bluuebunny/crossref_metadata_2025_split huggingface dataset:
6393 Prolactinoma with Concomitant Moyamoya Disease
Authors: Davis Adam N , Elshimy Ghada 
Published: October 2024

Abstract
Disclosure: A.N. Davis: None. G. Elshimy: None.
Introduction: Moyamoya disease is a cerebrovascular condition associated with stenosis of the intracranial internal carotid arteries and their proximal branches. Moyamoya is rare and has been reported to have an incidence of 0.086 cases per 100,000 persons. Only a few cases had reported concomitant prolactinoma with Moyamoya disease. We present a rare case of Moyamoya disease accompanied by a prolactin-secreting pituitary adenoma. Case: A 38-year-old female with history of prior CVA in 2019, 2022, and 2023 and prolactin-secreting pituitary macroadenoma diagnosed 2019 presented February 2023 to establish care in the Endocrine clinic for management of hyperprolactinemia. She reported history of hyperprolactinemia diagnosed 2019 and was treated with cabergoline in the past. She had CTA head January 2023 during admission for left sided weakness showing high-grade stenosis of the proximal M1 segment of the right MCA concerning for vasospasm versus occlusion with collateralization. Moreover, in January 2023 she had an angiogram performed demonstrating critical right MCA stenosis with Moyamoya changes with distal collaterals from the right ACA and PCA. When seen in clinic, she complained of galactorrhea with breast soreness and oligomenorrhea. Labs at this time were significant for prolactin level of 122.89ng/mL, estradiol 74pg/mL, LH 1.75mIU/mL, FSH 2.50mIU/mL. She was restarted on cabergoline 0.5mg twice weekly. Repeat prolactin level 8/16/23 was improved to 2.71ng/mL with improvement in her symptoms. Discussion: Moyamoya refers to the angiographic changes involving the occlusion of the arteries near the circle of Willis with arterial collateral development. Moyamoya disease refers to patients with Moyamoya findings potentially from a genetic predisposition, whereas Moyamoya syndrome refers to the presence of Moyamoya findings with associated medical conditions (history of radiation therapy, trauma, brain tumors, atherosclerosis, meningitis, hypercoagulability etc.) which may explain the occlusion. There have been several sellar and suprasellar masses reported in conjunction with Moyamoya disease including craniopharyngioma and other hormone-producing pituitary adenomas. It has been postulated that hypothalamic disturbances owing to reduced perfusion may lead to hyperprolactinemia via reduced downregulation of lactotrophs. Interestingly, our patient had unilateral rather than bilateral arterial stenosis which have been reported in other cases in the literature. Initial management is like other patients with prolactinomas and includes medical management with dopamine agonists. Conclusion: We report a rare case of Moyamoya disease with concomitant prolactinoma. This disease has been also reported with other hormone-producing pituitary adenomas and hypopituitarism. Hence, endocrinologists should be aware of these rare cases.
Presentation: 6/1/2024
8514 Rapid Improvement of Visual Field Defect with Medical Treatment in Giant Prolactinoma with Optic Nerve Compression
Authors: Sharma S , Acharya M , Sherpa C 
Published: October 2024

Abstract
Disclosure: S. Sharma: None. M. Acharya: None. C. Sherpa: None.
