bluuebunny/crossref_metadata_2025_split huggingface dataset:
8785 Does Somatostatin Receptor Expression Intensity Impact Prognosis in Non Pituitary Neuroendocrine Tumors Treated with Somatostatin Analogues?
Authors: Jouneghani Nasrin Saleh , Fazeli Sasan , Chang Sue , Hosseini Alireza , Marandi Roghayeh , Siddiqui Abdullah , Talley Min , Salehian Behrouz 
Published: October 2024

Abstract
Disclosure: N. Saleh Jouneghani: None. S. Fazeli: None. S. Chang: None. A. Hosseini: None. R. Marandi: None. A. Siddiqui: None. M. Talley: None. B. Salehian: None.
Does Somatostatin Receptor Expression Intensity Impact Prognosis in Non Pituitary Neuroendocrine Tumors Treated with Somatostatin Analogues? Introduction: Non-pituitary neuroendocrine tumors (NETs) show different somatostatin receptor subtype (SSTR) expression, but their role in tumor progression and prognosis is not well known. We hypothesized that NETs with higher expression of SSTR2, SSRT5, or co-expression of SSTR2 and SSTR5 will have better outcome when treated with Somatostatin Analogues (SSA). Method: Retrospectively, patients with non-pituitary neuroendocrine tumors, followed for more than one year between 1985 and 2022, and treated with SSA (Octreotide or Lanreotide) who had available tissue were selected. Tissue immunostaining performed for SSTR2 and SSTR5 with use of monoclonal antibodies. Expression analysis of the SSTR2 and SSTR5 were evaluated by the validated semi-quantitatively method, reported by an intensity score of 0 -3. The progression free survival and overall survival were calculated by Kaplan Meier and compared in different subgroups with SSTR expression intensity. Response evaluation was assessed using RECIST v1.1. Results: Of 279 non-pituitary neuroendocrine tumors, 51 meet the criteria and tissue sent for analysis. The median age at diagnosis was 62; male 49%, with median follow up 7 years, 85% stage IV at diagnosis, most common primary tumor was in gut 54% followed by pancreas 33%. Positive SSRT5 tumors had 93% SSRT2 co-expression. There were no significant differences in progression-free survival (PFS) observed between tumors with low or high SSTR2 intensity expression (P=0.62). The presence or absences of SSRT5 expression did not have any impact on PFS (p=0.57) or overall survival (p=0.3). Conclusion: in the patient with non-pituitary neuroendocrine tumors, higher SSTR2 expression intensity or having SSRT5 co-expression, did not correlate with a better PFS or overall survival in response to SSA, in our study. Further prospective studies are needed to clarify if higher expression intensity of SSRTs correlates with better response to SSAs in NETs.
Presentation: 6/1/2024
7166 EFFECT OF ANTI-NEOPLASTIC THERAPIES ON CARCINOMA AND AGGRESSIVE PITUITARY TUMORS : A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Nunes-Nogueira Vania dos Santos , Cardoso Ana Beatriz Ribeiro , Zimmermann Amanda Cristina 
Published: October 2024

Abstract
Disclosure: V.D. Nunes-Nogueira: None. A.R. Cardoso: None. A.C. Zimmermann: None.
Introduction: Approximately 10% of the pituitary adenomas can have an aggressive behavior and 0.2% can present metastasis, being classified as pituitary carcinomas. Objective: Evaluate the tumor control obtained by anti-neoplastic therapies that are still little explored in the context of carcinoma and aggressive pituitary tumors. Methods: A systematic review according to the Joanna Briggs Institute has been conducted. We have included studies that evaluated patients with carcinoma or aggressive pituitary tumors who underwent treatment with at least one of the following therapies: Temozolomide, VEGF Inhibitors, Peptide Receptor Radionuclide Therapy (PRRT), Everolimus, Immune Checkpoint Inhibitors, EGFR Inhibitors, Capecitabine and temozolomide (CAPTEM). The main outcome assessed by the study was the frequency of tumor response according to the RECIST protocol classification. Embase, Medline, LILACS, and CENTRAL were our source databases. Proportional meta-analyses were performed to calculate the overall frequencies of complete remission (CR), partial remission (PR; minimum shrinkage of 30%), stable disease (SD) and progression disease (PD). We used Stata Software 18, the updated command “metaprop_one” and fit the logistic normal random effect model. Results: None clinical trial was found, and sixty case report/case series were included. The most frequent therapy used was temozolomide (101 patients), followed by PRRT, pembrolizumab, lapatinib, CAPTEM, bevacizumab, ipilimumab/ nivolumab and everolimus, with respectively 9, 6 ,6, 6, 4, 3 and 1 individuals. The majority of patient in temozolomide studies had prolactinomas (40/101), followed by Cushing’s disease (25/101), the overall frequency of CR with this drug was 1% (ch^2=2.7; p=0.049, Predictive Interval (PI) 1% to 93%, 7 events), PR was 45% ( ch^2=1.8, p=0.091, PI= 8-89%, 46 events), SD 14% (CI 95%=5 a 33%, 20 events), and PD was 25% (95%CI: 14-40%, 28 events). Two patients receiving CAPTEM presented CR, no other studies presented this outcome. In the PRRT studies, the overall frequency of PR was 22% (95%CI 6 to 58%) and PD was 44% (95%CI 18 to 75).Conclusion: Temozolomide has been the therapy most frequent used in the management of carcinoma and aggressive pituitary tumor, being PR the most frequent outcome, followed by PD and SD, with low percentage of CR. The other drugs approached by this review showed similar poor response although they were less tested in the context of this neoplasms.
