wang B, Zhu L: \u003cstrong\u003eIndependent associations of serum calcium with or without albumin adjustment and serum phosphorus with nonalcoholic fatty liver disease: results from NHANES 1999-2018\u003c/strong\u003e. \u003cem\u003eFrontiers in endocrinology \u003c/em\u003e2024, \u003cstrong\u003e15\u003c/strong\u003e:1323990.\u003c/li\u003e\n\u003cli\u003eAl Hassan MS, El Ansari W, Issa N, Darweesh A, Abdelaal A: \u003cstrong\u003eSevere hypercalcemia secondary to parathyroid adenoma: Series of four consecutive cases at a tertiary care hospital in Qatar\u003c/strong\u003e. \u003cem\u003eInternational Journal of Surgery Case Reports \u003c/em\u003e2023, \u003cstrong\u003e109\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eVasquez L, Cortes T: \u003cstrong\u003eHypercalcemia of Malignancy Complicated by Osteonecrosis of the Jaw Treated With Cinacalcet\u003c/strong\u003e. \u003cem\u003eJCEM case reports \u003c/em\u003e2023, \u003cstrong\u003e1\u003c/strong\u003e(5):luad105.\u003c/li\u003e\n\u003cli\u003eCarpenter TO: \u003cstrong\u003eCase 32-2021: A 14-Year-Old Girl with Swelling of the Jaw and Hypercalcemia. Reply\u003c/strong\u003e. \u003cem\u003eThe New England journal of medicine \u003c/em\u003e2022, \u003cstrong\u003e386\u003c/strong\u003e(3):296.\u003c/li\u003e\n\u003cli\u003eIssa PP, Kandil E, Lee GS: \u003cstrong\u003eRadiofrequency ablation as a treatment modality for primary hyperparathyroidism: a systematic literature review\u003c/strong\u003e. \u003cem\u003eGland surgery \u003c/em\u003e2024, \u003cstrong\u003e13\u003c/strong\u003e(1):87-99.\u003c/li\u003e\n\u003cli\u003eIbrahem HM: \u003cstrong\u003eGnathic Bones and Hyperparathyroidism: A Review on the Metabolic Bony Changes Affecting the Mandible and Maxilla in case of Hyperparathyroidism\u003c/strong\u003e. \u003cem\u003eAdvances in medicine \u003c/em\u003e2020, \u003cstrong\u003e2020\u003c/strong\u003e:6836123.\u003c/li\u003e\n\u003cli\u003eMajic Tengg A, Cigrovski Berkovic M, Zajc I, Salaric I, M\u0026uuml;ller D, Markota I: \u003cstrong\u003eExpect the unexpected: Brown tumor of the mandible as the first manifestation of primary hyperparathyroidism\u003c/strong\u003e. \u003cem\u003eWorld journal of clinical cases \u003c/em\u003e2024, \u003cstrong\u003e12\u003c/strong\u003e(7):1200-1204.\u003c/li\u003e\n\u003cli\u003eErgen FB, Ayvaz M, Yildiz AE, Aydingoz U, Gedikoglu G: \u003cstrong\u003eBrown tumour presenting as a soft-tissue mass\u003c/strong\u003e. \u003cem\u003eClinical radiology \u003c/em\u003e2012, \u003cstrong\u003e67\u003c/strong\u003e(3):286-289.\u003c/li\u003e\n\u003cli\u003eHoshi M, Takami M, Kajikawa M, Teramura K, Okamoto T, Yanagida I, Matsumura A: \u003cstrong\u003eA case of multiple skeletal lesions of brown tumors, mimicking carcinoma metastases\u003c/strong\u003e. \u003cem\u003eArchives of orthopaedic and trauma surgery \u003c/em\u003e2008, \u003cstrong\u003e128\u003c/strong\u003e(2):149-154.\u003c/li\u003e\n\u003cli\u003eMat\u0026iacute;as-Garc\u0026iacute;a B, Mendoza-Moreno F, D\u0026iacute;ez-Alonso M, Ovejero-Merino E, Vera-Mansilla C, Bl\u0026aacute;zquez-Mart\u0026iacute;n A, Quiroga-Valc\u0026aacute;rcel A, Jim\u0026eacute;nez-Mart\u0026iacute;n R, D\u0026apos;Amico R, Lasa-Unz\u0026uacute;e I\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSpontaneous cervical hematoma caused by giant parathyroid adenoma in an elderly patient: A case report\u003c/strong\u003e. \u003cem\u003eMedicine international \u003c/em\u003e2024, \u003cstrong\u003e4\u003c/strong\u003e(1):1.\u003c/li\u003e\n\u003cli\u003ePapanikos V, Papadodima E, Bantouna D, Paparodis RD, Livadas S, Angelopoulos N, Karvounis E: \u003cstrong\u003eHypercalcemic Crisis Due to a Giant Intrathyroidal Parathyroid Adenoma, with Postsurgical Severe Hypocalcemia and Hungry Bone Syndrome: A Case Report\u003c/strong\u003e. \u003cem\u003eClinics and practice \u003c/em\u003e2024, \u003cstrong\u003e14\u003c/strong\u003e(1):179-187.