Parathyroid Tumors Research Articles

Parathyroid carcinoma with pancreatitis causing hypercalcaemic emergency treated with extracorporeal membrane oxygenation-assisted parathyroid resection.

Emergencies due to malignancies usually have a severe clinical course and require urgent treatment. These scenarios are dubbed 'oncologic emergencies'. Parathyroid tumours often cause hypercalcaemia but not oncologic emergencies. We present a case of parathyroid carcinoma with severe hypercalcaemia and pancreatitis, resolved by surgical resection of the tumour assisted by extracorporeal membrane oxygenation (ECMO). A 66-year-old woman presented to our hospital because of haematuria. Laboratory findings were as follows: white blood cell count: 30 000, C-reactive protein: 17.7, calcium: 21.9, creatine kinase: 316, creatine kinase-myoglobin binding: 20, troponin I: 1415.8, amylase: 1046, lipase: 499, blood urea nitrogen: 57, and creatinine: 2.42. ECG was unremarkable. CT revealed a 4-cm low-density irregular tumour in the left lobe of the thyroid gland and severe pancreatitis. We diagnosed hypercalcaemia and pancreatitis due to parathyroid carcinoma. Volume expansion with isotonic saline was started immediately. Calcitonin, followed by denosumab, calcimimetic agents, and continuous hemodiafiltration were administered. The patient's general condition worsened due to uncontrolled hypercalcaemia. Urgent tumour resection was planned, assisted with ECMO for cardiopulmonary support and surgical field venous pressure reduction. Tumour histology was suggestive of parathyroid carcinoma. Hypercalcaemia and the patient's general condition improved gradually postoperatively. Hypercalcaemia is one of the oncologic emergency symptoms, commonly occurring because of lytic bone metastasis. However, reports about parathyroid carcinoma-causing life-threatening hypercalcaemia and pancreatitis are scarce; the fatality of this condition is estimated to be 30-70%. We report a case of survival of hypercalcaemia of malignancy. Parathyroid carcinoma is relatively rare and sometimes causes emergent conditions such as hypercalcaemia and severe pancreatitis. General therapy for hypercalcaemia including aggressive saline dehydration, administration of furosemide, calcitonin, zoledronic acid, and evocalcet, and dialysis is sometimes ineffective for parathyroid carcinoma. Therefore, careful planning of therapy in case of exacerbation is important. During an emergency, rapid surgical treatment despite high calcium level is the best potential therapeutic strategy.

The Role of Frozen Section Examination in Thyroid Surgery.

In endocrine pathology, frozen section (FS) examination is most commonly used for the intraoperative evaluation of thyroid and parathyroid tumors, as well as cervical lymph nodes. In the past, frozen section was considered a fundamental tool in thyroid surgery. However, with advancements in preoperative ultrasound and fine-needle aspiration biopsy (FNAB), there have been increasing queries about its routine use due to the improved preoperative diagnosis. Nowadays, while the use of FS during thyroidectomy has decreased, it is still used as an additional method for different purposes intraoperatively. FS may not always provide definitive results. If FS will alter the surgical plan or extent, it should be applied. Routine FS is not recommended for evaluating thyroid nodules. But in addition to FNAB, if FS results may change the operation plan or extent, they can be utilized. FS should not be applied for thyroid lesions smaller than 1 cm, and the entire lesion should not be frozen for FS. For the assessment of thyroid nodules, the use of FS is recommended based on the Bethesda categories of FNAB. In Bethesda I category nodules, FS may contribute to distinguishing between malignant and benign lesions and guide surgical treatment. In Bethesda II nodules, where the malignancy rate is low, the performance of FNAB and FS can be compared, but it's not recommended due to the lack of a significant contribution to the surgical strategy. The sensitivity of FS in Bethesda III and IV nodules is low; its contribution to the diagnosis is limited, and it does not provide an apparent benefit to treatment; therefore, it is not recommended. In Bethesda V nodules, FS can effectively confirm the malignancy diagnosis, contribute to the surgical strategy, and reduce the possibility of completion thyroidectomy, and accordingly, it is recommended for use. Nonetheless, in Bethesda V nodules with a benign FS report, the malignancy rate remains high, so it should not be used to rule out malignancy. In Bethesda VI nodules, the performance of FS is lower or comparable to FNAB and does not significantly contribute to the treatment strategy; hence, it is not recommended. Particularly in patients with papillary thyroid cancer, intraoperative FS can be effective in detecting extrathyroidal extension and can assist the surgeon in determining the extent of thyroid surgery and central neck dissection. FS has high sensitivity and specificity in evaluating the lymphatic status of the central region intraoperatively and can be used to determine the extent of central compartment node dissection. During thyroidectomy, FS examination can be used in recognizing parathyroid tissue and distinguishing it from fatty tissue, thymus, thyroid, lymph nodes, especially in differentiating metastatic lymph nodes.

