Multiple Endocrine Neoplasia Research Articles

THU521 A Case Of Multifocal Pancreatic Neuroendocrine Tumor With Multiple Twists

Abstract Disclosure: A. Syeda: None. V. Kantorovich: None. Background: Multifocal pancreatic neuroendocrine tumors (PNETs) are rare and are usually associated with genetic syndromes like Multiple Endocrine Neoplasia 1 (MEN1). Sporadic multifocal PNETs have been infrequently reported. Case: A 68-year-old Caucasian female with a past medical history of hypertension, hyperlipidemia, type 2 diabetes mellitus, morbid obesity, multiple renal cysts, and Barrett’s esophagus presented to endocrinology for evaluation of PNET. An MRI performed for evaluation of renal cysts demonstrated pancreatic lesions suspicious for neoplasm. An endoscopic ultrasound (EUS) guided fine needle aspiration biopsy (FNAB) of the largest lesion was consistent with low grade PNET positive for chromogranin A (CgA) and synaptophysin. Biochemical workup was remarkable for elevated CgA of 4800 ng/mL (n: <311 ng/mL) and elevated gastrin level of 700 pg/mL (n: <100 pg/mL); however, the patient was on proton pump inhibitors. A Ga-68 DOTATATE scan revealed 4 DOTATATE avid masses in the pancreatic head, neck, body and tail, the largest measuring 2.3 cm in the pancreatic head. No metastatic lesions were identified. Family history is significant for hyperparathyroidism in one sister and endometrial cancer in another sister. Genetic testing was negative for 86 genetic mutations including MEN1, VHL, TSC1 and TSC2. The patient underwent a successful total pancreatectomy, splenectomy and duodenectomy with a hepaticojejunostomy and gastrojejunostomy. Surgical pathology revealed 5 multifocal tumors, measuring 0.4-2.2 cm in diameter, with clear margins, without any lymphovascular invasion and 19 lymph nodes negative for malignancy. Mitotic rate was <2 mitoses per mm2 and Ki-67 index was < 3 %. Next Generation Sequencing of the surgical specimen was positive for ATM gene deletion. Interestingly, immunohistochemistry stained strongly for insulin, glucagon and INSM1 suggestive of nesidioblastosis although the patient did not have preoperative hypoglycemia that would raise a clinical suspicion. Discussion: This case highlights several unique features in a multifocal PNET. A recent study suggested that multifocality is not associated with worse prognosis or increased risk of recurrence. Another distinctive finding in our patient is the ATM gene mutation. Heterozygous pathogenic variants in ATM gene are known to be associated with hereditary pancreatic cancer but there has been no reported association with PNETs. ATM gene down regulation is linked with metastatic NETs and was proposed as a potential predictive marker for metastasis and as a novel target in metastatic gastroenteropancreatic NETs. Concurrent occurrence of nesidioblastosis and PNET has been rarely reported in the literature, however, it was a clinically silent phenomenon in our case. Presentation: Thursday, June 15, 2023

SAT521 Predictive Value of Tumor Volumetrics in Patients with Medullary Thyroid Cancer

Abstract Disclosure: N. Behairy: None. S. Gubbi: None. M.G. Pascoal: None. A. Bharadwaj: None. E.C. Wright: None. T. Abijo: None. N. Uttarkar Vikram: None. P. Veeraraghavan: None. C. Cochran: None. J. Glod: None. J. Klubo-Gwiezdzinska: None. Predictive Value of Tumor Volumetrics in Patients with Medullary Thyroid Cancer Background Medullary thyroid cancer (MTC) is a rare endocrine malignancy that can present either as a sporadic disease or as a part of inherited autosomal dominant multiple endocrine neoplasia type 2A (MEN2A) and 2B (MEN2B) syndromes. There is limited data on the prognostic value of the tumor volume (TV) doubling time (TVDT) in patients with sporadic and familial MTC. Therefore, the goal of this study was to examine the association between TVDT and disease-specific survival (DSS) in patients with metastatic MTC. Material and Methods This cohort study included patients with metastatic MTC for whom at least 3 follow-up CT/MRI scans revealed ≥2 measurable lesions and up to the 5 largest lesions in each affected organ were analyzed. The tumor volumes were measured in 2 dimensions (2D) per standard practice reporting and 3 dimensions (3D) using an ellipsoid formula. The average TVDT of all measured lesions in each organ with metastatic deposits was calculated using a previously reported formula. Calcitonin (Ct-DT) and CEA doubling times (CEA-DT) were assessed using the American Thyroid Association Guidelines calculator. The association between DSS and TVDT, Ct-DT, and CEA-DT was tested using Cox regression. Correlations were assessed using a Spearman correlation coefficient. The study was approved by the Institution Review Board. Results The study cohort consisted of 51 patients (27 women, 53%) with age at the initial scan 24 ± 17 years and an average primary tumor size of 3.3±2.0 cm. Seven patients presented with sporadic MTC, 12 with MEN2A and 32 with MEN2B. During a follow-up of 8.0±4.3 years, 28/51 (55%) patients had disease progression and required systemic or local therapies and 9/51 (18%) patients died. A total of 456 scans were analyzed documenting that the organs with the most rapid TVDT were neck masses in 25/51 (49%), liver metastases in 16/51 (31%), lung nodules in 7/51 (14%) and prostate lesions in 3/51 (6%) patients. There was a strong correlation between 2D and 3D TVDT (r = 0.96) as well as between Ct-DT and CEA-DT (r = 0.82). However, the correlation between 2D TVDT and Ct-DT and CEA-DT were low (r = 0.45 for both). The DSS hazard ratios (HR) for DT <1 year compared to ≥3 years were 8.2 (1.5-45.4) for 2D TVDT, 8.7 (1.6-48.2) for 3D TVDT, 15.9 (1.72-146.7) for Ct-DT, and 11.72 (2.0-68.7) for CEA-DT. DSS was not associated with either familial or sporadic etiology of MTC (p = 0.38), gender (p = 0.12), or age at initial scan (p = 0.85). Conclusions Apart from Ct-DT and CEA-DT, TVDT is a valuable prognostic factor in metastatic MTC. Given a strong correlation between 2D and 3D TVDT, standard 2D-based TVDT measurements might be used as an easily obtained and clinically feasible prognostic marker of DSS in MTC patients. Presentation Date: Saturday, June 17, 2023

