Parathyroid Adenoma Research Articles

SAT177 Molecular Analysis Of AMBRA1 As A Candidate Tumor Suppressor In Sporadic Parathyroid Adenomas

Abstract Disclosure: S. Chinwo: None. J. Costa: None. A. Arnold: None. J. Bellizzi: None. Primary hyperparathyroidism is a common endocrine disorder that is most often caused by a sporadic single-gland parathyroid adenoma. Currently, the only known and experimentally validated oncoprotein for parathyroid adenomas is cyclin D1. The overexpression of cyclin D1 protein has been reported in 20-40% of cases and about 8 percent of cases harbor a DNA rearrangement involving the cyclin D1 (CCND1) locus. Otherwise, the molecular mechanisms underlying this cyclin D1 overexpression have yet to be identified. Here, we explored a potential parathyroid tumorigenic mechanism that could increase cyclin D1 stability through a defect in the AMBRA1 E3 ligase adaptor, a molecule responsible for its degradation. Evidence that AMBRA1 may be a tumor suppressor gene includes the accumulation of cyclin D with hyperproliferation in AMBRA1-deficient cells, the context-dependent growth of tumors in Ambra1-deficient mice, and the finding that low levels of AMBRA1 correlated with poor clinical outcomes in The Cancer Genome Atlas. Therefore, we proceeded to examine AMBRA1 for evidence of tumor suppressor-type inactivation within a cohort of 98 typical parathyroid adenomas. Genomic DNA samples from these tumors were subjected to PCR-amplification of all 18 coding exons of AMBRA1, followed by Sanger sequencing. Sequences were analyzed by comparison to the normal reference sequence: ENST00000683756.1, seeking to assess any observed intragenic or splice-site variants as potential or likely loss-of-function mutations. Thus far, with 97 percent of the coding region for this 1298-amino acid protein fully sequenced, we have identified an inactivating mutation in 1 of the 98 tumors (1%): c.126G>A in exon 2, resulting in an early stop codon p.Trp42*. Sequencing the patient’s matched germline DNA confirmed the mutation was somatic and showed loss of heterozygosity. We also identified likely-nonpathogenic variants in 5 parathyroid adenomas: missense variant c.3385G>T (p.Ala1129Ser), 3’ UTR variants c.*576A>T and c.*491T>C and synonymous variants c.579C>T and c.2776C>T, each in a single tumor. 4 of 5 were found as germline variants in the normal population and the one missense scored benign by in silico criteria. To conclude, our observations suggest that AMBRA1 may function as a classical tumor suppressor gene in sporadic parathyroid adenomas at very low frequency. Further study may include protein expression analysis of AMBRA1 to investigate influences on gene expression. To further elucidate the mechanisms behind cyclin D1 overexpression in parathyroid adenomas, other molecules that participate in its degradation should be explored as potential tumor suppressors. Presentation: Saturday, June 17, 2023

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

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

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

SAT193 Double Trouble: A Case of Ipsilateral Double Parathyroid Adenoma

Abstract Disclosure: J.P. Suelto: None. G.D. Wassmer: None. Background: Eighty percent of the cases of Primary Hyperparathyroidism is caused by a single adenoma and only about 15% are multiglandular adenoma. Parathyroid imaging like Sestamibi is less sensitive in detecting multiglandular disease. Clinical Case: A 63 year-old female presented with intermittent left lower back pain for 7 years. There was no joint pain, weakness, urinary symptoms, constipation and abdominal pain. In 2019, due to persistence of left back pain, abdominal ultrasound done showed a right non-obstructing nephrolithiasis. Ionized and total calcium were elevated at 1.53 meq/L (NV 1.12-1.32 meq/L) and 11.35 ng/dl (NV 8.42-10.23 ng/dl) respectively with normal creatinine, phosphorus and albumin. PTH was elevated at 116.6 pg/ml (NV 10-65 pg/ml). Primary Hyperparathyroidism probably secondary to parathyroid adenoma was considered. Thyroid ultrasound showed right thyroid cyst but no enlarged parathyroid gland. Parathyroid imaging using Dual Isotope Subtraction Method neither showed evidence of adenoma. Patient was advised parathyroidectomy but did not consent hence started on Cinacalcet. In 2021, ionized calcium was still elevated to 1.58 meq/L with elevated PTH 151 pg/ml and low Vitamin D level 22.76 ng/ml (>30 ng/mL). Patient was given Vitamin D3 2000 IU daily and Cinacalcet was up-titrated to 60mg daily. Sestamibi/SPECT CT showed faint focus of radioactivity in the right thyroidal bed area suspicious for parathyroid adenoma or hyperplasia. She then agreed to have parathyroidectomy. There was no decrease in PTH after removal of the right inferior parathyroid gland (measuring 1.8x0.6x0.6cm, weighs 500mg), hence re-exploration was done. It was only after the removal of the right superior parathyroid gland (measuring 2.8x0.9x0.7cm, weighs 1 gram) when the 5 and 10 minute post excision PTH decreased to 123.91 and 76.01 pg/ml respectively from preincision PTH of 407.19 pg/ml. Histopathology showed Parathyroid adenoma of right inferior and superior parathyroid glands. No further evidence of hypercalcemia was noted at 6-month follow-up. Conclusion: Double adenoma is reported in 2% to 12% of patients with primary hyperparathyroidism. This occurs predominantly as bilateral superior in 45% and on same side of the neck in 18%. Sestamibi scanning is poor in the presence of multiglandular disease. It was observed that the presence of oxyphil cells may cause longer sestamibi retention in parathyroid tissues. Given the same amount of oxyphil cells in ipsilateral adenomas, the tracer may be distributed hence faintly seen on imaging. Addition of SPECT/CT/4D CT may improve the anatomical localization. Another reason for false negative imaging in this patient can be due to use of Cinacalcet which may decrease scintigraphy uptake of parathyroid adenoma. The combination of preoperative imaging localization and intraoperative PTH monitoring permits successful surgical outcome. Presentation: Saturday, June 17, 2023

