Parathyroid Carcinoma Research Articles

SAT203 Parathyroid Adenoma Masquerading As Parathyroid Carcinoma

Abstract Disclosure: M. Fariduddin: None. A. Lupieri: None. H.L. Calero: None. A. Rubenfeld: None. Y. Eisenberg: None. Case: 22 y/o pregnant female (5 weeks gestation) presented to the endocrinology clinic after a hospital admission for nausea, vomiting, constipation, fatigue and joint pain with labs showing calcium (corrected) of 14 mg/dL and PTH of 1200 pg/ml. Labs in the clinic showed calcium at 16 mg/dL and PTH 1500 pg/ml. She was re-admitted for IV fluids, calcitonin and zoledronic acid. Severe hypercalcemia, young age, and extremely high PTH levels were highly suggestive of parathyroid cancer. CT of neck showed a 2 cm right inferior parathyroid mass abutting the esophagus with concern for esophageal invasion with no evident plane between the mass and the esophagus. No cervical adenopathy was noted. Patient in conjunction with her obstetrician made an informed decision to terminate the pregnancy as this was an undesired pregnancy. She underwent an urgent right inferior gland parathyroidectomy. The mass was not fixed to underlying structures and was resected in-toto. Pathology showed chief cells with clear cytoplasm, and homogeneously round nuclei. There were no atypical mitoses, lymphovascular invasion, perineural invasion, or other invasive features concluding the final pathology as parathyroid adenoma. Discussion: Primary hyperparathyroidism predominantly affects postmenopausal women. Most common cause is parathyroid adenoma (80-85%). Parathyroid carcinoma is a rare cause of primary hyperparathyroidism (1-2%).80% people with parathyroid adenoma and primary hyperparathyroidism are diagnosed incidentally with mildly elevated calcium. PTH elevation is around 1.5-2 times the upper limit of normal. Symptoms are mild sequelae of hypercalcemia. PTH levels 5-10 times upper limit of normal, severe hypercalcemia (Ca > 14 mg/dl) or a hypercalcemia crisis are highly suspicious for parathyroid cancer. Surgical resection is the mainstay of treatment. Clinical criteria play a key role in early identification of parathyroid carcinoma in order to get these patients to surgery before tumor spread and improve long term survival. Our patient with significantly elevated calcium and parathyroid hormone had an atypical presentation of a parathyroid adenoma thus uncovering the limitations of clinical criteria in identifying a parathyroid carcinoma. Most of the patients with a parathyroid adenoma will eventually require surgery, however the technique, extent and urgency of surgery is affected based on clinical situations like these. The timing of the surgery could be detrimental when coupled with a scenario like our patient’s pregnancy wherein you could delay the surgery until the second trimester had the patient wanted to continue the pregnancy. This case highlights the importance of awareness of atypical presentations of parathyroid adenomas and to have a cautious approach in patients with clinical concern for parathyroid carcinoma especially if there is a potential benefit to delay surgery. Presentation: Saturday, June 17, 2023

OR05-03 Treatment Of Parathyroid Neoplasia By Pharmacologic cdk4/6 Inhibition

Abstract Disclosure: J. Costa-Guda: None. J. Bellizzi: None. S. Gorka: None. C. Titarenko: None. A. Arnold: None. Parathyroid carcinoma (PC) is a rare, life-threatening malignancy. Despite relatively slow growth, recurrent or metastatic disease is typically incurable and often fatal due to cumulative complications of sustained elevation of parathyroid hormone (PTH) and accompanying hypercalcemia. Medical therapy aids in managing sequelae of hyperparathyroidism (HPT) but non-surgical interventions to reduce tumor burden have been largely ineffective in PC. Cyclin D1 amplification is seen in nearly 30% of PC, making it a key potentially actionable therapeutic target. Importantly, in contrast to other tissue contexts, cyclin D1-driven parathyroid neoplasia has been experimentally demonstrated to depend on cyclin D1’s ability to bind and activate its partner cyclin dependent kinases (cdk). This suggests that parathyroid tumor cells may be more sensitive to alterations in cdk-mediated proliferation control, and thus more responsive to pharmacologic cdk inhibition, compared with other tumor types. We sought to test the efficacy of cdk4/6 inhibitor therapy in cyclin D1-overexpressing parathyroid tumors in a pre-clinical system. We utilized a mouse model, harboring a PTH-CCND1 (PCD) transgene to drive parathyroid-specific cyclin D1 overexpression, which develops hormonally-active parathyroid tumors with known kinetics. Transgenic mice with established hyperparathyroidism and wild type littermates were treated with the cdk4/6 inhibitors palbociclib or abemaciclib for three weeks. While vehicle-treated PCD mice showed a 7% increase in serum calcium (Ca) levels over the course of treatment, Ca decreased by 1.8% and 0.5% in palbociclib- and abemaciclib-treated PCD mice, respectively, from pre-treatment levels. This treatment effect persisted for at least 60 days after discontinuation of treatment. Decreased parathyroid proliferation, as evidenced by 4.7-fold and 17.3-fold fewer Ki-67-positive cells in palbociclib- and abemaciclib-treated PCD mice, respectively, compared with vehicle-treated PCD mice, was also seen. Cdk inhibitor treatment had no effect on Ca or parathyroid cell proliferation in wild type mice. These results demonstrate that palbociclib and abemaciclib can significantly slow the progression of hypercalcemia and parathyroid proliferation in a cyclin D1-driven parathyroid tumor model, suggesting that cyclin D1 overexpressing parathyroid cells may be particularly sensitive to cdk4/6 inhibition. Our findings provide the first evidence of a direct pharmacologic effect in a relevant preclinical system to support the hypothesis that selected HPT patients, eg those suffering from advanced PC with activated cyclin D1, could substantially benefit from cdk4/6 inhibitor therapy. This evidence may aid clinicians in selecting therapeutic interventions, including when considering such drugs for off-label use or inclusion of PC patients in “basket” clinical trials. Presentation: Thursday, June 15, 2023

