bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI347 Lymphocytic Hypophysitis In The Setting Of Necrotizing Granulomatous Inflammation
Authors: Kelly Clare , Ghalib Luma 
Published: October 2023

Abstract
Disclosure: C. Kelly: None. L. Ghalib: None.
Hypophysitis is rare; accounting for 0.24-0.39% of all pituitary diseases. Hypophysitis can be primary or secondary in nature. Granulomatous disease rarely causes pituitary enlargement, but Sarcoidosis and Granulomatosis with Polyangiitis have been documented to cause granulomatous infiltration of the pituitary. This case regards a man with granulomatous infiltration of the pituitary not consistent with either of the aforementioned disease processes. A 40 year old male presented to Urgent Care with headaches and blurry vision. Headaches were unresponsive to analgesics. The patient then presented to his PCP with the same complaints. MRI was then performed which showed a heterogeneously enhancing sellar and suprasellar mass. He was evaluated by Neurosurgery who recommended he undergo endoscopic resection of the pituitary lesion. Preoperative evaluation of pituitary axes were concerning for central hypothyroidism with a TSH of 1.046 uIU/mL (0.550-4.780) and free T4 of 0.76 ng/dL (0.89-1.76),as well as central hypogonadism with a FSH of 0.4 mIU/mL (&lt;18.1), LH of 0.18 mIU/mL (1.5-9.3),and testosterone of 17 ng/dL (87-814). All other axes normal. Resection of the pituitary mass occurred approximately one week later at which time he was evaluated by Endocrinology for the first time. Prior to discharge, the patient was started on levothyroxine, but gonadal replacement was deferred to outpatient setting. Grossly the pituitary mass was concerning for lymphocytic hypophysitis (LH), and thus the patient was discharged on prednisone for empiric therapy. At the time of his endocrinology follow up, his headaches and visual changes had improved, but he was experiencing polydipsia, polyuria, and nocturia. Labs were consistent with Diabetes Insipidus (DI), and he was started on desmopressin. Surgical pathology had returned “acute and chronically inflamed granulation-like tissue associated with necrosis” confirming LH. CT chest was performed to evaluate for secondary causes of granulomatous disease which showed mediastinal lymphadenopathy without parenchymal lung disease. Serologic evaluation was positive for ANA, myeloperoxidase antibody, and SS-B antibody. While attempting to wean his prednisone the patient experienced recurrence of his headaches, which resolved when he returned to higher doses. The patient was evaluated by Pulmonology given the mediastinally mphadenopathy, who recommended bronchoscopy. When specimens from the mediastinal lymph nodes were evaluated by pathology, it was again significant for necrotizing granulomatous disease, but ACE and IL-2 were negative which argued against a diagnosis of sarcoidosis. He was evaluated by Rheumatology who recommended further infectious work upas well as consideration of initiation of a steroid-sparing agent for granulomatous disease. Workup of secondary etiologies for LH is ongoing given the systemic involvement.
Presentation: Friday, June 16, 2023
FRI370 Hyperthyroidism And Acromegaly In A Patient With A Mature Plurihormonal PIT1 Lineage PitNET/Adenoma
Authors: Slack Daniel , Levine Alice C 
Published: October 2023

Abstract
Disclosure: D. Slack: None. A.C. Levine: None.