Introduction: Prolactinomas are the most common form of pituitary adenomas of which micro-prolactinomas comprise of 90% and measure less than 1 cm and occur mostly in women. Giant prolactinoma, defined as a prolactinoma &gt;4 cm, serum prolactin concentration higher than 1000 ng/mL, and invasive tumor growth pattern with mass effects occur mostly in men. Giant prolactinomas have an estimated prevalence of 0.5-4.4% of all pituitary tumors. We report a case of giant prolactinoma causing optic nerve compression that responded well to Cabergoline. Case description: 47-year-old male with no significant past medical history was having vision disturbances for 6 months which included blurry vision and was seen by ophthalmologist. Visual field testing was done and was found to have bitemporal visual field defect/heteronymous hemianopia which prompted an emergent MRI of brain which showed 4.1x3.1x3.1 cm pituitary macroadenoma with suprasellar extension compressing the optic chiasm and optic nerves as well as the inferior anterior portion of the third ventricle and adjacent cerebrum. He was referred to neurosurgery and endocrinology. He reported intermittent headaches occurring 3-4 times a week. Denied any weakness, bowel/bladder incontinence. He denied any significant weight gain or weight loss, no palpitations, or severe fatigue. Hormonal work up showed: Elevated Prolactin level 9226 ng/ml (Reference range 2-18 ng/ml), Low Total testosterone was 213 ng/dL (Reference range 250-1100 ng/dL), low free testosterone 31.3 pg/ml (Reference range 35-155 pg/ml), with inappropriately normal luteinizing hormone and follicle stimulating hormone consistent with central hypogonadism. Thyroid stimulating hormone, free thyroxine, adrenocorticotropic hormone, am cortisol, Insulin like growth factor-1, and serum sodium were normal. He was seen in endocrinology clinic and started on cabergoline 0.5 mg twice a week. Repeat prolactin level in 3 weeks decreased to 285 ng/ml. Repeat visual field testing in 2 weeks after starting cabergoline showed that the bitemporal visual field defect had improved. His headache has improved and has intermittent episodes of dizziness. Discussion: There are few case reports describing giant prolactinoma, however there are no clear guidelines for management of giant prolactinomas causing optic nerve compression leading to visual field defects. Medical management of prolactinomas include dopamine agonists like Cabergoline, bromocriptine which are first line. The dilemma between choosing medical versus surgical management occurs in cases where there is worsening of visual field defects. Our case report highlights the drastic improvement in visual field defect and prolactin level after starting cabergoline within 3 weeks.
Presentation: 6/2/2024
8782 Rare presentation of a rapidly progressive metastatic paraganglioma in an elderly man
Authors: Haddad Joseph , Acosta Gonzalo 
Published: October 2024

Abstract
Disclosure: J. Haddad: None. G. Acosta: None.
Background: Pheochromocytomas and paragangliomas (PPGLs) are endocrine tumors originating from neural crest-derived cells of the adrenal medulla or from the sympathetic or parasympathetic paraganglia. According to the World Health Organization classification, all PPGLs are considered to have metastatic potential. Treatment is challenging and a multidisciplinary approach is needed to manage such complex cases.Case: A 73-year-old male with a history of melanoma s/p resection, obstructive sleep apnea, left neck vagal paraganglioma s/p radiation therapy in 2011 and hypogonadism presents for evaluation of progressive hoarseness. Associated symptoms included vertigo, left facial numbness/tingling and left sided hearing loss. Physical examination revealed a red mass visible behind the tympanic membrane and a leftward tongue deviation. MRI showed rapid tumor growth in the jugular fossa with transcranial extension to the left cerebellar hemisphere concerning for tumor progression; of note, tumor size had been stable on serial neck imaging, last done one year prior. Plasma free metanephrines and 24-hour urine fractionated metanephrines were normal. The patient underwent intracranial tumor resection by neurosurgery, pathology consistent with paraganglioma; immunohistochemical staining showed loss of SDHB and next generation sequencing revealed a pathogenic variant of SDHC gene (SDHC p.M1V). At 6 months post-op, MRI scan showed stable size of residual tumor and evolving post-op changes. However, six months later, brain MRI showed growth of both intracranial and extracranial tumor components, compatible with disease progression. Ga-DOTATATE PET/CT scan showed avid uptake in left skull base (primary tumor) with extensive bony involvement in the spine, hips, sternum, ribs and left shoulder. Chromogranin A level was slightly elevated at 134.7 ng/mL (0.0 - 101.8 ng/mL) and repeat 24-hour urine fractionated metanephrines remained negative.The patient was initially prescribed octreotide and sunitinib; however, due to insurance issues, he was only able to receive one dose of octreotide. After multidisciplinary discussion between neuro-oncology, neurosurgery and endocrinology, decision was made to start systemic therapy with temozolomide and zoledronic acid. Given potential risk of catecholamine surge, alpha blockade therapy with doxazosin was recommended. Plan to monitor treatment response with Ga-DOTATATE PET/CT every 2 months. Conclusion: Metastatic paragangliomas pose diagnostic and therapeutic challenges, especially when exhibiting an aggressive behavior. A multidisciplinary approach is paramount in managing metastatic paragangliomas given the complex nature of this disease.
Presentation: 6/3/2024
7379 Shining Light on the Teleost Pituitary: Generating a Zebrafish Prop1 Reporter
Authors: Mayer Julián Jorge Martínez , Balakrishnan Mridula , Stainier Didier , Perez-Millan Maria Ines 
Published: October 2024

Abstract
Disclosure: J.J. Martínez Mayer: None. M. Balakrishnan: None. D. Stainier: None. M. Perez-Millan: None.