SAT209 Metastatic Parathyroid Carcinoma And The Challenge Of Maintaining Calcium Balance

Abstract Disclosure: K.M. Tuna: None. S. Badour: None. E.P. Monsour: None. G. Acosta Garcia: None. D. Barb: None. Background: Parathyroid carcinoma is a rare malignancy representing less than 1% of all parathyroid disorders. Presentation is significant for highly elevated calcium (Ca) and parathyroid hormone (PTH) levels, and usually a palpable neck mass (>3cm). Diagnosis is often made after surgery based on histopathology findings. The primary treatment modality remains surgical, but there is no effective approach for metastatic disease. Case presentation: A 51-year-old woman initially presented with multinodular goiter and compressive symptoms in 2008. Workup showed an elevated Ca of 14.4 mg/dl (normal 8.4-10.2 mg/dl) and PTH of 502 pg/ml (normal 12-88 pg/ml) while albumin 4.3 g/dl (normal 3.5-5.2 g/dl) and normal thyroid function tests. Radioactive Iodine uptake scan showed a 4.4 cm cold nodule on the right inferior pole. Sestamibi scan showed increased left upper pole activity. The patient underwent total thyroidectomy with surgical exploration for parathyroid adenoma. Pathology showed right intrathyroidal parathyroid carcinoma with lymphovascular invasion. The patient was lost to follow-up until 2022 when she was admitted with severe hypercalcemic crisis (Ca 15.8 mg/dl, Albumin 3.9 g/dl, and PTH 805 pg/ml). The patient was treated with IV fluids, calcitonin, and multiple rounds of bisphosphonates, and was then maintained on high-dose cinacalcet due to refractory and recurrent hypercalcemia. Repeat Sestamibi and neck US were unremarkable, although CT chest showed a 1.3 cm nodule in the right lower lung lobe. This was not FDG- nor DOTATATE-avid on PET-CT. The patient underwent laparoscopic wedge resection of the right lung nodule, and the pathology was consistent with metastatic parathyroid carcinoma. Her Ca and PTH levels normalized immediately after surgery (PTH decreased from 883 to 27 pg/ml) suggesting possible remission. Prior to discharge, she was started on oral calcium and vitamin D due to dropping Ca levels and clinical signs of hungry bone syndrome. She was readmitted one month later for preexistent heart failure exacerbation and declining renal function. Her PTH was noted to be elevated again, although Ca remained normal, raising concern for recurrent or persistent disease. However, the patient’s renal impairment and lung effusion limited further imaging. Ca and PTH were monitored frequently during hospitalization and weekly after discharge. PTH levels peaked at 634 pg/ml and then dropped to 127 pg/ml without intervention. Ca remained in the normal range while on calcium citrate and calcitriol. Conclusion: Treatment of metastatic parathyroid carcinoma remains a challenge. Mortality is secondary to complications of hypercalcemia; therefore, controlling calcium levels should be the main therapeutic goal. Hungry bone syndrome should be considered after surgery. Metastatic disease may occur even after 20 years; thus, lifelong close monitoring is indicated. Presentation: Saturday, June 17, 2023

SAT187 A Case Of CDC73 Mutation Related Primary Hyperparathyroidism With Ectopic Parathyroid Hyperplasia

Abstract Disclosure: T. Wu: None. N. Dhir: None. M. Bollineni: None. Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia, and most cases are sporadic. However, in 5-10% cases, it may occur as a syndromic and hereditary disease, like Multiple endocrine neoplasia type 1, type 2A, type 4, or CDC73 mutation related hereditary benign or malignant hyperparathyroidism. In patients with severe or early onset primary hyperparathyroidism, screening for genetic etiology should be considered. Case Presentation: A 35-year-old woman with a medical history of hypertension, kidney stones, and post-operative hypothyroidism presented to the endocrinology clinic due to recurrent hyperparathyroidism. She initially had a parathyroidectomy in 2008 and her calcium corrected at that time. She was again diagnosed with hypercalcemia due to primary hyperparathyroidism in 2021. She underwent re-exploration and had a right thyroid lobectomy with removal of three parathyroid glands. Her PTH was still 309 pg/mL (9-77 pg/mL) and calcium was 11.2 mg/dL (8.6-10.5 mg/dL), and she was started on Cinacalcet. The patient continued to have elevated calcium, bone pain, fatigue, and constipation. A 4D CT scan was ordered, which localized activity to a 1.5 cm arterial enhancing nodule in the anterior mediastinum, with intrathymic location. She underwent right video-assisted thoracoscopic total thymectomy with en bloc and the nodule was found to be ectopic parathyroid tissue. Post-operatively, her calcium normalized to 8.6 mg/dL and PTH was undetectable. She underwent genetic testing due to her recurrent hyperparathyroidism, which showed a CDC73 mutation. She is currently on calcitriol and calcium supplements, and serum calcium has been maintained in the low-normal range. Discussion: The CDC73 gene encodes a protein called parafibromin, which acts as a tumor suppressor, prohibiting cells from proliferating. Mutations in this gene are linked to jaw-tumor syndrome, familial isolated primary hyperparathyroidism (FIHP), and parathyroid carcinoma. These three CDC73-related disorders are clinically overlapping and inherited in an autosomal dominant manner. Biallelic mutations of the CDC73 gene are associated with a high risk of parathyroid cancer since the parafibromin protein is usually absent in parathyroid carcinoma and occasionally in atypical adenomas. FIHP tends to have a more severe clinical presentation with earlier onset (younger than 45 years). Additionally, patients with CDC73 related disorders are more prone to developing ossifying fibroma(s) of the jaw, uterine tumors, and various renal lesions. In summary, this case highlights the diagnostic and therapeutic challenges in a patient with persistent primary hyperparathyroidism after a failed second surgery. Genetic testing is vital for early detection, surveillance, and familial genetic counseling in patients with CDC73 related disorders. Presentation: Saturday, June 17, 2023