Background: TSH- and GH-secreting pituitary neuroendocrine tumors (PitNETs) are both rare entities, with an incidence of 1 per million people and 1-4 per million people, respectively. Thyrotroph, somatotroph, and lactotroph cells have the same progenitor, regulated by the PIT1 transcription factor. Thus, it is not unusual for PIT1 positive tumors to exhibit immunhistochemical expression of TSH, GH, and prolactin. It is vanishingly rare, however, for these tumors to secrete multiple biologically active hormones with apparent clinical sequelae. We herein report on a case of a patient with a plurihormonal PIT1 lineage PitNET secreting prolactin with secondary amenorrhea, TSH causing central hyperthyroidism and GH resulting in acromegaly. Clinical Case: A 42-year-old woman with a 1-year history of amenorrhea presented with 3 months of progressive weight loss, fatigue, palpitations, and tremulousness. She was found to have central hyperthyroidism, with an elevated free T4 (&gt;7.77 ng/dL, nl 0.82 – 1.77) and inappropriately normal TSH (3.25 uIU/mL, nl 0.45 – 4.5). Full endocrine workup confirmed central hyperthyroidism with elevated free T4 (5.02 ng/dL) and TSH (4.68 uIU/mL) and also demonstrated hyperprolactinemia (122 ng/mL, nl 4.8 – 23.3 ng/mL), elevated IGF-1 (795 ng/mL, nl 91 – 308 ng/mL), GH (19 ng/mL, nl 0 – 10) and free alpha subunit (28 ng/mL, nl &lt;1.02). Over the ensuing 4 months, she noted enlargement of her lips, nose, feet, and hands. MRI demonstrated a pituitary macroadenoma measuring 2.2 cm x 2.7 cm x 2 cm with asymmetric extension into the left cavernous sinus and mild elevation of the adjacent optic chiasm. She underwent an uncomplicated transsphenoidal resection of the tumor with no residual tumor noted on post-op MRI. Discharge medications were hydrocortisone 10 mg AM and, 5 mg early afternoon and levothyroxine 50 mcg daily. One month postoperatively, labs were notable for a low TSH (0.16 mIU/L), normal free T4 (1.62 ng/dL), down-trending IGF-1 (339 ng/mL), and normal prolactin (15.1 ng/mL). Additionally, AM cortisol and ACTH levels remained normal after holding her morning dose of hydrocortisone. She reported resolution of all presenting symptoms of thyrotoxicosis as well as decreasing size of her hands, feet, and nose. Pathology revealed a mature plurihormonal PIT1-lineage PitNET, with immunoreactivity for PIT1, GH, TSH, and prolactin and MIB-1 index of 3%. Conclusion: This case demonstrates the potential for PitNETs to secrete multiple biologically active pituitary hormones, including prolactin, TSH and GH, highlighting the importance of maintaining an index of suspicion for pituitary causes in the evaluation of thyrotoxicosis and of considering the plurihormonal potential of PitNETs in patients presenting with multiple endocrinopathies.
Presentation: Friday, June 16, 2023
OR17-02 Combining Transcriptomics And Proteomics To Unveil Possible PROP1 Interactors During Embryonic Pituitary Development
Authors: Garcia Lucia Iglesias , Mercogliano María Florencia , Schuster Claudio , Cheung Leonard , Camper Sally Ann , Marti Marcelo , Perez-Millan Maria Ines 
Published: October 2023

Abstract
Disclosure: L. Iglesias Garcia: None. M.F. Mercogliano: None. C. Schuster: None. L. Cheung: None. S.A. Camper: None. M. Marti: None. M.I. Perez-Millan: None.
Congenital hypopituitarism (CH) is a deficiency of one or more hormones produced by the anterior pituitary. The most frequently mutated gene in CH is PROP1, which has a very dynamic expression pattern. In Prop1 mutant mice, the pituitary is dysmorphic, with increased apoptosis and abnormal vascularization. These mutant mice are dwarfs and develop hypopituitarism. In previous work we have shown that PROP1 has a key role in stimulating progenitors to undergo an EMT-like transition before differentiation. The general objective of this work was to elucidate the PROP1 protein complexes in order to understand its role during pituitary development and to evaluate them as candidate genes that can cause congenital hypopituitarism. A GHFT-1 murine cell line expressing biotinylated Prop1 was used and co-immunoprecipitation (Co-IP) assays were performed, followed by Rapid Immunoprecipitation Mass spectrometry of Endogenous (RIME). We obtained an initial set of 786 proteins that co precipitate with PROP1. Ontology enrichment analysis shows that PROP1 immunoprecipitated with several nuclear proteins related to transcriptional regulation and splicing and also with many non nuclear proteins related to cell adhesion and migration. We used LISA and TRANSFAC to predict transcriptional regulators using as input the genes that intersected from Prop1-ChIP-Seq and RNA-seq experiments and obtained 536 genes. We compared this result with the potential PROP1 interaction proteins derived from the RIME to obtain a final list of 37 transcription factors. One possible candidate from this list is the Nuclear Factor I/B or NFIB. Mutations in this gene are related to macrocephaly with impaired intellectual development. We performed a scRNA-Seq at P4 and it showed that NFIB expresses in the same cell clusters as Prop1. Also, we have preliminary results indicating that the pituitary in NFIB KO mice at E13.5 is dysmorphic.
Further experimental work is needed to validate Prop1 interaction partners and to have a better understanding of Prop1 mechanism during pituitary development.