Радионуклидная диагностика в определении сопутствующей патологии у онкологических больных

The aim of this study is to demonstrate the significance and necessity of radionuclide diagnostics of oncologic pathology of different nature on the instance of a clinical case of detection of multiple foci of secondary nature (mts) of parathyroid gland tumor by skeletal bone scintigraphy in the course of routine examination of a patient for breast cancer. The data from the medical records, protocols and radiation methods of examination of the patient were used as the study material. During a routine examination for metastases of breast cancer through radionuclide examination of the parathyroid glands and scintigraphic examination of the skeletal bones, pathologic foci of radiopharmaceutical (RP) hyperfixation were detected in the patient. On further computed tomography (CT) of the knee joints it was found that the picture may correspond to multiple secondary lesions of the skeletal bones on the background of parathyroid gland disease. After a week the patient underwent a biphasic radionuclide study of the parathyroid glands, which made it possible to assess the presence of obvious scintigraphic signs of hyperfunctioning adenoma of the left lower parathyroid gland. Further, a thyroid gland (TG) tissue biopsy study was performed, which showed that the tissue fragment on the section was light brown with the presence of a cyst filled with brown fluid, which may correspond to a brown tumor. Thus, a patient with main breast disease is likely to be diagnosed with other unrelated cancers. The key diagnostic method in this case will be a scintigraphic study with single photon emission computed tomography (SPECT), which provides the most accurate visualization of pathology, its description and prediction of further therapy both in outpatient and inpatient settings. For the majority of cancer patients it is advisable to conduct regular examination with the help of scintigraphy for the purpose of prevention and early detection of concomitant pathology.

Atypical parathyroid tumor: clinical and parathyroid hormone response to surgical treatment.

Primary hyperparathyroidism (PHPT) is caused by typical adenoma (TA), multiglandular disease (MD), or parathyroid carcinoma (PC), and in a smaller percentage of cases by atypical parathyroid tumor (APT). The objective of this study is the retrospective analysis of clinical features and parathyroid hormone (PTH)/calcium response to surgery in patients who underwent parathyroidectomy for symptomatic PHPT with histological evidence of APT. We retrospectively reviewed our institutional experience in the management of PHPT from January 2016 to December 2021 focusing on those patients presenting APTs. We analyzed the clinical features of this disease and PTH/calcium response to surgical treatment in APTs compared to the other pathological conditions causing PHPT. In a cohort of 125 patients with PHPT we found 112 TAs (89.6%), 6 APTs (4.8%), 6 PCs (4.8%), and only 1 MD (0.8%). APTs in comparison to other parathyroid diseases showed peculiar features such as adhesion to the surrounding structures and a frequent intrathyroidal location, which may justify thyroid loboistmectomy adopted in most of the observed cases. APTs showed significantly higher preoperative PTH values compared to TA + MD and were relevant to PC. Due to its rarity, there is a lack of specific indications in the management of APTs. Biochemical features observed in APT and PC can be related to similar biological behavior. However, some specific features observed preoperatively in some cases of PHPT might suggest presence of an APT, which could be helpful mostly in surgical and postoperative management. Further studies are required to confirm the results of the present preliminary report.

Features of the diagnosis of primary hyperparathyroidism in children

Background. Primary hyperparathyroidism (PHPT) is a rare pathology in pediatric and adolescent patients. Collection, analysis and generalization of the literature data and experience of the leading clinics allow to develop unified, statistically substantiated approaches to diagnostics and surgical treatment of this group of patients.Material and methods. The article presents a retrospective analysis of 17 cases of PHPT in children and adolescents aged from 6 to 18 years operated on in the department of Surgery of St.-Petersburg State Pediatric Medical University in the period from 1973 till 2021. Among those operated there were 10 girls and 7 boys, the M:F ratio was 1:1.4. The mean age of the patients was 12,9±0,71 years.Results and discussion. The main criteria of the disease diagnosis were elevated blood calcium and parathormone levels, excessive urinary calcium secretion. Manifest forms of the disease were diagnosed in 10 (58,8%) of 17 children. In 3 (17,6%) cases the parathyroid neoplasms were accompanied neither by clinical, nor laboratory manifestations of the disease and were regarded as incidentalomas. Another 4 (23.5%) patients had only laboratory changes (hypercalcemia and hyperparathyrinaemia) that manifested themselves preoperatively. These observations were referred to the asymptomatic form of PHPT.In 7 (41.2%) cases parathyroid adenomas were found and removed during surgeries for various thyroid diseases (thyroid cancer in 5 cases, diffuse toxic goiter in 1 case). An incidental finding of parathyroid adenoma was during prophylactic thyroidectomy for Sipple syndrome.A radioisotope method proved to be the most informative way to localize parathyroid tumors.Conclusion. The diagnosis of the disease in manifest sporadic cases does not differ from that in adults. Genetic study is indicated in the presence of a family history of multiple involvement of the parathyroid glands. Surgical treatment with removal of parathyroid tumor is the main method, which allows to achieve complete recovery.

