bluuebunny/crossref_metadata_2025_split huggingface dataset:
8209 Silent Somatotroph Adenoma Unmasked as Pituitary Apoplexy, Disguised as Subarachnoid Hemorrhage
Authors: Vemparala Pranathi , Challagulla Sabita 
Published: October 2024

Abstract
Disclosure: P. Vemparala: None. S. Challagulla: None.
Introduction - Pituitary apoplexy is a rare and potentially life-threatening complication associated with pituitary adenomas, particularly in cases of nonfunctioning macroadenomas. Silent somatotroph adenomas, characterized by the presence of growth hormone (GH) immunoreactivity without manifesting signs and symptoms of acromegaly, are uncommon. This case report presents a distinctive instance where pituitary apoplexy served as the initial manifestation of a GH-immunoreactive tumor. CASE PRESENTATION- A 45-year-old male with a medical history of hypertension, sleep apnea, and hypogonadism sought emergency medical attention following a syncopal episode. Post-syncope, he reported severe headache and neck pain, with no other associated symptoms. Imaging revealed a subarachnoid hemorrhage and a sellar/suprasellar mass measuring approximately 2.8 x 3.6 x 4.2 cm. CT angiography ruled out an aneurysm or vascular malformation. The subarachnoid hemorrhage was attributed to hemorrhage within the sellar mass. Treatment with Nimodipine and levetiracetam was initiated. Laboratory investigations indicated normal insulin-like growth factor 1 (IGF-1) levels. Brain MRI revealed a 4.2 x 2.3 x 2.6 cm heterogeneous enhancing cystic sellar/suprasellar lesion causing mass effect on the hypothalamus and third ventricle. The patient underwent endoscopic transsphenoidal hypophysectomy, revealing a tumor that was diffusely positive for GH and synaptophysin immunostaining and negative for prolactin and ACTH. Ki67 was less than 5%, with no apparent mitotic activity, atypia, or tumor necrosis. The postoperative course was uneventful, and the patient was discharged on oral steroids. Conclusion- Silent somatotroph adenomas constitute a small percentage (2-4.2%) of pituitary adenomas. In contrast to silent gonadotroph adenomas, these tumors are more prevalent in women, tend to present earlier and exhibit higher recurrence rates. This case emphasizes the potential of silent somatotroph adenomas to manifest initially as pituitary apoplexy. It underscores the importance of vigilant post-surgical follow-up due to the possibility of recurrence. Additionally, recognizing pituitary apoplexy as subarachnoid hemorrhage is crucial for timely intervention and appropriate management.
Presentation: 6/2/2024
7248 Spliceosome component TCERG1 regulates the aggressiveness of somatotroph adenoma
Authors: Kim Kyungwon , Shin Hye Ju , Kang Chan Woo , Lee Eun Jig , Ku Cheol Ryong 
Published: October 2024

Abstract
Disclosure: K. Kim: None.
The role of the spliceosome in the development of pituitary tumors is not well understood, despite preliminary studies indicating abnormal expression of oncogenic splicing variants in these neuroendocrine tumors. We aimed to identify differentially expressed spliceosome components in growth hormone (GH)-secreting pituitary tumors and investigate their roles in pathogenesis.We performed transcriptome analysis of 20 somatotroph adenomas and 6 normal pituitary tissues to select dysregulated spliceosome components. Clinical characteristics were analyzed based on gene expression in 64 patients with acromegaly. GH secreting pituitary adenomas were confirmed by 75 g oral glucose tolerance and immunohistochemical staining. Proliferation, invasion, and hormonal activity of GH secreting pituitary adenoma cells were investigated after modulating gene expression.TCERG1 expression was significantly higher in somatotroph adenomas than in normal cells (log2 fold change 0.59, adjusted P=0.0002*). Genotype-phenotype analysis revealed that patients with higher TCERG1 expression had lower surgical remission rates than those with lower expression (63.64% vs. 95.45%, P=0.009*). TCERG1 expression was significantly higher in groups with cavernous sinus (CS) invasion or Ki67 index over 1.5 (2.06 vs. 1.65, P=0.011*; 2.02 vs. 1.66, P=0.043*). TCERG1 overexpression led to a 16.91% increase in proliferation after 72 h (P&lt;0.001*) and a 249.47% increase in invasion after 48 h in GH3 cells (P=0.026*). Conversely, TCERG1 silencing significantly decreased cell proliferation (10.15% at 72 h, P&lt;0.001*) and invasion (96.87% at 48 h, P=0.029*). Vimentin was increased, but E-cadherin was decreased in both TCERG1 overexpressed GH3 cells and somatotroph adenomas. And TCERG1 silence reversed the expression of the genes (CDH2, SNAI1, ZEB2, and VIM) in GH3 cells. Additionally, GH secretion increased when TCERG1 was overexpressed in GH3 cells. Spliceosome machinery provide novel insights into the pathogenesis of GH-secreting pituitary tumor and highlight the potential role of TCERG1 as a therapeutic target.