Anterior pituitary gland development is conserved across vertebrates, with zebrafish possessing all hormone-producing cell populations found in mammals. The transcription factor PROP1 is the primary transcription factor defining the anterior pituitary hormone-producing lineages, and PROP1 mutations in mammals cause congenital hypopituitarism. Here, we aimed to establish a transgenic zebrafish line to study pituitary development by tracking prop1+ cells in vivo. We first decided to use Tol2 mediated transgenesis to express EGFP under a prop1 promoter region. To define which sequences drive prop1 expression, we looked for open chromatin marks (H3K4me1) and interspecies conservation using the UCSC Genome Browser Zv9/danRer7. We found a conserved element 6 kb upstream of the promoter as well as a conserved sequence in the first intron, with a putative GLI2 binding site. Because these two regions were separated by a highly repetitive sequence and extended over 10kb, three different constructs were tested separately: 1) 2kb upstream conserved sequence (construct 1); 2) upstream promoter region up to 6 kb upstream (construct 2 - which includes construct 1) and 3) a minimal promoter (500 bp) plus exon 1 and intron 1 (construct 3). After microinjection we observed transient EGFP expression in pituitary cells at 30 and 48 hpf in transgenic animals for constructs 1 and 3, respectively. Transgenic zebrafish for construct 2 displayed no EGFP expression. These results suggest that the repetitive region in the prop1 promoter may act as a silencer and that prop1 expression relies on several genetic elements that can not be easily captured in a single construct. These observations led us to opt for a knock-in approach, which would recapitulate prop1 expression more faithfully. Using CRISPR-Cas9 coupled with modified double stranded DNA donors, a P2A-GAL4-VP16 construct was inserted into exon 2 of prop1. After founder screening by PCR, positive fish were crossed with UAS:mCherry-CAAX to enable live imaging of early pituitary development. The fluorescent signal was detectable from 26 hpf and persisted until day five, which was the final time point assessed. We performed live-imaging of early anterior pituitary development in prop1 reporter zebrafish at high resolution. Interestingly, we found a previously undescribed population of prop1 expressing cells that resides outside the pituitary gland. This population is likely to represent a unique feature of teleost development and is currently under investigation.
Presentation: 6/2/2024
8574 Single-Cell Assessment of Gene Expression of the Tuberal Hypothalamus and Preoptic Area From Birth to Puberty in Male and Female Mice
Authors: Ruiz Daniel , Corces Victor 
Published: October 2024

Abstract
Disclosure: D. Ruiz: None. V. Corces: None.
The hypothalamus houses numerous cell types that control essential physiological functions and behaviors. Early postnatal life is a critical period of development where hypothalamic cells mature in function, hypothalamic circuits are refined, and sex differences in cell populations are established. Nonetheless, we have a limited understanding of the cell-specific changes in gene expression that occur throughout hypothalamic postnatal development. Having a detailed understanding of transcriptomic dynamics during this critical period of development will help our understanding of metabolic, reproductive, and behavioral disorders whose pathogenesis has been linked to insults during early postnatal life. Here, we perform single-cell RNA seq separately in microdissected tuberal hypothalamus and preoptic area (POA) from C57Bl6/J male and female mice at multiple time points throughout postnatal development, including within an hour after birth, during minipuberty and puberty. We identify changes in gene expression in cells that control reproduction including GnRH and GnIH neurons, as well as Kisspeptin neurons from the Arcuate nucleus and the Anteroventral Periventricular nucleus. We also identify changes in cell types that control appetite, including POMC and AgRP neurons, as well as SF-1 neurons of the Ventromedial Hypothalamus. Subclustering of neurons allows us to identify extensive transcriptomic heterogeneity in some well-known hypothalamic neurons that can help us understand previously unrecognized functions. Additionally, we find extensive transcriptomic changes in non-neuronal cells, including microglia, astrocytes, ependymal cells, and cells from the pars tuberalis throughout postnatal development. Current work aims to understand the function and physiological relevance of these extensive temporal and sex-driven changes in gene expression.
Presentation: 6/2/2024
12471 Spasms, Salt And Stroke; A Sequelae Of Post-operative Complications Of Pituitary Adenoma Resection
Authors: Jamshed Irha , Bhandari Shreya , Rastogi Natasha 
Published: October 2024

Abstract
Disclosure: I. Jamshed: None. S. Bhandari: None. N. Rastogi: None.