Presentation: 6/2/2024
8142 Endocrine Considerations Prior to Pituitary Tumor Resection
Authors: Einafshar Parastou , Delibasi Tuncay 
Published: October 2024

Abstract
Disclosure: P. Einafshar: None. T. Delibasi: None.
Endocrine Considerations in Pituitary Tumor Resection Introduction: Diabetes Insipidus (DI) is an endocrine condition involving a disturbance to the action of Anti-Diuretic Hormone (ADH) resulting in polyuria, and polydipsia with complications such as severe water and electrolyte disturbances. It can be classified into Central DI which affects the secretion of ADH or Nephrogenic DI which affects peripheral ADH receptors in Distal Convoluted Tubules (DCTs) in the renal system. Both subtypes however present similarly and are usually known to be transient. It is important to consider the most common etiologies contributing to both central and nephrogenic DI as severe complications may arise if not diagnosed and treated promptly. The most important step is to monitor and manage water and electrolytes and avoid excessive water loss which can lead to irreversible complications. This can be accomplished by introducing synthetic ADH called DDAVP or Desmopressin. Case Description: A 57-year-old female was admitted in preparation for a supra-orbital resection of a suprasellar mass. Two hours post-procedure, she was found to have an increase in urine output with her labs notable for a significant acute increase in serum sodium and a decrease in urine osmolality. Upon emergent Endocrinology evaluation, due to concerns of Acute Diabetes Insipidus in the setting of insult to the pituitary stalk, she was started on emergent treatment with IV DDAVP. Her course was complicated with persistent DI resulting in a case of permanent DI requiring out-patient daily treatments with DDAVP. Discussion: Injury to the pituitary stalk resulting in various endocrine abnormalities has been studied involving a trans-sphenoidal resection of pituitary tumors, but there is a paucity of cases reported when patients undergo a supra-orbital surgical approach. It is vital for Endocrinology and Neurosurgical services to be aware of this phenomenon, and a multi-disciplinary approach to patient management should be considered. Furthermore, close follow-up of pituitary hormones in the post-operative setting is imperative in order to avoid severe complications, such as brain damage or poor mental status. We hope to educate residents and fellows about this phenomenon that is rarely reported in the literature but can have profound effects on patient’s quality of life if not considered by the consulting Endocrinology team. References Christ-Crain, M., Winzeler, B., & Refardt, J. (2021). Diagnosis and management of diabetes insipidus for the internist: an update. Journal of internal medicine, 290(1), 73-87. Mutter, C. M., Smith, T., Menze, O., Zakharia, M., & Nguyen, H. (2021). Diabetes insipidus: pathogenesis, diagnosis, and clinical management. Cureus, 13(2).
Presentation: 6/1/2024
9377 Exploring Strategies To Reverse Cellular Characteristics Of Succinate Dehydrogenase B-loss Immortalized Chromaffin Cells
Authors: Rahimi Leili , Al-Khazal Fatimah , Becker Nicole A , James Maher L 
Published: October 2024

Abstract
Disclosure: L. Rahimi: None. F. Al-Khazal: None. N. Becker: None. L. Maher, III: None.