Presentation: 6/2/2024
8442 Successful Pregnancy in the Setting of Medically Untreated Acromegaly
Authors: Chlebek Sylvia , Guerra Yannis Sergio 
Published: October 2024

Abstract
Disclosure: S. Chlebek: None. Y.S. Guerra: None.
Background: Acromegaly is a rare disease due to excessive GH secretion, usually from a benign pituitary adenoma. Gonadal dysfunction and infertility are common in acromegalic women within reproductive age [1]. Effective treatment typically improves fertility. Minimal data, mostly in the form of isolated cases, is available on pregnancy in acromegaly. Clinical Case: A 39-year-old woman presented to outpatient Endocrinology for management of acromegaly. Past medical history was notable for a GH secreting pituitary adenoma, of unknown size, which was initially found in Mexico during work-up for progressive, chronic headaches and gradual enlargement of her facial features, feet, and hands. The patient subsequently underwent trans-sphenoidal resection of the pituitary adenoma. A post-operative MRI revealed a residual adenoma with a 94% decrease in size. She declined further therapy at that time. The patient reported improvement in her symptoms, however, these gradually recurred over two years. She traveled to the U.S. from Mexico and sought Endocrine evaluation. Clinically, the patient exhibited features of acromegaly: coarse facial features and acanthosis nigricans at the nape. She was found to have biochemical persistence: GH at the upper limit of normal (3.479 ng/mL, normal 0.010-3.607 ng/mL) and IGF-1 elevation (573 ng/mL, normal 53-331 ng/mL). The remainder of the results were unremarkable, and an MRI was scheduled. The patient returned to clinic, 3-months later, 11-weeks pregnant. While pregnant, the MRI Brain revealed a macroadenoma without optic chiasm compression. Furthermore, there were no visual field defects on Ophthalmology evaluation. The patient decided to forego medical therapy for acromegaly during pregnancy. Notably, she was diagnosed with gestational diabetes and preeclampsia. She delivered a healthy baby without complications and with no fetal malformations. Post-partum, the patient was initiated on a somatostatin analog with a plan for repeat biochemical testing at her next appointment. Conclusion: As pregnancy is rare in women with acromegaly, few case reports have been published on this clinical presentation. Pregnancy warrants consideration of adenoma growth and the impact of hormone hypersecretion on the patient and fetus. Failure to achieve biochemical control may increase the risk of gestational diabetes and hypertension, as seen in this patient. Post-partum treatment and regular follow-up are important for managing acromegaly and associated complications. Reference:1.Pirchio et al. Fertility in Acromegaly: A Single-Center Experience of Female Patients During Active Disease and After Disease Remission, The Journal of Clinical Endocrinology & Metabolism, Volume 108, Issue 8, August 2023, Pages e583–e593, https://doi.org/10.1210/clinem/dgad042
Presentation: 6/2/2024
6444 The Cortisol Conundrum: A Case of Cushing’s Disease Masked by Cabergoline
Authors: Khan Aysha , Vedere Tarunya 
Published: October 2024

Abstract
Disclosure: A. Khan: None. T. Vedere: None.