Introduction: Pituitary adenomas are neoplasms of pituitary adenonophyseal lineage accounting for approximately 15% of all intracranial tumors. Surgical resection is considered first-line therapy for all adenoma subtypes except prolactinomas. Multiple medical and surgical complications can occur following trans-sphenoidal resection of adenomas. Clinical presentation: A 73-year-old male with history of previously resected pituitary adenoma 6 years ago, presented for elective endoscopic trans-sphenoidal surgery due to recurrence. Postoperatively, the patient exhibited worsening mental status, left-sided hemiparesis and urine output of 8 liters in 2 hours, leading to a severe free water deficit of 1.7 liters. Labs revealed sodium 155(n 136-145 mmol/l) from 149 pre-operatively, serum osmolality 322(275-300 mOsm/ kg) and urine osmolality 768(n 50-1200 mmol/kg), in keeping with diagnosis of Central Diabetes Insipidus. Subsequent CTH showed bilateral cerebral subarachnoid and intraventricular hemorrhage and a central midbrain infarct with accompanying edema. Patient was commenced on intravenous DDAVP and D5W infusion. However, his condition deteriorated, culminating in unresponsiveness. Repeat imaging revealed new bilateral watershed infarctions, likely attributed to diffuse multivessel vasospasm, as seen on CTA head. No clinical improvement was noted with Nimodipine. Hence, the family opted for comfort care measures and the patient expired shortly after. Surgical resection of pituitary tumors, while considered safe, is not without risks, including diabetes insipidus, cerebral hemorrhage, infarction, and vasospasm. Important markers for predicting the onset of DI include serum sodium levels after surgery, the shift in sodium levels from before to after the procedure, and the volume of urine produced prior to administering DDAVP. Subarachnoid hemorrhage and hemiparesis shortly after surgery could be linked to vasospasm that has shown to be responsive to nimodipine. However, nimodipine treatment has proved to be beneficial in those patients who incurred full recovery neurologically (1). Conclusion: The case underscores the inherent risks associated with trans-sphenoidal resection of pituitary tumors. While the procedure is predominantly safe, it can occasionally lead to severe complications contributing to morbidity and mortality. It is imperative that patients are fully briefed on these potential outcomes before undergoing surgery. References: 1.EseonuCI,ReFaeyK,GeocadinRG,Quinones HinojosaA.PostoperativeCerebral Vasospasm Following Transsphenoidal Pituitary Adenoma Surgery. World Neurosurg. 2016 Aug;92:7-14. doi: 10.1016/j.wneu.2016.04.099. Epub 2016 May 4. PMID: 27155378.
Presentation: 6/1/2024
8801 Towards Safe and Efficacious Medical Therapy for Patients with Clinically Non-Functioning Pituitary Tumors
Authors: Zhang D , Bergsneider M , Kim W , Wang M B , Vinters H , Heaney A P 
Published: October 2024

Abstract
Disclosure: D. Zhang: None. M. Bergsneider: None. W. Kim: None. M.B. Wang: None. H. Vinters: None. A.P. Heaney: None.
