bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP340 NOVEL THERAPY OSILODROSTAT AS AN OPTION FOR RECURRENT CUSHING'S DISEASE
Authors: Marin Luis Madera , Nieves Yadiel Rivera , Rivera Monica Ortiz , Burgos Alexandra Rosado , Cordero Nicole Hernandez , Ortega Nydia Burgos , Vick Margarita Ramirez , Rodriguez Loida Gonzalez , Alvarado Milliete 
Published: November 2022

Abstract

Introduction
Cushing's Disease (CD) denotes a pathologic endogenous hypercortisolism secondary to excessive adrenocorticotropic hormone (ACTH) production. Cushing Disease is a rare condition with an estimated incidence of approximately 1.2-1.4 new cases / 1. 000. 000 per year. Although surgical intervention is the gold standard in the management of CD, many patients may present persistence or recurrence of disease despite surgical intervention, resulting in significant deterioration of their quality of life (QoL). For those in whom pituitary surgery is not an option or has not been curative, medical therapies have been developed. One of these newer treatments is the drug Osilodrostat, an inhibitor of the enzyme 11-beta-hydroxylase, responsible for the final step of cortisol biosynthesis in the adrenal glands.

Case Discussion
Case of a 21 year-old female patient with history of Cushing's Disease status post-transsphenoidal surgery (TSS) in 2017, obesity and oligomenorrhea who presented to our clinics showing signs and symptoms of hypercortisolism despite previously documented post-surgical remission in 2017. Patient reported recent development of acne, weight gain, round face, elevated blood pressure and mood changes. At the moment of evaluation, her most recent MRI showed post-surgical changes without a discrete lesion. Work-up was compatible with recurrence of Cushing's with an ACTH at 75pg/mL (nl, 10-60pg/mL), urinary free cortisol (UFC) at 1,122mcg/24h (nl, 4-50mcg/24h) and serum morning cortisol at 24. 0mcg/dL (nl, 5-20mcg/dL). In view of a negative MRI for a pituitary lesion, a Bilateral Inferior Petrosal Sinus Sampling (BIPSS) was performed. The BIPSS procedure revealed a pituitary source with a right pituitary lateralization suggestive of a right ACTH-producing tumor. The patient was consulted to Neurosurgery Service, but while waiting for repeat surgery, control of hypercortisolism was needed. The patient was started on Osilodrostat 2mg twice a day and was able to achieve normalization of UFC to 4mcg/24h, serum morning cortisol 5mcg/dL and late-night salivary cortisol (LNSC) of 30ng/dl (&lt;90ng/dL) with significant improvement in her QoL, depression and clinical manifestations. The patient tolerated therapy well.

Conclusion
Cushing's Disease is a complex condition with potential serious complications if untreated. Even though TSS is the first line therapy, approximately 25% of patients show persistence of disease, and a similar proportion may experience recurrence. When surgery fails, medical treatment such as Osilodrostat, can temporarily suppress excessive cortisol production and ameliorate its clinical manifestations improving patients’ QoL while more definitive therapy is established.
Presentation: No date and time listed
ODP021 A Feminizing Adrenocortical Carcinoma Presenting with Marie-Antoinette Syndrome
Authors: Alnuaimi Abdulla , Alameri Majid , Marco Aimee D , Wernig Florian 
Published: November 2022

Abstract

Introduction
Adrenocortical carcinomas (ACCs) are rare and aggressive malignant tumors often with an unfavorable prognosis accounting for 0. 05-0.2% of all cancers. ACCs can be separated into 2 groups: Functioning (hormone-producing) and non-functioning tumors. About 60% of ACCs synthesize hormones. Hormone-secreting ACCs most commonly cause virilization or Cushing's syndrome. On very rare occasions, ACCs can lead to feminization in male subjects. Clinical manifestations are gynecomastia and/or hypogonadism. Here, we present a case of an estradiol-secreting adrenal cortical carcinoma.