SAT561 Pathogenic RET V804M Germline Variant Without Clinical Manifestations Of Multiple Endocrine Neoplasia Type 2 In An Elderly Male

Abstract Disclosure: R. Ghosh: None. G. Al-Naqeeb: None. P. Veeraraghavan: None. C. Craig: None. J. Klubo-Gwiezdzinska: None. S. Gubbi: None. Background: Germline pathogenic variants in the RET protooncogene give rise to multiple endocrine neoplasia (MEN) types 2A and 2B. MEN2A is mainly characterized by MTC (∼100%), pheochromocytoma (PHEO; 4% - 88%), and primary hyperparathyroidism (HPTH; 2% - 30%), while MEN2B predominantly manifests with MTC (100%), PHEO (50%), mucocutaneous neuromas, and marfanoid habitus. Both MEN2A and 2B follow an autosomal dominant mode of inheritance. While certain pathogenic RET variants (M918T, A883F, and C634X) have high penetrance and present with aggressive disease, other variants such as V804M are of low penetrance and manifest with clinically mild disease.Clinical case: A 75-year-old male was referred to our center for further evaluation of the finding of an abnormal RET gene that was identified on a peripheral blood whole-exome gene sequencing research panel performed at an outside center. The patient was noted to have a germline RET c.2410 G>A, p.V804M heterozygous pathogenic variant. The patient denied any history of lump in the neck, symptoms of hyper- or hypothyroidism, tremors, headaches, fatigue, facial flushing, palpitations, constipation, diarrhea, anxiety, depression, or history of fragility fractures. Medical history consisted of hypertension, nephrolithiasis, type 2 diabetes mellitus, obstructive sleep apnea, interstitial pulmonary fibrosis, and colonic diverticula and polyps. Family history was significant for leukemia, colon, and breast cancers, but none of the relatives had a history of MTC, PHEO, or MEN2, and his children, while healthy, had not undergone RET germline testing. Physical examination showed no evidence of hypothyroidism or hyperthyroidism. Neck examination showed no evidence of thyromegaly or cervical lymphadenopathy. Laboratory investigations were unremarkable [serum calcitonin: 7.9 pg/ml (NL: </=14.3), CEA 2.8 mcg/L (NL: 0.8-3.4), thyrotropin (TSH): 1.92 microIU/ml (NL: 0.35-4.94), free thyroxine: 0.9 ng/dl (NL: 0.7-1.5), plasma free normetanephrine: 0.31 nmol/L (NL: <0.9), plasma free metanephrines 0.24 nmol/L (NL: <0.5), parathyroid hormone: 28.2 pg/ml (NL: 15-65), and ionized calcium 1.23 mmol/l (NL: 1.09-1.30)]. Thyroid sonogram was normal. We recommended active annual surveillance with biochemical markers and imaging along with genetic testing of the RET gene in his children. Conclusion: The V804M RET variant has been often associated with MTC or MEN2A phenotypes [1]. However, the variable expression of this variant may lead to a mild clinical phenotype or even absence of MTC/MEN2A manifestations. Hence, active surveillance as opposed to radical surgery like prophylactic thyroidectomy would be more beneficial in patients with no clinical or biochemical evidence of disease. Reference: Pinna et al., 2007, V804M is the most frequent mutation and may be associated with FMTC/MEN-2A phenotype. Thyroid, 17(2), 101-104. Presentation Date: 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

FRI367 An Unusual Presentation Of A Thyroid Nodule: A Thyroid Paraganglioma

Abstract Disclosure: M. Owrangi: None. F. Hasan: None. Introduction: Thyroid paraganglioma (PGL) is a rare thyroid tumor that originates from inferior laryngeal paraganglia. We present a case of a patient initially believed to have a thyroid nodule which turned out to be a PGL. Case Presentation: A 49 year-old white female with history of GERD and mild dysphagia who was found to have a left parathyroid adenoma vs. a left exophytic thyroid nodule. Previous ultrasounds had all showed slow but progressive enlargement of the lesion. Her labs had showed iPTH, Ca, TSH, and free T4 all within reference range and she was clinically euthyroid. She had 2 fine needle aspirations (FNA) which were both non diagnostic. She ultimately underwent surgical excision of the mass. The pathological examination showed cells that were positive for synaptophysin, chromogranin, GATA-3, S100, and neuron-specific enolase. They were negative for Ki-67, PTH, thyroglobulin, TTF-1, CK AE1/AE3, and CD 138. The overall findings were consistent with thyroid PGL. Discussion: In this case Thyroid PGL was diagnosed after pathological examination, including immunohistochemistry, was performed on a surgically excised sample, after 2 FNAs were non-diagnostic. Thyroid PGLs are elusive tumors. One study suggested that since they were first described in 1964, until 2015, there have only been 54 reported cases of thyroid PGLs, with a strong female predominance (88.9%). They often present as asymptomatic thyroid nodules and their diagnosis can be difficult by FNA alone as they can morphologically mimic medullary thyroid carcinoma, intrathyroidal parathyroid proliferation, metastatic neuroendocrine tumor, or calcitonin-negative neuroendocrine tumor of the thyroid gland (CNNETT). Thyroid PGLs are often benign, slow growing tumors and account for only 0.012% of all head and neck tumors with a malignancy rate of 4-16%. They usually present as single nodules averaging 3.5 cm and are often diagnosed with routine ultrasound assessment of the neck. Since they are associated with the parasympathetic nervous system, signs and symptoms including tachycardia, palpitations, and weight loss due to hormonal activity are classically absent from thyroid PGLs. In about 30% of cases, thyroid PGLs have a genetic predisposition and are more than one and associate with other tumors such as pheochromocytoma. Major hereditary disorders associated with paraganglioma include von Hippel-Lindau disease, multiple endocrine neoplasia, familial paraganglioma syndromes 1 to 4, and neurofibromatosis. Therefore, it is highly recommended that patients with a diagnosis of thyroid PGL undergo additional investigations with imaging, hormonal activity assessment, and genetic testing. Given the difference in management of thyroid PGLs compared to its cytology mimics, and their association with some familial cancer syndromes, use of immunohistochemical staining is crucial in making the correct diagnosis. Presentation: Friday, June 16, 2023