Mediastinal Parathyroid Cancer.

Parathyroid cancer (PC) is rare, but its pre-operative recognition is important to choose appropriate access strategies and achieve oncological clearance. This study characterizes features of mediastinal parathyroid cancer (MPC) and explores criteria aiding in the pre-operative recognition of malignancy. We assembled data from 502 patients with mediastinal parathyroid neoplasms (MPNs) from a systematic review of the literature 1968−2020 (n = 467) and our own patient cohort (n = 35). Thirty-two of the 502 MPNs (6.4%) exhibited malignancy. Only 23% of MPC patients underwent oncological surgery. Local persistence and early recurrence at a median delay of 24 months were frequent (45.8%), and associated with a 21.7-fold (95%CI 1.3−351.4; p = 0.03) higher risk of death due to disease. MPCs (n = 30) were significantly larger than cervical PC (n = 330), at 54 ± 36 mm vs. 35 ± 18 mm (χ2 = 20; p < 0.0001), and larger than mediastinal parathyroid adenomas (MPA; n = 226) at 22 ± 15 mm (χ2 = 33; p < 0.01). MPC occurred more commonly in males (60%; p < 0.01), with higher calcium (p < 0.01) and parathyroid hormone (PTH) levels (p < 0.01) than MPA. Mediastinal lesions larger than 3.0 cm and associated with a corrected calcium ≥ 3.0 mM are associated with a more than 100-fold higher odds ratio of being malignant (OR 109.2; 95%CI 1.1−346; p < 0.05). The composite 3 + 3 criterion recognized 74% of all MPC with an accuracy of 83%. Inversely, no MPN presenting with a calcium < 3.0 mM and size < 3.0 cm was malignant. When faced with pHPT in mediastinal location, consideration of the 3 + 3 rule may trigger an oncological team approach based on simple, available criteria.

Shear wave elastography for differentiating parathyroid neoplasms with malignant diagnosis or uncertain malignant potential from parathyroid adenomas: initial experience

ObjectiveParathyroid carcinoma (PC) and atypical parathyroid tumor (APT) are rare parathyroid disorders carrying the risk of recurrence of varying degrees. This study aims to explore the value of 2D-shear wave elastography (SWE) in the discrimination of PC/APT among suspicious parathyroid lesions.Methods and materialsIn this prospective study, patients with primary hyperparathyroidism and suspicious parathyroid lesions on ultrasonography (US) were recruited. All the lesions were assessed by SWE before surgery. The velocity (m/s), Young’s modulus (Kpa), and elastogram of SWE were compared between pathologically proven parathyroid carcinoma or atypical parathyroid tumor (Group1) and parathyroid adenoma (Group2). All the SWE parameters were displayed at the setting of 50 or 70 kPa. Correlations between SWE and the lesion size as well as biochemical parameters were analyzed.Results36 target lesions were enrolled for analysis. The mean shear wave velocity (SWV) between the two groups was 2.4 m/s vs 1.9 m/s, respectively, while the mean Young’s modulus was 11.1 kPa vs 18.2 kPa, respectively. The cut-off values are 2.35 m/s and 17.05 kPa correspondingly. The sensitivity and specificity of the selecting cut-off values were 0.56 vs 0.63 and 0.95 vs 1.0 (area under the curve [AUC]: 0.813 vs 0.852 [95% confidence interval (CI): 0.669–0.956 vs 0.720–0.983]; p < 0.001, p < 0.001; respectively). In contrast, the max SWV and Young’s modulus showed a better sensitivity of 0.75 and 0.81, respectively. The “colored lesion” and “stiff rim” patterns on the elastogram are more indicated in parathyroid carcinoma and atypical parathyroid tumor, whereas the negative elastogram prevails in parathyroid adenoma. The SWV and Young’s modulus of the parathyroid lesions were independent of the tumor size, but the max SWV and Young’s modulus slightly correlated with serum parathyroid hormone concentration (PTH) (r = 0.398, p = 0.016; r = 0.396, p = 0.017).Conclusions2D-shear wave elastography plays a useful role in the preoperative assessment of parathyroid lesions with suspicious malignancy. The mean SWV and Young’s modulus are advised as the favored diagnostic parameter with the best AUC and excellent specificities, while the max SWV and Young’s modulus are more sensitive to distinguish the PC and APT compared with other parameters.