Case presentation
A 58-year-old male presented with patchy hair loss, change in hair colour to white, loss of body hair and eyebrows, and breast tenderness. Hormone testing revealed significantly elevated estradiol came 582 pmol/L [NR&lt;190] with a very low testosterone of 1.6 nmol/L [NR10-30], low FSH 0.1 mIU/mL [NR 0.95-11.5] and LH of 0.6 mIU/mL [NR1.14-8.75]. A testicular ultrasound was unremarkable. An adrenal MRI revealed an 11 cm heterogeneous right adrenal mass invading the inferior vena cava. FDG PET-CT revealed an intensely metabolically active tumor without any evidence of metastatic disease. The tumor was successfully removed via an open procedure. Histology confirmed an adrenocortical carcinoma with a Weiss score of 8 with a mitotic account of 10/50 HPF and Ki-67 labelling index of 20-25%. There was vascular invasion with large areas of necrosis, ENSAT (European Network for the Study of Adrenal Tumours) stage II. Postoperatively, he made a good clinical recovery and was offered adjuvant Mitotane and EDP (Doxorubicin, Etoposide and Cisplatin) chemotherapy. Due to a significant rise in GGT and platelets, Mitotane had to be stopped temporarily. During the course of his treatment, he developed a hoarse voice and CT neck revealed abnormal thickening of the lateral aspects of the aortic arch suggesting possible tumor recurrence or aortitis. A biopsy was not diagnostic, but did not show any features of malignancy. He completed his five cycles of EDP chemotherapy. Estradiol has remained normal and his hoarse voice improved.

Conclusion
We describe a rare case of an estradiol-secreting ACC presenting with feminization and Marie-Antoinette syndrome as well as possible paraneoplastic aortitis. Targeted molecular tumor analysis may guide further treatment options and enrolment in clinical trials should be considered.
Presentation: No date and time listed
ODP343 Phoenixin as a Novel Autocrine/Paracrine Factor Stimulating Prolactin Secretion and Gene Expression at the Pituitary Level in Fish Model
Authors: Wong Anderson O L , Li Dongliang , Ye Cheng , He Mulan , Ko Wendy K W 
Published: November 2022

Abstract
Phoenixin (PNX), a new peptide first identified by bioinformatics, is widely expressed at tissue level and confirmed to be the ligand for the orphan receptor GPR173. Its mature peptide PNX 20 is highly conserved across species and emerged as a novel regulator for reproductive, appetite control, memory retention, plain perception and cardiovascular protection. However, not much is known for the comparative aspects of PNX and the post-receptor signaling mediating PNX action is still unclear. Using grass carp as a model for bony fish/teleost, carp PNX and its receptor GPR173 were cloned and confirmed to be single-copy genes in the carp genome. Using RT-PCR, transcript signals of PNX and GPR173 were found to be widely expressed in different tissues, including the brain-pituitary axis. As revealed by LC/MS/MS and ICC staining, protein signals of PNX and GPR173 could be detected in the pituitary and co-localized in immuno-identified lactotrophs. In primary culture of carp pituitary cells, static incubation with the synthetic peptide of carp PNX 20 was effective in increasing prolactin (PRL) release, PRL cell content and total production of PRL with a parallel rise in PRL mRNA level. The opposite was true for PRL secretion and transcript expression in parallel experiment with removal of endogenous PNX by immunoneutralization using PNX antiserum. Besides the stimulation on PRL signals, similar treatment with PNX 20 could also elevate cAMP and intracellular Ca 2+ levels with rapid phosphorylation of PI3K, Akt, MEK 1/2 and ERK 1/2 in carp pituitary cells. In the same model, except for a lack of effect with PKC blockade, co-treatment with the pharmacological inhibitors for different signalling components of the cAMP/PKA, PLC/IP 3, PI3K/Akt and MAPK cascades was effective in reducing/causing a total blockade of PNX 20 -induced PRL release and gene expression. Our results, as a whole, suggest that (i) PNX produced locally within the carp pituitary, presumably via activation of GPR173, could act as an autocrine/paracrine signal to stimulate PRL secretion and gene expression in carp lactotrophs, and (ii) the stimulatory effects on PRL regulation caused by the local actions of PNX probably are mediated by the cAMP/PKA-, PLC/IP 3 -, PI3K/Akt- and MAPK-dependent signaling mechanisms.
Presentation: No date and time listed
ODP348 Regional disparities in functional impairment due to arthropathy in patients with acromegaly.
Authors: Ahmad Syed , Chen Kevin , Chik Constance , Clarke David , Ibrahim Aisha , Imran Syed , Ladouceur Michel , Steeves Keillor , Title Michaela , Tramble Lisa , VanUum Stan , Wang Yuqi 
Published: November 2022

Abstract

Objective
While arthropathy is common in acromegaly (ACRO), its impact on the physical function of patients is not well understood. We sought to compare physical function between patients with a history of ACRO or with a nonfunctioning pituitary adenomas (NFA) who had previously undergone pituitary surgery.