THU081 Differences In Circulating Microrna Levels In Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Multiple Endocrine Neoplasia Type 1 Phenocopies As Assessed By Next Generation Sequencing

Abstract Disclosure: D.A. Trukhina: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). E.O. Mamedova: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). P.A. Koshkin: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). A.G. Nikitin: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). G.A. Melnichenko: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). Z.E. Belaya: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). Multiple endocrine neoplasia type 1 (MEN1) is a rare disease caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pituitary adenomas, as well as other endocrine and non-endocrine tumors. Patients with MEN1 phenotype without MEN1 mutations are considered MEN1 phenocopies (phMEN1). It has not been studied whether the development of MEN1 phenocopies is determined by epigenetic changes, particularly by altered microRNA expression, which can affect menin. Materials & methods Single-center, case-control study: assessment of plasma microRNA expression in patients with gMEN1, phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and gender-matched controls and stored at –80C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit. Circulating miRNA sequencing was performed on Illumina NextSeq 500. Subsequent data processing was performed using DESeq2 bioinformatics algorithm. Results We enrolled 24 patients with gMEN1 and 12 patients with phMEN1, along with 12 gender-matched controls. The median age of gMEN1 patients was 39 [35; 46]; in phMEN1 — 59 [51;60]; control — 59 [51.5; 62.5]. The gMEN1 group differed in age (p<0,01) compared to phMEN1 and control groups. We divided all assessed microRNAs into 3 groups based on the significance of the results: the first group consisted of samples with the highest level of detected microRNAs (>50 counts), the second group — moderate (10–50), the third group — the lowest (<10).98 microRNAs were differently expressed in groups gMEN1 and phMEN1 (84 upregulated microRNAs, 14 — downregulated). We found increased expression of microRNAs in gMEN1 which interact with menin: hsa-miR-421 (p adj = 0.0004362), hsa-miR-664a-5p (p adj = 0.0037814). We found several microRNAs associated with intestinal and pituitary tumors in gMEN1 and phMEN1 groups: up-regulated hsa-miR-7-5p (p adj = 0.0000084); downregulated hsa-miR-423-5p (p adj < 0.000001) and hsa-miR-432-5p (p adj = 0.0087227). 84 microRNA were differently expressed in groups gMEN1 and control (67 up-regulated microRNAs, 17 — downregulated). When comparing gMEN1 with phMEN1 and control a decrease in hsa-let-7a-5p miRNA was found, which, according to the literature, is downregulated in Men1 gene knockout cell lines. The phMEN1 vs control group showed downregulation of hsa-miR-122-5p (p adj = 0.0080138) and upregulation of hsa-miR-191-5p (p adj = 0.0002144), hsa-miR-486-5p (p adj = 0.0491822) that has been detected in GEP-NETs. Conclusion We found microRNAs which could potentially become biomarkers in the differential diagnosis of gMEN1 and phMEN1. The results need to be validated using a different measurement method with a larger sample size. Presentation: Thursday, June 15, 2023

SAT610 Multiple Endocrine Neoplasia Type 1 - The First Reported Case In An Indigenous Australian

Abstract Disclosure: E. Mignone: None. K. Neal: None. Background: Multiple Endocrine Neoplasia type 1 (MEN1) is a rare and under recognised syndrome. It has not been previously reported in Indigenous Australians for this reason. Clinical Case: A 48-year-old Indigenous Australian female was consulted on by an inpatient endocrine team in March 2020 for persistent hypercalcaemia on a background of a parathyroidectomy in 2011 for primary hyperparathyroidism (PHPTH). She was admitted to a remote Australian hospital for investigation and management of acute on chronic abdominal pain. Relevant medical history included a parathyroidectomy at age 40, multiple PE/DVT, MI, AF, CTEPH, right heart failure, HTLV-1 and recurrent abdominal pain presumed secondary to GORD. Gastroscopy from 2013 revealed chronic gastritis with hundreds of gastric polyps discovered on subsequent gastroscopy in 2015. The young age of PHPTH combined with her chronic gastritis and polyps prompted neuroendocrine tumour (NET) screening, including MEN1. At time of consult in 2020, laboratory studies were consistent with recurrence of PHPTH with a corrected calcium of 2.9 mmol/L (2.15-2.57mmol/L), serum PTH level 31.5 pmol/L (1-7pmol/L), vitamin D level 30 nmol/L, 24-hour urinary calcium variable between low and high. NET markers were markedly elevated with a gastrin level of 14042 ng/L (<100 ng/L), pancreatic polypeptide 2905 pmol/L (<55 pmol/L), urine 5HIAA ratio 8 mmol/L (<4 mmol/L), vasoactive intestinal peptide and glucagon levels normal. Pituitary studies, serum calcitonin, plasma metanephrines and PTH related protein levels were within normal limits. A CT of the abdomen showed thickened gastric folds, and persistent liver and IVC lesions from 2018. A diagnosis of Zollinger Ellison Syndrome (ZES) was made. Eventually, genetic testing was positive for a rare heterozygous variant of c.207dupC in exon 2 of MEN1 gene. A 68-gallium-DOTATATE PET/CT showed multiple avid pancreatic, gastric, nodal and liver lesions with high somatostatin receptor expression, suggestive of a neuroendocrine malignancy. Treatment was based largely on symptom control due to poor overall prognosis from underlying cardiorespiratory comorbidities. Abdominal pain from ZES was managed with a high dose PPI, H2 receptor antagonist and subcutaneous somatostatin analogue were trialled. Hypercalcaemia was treated with IV bisphosphonate therapy. Calcimimetic analogues were considered however patient declined. Genetic counselling was attempted however many cultural and logistical barriers were identified and family declined further testing. Unfortunately, our patient died in 2021 from presumed multifactorial respiratory failure. Conclusion: High index of suspicion is required to diagnose MEN1. This is particularly true within the Indigenous Australian population, with no prior documented cases reported. Presentation: Saturday, June 17, 2023

