Ectopic parathyroid tumors are uncommon, accounting for only 6% of parathyroid adenomas, and even fewer cases are attributed to parathyroid carcinomas. While ectopic parathyroid carcinoma in the anterior mediastinum is a rare condition, the occurrence of recurrent skeletal fractures in the presence of mild hypercalcemia is even rarer. In this report, we present the case of a 52-year-old man with a medical history of hypertension, chronic kidney disease, and a previous right-sided intertrochanteric fracture of the femur one year earlier. He presented to the emergency room with left-sided hip pain and shortness of breath due to volume overload. Laboratory tests revealed mild hypercalcemia and hyperparathyroidism, with normal vitamin D levels. An X-ray showed a left neck of femur fracture. Further evaluation with a three-phase skeletal scintigraphy indicated the presence of metabolic bone disease. A contrast-enhanced computed tomography of the chest revealed a solitary soft tissue nodule in the anterior mediastinum, representing an ectopic parathyroid adenoma. The lesion was successfully removed using video-assisted thoracic surgery, and the histopathological analysis confirmed the diagnosis of parathyroid carcinoma. The combination of mild hypercalcemia and recurrent fractures is an unusual presentation of ectopic parathyroid carcinoma, underscoring the importance of considering this condition as a potential cause in similar cases to ensure timely and appropriate treatment