Presentation: Saturday, June 17, 2023
SAT587 Methylation-based Machine Learning Classifiers Discriminate Sellar Tumors By Lobe Origin Using Liquid Biopsy Or Surgical Specimens
Authors: Herrgott Grayson A , Asmaro Karam P , Wells Michael , Nelson Kevin , Thomas Bartow , Hasselbach Laura A , Transou Andrea , Cazacu Simona , Tundo Kelly M , Nadimidla Sudha , Scarpace Lisa , Barnholtz-Sloan Jill , Sloan Andrew E , Selman Warren R , deCarvalho Ana C , Mukherjee Abir , Robin Adam M , Lee Ian Y , Craig John , Kalkanis Steven , Snyder James , Walbert Tobias , Rock Jack , Noushmehr Houtan , Barros Castro Ana Valeria 
Published: October 2023

Abstract
Disclosure: G.A. Herrgott: None. K.P. Asmaro: None. M. Wells: None. K. Nelson: None. B. Thomas: None. L.A. Hasselbach: None. A. Transou: None. S. Cazacu: None. K.M. Tundo: None. S. Nadimidla: None. L. Scarpace: None. J. Barnholtz-Sloan: None. A.E. Sloan: None. W.R. Selman: None. A.C. deCarvalho: None. A. Mukherjee: None. A.M. Robin: None. I.Y. Lee: None. J. Craig: None. S. Kalkanis: None. J. Snyder: None. T. Walbert: None. J. Rock: None. H. Noushmehr: None. A.B. Castro: None.
Background: The differential diagnosis of challenging sellar tumor cases can be inconclusive through imaging features and could benefit from noninvasive diagnostic approaches, such as liquid biopsy (LB). Similar to tissue, LB specimens carry tumor-specific DNA methylation signatures amenable to the construction of accurate machine learning models able to discriminate CNS tumors. We aimed to develop methylation-based classifiers which classify sellar tumors by lobe of origin, using either LB or tumor tissue specimens. Methodology: We analyzed the DNA methylome (EPIC array) of tumor tissue (T) and LB specimens from adult patients with tumors representing each of the three pituitary lobes (Anterior: T=177; LB=37; Intermediate: T= 7; LB: 10 and Posterior: T=44, LB=2 cases). Using the most variably methylated CpG probes derived from the unsupervised variance-based analyses across tumors from different lobes, we applied multi-class linear discriminant analysis to construct machine learning models to classify sellar tumor tissue and/or LB specimens. Results: We generated classifiers based on lobe-specific methylation signatures that were able to discriminate across sellar tumors either using tissue and/or LB specimens (500 and 600 CpGs, respectively) with observed accuracies of ∼99% across independent validation. DISCUSSION/CONCLUSION: Our findings suggest that methylation-based classifiers constitute an accurate diagnostic approach to discriminate sellar tumors according to the lobe origin, either pre-surgically through a blood draw or through surgical tumor specimens. These classifiers are objective approaches that could complement imaging and pathology reports for an accurate diagnosis of inconclusive cases, ultimately leading to optimal management of the patients with these diseases.
Presentation: Saturday, June 17, 2023
SAT590 Complex Migraine Manifesting As CDI - A Rare Occurrence
Authors: Shahid Maham , Sari Esra , Timirau Wendy , Hamza Ameer , Guzman Nilmarie , Sultan Senan 
Published: October 2023

Abstract
Disclosure: M. Shahid: None. E. Sari: None. W. Timirau: None. A. Hamza: None. N. Guzman: None. S. Sultan: None.
Introduction: There are many references in the literature to unexplained neurological symptoms occurring with complex migraines, however, complex migraine manifesting as central diabetes insipidus (CDI) is rare. Clinical Case: A 48-year-old female with past medical history of psoriatic arthritis, generalized anxiety disorder, and migraine presented with the worst headache of her life for 2 days, typical for her migraine but with increased severity, and minimally responsive to NSAIDs. Her headache was accompanied by nausea, photophobia, floaters, polydipsia and polyuria. She denied any neck pain/rigidity, focal deficits, or head trauma. She reported a similar episode with lesser severity 10 days ago which resolved in 3 days. She related her headache episodes with polyuria. Her medications included topiramate, escitalopram, apremilast, loratadine, and NSAIDs. She denied any new medications. Physical examination was unremarkable. Initial labs showed high-normal sodium 145 mMol/L, normal serum osmolality 292 mOsm/kg, low urine specific gravity 1.003, and low urine osmolality 117 mOsm/kg and urine sodium 32.4 mMol/L. HbA1c, B-hCG and urinalysis were normal. CT brain, CTA head and neck, MRI brain with/without IV contrast, and CSF analysis were unremarkable. The patient was started on abortive treatment for migraine. She had a negative fluid balance of 1500ml during first 24 hours. Polyuria did not resolve with water restriction but resolved with improvement of migraine; which favored the diagnosis of complex migraine manifesting with polyuria secondary to CDI. Patient was discharged on migraine prophylaxis and neurology follow-up. Conclusion: Link between migraine and endocrinological disorders has been well identified. Even though most cases are idiopathic, any disorder that acts at the hypothalamic-pituitary axis involved in ADH secretion can cause CDI, however migraines as an etiology remains rare. Early recognition of symptoms, treatment of migraine and introduction of migraine prophylaxis was crucial in our case to prevent further episodes of CDI.