FRI691 Intrathyroidal Parathyroid Adenoma With Congenitally Absent Contralateral Thyroid Lobe Treated With Thermal Ablation

Abstract Disclosure: L. Bilandzic: None. L. Bilandzic: None. H. Korkusuz: None. We present a rare case of primary hyperthyroidism with ectopic adenoma located in the right thyroid lobe with congenitally absent left thyroid lobe which was treated with thermal ablation. A 60-year-old woman was referred to endocrinology clinic for further evaluation of her elevated total serum calcium of 11.4 mg/dL (reference range 8.5-10.5), elevated parathyroid hormone (PTH) level of 106 (10-60 pg/mL). Bone mineral densitometry showed a total T score of -2.9 in L1-L4. Other results were vitamin D 25-OH 30 ng/mL (ref. range 30 - 100), TSH 3.36 µIU/mL (ref range 0.4-5.0), eGFR 83 (normal > 59 mL/min/ 1.73 m²). She was asymptomatic and had no history of kidney stones. Other causes of hypercalcemia were refuted. Given the osteoporosis in her lumbar spine, parathyroid localization and surgery were suggested. Thyroid and parathyroid sonography demonstrated a solid hypoechoic nodule in the right thyroid lobe, 12x10x11mm, with smooth margins, no calcifications, classified as ACR TI-RADS T4. Left thyroid lobe was not appreciated and was considered to be congenitally absent since the patient did not have a history of a previous thyroid resection. Further localization studies (99mTc Sestamibi parathyroid scintigraphy and 4D-CT of the neck) did not reveal any other possible candidates for parathyroid adenomas. Eventually, a fine needle aspiration of the nodule in the right thyroid lobe was performed. PTH needle wash showed a PTH value of 633 pg/mL whereas the PTH value ≥ 100 pg/mL is suggestive of the presence of PTH secreting tissue. Given the thyroid anatomy found with this patient, a right lobe hemithyroidectomy would result with a permanent substitution dependent hypothyroidism. As an alternative, thermal ablation was presented as a treatment option for which the patient opted. She underwent the procedure in local anesthesia. Sonographic imaging of the adenoma was followed by the percutaneous insertion of the coagulation electrode. The utilized high frequency ablator was used with an output of 9 to 40 W and a frequency of 470 ± 10 kHz. There were no complications developed during or after the procedure. Two weeks after the thermal ablation, PTH level was measured at 55 pg/mL, total serum calcium at 9.5 mg/dL, TSH 1.01 µIU/mL. Sonography showed a hyperechoic nodule at the former location of the parathyroid adenoma, which was evaluated as a scar tissue. Three months after the procedure total calcium was at 9.3 mg/dL, PTH at 58 pg/mL, hence no biochemical evidence of pHPT. This is a rare case of ectopic parathyroid adenoma located in the thyroid gland with hemi agenesis of the contralateral lobe. A minimally invasive thermal ablation was performed with the goal of inactivation of the adenoma and preserving the euthyroid function. Presentation: Friday, June 16, 2023

SAT186 Young Patient With Primary Hyperparathyroidism And Mutation Of CDKN1B Gene MEN 4 Variant

Abstract Disclosure: J.J. Faria Briceno: None. S.S. Jande: None. T. Lairmore: None. R.R. Yatavelli: None. Background: Parathyroid adenomas are the most common cause of primary hyperparathyroidism (PHPT)accounting for 80-85% of the cases. PHPT most commonly manifests between 50-60 years of age and when it presents at younger age, it can be associated with inherited genetic conditions like multiple endocrine neoplasia or Hyperparathyroid Jaw tumor syndrome. Clinical Case: A 34-year-old male without significant past medical history was noted to have elevated serum calcium on routine lab work and was advised to promptly go to the emergency room for further evaluation. In the ED, the patient’s corrected calcium was 13.8 mg/dL (normal range 8.7 - 10.5 mg/dL), ionized calcium elevated at 1.77 mmol/L (normal range 0.90 - 1.20 mmol/L), PTH was 786.2 pg/mL (normal range 9 - 77 pg/mL). The patient denied any history of fractures, kidney stones or bone pain. Patient was treated medically with IV fluids and calcium lowering agents. Given the elevated PTH, ultrasonography of the neck was done which revealed an oval, hypoechoic lesion measuring 1.2 x 2.25 cm with increased vascular flow posterior to the right thyroid lobe consistent with parathyroid adenoma. Parathyroidectomy was performed with excision of right inferior parathyroid adenoma measuring 2.7 x 1.2 x 0.6 cm (1.25 grams). The preoperative PTH level was 997.7 pg/mL, which rapidly improved 20 minutes post tumor excision to 75.9 pg/mL, a 90% fall in PTH level suggestive of successful tumor excision. The patient’s post-operative period was uneventful. Considering the very young age of presentation; hyperparathyroidism genetic panel was obtained to rule out any inherited conditions like MEN1 or Hyperparathyroid Jaw tumor syndrome. Genetic testing revealed a germline missense mutation in CKDN1B (variant c.287C &gt, heterozygous) and classified as Variant of Uncertain significance). Mutations in the cyclic dependence kinase inhibitor 1B (CDKN1B) have been identified as the culprit for tumor growth seen in multiple endocrine neoplasia 4. MEN4 is a rare autosomal dominant endocrine tumor syndrome characterized by hyperparathyroidism and pituitary adenomas. The variant described in our patient has classically not been associated with other tumors and the available evidence is currently insufficient to determine the role of this variant in disease and hence classified as Variant of Uncertain Significance. Conclusion: Genetic testing should be considered in patients with primary hyperparathyroidism who present at very young age or have multiglandular disease. Our patient does not have any other classic features of MEN 4 and as the genetic mutation is classified as Variant of Uncertain Significance, patient would be monitored clinically, and caution exercised before using this result to inform clinical management decisions. Presentation: Saturday, June 17, 2023