Jamal, Aisha

Mahmood, Saad Bin Zafar

Masood, Qamar

Mushtaq, Zain

English

eCommons@AKU

eCommons@AKU Section of Internal Medicine Department of Medicine 12-31-2023 A Rare Occurrence of Ectopic Parathyroid Carcinoma Presenting as a Case of Recurrent Fractures Saad Bin Zafar Mahmood Aga Khan University, saadbin.zafar@aku.edu Aisha Jamal Aga Khan University, aisha.jamal@aku.edu Zain Mushtaq Aga Khan University, zain.mushtaq@aku.edu Qamar Masood Agha Khan University, qamar.masood@aku.edu Follow this and additional works at: https://ecommons.aku.edu/pakistan_fhs_mc_med_intern_med  Part of the Hematology Commons, Integrative Medicine Commons, and the Internal Medicine Commons Recommended Citation Mahmood, S. Z., Jamal, A., Mushtaq, Z., Masood, Q. (2023). A Rare Occurrence of Ectopic Parathyroid Carcinoma Presenting as a Case of Recurrent Fractures. The Cureus Journal of Medical Science, 12. Available at: https://ecommons.aku.edu/pakistan_fhs_mc_med_intern_med/249 Review began 12/10/2023 Review ended 12/25/2023 Published 12/31/2023© Copyright 2023Mahmood et al. This is an open accessarticle distributed under the terms of theCreative Commons Attribution License CC-BY 4.0., which permits unrestricted use,distribution, and reproduction in anymedium, provided the original author andsource are credited.A Rare Occurrence of Ectopic ParathyroidCarcinoma Presenting as a Case of RecurrentFracturesSaad Bin Zafar Mahmood  , Aisha Jamal  , Zain Mushtaq  , Muhammad Q. Masood 1. Medicine, Aga Khan University Hospital, Karachi, PAK 2. Internal Medicine, Aga Khan University Hospital, Karachi,PAK 3. Medicine, Endocrinology, Aga Khan University Hospital, Karachi, PAKCorresponding author: Saad Bin Zafar Mahmood, saadbin.zafar@aku.eduAbstractEctopic parathyroid tumors are uncommon, accounting for only 6% of parathyroid adenomas, and even fewercases are attributed to parathyroid carcinomas. While ectopic parathyroid carcinoma in the anteriormediastinum is a rare condition, the occurrence of recurrent skeletal fractures in the presence of mildhypercalcemia is even rarer. In this report, we present the case of a 52-year-old man with a medical historyof hypertension, chronic kidney disease, and a previous right-sided intertrochanteric fracture of the femurone year earlier. He presented to the emergency room with left-sided hip pain and shortness of breath due tovolume overload. Laboratory tests revealed mild hypercalcemia and hyperparathyroidism, with normalvitamin D levels. An X-ray showed a left neck of femur fracture. Further evaluation with a three-phaseskeletal scintigraphy indicated the presence of metabolic bone disease. A contrast-enhanced computedtomography of the chest revealed a solitary soft tissue nodule in the anterior mediastinum, representing anectopic parathyroid adenoma. The lesion was successfully removed using video-assisted thoracic surgery,and the histopathological analysis confirmed the diagnosis of parathyroid carcinoma. The combination ofmild hypercalcemia and recurrent fractures is an unusual presentation of ectopic parathyroid carcinoma,underscoring the importance of considering this condition as a potential cause in similar cases to ensuretimely and appropriate treatment.Categories: Endocrinology/Diabetes/Metabolism, Internal MedicineKeywords: end-stage renal disease (esrd), skeletal fractures, hypercalcemia, ectopic parathyroid carcinoma, primaryhyperparathyroidismIntroductionPrimary hyperparathyroidism (HPT) is considered to be the most common cause of hypercalcemia, withparathyroid adenomas (nearly 80% of cases) forming the bulk of these cases [1]. Parathyroid hyperplasia(10% to 15% of cases) and, infrequently, parathyroid carcinomas (<1% to 5% of cases) can also lead to HPT[2]. Parathyroid carcinomas are an unusual cause of hypercalcemia, leading to poor outcomes, and arepreferably managed by surgical resection [3]. Ectopic parathyroid tumors are rare, with only 6% ofparathyroid adenomas attributed to ectopic growth and even fewer attributed to parathyroid carcinomas[3,4]. We present the case of a 52-year-old male who presented with hypercalcemia and recurrentpathological fractures and was found to have a parathyroid carcinoma.Case PresentationA 52-year-old man with a prior history of hypertension, chronic kidney disease (CKD), and a right-sidedintertrochanteric (IT) fracture one year ago presented to the emergency department with complaints of left-sided hip pain for the past two weeks. His hypertension and CKD (baseline creatinine between 2.0-2.5 mg/dL)were otherwise stable but he complained of intermittent dyspnea.On examination, he had a blood pressure of 110/70 mmHg, respiratory rate of 14 breaths per minute, heartrate of 68 beats per minute, and was afebrile. He was unable to move his left leg due to pain. The rest of thesystemic examination was unremarkable apart from bibasilar crepitation suggesting volume overload. Initiallaboratory investigations showed thrombocytopenia (platelets 140 x 109/L), with hemoglobin of 12.4 g/dL,total leukocyte count of 6.9 x 109/L, and erythrocyte sedimentation rate of 21 mm/first hour. He had anelevated creatinine level of 3.2 mg/dL, with hypokalemia (2.7 mmol/L), hypercalcemia (corrected calcium of12.1 mg/dL), and hyperphosphatemia (5.2 mg/dL). The rest of the investigations were normal. The patienthad no complaints of constipation, abdominal pain, increased urinary frequency, or muscle weakness. Apelvis X-ray revealed an undisplaced fracture of the left femoral neck (Figure 1). He was initially managedwith intravenous hydration and analgesics.1 2 2 3 Open Access CaseReport  DOI: 10.7759/cureus.51404How to cite this articleMahmood S, Jamal A, Mushtaq Z, et al. (December 