bluuebunny/crossref_metadata_2025_split huggingface dataset:
PMON69 Effective Suppression of Gonadotropins and Gonadal Steroids Following Oral Administration of Leuprolide
Authors: Shangold Gary , Rubin Arkady , Daggs Thomas , Vrettos John , Rasums Andrejs , Consalvo Angelo , Skeet Nicola , Shields Paul 
Published: November 2022

Abstract
A platform designed to enable systemic delivery of peptides via the oral-GI route was employed to deliver low doses of leuprolide --- 4 mg qd (Treatment A, n=9), 4 mg bid (Treatment B, n=9), and 10 mg bid (Treatment D, n=12) --- daily for 28 days to regularly-menstruating, healthy female volunteers. Pharmacodynamic (PD) effects on LH, FSH, estradiol, and progesterone, along with leuprolide drug levels, were assessed weekly and compared to those following a single intramuscular injection of leuprolide acetate 3.75 mg (Treatment C, n=5) in a parallel-group design. The primary PD endpoint was the subject incidence of E2 suppression to ≤40 pg/mL on Treatment Day 29; additional endpoints --- E2 suppression rates on Treatment Days 8, 15 and 22, incidence of 'ovulation' defined as progesterone level ≥3 ng/mL, and suppression of LH and FSH levels --- were assessed on Treatment Days 8, 15, 22, and 29. Safety and tolerability of the test drugs was also assessed. Dose-dependent suppression of E2 was seen, with 66.7%, 87.5%, 100% and 100% of subjects in Treatments A, B, C and D, respectively, achieving E2 ≤40 pg/mL. Median E2 levels on days 15, 22, and 29 were &lt;40 pg/mL after 4 mg bid po, and &lt;20 pg/mL after both 10 mg bid po and the 3.75 mg injection. 'Ovulation rates’ on days 22 and 29 were 0% after both 10 mg bid po and 3.75 mg im. Because of the initial burst following injection of the monthly depot, leuprolide Cmax was greater in Treatment C (17.5 ±2.7 ng/mL) on Dosing Day 1 than for oral leuprolide (3.7 ±3.2 ng/mL for 4 mg qd, 4.1 ±5.1 ng/mL for 4 mg bid), though by Day 29, Css in Treatment C (1.7 ±1.2 ng/mL) was lower than that day's Cmax for oral leuprolide (2.7 ±3.6 ng/mL for 4 mg qd, 4.8 ±6.2 ng/mL for 4 mg bid). Cmax and AUC0-24h were dose-dependent but not strictly dose-proportional. Leuprolide "trough" levels prior to oral dosing were frequently below LLQ (25 pg/mL) in subjects treated with 4 mg qd; this occurred in only 6% of samples on 10 mg bid, and 0% on 4 mg bid, thus confirming reliability of oral delivery of leuprolide. There were no Serious or severe Adverse Events, nor changes in laboratory values of concern. One subject discontinued the study due to a transient episode of nausea, vomiting, and headache during her initial dose of 4 mg po. A total of 80 AEs were treatment-emergent, generally mild in intensity, and spread relatively evenly across all 4 treatment groups. This investigation confirms effective suppression of gonadal steroids via oral administration of leuprolide, comparable to that of injectable leuprolide, and to some marketed doses of GnRH antagonists (historical data).
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON73 Lipid profile in patients with Cushing's syndrome and the impact of surgical treatment
Authors: Varghese Ron , McGlotten Raven , Shamburek Robert , Nieman Lynnette 
Published: November 2022

Abstract

Introduction
Cushing syndrome (CS) patients have an increased mortality rate, primarily due to increased cardiovascular and cerebrovascular disease. We postulated that lipoprotein or lipid profiles might underlie this risk.

Methods
We measured traditional lipid panels (Cholesterol, TC; calculated low density lipoprotein, LDL; triglycerides, TG; high density lipoprotein, HDL) by Abbot enzymatic assay and lipoprotein particles (particle size and number for HDL, LDL and VLDL) by nuclear magnetic resonance spectroscopy in CS patients before and after surgical remission. Values are shown as median (IQR or range).

