Multiple pathological fractures and muscle atrophy caused by a parathyroid carcinoma with postoperative hungry bone syndrome: A case report.

BACKGROUND: Parathyroid carcinoma (PC) is a rare endocrine malignancy causing pathological changes such as abnormal bone metabolism, elevated serum calcium, and impaired renal function, and uncontrollable hypercalcemia is the main cause of death in PC patients. The diagnosis of PC is challenging and relying on postoperative histopathology. Radical surgery at the first time is the only effective therapy to cure PC. Hungry bone syndrome (HBS) is a relatively uncommon complication of parathyroidectomy characterized by profound and prolonged hypocalcemia, timely electrolyte monitoring and alternative interventional protocols can prevent symptomatic hypocalcemia. CASE: A 57-year-old man presented with multiple pathological fractures and muscle atrophy as the main symptoms accompanied by bone pain, hypercalcemia, elevated parathyroid hormone (PTH), and an enlarged left-sided neck mass. After consultation of multidisciplinary team, he was treated conservatively with plaster bandage fixation and infusion of intravenous zoledronic acid; and then complete resection of parathyroid mass + removal of involved tissue structures + left thyroid and isthmus lobectomy + lymph node dissection in the VI region in left neck were performed. The postoperative histopathology suggested a diagnosis of parathyroid carcinoma. Calcium and fluid supplementation and oral levothyroxine tablets were given postoperatively. Unexpectedly, the patient's PTH level decreased rapidly at 24 h postoperative, and serum calcium and phosphorus decreased continuously, and he felt numb around perioral sites and fingertips, which considered to be postoperative HBS complicated by parathyroidectomy. Then, a large amount of calcium supplementation and vitamin D were given timely and the patient got better at 1 month postoperatively. At 9-month postoperative, his bone pain and fatigue were significantly relieved compared with before with calcium, phosphorus, and PTH levels at normal range. CONCLUSION: The possibility of parathyroid disease, particularly PC, should be considered in the presence of multiple pathological fractures, muscle atrophy, generalized bone pain, hypercalcemia, and clear neck mass. Radical resection of the tumor lesions at the first surgery is a key element affecting the prognosis of PC, and the effective management of preoperative hypercalcemia and postoperative HBS is also of great significance for improving prognosis.

Persistent hypercalcaemia associated with two pathogenic variants in the CYP24A1 gene and a parathyroid adenoma-a case report and review.

Introduction: 24-Hydroxylase, encoded by the CYP24A1 gene, is a crucial enzyme involved in the catabolism of vitamin D. Loss-of-function mutations in CYP24A1 result in PTH-independent hypercalcaemia with high levels of 1,25(OH)2D3. The variety of clinical manifestations depends on age, and underlying genetic predisposition mutations can lead to fatal infantile hypercalcaemia among neonates, whereas adult symptoms are usually mild. Aim of the study: We report a rare case of an adult with primary hyperparathyroidism and loss-of-function mutations in the CYP24A1 gene and a review of similar cases. Case presentation: We report the case of a 58-year-old woman diagnosed initially with primary hyperparathyroidism. Preoperatively, the suspected mass adjoining the upper pole of the left lobe of the thyroid gland was found via ultrasonography and confirmed by 99mTc scintigraphy and biopsy as the parathyroid gland. The patient underwent parathyroidectomy (a histopathology report revealed parathyroid adenoma), which led to normocalcaemia. After 10 months, vitamin D supplementation was introduced due to deficiency, and the calcium level remained within the reference range. Two years later, biochemical tests showed recurrence of hypercalcaemia with suppressed parathyroid hormone levels and elevated 1,25(OH)2D3 concentrations. Further investigation excluded the most common causes of PTH-independent hypercalcaemia, such as granulomatous disease, malignancy, and vitamin D intoxication. Subsequently, vitamin D metabolites were measured using LC-MS/MS, which revealed high levels of 25(OH)D3, low levels of 24,25(OH)2D3 and elevated 25(OH)2D3/24,25(OH)2D3 ratios, suggesting a defect in vitamin D catabolism. Molecular analysis of the CYP24A1 gene using the NGS technique revealed two pathogenic variants: p.(Arg396Trp) and p.(Glu143del) (rs114368325 and rs777676129, respectively). Conclusions: The diagnostic process for hypercalcaemia becomes complicated when multiple causes of hypercalcaemia coexist. The measurement of vitamin D metabolites using LC-MS/MS may help to identify carriers of CYP24A1 mutations. Subsequent molecular testing may contribute to establishing the exact frequency of pathogenic variants of the CYP24A1 gene and introducing personalized treatment.