\u003c/li\u003e\n\u003cli\u003eSalman MA, Rabiee A, Salman AA, Youssef A, Shaaban HE, Ftohy T, Maurice KK, Balamoun H: \u003cstrong\u003eRole of vitamin D supplements in prevention of hungry bone syndrome after successful parathyroidectomy for primary hyperparathyroidism: A prospective study\u003c/strong\u003e. \u003cem\u003eScandinavian journal of surgery: SJS: official organ for the Finnish Surgical Society and the Scandinavian Surgical Society \u003c/em\u003e2021, \u003cstrong\u003e110\u003c/strong\u003e(3):329-334.\u003c/li\u003e\n\u003cli\u003eBhadada SK, Bhansali A, Ahluwalia J, Chanukya GV, Behera A, Dutta P: \u003cstrong\u003eAnaemia and marrow fibrosis in patients with primary hyperparathyroidism before and after curative parathyroidectomy\u003c/strong\u003e. \u003cem\u003eClinical endocrinology \u003c/em\u003e2009, \u003cstrong\u003e70\u003c/strong\u003e(4):527-532.\u003c/li\u003e\n\u003cli\u003eBhadada SK, Arya AK, Mukhopadhyay S, Khadgawat R, Sukumar S, Lodha S, Singh DN, Sathya A, Singh P, Bhansali A: \u003cstrong\u003ePrimary hyperparathyroidism: insights from the Indian PHPT registry\u003c/strong\u003e. \u003cem\u003eJournal of bone and mineral metabolism \u003c/em\u003e2018, \u003cstrong\u003e36\u003c/strong\u003e(2):238-245.\u003c/li\u003e\n\u003cli\u003eBhadada SK, Arya AK, Parthan G, Singh P: \u003cstrong\u003eThe resolution of anemia after curative parathyroidectomy is sustained even after a decade\u003c/strong\u003e. \u003cem\u003eIndian journal of endocrinology and metabolism \u003c/em\u003e2015, \u003cstrong\u003e19\u003c/strong\u003e(5):691-692.\u003c/li\u003e\n\u003cli\u003eLotinun S, Sibonga JD, Turner RT: \u003cstrong\u003eEvidence that the cells responsible for marrow fibrosis in a rat model for hyperparathyroidism are preosteoblasts\u003c/strong\u003e. \u003cem\u003eEndocrinology \u003c/em\u003e2005, \u003cstrong\u003e146\u003c/strong\u003e(9):4074-4081.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Case report, Primary hyperparathyroidism, Parathyroid adenoma, Brown tumor, Hungry bone syndrome","lastPublishedDoi":"10.21203/rs.3.rs-4330728/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4330728/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: A parathyroid adenoma stands as the primary cause of primary hyperparathyroidism, and clinically it often presents with symptoms such as elevated blood calcium levels and recurrent kidney stones. Parathyroid adenoma discovered due to symptoms such as nausea and vomiting is relatively rare.\u003c/p\u003e\n\u003cp\u003eCase presentation: A 59-year-old woman was hospitalized due to symptoms of nausea and vomiting. Imaging studies unveiled a solid mass located on the posterior aspect of the left thyroid lobe, potentially of parathyroid origin, along with multiple bone destruction throughout the body. Laboratory tests showed elevated serum total calcium, low potassium, and increased parathyroid hormone levels. The final diagnosis was primary hyperparathyroidism complicated by the brown tumor. Symptomatic treatment, including calcium reduction, fluid replacement, and electrolyte supplementation, was initiated. Subsequently, parathyroid adenoma resection was performed. Postoperatively, the patient developed hungry bone syndrome, which was treated with calcium supplementation, and follow-up showed normalization of blood calcium levels.\u003c/p\u003e\n\u003cp\u003eConclusions: Unexplained nausea accompanied by electrolyte disturbances should raise suspicion of rare causes such as primary hyperparathyroidism. When there are multiple systemic osteolytic changes, brown tumor should be considered, along with assessment of serum calcium and parathyroid hormone levels for diagnosis.\u003c/p\u003e","manuscriptTitle":"A Case Report and Literature Review of a Giant Parathyroid Adenoma with Digestive System Symptoms and Brown Tumor","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-05-09 18:07:10","doi":"10.21203/rs.3.rs-4330728/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e32dd09c-e8dc-4687-965b-c73edfbe3f1f","owner":[],"postedDate":"May 9th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-14T04:53:58+00:00","versionOfRecord":[],"versionCreatedAt":"2024-05-09 18:07:10","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4330728","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4330728","identity":"rs-4330728","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}