Engineering functional 3-dimensional patient-derived endocrine organoids for broad multiplatform applications

BackgroundRecent advancements in 3-dimensional patient-derived organoid models have revolutionized the field of cancer biology. There is an urgent need for development of endocrine tumor organoid models for medullary thyroid carcinoma, adrenocortical carcinoma, papillary thyroid carcinoma, and a spectrum of benign hyperfunctioning parathyroid and adrenal neoplasms. We aimed to engineer functionally intact 3-dimensional endocrine patient-derived organoids to expand the in vitro and translational applications for the advancement of endocrine research. MethodsUsing our recently developed fine needle aspiration–based methodology, we established patient-derived 3-dimensional endocrine organoid models using prospectively collected human papillary thyroid carcinoma (n = 6), medullary thyroid carcinoma (n = 3), adrenocortical carcinoma (n = 3), and parathyroid (n = 5). and adrenal (n = 5) neoplasms. Multiplatform analyses of endocrine patient-derived organoids and applications in oncoimmunology, near-infrared autofluorescence, and radiosensitization studies under 3-dimensional in vitro conditions were performed. ResultsWe have successfully modeled and analyzed the complex endocrine microenvironment for a spectrum of endocrine neoplasms in 3-dimensional culture. The endocrine patient-derived organoids recapitulated complex tumor microenvironment of endocrine neoplasms morphologically and functionally and maintained cytokine production and near-infrared autofluorescence properties. ConclusionOur novel engineered endocrine patient-derived organoid models of thyroid, parathyroid and adrenal neoplasms represent an exciting and elegant alternative to current limited 2-dimensional systems and afford future broad multiplatform in vitro and translational applications, including in endocrine oncoimmunology.

LBSAT145 Localizing The "Difficult" Parathyroid Tumor

Abstract Background The identification of parathyroid tumor(s) in patients with persistent/recurrent primary hyperparathyroidism (PHPT) is critical for a successful re-operative surgery. We describe our experience with invasive studies for parathyroid tumor localization and provide follow-up data regarding our experience with selective arterial hypocalcemic stimulation with central venous sampling (SAHSCVS). Methods We identified patients who underwent pre-operative invasive testing for localization of parathyroid tumor at our center. At our center, only PHPT patients with history of prior neck surgery without definitive findings on non-invasive testing (sestamibi, ultrasound, CT, MRI) proceed to invasive studies. The result of each invasive localization study (arteriogram, SAHSCVS and selective venous sampling (SVS)) was categorized as true-positive (TP), false-positive (FP) and false-negative (FN) based on biochemical outcome. Results Ninety-five patients with 98 tumors underwent invasive testing for parathyroid tumor localization. All but one had recurrent disease. Sixty-two patients (65%) had "apparently sporadic" PHPT, 19/95 (20%) had MEN1, three had parathyroid cancer (PC) and the remaining had other heritable forms of PHPT. Median age of index PHPT presentation was 47 [34-58] years. Of 87 tumors with available operative details, 66 (76%) were in the neck, 20 in the mediastinum (23%), and one in the forearm at site of prior autograft. Seventy-two (83%) showed hyperplasia or hypercellularity on histology. Median tumor size was 5 mm. Arteriogram, SAHSCVS and SVS accurately localized the tumor in 47/90 (52%), 54/90 (60%) and 49/61 (80%) tumors respectively. Positive Predictive Value of arteriogram, SAHSCVS and SVS was 47/50 (94%), 55/64 (86%) and 49/59 (83%) respectively. Both sensitivity and PPV showed no significant difference between patients with MEN1+PC vs. others. Among the 54 tumors accurately localized by SAHSCVS, SVS was performed in 29/54 with complete concordance. Twenty-seven tumors (30%) were missed (FN) on SAHSCVS, of these 14/25 (56%) were also missed on arteriogram. Nevertheless, 16/20 (80%) localized accurately on subsequent SVS. SAHSCVS was FP in localizing nine tumors - seven (78%) of these did not show a blush on arteriogram. All pre-operative localizing studies were unrevealing in 9/98 presentations (10%). Conclusion Patients with difficult to localize parathyroid tumors have clinical features suspicious for germline-predisposition forms of PHPT indicated by recurrent disease, hyperplastic glands, and age of index presentation. SAHSCVS can be a useful adjunct in patients who require invasive localization. 90% of these tumors are localized with combination of current non-invasive and invasive testing. AcknowledgementThis research is supported by the Intramural Research Program of NIDDK, NCI and NIH Clinical Center. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP121 Recurrent atypical parathyroid adenoma: a case report

