bluuebunny/crossref_metadata_2025_split huggingface dataset:
RF36 | PSUN93 A Role for Somatostatin in Regulating Weight Regain after Bariatric Surgery in Mice
Authors: Arad Yhara , Ben-Zvi Prof Danny , Kleiman Doron , Schyr Rachel Ben-Haroush 
Published: November 2022

Abstract
Somatostatin is an inhibitory neuropeptide expressed in several neural and endocrine systems. For example, Somatostatin represses the secretion of growth hormone from the pituitary gland, and the secretion of gastrointestinal and pancreatic hormones. It is therefore surprising that Somatostatin knockout (sst-ko) mice have a very mild metabolic phenotype under normal conditions.
Here, we studied the role of Somatostatin in weight gain and weight loss using sst-ko mice.
We found that sst-ko mice gained weight, lost weight, and regained weight at an equal rate to heterozygous siblings following dietary interventions. However, overweight sst-ko mice did not regain weight after sleeve gastrectomy bariatric surgery compared to heterozygous siblings that underwent the same surgery. This phenotype persisted for three months after surgery, whilst a high-fat high-sucrose diet was provided. Mechanistically, the surgery led to hypersecretion of glucagon-like peptide 1 (Glp1), which was not observed in sham-operated sst-ko mice. Moreover, Glp1 hypersecretion was greater than that of heterozygotes sleeve gastrectomy operated mice. Sleeve gastrectomy sst-ko mice displayed lower levels of fasting insulin, and very rapid response to glucose loading. In conclusion, a metabolic and endocrine phenotype of sst-ko mice was exposed following bariatric surgery. These mice remained lean and increased Glp1 secretion, suggesting that somatostatin has an important role in regulating gastrointestinal hormone secretion, especially following bariatric surgery. Further study is required to determine whether pharmacological inhibition of somatostatin signaling can enhance the outcomes of bariatric surgery in mice and in patients.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:48 p.m. - 12:53 p.m.
PSAT050 An Unusual Case of Adrenal Insufficiency After Using Budesonide for Treatment of Microscopic Colitis
Authors: Barua Nabonita , Riaz Aiman , Osakwe Ibitoro 
Published: November 2022

Abstract

Introduction
Long term use of systemic glucocorticoids are a common cause of secondary adrenal insufficiency from 1.4-27.5% of cases. On the other hand, Budesonide, a non-halogenated steroid that is widely used for its low systemic absorption is rarely reported to cause secondary adrenal insufficiency.

Case
A 39-year-old female with significant medical history of anxiety, bipolar disorder, hypothyroidism, type 2 DM and lymphocytic colitis was admitted to the hospital with acute mental status change and lethargy. She reported a 3-week history of diffuse abdominal pain and diarrhea. She endorsed weight loss but denied any fever, vomiting, recent infection or any significant history of hepatitis. In ER, her vitals were notable for a BP of 105/68 mm Hg, Pulse 76 beats/min, temperature 97.5F, pulse oximetry 100% with 2 L nasal canula. On examination she appeared frail, alert but mildly confused. Admission labs showed sodium 143, potassium 4.3, bicarbonate 15, creatinine 1.2, GFR 57, blood glucose 67, Hemoglobin 6.3 and WBC 4.3, UA negative. During the ER course she became hypotensive with SBP in 80s. She was fluid resuscitated with a total of 4 L of normal saline and was eventually started on vasopressor support due to profound hypotension unresponsive to fluids. One unit of PRBC was transfused and she was transferred to MICU for further monitoring. Baseline cortisol level was drawn, and she was started on dexamethasone for presumed adrenal insufficiency, while awaiting the result of her labs. Her cortisol was subsequently confirmed to be 5.5mcg/dl. She was maintained on stress dose steroids and experienced dramatic improvements in her clinical status and BP. A review of her medical history revealed that she was diagnosed with microscopic colitis 5 months prior to the current admission and had been placed on budesonide 9mg/day, tapered slowly to the current dose of 3mg/day. She reported compliance with her budesonide up to the date of the admission.

