Endocrine Tumors Research Articles

SURG-59. A RARE CASE OF COMBINED OCCURRENCE OF GLIOBLASTOMA MULTIFORME AND PHEOCHROMOCYTOMA: A CASE REPORT AND LITERATURE REVIEW

Abstract Glioblastoma is most common and malignant primary brain tumors. However, combined other solid organ malignancies sometimes occurred. To our knowledge, the combination of glioblastoma multiforme and pheochromocytoma is an exceedingly rare occurrence. As a result, we present the case of a 61-year-old male patient who suffered from slurred speech and unsteady gait due to left frontal glioblastoma with concurrent pheochromocytoma. The clinical course was retrospectively collected from medical records, including the lab data, imaging, surgical procedure and neurological examination results. We also provide a comprehensive review and discussion of the association between pheochromocytoma and glioblastoma, including genetic disorder the management strategy. The fluctuated blood pressure during brain surgery implied suspicious concurrent endocrine tumor in this patient. The patient was ultimately diagnosed with adrenal pheochromocytoma after left adrenalectomy and radical nephrectomy by urologist. No other malignancies or genetic disorders were found in this patient. Subsequently, this patient recovered well without any neurologic deficit and with effectively controlled blood pressure. The presence of a concomitant pheochromocytoma may precipitate paroxysmal catecholamine surges, fluctuations in cerebral perfusion, and an elevated risk of significant intra-cranial blood loss during neurosurgery. Once patient of brain tumors presented with uncontrolled or fluctuated blood pressure occurred, concurrent endocrine tumor should be considered.

Investigation of risk signatures associated with anoikis in thyroid cancer through integrated transcriptome and Mendelian randomization analysis

BackgroundAnoikis is intricately associated with the malignant progression of cancer. Thyroid cancer (THCA) is the most common endocrine tumor, metastasis is closely related to treatment response and prognosis of THCA. Hence, it is imperative to comprehensively identify predictive prognostic genes and novel molecular targets for effective THCA therapy.MethodsDifferential expression analysis and weighted gene co-expression network analysis (WGCNA) were utilized to mine differentially expressed anoikis-related (DE-ARGs). Then, the prognostic genes were identified and a risk signature was constructed for THCA using univariate Cox analysis and least absolute shrinkage and selection operator (LASSO) method. Furthermore, the associations between risk signature and immune infiltration, immunotherapy, as well as potential mechanisms of action were determined using multiple R packages and Wilcoxon test. Finally, Mendelian randomized (MR) analysis was conducted to investigate the causal relationship between the prognostic genes and THCA.ResultsIn total, six prognostic genes (LRRC75A, METTL7B, ADRA1B, TPD52L1, TNFRSF10C, and CXCL8) related to anoikis were identified, and the corresponding risk signature were constructed to assess the survival time of THCA patients. Immunocorrelation analysis demonstrated the anoikis-relevant risk signature could be used to evaluate immunotherapy effects in THCA patients, and the infiltration of immune cells was correlated with the degree of risk in THCA patients. According to two-sample MR analysis, there was the significant causal relationship between CXCL8 and THCA (odds ratio [OR] > 1 & p< 0.05), and the increase of its gene expression would lead to an increased risk of THCA. Furthermore, real-time quantitative polymerase chain reaction (RT-qPCR) confirmed the upregulated expression patterns of these prognostic genes in THCA tissues.ConclusionIn conclusion, we constructed the risk signature related to anoikis for THCA, which might have important clinical significance for improving the quality of life and treatment effect of THCA patients.

Incidence and Temporal Patterns of Differentiated Thyroid Carcinoma in Children and Adolescents in Germany: A Pooled Analysis Based on Data from the German Malignant Endocrine Tumor Registry and the German Childhood Cancer Registry.

Introduction: The increasing incidence of differentiated thyroid carcinoma (DTC) in children and adolescents has become a growing concern. This study provides the first extensive assessment of incidence patterns and temporal trends of pediatric DTC in Germany, using the best available data from the German Malignant Endocrine Tumor (MET) Registry and the German Childhood Cancer Registry (GCCR) covering a period of 25 years. Patients and Methods: We conducted a register-based incidence and time series analysis, identifying all children and adolescents diagnosed with DTC at ages 0-17 years between 1997 and 2021 in Germany, as recorded in the German MET Registry and/or the GCCR. Age-specific and age-standardized incidence rates (ASR) over time, average annual percentage changes (AAPC), and cross-tabulations were used to evaluate incidence and temporal patterns. Results: We identified 469 DTC cases, including 85.7% papillary thyroid cancer and 9.4% follicular thyroid cancer. The average ASR for the period 1997-2021 was 1.16 per million, with higher rates in females compared with males (1.64 vs. 0.72 per million, respectively). Incidence rates increased with increasing age. The overall ASR increased from 0.84 per million in 1997-2001 to 1.48 per million in 2017-2021, with an AAPC of 3.46% [confidence interval or CI: 2.12-4.83]. The increase was most pronounced in adolescents aged 15-17 years (AAPC: 6.79% [CI: 4.43-9.19]). The proportion of incidentalomas rose from 5% in 1997-2001 to 26% in 2017-2021, yet we observed no marked shift in tumor size between symptomatic and incidental cases. Conclusions: Our study revealed a significant increase in pediatric DTC incidence in Germany, most pronounced among adolescents. The observation of an increasing incidence mirrors global trends and presents a complex public health challenge. While improved detection likely contributes to this trend, the stable tumor size distribution suggests that other factors are also in play. The rising detection of incidentalomas suggests enhanced diagnostic practices unrelated to symptoms of thyroid neoplasia. These findings highlight the need to carefully evaluate diagnostic and screening practices in pediatric populations.