THU613 Multiple Endocrine Neoplasia Type 5 Associated With Germline Max Mutations—New Insights Into This Proposed Entity

Abstract Disclosure: N. Charoenngam: None. P. Likasitwatanakul: None. C. Kansuttiviwat: None. B. Ponvilawan: None. A. Jaroenlapnopparat: None. M. Tanariyakul: None. M. Mannstadt: None. Heterozygous germline loss-of-function mutations in the MAX gene, encoding the tumor suppressor MYC-associated factor X, are associated with hereditary pheochromocytoma-paraganglioma (PCC/PGL) syndrome. Furthermore, there are reports of patients who developed additional endocrine and non-endocrine tumors. Thus, presence of multiple endocrine tumors associated with germline MAX mutations has been proposed to comprise “Multiple Endocrine Neoplasia type 5”. Despite multiple reports, a summary of phenotypic manifestations of germline MAX mutations is lacking. Therefore, using systematic review, we aimed to establish a summary of all reported patients with germline MAX mutations to comprehensively describe the phenotype of this syndrome. Potentially eligible articles were retrieved from MEDLINE and EMBASE databases from inception to February 2023 using search terms related to “MAX gene” and “Neoplasm”. Additionally, we identified supporting references of MAX variants reported in the ClinVar database. Eligible articles must report patient-level data on individuals with germline MAX mutations. We extracted data of all reported patients to generate a database. After systematic review, 113 patients with germline MAX variants were identified from 37 articles. Data were presented as median [IQR] or number of patients per available data point (%). Age onset of first tumor of the patients was 28.5 (22.0-38.3) years and 45/102 (44.1%) patients were female. The most common tumors/endocrinopathies were PCC (99/113, 87.6%; age onset 28.5 [23.0-37.8] years) and PGL (9/113, 8.0%; age onset 43.0 [32.0-46.0] years). Other tumors include pituitary adenoma (9/113, 8.0%; age onset 24.0 [29.5-34.3] years), ganglioneuroma (6/113, 5.3%; age onset: 5, 15, 20, 28, 61, N/A years), neuroblastoma (6/113, 5.3%; age onset: 8, 9, 11, 17 months, 27, N/A years), primary hyperparathyroidism (4/113, 3.5%; age onset 40, 49, 69, N/A years) and lung cancer (4/113, 3.5%; age onset 47, 64, N/A, N/A years). Among the 99 patients with PCC, 34/93 (36.6%) had unilateral PCC, 59/93 (63.4%) had bilateral PCC (14/31 synchronous, 17/31 asynchronous). There were 14/50 (28.0%) with metastatic PCC. Most of the PCCs were norepinephrine-producing (32/40, 80.0%), followed by norepinephrine+epinephrine-producing (4/40, 10.0%) and epinephrine-producing (2/40, 5.0%). In tumor tissue, loss of heterozygosity was observed in 27 patients with PCC/PGL, one with pancreatic neuroendocrine tumor, one with renal cell carcinoma and one with renal oncocytoma. In summary, pathogenic MAX mutations cause PCC/PGL with the age of onset in the 20s for PCC and 30s-40s for PGL. Other associated conditions include ganglioneuroma, neuroblastoma, primary hyperparathyroidism, lung cancer, pancreatic neuroendocrine tumor, renal cell carcinoma and renal oncocytoma. Future research will clarify which tumors are caused by the MAX mutations. Presentation: Thursday, June 15, 2023

SAT180 Comparison Between Sporadic Primary Hyperparathyroidism And Multiple Endocrine Neoplasia Type 1 (MEN1)-Associated Primary Hyperparathyroidism: A Retrospective Analysis Of The Indian PHPT Registry

Abstract Disclosure: S. Bhadada: None. A.M. Chakraborty: None. P. Kumari: None. R. Pal: None. A. Sood: None. D. Dahiya: None. S.D. Rao: None. Introduction: Multiple endocrine neoplasia type 1 (MEN1)-associated tumours are located in parathyroid, pituitary and pancreatoduodenal locations. Though heterogenous, the most consistent presentation of MEN1 is primary hyperparathyroidism (PHPT) seen in almost 100% of cases. Comparisons between sporadic and MEN1 PHPT patients are sparse in the literature. Objective: To retrospectively compare the demography, clinical manifestations, management, and outcome of sporadic PHPT and MEN1-associated PHPT patients. Design and setting: A registry-based (www.indianphptregistry.com) retrospective cohort study from a tertiary care hospital in North India. Methods and patients: The medical records and clinical data of sporadic PHPT patients and MEN1-associated PHPT patients registered in the Indian PHPT registry were analysed. Result: A total of 616 PHPT patients have been registered in the electronic registry, 72 of whom (11.68%) were MEN1-associated PHPT. The mean age of sporadic PHPT patients was 43.4 ± 14.3, whereas MEN1-associated PHPT was 35.8 ± 13.5 years (p<0.05). Among MEN1-associated PHPT cases, 66 (90%) were index cases at the time of presentation, and the rest were detected on family screening. For both sporadic PHPT and MEN1-associated PHPT, the most common presenting symptom was bone pain, followed by renal stone disease. Sporadic PHPT and MEN1 PHPT both had comparable mean calcium (11.9 ± 1.5 vs 11.9 ± 1.6 mg/dl), mean phosphate (2.7 ± 1 vs 2.58 ± 0.7 mg/dl), median PTH (314; IQR 161-984 pg/ml vs 292; IQR 180-818 pg/ml) level at presentation. Median 25-hydroxyvitamin D level was 19.3; IQR 10.4-30.4 ng/dl, and 15; IQR 8.1 – 25.1 ng/dl (p<0.05) for sporadic PHPT and MEN1-associated PHPT respectively. Multiglandular disease was common in MEN1-associated PHPT (40.2%) compared to sporadic cases (3%). Median tumour weight was higher in sporadic cases (2.5; IQR 0.8- 7.3 gm) compared to MEN1 cases (1.9; IQR 1.08 – 4.05 gm). Ultrasound neck and Sesta-MIBI concordance rate among sporadic cases was 57%, whereas MEN1 cases were 70.8%. Median post-surgery decline in PTH and calcium was more in the case of sporadic PHPT in comparison to MEN1-associated PHPT 84.81% vs 46.7% and 23.4% vs 16.59 % respectively (p<0.05). Discussion: MEN1-associated PHPT patients presented at an earlier age than sporadic cases. There was no statistical difference in PTH, calcium or phosphate levels between the two cohorts, but 25-hydroxyvitamin D levels were lower in MEN1-associated PHPT. Localisation was better in the case of the MEN-1 cohort as per as the Sesta-MIBI and USG concordance was concerned. Postoperative fall of PTH and calcium was more in sporadic cases than in MEN1 cases. Presentation: Saturday, June 17, 2023