Abstract Background Atypical parathyroid adenoma is a rare cause of hyperparathyroidism, with an incidence ranging from 0.5 to 4.4%. Its recurrence rate is low, around 3%. We describe a young patient with an atypical parathyroid adenoma that recurred twice at the right neck. Case presentation A 39-year-old woman presented to the ER with low back pain, hyporexia, weight loss, and an oral lesion with purulent discharge. She was diagnosed with nephrolithiasis, severe hypercalcemia (serum calcium concentration: 21,2 mg/dl (Reference range 8,5-10,5) and hyperparathyroidism (serum PTH: 703 pg/mL; reference range 15-45pg/mL). Parathyroid scintigraphy identified an uptake at the site of the lower right parathyroid. A cervical US confirmed the presence of a 3 cm markedly hypoechoic nodule in that location. Fine needle aspiration (FNA) suggested parathyroid adenoma, and PTH washout levels were 1900 pg/ml. Screening for multiple endocrine neoplasia was negative. Biopsy of the mandibular alveolar bone, around the oral lesion, showed giant cell lesion. Lower right parathyroidectomy was performed, and the histopathology showed parathyroid neoplasm with features favoring atypical parathyroid adenoma (lesion measuring 3×2×1.8 cm). Fifteen months after the surgery, the patient presented symptoms of hypercalcemia, with a new elevation of serum PTH levels (738 pg/ml), confirmed with radiotracer uptake at the site of the upper right parathyroid gland. She underwent right parathyroidectomy and hemithyroidectomy. Histopathology revealed an atypical parathyroid adenoma. Immunohistochemistry was positive to galectin 3 in rare cells; Ki 67 positive (2%). After nine months, the patient noticed a subcutaneous nodule in the right anterior cervical region associated with symptomatic hypercalcemia, and a new increase in serum PTH levels (469.5 pg/mL). Parathyroid scintigraphy confirmed radiotracer activity at the nodule described, that was surgically resected. Histopathology was compatible with an atypical parathyroid neoplasm (uncertain malignant potential). The patient remains in regular follow-up, asymptomatic and normocalcemic. Conclusion While 96% of patients with atypical parathyroid adenomas are cured with parathyroidectomy, this case shows a very rare description of two recurrences in a short time of follow-up, with an ectopic location in the last one. It should be noted that atypical paratyroid adenomas are already an uncommon presentation of primary hyperparathyroidism. Genetic investigation is warranted in such cases. Presentation: No date and time listed

LBSAT144 Single-center Experience With Hyperparathyroidism-jaw Tumor Syndrome - Where Do We Stand?

Abstract Background Hyperparathyroidism-jaw tumor (HPT-JT) syndrome is a heritable form of primary hyperparathyroidism (PHPT) associated with tumors in parathyroid, jaw, kidney, and uterus. This work aims to provide a natural history of HPT-JT from a long-term follow-up of a large single-institution cohort. Methods We identified patients with HPT-JT seen under the natural history study of parathyroid disorders from 1991-2020 and analyzed their disease manifestations and treatment outcomes. Results Sixty-six patients (50% males) from 32 kindreds with HPT-JT (genotype-positive: 46, presumed genotype-positive: 20). Median age at presentation of index patients was 24 [19-33] years. PHPT was prevalent in 51/61(84%) patients, of which seven had ectopic parathyroid tumors and 20/50 (40%) had multi-gland disease. Eighty-two parathyroid tumors were removed from 52 patients through 66 surgeries -17/66 (26%) unilateral; 23/66 (35%) bilateral neck explorations. Parathyroid cancer (PC) was seen in 16/78 tumors (21%), atypical parathyroid in 2/78(3%), parathyroid adenoma (PA) in 12/78 (15%), hyperplasia in 27/78 (35%) and microscopically normal but enlarged parathyroid in 21/78 (27%). PAs had median tumor size 10 [7-17] mm, PC: 19 [11-25] mm. We found a significant correlation between tumor size and serum PTH (r=0.55, p=0. 007). Uterine tumor was second most common disease manifestation (10/36 females, 28%) - initial manifestation in 5/10. Median age of presentation was 18 [15-21] years with presentations of menorrhagia, abdominal pain, or miscarriage. The histology of uterine tumors included adenomyoma, fibroids or leiomyomata. JT was noted in 5/70 (7%) patients (three mandibular, two maxillary tumors) - initial manifestation in 3/5. Median age of presentation with JTs was 23 [20-31] years. Microscopically, JTs were diagnosed as cysts (n=2), cemento-ossifying fibroma (n=2) and fibro-osteoid lesions (n=1). Kidney tumors were observed in three patients - one presented with abdominal pain, two were diagnosed on surveillance scans. Median age at presentation was 25 [6-44] years. Two related patients had bilateral mixed epithelial and stromal tumors while a 6-year-old male had Wilm's tumor. Median age at last follow-up was 37 [28-49] years. Recurrent PHPT was seen in 5/35(14%) patients with PA or hyperplasia (Median recurrence time: 10[7 - 16] years) and 12/15(80%) with PC (Median recurrence time: 2[1 - 5] yeas. Co-existing psychiatric disorder, mainly depression and anxiety were seen in 16/68 (24%) patients, consistent with published literature for other chronic conditions. Conclusion Most (60%) patients with HPT-JT have single-gland disease with recurrence seen in only a minority of patients (14%) with PAs. JTs are not as common as the name suggests while uterine tumors appear to be relatively frequent. Acknowledgement: This research is supported by the Intramural Research Program of NIDDK and NCI. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP102 Indicators for the effects of calcimimetics on hypercalcemia in the elderly patients with primary hyperparathyroidism.