Discussion
Iatrogenic adrenal insufficiency from Budesonide is rarely reported in the literature. Budesonide is a common choice for IBD, especially Crohn's disease and microscopic colitis. It has a high first pass metabolism (80-90%), thus limiting its systemic bioavailability to as low as 9-21%. Despite that, a few cases of chronic oral Budesonide use resulting in AI have been reported. As it is metabolized in the liver via CYP450 isoenzymes, concurrent use of CYP450 inhibitors or hepatic cirrhosis can also potentially interfere with its metabolism and increase its systemic bioavailability. According to literature there have been a few descriptions of patients developing AI without prior liver disease, similar to our patient. Caution should therefore be exercised in prescribing budesonide and physicians should have a high index of suspicion when patients on budesonide present with symptoms suggestive of adrenal insufficiency.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT054 Isolated ACTH Deficiency in a Patient on Epoprostenol
Authors: Riordan Marianne , Bauer Jessica , Panvelker Samir 
Published: November 2022

Abstract

Introduction
Epoprostenol is a prostacyclin analog used to treat severe pulmonary arterial hypertension (PAH). Endocrine abnormalities in patients on epoprostenol have been reported, most commonly autoimmune thyroid dysfunction.

Case Description
A 36-year-old woman with weight loss and dyspnea on exertion was diagnosed with pulmonary artery hypertension following right heart catheterization. Her symptoms initially improved after starting IV epoprostenol. Over the following two years, she experienced weight loss and anorexia. Due to concerns that her symptoms were caused by epoprostenol, her dose was reduced. After new-onset tremors and palpitations, thyroid studies were checked demonstrating TSH &lt;0.01 (previously normal) and total T4 18.69 with anti-thyroid peroxidase &gt;900.0 (≤8.9 IU/mL). Repeated thyroid studies 4 weeks later showed transition to the hypothyroid phase of Hashimoto's thyroiditis with TSH 6.65 and total T4 3.21. She was prescribed 50 mcg levothyroxine daily. Despite normalization in thyroid function, she continued to lose weight over the next year with ongoing nausea and anorexia unchanged by decreases in epoprostenol dosing. Her weight dropped to 76 lbs and she was admitted for further work-up. Repeat thyroid studies were normal but cortisol was &lt;1.0 ug/dL and ACTH was &lt;1.1 (7.2 - 63.3 pg/mL). Remainder of pituitary hormonal evaluation showed normal FSH & LH and low IGF-(63 ng/mL, Z-score -2.9). She denied recent steroid use. MRI head was normal as was CT of the adrenal glands. Her symptoms rapidly improved after initiation of 15 mg hydrocortisone. Repeat RHC showed marked improvement in hemodynamics.

Discussion
The association between autoimmune thyroid disease and PAH has been relatively well described and hypothyroidism seems to be more prevalent than hyperthyroidism. We found just 3 other cases of adrenal insufficiency in patients on epoprostenol. The mechanism for endocrinopathies in this population is unclear. In addition to their effects on endothelial cells, PGI2 analogs have been noted to have a role in T helper cell differentiation. Th17 cells are implicated in autoimmune diseases like multiple sclerosis, so prolonged use of PGI2 analogs may cause systemic inflammation and trigger autoimmunity. It is important for clinicians to be aware that diagnosing adrenal insufficiency in this population can be difficult as the side effects of epoprostenol (lightheadedness, nausea, vomiting, weight loss, and anorexia) are similar to the symptoms of adrenal insufficiency. With this in mind, it is important that adrenal insufficiency remains high on the differential diagnosis of patients presenting with such symptoms when on epoprostenol treatment to prevent delays in diagnosis.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT073 The Human Gonads Do Not Contribute to the Circulating Pool of 11-Oxygenated Androgens
Authors: Rabbah Amira , Davio Angela , Liu Haiping , Marko Xhorlina , Sherk William , Rege Juilee , Rainey William , Turcu Adina 
Published: November 2022

Abstract

Background
Androstenedione (A4) and testosterone (T) are produced by both the adrenal glands and the gonads. The adrenal enzyme steroid 11β-hydroxylase (CYP11B1) executes the last step in cortisol synthesis; CYP11B1 also uses A4 and T as substrates, generating 11-hydroxyadrostenedione (11OHA4) and 11-hydroxytestosterone (11OHT), respectively. 11OHA4 and 11OHT are further metabolized, primarily in periphery, to 11-ketoandrostenedione and 11-ketotestosterone. It has been suggested that CYP11B1 is expressed in the gonads, yet the circulating levels of all 11-oxygenated C19 steroids (11-oxyandrogens) are similar in males and females of reproductive ages, despite enormous differences in T.