Presentation: Saturday, June 17, 2023
SAT591 Abnormal Levels Of Thyroid Hormones During Development Alters The Migration And Activity Of GnRH Reproductive Neurons
Authors: Quignon Clarisse , Backer Annika , Wray Susan 
Published: October 2023

Abstract
Disclosure: C. Quignon: None. A. Backer: None. S. Wray: None.
Clinical studies have shown that thyroid hormones disorders and alteration of thyroid hormone production by environmental endocrine disruptors, have deleterious effects on reproduction. By acting in the brain on the hypothalamic component of the reproductive axis, abnormal levels of thyroid hormones can disturb sex hormones production, oestrus cycles or puberty onset, possibly leading to subfertility. Moreover, in animal models, endocrine disruptors and thyroid hormones have been shown to have long-lasting transgenerational effects with the maternal hormones influencing the development of foetal reproductive functions. Despite clear evidence of an interaction between the thyroid and reproductive systems, the effect of T3, the active form of thyroid hormones, on the GnRH neurons controlling reproduction, have been poorly studied. In this work we investigated how T3 functionally interacts with GnRH neurons and how abnormal concentration of T3 alters the migration of these neurons during development. Calcium imaging was used to study the direct effect of T3 on GnRH neuronal activity in an ex vivo nasal explants model. Acute administration of T3 (30nM) was found to stimulate the activity of GnRH cells. Dual labelling of GnRH and thyroid hormone receptors (TR) showed that the GnRH neurons express both nuclear and membrane receptors. However, the use of an antagonist that specifically blocks the TR nuclear receptors (1-850), didn’t inhibit the T3 stimulatory effect. In contrast, blockage of integrin αV/β3 membrane receptors (with cilengitide), which have been shown to be activated by T3, prevented the T3-induced increase in GnRH neuronal activity. During development GnRH neurons migrate from the nasal placodes into the brain. Acute administration of T3 for 1hr significatively decreased the migration rate of the GnRH neurons in our ex vivo model. To assess the effect of thyroid disruption during pregnancy on the development of reproductive axis in utero, pregnant females mice have been treated with methimazole to induce hypothyroidism from gestational day 6 to 13. E13 embryos have been collected from treated and control dams and the distribution of migrating GnRH neurons will be compared between both groups. Together these studies are the first to report a direct effect of thyroid hormones on GnRH neuronal activity, through the integrin αV/β3 membrane receptors and show that T3 can modulate the migration of GnRH neurons during development. These results will bring new insights on how thyroid disruption by endocrine disruptor chemicals or thyroid diseases, especially during foetal development, can lead to long term reproductive defects.
Presentation: Saturday, June 17, 2023
SAT592 Sexually Dimorphic Modulation Of Arcuate Kisspeptin Neurons Activity In Response To NPY
Authors: da Silva Mansano Naira , Frazao Renata 
Published: October 2023

Abstract
Disclosure: N.D. Mansano: None. R. Frazao: None.