Diagnosis of invasive encapsulated follicular variant papillary thyroid carcinoma by protein-based machine learning.

Although the criteria for follicular-pattern thyroid tumors are well-established, diagnosing these lesions remains challenging in some cases. In the recent World Health Organization Classification of Endocrine and Neuroendocrine Tumors (5th edition), the invasive encapsulated follicular variant of papillary thyroid carcinoma was reclassified as its own entity. It is crucial to differentiate this variant of papillary thyroid carcinoma from low-risk follicular pattern tumors due to their shared morphological characteristics. Proteomics holds significant promise for detecting and quantifying protein biomarkers. We investigated the potential value of a protein biomarker panel defined by machine learning for identifying the invasive encapsulated follicular variant of papillary thyroid carcinoma, initially using formalin- fixed paraffin-embedded samples. We developed a supervised machine-learning model and tested its performance using proteomics data from 46 thyroid tissue samples. We applied a random forest classifier utilizing five protein biomarkers (ZEB1, NUP98, C2C2L, NPAP1, and KCNJ3). This classifier achieved areas under the curve (AUCs) of 1.00 and accuracy rates of 1.00 in training samples for distinguishing the invasive encapsulated follicular variant of papillary thyroid carcinoma from non-malignant samples. Additionally, we analyzed the performance of single-protein/gene receiver operating characteristic in differentiating the invasive encapsulated follicular variant of papillary thyroid carcinoma from others within The Cancer Genome Atlas projects, which yielded an AUC > 0.5. We demonstrated that integration of high-throughput proteomics with machine learning can effectively differentiate the invasive encapsulated follicular variant of papillary thyroid carcinoma from other follicular pattern thyroid tumors.

Preoperative Epidural Infusion for Blood Pressure Control in Phaeochromocytoma

The 2004 World Health Organization (WHO) classification of endocrine tumours defines phaeochromocytoma as a catecholamine-producing intra-adrenal tumour arising from the chromaffin cells. The most important functional characteristics of the adrenal and extra-adrenal sympathetic tissue derived tumours is the production of various types of catecholamines and the related clinical attributes [1]. Preoperative blood pressure control in phaeochromocytoma is an uphill task using multiple medications leading to post operative hypotension. It is well known that complete prevention of perioperative hypertension and tachycardia cannot be achieved by any dose or combination of drugs. Epidural anesthesia is often used for pain control in open resection of these tumours; one of its side effects is hypotension [2]. We describe here a case of phaeochromocytoma in whom perioperative blood pressure control was achieved with the help of epidural drugs instead of systemic antihypertensive medications.

Coagulation-related genes for thyroid cancer prognosis, immune infltration, staging, and drug sensitivity.

Thyroid cancer (THCA) is the most common endocrine tumor. Coagulation may be associated with the development of cancer, but its role in THCA patients is not yet clear. In this study, we determined the predictive value of coagulation biomarker D-dimer for THCA patient lateral lymph node metastasis (LLNM) through receiver operating characteristics (ROC) analysis and logistic regression analysis. Subsequently, this study used the TCGA database to identify coagulation-related molecular subtypes through consensus clustering analysis and compared their prognosis. We identified coagulation-related genes (CRGs) associated with prognosis in thyroid cancer through gene expression data and clinical information, and constructed a prognostic model by selecting the prognostic CRGs using LASSO regression. Patients were divided into high-risk and low-risk groups based on the median score. Subsequently, prognosis, clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity of the two groups were analyzed. We also constructed a nomogram combining the model and clinical features. Finally, the expression of the prognostic CRGs was validated by RT-qPCR. D-dimers had better performance in predicting LLNM(the area under the curve was 0.656 (95% CI 0.580-0.733), with a cut-off value of 0.065 mg/l), and D-dimer>0.065mg/l was an independent predictor of LLNM. Then, we selected 8 prognostic CRGs to construct a predictive model. The prognosis of low-risk group patients was significantly better than that of high-risk group (P<0.001). The results showed significant differences in clinical characteristics, gene mutation occurrence, immune infiltration, function, and drug sensitivity between the high-risk and low-risk groups. We validated by qPCR that these 8 prognostic CRGs were overexpressed in THCA cell lines. Overall, this study provided an in-depth exploration of the potential role of the coagulation in thyroid cancer and its clinical significance, offering a new theoretical basis and research direction for personalized therapy and prognostic evaluation.