SAT181 Clinical Profile And Treatment Outcomes Of Patients With Sporadic And Multiple Endocrine Neoplasia Syndrome-related Primary Hyperparathyroidism

Abstract Disclosure: U.E. Mathew: None. V.P. Jyotsna: None. A.S. Upadhyay: None. A. Goyal: None. D. Kandaswamy: None. C. Bal: None. A. Sharma: None. C.K. Sharma: None. S. Aggarwal: None. N. Tandon: None. Primary hyperparathyroidism (PHPT) is the most frequent endocrine disorder in MEN-1. The MEN-1 related PHPT (MPHPT) differs from sporadic (SPHPT) in many aspects. The distinction between them is very important at the point of diagnosis as it enables planning on treatment and subsequent surveillance for other endocrine tumours. Objective: The aim of study was to compare the clinical, biochemical, radiological features and surgical outcome in patients with MPHPT versus SPHPT and to identify the predictors of MEN-1 among apparently sporadic hyperparathyroidism. Design: Ambispective cross-sectional study from 2015-2021. Participants: 251 subjects with SPHPT and 23 subjects with MPHPT. Setting: The endocrine clinic of All India Institute of Medical Sciences, New Delhi, India. Results: The classical symptoms of hyperparathyroidism (80.5% vs 47.8%, p<0.001), mean serum calcium (12.7 vs 11.8 mg/dl, p=0.01) and alkaline phosphatase (ALP) levels (p=0.03) were significantly seen higher in SPHPT than MPHPT. MEN-1 patients showed low bone mineral density (BMD) at lumbar spine (-1.52±1.44 vs -2.6±1.25, p=0.001) and femoral neck (1.13±1.37 vs-1.81±1.01, p=0.002) and higher prevalence of complicated nephrolithiasis (34.5 % vs 56.5%, p=0.03) for the age. BMD at their lumbar spine showed an inverse correlation with serum PTH (r=-0.51, p=0.01). Whereas the typical radiological features of hyperparathyroidism and severe skeletal manifestations including brown tumours and fractures were observed less in MEN-1 (44.8% vs 21.7% vs, p=0.02). The overall remission rate was 98.6% in SPHPT and 90% in MPHPT on long term follow up.Despite milder biochemical features, the frequency of hungry bone syndrome was not different from SPHPT (11.6% vs 15.8%, p=0.32). The transient and permanent hypoparathyroidism were more common in MPHPT group (24.4% vs 50%, p=0.01: 0.4% vs 15%, p=0.002).The factors strongly predictive of MEN-1 in multivariate analysis were ALP within the normal range (OR 4.2(95% CI 1.1-16.9), p=0.038), lower lumbar spine BMD (OR 0.47 (95% CI (0.28-0.76), p=0.003) and hyperplastic parathyroid gland on histopathology (OR 37.1(95% CI (9.9-138.6), p<0.001). The multivariate predictive model showed an excellent discrimination between two classes with area under curve in ROC was 0.91. Conclusions: MEN-1 associated PHPT have severe bone and renal involvement despite milder biochemical features, even in Indian settings, where there is a higher frequency of severe symptomatic sporadic hyperparathyroidism. MEN-1 should be suspected when, a discordant finding of severe degree of bone demineralisation at lumbar spine and in normal range of ALP, has observed among apparently SPHPT. Our model can assist in deciding on screening for MEN-1 as the family history and multiglandular involvement may be absent at the presentation, and delay in development of other endocrine tumours. Presentation: Saturday, June 17, 2023

SAT309 Clinical And Genetic Profiling Of Patients With Multiple Endocrine Neoplasia Type 2 Syndrome And Screening for Medullary Thyroid Carcinoma In Asymptomatic First-degree Relatives