SAT204 Parafibromin: Key To The Diagnosis Of Atypical Parathyroid Adenoma In A Patient With Suspected Carcinoma

Abstract Disclosure: V. Anunobi: None. K. Fernandez-Lopez: None. C. Clement: None. N. Shah: None. L. Belalcazar: None. Introduction: Parathyroid carcinoma (PTCa), although a rare endocrine malignancy, should be considered in the differential diagnosis of severe parathyroid (PTH)-mediated hypercalcemia. We present the case of a patient in whom clinical presentation suggested a PTCa, but histological analysis with the use of a parafibromin (PF) stain helped identify the patient’s parathyroid mass as an atypical parathyroid adenoma (APTa). PF stain is now in the World Health Organization (WHO) guidelines for the differentiation of PTCa and APTa. Case Presentation: A 71-year-old woman was admitted to the hospital for an incidental finding of hypercalcemia and complaints of fatigue, myalgias, constipation and generalized weakness. On exam, the patient was alert and oriented; she had a palpable right neck nodule. Laboratory testing included serum calcium of 13.9 mg/dL (8.6-10.6mg/dL) and phosphorus of 2.4 mg/dL (2.5-5.0 mg/dL). PTH level was 3,547.4 pg/mL (12-88 pg/mL) and eGFR was 67ml/min/1.73m2. Patient had undergone a neck ultrasound prior to admission that described a 2.6 cm right thyroid nodule, however fine needle aspiration revealed that the nodule was a parathyroid mass. Further imaging, including a sestamibi nuclear scan and a neck tomography, confirmed the presence of a large right inferior parathyroid adenoma. After correction of hypercalcemia, the patient underwent a right parathyroidectomy and right hemithyroidectomy. Pathology identified a 7.7 g mass, 3 cm. on its greatest diameter. There was no evidence of lymphovascular or perineural invasion, or extension into the parathyroid capsule or thyroid gland. The mass was strongly positive for PF staining in more than 50 % of tumor cells and was categorized as an APTa. Discussion: Differentiating APTa from PTca is challenging. Preserved PF tumor expression in parathyroid tumors makes PTca unlikely and is linked with a low risk of tumor recurrence. Endocrinologists need to be aware of the utility of the PF stain when evaluating patients suspected to have a PTca. The WHO now recommends that a PF stain be included in the pathological evaluation of these tumors. Presentation: Saturday, June 17, 2023

SAT185 Parathyroid Adenoma Localized By Cytogenetic Testing

Abstract Disclosure: S. Khadija: None. A. Rao: None. Introduction: Primary hyperparathyroidism can be caused by a parathyroid adenoma, hyperplasia or rarely by parathyroid carcinoma. Most patients have few or no symptoms. Diagnosis of primary hyperparathyroidism can be challenging in the setting of secondary/tertiary hyperparathyroidism. Correct diagnosis can be reached by clinical evaluation, biochemical and radiological tests. We describe a case that was diagnosed by cytogenetic testing of the biopsy specimen. Case Report: We report a case of a 64-year-old man. He was referred to the endocrine clinic for an incidental thyroid nodule on CT scan. He had hypothyroidism after I-131 treatment for Graves’ disease 15 years back. He had a long history of hypertension with renal failure. He had a renal transplant in 2017 and had hypercalcemia intermittently with elevated PTH since 2012. Ultrasound of thyroid reported a 1.6 x 1.7 x 2.0 cm nodule in the left thyroid lobe. He denied any compressive symptoms and was euthyroid on levothyroxine. An ultrasound guided FNA of the left thyroid nodule was reported as Bethesda III FLUS and sent to Veracyte for Affirma, which indicated a parathyroid adenoma. A sestamibi scan indicated a left lower parathyroid adenoma. He had surgery and intraoperative parathyroid hormone (PTH) dropped from 122pg/ml to 35.8pg/ml(29.1-79.7 pg/ml). Pathology confirmed parathyroid adenoma 3.8 grams in weight. Postoperatively calcium normalized with drop in PTH to 36.1pg/ml. After 2 weeks his calcium remained normal. Discussion: Parathyroid adenoma is a relatively rare condition and causes a majority of cases of primary hyperparathyroidism. A few cases are due to hyperplasia, more common in secondary hyperparathyroidism due to renal disease. Parathyroid adenoma is difficult to diagnose in patients with underlying hyperplasia due to chronic renal disease. Sonography and 99mTc preoperative sestamibi (MIBI) scan are the primary imaging modalities utilized for the visualization of diseased glands. MIBI scan is approximately 90% sensitive for localizing a parathyroid adenoma. Ultrasonography is the first-line imaging modality and parathyroid adenomas are nearly always homogeneously hypoechoic to the overlying thyroid gland and are commonly detected using gray-scale imaging alone when they are larger than 1 cm in diameter. Nodular goiter or enlarged lymph nodes are causes of false-positive results. Biopsy is very rarely used to diagnose a parathyroid adenoma with cytogenetic testing. Conclusion: Parathyroidectomy is the main stay in management of primary hyperparathyroidism due to parathyroid adenoma. Cervical sonography and sestamibi imaging are used for prediction of adenoma location. Both are limited by increased thyroid volume. Biopsy with cytogenetic testing can help in diagnosis in difficult patients. Presentation: Saturday, June 17, 2023