A Qualitative Thematic Analysis Exploring Chinese Young Adults' Experiences in Decision Making on the Management of Low-Risk Papillary Thyroid Cancer.

Background: Thyroid cancer is the most common endocrine neoplasm in China. Questions regarding the extent of patient involvement in shared decision-making (SDM) processes persist; this is particularly pertinent to patients considering treatment options for low-risk papillary thyroid cancer (PTC). In this study, we aimed to explore Chinese young adults' experiences of SDM relating to the choice of treatment for low-risk PTC. Methods: The study used a qualitative descriptive design and semistructured interviews. Interviews were conducted with 24 patients (ages ranging from 18 to 38 years; 4 men and 20 women) diagnosed with low-risk (PTC) between March 2023 and May 2024. Twenty-two of 24 patients' tumor size measured 1 cm or smaller; the largest tumor size measured 1.47 cm. Reflexive thematic analysis was used to identify key themes from the transcribed interviews. Results: The analysis revealed that the SDM experiences of young patients with low-risk PTC involve four themes: challenges in information sharing; reasons for information seeking; factors influencing decision making; and self-positioning in treatment decision making. Three self-positions relating to treatment decision making were identified. These included dependent positioning, which reflects a "paternalistic" decision-making pattern; collaborative positioning, reflecting a "sharing" of decision making; and autonomous positioning, reflecting an increased sense of personal responsibility for both managing their health and engagement in decision making. Limited treatment options being offered, overuse of medical terminology, and communication gaps between clinicians and patients were the main challenges described during the information-sharing process. Information that needs persisting after physician-patient consultations resulted in active information-seeking behavior. The key variables identified in this study that potentially affected the decision-making process were future personal considerations, language used to discuss cancer, and negative emotions. Conclusions: These results highlight the necessity of adopting flexible strategies when supporting collaborative treatment decision making in the context of the doctor-patient interaction for low-risk PTC. Based on these findings, clinicians can take measures to enhance the quality of SDM by inquiring about patients' role preferences, providing details of the full range of treatment options, and encouraging patients to share their preferences and concerns relating to possible treatment options.

Pancreatic insulinomas: Our 15-year surgical experience.

Insulinomas are rare endocrine tumors of the pancreas. The majority are benign, sporadic, and solitary. Surgery is the only curative treatment. In this study, we present our experiences with the perioperative management of sporadic and benign pancreatic insulinomas. Patients who underwent surgery for pancreatic insulinoma in our clinic between 2008 and 2023 were retrospectively reviewed. Demographic data, preferred radiological methods, surgical procedures, and morbidity and mortality data were evaluated. Patients with malignant, invasive, or familial multiple endocrine neoplasia mutations were excluded from the study. Nineteen patients underwent surgery, with a median age of 49 years (range: 33-85). Symptoms related to hypoglycemia were the most commonly observed. The tumor location was identified preoperatively in 74% of cases using computed tomography. Palpation and intraoperative ultrasound identified the tumor location in 88% of patients. Enucleation (53%) were the most common surgical procedures. Pancreatic fistula occurred in three patients (17%). While serious morbidity was lower in patients who underwent enucleation, the rate of fistula formation was higher. The accurate localization of insulinomas plays a crucial role in determining the appropriate surgical procedure. With high success rates and lower morbidity, enucleation is the recommended procedure for suitable patients.

Nationwide questionnaire survey on pediatric pancreatic tumors in Japan.