Abstract Disclosure: K. Kumar P: None. Y. Gupta: None. A. Goyal: None. D. Kandasamy: None. N. Tandon: None. Background: Multiple endocrine neoplasia type 2 (MEN2) syndrome is a rare disorder with autosomal dominant inheritance, characterised by the presence of two of the following three endocrine manifestations: medullary thyroid carcinoma (MTC), pheochromocytoma (PCC) and primary hyperparathyroidism (PHPT) [1-2]. There is a paucity of data on clinical and genetic profile of MEN2 syndrome in the Indian subcontinent. Objectives: We aimed to evaluate the clinical and genetic profile of patients with MEN2 syndrome and perform screening for MTC among asymptomatic family members with serum calcitonin. Materials and Methods: This was an ambispective study conducted in the Department of Endocrinology at AIIMS New Delhi, involving diagnosed patients of MEN2 syndrome between January 2016 and December 2022. Results: We evaluated a total of 24 families with MEN2 syndrome comprising 61(MEN2A, n=56; MEN2B, n=5) patients, 18 patients were diagnosed as index cases. Data were derived retrospectively for 46 patients (MEN2A, n=43 MEN2B, n=3) and prospectively for 15 patients (MEN2A, n=13; MEN2B, n=2). The mean age at presentation of MEN2A and MEN2B were 28.6 ± 13.52 years and 22 ± 4.44 years, respectively. Of the study patients, 35 (57.38%) were females, among them 32 were MEN2A. Among 18 index patients 67% were synchronously detected to have MTC and PCC while 33% had MTC preceding PCC. Among patients with MEN2A syndrome 33 (59%) had MTC, 21(38%) had simultaneous PCC and MTC and one patient had PCC as presentation. We noted PHPT in 5 (9%) patients with MEN2A syndrome. Of the 5 patients with MEN2B syndrome, 4 (80%) presented with synchronous MTC and PCC and one (20%) presented with MTC aloneMetastatic MTC was noted in six patients with MEN2A syndrome and two patients with MEN2B syndrome. Median baseline Sr calcitonin level was 42 (4-1721) pg./ml in non-Metastatic group vs 3945(928-35572) pg./ml in distant metastasis group. 1 patient had metastasis from PCC to liver. Mutational analysis data are available for 40 patients. The most common mutations in MEN2A and MEN2B groups were C634R (exon 11 of RET gene, n=21) and M918T (exon 16 of RET gene, n=4), respectively.A total of 177 eligible family members of index patients with MEN2A syndrome were contacted, of whom 83 turned up for screening and 42 (50.6%) had elevated serum calcitonin levels (>10 pg./ml). Of the 26 eligible family members of index patients with MEN2B syndrome, only 9 could be screened and all had normal serum calcitonin levels (<10 pg./ml). Discussion & Conclusion: 1) This is the largest study comprising 61 patients after screening 24 family members in India. 2) Synchronous presentation of MEN2 with PCC and MTC is 67% vs 17% in western literature in Index patients. 3) MEN2 syndrome should be suspected in patients with MTC and young-onset PCC and all first-degree relatives of index patients with this syndrome. Presentation: Saturday, June 17, 2023

SAT555 Utility of 18F-DOPA PET/CT in the Diagnosis of Medullary Thyroid Cancer in a Patient with Multiple Endocrine Neoplasia Type 2B

Abstract Disclosure: D.G. Varghese: None. S. Akshintala: None. A. Jha: None. S. Gubbi: None. A. Reno: None. J. Klubo-Gwiezdzinska: None. K. Pacak: None. J. Glod: None. J. Del Rivero: None. Background: MEN2B is a cancer predisposition syndrome caused by an activating mutation in the RET proto-oncogene. It is characterized by medullary thyroid cancer (MTC), pheochromocytoma (PHEO), and extra endocrine features. U/S, CT, MRI and 18F-fluorodeoxyglucose (18F-FDG), 18F-fluorodihyroxyphenylalanine (18F-FDOPA), 68Ga-DOTA-(0)-Tyr(3)-octreotate (68Ga-DOTATATE) PET/CT scans have been used for the diagnosis and follow up of MTC. However, there is increasing evidence of 18F-FDOPA PET as more specific imaging modality in the diagnosis of MTC since L-type amino acid transporters have shown to be present in MTC cells.Clinical Case: 26-year-old female presented with HTN at the age of 17. The patient developed episodes of nausea/vomiting, intermittent headaches with systolic BP in the 190’s. Further work-up revealed bilateral adrenal nodules with elevated plasma metanephrines. The patient underwent left adrenalectomy and a year later, right adrenal nodule resection confirming PHEO. On follow up, calcitonin was elevated, and the patient underwent a total thyroidectomy with bilateral central lymph node dissection. At age 19 she was diagnosed with MEN2B (RET mutation, p.Met918Thr). With rising calcitonin, she was referred to our institution for further evaluation. Her serum calcitonin was 31986(<7.6 pg/ml), CEA 631 (0.8-3.4 ng/ml), fractionated plasma normetanephrine 565 (18-112 pg/ml), and metanephrine 304 (12-61 pg/mL). MRI of the abdomen showed enlarging adrenal masses. 18F-FDG PET/CT scan showed a focus of uptake (SUVmax of 8.5) in posterior right thyroid bed, uptake in the liver (SUVmax of 7.5) and uptake in the right adrenal gland and left adrenal bed; 68Ga-DOTATATE PET/CT scan showed a faint uptake in the right thyroid lobe (SUVmax of 2.7) and an 18F-FDOPA PET/CT scan showed intense uptake in both lobe of the thyroid, multiple lesions in the liver and suspicious focus in the right adrenal bed. The patient underwent bilateral adrenalectomy for recurrent PHEO and her plasma metanephrines normalized. Conclusion: This case adds to the mounting evidence in the usage of 18F-FDOPA PET/CT scan as a useful imaging modality for MTC especially in the setting of MEN2B syndrome. A head-to-head comparison in 18 patients, both per patient and per lesion sensitivity by 18F-FDOPA PET/CT (72%, 85%) was found to be statistically superior compared to 68Ga-DOTATATE PET/CT (33%, 20%), and 18F-FDG PET/CT (17%, 28%). A meta-analysis conducted in MTC consisting of 306 patients from 14 studies, 18F-FDOPA compared to 18F-FDG and 68Ga-DOTATATE showed the highest surface under the cumulative ranking curve (SUCRA) value in both patient and lesion-based analyses irrespective of serum calcitonin/CEA values or calcitonin doubling time. The potential for use of 18F-FDOPA as a diagnostic agent and the potential to provide insight into possible therapeutic targets are unknown and should be further studied. Presentation Date: Saturday, June 17, 2023

SAT335 Bilateral Pheochromocytomas In Multiple Endocrine Neoplasia Type 2B: A Frozen Abdomen, A Slow Growing Mass, And A Backdoor Solution