Results
After initial evaluation, 41 subjects (median age 53 (IQR 39-63) years; 27 female) had presumed Cushing's disease (CD, n=23), ectopic ACTH secretion (EAS, n=17), or adrenal adenoma (AA, n=1). Fourteen were on chronic statin therapy. All median lipid values were normal except HDL, at 55mg/dl (range 27 - 59mg/dl, normal (RR) &lt;60). Twenty-six patients had decreased HDL; of these, other abnormal values included TC and LDL (n=4), TG (n=4), TC, LDL, TG (n=2), LDL and TG (n=2) or LDL only (n=2). Other elevated LDL levels occurred alone (n=1) or with TC (n=2). Three patients had only an increase in TC, LDL, or TG. Median LDL particle number was increased at 1015 (IQR 809-1353; RR &lt;1000), with normal particle size. Eighteen patients had increased LDL particle number (1005 - 2989); 7/18 had increased TC and/or LDL. The median particle size and number for HDL and VLDL were normal in all patients except for one with an increased VLDL particle number of 199.7 (RR 6.8 - 126.1; TGs 302mg/dl, LDL 61 mg/dl, HDL 36 mg/dl, Chol 158 mg/dl). Sixteen subjects with CD (n=10), EAS (n=5) or AA (n=1) (13 females, median age 53 (IQR 40-58) years) had data at last study visit (LSV) after surgical remission. At LSV (median 13 months, range 3-26 months) abnormal preoperative LDL particle size persisted in 5/10, with new abnormalities (to 1450nm) in 3 patients. Initially high LDL and TC normalized in 3/6 and 4/5 patients. Abnormal HDL values were new in 2 patients and persisted in 7/8 from baseline. HDL particle number was low in two of these patients, while one with an HDL of 90mg/dl had increased particle size (10.6nm). TG and VLDL particle number and size remained normal except for one patient with low values. A statistically significant decrease (p=0.03) of median VLDL particle size from 49.5 nm (IQR 47.8-52.5) to 45.5nm (IQR 43.3–49.6), was noted at LSV.

Conclusions
While the numbers are small, these data suggest that the moderate cardiovascular risk conferred by elevated LDL particle size and low HDL persisted for up to 26 months of remission. Improved initiation and modification of treatment for these abnormalities might improve outcomes.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP036 Cortisol Values During the Standard-Dose Cosyntropin Stimulation Test: Personal Experience with Elecsys Cortisol II Assay
Authors: Hamrahian Amir , Dinparastisaleh Roshan , Husni Hasan , Abusamaan Mohammed , Sokoll Lori , Salvatori Roberto 
Published: November 2022

Abstract

Background
There has been debate regarding the appropriate cortisol cutoffs during the cosyntropin stimulation test (CST) when the newer cortisol assays are used. Recent studies have recommended cortisol cutoffs lower than previously recommended. We aimed to evaluate the cortisol levels during the standard dose CST in patients evaluated for adrenal insufficiency and found to have a normal HPA axis using the Elecsys ® Cortisol II (Roche Diagnostics)assay. METHODS: This was a retrospective chart review study of adult patients who had the CST performed within an academic ambulatory setting from January 2018 to December 2020. They had ICD-10 codes of pituitary gland disorders in their problem list or diagnoses at the time of data extraction. Only patients with a normal HPA axis were included in the analysis, which was defined based on evaluation by an endocrinologist, restrictive exclusion criteria, and a lack of glucocorticoid administration for at least 6 months after CST. Exclusion criteria included oral glucocorticoid use within 6 months before the CST or 3 months for other routes, albumin &lt; 2.5 g/dL, liver disease, pituitary insult within 6 weeks before the CST, estrogen and opioid use within 3 months before the CST, and pregnancy. The results are reported in the median (range).

Results
Out of 305 patients, 63 (20.6) met the study criteria. The median age was 54.7 (27.6-89.1) years; 32 (51%) were females, and 27 (43%) were white. The duration of follow-up after the CST was 13.9 (6.3-43.9) months. Cortisol values at 30- and 60-minutes post-CST were available for 43 (68.2%), and 61 patients (96.8%), respectively. The cortisol levels at 30- and 60-minutes after the CST were 21.7 (15.7-29.1) µg/dL and 24.4 (17.9-35.8) µg/dL, respectively. The lowest cortisol levels at 30 and 60 minutes after the CST for patients with either normal TSH or gonadal axis (n=47) or in whom both axes were normal (n=18) were similar to the entire cohort.