Persistent Primary Hyperparathyroidism Secondary to an Ectopic Mediastinal Adenoma in a Young Adult: A Case Report.

Primary hyperparathyroidism commonly affects elderly women. When present in the young population, it is usually asymptomatic, most frequently due to a parathyroid adenoma and the definitive management is surgical excision. Uncommonly, 5-10% of patients fail to achieve long-term cure after initial parathyroidectomy and 6-16% of them is due to an ectopic parathyroid adenoma that will require focused diagnostic and surgical approaches. We report a 21-year-old male who had bilateral thigh pain. Work-up revealed bilateral femoral fractures, brown tumors on the arms and multiple lytic lesions on the skull. Serum studies showed hypercalcemia (1.83 mmol/L), elevated parathyroid hormone [(PTH) 2025.10 pg/mL], elevated alkaline phosphatase (830 U/L), normal phosphorus (0.92 mmol/L) and low vitamin D levels (18.50 ng/mL). Bone densitometry showed osteoporotic findings. Sestamibi scan showed uptake on the left superior mediastinal region consistent with an ectopic parathyroid adenoma. Vitamin D supplementation was started pre-operatively. Patient underwent parathyroidectomy with neck exploration; however, the pathologic adenoma was not visualized and PTH levels remained elevated post-operatively. Chest computed tomography with intravenous contrast was performed revealing a mediastinal location of the adenoma. A repeat parathyroidectomy was done, with successful identification of the adenoma resulting in a significant drop in PTH and calcium levels. Patient experienced hungry bone syndrome post-operatively and was managed with calcium and magnesium supplementation. A high index of suspicion for an ectopic adenoma is warranted for patients presenting with hypercalcemia and secondary osteoporosis if there is persistent PTH elevation after initial surgical intervention. Adequate follow-up and monitoring is also needed starting immediately in the post-operative period to manage possible complications such as hungry bone syndrome.

Incidental Detection of Parathyroid Adenoma on 18F-PSMA PET/CT.

ABSTRACT: A 70-year-old man, diagnosed with prostate cancer, was referred to the Department of Nuclear Medicine for tumor staging with prostate-specific membrane antigen (PSMA) PET/CT. High PSMA uptake was observed in the prostate without PSMA-avid lymph nodes or distant metastases. Coincidentally, a PSMA-avid nodule was observed dorsal to the right thyroid lobe. A complementary 4-dimensional CT showed a round nodule of 18 mm with quick contrast enhancement well demarcated from its surroundings. Blood tests revealed elevated serum calcium and parathyroid hormone consistent with primary hyperparathyroidism. Subsequently, parathyroidectomy was performed, and histopathological examination of the nodule confirmed a parathyroid adenoma.

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

BACKGROUND: Primary 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 PRESENTATION: The 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. CONCLUSION: We 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.

Parathyroid carcinoma: impact of preoperative diagnosis on the choice of surgical procedure.

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

Calcitriol supplementation before parathyroidectomy and calcium level after surgery in parathyroid adenoma patients: a randomized controlled trial.

BACKGROUND: Hypocalcemia is the most common complication after parathyroidectomy, contributing to extended hospital stays and higher hospitalization costs. The present study aimed to evaluate whether preoperative Calcitriol could help reduce hypocalcemia rates. METHOD: In this randomized controlled trial, we included 80 patients with primary hyperparathyroidism candidates for parathyroidectomy. The intervention group received Calcitriol 0.25 µg/day 1 week before parathyroidectomy. Baseline laboratory data, parathyroid hormone level (before, during, after 5, and 10 min of operation), calcium level (6, 24, and 48 h after operation), and clinical signs and symptoms were recorded. RESULTS: Of the 80 participants, 40 (mean age: 53.36 ± 12.97) were randomized to the intervention, and 40 (mean age: 52.84 ± 12.32) to the control group. There were no statistically significant differences in age, tumor size, gender, baseline laboratory data, intra-operative PTH, and calcium level 6 and 24 h after the operation. We observed a significantly higher calcium level in the intervention group 48 h post-operation (8.57 ± 0.30 vs. 8.33 ± 0.38). Also, days of hospital stay and symptomatic hypocalcemia rate were significantly lower in the intervention group. CONCLUSION: In patients with primary hyperparathyroidism, preoperative Calcitriol may be of value in preventing post-parathyroidectomy hypocalcemia and subsequent complications.