Pediatric pancreatic tumors are rare and account for < 0.1% of all childhood cancers. The primary treatment for pancreatic tumors is surgical resection. However, because of the lack of knowledge regarding pediatric pancreatic tumors, no comprehensive treatment plans for pediatric pancreatic tumors have been developed. To compared the clinical features, treatment methods, and prognosis of pediatric pancreatic tumors in Japan with those in other countries. Questionnaires were sent to 213 pediatric surgical units in Japan. Pancreatic tumors that were not surgically treated were excluded from the survey. The primary survey investigated the number of patients aged 0-18 years who underwent pancreatic tumor surgery and the type of tumors managed during the 22-year study period (from January 1, 2000 to December 31, 2021) by post card. The secondary survey assessed the clinical images, treatment methods, and tumor outcomes via email. The primary survey enrolled 228 patients. In the secondary survey, 213 patients were eventually enrolled. The most common type of pancreatic tumor was solid pseudopapillary neoplasm (SPN) [n = 164 (77.0%)], followed by pancreatoblastoma [n = 16 (7.5%)], pancreatic endocrine tumor [n = 14 (6.6%)], non-epithelial tumor [n = 9 (4.2%)], pancreatic tumor [n = 7 (3.3%)], and metastatic pancreatic tumor [n = 3 (1.4%)]. Overall, 123 (57.7%) patients underwent distal pancreatectomy, of whom 49 underwent laparoscopic surgery. Forty-four (20.7%) patients underwent enucleation, of whom eight underwent laparoscopic surgery. Thirty-two (15.0%) patients underwent pancreaticoduodenectomy, of whom one underwent laparoscopic surgery. All patients with SPN, including those with distant metastases and recurrent disease, survived. SPN was more common in Japan than in other countries. Regardless of the histological type, resection is the most effective treatment for pediatric pancreatic tumors.

Estetrol Inhibits the Prostate Cancer Tumor Stimulators FSH and IGF-1

Background: The co-treatment of androgen deprivation therapy (ADT) for advanced prostate cancer (PCa) with the fetal estrogen estetrol (E4) may further inhibit endocrine PCa tumor stimulators. We previously reported the suppression of follicle-stimulating hormone (FSH), total and free testosterone, and prostate-specific antigen by ADT+E4. Here, we provide more detailed data on FSH suppression by E4 and present new findings on the effect of ADT+E4 on insulin-like growth factor-1 (IGF-1). Methods: A Phase II, double-blind, randomized, placebo-controlled study (the PCombi study) was conducted in advanced PCa patients treated with ADT. The study assessed the effect of E4 co-treatment with LHRH agonist ADT on tumor stimulators, including FSH and IGF-1. Patients starting ADT were randomized 2:1 to receive either 40 mg E4 (n = 41) or placebo (n = 21) for 24 weeks. Non-parametric analyses were performed on the per-protocol population (PP) and individual changes were visualized. Results: The PP included 57 patients (37 ADT+E4; 20 ADT+placebo). ADT+E4 almost completely suppressed FSH in all patients (98% versus 37%; p &lt; 0.0001). IGF-1 levels decreased by 41% with ADT+E4 versus an increase of 10% with ADT+placebo (p &lt; 0.0001). Conclusions: The almost complete suppression of the tumor stimulator FSH using ADT plus E4 observed in all individual patients in this study, along with the augmented suppression of IGF-1 versus an increase by ADT only, may be clinically relevant and suggest the enhanced anti-cancer treatment efficacy of E4 in addition to the previously reported additional suppression of total and free T and PSA.

Cohort review of patients with parathyroid cancer in End Stage Renal Disease (ESRD).

Parathyroid carcinoma (PTTC) is a rare malignant endocrine tumor seen in up to 1-2% of all cases of primary hyperparathyroidism. However, incidence of parathyroid carcinoma in renal hyperparathyroidism is a rare phenomenon. We aimed to evaluate the outcomes of PTTC in renal hyperparathyroidism published in the literature. Cohort review of parathyroid cancer cases reported in Medline (via PubMed), COCHRANE and EMBASE between the period 1985 - 2023 in patients with renal hyperparathyroidism. A total of 48 patients (20M: 28F), with a mean age of 49.8 (± 11.7 SD: range 20-75) years. Dialysis vintage was for a period of 8.9 (± 7.2; range 6months to 40years). The mean preoperative values were as follows: serum corrected calcium-2.87 IQR 2.56-3.01), PTH - 221.8 (IQR 86.6 -257.2pmol/L) and serum phosphate - 2.07 (IQR 1.72-2.28) mmol/L. Preoperative imaging was in the form of ultrasound of the neck in 21 of 48 (44%), MIBI scan in 27/48 (56%), contrast enhanced computerized tomography in 14/48 (29%) and MRI neck in 1/48 (2%). The mean size of the cancer was 2.7 (± 1.35) cm and weight of the gland ranged between 0.9 to 4.98g. 18/48 (37%) patients underwent a total parathyroidectomy and 30/48 (63%) had subtotal parathyroidectomy. En bloc excision of the tumour along with the thyroid along and central compartment lymph nodes was only performed in 12/48 (25%), of whom 9 (19%) had it performed at index surgery, whereas in the rest was done for persistent or recurrent disease. After a mean follow up of 34months, 14 (29%) had local recurrence, 1 (2%) had distant metastasis to the skeletal system, and 12 (25%) to the lungs. Cohort mortality was 6 (13%) due to refractory hypercalcemia. Parathyroid carcinoma in renal hyperparathyroidism is rare but when encountered, en bloc excision with parathyroidectomy provides the best chance of cure. Recurrences can be difficult to treat but may be needed to treat intractable hypercalcaemia.