THU525 Atypical Presentation Of Parathyroid Carcinoma In The Lungs

Abstract Disclosure: J.N. Jacinto: None. O. Reyes: None. M. Cating-Cabral: None. R. Santiago: None. J. Andal: None. A 66-year-old female with a history of parathyroid adenoma underwent partial parathyroidectomy and thyroidectomy of the right lobe in 2006. She has the following comorbidities: pre-diabetes, hypertension, multiple liver cysts, medullary nephrocalcinosis and nephrolithiasis, ureterolithiasis and uterine intramural myoma. She also has a strong familial disposition of endocrine tumors. During the last quarter of 2018, parathyroid hormone and calcium levels were elevated and parathyroid imaging revealed an adenoma on the posteromedial aspect of the left thyroid lobe. Removal of the adenoma was offered but insisted on medical treatment. In 2022, she was admitted for subarachnoid hemorrhage due to fall. There was an incidental finding of a lung mass with minimal pleural effusion on the right lung lobe. PET-scan revealed five FDG-avid nodules (SUV up to 9.6) with the largest in the right middle lobe measuring 2 x 2 x 2 cm. Percutaneous needle biopsy was performed which showed a tumor with fairly uniform cells in organoid nests and solid clusters. By immunohistochemistry (IHC), the tumor cells were diffusely and strongly positive for CK and GATA-3; focally positive for chromogranin and synaptophysin; and negative for TTF-1, Pax-8, and S100. This was signed out as an epithelial tumor with neuroendocrine features; the differential diagnosis includes pulmonary neuroendocrine tumor versus metastasis from the prior parathyroid lesion. She subsequently underwent completion thyroidectomy and video-assisted thoracoscopic surgery. The lung wedge resections both showed tumors with similar morphology and IHC staining pattern as the biopsy. Additional stains were also performed to rule out other entities, which were all negative (CK7, CK20, CD56, mammaglobin, GCDFP-15, TTF-1, S100, ER, Pax-8, HSA, and SALL-4). The Ki-67 proliferation index was 17.26%. Because the overall findings were not definitive, comprehensive genomic profiling by next generation sequencing (NGS) was recommended and subsequently performed. NGS showed gene alteration in CDC73, with a variant allele frequency of 50%; this finding has been documented in parathyroid carcinoma. Pre-operative parathyroid hormone levels remained unchanged (408 to 397 pg/ml) despite surgery. Currently, there is no available targeted therapy to address her genomic alteration. Hyperparathyroidism-jaw tumor syndrome was entertained. The multidisciplinary team advised en-bloc resection of the lung tumor and additional gene testing for family members. She opted for palliative care and is on cinacalcet for her hyperparathyroidism. Presentation: Thursday, June 15, 2023

FRI686 Phenotypic Profiling And Molecular Mechanisms In Hyperparathyroidism-jaw Tumor Syndrome

