bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU018 Remarkable Response Of ACTH-secreting Pituitary Carcinoma To Immune Checkpoint Inhibitors: A Case Report
Authors: Park Ji Yong , Choi Wonsuk , Ram Hong A , Yoon Jee Hee , Kim Hee kyung , Kang Ho-Cheol 
Published: October 2023

Abstract
Disclosure: J. Park: None. W. Choi: None. A. Hong: None. J. Yoon: None. H. Kim: None. H. Kang: None.
Background: ACTH-secreting pituitary carcinoma transformed from Cushing’s disease is very rare and has aggressive characteristics with limited treatment options. We report a case of ACTH-secreting pituitary carcinoma patient who showed a excellent response to immune checkpoint inhibitors (ICIs). Clinical Case: A 70-year-old female presented with a rapidly growing pituitary carcinoma transformed from Cushing’s disease after bilateral adrenalectomy. Her tumor initially responded to 6 cycles of temozolomide and 7 cycles of temozolomide plus capecitabine. However, multiple brain and pulmonary metastases were newly seen on following imaging studies and the patient had worsening generalized pigmentation on her whole body with newly developed headache, diplopia, and ptosis of the left eye. After introduction of three cycles of ipilimumab plus nivolumab therapy, her plasma ACTH level decreased dramatically from 58,000 pg/ml to 198 pg/ml with improving skin pigmentation and headache episodes. We maintained nivolumab and observed that the plasma ACTH level be normalized to 44 pg/ml (normal range: 6 – 60 pg/ml). Her follow-up brain MRI and chest CT scan also showed marked response, some of the chest lesions even showed nearly complete response (figure 1). On the last follow-up visit, we confirmed that she was in good general condition and tolerable to nivolumab maintenance therapy with glucocorticoid replacement. Conclusion: Immune checkpoint inhibitors (ICIs) may be effective therapeutic options in aggressive pituitary carcinoma and can be considered in temozolomide resistant cases. Moreover, because of the excessively high cost, we emphasize the necessity of clinical trials of ICIs for rare diseases like pituitary carcinomas to expand insurance coverage and reduce the unmet needs of medical care.
References:(1) Reincke, M., et al., Corticotroph tumor progression after bilateral adrenalectomy (Nelson's syndrome): systematic review and expert consensus recommendations. Eur J Endocrinol, 2021. 184(3): p. P1-P16.
(2) Raverot, G., et al., Temozolomide treatment in aggressive pituitary tumors and pituitary
carcinomas: a French multicenter experience. J Clin Endocrinol Metab, 2010. 95(10): p. 4592-9.
(3) Lin, A.L., et al., Marked Response of a Hypermutated ACTH-Secreting Pituitary Carcinoma to Ipilimumab and Nivolumab. The Journal of Clinical Endocrinology & Metabolism, 2018. 103(10): p. 3925-3930.
(4) Raverot, G., et al., Aggressive pituitary tumours and pituitary carcinomas. Nat Rev Endocrinol, 2021. 17(11): p. 671-684.
Presentation: Thursday, June 15, 2023
THU026 Severe Insulin Resistance In Type 1 Diabetes Due To Growth Hormone Producing Pituitary Macroadenoma
Authors: Pansare Rahul , Khurram Daniyeh , Folsom Lisal 
Published: October 2023

Abstract
Disclosure: R. Pansare: None. D. Khurram: None. L. Folsom: None.