Conclusion
Our study supports using a lower cortisol cutoff value at 30 minutes after the CST using the Roche Elecsys ® Cortisol II assay. The lowest cortisol level in our cohort was 15.7 ug/dL. However, the same pass criteria cannot be used at 60 minutes. Therefore, it is essential to consider the time of cortisol draw after the CST.
Presentation: No date and time listed
PMON84 A Unique Case of Diabetes Insipidus Revealing Hodgkin's lymphoma
Authors: Akcan Tugce , Patel Hiral , Pathak Ram 
Published: November 2022

Abstract

Introduction
While diabetes insipidus rarely presents as a symptom of non-Hodgkin's lymphoma, it is very rarely a revealing symptom of Hodgkin's lymphoma. We present a case of this unique association.

Case presentation
We report a case of a 25-year-old previously healthy male with no significant past medical history who presented with complaints of polydipsia, polyuria, and nocturia. A water deprivation test confirmed central diabetes insipidus. He started therapy with oral desmopressin and had clinical improvement. Magnetic resonance imaging (MRI) of his head showed thickened infundibulum and a lack of posterior pituitary bright spot, consistent with infundibulo-neurohypophysitis. There were no obvious masses within the anterior or posterior lobe, nor were suprasellar soft tissue masses noted. Diabetes mellitus (DM), autoimmune diseases, and infectious diseases were excluded. A chest x-ray revealed a superior mediastinal mass and a CT scan confirmed multiple mediastinal lymphadenopathies. A biopsy of pre-tracheal lymph node revealed nodular sclerosing Hodgkin's lymphoma. The patient received six cycles of chemotherapy with Adriamycin, Bleomycin, Vinblastine and Dacarbazine (ABVD) and achieved a complete remission. A follow up MRI head scan showed a decreasing in the thickness of infundibulum along with non-visualization of the posterior pituitary bright spot. Finally, his symptoms resolved with DDAVP therapy.

Conclusions
Diabetes insipidus involving the pituitary gland of Hodgkin's lymphoma is an extremely rare presentation of endocrine deficiency and malignancy. The literature describes only a few such cases. Clinicians should be aware diabetes insipidus might rarely present as a symptom of Hodgkin's lymphoma without obvious metastatic involvement of the neurohypophysial system. Continuing to report anecdotal experiences in managing similar complex scenarios is essential and remains the only reference for clinicians who handle patients with a similar presentation.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP038 Efficacy of Medical Treatment Compared to Unilateral Adrenalectomy in a Cohort of Patients with Primary Aldosteronism Treated at the Centre Hospitalier Universitaire de Sherbrooke – CHUS
Authors: Boily Pascale , St-Jean Matthieu 
Published: November 2022

Abstract

Background
Primary aldosteronism (PA) is associated with a high burden of cardiometabolic complications such as coronary heart disease, atrial fibrillation, left ventricular hypertrophy, stroke and chronic kidney disease. It is therefore essential to screen, confirm the diagnosis and then implement a targeted treatment, to lower the rate of these complications. According to the latest Endocrine Society guidelines for the management of PA, unilateral adrenalectomy is recommended when the secretion of aldosterone is mostly coming from one adrenal. If the secretion is bilateral or if the patient refuse surgery, medical treatment with mineralocorticoid receptor antagonist is indicated. Nevertheless, there are limited data comparing these two treatments on their impact on the number and dosage of anti-hypertensive drugs needed to control the disease.

Objective
The objective was to compare the impact of medical or surgical treatment on the antihypertensive defined daily dose (DDD) after 6 months of treatment in our cohort of PA patients followed at the CHUS. We've also evaluated the kalemia, blood pressure and renin after 6 and 12 months of treatment. Long term blood pressure control has also been evaluated.

Methodology
To answer this question, we conducted a single-center retrospective cohort study. Adults followed at CHUS between 2000 and 2021, with a confirmed diagnosis of PA and a follow-up of at least 6 months were included. Pregnancy was the only exclusion criteria. The primary outcome was the variation in the antihypertensiveDDD in patients medically treated compared to those surgically treated after 6 months.

Results
A total of 46 patients were included in our cohort, from which 28 were medically treated. Patients in the surgical group were younger, had a higher diastolic blood pressure and aldosterone/renin ratio. Among the 18 patients who underwent unilateral adrenalectomy, only 6 of them had a clearly lateralized secretion confirmed by adrenal veins sampling. At 6 months, the antihypertensive DDD variation was statistically significantly higher in the surgical group, with a decrease of 1.7 compared to a decrease of 0.6 in the medical group. Even after age, diastolic blood pressure and aldosterone/renin ratio adjustments, the difference between the 2 groups remains statistically significant, with a p value of 0. 033.