Abstract Disclosure: O.A. Shariq: None. T.J. McKenzie: None. W.F. Young: None. Background: Multiple endocrine neoplasia type 2B (MEN2B) is most commonly caused by a germline methionine-to-threonine substitution at codon 918 (M918T) of the RET proto-oncogene. The syndrome is characterized by medullary thyroid carcinoma, pheochromocytoma, and extra-endocrine manifestations (intestinal ganglioneuromas, mucosal neuromas, and skeletal and ophthalmic abnormalities). We describe a patient with MEN2B and bilateral pheochromocytomas, in whom the slow-growing nature of the lesions, and previous history of an extra-endocrine manifestation, precluded the typical approach to surgical resection. Clinical Case: A 58-year-old-male with MEN2B, diagnosed at age 15, presented with a 6-month history of episodic palpitations and labile blood pressures. His past surgical history included a total abdominal colectomy and ileorectal anastomosis at age 7 years for megacolon, secondary to intestinal ganglioneuromatosis. He subsequently required multiple laparotomies and adhesiolysis procedures for recurrent small bowel obstructions. During his most recent laparotomy at age 44, he was noted to have a ‘frozen’ abdomen with dense adhesions involving the small bowel. CT abdomen revealed bilateral adrenal masses, measuring 2.9 cm and 1.5 cm on the right and left, respectively. Review of previous imaging revealed that the right adrenal mass had been present 16 years prior, measuring 1.0 cm at that time, while the left-sided mass was not seen. Biochemical workup was negative previously, but now showed elevated plasma metanephrine (4.1 nmol/L [N<0.5 nmol/L ]) and normetanephrine 2.3 nmol/L [N<0.9 nmol/L ]) levels. In the setting of extensive intra-abdominal adhesions and the slow-growing nature of both masses, the decision was made to perform a unilateral right adrenalectomy through a retroperitoneoscopic, rather than a transabdominal, approach. Pathology confirmed a 4.4 cm pheochromocytoma. The patient was discharged on postoperative day 1 and was symptom free at 1 year follow-up. His most recent plasma metanephrine and normetanephine levels were 0.7 nmol/L and 0.5 nmol/L, respectively. Clinical Lessons: Patients with MEN2B have a 50% lifetime risk of developing pheochromocytoma. Unlike medullary thyroid cancer, which exhibits an aggressive phenotype in this syndrome, MEN2B-associated pheochromocytomas may be slow growing, thereby avoiding the need for an initial bilateral adrenalectomy. Many patients with MEN2B develop gastrointestinal manifestations, including megacolon during infancy, for which multiple surgical interventions may be required. These procedures carry a risk of adhesion formation, which presents a challenge if further abdominal surgery is required later in life for pheochromocytoma. Retroperitoneoscopic adrenalectomy provides a safe approach in such patients, as the need to perform risky adhesiolysis and mobilize adjacent organs is obviated. Presentation: Saturday, June 17, 2023

Molecular Basis and Natural History of Medullary Thyroid Cancer: It is (Almost) All in the RET.

Medullary thyroid cancer (MTC) is a rare disease, which can be either sporadic (roughly 75% of cases) or genetically determined (multiple endocrine neoplasia type 2, due to REarranged during Transfection RET germline mutations, 25% of cases). Interestingly, RET pathogenic variants (mainly M918T) have also been reported in aggressive forms of sporadic MTC, suggesting the importance of RET signalling pathways in the pathogenesis of MTC. The initial theory of RET codon-related MTC aggressiveness has been recently questioned by studies suggesting that this would only define the age at disease onset rather than the aggressiveness of MTC. Other factors might however impact the natural history of the disease, such as RET polymorphisms, epigenetic factors, environmental factors, MET (mesenchymal-epithelial transition) alterations, or even other genetic alterations such as RAS family (HRAS, KRAS, NRAS) genetic alterations. This review will detail the molecular bases of MTC, focusing on RET pathways, and the potential mechanisms that explain the phenotypic intra- and interfamilial heterogeneity.

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

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

THU094 Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss To Follow Up

Abstract Disclosure: S.J. Sternlieb: None. K.G. Romo: None. R.S. Boothe: None. D. Englert: None. N. Manuel: None. Q.Z. Iqbal: None. Multiple Endocrine Neoplasia Type 1 Tumor Recurrence After Loss to Follow-up Sternlieb, S. J., Romo, K.G., Boothe, R., Manuel, N., Iqbal, Q.Z., Grissett, B., Englert, D. Background: MEN1 is a rare, autosomal dominant tumor disorder due to mutations in the MEN1 tumor suppressor gene. It is characterized by parathyroid, enteropancreatic and pituitary tumors. We present a young woman with MEN1 with prolactinoma, primary hyperparathyroidism and multiple pancreatic neuroendocrine tumors. Clinical Case: A 30-year-old woman with MEN1 presented with complaints of abdominal pain and GI bleeding (GIB). She was diagnosed with a prolactinoma at age 14 after presenting for primary amenorrhea and galactorrhea. She didn’t tolerate medical therapy with bromocriptine or cabergoline and required transphenoidal resection. At age 19, she presented with hypoglycemia and was found to have multiple pancreatic neuroendocrine tumors (NET) as well as a left (L) adrenal gland tumor. She underwent distal pancreatectomy and L adrenalectomy. Ten tumors in the pancreas stained variably for insulin, glucagon, gastrin and VIP. Multiple cortical adenomas were found in the adrenal gland. Post-operatively she developed a spinal cord hematoma related to placement of an epidural catheter for pain control, which led to permanent paraplegia. At age 21, she was diagnosed with primary hyperparathyroidism. She underwent left parathyroidectomy, then was lost to follow-up for 9 years. EGD showed multiple superficial duodenal ulcers. MRI brain identified a right (R) cavernous sinus mass inseparable from the R pituitary. CT abdomen showed a pancreatic head mass. Given the concern for neuroendocrine etiology, she underwent an EUS showing a pancreatic mass and a liver mass. Pancreatic mass pathology confirmed low-grade NET with Ki67 proliferation rate <1%, positive synaptophysin and chromogranin staining. After multidisciplinary discussion, the consensus was to continue PPI and sucralfate for GI ulcers, start lanreotide, and obtain somatostatin receptor scintigraphy. Surgery was not recommended unless significant GIB occurred on maximal therapy. She was referred to follow-up with GI, endocrinology, and NSGY. Since discharge, she has presented several times to other hospitals for abdominal pain, but has not adhered to follow-up. Conclusions: This case of recurrent neuroendocrine and pituitary tumors despite prior resections demonstrates the consequences of prolonged loss to follow-up with MEN1. Without routine surveillance, recurrence is likely. This patient lives in a rural area with lack of access to nearby subspecialty care, which is a barrier. More resources are needed to support patients with social barriers and progressive endocrinopathies. Key words: MEN1, prolactinoma, gastrinoma, NET, health care barriers Presentation: Thursday, June 15, 2023

Pediatric head and neck manifestations associated with multiple endocrine neoplasia syndromes.