Background: Acromegaly is a rare disorder with an incidence ranging from 28 to 137 per million. Elevated IGF-1 in acromegaly is associated with severe insulin resistance and diabetes mellitus in the absence of visceral adiposity. We present a case of acromegaly identified in a lean individual with type 1 diabetes with progressive, severe insulin resistance requiring U-500 insulin via insulin pump. Clinical Case: A 28-year-old individual with type 1 diabetes mellitus diagnosed at age 17 years, hyperlipidemia, PCOS, rheumatoid arthritis, depression, and fibromyalgia presented with symptoms of brain fog, fatigue, functional decline, and nocturnal hyperhidrosis. Vital signs obtained in endocrinology clinic revealed blood pressure 100/70 mmHg and BMI 27 kg/m2. Glycemic control was suboptimal with HbA1c ranging from 7.5-9.5% over the past 2 years. The patient had developed progressive insulin resistance with subsequently increased insulin needs, ultimately requiring U-500 insulin administered via insulin pump. Brain MRI ordered due to additional symptoms revealed a sellar mass. Dedicated pituitary MRI confirmed a 2.1 cm anterior pituitary macroadenoma with compression of the optic chiasm, without cavernous sinus invasion. Biochemical evaluation at 9:57am revealed elevated IGF-1 801 ng/ml (93 - 297), Z-score +5.1. Additional testing revealed ACTH 17.9 pg/ml (7.2 - 63.3), cortisol 9.6 mcg/dl (3.7 - 19.4), TSH 0.741 mIU/L (0.27 - 4.2), free T4 1.32 ng/dl (0.93 - 1.7), prolactin 8.4 ng/ml (5.2 - 26.5), leptin 14.4 ng/ml (0.5 - 15.2), LDL 151 mg/dl (0 - 100), triglycerides 203 mg/dl (0 - 149). The patient subsequently underwent transsphenoidal resection of the pituitary macroadenoma. Discussion: Diabetes mellitus in acromegaly is associated with increased mortality. When elevated, IGF-1 level has been shown to be an independent predictor for risk of development of diabetes mellitus in acromegaly and correlates with insulin resistance. A unique challenge arises when the diagnosis of acromegaly is suspected in existing uncontrolled diabetes, as IGF-1 levels may be elevated, normal, or low. Post-surgical reduction in serum IGF-1 level is associated with early postoperative improvement in glucose tolerance. As such, once the diagnosis is confirmed, prompt surgical intervention is imperative to decrease this risk, as well as to improve hyperglycemia and decrease insulin requirements. Although de novo type 2 diabetes in acromegaly is common, our case is novel as it highlights the need to expand the differential diagnosis to include exogenous causes for progressively worsening insulin resistance in individuals with type 1 diabetes.
Presentation: Thursday, June 15, 2023
THU044 The Subcellular Localization Of β-Catenin Is Associated With Tumor Size And The Surgical Remission Rate In Growth Hormone-producing Pituitary Adenomas
Authors: Kuwabara Saki , Kameda Hiraku , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , Ishi Yukitomo , Motegi Hiroaki , Miki Fujimura , Miyoshi Hideaki , Atsumi Tatsuya 
Published: October 2023

Abstract
Disclosure: S. Kuwabara: None. H. Kameda: None. H. Nomoto: None. K. Cho: None. A. Nakamura: None. Y. Ishi: None. H. Motegi: None. F. Miki: None. H. Miyoshi: None. T. Atsumi: None.
The Wnt/β-catenin pathway is the best understood Wnt signaling pathway and controls cell proliferation. In the presence of Wnt, the translocation of β-catenin from the cytoplasm to the nucleus leads to pathway activation. It has been reported that the nuclear accumulation of β-catenin is associated with Ki-67 expression in pituitary adenomas and that the invasiveness of growth hormone (GH)-producing pituitary adenomas is associated with β-catenin expression. We aimed to clarify the effects of the Wnt/β-catenin pathway in GH-producing pituitary adenomas. We performed immunofluorescence staining using antibodies against GH and β-catenin in pathological samples of pituitary adenoma from 62 patients with acromegaly who underwent pituitary surgery at our hospital between January 2008 and December 2021. We also obtained clinical data for the patients, including the results of endocrine testing, and evaluated the relationships of key indices with the intracellular localization of β-catenin. Samples from 26 cases (42%) showed strong punctate expression of β-catenin in the nuclei (dot pattern (DP) group), and samples from 36 cases (58%) showed β-catenin expression in the cytoplasm or cell membrane (non-DP group). There were no differences in the sex, age, GH concentration, or insulin-like growth factor I (IGF-1) SD scores of the two groups, but the DP group had larger tumors (diameters 18±8 vs. 13±7 mm) and a higher prevalence of macroadenomas (77% vs. 53%). In the DP group, a paradoxical preoperative GH response (an increase of ≥30% of the basal concentration) to 75-g oral glucose tolerance testing was more frequent (46 vs. 22%, p&lt;0.05) and postoperative remission was less frequent (23% vs. 50%, p&lt;0.05). Accordingly, the Wnt/β-catenin pathway appears to be more active in the DP group. The larger tumors and lower postoperative remission rate of the DP group suggest that the Wnt/β-catenin pathway may influence tumor growth. Wnt/β-catenin pathway could play a major role in GH-producing pituitary tumor growth, therefore this pathway would be a potential therapeutic target in the affected patients.
Presentation: Thursday, June 15, 2023
SAT667 Follicle-Stimulating Hormone Does Not Directly Regulate Adipogenesis Via The FSH Receptor In Mice
Authors: Loka Mary , Gambino Luisina Ongaro , Uliasz Tracy , Jaffe Laurinda A , Kazak Lawrence , Bernard Daniel J 
Published: October 2023

Abstract
Disclosure: M. Loka: None. L. Ongaro Gambino: None. T. Uliasz: None. L.A. Jaffe: None. L. Kazak: None. D.J. Bernard: None.