SAT573 Incidental Discovery Of CHEK2 Mutation With Papillary Thyroid Cancer

Abstract Disclosure: F.L. Thelmo: None. A. Mehrab: None. S.A. Jabbour: None. A 66-year-old white male had been following steadily with our practice for greater than a decade where we were managing his post-ablative hypothyroidism from toxic multinodular goiter 20 years prior. Many years later, the patient developed hypercalcemia and was found to have asymptomatic primary hyperparathyroidism. He did not meet any indication for parathyroidectomy. In early January 2021, the patient was referred to a clinical geneticist at the behest of his wife as she was concerned that he had a very high rate of cancer in his family. The patient had a total of 11 relatives who either currently had or previously died from a malignancy, of which only one of them was on his maternal side. The patient’s father had a personal history of breast cancer, prostate cancer, and bone cancer at the time he passed away. The patient underwent a full panel of genetic testing and was found to be positive for a CHEK2 (Checkpoint Kinase 2) mutation. Around this time, the patient’s hypercalcemia escalated up to 13mg/dL without evidence of hypoalbuminemia. Decision was made to pursue surgery. In order to localize the parathyroid adenoma, a technetium sestamibi scan and a neck ultrasound were obtained. Sestamibi scan showed increased parathyroid adenomatous activity in the left lower portion of the thyroid bed and ultrasound confirmed the left lower pole parathyroid adenoma with a dominant hypoechoic 2.5cm TI-RADS 5 thyroid nodule which on biopsy was suspicious for papillary thyroid carcinoma. The patient underwent a total thyroidectomy in addition to the parathyroidectomy. Pathological evaluation confirmed a parathyroid adenoma and a classic variant of papillary thyroid carcinoma without angioinvasion and minimal extrathyroidal invasion classified as Stage 1 T2N0M0. The patient did not meet criteria for treatment with radioactive iodine and at the time of this writing is doing well, on levothyroxine with low-normal TSH and undetectable thyroglobulin with normal serum calcium. He has no other signs of malignancy at this time. However, given his CHEK2 mutation, he will require ongoing multi-disciplinary cancer surveillance. We would like to draw attention to this not uncommon oncogenic mutation that due to its incomplete penetrance does not always present such a staggering family history of cancer and thus may go undetected. CHEK2 mutations occur in roughly 1% of all individuals who undergo genetic evaluation for cancer. The mutation moderately increases the patient and their family’s risk for multiple malignancies including: breast, thyroid, prostate, stomach, kidney, and plasma cell malignancies. Individuals with this mutation should be screened thoroughly by a multi-disciplinary team based on the severity of their inherited mutation. These individuals should also receive counseling on family planning if conception is desired. Presentation: Saturday, June 17, 2023

SAT205 99Technitiumm Sestamibi Negative Sporadic Metastatic Parathyroid Carcinoma In A Young Female-A Diagnostic Conundrum