9220 Machine Learning Methods In Differential Diagnosis Of Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Its Phenocopies

Abstract Disclosure: D. Trukhina: None. K. Voronov: None. E. Mamedova: None. A. Solodovnikov: None. Z. Belaya: None. Background. MEN-1 is a rare autosomal dominant disorder caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterised by the occurrence of parathyroid tumours, gastroenteropancreatic neuroendocrine tumours, pituitary adenomas, and other endocrine and non-endocrine neoplasms. If a patient with the MEN-1 phenotype does not have any mutation in the MEN1 gene, the condition is considered a phenocopy of the syndrome (phMEN1). The goal of this study was to develop a machine learning algorithm to estimate the probability of gMEN-1 vs phMEN-1 based on easily available clinical features at first line differential diagnostics. Materials and methods. A single-center, one-stage, cohort, retrospective study was carried out. Patients were randomly stratified into 2 cohorts: training (80%) and test (20%). Eight machine learning algorithms were used to develop predictive models: Logistic Regression, k-nearest neighbors (kNN), Naive Bayes, binary decision tree (CART), C5.0 decision tree algorithms, Bagged CART, Random Forest, Gradient Boosting (Stochastic Gradient Boosting, GBM). Results. The study included 95 patients with genetically confirmed gMEN-1 syndrome and 60 patients with its phenocopies. As a result of preliminary data processing and selection for the most informative features, the final variables for the classification and prediction of gMEN-1 syndrome were identified: the number of affected parathyroid glands, age at diagnostics, pancreatic tumour existence, heredity, type of pituitary adenoma secretion, and gender. The kNN algorithm demonstrated the best diagnostic performance in a training sample (ROC-AUC - 0.96, sensitivity - 84%, specificity - 100%), which was confirmed in a test sample (ROC-AUC - 1.0; sensitivity - 94.4%, specificity - 100%) to determine genetically confirmed MEN-1 syndrome. Conclusion. The k-nearest neighbours (kNN) algorithm may be used as a first-line differential diagnostics method to select patients to be refered for genetic testing for gMEN-1. Presentation: 6/1/2024

7845 Machine Learning Methods In Differential Diagnosis Of Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Its Phenocopies

Abstract Disclosure: D. Trukhina: None. K. Voronov: None. E. Mamedova: None. A. Solodovnikov: None. Z. Belaya: None. Background. MEN-1 is a rare autosomal dominant disorder caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterised by the occurrence of parathyroid tumours, gastroenteropancreatic neuroendocrine tumours, pituitary adenomas, and other endocrine and non-endocrine neoplasms. If a patient with the MEN-1 phenotype does not have any mutation in the MEN1 gene, the condition is considered a phenocopy of the syndrome (phMEN1).The goal of this study was to develop a machine learning algorithm to estimate the probability of gMEN-1 vs phMEN-1 based on easily available clinical features at first line differential diagnostics. Materials and methods. A single-center, one-stage, cohort, retrospective study was carried out. Patients were randomly stratified into 2 cohorts: training (80%) and test (20%). Eight machine learning algorithms were used to develop predictive models: Logistic Regression, k-nearest neighbors (kNN), Naive Bayes, binary decision tree (CART), C5.0 decision tree algorithms, Bagged CART, Random Forest, Gradient Boosting (Stochastic Gradient Boosting, GBM). Results. The study included 95 patients with genetically confirmed gMEN-1 syndrome and 60 patients with its phenocopies. As a result of preliminary data processing and selection for the most informative features, the final variables for the classification and prediction of gMEN-1 syndrome were identified: the number of affected parathyroid glands, age at diagnostics, pancreatic tumour existence, heredity, type of pituitary adenoma secretion, and gender. The kNN algorithm demonstrated the best diagnostic performance in a training sample (ROC-AUC - 0.96, sensitivity - 84%, specificity - 100%), which was confirmed in a test sample (ROC-AUC - 1.0; sensitivity - 94.4%, specificity - 100%) to determine genetically confirmed MEN-1 syndrome. Conclusion. The k-nearest neighbours (kNN) algorithm may be used as a first-line differential diagnostics method to select patients to be refered for genetic testing for gMEN-1. Presentation: 6/1/2024

6564 A Case of Severe Hypercalcemia in Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (&amp;lt;6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