Rising rates of obesity are a serious public health challenge. Post-menopausal women are at higher risk of developing obesity and associated comorbidities than premenopausal women, with hormonal changes, such as reduced estrogens, likely to be contributing factors. Menopause is also characterized by increases in pituitary-derived follicle-stimulating hormone (FSH). Recent data suggest that FSH may directly stimulate adipogenesis and block thermogenesis in adipocytes. FSH reportedly decreased expression of thermogenic genes (Cox8b and Ucp1) in murine 3T3-L1 cells differentiated into adipocytes. FSH’s inhibitory effects were no longer apparent in the presence of an FSH-neutralizing antibody. The same FSH antibody reduced fat mass and increased lean mass in ovariectomized (OVX) female mice, a rodent model of menopause. In these studies, it was not established whether FSH acted directly through its canonical receptor (FSHR) in adipocytes to mediate its effects. To address this gap, we differentiated 3T3-L1 cells to adipocytes and treated with FSH. In contrast to the earlier report, FSH did not alter the expression of markers of lipogenesis (Cebpa and Pparg2) or thermogenesis (Cox8b and Ucp1) nor did it impact mitochondrial respiration or lipid accumulation. We also did not detect Fshr mRNA in these cells. We next differentiated the stromal vascular fraction from inguinal adipose tissue of adult male mice into white adipocytes. After 10 days of differentiation, FSH treatment did not alter expression of several markers of adipogenesis and did not affect lipid accumulation. To assess FSH actions in vivo, we generated adipocyte-specific Fshr knockout mice (Fshrfx/fx;Adipoq-Cre, hereafter cKO). Ten-week-old cKO and control female mice were OVX and maintained on standard chow. Eight to 10 weeks later, we performed glucose tolerance and insulin tolerance tests, and determined body composition by EchoMRI. Cre-mediated recombination of the floxed Fshr locus in adipocytes was successful, but did not alter body weight, fat or lean mass, or glucose metabolism in cKO relative to control OVX mice. Furthermore, using a newly developed FSHR-3xHA knockin mouse model, we detected FSHR protein expression in ovary, but not in inguinal and perigonadal white adipose depots or in intrascapular brown adipose tissue. We similarly failed to detect Fshr mRNA in various fat depots in control mice. Collectively, our results fail to show FSH effects on adipogenesis in vitro and challenge the hypothesis that FSH acts through the classical FSHR in adipocytes in vivo.
Presentation: Saturday, June 17, 2023
THU083 Disulfiram Mediated Anti-tumor Effect In Pituitary Neuroendocrine Tumors By Inducing Cuproptosis
Authors: Huang Ning , Zhang Yong , Liu Yan Ting , Feng Yao , Xue Li , Wu Zhe Bao 
Published: October 2023

Abstract
Disclosure: N. Huang: None. Y. Zhang: None. Y. Liu: None. Y. Feng: None. L. Xue: None. Z. Wu: None.
Pituitary neuroendocrine tumors (PitNETs) are common intracranial tumors. Dopamine agonists and somatostatin analogues are the first-line drugs for PRL and GH-secreting PitNETs clinically. However, there is no effective drug for other subtypes and drug-resistant PitNETs. Thus, it’s impending to discover new therapeutic targets and medicine. Cuproptosis is a copper-dependent form of cell death driven by lipoylated protein aggregation, loss of Fe-S cluster-containing proteins, and induction of HSP70. However, the role of cuproptosis in PitNETs is not clear. In this study, a total of 17 primary samples of PitNETs were collected to perform high-throughput drug screening, an anti-abuse drug disulfiram (DSF) was identified that can induce cell death effectively. We found that disulfiram also has a strong inhibitory effect on pituitary tumor cell lines MMQ, Att20 and GH3 (-87.1%, -62.5%, -92.7%, p&lt;0.001), but the inhibitory effect was eliminated by copper chelator TTM/BCS. This indicated that DSF played the anti-tumor effect requiring the participation of copper ions. To explore the underlying mechanism that DSF induces the cell death of PitNETs, we detected the hallmark of cuproptosis and found that DSF leads to a decrease in the acylation level of proteins related to the tricarboxylic acid cycle, limiting the function of the protein. On the one hand, DSF leads to the downregulation of iron-sulfur cluster-associated proteins, and the oligomerization of dihydrolipoamide S-acetyltransferase (DLAT), which is eventually accompanied by an increase in the protein level of heat shock protein 70 (HSP70) at protein and mRNA level, causing proteotoxic stress leading to cell death. Finally, DSF treatment inhibited the tumor growth in MMQ cell transplanted mouse model and destructed the morphology of the pituitary tumor 3D sphere similarly demonstrating the inhibition effect. In conclusion, we find that the anti-abuse drug disulfiram can induce coproptosis in pituitary tumor cells in a copper-dependent manner and is a potential drug for the treatment of PitNETs.