Introduction: The most common cause of endogenous hypercortisolism is Cushing’s disease (CD) accounting for 70% of the cases. We describe a case where the diagnosis of CD was delayed due to cabergoline (CBG) use. Case A 25-year-old male with history of OSA, multiple sclerosis, obesity, recurrent kidney stones, and a pituitary microadenoma, presumed to be a prolactinoma, presented with gynecomastia and erectile dysfunction (ED). He had developed gynecomastia in his teenage years. Workup showed elevated prolactin level (PRL) and MRI pituitary showed a 5mm pituitary adenoma. Patient was started on CBG 0.5 mg once a week and had been on it for 4 years at presentation. Most recent PRL had normalized to 13.7 (12.0-18.0) ng/ml and MRI pituitary showed stable size of the adenoma. He reported generalized weakness with proximal muscle weakness, weight gain, easy bruising, ED, decreased libido, and persistent gynecomastia for a few years. Interestingly, he had noted a 50 lb weight gain, low mood, and worsening striae when he was taken off CBG for 3 months in the past. Physical exam was significant for obese male with dorsocervical and supraclavicular fat pads, facial plethora, reduced motor power in proximal upper extremities and prominent wide purple striae on the abdomen. In the past, while on CBG, 24-hour urine free cortisol levels were 85.9 and 40.9 (4.0-50.0) mcg/24hrs in two collections. While briefly off CBG, 24-hour urine cortisol level was 254.2 mcg/24hrs. We obtained salivary cortisol levels which were elevated at 0.666 (&lt;0.308) mcg/dL and 1.005 mcg/dL on two samples and ACTH was 67.6 (7.2-63.3) pg/ml while on CBG. IPSS results pointed to a pituitary source. Patient underwent transsphenoidal hypophysectomy and was discharged on hydrocortisone (HC). Pathology showed minute pituitary tissue, possible pituitary adenoma. Specimen was too small to perform staining for ACTH and PRL. Postoperatively, he has done well off HC with significant clinical improvement and normalization of salivary cortisol levels. Discussion Dopamine agonist such a CBG is the first line treatment of prolactinomas. The evidence for CBG use in CD has been controversial; some studies show almost a 40% decrease of cortisol levels. Given that CBG suppresses ACTH secretion by acting on dopamine receptor subtype 2, it would also mask CD by reducing cortisol levels in urine and serum. Our patient had equivocal results for 24-hour urine cortisol level for CD. While CBG adds to the armamentarium for these ACTH-PRL secreting pituitary adenomas, its use interferes with work up in patients with pituitary adenoma who are still undergoing diagnostic tests for pituitary function evaluation. Our case highlights a unique diagnostic challenge in the work up of CD.
Presentation: 6/3/2024
7089 The Effects of Asprosin on Reproductive Parameters in the Rats
Authors: Kelestimur Haluk , Oz Zeynep Dila , Ozdede Mehmet Ridvan , Serhatlioglu İhsan , Kacar Emine , Yilmaz Bayram 
Published: October 2024

Abstract
Disclosure: H. Kelestimur: None. Z. Oz: None. M. Ozdede: None. &. Serhatlioglu: None. E. Kacar: None. B. Yilmaz: None.
Purpose: Asprosin, a novel glucogenic adipokine produced by the fibrillin 1 (FBN1) gene, is integral to the body's energy regulation processes. Generated and released by white adipose tissue during fasting, asprosin affects the hypothalamic-pituitary-gonadal (HPG) axis, impacting reproduction. While its effects on metabolic parameters are well established, the understanding of its impact on reproductive health and functionality is still emerging. This study investigates the effects of exogenous asprosin administration on the reproductive capabilities of male and female rats. Materials and Methods: Forty-eight Sprague-Dawley rats, 21 days old and weighing 35±2 grams, were divided into control and asprosin-treated groups (n = 12 per group, for both genders). This approach allowed direct comparison between treated and untreated groups. From postnatal day 21, treatment groups received daily intraperitoneal injections of asprosin (500 ng/kg) for ten weeks (male) and eight weeks (female), while control groups received only saline (1 ml/kg). The study examined various reproductive parameters, including those related to pubertal maturation and sexual behavior, and conducted hormonal analyses on blood samples collected at the experiment's conclusion. Results: Asprosin administration did not alter puberty onset or weight in either gender. However, asprosin-treated rats showed significantly earlier sperm formation in males and earlier estrus in females compared to controls. In male sexual behavior, asprosin reduced intromission latency and increased ejaculation frequency. While interaction with females remained unchanged, asprosin notably increased time near males and male preference ratio. The rate of male investigation preference and the activity index (frequency of passing through the test device's center) also significantly increased in the asprosin-treated group. Conclusion: These findings suggest that asprosin may stimulate the reproductive system in both male and female rats. They highlight the potential role of asprosin in reproductive biology and underscore the need for further research to fully understand the mechanisms by which asprosin influences reproduction. Such studies could significantly advance our knowledge in endocrine regulation. Acknowledgement: This study was supported by TUBITAK (Project No: 220S744).
Presentation: 6/1/2024
6529 The Risk of Hypophysitis Following Treatment With Relatlimab+Nivolumab Appears Higher Than Expected
Authors: Chamorro-Pareja Natalia , Faje Alexander Terence , Miller Karen Klahr 
Published: October 2024

Abstract
Disclosure: N. Chamorro-Pareja: None. A.T. Faje: None. K.K. Miller: Stock Owner; Self; Bristol-Myers Squibb.