The Clinical Features and Treatment Strategy of Parathyroid Cancer: A Retrospective Analysis.

Objective: To review the features and treatment of parathyroid cancer in our series. Explore the suitable extent of initial surgery and the effect of adjuvant radiotherapy in local recurrence. Methods: Seven cases of parathyroid cancer presented from 2014 to 2021. The presenting features, diagnosis, and treatment are presented. Results: Only two patients had multiple manifestations of hypercalcemia. Marked hypercalcemia, which was revealed to be an average of 13.9 mg/dl (range from 11.8 mg/dl to 15.8 mg/dl), was observed in four patients (57%). The others' serum calcium levels were in the normal range with an average of 9.9 mg/dl (range from 8.6 mg/dl to 10.8 mg/dl). All seven patients had hyperparathyroidism with an average of 733 pg/ml (range from 113 pg/ml to 3193 pg/ml). En bloc resection was performed in two patients with neighboring structure invasion, and four patients with complete tumor capsules underwent tumor resection with limited resection of the thyroid gland. Postoperative adjuvant radiotherapy appeared unsuccessful for local recurrence. Conclusion: High calcium, high PTH, parathyroid occupation by ultrasound, and intraoperative invasion should be considered to have the possibility of parathyroid cancer. Open surgery is recommended and protecting tumor integration is the elementary surgery principle. The initial surgical extent should be decided by the invasion of the tumor. When PC has a local recurrence, the debulking surgery and adjuvant radiotherapy are always fake.

Parathyroid carcinoma during pregnancy: a novel pathogenic CDC73 mutation - a case report.

BACKGROUND: Parathyroid carcinoma is an uncommon cause of PTH-dependent hypercalcemia. Only a handful of cases have been reported of parathyroid carcinoma during pregnancy. CASE PRESENTATION: Twenty-four - Year - old female presented with proximal myopathy was found to have hypercalcemia. Her serum corrected total calcium was - 15 mg/dl (8.5 - 10.3), serum phosphate - 2.3 mg/dl (2.5 - 4.5), intact PTH - 118 pg/ml (20 - 80), Vitamin D - 15 ng/ml and Urine Ca/Cr ratio - 2.1 (0.1 - 0.2). Her CECT-neck revealed a well-defined mass lesion posterior to the right lobe of the thyroid - 2.6 cm × 2.5 cm × 2.9 cm in size. She was started on vitamin D supplementation, and she underwent right lower focal parathyroidectomy. Her PTH levels normalized following surgery. Her histology revealed an atypical parathyroid adenoma. She was treated with calcium and vitamin D. Her follow up was uneventful. One year following initial surgery the patient became pregnant and at 16 weeks of POA, the patient presented with a rapidly enhancing neck mass for one week duration. Her biochemical investigations were suggestive of a recurrence of primary hyperparathyroidism. Her ultrasound scan of the neck revealed a well-defined discreate hypoechoic nodule, superior to the thyroid isthmus which was confirmed by a non-contrast MRI scan of the neck. She underwent an uncomplicated second trimester parathyroid tumour excision with normalization of post op PTH. Her histology revealed a parathyroid carcinoma with vascular and capsular invasion. Her genetic studies revealed a novel frameshift mutation of the CDC73 gene. She was treated with calcium and vitamin D supplementation and closely followed up with ionized calcium and PTH levels which were normal throughout the pregnancy. She had an uncomplicated caesarean section at a POA of 37 weeks. Currently she is twelve weeks post-partum, in remission of disease. CONCLUSION: This case shows the importance of stringent follow up of atypical parathyroid adenoma patients, the benefit of second trimester surgery in management of hypercalcemia due to parathyroid carcinoma during pregnancy and the importance of identifying the novel CDC73 gene mutation.

Successful Control of Hypercalcemia with Sorafenib, Evocalcet, and Denosumab Combination Therapy for Recurrent Parathyroid Carcinoma.

Parathyroid carcinoma (PC) is a rare type of endocrine cancer. Recurrence and metastasis are common after surgery, and refractory hypercalcemia often leads to a poor prognosis. However, there are currently no specific strategies for PC recurrence. We herein report a 61-year-old Japanese man with metastatic PC who was treated with sorafenib, a multikinase inhibitor. In this case, the serum calcium level was under control for 10 months after the initiation of sorafenib. This case suggests that combination therapy with sorafenib, evocalcet, and denosumab may be an alternative, stronger management option for refractory hypercalcemia in recurrent PC.