Kisspeptin neurons are part of an intricate brain circuit that receives neuronal inputs related tonutritional status from at least three neuronal populations, including NPY/AgRP and POMC neurons of the arcuate nucleus of the hypothalamus (ARH) and cells in the ventral premammillary nucleus. Its well-known action on the HPG axis, hypothalamic kisspeptin neurons also modulate the activity of specific neurons of the paraventricular and the dorsomedial nuclei of the hypothalamus, regions involved in the regulation of appetite and energy expenditure. However, it is not completely elucidated if NPY can influence the HPG axis through the modulation of kisspeptin neuron activity. To determine the NPY effect in the hypothalamic kisspeptin neurons we performed whole-cell patch-clamp recordings. The hypothalamic slices were obtained from the adult Kiss1/hrGFP female (diestrus-stage) or male mice. Kisspeptin cells located in the arcuate nucleus of the hypothalamus (ARHkisspeptin) and at the anteroventral periventricular and rostral periventricular nuclei (AVPV/PeNkisspeptin) were recorded. On female mice, ARHkisspeptin neurons exhibited a rest membrane potential (RMP) average of -52.5±2.5 mV (-40 to -62 mV) and 1.3±0.2 GΩ input resistance (IR). NPY induced the hyperpolarization of 45% of the ARHkisspeptin neurons (n= 9 of 20 cells, out of 9 mice). ARHkisspeptin neuron’s RMP hyperpolarization was followed by a significant decrease in IR and frequency of action potentials (fAPS). In the AVPV/PeNkisspeptin neurons showed RMP average of -69.6±1.9 mV (-51 to - 88 mV) and IR of 0.8±0.09 GΩ (n=18 cells out of 9 mice). No significant NPY-induced effect was noted when recordings were performed on AVPV/PeNkisspeptin cells from female mice. To elucidate if the ARHkisspeptin neuron’s hyperpolarization depends on action potentials (APs) mediated by synaptic transmission we further evaluated NPY effects in the presence of TTX and amino acid receptor antagonists (6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10μM), DL-2-amino-5-phosphonopentanoic acid (AP5, 50μM), and picrotoxin (50μM). NPY induced no effect on ARHkisspeptin neuron’s RMP, and IR in the presence of TTX and amino acid receptor antagonists. Suggesting that NPY-induced hyperpolarization of ARHkisspeptin neurons is an indirect effect. To further verify whether sex must be considered as a biological variable to study the NPY effect, we recorded ARHkisspeptin cells from male mice. ARHkisspeptin neurons recorded from male mice exhibited RPM average of -55.6±1.5 (-45 to -66 mV) and IR of 1.5±0.15 GΩ (n= 13 cells out of 10 mice). Interestingly, NPY induced no effect on RMP, IR, or fAPs in male animals. In conclusion, our results suggest that NPY-induced hyperpolarization of ARHkisspeptin cells depends on AP’s mediate synaptic transmission, as a sex-specific effect.
Presentation: Saturday, June 17, 2023
SAT598 7mg-dexamethasone Suppression Test For The Differential Diagnosis Of Cushing’s Syndrome
Authors: Ramos Daniel Cuevas , García Gabriela Garza , Hernández Núñez Wellbert Elías , Gómez Pérez Francisco Javier 
Published: October 2023

Abstract
Disclosure: D. Cuevas Ramos: None. G. Garza García: None. W. Hernández Núñez: None. F.J. Gómez Pérez: None.
Introduction: Establishing the cause of Cushing’s syndrome remains challenging. Bilateral Inferior Petrosal Sinus Sampling (BIPSS) is the gold standard for distinguishing between Cushing's disease (ACHT-secreting pituitary adenoma) and an ectopic source of ACTH. However, BIPSS is an invasive test and is not widely available. Therefore, we sought to explore the diagnostic efficacy of the 7 mg dexamethasone suppression test (7mg-dexa) for establishing the diagnosis of Cushing's disease (CD). Methods: We reviewed 1375 cases with pituitary adenomas. From them, 191 cases had confirmed diagnosis of CD from 1999 to 2022. Of these, 25 patients underwent 7 mg dexamethasone suppression test together with BIPSS during their diagnosis workup. A diagnosis of CD was established in 21 patients, confirmed after neurosurgery, with a pathology report of ACTH+ secreting pituitary adenoma, and a biochemical resolution of CS. The additional 4 cases showed an adrenal source of CS. Suppression of 50% or more in the afternoon (of day 1 after 7 mg-dexa IV infusion by 7h starting at 7:00 hrs at 1 mg/hr) was considered consistent with CD. A central-to-peripheral plasma ACTH gradient of ≥2 before and after desmopressin stimulation was also considered consistent with CD during the BIPSS. We calculated kappa index to evaluate concordance between diagnostic test. Also, sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were calculated. Results: The mean age was 43±12.1 years, with a BMI of 30±5.6 kg/m2, 86% females. For the basal ACTH values during BIPSS, the S=76%, E=75%, PPV=94%, NPV=37%, LR+=3, LR-=0.3. For the post-stimulation BIPSS, the S=95%, E=75%, PPV=95%, NPV=75%, LR+=3, LR-=0.06. Using the 7mg-dexa, a S=91%, E=75%, PPV=95%, NPV=60%, LR+=3.6, LR-=0.12. Kappa between test was 0.6 before stimulation, and 0.7 after desmopressin stimulation showing acceptable concordance. Conclusion: The 7 mg-dexa showed similar and acceptable diagnostic performance in comparison with basal or stimulated BIPSS. Since 7mg-dexa inhibition test is less invasive and less expensive, further clinical research to evaluate its utility in CD diagnostic approach is in order.
Presentation: Saturday, June 17, 2023