12363 A Unique Case Of hüRthle Cell Carcinoma of the Thyroid Gland and Meningioma

Abstract Disclosure: I. Elsayed: None. R. Khan: None. H. Dhaliwal: None. Introduction: MEN1 gene is a tumor suppressor gene on chromosome 11q13 that encodes the nuclear protein menin, which regulates cell growth and cycle. When menin protein is deficient, MEN1 develops. MEN1 mutation usually involves tumors within the parathyroid glands, pancreas, or pituitary. Case Description: A 66-year-old male with past medical history of hypertension, hyperlipidemia, and coronary artery disease presented with sudden onset dizziness, nausea and vomiting for 1 hour. He had similar symptoms on and off for several months, however on the day of presentation, these symptoms were much more acute and severe. Stroke work-up was done including CT and CTA head which revealed a 1.7cm enhancing lesion to R temporal lobe with surrounding edema with an incidental 3 x 3 cm heterogeneous mass in the large portion of the right thyroid gland. Steroids initiated. MRI brain imaging revealed findings consistent with meningioma with local mass effect and pronounced parenchymal edema. Patient underwent successful resection of the mass and pathology confirmed diagnosis of Meningioma, WHO Grade 1. Ear Nose Throat specialist was consulted for incidental thyroid mass. Ultrasound guided Fine needle aspiration biopsy was, Pathology report returned suspicious for follicular neoplasm, Hürthle cell-type. Patient initially underwent right substernal semi-thyroidectomy. Pathology confirmed diagnosis of Oncocytic (Hürthle cell) carcinoma, minimally invasive, 4.3 cm with a single focus of capsular invasion, negative for lymphovascular invasion Discussion: This case presents a 66-year-old male with a rare coexistence of two distinct tumors: a meningioma and a Hürthle cell carcinoma of the thyroid gland. While meningiomas and Hürthle cell carcinoma are not commonly associated with MEN1 syndrome, there have been reports of atypical cases with unusual tumor associations. MEN1 is usually characterized by abnormalities in at least two affected endocrine glands, but variations can involve other endocrine and non-endocrine tumors as well. 25% of thyroid disease can be seen in MEN 1 syndrome; typically papillary thyroid cancer. Only one case in literature found Hürthle cell carcinoma and meningioma in the setting of MEN-1 phenotype. A second case unique case was Hürthle cell carcinoma with metastases to the meninges. The discovery of both a meningioma and a Hürthle cell carcinoma in this patient emphasizes the importance of clinicians being vigilant for the possibility of multiple neoplasms. This case highlights that there may be a relation between role of MEN1 with atypical neoplasms not commonly seen. Presentation: 6/2/2024

6564 A Case Of Severe Hypercalcemia In Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (&amp;lt;6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

7040 Embolization Of Hepatic Metastases Is Effective For Palliative Management Of Severe Cushing Syndrome

Abstract Disclosure: S. Zhang: None. C. Musonza: None. A. Pillai: None. M. Ramos-Roman: None. J. Abramowitz: None. S. Mirfakhraee: None. P. Polanco: None. A.P. Dackiw: None. S. Al Mutar: None. A. Mallik: None. L. Jia: None. O. Hamidi: None. Background: Cushing syndrome (CS) due to metastatic endocrine neoplasms poses substantial treatment challenges. Arterial embolization and Yttrium-90 (Y-90) radioembolization for hepatic metastases are effective in the management of metastases due to neuroendocrine tumors (NETs). However, data are scarce on the role of embolization of liver metastases in patients with CS. Here, we report two cases of severe CS due to bulky hepatic metastases treated with embolization techniques. Case 1 A 49-year-old woman presented with severe ectopic CS and a 15-cm hepatic metastatic conglomerate. Liver biopsy showed NET of unknown primary. Treatment with subcutaneous octreotide and metyrapone (total daily dose 3000mg) resulted in modest improvement of serum cortisol from 89.8 to 45.8 mcg/dL. She was not a candidate for bilateral adrenalectomy or hepatectomy due to bulky hepatic metastases and subsequently underwent bland embolization to the hepatic conglomerate. Cortisol decreased from 63.9 mcg/dL to 13.8 mcg/dL after the initial procedure, but then rebounded to 35.8 mcg/dL. Serum cortisol decreased to 19.4 mcg/dL following additional embolization, and she was discharged on metyrapone 500mg three times daily. CS remained controlled 12 weeks after the procedure. Interval imaging showed a decrease in size of the dominant hepatic mass (9.7 cm). The patient is currently undergoing chemotherapy with carboplatin and etoposide. Case 2: A 40-year-old man presented to an outside institution with CS due to a 6.9 cm right adrenal mass and underwent adrenalectomy. Pathology showed oncocytic neoplasm of uncertain malignant potential. A year later, he presented to our hospital with recurrent CS and was found to have a 10.2 cm liver lesion, confirming stage IV adrenocortical carcinoma. FDG PET/CT did not show additional lesions. He was treated with osilodrostat and mitotane but his hypercortisolism remained uncontrolled. Mitotane was discontinued after a few doses due to side effects. Metastasectomy was attempted but halted due to extensive peritoneal carcinomatosis noted in the operating room. He was subsequently treated with Y-90 radioembolization to the liver metastasis. Afterwards, osilodrostat was held and serum cortisol decreased from 49.6 to 6.9 mcg/dL on day 14 post-procedure. Hydrocortisone was initiated for treatment of adrenal insufficiency. He received cisplatin, doxorubicin, and etoposide, but stopped after the first cycle due to side effects. Recent imaging showed a decrease in the hepatic lesion to 6.5 cm. Presently, the patient continues to have persistent adrenal insufficiency confirming remission of CS. Conclusion: These cases illustrate the potential efficacy of bland embolization and Y-90 radioembolization for palliative treatment of severe CS in patients with hepatic metastases. Presentation: 6/2/2024