Multiple endocrine neoplasia (MEN) syndromes are a group of hereditary cancer syndromes that can predispose children to endocrine neoplasms developing within the head and neck. To examine the neoplastic manifestations of MEN type 1 (MEN1) and MEN type 2 (MEN2) in the pediatric head and neck. Single-institution, retrospective review of pediatric MEN between 2005 and 2022. Fifty-three children were genetically confirmed with MEN (15 MEN1, 34 MEN2A, and 4 MEN2B), while three patients received clinical diagnoses of MEN1. The male to female ratio was essentially equal (1.15:1), and a documented family history of cancer was present in 89% (50/56). After multidisciplinary evaluation, a familial MEN diagnosis was confirmed in 91% (51/56). The mean ages of initial presentation and surgical intervention were 8.9 years (SD 5) and 9.8 years (SD 4.8), respectively. Although patients with MEN2 received surgery earlier than patients with MEN1 (8.7 vs 12.7 years), surgical patients with MEN2 in this cohort were older relative to current American Thyroid Association (ATA) guidelines primarily due to late presentation. Thyroid malignancies were identified in 36% (9/25) of thyroidectomy specimens (21 MEN2A, 4 MEN2B), with medullary thyroid carcinoma (MTC) present in five MEN2A patients and three MEN2B patients (89%), and papillary thyroid carcinoma (PTC) present in one MEN2A patient (11%). Nearly 90% (8/9) of thyroid malignancies were occult, with some occurring earlier than predicted by current guidelines (ATA-MOD and ATA-H). Central neck dissections were performed in 24% (2 MEN1, 2 MEN2A, and 4 MEN2B), with two MEN2B (50%) demonstrating cervical lymph node (LN) metastases. Additional histopathologic findings included C-cell hyperplasia in 57% (12/21) of MEN2A thyroidectomy patients. Of the eight MEN1 parathyroidectomy patients, four demonstrated parathyroid hyperplasia and four presented with parathyroid adenoma. Nearly 60% required head and neck procedures. While MEN1 guidelines were appropriate for our cohort, we identified patients with MEN2 that developed MTC earlier than expected based on current ATA guidelines, including children in categories considered lower risk. In conjunction with a multidisciplinary approach, pediatric head and neck surgeons should be aware of the potential need for earlier surgical intervention in the pediatric MEN2 population.

Calciphylaxis in a patient with hypoparathyroidism and MEN-1 syndrome.

Calciphylaxis is a rare disorder characterised by the development of painful necrotic skin lesions. Occlusion of cutaneous arterioles due to ectopic calcification leads to potentially life-threatening widespread skin loss. Most cases occur in patients with chronic renal disease, which leads to dysregulation of calcium and phosphate homeostasis. Only a handful of case reports exist describing calciphylaxis occurring in patients without chronic renal disease but with hypoparathyroidism. We report on a unique case of a 53-year-old man with multiple endocrine neoplasia type 1 syndrome and acquired hypoparathyroidism due to total parathyroidectomy who went on to develop calciphylaxis following cardiac surgery. Calciphylaxis most commonly occurs in the context of chronic renal disease but can rarely occur in its absence as a consequence of calcium and phosphate dysregulation. Patients who develop necrotic skin lesions in the presence of hypoparathyroidism require an urgent dermatological opinion. Mortality from calciphylaxis is high, with the majority of deaths occurring secondary to sepsis. Management of calciphylaxis requires a multidisciplinary team approach to manage wound healing, infections and pain. Recovery with full rehabilitation from calciphylaxis can take months to years.

S2644 A Case of Synchronous Primary Pancreatic and Biliary Neuroendocrine Tumors With Multiple Endocrine Neoplasia Type 1

S2644 A Case of Synchronous Primary Pancreatic and Biliary Neuroendocrine Tumors With Multiple Endocrine Neoplasia Type 1

Molecular features of thyroid cancer in children

Background. Malignant neoplasms of the thyroid gland are the most common endocrine malignant neoplasms in the children’s age group. Unlike adults, who most often have BRAF and RAS mutations, children have chromosomal displacements. The relevance is explained by the lack of comprehensive studies on thyroid cancer in children in the Russian-language literature.The aim of the study is — to summarize and systematize the literature data on the molecular features of thyroid cancer in children.Materials and methods. The authors conducted a search for publications in the PubMed electronic database using the following algorithm: Molecular AND Thyroid cancer AND pediatrics. We found 451 publications, and after reviewing the annotations, 111 studies describing the molecular features of thyroid cancer in the pediatric population were included in the review. Publications were excluded due to duplication and inconsistency with the subject of this study.Results. Instead of point mutations of BRAF and RAS, characteristic of adults, regardless of radiation status, chromosomal displacements are more common in children. Re-arrangement of RET/PTC genes is the most common, followed by BRAF fusions. Mutations of the TERT promoter, which are markers of the aggressive course of the disease in adults, are rare in children. DICER1 mutations appear to play a key role in pediatric cases of follicular and papillary thyroid cancer. Medullary thyroid cancer (MTC) in children requires the exclusion of multiple endocrine neoplasia syndrome (MEN type 2). Tumors originating from follicular cells other than MTC can rarely be familial. Literature data on the role of microRNA as a biomarker in thyroid carcinomas in children is currently limited.