Abstract Disclosure: D.V. Reddy: None. S. Paidipally: None. V. kyatham: None. S. Palle: None. C. Bhandiwad: None. Background: Parathyroid carcinoma (PC) is a very rare and indolent endocrine malignancy occurring a decade earlier than parathyroid adenoma. It can present as recurrent pancreatitis, anemia, and peptic ulcers. Serum calcium >14mg/dl, 3-10 times ULN of PTH, and concomitant renal and bone involvement should arise suspicion for PC. PC is diagnosed only through histopathology in the majority. It can also present during a prolonged follow-up, either by local recurrences or distant metastases. Clinical Case: A 27 year old female presented with hypercalcemic crises (as pancreatitis). At admission serum calcium and PTH were grossly elevated; 15.1 mg/dl (8.5-10 mg/dl) and 363 pg/ml (10-55 pg/ml) respectively. Abdominal CT revealed acute pancreatitis with medullary nephrocalcinosis. Ultrasonography of the neck revealed a colloid cyst in the right lobe of thyroid.99Tc m-sestamibi /SPECT-CT revealed no uptake. CT neck and chest showed a 13 mm X 13 mm well-defined round nodular lesion in the left apico-posterior segments of the lung. 18F-FDG PET/CT revealed uptake in the lesion with an SUV max of 10, suggestive of a metabolically active solitary pulmonary nodule. She had a similar presentation 8 years back and was diagnosed to have parathyroid adenoma for which she underwent resection. Serum PTH and calcium levels normalized postoperatively and also on follow-up till 3 years. Differentials include-recurrent ectopic parathyroid adenoma, parathyromatosis, and metastatic parathyroid carcinoma. After managing hypercalcemia medically, the patient underwent video-assisted thoracoscopic surgery with left lung wedge resection. Postoperatively serum calcium and PTH normalized. Histopathology revealed a grey-white nodule of 1.4X1.5X1.2 cm with sections, showing a well-defined lesion composed of lobules and nests of tumor cells separated by thin-walled vascular sinusoids. Tumor cells were polygonal with well-defined margins, moderate granular cytoplasm, and vesicular nuclei showing prominent nucleoli with a mitotic activity of 9/hpf. Immunohistochemistry revealed staining with PanCK, GATA3, and S100 with focal PAX 8 activity in the periphery. MIB index was 18%.IHC was suggestive of a neuroendocrine tumor consistent with metastatic parathyroid carcinoma. Whole exome sequencing did not reveal any pathogenic variants. Conclusion: Though 99Tc MIBI is useful in localizing PC, there are reports of false negative MIBI in documented cases of PC, which has been ascribed to the defective transport to the interior of the malignant cells. This demonstrates the importance of a multimodality imaging approach in such cases. 99Tc MIBI may miss certain cases of PC substantiating the importance of 18F-FDG PET/CT in diagnosis as well as follow-up. Reference: Evangelista L et al. FDG-PET/CT and parathyroid carcinoma: Review of literature and illustrative case series. World J Clin Oncol 2011; 2(10): 348-354. Presentation: Saturday, June 17, 2023

SAT567 Collision Tumor Of The Thyroid With Papillary Thyroid Carcinoma And Metastatic Renal Clear Cell Carcinoma With Concomitant Parathyroid Adenoma

Abstract Disclosure: C.M. Mirano: None. R.C. Mirasol: None. INTRODUCTION Collision tumors of the thyroid are rare diseases that have two or more histologically and morphologically distinct tumors that occur simultaneously within the thyroid. There are only a few reported cases of collision tumors involving a metastasis from a distant tumor and a papillary thyroid cancer. In addition, the coexistence of Primary Hyperparathyroidism (PHPT) with nonmedullary thyroid cancers is unusual with an incidence range between 2 to 24%. Here, we describe an unusual case of a patient with Papillary Thyroid Carcinoma and Metastatic Renal Clear Cell Carcinoma complicated with a Parathyroid Adenoma. CASE The patient is a 65 year-old female, known Renal Clear Cell Carcinoma Stage IV who underwent left nephrectomy, distal pancreatectomy splenectomy, and adjuvant chemotherapy. She then developed subclinical hyperthyroidism with bilateral thyroid nodules on ultrasound 13 years post nephrectomy. Thyroid Scintigraphy showed hypofunctioning nodules on both lobes. Biopsy of the thyroid nodules was done on showing a Metastatic Renal Cell Carcinoma. Laboratory tests also showed hypercalcemia and an elevated iPTH. SPECT-CT images showed uptake in the left thyroid suggestive of a parathyroid adenoma. She underwent four gland exploration with parathyroidectomy. Intraoperatively, pre-excision PTH assay extracted peripherally was 386.10 pg/mL. The right superior, right inferior, and left superior parathyroid gland were normal in size. The left inferior parathyroid gland was found to be enlarged measuring 2.5 x 2.0 cm, intrathyroidal in location and was encapsulated. The left inferior parathyroid was dissected and sent for histopathology. 10 minutes post excision PTH levels declined by 57%. After which, total thyroidectomy was done with note of a 2.5 x 2 cm firm mass at the right thyroid lobe slightly adherent to strap muscles. The left thyroid lobe had no palpable nodules, Histopathology of the thyroid isthmus showed one focus of follicular cells exhibiting nuclear changes consistent with papillary thyroid carcinoma. Microsections of the right thyroid lobe show a malignant neoplasm composed of atypical cells arranged in sheets that have enlarged, hyperchromatic to vesicular, pleomorphic, prominent nucleoli, irregular nuclear border, and clear cytoplasm consistent with metastatic clear cell carcinoma. Histopathology of the Left inferior parathyroid gland revealed findings consistent with Parathyroid Adenoma. She was discharged stable with normal calcium levels. CONCLUSION Collision tumors are rare and an adequate histologic assessment of these tumors are important for decisions regarding management. Differentials with patients with nodular goiter should always include metastatic disease in the background of an underlying carcinoma. It is equally important to be aware of concomitant PHPT and thyroid diseases in the management of patients with hypercalcemia. Presentation: Saturday, June 17, 2023

THU396 Digital Spatial Profiling Of Human Parathyroid Tumors Reveals Distinct Cellular And Molecular Alterations Linked To Vitamin D Deficiency