Carriers of loss-of-function alleles in genes encoding the four succinate dehydrogenase (SDH) subunits exhibit a heightened risk for pheochromocytoma/paraganglioma (PPGL), a rare neuroendocrine tumor of chromaffin cells. Tumorigenesis begins with the somatic loss of the remaining functional gene copy, resulting in a cell devoid of functional SDH. Compared to wild-type immortalized chromaffin cells (WT imCCs), SDHB-KO immortalized chromaffin cells (SDHB-KO imCCs) are larger, grow more slowly, display deformed mitochondria, show strikingly heightened succinate accumulation, and altered metabolism. Among several mechanisms proposed to link SDH deficiency with PPGL tumorigenesis, the accumulation of succinate as an oncometabolite is a leading hypothesis. We describe two attempts to suppress succinate accumulation in SDHB-KO imCCs. First, riboflavin has previously been shown to enhance residual SDHA flavinylation and enzymatic function, possibly reducing succinate levels by supporting conversion of accumulated succinate to fumarate in the absence of SDHB. We tested this by treating WT and SDHB-KO imCCs with 5 µM riboflavin for 2 weeks. Metabolomic analysis did not show decreased succinate, suggesting that enzyme activity of any remaining SDHA subunit was not rescued by increased flavinylation. Second, we envisioned a gene therapy approach to replace defective SDHB with a rescuing transgene. SDHB-KO imCCs received DNA encoding SDHB or SDHC cDNAs via transposon technology, confirmed by PCR and analyzed by western blot analyses. These studies showed that whereas WT imCCs successfully expressed processed transgene products in mitochondria, SDHB-KO imCCs could not process or transport rescuing SDH subunits into mitochondria. This shows that transposed SDHB-KO imCCs cannot properly express a rescuing SDHB subunit and do not revert to a wild-type phenotype. It is likely that the severely damaged mitochondria of SDHB-KO imCCs are incompetent to process and import rescuing SDHB subunits, so unprocessed protein accumulates without effect. This defect may lie in the mitochondrial targeting peptide recognition system because the targeting peptide of rescuing SDHB protein is not removed in SDHB-KO imCCs as judged by western blotting. In summary, we show the failure of two conceptually simple tactics to suppress succinate accumulation in SDHB-KO imCCs with highly defective mitochondria: rescue of SDHA by supporting flavinylation, or rescue of SDHB with a replacement gene copy. Further research may allow screening for small molecules that suppress succinate accumulation by other mechanisms. It remains to be determined if blocking succinate accumulation would be therapeutic in SDH-loss PPGL tumors.
Presentation: 6/1/2024
12562 Extraocular Muscle Enlargement With Proptosis In A Patient With Non Thyroidal Disease
Authors: Bantu S S , Kabir P N , Gondhi A , Vaughan T B 
Published: October 2024

Abstract
Disclosure: S.S. Bantu: None. P.N. Kabir: None. A. Gondhi: None. T.B. Vaughan: None.
Extraocular muscle enlargement with proptosis in a patient with Nonthyroidal disease Introduction: Majority of cases with extraocular muscle enlargement (EOME) is due to Graves’ disease, commonly in about 95% cases and another 5% make up other causes including inflammatory, neoplastic, vascular, infectious and acromegaly. We present a patient with sudden loss of vision, retroorbital pain with visual field deficits found to have EOME and subsequently a pituitary macroadenoma on imaging. Case: We present a 54-year-old male with history of hypertension, obstructive sleep apnea and morbid obesity who presented to us with complains of left sided vision loss. Patient was evaluated by ophthalmology and noted to have unilateral, left-sided, change in visual acuity. Physical exam was notable for macrognathia, skin tags, enlarged hands, excessive sweating. MRI brain revealed bilateral EOME with proptosis and a pituitary macroadenoma measuring 1.5x1.7x1.3cm, abutting the pre-chiasmatic left optic nerve. On biochemical evaluation he was noted to have elevated IGF1 of 979 confirming the diagnosis of acromegaly. ((hemoglobin A1C of 5.5%, prolactin 5.1, FT4 0.89, TSH 0.692, total testosterone 61, IGF1 level was 979)). He underwent transsphenoidal resection of the pituitary macroadenoma. Pathology showed sparsely granulated somatotroph adenoma. Discussion: Acromegaly has an incidence of 3-4 cases per million per year. The characteristics of the disease are due to chronic growth hormone hypersecretion resulting in the excessive growth of tissue due to the stimulation of insulin-like growth factor 1 (IGF-1). EOME with proptosis in acromegaly is seen rarely. Visual symptoms may manifest as visual field deficits due to compression of the optic pathway in 18-25% cases, increased intraocular pressure, increase in corneal thickness and a diffuse symmetrical enlargement of the extraocular muscles which cannot be distinguished from thyroid orbitopathy on imaging. The degree of enlargement appears to correlate with the duration of the disease rather than the levels of IGF1. EOME improves with the treatment of acromegaly. Although visual symptoms may be a rare presentation of acromegaly, if the clinical suspicion exists, one may consider obtaining an IGF-1 level to complete the evaluation of EOME if the thyroid levels are normal.