Contemporary Multimodality Imaging of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a disorder characterized by hypercalcemia and an elevated or inappropriately normal parathyroid hormone level. Classic features include bone pain, fractures, renal impairment, nephrolithiasis, and mental disturbance. However, most cases of PHPT are now asymptomatic at diagnosis or associated with nonspecific neurocognitive changes. The most frequent cause of PHPT is a solitary adenoma that secretes parathyroid hormone without the normal suppressive effect of serum calcium. A smaller number of cases can be attributed to multigland disease. Parathyroidectomy is curative and is considered for nearly all affected patients. Although PHPT is primarily a clinical and biochemical diagnosis, imaging is key to the localization of adenomas, which can lie in conventional locations adjacent to the thyroid gland or less commonly at ectopic sites in the neck and mediastinum. In addition, accurate localization facilitates the use of a minimally invasive or targeted surgical approach. Frequently used localization techniques include US, parathyroid scintigraphy, and four-dimensional CT. Second- and third-line modalities such as MRI, PET/CT, and selective venous sampling with or without parathyroid arteriography can increase confidence before surgery. These localization techniques, along with the associated technical aspects, relative advantages, and drawbacks, are described. Local expertise, patient factors, and surgeon preference are important considerations when determining the type and sequence of investigation. A multimodality approach is ultimately desirable, particularly in challenging scenarios such as multigland disease, localization of ectopic adenomas, and persistent or recurrent PHPT. Online supplemental material is available for this article. ©RSNA, 2022.

Parathyroid carcinoma: Single centre experience.

OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

Incidence, survival time, and surgical treatment of parathyroid carcinomas in dogs: 100 cases (2010-2019).

OBJECTIVE: To evaluate outcomes of dogs with parathyroid carcinoma (PTC) treated by surgical excision and to describe the incidence of postoperative hypocalcemia, degree of hypocalcemia, duration of hospitalization, duration of calcium supplementation, and survival time. ANIMALS: 100 client-owned dogs with PTC admitted to academic, referral veterinary institutions. PROCEDURES: In a retrospective multi-institutional study, medical records of dogs undergoing surgical excision of PTC between 2010 to 2019 were reviewed. Signalment, relevant medical history, clinical signs, clinicopathologic testing, imaging, surgical findings, intraoperative complications, histologic examination, and survival time were recorded. RESULTS: 100 dogs with PTC were included, and 96 dogs had clinical or incidental hypercalcemia. Common clinical signs included polyuria (44%), polydipsia (43%), hind limb paresis (22%), lethargy (21%), and hyporexia (20%). Cervical ultrasonography detected a parathyroid nodule in 91 of 91 dogs, with a single nodule in 70.3% (64/91), 2 nodules in 25.3% (23/91), and ≥ 3 nodules in 4 (4/91)% of dogs. Hypercalcemia resolved in 89 of 96 dogs within 7 days after surgery. Thirty-four percent of dogs developed hypocalcemia, on the basis of individual analyzer ranges, within 1 week after surgery. One dog had metastatic PTC to the prescapular lymph node, and 3 dogs were euthanized for refractory postoperative hypocalcemia. Estimated 1-, 2-, and 3-year survival rates were 84%, 65%, and 51% respectively, with a median survival time of 2 years. CONCLUSIONS AND CLINICAL RELEVANCE: Excision of PTC results in resolution of hypercalcemia and excellent long-term tumor control. Surgical excision of PTC is recommended because of resolution of hypercalcemia and a good long-term prognosis. Future prospective studies and long-term follow-up are needed to further assess primary tumor recurrence, metastasis, and incidence of postoperative hypocalcemia.

Brown tumour mimicking skeletal metastasis.