Abstract Disclosure: C. Tu: None. W. Chang: None. J.A. Sosa: Advisory Board Member; Self; Novo Nordisk, AstraZeneca, Eli Lilly & Company. Grant Recipient; Self; Exelixis, Inc., Eli Lilly & Company. J. Koh: None. Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population, but the pathophysiological basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from 9 vitamin D-deficient or 34 vitamin D-replete PHPT patients with 12 eucalcemic cadaveric donor parathyroid glands as normal tissue controls. Parathyroid oxyphil cell content is markedly higher in tumors from vitamin D-deficient PHPT patients (Def-Ts) relative to tumors from vitamin D-replete PHPT patients (Rep-Ts) (47.8% vs 17.8%, respectively; p <0.0001) and normal donor parathyroid glands (7.7%). Def-Ts display increased expression of genes encoding electron transport chain (corr. coefficient=0.546), proteasomal catabolism (corr. coefficient=0.587), and oxidative phosphorylation (corr. coefficient=0.982) pathway components. In contrast, Rep-Ts are characterized by upregulation of the ras (corr. coefficient=0.632) and myc (corr. coefficient=0.811) signaling pathways, suggestive of an oncogene-driven etiology. Parathyroid oxyphil cells are comparable to chief cells at the transcriptional level, and vitamin D-status is reflected in the transcriptional profiles of both cell types in a similar manner. Among PHPT patients who did not present as vitamin D deficient, three distinct tumor transcriptional profile clusters showed a dose-dependent relationship to pre-operative 25OHD levels (p <0.0001 by ANOVA). Relative to normal tissue, the abundance of calcium sensing receptor (CaSR) protein is reduced in Def-Ts (mean protein count 253.6 vs 492.3, respectively; p=0.039 for difference), while the type B γ-aminobutyric acid receptor 1 (GABAB1R) is increased (mean protein count 114.5 vs 64.65, respectively; p=0.0099 for difference). These expression changes resulted in a vitamin D dose-dependent reduction in the ratio of CaSR to GABAB1R receptors in Def-T tumor cells (r2 = 0.218, p<0.0001), favoring the formation of calcium sensing-attenuated CaSR:GABAB1R heteromers. The abundance of the amyloid precursor protein (APP) peptide derivative Aβ1-42, a putative GABAB1R ligand, is preferentially increased in Def-Ts compared to normal tissue (mean protein count 5797 vs 4500, respectively; p=0.0318). Collectively, these findings suggest a novel mechanism where chronic vitamin D deficiency can contribute to tonic PTH hypersecretion in PHPT patients by increasing GABAB1R-mediated antagonism of CaSR activity in parathyroid adenomas. Presentation: Thursday, June 15, 2023

SAT198 Parathyroid Adenoma Masquerading As A Thyroid Nodule

Abstract Disclosure: A. Arida: None. M. Papaleontiou: None. N. Esfandiari: None. Background: The diagnosis of parathyroid adenomas using a neck ultrasound (US) can be challenging when not performed by an experienced radiologist. Additional methods of diagnosis have been implemented to distinguish the differential diagnosis of a nodule in the neck. Clinical Case: A 48-year-old woman with a history of type 2 diabetes, hypercalcemia, and kidney stones presented for evaluation of a lump in the neck of 5 years duration. Prior thyroid US showed a solid hypoechoic nodule superior to the left thyroid lobe measuring 2.2 x 1.2 x 1.1 cm with hypervascularity. Her first FNA biopsy of this nodule reported benign cytology 5 years ago. A parathyroid scintigraphy scan was negative. Repeat FNA biopsy of this nodule showed follicular lesion of undetermined significance (Bethesda category III). Surgical consultation was recommended but she decided to seek a second opinion. A repeat neck US identified a solid vascular 1.6 cm nodule along the anterior margin of the superior left thyroid lobe. Some vascularity was extending from the thyroid tissue into the nodule. It was noted that this may represent an extrathyroidal nodule or arise from the thyroid gland with a score of TIRADS 4. Laboratory tests confirmed primary hyperparathyroidism with an iPTH of 126 pg/mL (normal range, 10-65 pg/mL) and serum calcium of 10.9 mg/dL (normal range, 8.6-10.3 mg/dL). After normalizing vitamin D levels, these values remained elevated. A repeat FNA biopsy of this nodule showed evidence of intrathyroidal parathyroid tissue. Immunostains were performed on the cell block material from the FNA biopsy. Scattered groups of cells were positive for PTH while being negative for TTF-1. Further needle washout for iPTH measurement revealed an iPTH >2000 pg/mL confirming the diagnosis of a parathyroid adenoma. Parathyroid surgery was recommended as per guidelines. Discussion: Once primary hyperparathyroidism is confirmed, the localization of parathyroid adenoma is pursued by a neck US and/or parathyroid scintigraphy. Parathyroid glands are located in the superior poles and in the inferior poles of the thyroid gland but ectopic locations like retropharyngeal, intrathyroidal, and mediastinal are possible. Typical US appearance is oval, solid, well-circumscribed, homogenous, and hypoechoic compared to the thyroid tissue. The color Doppler shows that the blood supply enters at the center and distributes peripherally presenting a “vascular arch” pattern that helps differentiate them from other lesions such as tumors or lymph nodes where the distribution is more centralized. Further needle washout for PTH level can confirm the diagnosis of parathyroid adenoma. Once a parathyroid adenoma is confirmed, minimally invasive parathyroid surgery can be recommended if surgery is indicated. Conclusion: A needle washout for measuring PTH in an FNA biopsy sample should be recommended when it is unclear whether a nodule is a thyroid nodule or a parathyroid adenoma. 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