Hypophysitis is a recognized complication of immune checkpoint inhibitor therapy; the risk of developing hypophysitis in patients receiving nivolumab (an anti-programmed death-ligand 1 [anti-PD-1]) is estimated to be &lt; 1%. Relatlimab is a human monoclonal antibody targeting lymphocyte activation gene 3 (LAG-3) recently approved in combination with nivolumab for the treatment of unresectable or metastatic melanoma. The risk of hypophysitis as a complication of relatlimab therapy is not well-defined. Objective: To examine the prevalence, identify risk factors, and characterize the clinical presentation of hypophysitis in patients receiving relatlimab+nivolumab. Methods: 159 patients received relatlimab+nivolumab at the Mass General Brigham health care system between 6/2015 and 11/2023. Twenty-seven patients were excluded because they were either diagnosed with adrenal insufficiency (AI) before receiving relatlimab+nivolumab or AI was secondary to other factors, primarily exogenous glucocorticoid administration, leaving a total of 122 patients. The medical records of these patients, including provider encounters, laboratory results, medication records, and radiologic images were reviewed. Data are presented as mean ± SD. Results: Central AI was diagnosed in 10 patients (7.5% of the cohort) after relatlimab+nivolumab administration. The mean age was 64.5±13.8 vs. 67.1±14.4 in patients with AI vs. patients without AI (p= 0.58). Sixty percent of patients in the AI group were male compared to 53% of patients without AI (p= 0.68). The development of AI was not related to the cumulative dose of relatlimab+nivolumab (mean number of cycles 6.4±3.2 vs. 4.9±5.0, p=0.35). The most common presenting symptoms of AI were fatigue, anorexia, nausea, and vomiting. No patients were diagnosed with additional anterior pituitary hormone deficiencies, though not all patients were evaluated for these diagnoses; none had diabetes insipidus. Nine patients had MRIs performed after the diagnosis of central AI; 7 of these patients had pre-treatment MRIs for comparison. Diffuse pituitary enlargement was seen on MRI after initiation of relatlimab+nivolumab in 3 patients up to 8 weeks prior to the diagnosis of hypopituitarism. All patients had persistent hypopituitarism at the most recent evaluation. Conclusions: This study is the first cohort analysis of hypophysitis in patients treated with relatlimab+nivolumab. A significant portion of patients were diagnosed with central AI, presumptively due to hypophysitis given the lack of an identifiable alternative etiology. Although the clinical phenotype of these patients paralleled published studies analyzing anti-PD-1 monotherapy, combination treatment with relatlimab+nivolumab appeared to confer a significantly higher risk of developing hypophysitis.
Presentation: 6/3/2024
7559 TRIM21 Regulates Activation of ERK1/2 to Promote Growth and Drug Resistance in Pituitary Neuroendocrine Tumors
Authors: Liu Yanting , Liu Fang , Li Chuanbao , Zhang Tao , Xue Li , Wu Zhe Bao 
Published: October 2024

Abstract
Disclosure: Y. Liu: None. F. Liu: None. C. Li: None. T. Zhang: None. L. Xue: None. Z. Wu: None.
Objective: To investigate the role of the TRIM family genes in pituitary neuroendocrine tumors (PitNETs) and provide new targets and strategies for the clinical treatment of these tumors. Methods: A CRISPR screening system targeting the TRIM family was constructed and validated using next-generation sequencing. Stable cell lines overexpressing or knocking out TRIM21 were generated, and functional validation was performed using assays such as CCK-8, colony formation, and xenograft tumor growth in nude mice. RNA-seq, mass spectrometry, immunohistochemistry, and immunoblotting were employed to explore the signaling pathways and mechanisms underlying TRIM21's actions. Immunoprecipitation, immunofluorescence, GST-pulldown, NanoBiT assays, and ubiquitination experiments were conducted to investigate the effects of TRIM21 on ERK1/2. Immunohistochemistry and immunoblotting were used to explore the role of TRIM21 in drug- resistant prolactinomas and the correlation between TRIM21 and p-ERK. Results: Through screening the proliferative and drug-resistant effects of the TRIM family in MMQ and GH3 cells, we found that knocking out TRIM21 may inhibit cell growth and enhance drug sensitivity. Subsequently, stable cell lines overexpressing or knocking out TRIM21 were generated in MMQ and GH3 cells, revealing that TRIM21 overexpression promotes pituitary tumor cell growth and resistance to drug treatment, while TRIM21 knockout inhibits cell growth and enhances drug sensitivity. Cell-derived xenograft models showed that TRIM21 overexpression promoted growth of GH3 cells in vivo and resistance to cabergoline (CAB), while TRIM21 knockout suppressed growth of MMQ cells in vivo. Further exploration of the signaling pathways influenced by TRIM21 revealed that TRIM21 knockout downregulates the MAPK signaling pathway, while TRIM21 overexpression upregulates it. TRIM21 overexpression upregulates p-ERK1/2 in the MAPK pathway, while TRIM21 knockout decreases p-ERK. However, there is no significant influence on ERK1/2, JNK, p-JNK, p38, or p-p38. Mechanically, TRIM21 interacted with ERK1/2, enhancing the K27-linked ubiquitination of ERK1/2 and promoting their interaction with MEK1/2. In addition, the TRIM21 with D-docking mutant or ERK1/2 with CD-domain mutant resulted in the loss of their interaction. Furthermore, TRIM21 and p-ERK levels were significantly elevated in drug-resistant prolactinomas and immunohistochemical semi-quantitative analysis demonstrated a positive correlation between TRIM21 and p-ERK. Conclusion: The ubiquitin ligase TRIM21 catalyzes K27-linked ubiquitination of ERK1/2, enhancing its interaction with MEK1/2 and activation, thereby promoting growth and drug resistance in pituitary neuroendocrine tumors. TRIM21 may serve as a potential target for the treatment of pituitary neuroendocrine tumors.