Abstract Primary hyperparathyroidism (PHPT) is the most common disorder causing hypercalcemia, in which parathyroid hormone (PTH) is excessively secreted from a parathyroid tumor. PHPT occurs mainly in elderly women, and patient with PHPT present symptoms including nephrolithiasis, bone fracture, and cognitive impairment or can be asymptomatic. Excessive secretion of PTH leads to elevated serum levels of alkaline phosphatase as well as calcium and decreased serum inorganic phosphate level. Parathyroid surgery is the only established treatment, and the treatment reduces elevated serum levels of calcium and PTH, increases bone mineral density, reduces the occurrence of bone fractures, and decreases the risk of renal stones. However, some PHPT patients, especially elderly patients, refuse to undergo surgical therapy for various reasons including perceived risk. Calcimimetic treatment, including cinacalcet and evocalcet administration, has also been reported to be effective for reducing serum calcium level in patients with PHPT. However, the relationship between the efficacy of calcimimetic treatment for PHPT and patient characteristics related to the effectiveness of calcimimetics remains to be elucidated. To investigate the relevance of clinical parameters to the effectiveness of calcimimetics for PHPT, we retrospectively analyzed patients with PHPT who received calcimimetic treatment in our department. We included nine patients including 8 females (88.9%) and one male (11.1%) in the study. The median age of the patients was 81 years (interquartile range (IQR): 61-86 years). Laboratory tests before calcimimetic treatment revealed that median level of serum corrected calcium (cCa) was high (11.1 (IQR: 10.5-12.7) mg/dL), serum inorganic phosphate was low (2.3 (2.3-2.4) mg/dL), and plasma intact PTH was high (251. 0 (198.3-498.5) pg/mL). The fractional excretion of calcium was higher than 1% (1.3% (1.12-1.48%)), %tubular reabsorption of phosphate was low (79.9% (77.1-83.9%)), nephrogenous cyclic adenosine monophosphate (cAMP) was high (3.4 (2.4-4. 0) nmoL/dL GF), and urinary cAMP was normal (4.3 (4. 0-5.3) μmoL/day). Median reduction rate of serum cCa level due to calcimimetic treatment was 5.8% (0-13.4%) at the first follow-up (median treatment duration: 22 (20-29) days). Notably, reduction rate of serum cCa level had significant correlations with age (R=0.95), dual energy X-ray absorptiometry % young adult mean (DEXA %YAM) in the femoral neck (R=-0.92), and urinary cAMP level (R=-0.85). Thus, the present study suggested that elevated serum cCa levels may be reduced by treatment with calcimimetics more effectively in PHPT patients of relatively advanced age, patients with low DEXA %YAM, and patients with low urinary cAMP. Presentation: No date and time listed

RF25 | PMON147 Plasma MicroRNA Expression in Phenocopy of Multiple Endocrine Neoplasia Type 1 Compared to Patients with Acromegaly and Primary Hyperparathyroidism: Potential Biomarkers of Multiple Endocrine Tumor Growth

Abstract Introduction Changes in the expression of microRNA facilitate in the formation of various tumors. MEN1 is a rare disease caused by mutations in MEN1 gene encoding the menin protein and characterize by the occurrence of parathyroid, pituitary, gastroenteropancreatic and other tumors. If a patient with the MEN1 phenotype carry no mutations in the MEN1 gene, the condition considers a phenocopy of syndrome (phMEN1). We hypothesize that the pathogenic link among the above sporadic tumors might be represented by molecular pathways involving the MEN1 gene and epigenetic regulations — particularly microRNAs. Materials &amp; methods Single-center, case-control study: assessment of plasma microRNA expression in patients with phMEN1, acromegaly (AM), primary hyperparathyroidism (PHPT) and healthy controls. Morning plasma samples were collected from fasting patients and age- and sex-matched controls and stored at –80°C. Total RNA isolation: miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit following the manufacturer. Circulating miRNA sequencing was done on Illumina NextSeq 500 (Illumina). Subsequent data processing was performed using the DESeq2 bioinformatics algorithm. Results We enrolled 36 consecutive patients (12 patients in each group) with phMEN1, AM, PHPT, along with 12 age and gender matched controls. Median age of phMEN1 group — 59 [52; 60.5]; AM — 59 [52; 63]; PHPT — 60.5 [54; 62.5]; control — 59 [51.5; 62.5]. The groups did not differ in age (p=0.88) and gender – in all groups were 11 women and 1 man (p=1.00). We divided all assessed microRNAs into 3 groups based on the significance of the results; the first group consisted of samples with the highest levels of detected microRNAs (&amp;gt;50), the second group — moderate (10–50), the third group — the lowest (&amp;lt;10). The microRNA expression pattern was almost the same between AM and phMEN1 groups (15 microRNAs upregulated, 10 — downregulated), we found slightly decreased hsa-miR-4301 (padj=0.038); it is interesting that phMEN group when compared to PHPT and control groups showed decline in hsa-miR-4301 too. PHPT and control groups had also quite similar expression profile (4 microRNAs upregulated, 19 — downregulated). 607 microRNA were differently expressed in groups phMEN1 and PHPT (473 upregulated microRNAs, 134 — downregulated). We found increased expression of some microRNAs that interferes with menin: hsa-miR-24-1-5p (padj=0.0008), hsa-miR-24-3p (padj=0.034), hsa-miR-26a-5p (padj=0.0005), hsa-miR-421 (padj=0.018), hsa-miR-762 (padj=0.027). In addition, we found decreased microRNAs with oncogene potential: miR-3182 (padj=0.007), hsa-miR-875-5p (padj&amp;lt;0.001), hsa-miR-6749-5p (padj&amp;lt;0.001). 173 microRNA differed in phMEN1 and control groups (11 microRNAs upregulated, 162 — downregulated). We detected several decreased microRNAs in phMEN1 that participate in tumor genesis: hsa-miR-625-3p (padj&amp;lt;0.005), hsa-miR-3168 (padj=0,028), hsa-miR-302b-3p (padj&amp;lt;0.001). Conclusion We found microRNAs, which could potentially become biomarkers in phMEN1 diagnosis. The results need to be validated using different measurement method with larger sample size. Likewise further assessment of plasma microRNA expression in genetically confirmed MEN1 patients is needed. Presentation: Monday, June 13, 2022 12:30 p.m. - 12:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