SAT207 Parathyroid Carcinoma: A Case Report

Abstract Disclosure: K.T. Sy: None. Background: Parathyroid carcinoma is a rare malignancy, accounting for less than 1% of causes of primary hyperparathyroidism. Case reports have mentioned of parathyroid carcinoma arising in patients with prior neck irradiation, in secondary and tertiary hyperparathyroidism and in patients with history of thyroid cancer and parathyroid adenoma. However, none of these reported associations have been completely established. Clinical Case: The is a case of a 59-year old male presenting with hypercalcemia. He was diagnosed with primary hyperparathyroidism secondary to a parathyroid adenoma, underwent parathyroidectomy with resolution of the hypercalcemia. Six years later, patient had recurrence of hypercalcemia with elevated PTH levels. Parathyroid imaging revealed a mild sestamibi-avid focus in the left retrosternal region, suggestive of an ectopic parathyroid gland and radio-guided neck exploration was done with excision of lesion. Histopathological report revealed parathyroid carcinoma. Two years later, there was recurrence of parathyroid carcinoma but mediastinal exploration revealed no lesions consistent with parathyroid carcinoma. Hypercalcemia with hyperparathyroidism persisted, and cinacalet was started but the patient could not tolerate the nausea associated with the medication. Repeat parathyroid imaging revealed sestamibi-avid lesions in the right retroclavicular, left prevascular/retrosternal, and a left paratracheal areas. Surgical exploration was offered but the patient refused. The patient also developed hypertension and low bone density was noted on dual X-ray absorptiometry (DXA) scan. He was started on denosumab 60 mg subcutaneously every 6 months, which was increased to 60mg every month and then 120mg every month to maintain normal calcium levels. The patient also developed chronic kidney disease, eventually requiring hemodialysis for elevated creatinine levels and hypercalcemic crisis. Soon after hemodialysis was started, the patient had a myocardial infarction and eventually expired. Conclusion: Complete surgical resection is the primary mode of therapy in parathyroid carcinoma, although hypercalcemia is the main cause of morbidity and mortality, rather than the tumor burden. The adjuvant use of radiotherapy and chemotherapy are still controversial. Some studies have shown that long term survival is favorable, but recurrences are frequent and patients tend to live a life filled with long-term follow up, multiple laboratory exams and imaging, hospitalizations and frequent reoperations. Mortality is usually due to uncontrollable hypercalcemia, leading to renal failure and cardiac arrhythmias. Presentation: Saturday, June 17, 2023

SAT191 Primary Hyperparathyroidism With Low-Normal Parathyroid Hormone Levels: Phosphorus Can Be The Key

Abstract Disclosure: D. He: None. T. Tavdy: None. Y. Tomer: None. D. Kalbi: None. V. Tabatabaie: None. Background: Primary hyperparathyroidism (PHPT) is characterized by the inappropriate secretion of PTH that leads to hypercalcemia. In patients with PHPT, 80-90% have PTH levels above the normal range and 10-20% have inappropriately “normal” PTH levels, most often in the high-normal range1. PTH levels below or in the lower end of the normal range prompt investigation of non-PTH mediated causes of hypercalcemia. We present a case of PHPT with low-normal PTH levels, and discuss how phosphorus levels guided our diagnosis of an underlying parathyroid adenoma. Clinical Case: An 83-year-old woman was found to have hypercalcemia with corrected calcium ∼13 mg/dL (8.5 - 10.5 mg/dL) and PTH of 36.7 pg/mL (20.0 - 80.0 pg/mL). Phosphorus was consistently low, ranging from 2.1 to 2.4 mg/dL (2.5 - 4.5 mg/dL). PTHrP was 18 pg/mL (11-20 pg/mL). 25-hydroxy vitamin D was 24.5 ng/mL (30-60 ng/mL). 1,25-dihydroxy vitamin D was 36 pg/mL (18-72 pg/mL). Serum and urine protein electrophoresis were normal. HTLV-1/2 antibody was negative. TSH was 1.15 uU/mL (0.30 - 4.20 uU/mL). The patient had no history of ingesting lithium or thiazide diuretics. Suspecting PHPT, the patient underwent a nuclear medicine parathyroid scan which showed abnormal parathyroid tissue in the left thyroid lobe. In the setting of volume overload, management of the patient’s persistent hypercalcemia of greater than 12 mg/dL (8.5 - 10.5 mg/dL) began initially with a dose of pamidronate 60 mg and gentle hydration followed by furosemide. Corrected calcium improved to 12.3 mg/dL (8.5 - 10.5 mg/dL). Given the patient’s decreased functional status (bedbound) and high surgical risk, after discussion with the patient and her family, a decision was made to proceed with medical management and not with parathyroidectomy. She was treated with cinacalcet 30 mg twice daily. The goal calcium of < 1 unit over the upper limit of normal (11.5 mg/dL) was achieved on day of discharge of the patient back to her nursing home. Conclusion: In patients with hypercalcemia, low serum phosphorus can point to a PTH- or PTHrP-mediated process. Inappropriate secretion of PTH or PTHrP results in high serum calcium and low phosphorus levels by increasing bone resorption and renal calcium reabsorption, and decreasing renal phosphorus reabsorption. This case shows that in patients with hypercalcemia and concomitant hypophosphatemia with normal PTHrP, PHPT should still be considered as a potential etiology, even in the setting of a low-normal PTH level. In our patient, the presence of a parathyroid adenoma was demonstrated with a conclusive parathyroid scan.