Methods
Sex- and age-matched participants (n=34 for both groups) were recruited from the Halifax Neuropituitary Program. All ACRO patients were in remission with or without medical therapy. All patients completed validated questionnaires related to musculoskeletal disability and symptoms of the upper extremity (QuickDASH), functional impact of arthropathy in the weight-bearing joints (hips: HOOS-JR, knees: KOOS-JR, ankles: Quick-FAAM), and balance (ABC-6). We also assessed the number of falls in the past 12 months. HOOS-JR and KOOS-JR scores were compared using paired t-tests, whereas the Wilcoxon signed-rank test was used to compare DASH, DASH-Work, DASH-Instrument, Quick-FAAM, and ABC-6 scores between the two groups.

Results
ACRO compared with NFA patients, respectively, had higher upper-limb musculoskeletal disability and symptoms scores [17. 04 (0-70.45) vs. 4.55 (0-50. 00); p=0. 009]. However, there were no significant differences between the DASH-Work score or DASH-Instrument score between the two groups (p=0.317 and 0.18, respectively). ACRO patients had poorer functional scores for the hip compared with NFA (73.43±22.41 vs 86.45±15.43, p=0. 014) and knee (72.69±22.15 vs. 83.30±17.67, p=0. 056). However, there were no differences in ankle scores (p=0. 097). The number of falls within the last 12 months did not differ between the two groups (p=0.424), but there was a trend towards lower levels of self-confidence to maintain balance in ACRO patients compared with NFA patients (75% (8.33-100% vs90% (28.33-100%, p=0. 051).

Conclusion
ACRO patients showed significantly lower functionality of upper extremities and hips and a trend to greater functional impairment in the knee joints. Even though the number of falls was not different between the two groups, we did note a trend towards reduced levels of self-confidence to maintain balance in ACRO patients.
Presentation: No date and time listed
ODP354 Telomeres Length and Wnt/beta-catenin Pathway in Adamantinomatous Craniopharyngiomas
Authors: Ítalo S. Mota José , Silva-Júnior Rui M Patrício , Martins Clarissa Silva , Bueno Ana Carolina , Eduardo Wildemberg Luiz Eduardo Luiz , da Silva Antunes Ximene L , Okanobo Ozaki Jorge G , Coeli-Lacchin Fernanda B , Garcia-Peral Carlos , Oliveira Antonio Edson R , dos Santos Antonio Carlos , Moreira Ayrton C , Machado Helio Rubens , dos Santos Marcelo V , Colli Leandro M , Gadelha Mônica R , Antonini Sonir R , de Castro Margaret 
Published: November 2022

Abstract

Objectives
To evaluate how telomeres length behaves in adamantinomtous craniopharyngioma (aCP) and if it contributes to the pathogenesis of aCPs with and without CTNNB1 mutations. Design: Retrospective cross-sectional study enrolling 42 aCPpatients from two tertiary institutions.

Methods
Clinicopathological features were retrieved from patient's charts. Fresh frozen tumors were used for RNA and DNA analyses. Telomere length was evaluated by qPCR (T/S ratio). Somatic mutations in TERT promoter (TERTp) and CTNNB1 were detected by Sanger and/or whole-exome sequencing. We performed RNA-Seq to identify differentially expressed genes in aCPs presenting with shorter or longer telomere lengths.

Results
Mutations in CTNNB1 were detected in 29 (69%) tumors. There was higher frequency of CTNNB1mutations in aCPs from patients diagnosed under the age of 15 years (85% vs 15%; p=0. 04) and a trend to recurrent disease (76% vs 24%; p=0.1). No mutation was detected in the TERTp region. The telomeres were shorter in CTNNB1-mutated aCPs (0.441, IQR: 0.297-0.597 vs 0.607, IQR: 0.445-0.778; p=0. 04) but it was neither associated with clinicopathological features nor with recurrence. RNAseq identified a total of 387 differentially expressed genes, generating two clusters, being one enriched for short telomere and CTNNB1-mutated aCPs.

Conclusions
CTNNB1 mutations are more frequent in children and adolescents and appear to associate with progressive disease. CTNNB1-mutated aCPs have shorter telomeres. This is the first evidence for a relationship between the Wnt/beta-catenin pathway and telomere biology in the pathogenesis of aCPs.
Presentation: No date and time listed
ODP602 A Rare Case of Nonfunctional Metastatic Pancreatic Neuroendocrine Tumor Transformation into an Insulin-secreting Tumor: A Management Dilemma
Authors: Azmath Misbath , Faisal Sobia , Kantorovich Vitaly , Guruli Marie 
Published: November 2022