RF05 | PSUN364 A Rare Case of Bilateral Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 1

Abstract Background Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder classically characterized by parathyroid gland tumors, anterior pituitary adenomas, and tumors of the gastro-entero-pancreatic tract. The majority of MEN1 cases involving lesions of the parathyroid gland causing hyperparathyroidism are almost always benign. It is extremely rare for hyperparathyroidism to be caused by parathyroid carcinomas. We report a very rare case of parathyroid carcinoma presenting in MEN1 syndrome. Case Report We present the case of a 45 year old male with a history of untreated hypertension, nephrolithiasis, and CKD, who became suddenly unresponsive, was intubated, and found to have a severe acute intraparenchymal hemorrhage secondary to severe hypertension on Head CT. Secondary causes of hypertension were ruled out, with renin activity, aldosterone levels, and urine metanephrines unremarkable; abdominal ultrasound with doppler was also negative for renal artery stenosis. Stroke protocol was initiated, with CTA Head negative for any acute findings. However, CTA Neck showed bilateral large nodules posterior to the thyroid lobes measuring 4.0×3.2 cm on the right and 3.9×2.5 cm on the left, with mass effect on the thyroid and adjacent carotids. Routine labs showed hypercalcemia of 13.3 (8.4-10.2 mg/dL) in the setting of elevated PTH levels of 1085 (15-65 pg/mL), with repeat PTH level of 1106 confirming primary hyperparathyroidism. Other causes of hypercalcemia were investigated, with levels of Calcitonin and Calcitriol/1,25 vitamin D within normal limits, but a decreased level of 25 hydroxy vitamin D of &amp;lt;12.8 (30-100 pg/mL). Maxillofacial CT was negative for any ossifying fibromas, ruling out jaw tumor syndrome. CT Abdomen showed hyperdense nodular areas in the pancreas, and MRI Brain was negative for any discrete pituitary gland lesions. Thyroid US was performed and revealed mixed cystic and solid masses posterior to both lobes of the thyroid; as a result, FNA of the thyroid and posterior mass was done, confirming hypercellular parathyroid tissue and benign thyroid tissue. Due to high suspicion for parathyroid carcinoma, the patient underwent a parathyroidectomy, with pathology confirming bilateral parathyroid carcinoma. Genetic testing was positive for MEN1, with a frameshift variant mutation of c.1299_1312del (p.Val434Leufs*10). Conclusion This is a very rare case of bilateral parathyroid carcinoma presenting in MEN1. To the best of our knowledge, this genetic mutation has not been reported in online databases or published literature. The clinical presentation of parathyroid lesions and pancreatic nodules in the setting of hypercalcemia should prompt further evaluation of genetic disorders such as MEN1. In this context, it is essential that MEN1 patients be managed with a multidisciplinary approach given the disorder's complexity of diagnosis and treatment. Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Advances and Updates in Parathyroid Pathology.

Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.

RF07 | PSUN366 An Uncommon Path Leading to Diagnosis of Multiple Endocrine Neoplasia 2A