Presentation: Thursday, June 15, 2023
THU096 When TSH Alone Is Not Enough
Authors: Awasty Sanjana S , Ghalib Luma 
Published: October 2023

Abstract
Disclosure: S.S. Awasty: None. L. Ghalib: None.
Background: A Thyrotropinoma or TSHoma is the rarest of all pituitary adenomas approximately 1-2%. TSHomas are often only found due to symptoms from co-secreting tumors with TSHomas or routine laboratory testing. Misinterpretation of laboratory values can cause misdiagnosis and inappropriate treatment. Clinical Case: A 45-year-old female presented to her primary care physician for a routine appointment. The patient reported concerns regarding weight and a TSH was ordered, TSH 7.00 uIU/mL (0.49 - 4.67) with no other thyroid function values. The physician prescribed levothyroxine 50mcg treating for primary hypothyroidism and over the next 37 months the patient was prescribed increasing doses of levothyroxine based on TSH values. This patient was eventually referred to Endocrinology. At the initial Endocrinology visit TSH 7.59 uIU/mL (0.27 - 4.2 uIU/mL) and fT4 3.2 ng/dL (0.7 - 1.7) on levothyroxine 125mcg. Levothyroxine was discontinued and labs were repeated 6 weeks later TSH 5.9 uIU/mL (0.27 - 4.2), fT4 4.8 ng/dL (0.7 - 1.7), fT3 2.1 pg/mL (2 - 4.4), and alpha-subunit 1.5ng/mL (&lt;=1.2 premenopausal female, &lt;=1.8 postmenopausal female). A pituitary macroadenoma was discovered on MRI. The patient was referred to Pituitary Clinic and noted to have a prolactin of 53.8 ng/mL (non-pregnant females 2.8-29.2) and IGF-1 291.6 ng/mL (60.0 - 240.0). The patient underwent transsphenoidal pituitary surgery; pathology reported a plurihormonal subtype pituitary adenoma which stained positive for Prolactin, HGH, and TSH. One week after removal of the TSHoma, TSH 0.014 uIU/mL (0.550 - 4.780) fT4 0.65 ng/dL (0.89 - 1.76), and levothyroxine replacement was initiated with plans for continued outpatient monitoring to assess need for levothyroxine replacement. Conclusion: This case primarily demonstrates the importance of evaluating TSH levels in conjunction with free T4 levels to effectively interpret central versus primary causes of thyroid dysfunction. The high molar ratio of the alpha-subunit to the TSH level lends itself to a TSHoma differentiating it from a diagnosis of syndrome of resistance to thyroid hormone. While rare missing a TSHoma diagnosis could have devastating consequences. Checking other pituitary hormones pre-operatively even without symptoms also gave the indication that this was a co-secreting tumor. After adenoma removal rechecking pituitary hormones is of great importance as exemplified by pituitary-thyroid axis suppression noted post-operatively in this case.
Presentation: Thursday, June 15, 2023
THU102 A Case Of Papillary Craniopharyngioma WHO Grade 1 Turned Into Abscess
Authors: Shah Rutu Jatin , Patel Janki , Belany Paul A 
Published: October 2023

Abstract
Disclosure: R.J. Shah: None. J. Patel: None. P.A. Belany: None.