Conclusion
These results indicate that the surgical treatment of patient with primary aldosteronism leads to a greater DDD decrease at 6 months, even after adjusting for disease severity and despite the fact that the surgical group is not exclusively unilateral. However, the impact of disease control on long-term outcomes could not be assessed due to missing data.
Presentation: No date and time listed
PSUN343 Ectopic Prolactinoma in the Bony Clivus: A Common Disease in an Uncommon Location
Authors: Eisenberg Yuval , Pradeep Pallavi 
Published: November 2022

Abstract

Introduction
Ectopic prolactinoma has previously been reported and may be found in various locations, including sphenoid sinus, cavernous sinus, suprasellar region, nasopharynx, and rarely the clivus. We report a case of prolactinoma without any evidence of adenoma in the pituitary, which was subsequently found to be located to be in the bony clivus, after 36 years of initial presentation.

Case Description
A 66-year-old woman was seen in the clinic for known history of hyperprolactinemia. She was first diagnosed at the age of 30 when she presented with headaches, irregular menstrual cycles, and galactorrhea. MRI Pituitary at that time was not suggestive of a pituitary adenoma. She was thought to have a microadenoma not visualized on imaging and was only treated with dopamine agonist therapy for 2-3 years at that time. Presently, she complained of mild headaches intermittently but denied any symptoms of galactorrhea. Physical examination, including visual field testing, was unremarkable. Lab tests were suggestive of elevated prolactin levels, which had increased to 171ng/ml as compared to 121 ng/ml a year ago (RR: 3.3- 26.7 ng/ml). Chemistry panel, thyroid function test were in the normal range. Given uptrending prolactin levels, MRI Pituitary was repeated, which showed normal pituitary gland for age, and an enhancing mass with intermediate T1 and T2 signal in the bony sella measuring 1.4×1.1×1.5 cm, previously measuring 1.3×1.1×1.2 cm (3y ago), with loss of the normal bony cortex abutting the pituitary gland. Pt subsequently underwent endoscopic transsphenoidal biopsy of the clival lesion. Histopathology and immunochemical staining results showed findings consistent with pituitary adenoma, prolactinoma.

Discussion
Ectopic pituitary tissue, as well as prolactinoma, have been reported at various locations along the migratory path of the pituitary gland. The craniopharyngeal canal, which provides the opening for oral ectoderm, which is also known as Rathke's pouch, to migrate superiorly into the sella, leaves a bony layer separating the intracranial sella turcica from the extracranial sinuses and nasopharynx. Growing mass in the bony sella, as seen in our patient, is concerning for several rare pathologies with malignant potential, hence requiring biopsy. Tumors of the clivus constitute less than 1% of all intracranial neoplasms- which include chordoma, lymphoma, metastatic carcinoma, chondrosarcoma, meningioma, craniopharyngioma, germ cell tumor, astrocytoma, and pituitary adenoma. Less than 15 cases of clival ectopic prolactinoma have been reported in the past.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF13 | PMON142 Long Non-coding RNAs in Pituitary Differentiation and Endocrine Function
Authors: Camper Sally , Brinkmeier Michelle L , George Akima S , Melamed Philippa , Cheung Leonard Y M 
Published: November 2022

Abstract
Mammalian genomes contain thousands of genes for long non-coding RNA (lncRNAs) that affect the expression of other genes through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced and polyadenylated, but they are not translated into proteins. Nuclear lncRNAs modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins. Not much is known about the role of lncRNA in pituitary gland differentiation and function, but there are several examples that provide a strong premise for investigating this class of transcripts more deeply. For example, the lncRNA MEG3 is a tumor suppressor that is silenced in non-functioning pituitary adenomas; and lncRNAs have been implicated in regulating the function of key transcription factors such as POU1F1, PITX1, and PITX2. To develop a research resource for the study of lncRNA, we used cell-type specific cre transgenes to tag individual adult pituitary cell types with fluorescent markers and enriched for thyrotropes, gonadotropes and somatotropes using fluorescence activated cell sorting. We determined the transcriptome of each cell population using RNA sequencing and mined the data for lncRNA. We detected hundreds of lncRNA in adult pituitary cells, and some were cell-type specific, and located in immediate proximity of genes that encode pituitary hormones or lineage-specific transcription factors. We discovered that the lncRNA Nr5a1os is enriched in gonadotropes, while Foxl2os is enriched in gonadotropes and thyrotropes. The lncRNA Platr9 is located on the opposite strand near Cga, which encodes the alpha subunit of thyrotropin and gonadotropin. We also mined transcriptome data from pituitary glands collected at embryonic days 12.5 and 14.5 and identified 351 unique lncRNAs, many of which are exclusively expressed during development. Among these is Six3os1, which is located upstream of Six3, a gene associated with holoprosencephaly and hypopituitarism. The location of many of these lncRNAs suggests that they may have a cis-acting regulatory role in pituitary development or physiological function. This research resource sets the foundation for examining the actions of lncRNAs on expression of nearby genes during development and in response to physiological demand. Future research will elucidate their mechanisms of action, determining whether they recruit regulatory proteins to the chromatin and/or form R-loops in these regions, and how this affects expression of the target gene(s). We expect these studies to further our understanding of pituitary biology.
Presentation: Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF25 | PMON50 Insight into Integrated Control of Pituitary Function Revealed Through Analysis of Musashi Target mRNAs
Authors: Lim Juchan , Banik Jewel , Urbaniak Alicja , Bronson Katherine , Tomlinson Sophia , Hardy Linda , Gies Allen , Byrum Stephanie , Wilczynska Ania , MacNicol Melanie , Childs Gwen , MacNicol Angus 
Published: November 2022