31, 2023) A Rare Occurrence of Ectopic Parathyroid Carcinoma Presenting as a Case ofRecurrent Fractures. Cureus 15(12): e51404. DOI 10.7759/cureus.51404FIGURE 1: X-ray pelvis anteroposterior view.Visualized bones show a significantly reduced bone density. Suspicion of undisplaced left femoral neck fracture.Keeping in view the history of repeated pathological fractures, a three-phase skeletal scintigraphy wasordered which was suggestive of metabolic bone disease. Further workup was pursued to rule out causes ofpathological fractures. (Table 1) He was found to have hyperparathyroidism (parathyroid hormone (PTH)level 1,347 pg/mL) with a normal 25 hydroxy vitamin D (23.6 ng/mL). Ultrasound of the neck showed anormal thyroid with a small nodule in the lower pole of the right lobe. Ultrasound of the kidneys showedechogenic kidneys bilaterally with altered corticomedullary differentiation suggestive of bilateral renalparenchymal disease.Laboratory parameters Reference range Lab valuesSerum prostate-specific antigen (ng/mL) 0–3.5 1.05Erythrocyte sedimentation rate (mm/first hour) 0–15 21Serum 25-hydroxy vitamin D (ng/mL) >30 23.6Brucella antibody <1:80 <1:80Serum calcium (mg/dL) 8.6–10.2 10.8Serum albumin (g/dL) 3.5–5.2 3.7Plasma parathyroid levels (pg/mL) 16–87 1347Serum phosphate (mg/dL) 2.5–4.5 5.2Serum alkaline phosphatase (g/dL) 45–129 1,134TABLE 1: Laboratory investigations.2023 Mahmood et al. Cureus 15(12): e51404. DOI 10.7759/cureus.51404 2 of 7Further radiographic imaging studies including parathyroid scintigraphy and computed tomography (CT) ofthe chest (without contrast due to raised creatinine) were performed for localization of a lesion whichshowed a solitary soft tissue nodule in the anterior mediastinum representing ectopic parathyroid adenoma(Figures 2, 3). The patient underwent video-assisted thoracoscopic (VATS)-guided removal of parathyroidtissue. Histopathology later revealed it to be a parathyroid carcinoma (Figure 4).FIGURE 2: Parathyroid scintigraphy with 622 MBq of Tc-99m sestamibiinjected intravenously.Solitary parathyroid adenoma posterior to manubrium sterni (ectopic position).2023 Mahmood et al. Cureus 15(12): e51404. DOI 10.7759/cureus.51404 3 of 7FIGURE 3: CT of the chest without contrast showing a well-circumscribed soft tissue nodule in the anterior mediastinum.FIGURE 4: Histopathology showing an encapsulated, circumscribedneoplasm in the parathyroid gland. It is composed of a mixture ofeosinophilic and pale cells, with predominantly round, bland nuclei.Additionally, there are areas showing random nuclear atypia, along withfoci of fibrocollagenous septae. Findings are suggestive of parathyroidcarcinoma.Postoperatively, the patient remained in the intensive care unit and developed worsening renal functions forwhich he required hemodialysis; however, other than that he made an uneventful recovery. There were nosigns or symptoms of hungry bone syndrome and was subsequently discharged from the hospital. Thepatient was followed up in the clinic after one month. He had no active complaints, and a summary of hiscurrent and previous labs is presented in Table 2.2023 Mahmood et al. Cureus 15(12): e51404. DOI 10.7759/cureus.51404 4 of 7Laboratory parameters Reference range Preoperative labs Postoperative labs (1 month)Fasting parathyroid levels (pg/mL) 16–87 1,347 902Serum calcium (mg/dL) 8.6–10.2 10.8 7.8Serum phosphate (mg/dL) 2.5–4.5 5.2 2.4Serum magnesium (mg/dL) 1.6–2.6 1.9 2.2Serum 25-hydroxy vitamin D levels (ng/mL) >30 23.6 26.7TABLE 2: Laboratory analysis before and after surgery.DiscussionWe report a rare case of mediastinal parathyroid carcinoma presenting with repeated neck of femurfractures. Parathyroid carcinomas are a rare condition, accounting for only 1% of HPT cases which occurequally in males and females, typically presenting at around 45-51 years old [5]. Ectopic parathyroidcarcinomas are even rarer, with only 31 cases of ectopic mediastinal parathyroid carcinomas reported todate, mostly in the superior mediastinum [6]. Diagnosis of parathyroid carcinoma is more likely if the patienthas high serum calcium levels (≥14 mg/dL), high parathyroid hormone levels (twice the upper limit ofnormal), and osteitis fibrosa cystica (a bone condition associated with long-standing hyperparathyroidism)[7].The rarity of our case appears to be the absence of any symptoms related to hypercalcemia and the onlypresenting complaints of recurrent neck of femur fracture and mild hypercalcemia. Despite havinggeneralized bone pain indicative of osteitis fibrosa cystica, there was no palpable neck lump uponexamination. Although a literature review does show that 14.3% of parathyroid carcinoma exhibited skeletalcomplications, only two other case reports have described ectopic parathyroid carcinomas with presentingfeatures of recurrent fractures [8,9].Our patient also had asymptomatic nephrolithiasis and an advanced CKD which progressed to end-stagerenal disease requiring renal replacement therapy during his illness requiring long-term hemodialysis.Literature reports that approximately 28.6% of parathyroid carcinoma had renal involvement with the mostcommon renal manifestations being nephrolithiasis (and reduced glomerular filtration rate) [10]. To ourknowledge, end-stage renal disease, as in our case, has only been reported in three other cases of ectopicparathyroid carcinoma [11-13].Our patient’s diagnosis was determined by a combination of his clinical and pathological features. A study byRobert et al., which reviewed 311 patients with HPT, including nine with parathyroid carcinomas, found thatwhen PTH levels are less than four times the upper limit of normal and tumor weight is less than 1.9 g, thelikelihood