Abstract
Pancreatic neuroendocrine tumors (PNETs) although rare, have recently increased in incidence . Clinically they can be classified as functional or nonfunctional depending on presence or absence of active hormone symptomatology and this has a bearing on prognosis and management . Rarely nonfunctioning tumors can undergo biological transformation into a hormone-secreting tumor. We present a rare clinical scenario of a young male with widely metastatic nonfunctional PNET who later presented with profound hypoglycemia with concerns for transformation into an insulin secreting tumor.
Presentation: No date and time listed
ODP026 An Incidental Giant Normotensive Pheochromcytoma with Elevated Metanephrines demonstrated no evidence of hypertensive crisis during a major surgery
Authors: Camacho Yudi , Jamal Yusra , Brutsaert Erica , Goswami Gayotri 
Published: November 2022

Abstract
A 48-year-old Caucasian male with no known past medical history admitted to our hospital following MVA resulting in acute severely comminuted displaced fracture of the left femur and tibia. On admission, the patient was in severe pain. His vitals were significant for elevated blood pressure (BP) of 137/100 and pulse rate of 161 per minute, which resolved soon after pain medications and splint placement. On review of systems, he denied episodic spells of headaches, palpitations, pallor, tremors, anxiety, abdominal pain, or diaphoresis. He denied any family history of endocrine disorders. Physical exam was unremarkable, except for the left femur traction splint. He had multiple CT imaging performed for evaluation of his injuries. On CT scan of the abdomen, he was found to have a 7.2cm adrenal incidentaloma with imaging characteristics consistent with pheochromocytoma. He was admitted to the intensive care unit for one day for closer monitoring where he remained hemodynamically stable without any BP lowering medications. Laboratory work up for a pheochromocytoma was pending. However, due to concern of compartment syndrome of left lower extremity, patient underwent two emergent procedures of open reduction and internal fixation of left femur and tibial fracture repair. Robust monitoring of hemodynamics was performed during both surgeries but patient did not require any antihypertensive medications during the procedures. Eventually, serum total metanephrines drawn on admission day two, resulted as 7848 pg/ml (normal &lt;205pg/ml), normetanephrines 3626 pg/ml (normal &lt;148pg/ml), and metanephrines 4224 pg/ml (normal&lt;57pg/ml). Serum cortisol, aldosterone, renin, dehydroepiandrosterone sulfate, and glucose were within normal limits. On day 3 of admission, repeated serum metanephrines were persistently elevated in 4000s. 24-hour (hr) urine studies showed total metanephrines 7353 mg/24hr (normal &lt;832 mg/24hr), metanephrines 4934 mg/24hr (normal &lt;315 mg/24hr), normetanephrines 2419 mg/24hr (normal &lt;676 mg/24hr) and creatinine2.3g/24 hr (normal &lt;2. 0g/24hr) . MRI abdomen confirmed pheochromocytoma abutting the pancreas and left upper pole of kidney. Interestingly, patient remained hemodynamically stable with highest BP measurement of 120/90 throughout the hospital course. He was eventually discharged on Prazosin 1 mg twice daily which was gradually increased to 5 mg daily in divided doses; increase fluid intake and high salt diet. Beta-blocker was not added due to borderline blood pressure. The patient underwent robotic left radical adrenalectomy without any intraoperative hemodynamic instability. Pathology was consistent with pheochromocytoma, confined to the adrenal gland without no capsular invasion. The patient refused genetic testing.
Presentation: No date and time listed
PMON106 Persistent Prolactin Levels in a Patient with Pituitary Adenoma
Authors: Kadakia Natasha , Sadiq Sobia 
Published: November 2022