Abstract Disclosure: R. Tora: None. J. Welch: None. J. Sun: None. S.K. Agarwal: None. D.A. Bell: None. M. Merino: None. L.S. Weinstein: None. W.F. Simonds: None. S. Jha: None. Background: Hyperparathyroidism-Jaw Tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism (PHPT) that is associated with tumors in the parathyroid, jaw, kidney, and uterus. We previously presented on the clinical characteristics of primary hyperparathyroidism in our cohort. Methods: We now expand on the report through review of uterine tumors, immunohistochemical staining for parafibromin, sequencing of parathyroid and kidney tumor tissue, and RNA-seq of parathyroid tumors. Results: We identified 68 patients (36 males, 32 females) from 29 kindreds with HPT-JT with median age at last follow-up of 39 [29-53] years. Of these, 7 patients were unaffected (2 males, 5 females). Among females, 12/32 (38%) developed uterine tumors with multiple adenomyomatous polyps, an unusual form of endometrial polyps seen in 10/24 tumors (42%). Given that these types of lesions are very rare in the general population, it is likely that such epithelial-mesenchymal uterine proliferations are a characteristic feature of HPT-JT syndrome.Solid kidney tumors were seen in 4/61 patients (7%). Three had surgery for the tumors - 2/3 were female and had mixed epithelial stromal tumor, while the third patient, a 6-year old male, had metastatic Wilm’s tumor as his initial disease-related manifestation. Among these, two had a germline CDC73 variant at the p.M1 residue while the third patient had the germline variant p.L95P; however, sequencing of his tumor tissue showed a “second hit” at the p.M1 residue resulting in loss of heterozygosity in the tumor. The fourth patient, a female with p.Y55S variant, is being conservatively managed with no kidney surgery yet. All three women with kidney tumors also had a history of uterine tumors. Parafibromin staining of 19 available CDC73 related parathyroid tumors (13 adenomas and 6 carcinoma) did not correlate with histology or genotype. Pathway analysis of 21 parathyroid tumors (8 HPT-JT-related adenomas, 6 HPT-JT-related carcinomas and 7 sporadic parathyroid carcinoma with wild-type CDC73) showed a significant association of HPT-JT-related parathyroid carcinoma with growth, transmembrane receptor protein tyrosine kinase signaling and mesodermal commitment pathways. Conclusion: Multiple, recurrent atypical adenomyomatous uterine polyps appear to be characteristic of HPT-JT syndrome. Our findings support germline testing at a young age in first-degree relatives of patients with HPT-JT given onset of manifestations as early as 6 years. Variants at M1 residue appear to predispose to genitourinary tumors. At present, there are no therapeutic approaches to compensate for CDC73 inactivation. Future research to identify standards of care and therapeutics targets are warranted for this rare disease. Presentation: Friday, June 16, 2023

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

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

SAT249 Femur Lysis Calcium Crisis

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

SAT188 Atypical Parathyroid Adenoma: A Diagnostic Challenge Of Primary Hyperparathyroidism

Abstract Disclosure: S. Bendaram: None. L. Dulipsingh: None. Introduction: Atypical parathyroid adenomas(APA) are parathyroid neoplasms with some atypical histological features and of indeterminate malignant potential. They may occur sporadically or as a part of hereditary syndromes and contribute to 1.2-1.3% cases of Primary Hyperparathyroidism (PHPT). Here, we present an interesting case of hypercalcemia secondary to PHPT due to an underlying APA. Case Presentation: 28 year old white female with no known significant past medical history presented to ED with symptoms of nausea, vomiting and dizziness on standing. Physical examination was unremarkable except for dry mucous membranes and decreased bowel sounds. Initial labs revealed a total calcium of 19.6 mg/dl (8.4-10.2), PTH of 1161pg/ml (10-65), creatinine 1.2mg/dl (0.5-1.0), albumin 5.0 g/dl (3.5-5.0), ionized calcium 2.37 mmol/L (1.19-1.35), phosphorus 3.4 mg/dl (2.5-4.5), magnesium 1.6 mg/dl (1.7-2.8) TSH 0.51 uIU/ml (0.35-5.5), 25-hydroxy Vitamin D 24 ng/ml (30-100),1,25-dihydroxy Vitamin D 68 pg/ml (20-79) and PTHrP 19 pg/ml (11-20). Family history was negative for hypercalcemia, hyperparathyroidism, fragility fractures, pancreatic disease or any genetic syndromes. Inpatient treatment included IV fluids, 2 doses of calcitonin and Pamidronate 60 mg IV. Subsequently, over the hospital course, calcium improved to 11.9 mg/dl with improvement in her symptoms and she was discharged home. 24-hour urine calcium checked on an outpatient visit, after vitamin D replacement, revealed low urine calcium of 31 mg/24 hr. Ultrasound Thyroid demonstrated a 3.7 cm mass inferior to the right hemithyroid, suspicious for parathyroid adenoma versus abnormal lymph node. CT Parathyroid with and without contrast revealed normal thyroid and bilateral inferior parathyroid adenomas, right larger than left. She underwent en-bloc resection of right thyroid and right inferior parathyroid gland with final pathology showing atypical parathyroid adenoma, without evidence for obvious parathyroid carcinoma or metastatic disease. Genetic testing for a total of 53 genes including MEN, BRCA1, BRCA2 were negative. PTH levels normalized post-surgery. Conclusion: Atypical Parathyroid Adenomas have a clinical and biochemical profile more severe that the typical adenomas and, to some extent, similar but less severe to that of patients with parathyroid carcinoma, creating an overall diagnostic challenge. The molecular mechanisms are unclear, with germline CDC73 mutations appearing to be the most common defect. Due to uncertain malignant potential, a close and careful monitoring is recommended for these patients. Presentation: Saturday, June 17, 2023

FRI688 Efficacy Of 4D CT Scan And Tc-99m-MIBI-SPECT/CT For The Preoperative Localization Of Abnormal Parathyroid Glands In Patients With Primary Hyperparathyroidism