12214 Metastatic Functional Thyroid Carcinoma As An Unusual Cause Of Hyperthyroidism

Abstract Disclosure: S. Jimenez Salazar: None. N. Aristizabal Henao: None. C. Aguilar Londoño: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Differentiated thyroid carcinoma (DTC) represents the most prevalent endocrine neoplasm. Less than 10% present distant metastases, with the lung (50%), and skeleton (25%) being the most frequently affected sites. The location of bone metastases predominates in the spine and pelvis; usually as osteolytic lesions, being more frequent in follicular thyroid cancer (FTC) (7-28%) than in patients with papillary thyroid cancer (PTC) (1.4-7%). In rare cases this metastasis can be functional and trigger a thyrotoxicosis syndrome with or without recombinant human TSH injections prior to therapy with 131-I. Clinical case: 59-year-old woman with a history of bone metastatic follicular thyroid cancer (FTC) presented with 1 month of palpitations, 4 kg weight loss, non-dysenteric diarrhea and progressive dyspnea. Her FTC had been diagnosed 8 years prior her consultation. In that time iodine refractoriness was considered due to the progression of bone lesions, and Sorafenib 800 mg per day was initiated, which was not tolerated due to severe dermatological manifestations, and the patient decided not to continue with TKI therapy. Since then, she has been treated with zoledronic acid and local radiotherapy as part of palliative care. On physical examination, she was tachycardic (150 bpm), and hypertensive (BP 160/100 mmHg). A suppressed TSH (&amp;lt;0.01 uUI/mL, n: 0.4-4 uUI/mL) with elevation of thyroid hormones (free T4 3.99 ng/dL, n: 0.8-2 ng/dL and total T3 480 ng/dL, n: 45-140 ng/dL) was documented, associated with a patient who had required a dose adjustment of levothyroxine from 700 mcg to 350 mcg weekly 2 months prior to admission. Additionally, she had a significantly elevated thyroglobulin (&amp;gt;5000 ng/mL, n: 0.1-64.1 ng/mL) with undetectable antithyroglobulin antibodies (1.09 UI/mL, n: 0-4.11 UI/mL). Considering the history of total thyroidectomy and the high tumor burden, secondary thyrotoxicosis due to functioning bone metastases of DTC was considered. Levothyroxine was discontinued, and propranolol was initiated for the control of adrenergic symptoms, along with methimazole, cholestyramine, and systemic steroids to control thyroid hormone production. 3 days after therapy adjustment dyspnea, palpitations, and thyroid function tests improved significantly (free T4 1.43 ng/dL, n: 0.8-2 ng/dL and total T3 178 ng/dL, n: 45-140 ng/dL). A new administration of therapy with 131-I 200 mCi was indicated. Antithyroid therapy and beta-blockers were continued with sustained biochemical control. Conclusion: Functional bone metastases of FTC can lead to high morbidity and mortality. Treatment consists of surgical cytoreduction of any large accessible metastatic lesion, therapy with 131-I, and high-dose antithyroid drugs to control hyperthyroidism. It is important to avoid the use of recombinant human TSH due to the risk of secondary thyrotoxicosis following its administration. Presentation: 6/2/2024