Abstract
We present a peculiar case of persistently elevated prolactin levels with significant residual tumor in the setting of dopamine agonist therapy.This is a 45 year old male with no known medical history who presented with a seizure. Work up was significant for a large homogeneously extra-axial mass (57×35×44 mm) arising from the left clinoid extending anteriorly, inferiorly, and posteriorly to the planum sphenoidale, the sphenoid sinus, and the suprasellar cistern, respectively. The mass extended superiorly to compress the hypothalamus, and medially to the right cavernous sinus. This mass was causing elevation of the optic chiasm and encasement of the left optic nerve and the left internal carotid artery with displacement of the pituitary infundibulum to the right. Biochemical workup revealed hyperprolactinemia with a prolactin level greater than 2000, and secondary hypogonadism; free testosterone level of 27.1. He was started on therapy with a dopamine agonist, cabergoline at 0.5 mg. This dose was up titrated to a max dose of 12 mg weekly over 6 months. Subsequently, prolactin levels trended down from initial levels of &gt;2000 to 1142 to 1115 to 1045 to 710 with corresponding increases in cabergoline. He began to experience CSF rhinorrhea. Neurosurgery recommended medical therapy given the high risk anatomical location of the prolactinoma. In our interdisciplinary conference, discussion was had regarding other therapeutic agents. Patient was started on anastrozole and metformin. He subsequently started somatostatin, as well. Patient underwent a repeat MRI Sella on 9/2021 with a 50% decrease in size. Most recently, the patient has had a repeat seizure and is scheduled for a repeat MRI with possible consideration of surgical resection despite the high risk surgery.Current guidelines suggest symptomatic patients that do not achieve normal prolactin levels or show significant reduction in tumor size on standard doses of a dopamine agonist should be increased to maximal tolerable doses before referring for surgery There is literature regarding alternative treatment options in the setting of elevated prolactin levels with a discordant response to first line therapy. Options include switching to another dopamine agonist, radiotherapy, or alternative options. One of these options include aromatase inhibitors, with inhibitory effects on prolactin gene transcription. There are studies that outline use of Temzolamide for aggressive pituitary tumors and carcinomas, however, there is not enough data regarding its use in resistant Prolactinomas. Lastly, somatostatin analogues have been shown to reduce prolactin levels due to the presence of somatostatin receptors in prolactinomas. A published case series (Sosa-Eroza et al.) showed 5 patients with DA resistance with two cases with reduction in tumor volume and prolactin level. Our patient has had a response to sandostatin with most recent prolactin levels 111.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON117 IGF-1 Testing: Diagnostic Pitfalls
Authors: Perez-Martinez Sebastian 
Published: November 2022

Abstract

Introduction
Acromegaly is a rare endocrine disorder, with an incidence of 5.3/million/year, that results from persistent hypersecretion of growth hormone (GH), which stimulates hepatic secretion of insulin-like growth factor-1 (IGF-1). The best single test for the diagnosis of acromegaly is measurement of serum IGF-1; however, the result must be interpreted with caution, with understanding of potential pitfalls. Here we present a case of falsely elevated IGF-1 levels.

Case Description
A 43-year-old female with medical history of prediabetes, sleep apnea, and headaches was referred to endocrine clinic for evaluation of possible acromegaly. Patient had been evaluated by her primary care physician for frequent headaches, unintentional weight gain, and bilateral leg and hand swelling. Patient endorsed being unable to wear her wedding ring for a few years.
Initial laboratory evaluation by primary care physician 3 months prior revealed normal thyroid function, prolactin, FSH, LH, random cortisol, but elevated IGF-1 of 310 ng/mL (normal 71-258 ng/mL), with negative pregnancy test. Brain MRI at that time revealed a pineal gland cyst but no pituitary abnormality.
During her initial endocrine visit, IGF-1 was repeated, which was again elevated but improved to 283 ng/mL (normal 71-258 ng/mL). Other pertinent labs included a normal random ACTH of 18 pg/mL (normal &lt;47 pg/mL), and pm cortisol of 2.4 mcg/dL (normal 2.9-17.3 mcg/dL). Physical examination was notable for a few light purple striae on abdomen, acanthosis nigricans, and mild limb edema, but no macrognathia, enlarged hands or feet. Given patient's lack of typical features of acromegaly, normal pituitary imaging, and spontaneous IGF-1 improvement, it was decided to postpone GH measurements with oral glucose tolerance test but repeat IGF-1 in 6 months.
Patient was able to follow up 11 months after initial visit at which patient denied any worsening symptoms. At that time, repeat laboratory study showed normal IGF-1 of 231. Given spontaneous normalization of IGF-1 levels, no further laboratory testing or imaging studies were recommended, and patient was instructed to follow up in 11-12 months.

Discussion
Prompt diagnosis of acromegaly is crucial. However, it is important to note IGF-1 could be falsely elevated. A retrospective review by Erickson et. al of 2747 unique patients with IGF-1 elevation, 117 (4%) were found to have false-positive results following a review of the clinical data. In addition to acromegaly, other causes of elevated IGF-1 levels include high protein and high glycemic-index diet, pregnancy, hyperthyroidism, IGF-1 assay problems, and some rare tumors (carcinoids) secreting IGF-1. Discovery of "falsely" elevated IGF-1 may lead to unnecessary testing and physician visits. Therefore, clinicians should consider retesting patients after some time interval if spurious IGF-1 is suspected, before aggressively pursuing more extensive investigations.
Presentation: No date and time listed