Abstract Disclosure: E. Zareva: None. V. Rivera-Hernandez: None. S. Salpekar: None. J. Moyo: None. M. Bilbatua: None. Z. Lauer: None. A. Zare: None. P. Kaur: None. M. Deshmukh: None. Background: Primary hyperparathyroidism is a common endocrine disorder that often requires surgical intervention for a cure. Accurate localization of abnormal parathyroid glands is critical for successful surgical treatment. NM Parathyroid scan with single-photon emission computed tomography(Tc99m-MIBI-SPECT/CT) is considered the gold standard, but other options like ultrasound, CT, MRI, and PET have been used. Accurate preoperative imaging has become even more critical with the development of focused surgical approaches. This study aims to evaluate the accuracy of Tc99m-MIBI-SPECT/CT and 4D CT scan in localizing abnormal parathyroid glands in our institution. Objectives: To evaluate and compare the efficacy of 4D CT scan and Tc99m-MIBI-SPECT/CT for the preoperative localization of abnormal parathyroid glands in patients with primary hyperparathyroidism in a single health network. Methods and Design: We collected data on 100 patients with biochemically confirmed primary hyperparathyroidism regarding age, sex, image modalities such asTc99m-MIBI-SPECT/CT and 4D CT before surgery, and the surgical pathology results. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for both imaging modalities. Results: A total of 100 patient charts were reviewed, including 77 females and 23 males (3.35:1 female to male ratio),with an average age of 65.9 years (standard deviation 12.59). 90 patients had undergone surgical resection. 54 (60%) of them were diagnosed as parathyroid adenoma; 30 (33.3%) as parathyroid hyperplasia; 1 (1.1%) malignant parathyroid carcinoma; 5 (5.5%) were normal. 84 patients underwent Tc99m-MIBI-SPECT/CT and97 patients - 4D CT. 4D CT scan had a sensitivity of 90.36% (95% CI,81.89%-95.75%) and specificity of 50.00% (95% CI, 6.76%-93.24%) and outperformed Tc99m-MIBI-SPECT/CT which had a sensitivity of 45.71% (95% CI,33.74%-58.06%) and specificity of 80.00% (95% CI, 28.36%-99.49%). 4D CT had a positive predictive value (PPV) of 97.40% (95% CI, 90.93%-99.68%) and a negative predictive value (NPV) of 20.01% (95% CI, 2.52%-55.62%) compared toTc99m-MIBI-SPECT/CT which had PPV of 96.95% (95% CI, 84.22%-99.92%) and NPV of9.57% (95% CI, 2.68%-22.68%). 4D CT also had higher accuracy (85.5%; 95% CI,79.87%-94.35%) compared to Tc99m-MIBI scan (48.01%; 95% CI,36.32%-59.86%). Conclusion: Diagnostic imaging plays a crucial role in the management of primary hyperparathyroidism. Among the patients who had Tc99m-MIBI-SPECT/CT, less than half had positive scans suggestive of abnormal parathyroid tissue. This highlights the need for additional imaging methods for patients with negative scans. 4D CT is widely used in our institution and is more effective than Tc99m-MIBI-SPECT/CT in the preoperative localization of abnormal parathyroid glands. Presentation: Friday, June 16, 2023

SAT212 Collateral Damage A Case Of Refractory Hyperparathyroidism In A Young Woman With End Stage Renal Disease

Abstract Disclosure: E.W. Alvarado: None. V. Alia: None. H. Reinhart: None. R. Giese: None. Background: The Rio Grande Valley (RGV) is a community with the highest incidence of ESRD in the USA. Hyperparathyroidism (HPT), defined as a serum PTH >65 pg/mL, HPT is a secondary complication of ESRD affecting 80% of individuals in this population. Although hyperparathyroidism may be asymptomatic, a severe form, refractory to medication can occur. Refractory HPT is defined as a PTH level 9 times the upper-limit or a serum level >800 pg/mL. This disease causes mutations in parathyroid cells causing parathyroid-gland hyperplasia. Once PTH levels increase to this extent, systemic issues including electrolyte derangements, weight loss, pathologic fractures, osteoporosis, and death can ensue. Due to the high mortality associated with this condition; it is paramount that patients are referred for surgery when medical management is inadequate. Clinical Case: A 31-year-old female with a significant medical history of ESRD on hemodialysis presented for evaluation of a suspected parathyroid carcinoma. Physical examination revealed a frail, short-statured woman who ambulated with a walker. Patient endorsed a 13-year history of uncontrolled HTN on antihypertensives, with a BP of 226/124. The patient presented with a BMI of 16.7, and endorsed a history of multiple fractures, musculoskeletal-pain, fatigue, palpitations, and a 33 pound weight loss over 1.5-years. Labs showed a total calcium of 9.4, phosphorus 6.9, ALP 652, and a PTH of 2423, meeting criteria for refractory HPT. Of note, records received five-months prior to referral showed a PTH of 5343 pg/ml, suggesting earlier surgery could have minimized disease progression. Based on the patient's presentation, MEN was suspected, however workup was negative. The patient was referred to a nearby ER for hemodynamic-stability and further workup of her underlying conditions. Ultrasound revealed two putative inferior parathyroid-glands presumptive for a diagnosis of severe tertiary HPT, but due to PTH>1000 carcinoma could not be excluded. Patient was taken to surgery and intra-operatively 4-gland hypertrophy was noted and a 3.5-gland excision was performed. Intraoperative PTH decreased to 120, and pathology showed benign parathyroid hyperplasia. Post-op day 1 the patient received hemodialysis and lab values revealed severe hypocalcemia prompting close monitoring and aggressive calcium supplementation. The patient’s electrolyte levels stabilized, she was discharged, and follow-up 2-weeks later revealed a PTH of 14.5. Conclusion: This case of a young patient with refractory HPT highlights the region's early onset of ESRD and its subsequent conditions. Noteworthy, the RGV is associated with a multitude of socioeconomic factors that precipitate neglect of chronic illnesses, indicating the substantial need for early identification and intervention to prevent long-term complications to disease in this vulnerable population. Presentation: Saturday, June 17, 2023