Clinically non-functioning pituitary tumors (CNFTs) account for one-third of all pituitary adenomas. They do not cause clinical and/or biochemical evidence of tumor-related hormone hypersecretion, grow insidiously and typically present with mass effect symptoms such as headache and visual field deficits. Surgical resection is the current standard of care for CNFTs but complete resection is infrequently achieved due to their size and invariable invasion of locally adjacent structures. CNFT remnant tumor regrowth rates approach 50% and these patients may need repeat surgery and/or radiotherapy (RT). The latter is quite effective in achieving tumor control, but carries a risk of hypopituitarism of ∼ 40% at 10 years. Although dopamine agonists and somatostatin receptor ligands have been explored as medical therapy, there are currently no consistently effective medical treatments for CNFTs. There is a clear unmet need for novel safe and effective medical therapies for these comparatively common tumors. In a highly innovative approach we have used patient-derived ex vivo 3D tumoroid human CNFTs in an automated high throughput compound screen (HTS) to identify novel tumoricidal and growth inhibitory compounds for CNFTs. To date, we have screened ∼4,000 compounds and have identified 13 potential hits that inhibited tumor cell proliferation (a reduction of 76±15%) and induced apoptosis (induction rate of 8.2 ± 6.6) in the CNFT tumoroids respectively. The hit compounds to date fall into 3 categories based on their targets, namely Na+/K+-ATPase inhibitors (n=6), reactive oxygen species (ROS) regulators (n=4), and cell cycle inhibitors (n=3). Representative “hit” compounds from each group identified in our primary screen were rescreened in triplicate in 20 concentrations from 25µM to 50pM at 2-fold dilutions. Dose-response curves characterized compound doses that inhibited cell viability by 50% (IC50) and ranged from 13nM to 103nM. Two of these 3 compounds also induced 2-3-fold apoptosis at 0.1uM with the final compound displaying a potent 5-10-fold pro-apoptotic effect at 0.15uM concentration. In parallel, we used single cell RNA sequencing to validate targets that emerged from our HTS and to characterize the mechanism of action (MOA) of these hit compounds. As proof of concept, several of the known drug targets were noted to be amongst the highest differentially expressed genes in the CNFT tumor cell population. This approach validating a candidate target in conjunction with demonstrable activity of a drug for that same target in CNFTs may simultaneously provide us with a back-bone molecule to further develop with structural activity relationship analysis and/or allow us to individualize drug choice in patients based on immunocytochemical tumor target expression.
Presentation: 6/1/2024
5034 Characterizing the Physiological Side-Effects of Over-the-Counter Arthritis Supplements
Authors: Wei K S , De La Torre M O , Flores A , Chiu C E , Angell T E 
Published: October 2024

Abstract
Disclosure: K.S. Wei: None. M.O. De La Torre: None. A. Flores: None. C.E. Chiu: None. T.E. Angell: None.
Introduction: Over the counter (OTC) health supplements are commonly used by patients for a variety of ailments but may contain active ingredients that are not stated, such as glucocorticoids. Here, we present a case series of 12 patients seen by the Endocrinology Consult service at an urban safety net hospital during 2022-2023 and determined to have iatrogenic adrenal insufficiency (AI) from specific OTC supplements that surreptitiously contained glucocorticoids. Clinical Cases:12 patients using OTC arthritis supplements [Artri King (n=8), Ardosons (n=3), and Ajo Rey (n=1)] were identified. Median age was 52 years and 33.3% were female. All started using the supplements because of joint pain. Median length of use prior to cessation was 6 months. The most common presenting symptoms were nausea/vomiting (42%), fatigue (42%), abdominal pain (33%), and dizziness (17%). The most common physical exam findings of steroid excess included moon facies (66%), central adiposity (66%), abdominal striae (50%), dorsocervical fat pad (33%), and bruising (33%). 3/12 patients required ICU admission. Cortisol assessment was performed in 11/12 patients, which showed normal cortisol level in 1 patient (cortisol ≥16 mcg/dL), AI in 3 patients (cortisol ≤3 mcg/dL), and an equivocal level (cortisol 3-16 mcg/dL) in 7 patients. Cosyntropin stimulation testing in 6/7 patients with equivocal cortisol levels suggested AI in 4 (cortisol level &lt;16 mcg/dL at 60 minutes after ACTH stimulation), whereas 2 showed lower but normal response (cortisol levels 18.2 mcg/dL and 18.4 mcg/dL). In total, 10/12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis. The most common regimens were hydrocortisone 20mg qAM/10mg qPM (33%) and hydrocortisone 5mg qAM/5mg qPM (17%). To date, 2/10 patients have successfully discontinued steroid replacement. Conclusion: These cases demonstrate possible Cushing’s syndrome and/or adrenal insufficiency after unintentional exposure to glucocorticoids in these OTC arthritis supplements, which has only previously been reported in a small number of case reports (1). This series collected over a 2-year period offers important clinical insights: Because patients may not identify or recall a supplement, possible use of OTC medications for arthritis or other anti-inflammatory purposes should be specifically assessed in patients presenting with adrenal insufficiency (especially with concomitant findings suggesting Cushing’s syndrome). For patients on such supplements, immediate discontinuation may not be possible without cortisol replacement and should be done with caution. 1) Boncompagni A.C. et al. A case of iatrogenic Cushing syndrome and subsequent adrenal insufficiency from a hidden ingredient in the supplement Artri Ajo King. J Am Coll Emerg Physicians Open. 2023;4(4):e13007.
Presentation: 6/1/2024