SAT208 Hypercalcemic Crisis In Metastatic Parathyroid Carcinoma: An Unusual Presentation Of A Rare Endocrine Disease

Abstract Disclosure: A. Barnett: None. T. Sliker: None. R.J. Harper: None. G. Elshimy: None. Introduction: Hypercalcemia can be life-threatening with a wide differential, including parathyroid carcinoma (PC), which accounts for only 0.005% of all malignancies in the U.S. Maintaining an index of suspicion for PC in PTH-mediated hypercalcemia is vital for improving long-term survival and outcomes. Frozen section can be misleading when PC is suspected. We describe a case of hypercalcemia due to recurrent metastatic PC 9 years after initial diagnosis. Case: A 57-year-old male presented for endophthalmitis and altered mentation. Records revealed primary hyperparathyroidism with calcium 11.7 mg/dL, PTH 337 (11.1-79.5pg/mL), and 24-hour urine calcium 810 mg/day. Sestamibi showed right lower parathyroid adenoma and a possible right upper parathyroid adenoma. Right superior parathyroidectomy revealed PC invasive into adipose tissue, increased vascularity and positive margins. A hemithyroidectomy and central neck dissection was performed with intraoperative report noting normal-appearing right inferior parathyroid affixed to thyroid, confirmed by frozen section biopsy. The right inferior parathyroid was minced and re-implanted into the right strap muscle. Patient did not return for follow-up. Recent admission labs showed calcium 15.2 mg/dL, ionized calcium 6.8 (4.5-5.3mg/dL), PTH 546 pg/mL, creatinine 1.54 mg/dL, 25-OH vitamin D 21.64 ng/mL, and phosphorus 1.9 mg/dL. He was treated with intravenous fluids, zoledronic acid, and calcitonin. Due to a high suspicion of locally recurrent or metastatic PC, further imaging obtained. A Neck CT and US showed no abnormalities of right surgical bed or cervical lymphadenopathy. Sestamibi revealed a right lower lung lobe nodule, measuring 2.3cm, with intense immediate and delayed uptake concerning for metastatic or primary lung neoplasm and mild focal retention in the right paratracheal region, suspicious for tumor recurrence. PTHrP was negative. He underwent video-assisted thoracoscopic right lower lobectomy that showed an ovoid, well-circumscribed 2.5 x 2.3 x 2.3cm tumor, which stained positive for PAX-8 and synaptophysin, consistent with PC. Discussion: Clinicians should suspect PC in cases with severe hypercalcemia or absolute PTH above 500mg/dL to allow for better surgical planning. Complete en bloc resection is the standard treatment to improve long-term outcomes and reduce disease recurrence. Diagnosis of PC following incomplete surgical resection has increased recurrence rates of greater than 50%. Our patient’s recurrence was 9 years after diagnosis, but most recurrences occur within 2-3 years and occasionally more than 20 years later. The ipsilateral parathyroid was re-implanted based on frozen section results in this patient, which may have been misleading. Frozen sections of parathyroid tissue are notoriously difficult to distinguish normal parathyroid versus PC and only diagnostic in 15% of cases as described in one case series. To reduce the risk of recurrent disease, physicians shouldn’t entirely depend on these results when there is high suspicion for PC. Presentation: Saturday, June 17, 2023

SAT189 Giant Parathyroid Adenoma

Abstract Disclosure: S. Shah: None. P. Fujikawa: None. Parathyroid adenomas rarely weigh more than 4 grams. Our patient had a 5.3gram adenoma causing bilateral knee pain limiting mobility, constipation, low back pain, and frontal headache. Presenting with calcium of greater than 17 mg/dL, patient was treated with 2 rounds of hemodialysis, calcitonin, Zoledronate, and aggressive IV hydration to decrease calcium levels prior to parathyroidectomy. Patient then went onto develop Hungry bone syndrome which was treated with calcium carbonate and calcitriol. This rare giant parathyroid adenoma presents a unique opportunity to learn about pathogenesis and treatment of longstanding hyperparathyroidism causing hypercalcemia associated symptoms and hungry bone syndrome after parathyroidectomy. Presentation: Saturday, June 17, 2023

SAT200 A Case Of Ectopic Parathyroid Adenoma With Significantly Improved Renal Function And Insulin Resistance After Parathyroidectomy