Abstract Introduction MEN2 is a rare Autosomal Dominant disorder resulting from mutations in the RET proto-oncogene. MEN2 is classified into two distinct syndromes: MEN2A and MEN2B. MEN2A is a syndrome that presents with Medullary Thyroid Carcinoma (MTC) in 90% of adult gene carriers, unilateral or bilateral pheochormocytoma in 50%, and multigland parathyroid tumors in 20-30% of affected individuals. Other rare variants of MEN2 include Familial Medullary Thyroid Carcinoma (FMTC), MEN2A with cutaneous lichen amyloidosis, and MEN2A or FMTC with Hirschprung's disease. We present a patient with incidentally noted elevated calcitonin levels, later diagnosed with MEN2A. Clinical Case 37-year-old Caucasian male was referred to our clinic for elevated calcitonin levels noted on lab work done as part of evaluation and management for weight loss prior to initiating GLP-1 agonists. He was diagnosed with hypothyroidism and multinodular goiter and started on Synthroid. His only symptoms were weight gain, tiredness, soft stools and facial flushing He denied any family history of endocrine disorders. Physical exam was unremarkable. Pertinent labs included serum calcitonin 93 pg/mL (&amp;lt;10 pg/mL), serum CEAg 5.2 ng/mL (0-3 ng/mL), and work up for pheochromocytoma and hyperparathyroidism was negative. USG thyroid showed a left lobe thyroid nodule measuring 7×5×7 mm with macrocalcifications, a right lobe thyroid nodule measuring 8×5×10mm, and an abnormal left lateral level III LN. He underwent left thyroid lobectomy with level VI neck dissection (total thyroidectomy aborted due to hypoxia), and subsequently completion thyroidectomy with right central neck dissection. Pathology showed metastatic MTC with pathologic staging pT1aN1a. Genetic testing showed RET c. 1826G&amp;gt;A (p. C609Y) which is ATA – MOD risk. Patients’ father was also genetically screened and diagnosed with MEN2A and noted to have elevated calcitonin levels. He also subsequently underwent total thyroidectomy, which revealed medullary thyroid microcarcinoma. Conclusion A number of studies support that measurement of serum calcitonin is the most sensitive screening test for detecting occult MTC in individuals with thyroid nodules. Yet, the use of serum calcitonin in the routine evaluation of thyroid nodules is controversial due to absence of uniform calcitonin thresholds, high false positive values and unavailability of pentagastrin stimulation testing. Moreover, there are no recommendations based on the current data to check calcitonin levels prior to initiating GLP-1 agonists but their use is not recommended in patients with personal or family history of MTC/MEN2. Based on the above case, measurement of calcitonin levels should be a part of the work up in patients who present with thyroid nodules and are receiving GLP-1 agonists. Attention should also be paid to the importance of genetic counseling in first-degree relatives of patients with MEN2A. This allows for timely diagnosis and reduces morbidity and mortality. Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

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

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

Genetic and Epigenetic Alterations in Parathyroid Neoplasms.

The exact etiology of parathyroid carcinomas (PC) is still unknown. Their associations have with several inherited syndromes or specific genetic lesions have been established. The management of PC is challenging for clinicians. The complexity of molecular phenotypes increases with tumor aggressiveness. Lack of parafibromin on immunohistochemistry staining and HRPT2 mutation would be helpful in differentiation of carcinoma from adenoma. Lack of parafibromin expression, the gene product of HRPT2 is now used as a diagnostic, prognostic, and predictive marker for parathyroid carcinoma. The epigenetic alteration, for example, DNA methylation and modifications in the chromatin structure, are known as significant events involved in the parathyroid tumorigenesis. We suggest that adjuvant genetic and epigenetic target therapy should be considered in treatment of the patients with PC.

BRONCHOPULMONARY CARCINOID AND TYPE 1 MULTIPLE ENDOCRINE NEOPLASIA (MEN)

BRONCHOPULMONARY CARCINOID AND TYPE 1 MULTIPLE ENDOCRINE NEOPLASIA (MEN)

Environmental Chemicals and their Association with Hyperparathyroidism.

The incidence of hyperparathyroidism has increased in the USA. The previous work from our institution detected environmental chemicals (EC) within hyperplastic parathyroid tumors. The National Health and Nutrition Examination Survey (NHANES) is a program designed to assess the health status of people in the USA and includes measurements of EC in serum. Our aim was to determine which EC are associated with elevated parathyroid hormone (PTH) and calcium levels within NHANES. NHANES was queried from 2003-2016 for our analysis with calcium. A separate subgroup was queried from 2003-2006 that included PTH levels. Subjects with elevated calcium, and elevated PTH and normal Vitamin D levels were identified. Wilcoxon rank sum tests were used to analyze levels of EC in those with elevated calcium, and those with elevated PTH in the subgroup. All EC with p < 0.05 were then included in separate multivariate models adjusting for serum vitamin D and creatinine for PTH and albumin for calcium. There were 51,395 subjects analyzed, and calcium was elevated in 2.1% (1080) of subjects. Our subgroup analysis analyzed 14,681 subjects, and PTH was elevated without deficient Vitamin D in 9.4% (1,377). Twenty-nine different polychlorinated biphenyls and the organochlorine pesticides hexachlorobenzene, transnonachlor, oxychlordane, and p,p'-dichlorodiphenyldichloroethylene (DDE) were found to be associated with elevated calcium and separately with elevated PTH (all p < 0.05). In NHANES, 33 ECs were found to be associated with elevated calcium as well as elevated PTH levels on our subgroup analysis. These chemicals may lead us toward a causal link between environmental factors and the development of hyperparathyroidism and should be the focus of future studies looking at chemical levels within specimens.