SAT556 An Unusual Case of Papillary Thyroid Carcinoma With Biallelic MEN1 Variants In a Patient With MEN1

Abstract Disclosure: E. Chuki: None. M. Raffeld: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. S. Jha: None. Introduction: Multiple endocrine neoplasia (MEN1) syndrome is caused by germline variants in MEN1. Papillary Thyroid Cancer (PTC) is not regarded as a canonical MEN1-related endocrine tumor. Pathogenic variants in MEN1 are rare in PTC. Herein, we report an MEN1 patient with biallelic loss of MEN1 in PTC.Clinical case: A 59-year-old Hispanic female presented with asymptomatic hypercalcemia due to primary hyperparathyroidism [serum calcium: 13.9 mg/dl (8.4-10.2), PTH: 314 pg/ml (15-65) and 25 hydroxy vitamin D: 15 ng/ml (33 – 100)]. Physical examination was unrevealing for any neck mass or lymph nodes. Kidney function was normal with no history of or imaging evidence of kidney stones or calculi. Bone densitometry revealed osteoporosis [lowest T-score of -2.7 in spine]. Germline genetic testing was performed given large size of the parathyroid tumor and biochemical presentation suspicious for parathyroid cancer. A pathogenic MEN1 p.Ile54Serfs*65 was identified. A neck sonogram and 99-technetium sestamibi scan showed a 4.1 cm left parathyroid adenoma and incidental 3.5 cm, heterogeneous right thyroid lobe nodule having smooth margins without microcalcifications, and no cervical lymphadenopathy. Thyroid function studies were normal. Fine needle aspiration of right thyroid nodule revealed epithelial neoplasia containing many atypical cells with enlarged nuclei, nuclear grooves, fine chromatin, and moderate amounts of granular to oxyphilic cytoplasm. Patient underwent left inferior parathyroidectomy and right thyroid lobectomy. Histology was consistent with parathyroid adenoma and a hyperplastic adenomatous thyroid nodule with a 1.1 cm focus of classic PTC with minor follicular and oncocytic components, limited to the thyroid with clear margins and no lymphovascular invasion (pT1bNxMx). Genetic sequencing of the PTC (TSO500 gene panel) revealed two pathogenic frameshift variants in MEN1 p.I54fs*65 and p.D33fs*82 at variant allele frequency (VAF) of 53% and 42% respectively, TERT promoter (TERTp) variant [C228T (c.-124C>T)] at VAF of 44.8% and an NRAS p.Q61K variant at VAF of 39%. The two MEN1 variants were in trans to each other on opposite alleles, suggestive of a second-hit leading to a loss of biallelic function of MEN1.Conclusion: PTC in MEN1 has been rarely reported in the literature [1]. However, per our knowledge, this is the first report of a PTC with second-hit in the MEN1 gene. Somatic MEN1 pathogenic variants have been reported in occasional cases of thyroid oncocytic tumors and NRAS is more frequently associated with follicular or oncocytic thyroid tumors. Thus, whether this tumor should be regarded as a rare manifestation of the MEN1 syndrome is unclear. The histopathologic and molecular characteristics of thyroid tumors in MEN1 warrant further investigation. Reference: 1. Desai et al. Ann Surg Oncol 2001;8(4):342-6. Presentation Date: Saturday, June 17, 2023

Recurrence hyperparathyroidism caused by synchronous parathyroid carcinoma and parathyromatosis in a patient with long-term hemodialysis

BackgroundParathyroid carcinoma and parathyromatosis are very rare diseases in patients on hemodialysis. Its pathogenesis, clinical features, preoperative diagnosis, and surgery are challenging. We describe a rare case of recurrent hyperparathyroidism due to synchronous parathyroid carcinoma and parathyromatosis.Case presentationA 46-year-old Chinese woman was diagnosed with end-stage renal disease and received regular hemodialysis. Four years later, she experienced discomfort due to itching and was diagnosed with drug-resistant secondary hyperparathyroidism. Parathyroidectomy was performed, and her parathyroid hormone (PTH) levels were reduced. The pathology also revealed that the four nodules were parathyroid nodular hyperplasia without evidence of malignancy. Five years after surgery, the right subcutaneous nodule and left inferior nodule were detected by multiple imaging modalities, and the nodules were accompanied by recurrence itching and elevation of PHT. A complete resection of two nodules was performed, and the patient was diagnosed with parathyroid carcinoma and parathyromatosis. At 8 months postsurgery, her PHT and serum calcium levels were stable, and there were no signs of recurrence.ConclusionsThis is a rare case of synchronous parathyroid carcinoma and parathyromatosis in a patient with secondary hyperparathyroidism after parathyroidectomy. We suggest meticulous handling of parathyroid hyperplasia to avoid rupture and spillage during surgery, and precise pro-operation location by multiple imaging modalities is crucial for successful parathyroidectomy.

Parathyroid Retrospective Analysis of Neoplasms Incidence (pTRANI Study): An Italian Multicenter Study on Parathyroid Carcinoma and Atypical Parathyroid Tumour.