Presentation: 6/3/2024
7521 Unmasking of PCOS after Microprolactinoma Treatment
Authors: Erenler Feyza , Mathyk Begum Aydogan 
Published: October 2024

Abstract
Disclosure: F. Erenler: None. B. Aydogan Mathyk: None.
Background: PCOS and prolactinomas are two of the leading causes of secondary amenorrhea. Hirsutism is a common finding for both diagnosis and can be the presenting symptom. We are presenting a case of secondary amenorrhea, initially diagnosed with microprolactinoma without signs of hyperandrogenism, which progressed to overt PCOS after prolactinoma treatment. Case: A 22-year-old female with history of Hashimoto’s hypothyroidism presented with secondary amenorrhea. Patient was on combined oral contraception pills (COC) for menstrual regulation and discontinued them with a desire of natural cycles. After the discontinuation of COC, her menstrual cycles did not return for four months and patient was subsequently found to have a microprolactinoma with prolactin (PRL) level 70.6 ng/mL - high (nl: 2.8-29.2 ng/mL), LH 6.1 mIU/mL (follicular phase: 1.9-12.5 mIU/mL), FSH 2.4 mIU/mL - low (follicular phase: 2.5-10.2 mIU/mL), androstenedione 132 ng/mL (follicular phase: 51-213 ng/mL), testosterone 36 ng/mL (nl: 2-45 ng/mL), AMH 33 ng/mL - high (nl: 1.02-14.63 ng/mL), DHEA-S 241 mcg/dL (nl: 44-286 mcg/dL), HCG neg. MR Sella showed a 0.5 cm hypoenchancing pituitary lesion, confirming the diagnosis of prolactinoma. Patient was started treatment with cabergoline 0.25 mg twice a week and PRL level trended down to 3.9 ng/mL. With normalization of PRL, patient started complaining of new onset hirsutism without return of her menses. Ferriman Gallway score was 8. Further workup showed elevated androgen markers: LH 25.7 mIU/mL - high (follicular phase: 1.9-12.5 mIU/mL), FSH 5.0 mIU/mL (follicular phase: 2.5-10.2 mIU/mL), PRL 4.7 ng/mL -low (nl: 4.8-23.2 ng/mL), androstenedione 341 ng/mL -high (41-262 ng/mL), E2 63.4 pg/mL (nl: 12.5-160 pg/mL), AMH 22.3 ng/mL – high (nl: 1.23-11.61 ng/mL), testosterone 94.7 ng/mL - high (nl: 10-55 ng/mL), DHEA-S 261 mcg/dL (nl:110-431.7 mcg/dL). ACTH stimulation test pursued to rule out NCAH and17-OH progesterone levels were within normal range after stimulation. Pelvis US obtained due to high suspicion for PCOS and was consistent with polycystic ovaries. The diagnosis of PCOS confirmed by Rotterdam criteria. Patient has phenotype A PCOS by the definition of NIH 2012 consensus. Conclusion: Hyperprolactinemia and pituitary adenomas can cause secondary amenorrhea. In our case, the treatment of hyperprolactinemia with cabergoline unmasked the underlying PCOS. The clinical and biochemical manifestation of PCOS became apparent following the removal of prolactin’s suppressive effect on GnRH.
Presentation: 6/2/2024