Brown tumours of bone are highly vascular osteolytic lesions that depict a reparative cellular process instead of a neoplastic process in hyperparathyroidism (HPT) patients. These tumours have the potential to be aggressive and destructive. We report a case of a 30-year-old woman who presented with left thigh and lower back pain. The radiological evaluation showed multiple bony lesions in the pelvis and the spine, which mimicked multiple metastatic tumours. However, on biochemistry evaluation, serum calcium, alkaline phosphatase, and parathyroid hormone were all high, while serum phosphate was low, indicating primary HPT (PHPT), which was confirmed by parathyroid scintigraphy showing left parathyroid adenoma. Hence, the bony lesions were diagnosed as brown tumours secondary to PHPT. The patient underwent parathyroidectomy and developed severe hungry bone syndrome requiring parenteral calcium infusion along with oral calcium and active vitamin D supplementation. The clinical symptoms of bone pain improved after surgery.

A germline c.1546dupC MEN1 mutation in an MEN1 family: A case report.

RATIONALE: Multiple endocrine neoplasia type 1 (MEN1) is a rare tumor syndrome with an autosomal dominant inheritance, and genetic testing for MEN1 gene is important for both affected individuals and their relatives. We present a 2-person family affected by a germline c.1546dupC MEN1 mutation, and one of them had a full-spectrum of MEN-related endocrine tumors. PATIENT CONCERNS: A female patient aged 32 years presented with jejunal ulcer perforation due to gastrinoma. DIAGNOSES: We conducted genetic analysis and extensive biochemical/radiological evaluation for detecting other endocrine tumors. Multiple pancreatic neuroendocrine tumors (NETs), prolactinoma and primary hyperparathyroidism were diagnosed, and a frame-shift mutation, NM_130799.1:c.1546dupC (p.Arg516Profs∗15), was detected. One daughter of the proband, aged 12 years, had the same mutation for MEN1. INTERVENTION: She underwent pancreatic surgery for pancreatic NETs and total parathyroidectomy for primary hyperparathyroidism. OUTCOMES: After pancreatic surgery, long-term symptoms of epigastric soreness, acid belching, sweating, and palpitation in fasting were improved. Hypercalcemia was improved after parathyroidectomy and she was supplemented with oral calcium and vitamin D. Her daughter showed normal biochemical surveillance until 15 years of age. LESSONS: We report 2 people in a family affected by MEN1 with the heterozygous germline c.1546dupC mutation, a variant that should be surveilled for early development of full-blown MEN1-associated endocrine tumors.

Nonfunctional parathyroid cancer a case report.

INTRODUCTION: Parathyroid cancer is a rare endocrine malignancy. These tumors are typically functional, causing severe hypercalcemia due to primary hyperparathyroidism. Nonfunctional parathyroid cancer with normal serum calcium and parathyroid hormone levels is extremely rare. The disease is usually indolent but progressive with a tendency to metastasize. It is very difficult to diagnose this malignancy. The definitive diagnosis is made by histopathological examination. Radical surgery with ipsilateral lobectomy and en bloc neck dissection is considered to be the most appropriate therapeutic approach. There is no evidence of efficiency of adjuvant cancer therapy and its indication has not been defined. Disease recurrence is common. CASE REPORT: We report the case of a 26-year-old female patient who underwent left hemithyroidectomy for growth progression of a hypoechoic lesion behind the left thyroid lobe detected by ultrasonography. Preoperative cytology and imaging assessments were not suspicious for malignancy. Serum parathyroid hormone and calcium levels were normal. The diagnosis of nonfunctional parathyroid carcinoma was determined based on histopathological examination. No further surgery or adjuvant therapy was indicated. No signs of recurrence or generalization have been observed at 36 months after the surgery. CONCLUSION: Nonfunctional parathyroid cancer is extremely rare. In many cases, the diagnosis is made in advanced stages of the disease. No formal classification or treatment protocol has been established so far. A new staging system has been proposed in the 8th edition of AJCC/UICC. Early detection, radical surgery and close follow-up are crucial aspects to affect the mortality and morbidity of patients with this type of malignancy.

[Parathyroid carcinoma: a rare and aggressive tumor]. / Nebenschilddrüsenkarzinom: ein seltener und aggressiver Tumor.

Parathyroid carcinoma is a very rare disease that is accompanied by a poor prognosis. Diagnosis is based on laboratory tests (calcium, parathyroid hormone), sonography, and scintigraphy. Complete surgical resection is the treatment of choice. Adjuvant therapy is controversial. The lack of treatment guidelines and experience with this disease often delay timely therapy. In the following article, we report on two female patients with parathyroid carcinoma who underwent surgery in our clinic.

Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography for the localization of abnormal parathyroid glands in patients with primary hyperparathyroidism: What clinicopathologic factors affect its accuracy?