of parathyroid carcinoma is zero [14]. Our patient had mild hypercalcemia (12.4 mg/dL),significantly elevated PTH levels (1,347 pg/mL), a tumor weight of 5 g, and a history of recurrent femurfractures.Imaging plays an important role in distinguishing between benign and malignant parathyroid lesions.Ultrasound is the safest and simplest modality, with a sensitivity of 71% and a specificity of 100% [15]. Incontrast, 99mTc-MIBI scintigraphy is the preferred diagnostic test for identifying and localizing parathyroidcarcinoma, as noted by studies [16]. A combination of imaging techniques, such as ultrasound, CT scan, andMIBI scintigraphy, has a sensitivity of 100% in identifying parathyroid carcinoma [17]. Our case followed asimilar diagnostic algorithm starting with an ultrasound of the neck, followed by a 99mTc-MIBI scintigraphyand a CT scan. Although the location was identified appropriately, the presumed diagnosis before thehistopathological diagnosis was of a parathyroid adenoma. The definitive diagnosis of our case was alsobased on the capsular and lymphovascular invasion. A previous study postulated that the definitivediagnosis of parathyroid carcinoma can be made by invasion of surrounding tissues or distant metastasis.Hence, it is very difficult to diagnose and is mostly confirmed postoperatively on histopathology [18].Surgical treatment via en bloc resection remains the gold standard treatment for parathyroid carcinoma witha five-year survival rate of 60-93% and hypercalcemia being a major cause of mortality in such patients [18].Our patient underwent a VATS-guided removal which has been to be a better modality for parathyroid tumorexcision in contrast to open surgery in terms of short intraoperative time, bleeding, as well as reducedlength of hospital stay and swift recovery [18]. Amer et al., in their case series of seven cases undergoingVATS between 2004 and 2009 also reported similar findings and postulated that VATS should be consideredthe first-line modality for mediastinal ectopic parathyroid adenoma resection [19]. Our patient followed upin the clinic twice in the next six months and showed remarkable improvement in all laboratory parameters.2023 Mahmood et al. Cureus 15(12): e51404. DOI 10.7759/cureus.51404 5 of 7However, it remains to be seen if these improvements sustain over an extended period.ConclusionsWe report a rare case with an incidental finding of ectopic mediastinal parathyroid carcinoma whichprimarily presented with a pathological fracture. Due to the rarity of the disease, these carcinomas can beeasily missed; however, early detection with laboratory tests and imaging (MIBI scintigraphy combined withCT scan or MRI) can effectively help physicians diagnose, and early intervention can be curative.Additional InformationAuthor ContributionsAll authors have reviewed the final version to be published and agreed to be accountable for all aspects of thework.Concept and design:  Saad Bin Zafar Mahmood, Aisha Jamal, Zain Mushtaq, Muhammad Q. MasoodAcquisition, analysis, or interpretation of data:  Saad Bin Zafar Mahmood, Aisha Jamal, Zain Mushtaq,Muhammad Q. MasoodDrafting of the manuscript:  Saad Bin Zafar Mahmood, Aisha Jamal, Zain Mushtaq, Muhammad Q. MasoodCritical review of the manuscript for important intellectual content:  Saad Bin Zafar Mahmood, AishaJamal, Zain Mushtaq, Muhammad Q. MasoodSupervision:  Saad Bin Zafar Mahmood, Aisha Jamal, Zain Mushtaq, Muhammad Q. MasoodDisclosuresHuman subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: Incompliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/servicesinfo: All authors have declared that no financial support was received from any organization for thesubmitted work. Financial relationships: All authors have declared that they have no financialrelationships at present or within the previous three years with any organizations that might have aninterest in the submitted work. Other relationships: All authors have declared that there are no otherrelationships or activities that could appear to have influenced the submitted work.References1. Sato S, Kitahara A, Koike T, Hashimoto T, Ohashi R, Motoi N, Tsuchida M: Resection of a large ectopicparathyroid adenoma: a case report. Int J Surg Case Rep. 2016, 23:8-11. 10.1016/j.ijscr.2016.04.0072. Mantzoros I, Kyriakidou D, Galanos-Demiris K, et al.: A rare case of primary hyperparathyroidism caused bya giant solitary parathyroid adenoma. Am J Case Rep. 2018, 19:1334-7. 10.12659/AJCR.9114523. Storvall S, Ryhänen E, Bensch FV, et al.: Recurrent metastasized parathyroid carcinoma-long-termremission after combined treatments with surgery, radiotherapy, cinacalcet, zoledronic acid, andtemozolomide. JBMR Plus. 2019, 3:e10114. 10.1002/jbm4.101144. Cao C, Dou C, Chen F, Wang Y, Zhang X, Lai H: An unusual mediastinal parathyroid carcinoma coproducingPTH and PTHrP: a case report. 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Roser P, Leca BM, Coelho C, et al.: Diagnosis and management of parathyroid carcinoma: a state-of-the-artreview. Endocr Relat Cancer. 2023, 30:e220287. 10.1530/ERC-22-028719. Amer K, Khan AZ, Rew D, Lagattolla N, Singh N: Video assisted thoracoscopic excision of mediastinalectopic parathyroid adenomas: a UK regional experience. Ann Cardiothorac Surg. 2015, 4:527-34.10.3978/j.issn.2225-319X.2015.09.042023 Mahmood et al. Cureus 15(12): e51404. DOI 10.7759/cureus.51404 7 of 7

A Rare Occurrence of Ectopic Parathyroid Carcinoma Presenting as a Case of Recurrent Fractures

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A Rare Occurrence of Ectopic Parathyroid Carcinoma Presenting as a Case of Recurrent Fractures

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