Abstract
The anterior pituitary controls growth, metabolism, reproduction and stress responses through the synthesis and secretion of specific hormones. Distinct cell lineages within the anterior pituitary generate specific hormones. Interestingly, the anterior pituitary exhibits a high level of adult cell plasticity that allows committed hormone-producing cells to alter their cell fate and produce different hormones to meet altered organismal demands. The molecular mechanisms underlying this adult cell plasticity have not been fully characterized. Our recent work has implicated the stem cell determinant and sequence-specific mRNA binding protein, Musashi, as a regulator of pituitary cell plasticity. The mechanisms by which Musashi controls pituitary cell plasticity are unknown. In this study, we have sought to identify the mRNA regulatory targets of Musashi in the adult mouse pituitary. Through the use of Musashi-RNA-immunoprecipitation we report a cohort of 1192 pituitary mRNAs that specifically interact with Musashi. mRNAs specific to each of the hormone-producing cell lineages were identified, as well as mRNAs specific to immature stem and progenitor cell lineages. The biological pathways encoded by the Musashi-enriched mRNAs include cell adhesion, cellular homeostasis, unfolded protein responses, protein trafficking, endocrine processes and female pregnancy. Functional analysis of validated mRNAs reveals both activating and inhibitory control of mRNA translation by Musashi. Together, our findings indicate a broad and complex role for Musashi in the post-transcriptional regulation of adult pituitary function.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:58 p.m. - 1:03 p.m.
PMON184 Ligand-dependent interaction between phosphatidylcholine transfer protein and PPARδ: therapeutic implications for metabolic syndrome
Authors: Druzak Samuel , Tardelli Matteo , Mays Suzanne , Bejjani Mireille , Cato Micheal , Tillman Matthew , Cohen David , Mo Xiulei , Fu Haian 
Published: November 2022

Abstract
Phosphatidylcholine transfer protein (PC-TP; synonym StarD2) is a soluble lipid binding protein that transports phosphatidylcholine (PC) between cellular membranes. PC-TP knockout mice are more sensitive to glucose and insulin, have increased beta oxidation and improved liver health compared to wild-type mice. To better understand the protective metabolic effects associated with PC-TP deletion, we investigated how hepatic PC-TP affects lipid metabolism, sensitivity to glucose and insulin, and energy homeostasis in a mouse model of diet-induced obesity. We generated a liver-specific PC-TP knockout mouse (L-Pctp-/-), which gains less weight and accumulates less liver fat compared to wild-type mice when challenged with a high fat diet. Hepatic deletion of PC-TP also reduces levels of triglycerides and phospholipids in skeletal muscle, suggesting that PC-TP in the liver influences lipid metabolism in the muscle. Gene expression analyses suggest that the observed metabolic changes are related to transcriptional activity of peroxisome proliferative activating receptor (PPAR) family members. An in-cell protein complementation screen between lipid transfer proteins and PPARs uncovered a novel, direct interaction between PC-TP and PPARδ that was not observed for other PPAR family members. We confirmed the PC-TP-PPARδ interaction in Huh7 hepatocytes, where it was found to repress PPARδ-mediated transactivation. Mutations of PC-TP residues implicated in PC binding and transfer combined with a reduction of exogenously supplied lipids through serum starvation relieves PC-TP mediated PPAR repression. Together our data points to a ligand sensitive PC-TP– PPARδ interaction that suppresses PPAR activity.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.