Craniopharyngioma is a rare primary brain tumor located in the suprasellar region. Papillary craniopharyngiomas (PC) occur mostly in adults, between age 40-50. Despite surgery being the primary treatment, PCs have a high tendency for relapse. We present a case of PC WHO grade 1, positive for BRAF V600E mutation concerning for regrowth 10 months following surgical resection. A 45-year-old male presented to the emergency department with complaint of right orbital headaches, vision change and severe fatigue. CT head was normal and was discharged home. Headaches, fatigue, and vision change progressively worsened over the next week with new symptoms of erectile dysfunction, low libido, weight loss, polyuria, polydipsia and proximal muscle weakness developing. Morning labs showed FT4 0.5ng/dl, TSH 2.32uIU, cortisol 1.5ug/dl, ACTH 14 pg/mL, FSH 1.5mIU/mL, LH 0.2mIU/mL, total testosterone 6ng/dl, prolactin 17.5ng/mL, IGF-1 134 ng/mL and GH 0.2ng/dl concerning for panhypopituitarism. Chemistry panel was unremarkable. MRI pituitary confirmed sellar mass measuring 2.1x1.3x2.1cm compressing the optic chiasm. Evaluated by endocrinology, patient was started on hydrocortisone, levothyroxine and desmopressin and referred to neurosurgery. Following endoscopic endonasal approach (EEA), pathology showed PC WHO Grade 1 and molecular testing positive for BRAF V600E mutation. Two-month post-surgical MRI showed residual 8mm lesion. Active surveillance showed regrowth of sellar lesion to 1.8 cm with optic chiasm compression ten months following EEA. Repeat EEA was done with concern for relapse. Surprisingly, intraoperative purulent fluid draining from the sella was found and positive for Acinetobacter. Sellar abscess was drained and he received six weeks of intravenous antibiotics. Repeat MRI showed resolution of the entire sellar lesion, his vision normalized and continued to be on hormone replacement for panhypopituitarism. PCs are locally aggressive suprasellar lesions that can reach a large size prior to clinical symptoms developing. Around 90% of PC are positive for BRAF V600 mutation. Surgical resection and radiotherapy are the primary treatment, but newer studies have demonstrated tumor regression using BRAF targeted agents following relapse. Our case demonstrates a pituitary abscess (PA) found intraoperatively that was originally suspicious for tumor recurrence. PA is a rare and serious intrasellar infection associated with high mortality. It is difficult to diagnose preoperatively and can be misdiagnosed as recurrence or residual tissue. PA can be primary or secondary depending on etiology. PA associated with residual craniopharyngioma tissue is extremely rare and the exact pathophysiology is not well understood. If no evidence of sepsis or meningitis, treatment with transsphenoidal decompression and intravenous antibiotics has good clinical outcomes.
Presentation: Thursday, June 15, 2023
THU106 Malignant Epithelioid Neoplasm As The Cause Of A Rapidly Growing Pituitary Mass
Authors: Riahi Shayan , Chaidarun Sushela S 
Published: October 2023

Abstract
Disclosure: S. Riahi: None. S.S. Chaidarun: None.
Background: Malignant epithelioid neoplasm is a rare cause of a pituitary mass, and should be kept on the differential whenever evaluating patients with evidence of rapid pituitary enlargement. Clinical Case: A 43 year-old man presents with 3-month history of worsening severe headaches, decreased libido, erectile dysfunction, polydipsia, polyuria (6L/day) with nocturia every hour, and fatigue. He also noted some blurry vision without loss of his peripheral vision. MRI of the brain showed a 1.5cm mass in the sellar and suprasellar region abutting the optic chiasm. Of note, he had a brain MRI performed 18 months prior for vertigo which did not demonstrate any mass in the pituitary. He presented to the endocrinology office for evaluation. His laboratory tests demonstrated mildly elevated prolactin 31.2 ng/mL (n 4.0-15.2), and findings consistent with panhypopituitarism and central diabetes insipidus, including low FT4 of 0.46 ng/dL (n 0.93-1.70), FSH 0.7 mIU/mL (n 1.5-12.4), an undetectable LH (n 1.7-8.6mIU/mL), random cortisol of 1mcg/dL (n 4.8-19.5) ACTH 6.2 pg/mL (n 7.2-63), IGF-1 of 139 ng/mL (n 44-275), total testosterone undetectable (n 240-950 ng/dL), sodium 144mmol/L (n 135-145) with low urine specific gravity 1.008 and urine osmolality of 143mOsm/Kg (n 60-1200). HCG was undetectable (n 0-2mIU/mL) but LDH was elevated at 313 unit/L (n 110-220). He was started on corticosteroids, levothyroxine, DDAVP, and referred to neurosurgery. Specimens from his transphenoidal biopsy demonstrated findings consistent with a malignant epithelioid neoplasm. Further analysis and genetic testing is still pending. He has been referred to oncology service for further management and care. Conclusion: A rapidly growing symptomatic pituitary mass with central diabetes insipidus should raise suspicion for malignant etiology beyond the more prevalent pituitary adenoma. Malignant epithelioid neoplasm are uncommon tumors of the brain, however they are known to be aggressive tumors with high mortality. Treatment commonly includes some combination of surgery, radiotherapy, and chemotherapy1.
Reference: (1) Jog AP, Ronderos DM, Ali A, Niazi M, Diaz-Fuentes G. Malignant Epithelioid Neoplasm of the Brain. Cureus. 2020 Aug 27;12(8):e10079. doi: 10.7759/cureus.10079. PMID: 33005505; PMCID: PMC7523542.
Presentation: Thursday, June 15, 2023