Presentation: 6/3/2024
12580 Factitious Cushing’s Syndrome Secondary To Indiscriminate Use Of Brazilian Herbal Medicine: Case Report
Authors: Warszawski Leila , de Marca Seidel Karen F , Padilla Carlos , de Souza Valéria Priscila Neves , Calmon Júlia Ribeiro 
Published: October 2024

Abstract
Disclosure: L. Warszawski: None. K.F. Seidel: None. C. Padilla: None. V.N. de Souza: None. J.R. Calmon: None.
Background: Herbal medicines are obtained exclusively from active plant raw materials, which leads people to believe that these medications are safer and free from side effects. Moreira milk is a Brazilian herbal medicine used mainly for its supposed anti-inflammatory properties. This medication is not regulated by The Brazilian Health Regulatory Agency (Anvisa). Herein we report a case of exogenous Cushing's Syndrome (CS) caused by continuous use of Moreira milk. Case report: A 53-year-old female patient was seen in October 2018 at the endocrinology clinic due to progressive weight gain, mood swings, edema and weakness of the lower limbs, violet streaks on the flanks, easy bruising and dorsocervical fat pad. She brought tests to our specialized consultation that showed low basal cortisol (0.4 mcg/dL - RR 5 to 25 mg/dL) and ACTH ( %lt; 5 pg/ml - RR 10 to 60mg/dL), two HbA1c values above 6.5% and a sella turcica MRI revealing normal-sized pituitary gland with a hypo-enhancing contrast area, possibly corresponding to a microadenoma. New tests were carried out which showed the maintenance of low basal cortisol and ACTH. The patient reported background use of losartan and Moreira milk for 2 years - as a phytotherapy to control joint pain after Chikungunya. She denied use of topical, inhalatory or oral corticoids. Exogenous CS was suspected and the use of Moreira milk was interrupted. We proceeded to use prednisone for weaning, which had to be gradual, but the patient progressed with clinical improvement. Conclusion: There are some cases of hypercortisolism associated with herbal medicines, the majority of which are due to contamination with synthetic glucocorticoids, as is believed to occur with Moreira milk. Despite being widely sold in Brazil, because it is not approved by ANVISA, the production cannot be inspected, therefore, can be contaminated. Those cases of exogenous CS are challenging, and misidentifying Cushing's syndrome can result in a series of improper treatments with severe repercussions.
Presentation: 6/1/2024
12530 Inferior Petrosal Sinus Sampling In Cushing’s Disease
Authors: Gondhi A , Antharam S , Moledina I 
Published: October 2024

Abstract
Disclosure: A. Gondhi: None. S. Antharam: None. I. Moledina: None.
Inferior Petrosal Sinus Sampling in Cushing’s Disease Introduction: Cushing's disease (CD) is the most common cause of endogenous Cushing syndrome( CS) caused by ACTH secreting pituitary tumor. MRI is typically used for imaging, but standard MRI may only detect 50% of microadenomas. In these cases, inferior petrosal sinus sampling (IPSS) is the gold standard in detecting pituitary source of ACTH. Case presentation:A 53-year-old man presented with signs and symptoms of CS: fatigue, weight gain, decreased libido, mood swings, new onset prediabetes. Physical examination revealed cushingoid appearance with facial flushing, easy bruising, abdominal purple striae. Initial work up revealed ACTH dependent CS: elevated late night Salivary cortisol 0.39 mcg/dL (&lt;0.09 mcg/dL), 24hr urine free cortisol 192 mcg/24 hour (4 – 50 mcg/24 hour)Non suppressed cortisol 8.1 mcg/dL (&lt;1.8 mcg/dL) after 1mg dexamethasone suppression test8 AM ACTH 56 pg/ml (7.2 – 63 pg/ml), DHEAS 491 mcg/dL (38-318 mcg/dL)Pituitary hormonal work up: normal Prolactin 7.8 ng/mL (2.6-13.1 ng/mL)Low TSH 0.29 ng/ml (0.45-5.3 ng/ml) with normal Free T4 0.76 ng/dl (0.58-1.6 ng/dl)Low Total Testosterone 150 ng/dl (175-781 ng/dl), Low FSH&lt;0.7 mInt units/ml(1.27-19.26 mInt units/ml), Low LH 1 mInt units/ml (1.24- 8.62 mInt units/ml), Normal IGF 180 ng/mL (65-222 ng/mL), A1C 6% (Prediabetes – 5.7-6.4) MRI Brain showed normal pituitary gland. IPSS was performed with DDAVP: +2, +5, +10, +15: Right/ periphery ratio- 31.8, 10.75, 7.6, 5.3. left/periphery ratio- 26.6, 18.8, 8.3, 7.5. All the ratios &gt;=3, which showed clear central to peripheral gradient. and no left or right difference consistent with Cushing's disease. Subsequently, a transsphenoidal pituitary gland resection was performed. Suspicious tissue was excised from both sides during the surgery, showing positive ACTH immunostaining, consistent with pituitary microadenoma. Post-operative labs showed significant improvement with normalization of Cortisol 3.2 mcg/dl, ACTH 45 pg/ml, TSH 3.14 ng/ml, FT4 0.61 ng/dl, FSH 1.7 mInt units/ml, LH 2.4 mInt units/ml, Prolactin 7.1 ng/ml, A1C 5.4 %He was discharged on physiological dose of Hydrocortisone and passed cortisol stimulation test (3.4 mcg/dl ---&gt; 18.1 mcg/dl) Conclusion: Distinguishing between CD and ectopic ACTH secretion is crucial due to the differing treatment options. The most accurate method for differentiation is IPSS, which boasts high sensitivity and specificity compared to other analyses. Despite its invasiveness, IPSS is associated with rare adverse events, making it a valuable tool in clinical practice.
Presentation: 6/3/2024
8716 Late Onset of Temozolomide in Aggressive Pituitary Tumors: Insights From a Leading Oncology Center in Latin America
Authors: de Macedo Camila Regina Pereira Batista , de Magalhães Isabelle Pinheiro Amaro , Glezer Andrea , da Cunha Neto Malebranche Berardo Carneiro , de Castro Musolino Nina Rosa , Feher Olavo , Batista Rafael Loch 
Published: October 2024

Abstract
Disclosure: C.R. de Macedo: None. I.P. de Magalhães: None. A. Glezer: None. M. Berardo Carneiro da Cunha Neto: None. N.R. de Castro Musolino: None. O. Feher: None. R.L. Batista: None.
Introduction: Temozolomide (TMZ) is an oral alkylating agent used in management of glioblastoma multiforme. Since 2006, TMZ is used in patients with pituitary tumors (PITNets) with yielded promising outcomes as an alternative for aggressive PITNets. Objective: To evaluate the response to TMZ in patients with aggressive or metastatic PITNets within the largest tertiary oncology service in Latin America. Patients and Methods: We screened all cases that received TMZ at our institution between 2008-2023 (n=661, primarily glioblastoma cases). We identified 7 cases that TMZ was employed for treating PITNets. We assessed for PITNet characteristics, functionality, timelines of treatment initiation, correlation with radiotherapy, duration of TMZ usage and treatment response utilizing the RECIST criteria. Results: At the time of diagnosis, all patients presented with macro-PITNets and 6 were giant (size greater than 4 cm). In terms of hormonal production, 4 cases were prolactinomas and 3 were non-functioning PITNets. Over the follow-up period, these tumors exhibited an aggressive behavior, manifesting rapid tumor growth despite optimized treatments and one case was recategorized as metastatic PitNET. All cases demonstrated a Ki-67 index greater than or equal to 3%. The initiation of TMZ occurred on average 9.48 years after diagnosis and subsequent to multiple surgical interventions (average of 1.8 surgeries). In 5 cases, TMZ followed radiotherapy. Among the cohort, 3 of 7 patients underwent 6 cycles of TMZ, one underwent 5 cycles, another had an extended treatment of 10 cycles and 2 patients received only 3 cycles due to adverse effects. In terms of treatment response, 4 patients exhibited stable disease, one achieved a partial response (PR) and 2 had disease progression. The most commonly side effect was mild nausea and vomiting and one patient required dose adjustment due to thrombocytopenia. A second course of TMZ was warranted in 2 cases that previously demonstrated a PR (on average one year after the initial treatment). While one case sustained the PR, the other experienced disease progression. Conclusion: The administration of this treatment was often postponed, potentially attributed to the significant disparities in opinions regarding the optimal timing of treatment initiation and the most suitable duration of usage. However, TMZ demonstrated its efficacy in maintaining disease stability for the majority of cases, with good tolerability and safety, even when used later, after multiple surgical procedures, and in patients with high Ki67 levels.
Presentation: 6/2/2024