Parathyroid cancer (PC) is a rare sporadic or hereditary malignancy whose histologic features were redefined with the 2022 WHO classification. A total of 24 Italian institutions designed this multicenter study to specify PC incidence, describe its clinical, functional, and imaging characteristics and improve its differentiation from the atypical parathyroid tumour (APT). All relevant information was collected about PC and APT patients treated between 2009 and 2021. Among 8361 parathyroidectomies, 351 patients (mean age 59.0 ± 14.5; F = 210, 59.8%) were divided into the APT (n = 226, 2.8%) and PC group (n = 125, 1.5%). PC showed significantly higher rates (p < 0.05) of bone involvement, abdominal, and neurological symptoms than APT (48.8% vs. 35.0%, 17.6% vs. 7.1%, 13.6% vs. 5.3%, respectively). Ultrasound (US) diameter >3 cm (30.9% vs. 19.3%, p = 0.049) was significantly more common in the PC. A significantly higher frequency of local recurrences was observed in the PC (8.0% vs. 2.7%, p = 0.022). Mortality due to consequences of cancer or uncontrolled hyperparathyroidism was 3.3%. Symptomatic hyperparathyroidism, high PTH and albumin-corrected serum calcium values, and a US diameter >3 cm may be considered features differentiating PC from APT. 2022 WHO criteria did not impact the diagnosis.

Nanostructured Lipid Carrier of Cinacalcet HCl: Formulation, BBD Enabled Optimization, Pharmacokinetic and In-Vitro Cytotoxicity Study

Background: Cinacalcet hydrochloride (CINH) is a BCS class IV drug. It is mainly used for the treatment of chronic renal disease and parathyroid cancer. It exhibits poor oral bioavailabil-ity of less than 25%. Objectives: The main objective is to improve the bioavailability of CINH by formulating the nanostructure lipid carrier (NLC). Methods: In this research, glyceryl monostearate (GMS), labrasol, and tween 20 were the main ex-cipients selected for the formulation of NLC. Hot high-speed homogenization and ultra-sonication method was used for the NLC formulation of CINH. The characterization of the NLCs was done as per standard procedures. Optimization of the formulated NLC was carried out by applying Box-Behnken Design (BBD) with the help of the Design Expert software. The pharmacokinetic study was conducted to determine the improvement in the bioavailability of the CINH. The cytotoxicity study was performed by using the MTT assay method to know the cell viability. Results: The optimized NLC formulation exhibited high drug content with a particle size of less than 200nm. A pharmacokinetic study showed 4 fold increase in oral bioavailability for the opti-mized NLC in comparison to the aqueous suspension of CINH. Minimum viability was determined as 94%, which indicates the safety of the incubated formulations. Conclusion: NLC formulation has the potential to improve oral bioavailability with high drug load-ing and cell viability for CINH.

Primer Hiperparatiroidili Hastalarda Nodüler Guatr ve Papiller Tiroid Kanseri Birlikteliğinin Değerlendirilmesi

Aim: Primary hyperparathyroidism and differentiated thyroid carcinoma are the most common endocrinological diseases. Since its first definition in the 1950s, nodular goiter and differentiated thyroid carcinoma in patients with primary hyperparathyroidism have been examined in many studies and an increase in cancer incidence has been found. In this study, we aimed to investigate the co-incidence of nodular goiter and differentiated thyroid cancer in patients with primary hyperparathyroidism. Material and Methods: One hundred seventy-two patients who underwent parathyroid surgery in our hospital between 2012 and 2015 were included in this study. Demographic, clinic, and surgical data of the patients were reviewed retrospectively. Results: The mean age of the patients was 54.3±11.3 years and 85.5% (n=147) of them were female. Nodular goiter was observed at a rate of 61.0% (n=105) in preoperative evaluation. Parathyroidectomy was performed in 125 (72.7%) and simultaneous total thyroidectomy was performed in 32 (18.6%) and lobectomy in 15 (8.7%) of the patients. Histopathologically, 94.8% (n=163) were interpreted as adenoma, 2.9% (n=5) as parathyroid hyperplasia, and 2.3% (n=4) as parathyroid carcinoma. Patients with papillary thyroid carcinoma (n=30) and benign (n=17) histopathologically were compared in terms of clinical and laboratory characteristics, and no significant difference was observed in any parameter. Conclusion: There was no significant increase in thyroid nodularity, but a significant increase was found in differentiated thyroid carcinoma incidence in patients with primary hyperparathyroidism in this study in accordance with the literature. This finding highlights the importance of preoperative thyroid evaluation in this patient group.

Bilateral synchronous parathyroid carcinoma: a case report

El carcinoma de paratiroides (CP) es una neoplasia endocrina poco frecuente, ocurre con mayor frecuencia en pacientes con hiperparatiroidismo primario, con una incidencia del 0,5-4% de los pacientes tratados quirúrgicamente por hiperparatiroidismo primario. El diagnóstico de CP es difícil porque se superpone clínica, radiológica e histológicamente con adenoma/hiperplasia de paratiroides, se basa en la evidencia de invasión tisular local inequívoca y/o metástasis. El CP bilateral es anecdótico y el principal tratamiento es la resección quirúrgica.

Suspected parathyroid carcinoma: Clinical diagnosis of unique endocrine pathology

Parathyroid carcinoma is an extremely rare malignancy of the endocrine system with an incidence of 0.5 - 5% of patients with hyperparathyroidism worldwide. It typically presents with an indolent course, and manifestations of hyperparathyroidism usually appear well before local invasion