6981 Atypical hypoglycemia in a teenage boy with prediabetes

Abstract Disclosure: N. Shahid: None. C. salgado: None. N. Gurtunca: None. Background: Hypoglycemia in teenagers is seen less commonly than in younger children. Overweight children with prediabetes presenting with hypoglycemia symptoms are often considered to have reactive post-prandial hypoglycemia due to the degree of hyperinsulinemia with insulin resistance seen in these children. We present a 13-year-old boy with prediabetes, who presented with episodes of altered mental status and was found to have hypoglycemia due to a solitary insulin secreting tumor. Case presentation: A 13-yr old boy with pre-diabetes presented to the ER with altered consciousness and non-ketotic, non-acidotic hypoglycemia [25 mg/dl] &amp; trace ketonuria in the setting of Influenza A infection. Weight and BMI above the 99th%ile and acanthosis nigricans in the skin creases. No access to oral hypoglycemic agents. Urine toxicology was negative. EEG was normal. Euglycemia and level of consciousness restored after IV dextrose &amp; this was considered a possible hypoglycemic seizure episode secondary to poor oral intake. 4 months later he had another episode of altered mental status, jittery movements and was found to be hypoglycemic [41 mg/dl]. He was admitted for further workup of recurrent hypoglycemia. Adrenal insufficiency was ruled out and a diagnostic fast was started. After 15 hours, he developed non-ketotic hypoglycemia [&amp;lt;50 mg/dl]. Critical sample [Table 1] and Glucagon challenge [Table 2] at the termination of the fast confirmed hyperinsulinemic hypoglycemia. Given the unusual age and presentation, an MRI abdomen was done which showed a 1.6 cm lesion in the pancreatic body [Fig 1]. Dotatate whole body PET scan confirmed the insulinoma with no evidence of nodal or distant metastasis [Fig 2]. He underwent surgical enucleation of the insulinoma. Intraoperative secretin showed no evidence of pancreatic duct dilatation or leakage. Hereditary endocrine tumor panel including multiple endocrine neoplasia [MEN] gene analysis was negative. The postoperative course was complicated by a persistent pancreatic leak and pancreatitis eventually requiring an ERCP and stent placement 2 months post operatively. Conclusion: Insulinomas are very rare neuroendocrine tumors in pediatric population, with a prevalence of one in 250,000 and median age at presentation of 45-50 years. About 90% insulinomas are benign and less than 10% are associated with MEN-1 syndrome. Chronic hypoglycemia irrespective of the underlying insulin resistance of prediabetes can be seen with insulinoma and can cause hypoglycemia unawareness as seen in our patient. This has also been reported in literature to be misdiagnosed as refractory epilepsy or psychiatric disorders. Hypoglycemic symptoms at any age should be promptly worked up. Ruling out associated neuroendocrine hereditary tumor syndromes is crucial and prognosis of benign solitary insulinomas after surgical removal is mostly favorable. Presentation: 6/3/2024

7703 Adrenal Cortical Carcinoma With Vascular Involvement - Complex Case Requiring Life-Saving Surgery With Bovine Pericardium- IVC Reconstruction

Abstract Disclosure: V. mehta: None. M. Renzu: None. K.N. Pereira: None. S. Sampath: None. S. Sruthi: None. E.B. Ruby: None. Adrenocortical carcinomas (ACCs) are rare endocrine tumors that exhibit unusual biological characteristics. Roughly 66% of cases are functional and have excessive hormone release causing classic symptoms of hypercortisolism, including plethora, diabetes, muscle weakness/atrophy, virilization, and osteoporosis. Few present with vague signs due to mass effects, including but not limited to abdominal/flank pain, fullness, or early satiety; the rest are incidental findings. We present a case of a 55-year-old female with no medical history presented following weeks of progressive abdominal pain with abdominal wall erythema, leg swelling, and dyspnea along with hirsutism, leukocytosis, elevated BNP, hematuria concerning for abdominal wall cellulitis and new-onset CHF. Initial CT chest revealed incompletely visualized incidental adrenal mass. Further investigations with CT abdomen and lab work revealed a left adrenal mass suspicious for ACC, extending into the left renal vein and IVC, elevated urine metanephrines and normetanephrine, and elevated cortisol levels with low ACTH. The dexamethasone suppression test confirmed inadequate cortisol suppression. Patient underwent aggressive surgery with exploratory laparotomy revealing tumor thrombus in left renal vein extending into Inferior vena cava (IVC). A left adrenalectomy, nephrectomy, and IVC reconstruction using a Bovine Pericardial Patch (BPP), which is majorly used for arterial reconstruction, was performed. Pathology results indicated ACC, measuring 13.5 cm, with extension into renal vein and vascular invasion, staged as pT4pN0 cM0 without evidence of deficient mismatch repair protein expression. ACCs are rare and profoundly aggressive malignancies with an incidence rate of 0.7–2.0 per million per year with bimodal age distribution. Disease peaks before the age of five and in the fourth to fifth decade of life, with increased incidence in females. Diagnosis cannot be conclusively established by a single histological technique, imaging, hormonal work-up, or immunohistochemical labeling, but surgical excision is the gold standard. Complete surgical resection is the only possible approach for curing or improving survival chances in patients with adrenal mass/metastasis. A retrospective case study of 36 venous reconstructions using BPP showed few complications like thrombosis in 14% (versus 11% in autologous venous repair), 11% reoperated, 3-4% developed partial thrombus and hematoma. Our case exemplifies the successful management of challenging ACC with vascular involvement using BPP, which is mostly used for arterial repairs and is now expanding to venous repairs. Outcomes stress the ongoing need for research and collaborative efforts to refine and standardize the ideal approach to ACC patients with IVC thrombosis and the use of BPP in venous repair. Presentation: 6/1/2024