PURPOSE: Sestamibi Single-Positron Emission Computed Tomography/Diagnostic-quality Computed Tomography (MIBI-SPECT/CT) is a common technology used for primary hyperparathyroidism (PHPT) localization in clinical practice. However, the clinicopathologic factors affecting the accuracy of MIBI-SPECT/CT and the potential limitations remain unclear. METHODS: Retrospectively enrolled PHPT patients (n = 280) were analyzed from August 2017 to December 2019. RESULTS: Of 96 patients with PHPT (mean age, 54 years; 63 females), 17 had discordance between MIBI-SPECT/CT and intraoperative findings. Among the 17 patients with discordance, 58.8% had major discordance, which occurred in most patients with multigland disease (MGD). Compared with concordant patients, discordant patients exhibited increased frequencies of autoimmune thyroid disease (29.4% vs 10.1%, p = 0.035), MDG (41.2% vs 3.8%, p = 0.035), higher PTH (296 pg/mL vs 146 pg/mL; p = 0.012),and lower phosphorus levels (0.77 mmol/L vs 0.90 mmol/L; p = 0.024). MDG (odds ratio [OR], 16.95; 95% CI 2.10-142.86), parathyroid lesion size of 12 mm or less (OR, 6.93; 95% CI 1.41-34.10), and a PTH level higher than 192.5 pg/mL (OR, 12.66; 95% CI 2.17-71.43) were independently associated with discordant MIBI-SPECT/CT results. CONCLUSION: MGD was most strongly associated with discordance between MIBI-SPECT/CT and intraoperative findings followed by a PTH level higher than 192.5 pg/mL and parathyroid lesion size of 12 mm or less. Surgeons should recognize these potential limitations, which may improve the preoperative procedure by encouraging further localization imaging and promptly facilitate intraoperative troubleshooting.

Contemporary Evaluation and Management of Parathyroid Carcinoma.

Parathyroid carcinoma is a rare malignancy, representing 0.005% of all cancers and 0.5%-1% of all parathyroid disorders. Parathyroid carcinoma occurs equally in males and females, as opposed to primary hyperparathyroidism, which has a female predominance. Patients with parathyroid carcinoma present with symptoms of hypercalcemia, similar to those with benign primary hyperparathyroidism. Parathyroid carcinoma should be suspected when calcium or parathyroid hormone levels are high. Because of the difficulty of discerning parathyroid carcinoma from adenoma preoperatively, the diagnosis of carcinoma is often made only after parathyroidectomy. The goals of surgery are resection with negative margins because surgery represents the only opportunity for cure. Adjuvant therapy with chemotherapy or external beam radiation has not been proven to affect disease-free or overall survival for these patients. Recurrence is common, with reoperation recommended for resectable recurrent disease. Palliation with calcimimetic pharmacotherapy can aid with management of symptomatic hypercalcemia in recurrent or persistent disease after parathyroidectomy. Ultimately, patients succumb to sequelae of hypercalcemia rather than tumor burden.

Seven cases of parathyroid carcinoma and review of the literature.

Parathyroid cancer is a rare malignancy and an uncommon cause of hyperparathyroidism. In the present study, we present seven cases of parathyroid carcinoma. The female ratio was 5/7 (71.4%). Median age at diagnosis was 47 years, and median follow-up duration was 60 months (IQR 29-75). Mean calcium level at diagnosis was 12.7 mg/dL (range, 11.3-13.9), and mean parathormone level was 1115 ng/L (IQR 287-1470). Two patients (28.5%) had a palpable neck mass. Coexisting brown tumor was present in three patients (42.8%), and nephrolithiasis was found in one patient (14.2). Average tumor size was 29 mm (IQR 28-40). Capsular and vascular invasion were detected in six patients (85.7%), intrathyroidal spread was observed in two patients (28.5%), and soft tissue invasion was seen in three patients (42.8%). Parathyroid adenoma was present in one patient and parathyroid gland hyperplasia in another patient. Adjuvant radiotherapy was given to four patients (57.1%). There was no metastatic disease or death. At the last visit, two patients had increased parathormone levels and no additional focus could be detected in either. Patients with markedly elevated parathormone and calcium levels and a palpable larger mass on the neck should be evaluated for parathyroid cancer. En bloc resection is the mainstay treatment. Despite contradictory results, adjuvant radiotherapy to the neck may help to reduce the risk of local recurrence in patients with microscopic residual parathyroid carcinoma.