Abstract Disclosure: S. Lee: None. H. Ppyun: None. Y. Shin: None. N. Hong: None. H. Choi: None. Background: It is challenging to treat patients with clinically suspected hyperparathyroidism not localized by conventional imaging methods. Here, we present clinical evidence that supports new modalities for localization and ultimate surgical removal of a lesion. Clinical case: An increase in calcium and PTH was found incidentally in a 59 YO male patient who was followed up for type 2 diabetes mellitus and DMCKD (stage 4). Initial lab tests were as follows: Ca, 11.6 mg/dL (8.2∼10.8); P 3.3 mg/dL (2.5∼4.7); PTH 184.1 pg/mL (18.5∼88.0); BUN/Cr 4.84/3.38 mg/dL (8∼22/0.5∼1.2); protein in random urine 1020.1 mg/dL (6∼20). Suspected of primary hyperparathyroidism, ultrasonography and sestamibi scan were performed, but no parathyroid lesions were found. While only palliative treatment was maintained, parathyroid venous sampling (PVS) (1) and 18-fluorocholine PET/CT (2) were performed, and a mass within 2 cm in diameter was found in the left mediastinum, which was then removed by thoracoscopic robotic excision. Diffuse weak staining for PTH in the removed lesion confirmed that it was a tissue derived from the parathyroid gland. After surgery, lab tests were improved as follows: Ca 9.1 mg/dL; P 3.6 mg/dL; PTH 69 pg/mL. When 90 units of insulin were administered before surgery, HbA1c was 8.7%, but even after insulin was reduced to 15 units post-surgery HbA1c decreased to 7.2%, significantly reducing the need for insulin treatment. Proteinuria also decreased to 123.1 mg/dL, indicating that renal function was also improved. Conclusion: This case highlights the merit of newly introduced 18-fluorocholine PET/CT and PVS to find a parathyroid lesion that could not be found by conventional imaging methods. It is recommended to consider active surgical treatment for hyperparathyroidism, mainly to prevent deterioration of bone health and kidney function. In addition, since concurrent diabetes can be improved by parathyroidectomy (3), this case shows the need to more actively find lesions and take a causal approach. Reference: (1) Yamada T, Ikuno M, Shinjo Y, Hiroishi A, Matsushita S, Morimoto T, et al. Selective venous sampling for primary hyperparathyroidism: how to perform an examination and interpret the results with reference to thyroid vein anatomy. Jpn. J. Radiol. 2017;35:409-16. (2) Marina Orevi 1, Nanette Freedman, Eyal Mishani, Moshe Bocher, Orit Jacobson, Yodphat Krausz. Localization of parathyroid adenoma by ¹¹C-choline PET/CT: preliminary results. Clin. Nucl. Med. 2014;39:1033-8 (3) Noghani SN, Milani N, Afkhamizadeh M, Kabiri M, Bonakdaran S, Vazifeh-Mostaan L, et al. Assessment of insulin resistance in patients with primary hyperparathyroidism before and after Parathyroidectomy. Endocrinol Diab Metab. 2021;4:e00294. 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

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

SAT230 A Case Of Pseudohypoparathyroidism Without Any Hereditary Features

Abstract Disclosure: I. Haque: None. L.A. Robles: None. Background: Pseudohypoparathyroidism (PHP) refers to a heterogeneous group of disorders characterized by resistance to parathyroid hormone. PHP type Ib is characterized clinically by isolated renal PTH resistance manifesting as hypocalcemia, hyperphosphatemia, and increased serum PTH. About 60-70% of patients also present with elevated TSH levels due to TSH resistance. We present a unique case of adult onset PHP. Clinical Case: A 30-year-old woman admitted to the hospital for recent onset recurrent hypocalcemia with symptoms of weakness, muscle spasm and cramps. Until recently she was in a normal state of health. Admission labs revealed ionized calcium 0.78 (1.15 - 1.30 MM/L) , serum Ca 6.2 (Albumin 4.3). PTH elevated to 364. Creatinine 0.54 mg/dl, GFR 131 ml/min. Vit D level 35, Bone ALP 49.3 (premenopausal female :4.5-16.9 UG/L), Mag 1.9 , Ph 6.6. A 24-hour urine collection for Ca showed a value of 14 mg/24hr (50 - 400 MG/24H). Additionally, she was found to have a TSH <0.01 and Free T4 1.1. These labs confirmed PTH-resistant hypocalcemia and hyperphosphatemia with concurrent hyperthyroidism. Thyroid Ultrasound demonstrated a possible parathyroid adenoma on the left measuring 0.8x0.4x0.7 cm, which we suspect was a result of hyperplasia from PTH hypersecretion secondary to PTH resistance. TSI and TRAB antibodies were later found to be positive confirming grave’s hyperthyroidism. She had a similar presentation about 3 months earlier with symptomatic hypocalcemia and was discharged on Calcitriol, Ca CO3, and Cholecalciferol. Prior to this including through childhood, patient denies symptoms or lab abnormalities. Patients’ physical exam shows a height of 5ft 4-inch, weight 78kg, BMI 29.7. She had no abnormal facial features or skeletal/digit abnormalities. Patient reached all physical and cognitive milestones at expected times through childhood. Her calcium supplementation was adjusted to calcium carbonate 2000 mg every 8 hours, calcitriol 1 mcg twice daily, cholecalciferol 1000 units daily. Her total calcium improved to 7.4, ionized calcium improved to 0.93, phosphorus remained elevated at 6.1. Patient was discharged at her will due to personal social commitment. She was also started on Methimazole 5mg daily on discharge. Follow up labs showed Ca remained stable and eventually normalized on the above Ca supplementation 6 months after discharge. Conclusion: Unlike PHP Ia, patients with PHP Ib usually lack the physical characteristics of Albright hereditary osteodystrophy (round facies, short stature, short metacarpal bones (especially III-V), obesity, subcutaneous calcifications, and developmental delay), and typically show no other endocrine abnormalities, although our patient presented with subclinical hyperthyroidism. Typically, PTH-resistance disorders present as symptomatic hypocalcemia in childhood, however our patient presented in adulthood. Presentation: Saturday, June 17, 2023