Objective
To assess the gonadal contribution to the circulating pool of 11-oxyandrogens.

Methods
We used liquid chromatography-tandem mass spectrometry to measure 13 steroids, including traditional and 11-oxy-androgens in: (I) paired peripheral and gonadal vein serum samples from 11 patients (7 women), median age 37 years (range 31-51); and (II) 17 women, median age 57 years (range 41-81) before and after bilateral salpingo-oophorectomy (BSO). We also performed CYP11B1, 17α-hydroxylase/17,20-lyase, and cytochrome b5 immunohistochemistry in formalin-fixed paraffin-embedded ovaries and testes (10 each).

Results
A4, T, estradiol, estrone, progesterone, 17α- and 16α-hydroxyprogesterone were all higher in gonadal veins than in periphery (p&lt;0.001 for all), while all 4 11-oxyandrogens were similar between matched peripheral and gonadal vein samples. Similarly, in women who underwent BSO, A4 (median [interquartile range]: 33 [24.5-49] ng/dL vs. 60 [47.5-71] ng/dL, p=0.0008) and T (15 [12.5-20] vs. 24 [15.5-33.5], p=0.0005) were lower after vs. before surgery, while the four 11-oxyandrogens were not significantly different. Immunohistochemistry staining for CYP11B1 was negative in both ovarian and testicular tissue.

Conclusion
Our results indicate that despite producing substantial amounts of both A4 and T, the human gonads are not important sources of 11-oxyandrogens.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT082 A Survey of Patients Living with CAH Assessing Their Perceptions on Glucocorticoid Regimen and Glucocorticoid-Associated Side Effects
Authors: Barnes Chris , Dias Rosh , Feather Melodie , Sherpa-Pine Nina 
Published: November 2022

Abstract

Background
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder characterized by insufficient cortisol production resulting in excess adrenal androgen production. The standard of care to replace the insufficient cortisol production is the lifelong use of glucocorticoids (GCs), usually at supraphysiologic levels to control hyperandrogenemia. Chronic use of supraphysiologic GCs is associated with long-term comorbidities. The degree of patient awareness of GC associated comorbidities is unknown and of critical importance to focus patient education.

Methods
An online survey was conducted in the US and promoted through a nationally known patient advocacy organization and through social media. Survey questions assessed the perceptions of patients living with CAH regarding their GC regimens, most common side effects associated with GCs, patients understanding of the risk and benefit of GC use and patients’ attitude about adjusting their GC regimen.

Results
A total of 113 patients living with CAH completed the online survey. Over 97.5% reported taking GCs at the time of the survey, with 75% being satisfied and 85% rating their regimen effective or very effective. Commonly reported side-effects associated with GC use included increased weight gain and appetite, fatigue, "moon face," thin skin that bruises easily, and mood changes or depression. Less common side effects included osteoporosis, muscle weakness, high blood pressure and increased infections. Approximately half reported discussing the long-term risks of GC treatment with their healthcare provider, with the remaining half reported not having this discussion or were unsure. Approximately 43% of respondents reported being in situations where they were not given enough information about the risk of supraphysiologic GC use to make an informed decision on treatment. A majority of respondents (67%) reported a willingness to change their current regimen if there was a safe and effective way to reduce their current GC dose closer to physiologic levels.

Conclusions
While a majority of patients living with CAH are satisfied with their current GC regimen, there is a general lack of patient awareness of the long-term side effects associated with supraphysiologic GCs. Patients may benefit from more patient education to make informed decisions with their healthcare providers.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN09 An Unusual Presentation of Pheochromocytoma with Persistent Hypoglycemia, A Case Report
Authors: Alnahas Zeinab , Horani Mohamad H 
Published: November 2022

Abstract

Introduction
Pheochromocytoma is a rare chromaffin cells tumor of the adrenal medulla characterized by excessive catecholamines production. It can be manifested by various clinical presentations, ranging from being asymptomatic to having sustained or paroxysmal hypertension, or the classical triad of paroxysmal headache, palpitations, and sweating. It may be sporadic or inherited as part of other familial syndromes, including hereditary paraganglioma syndromes, and multiple endocrine neoplasia 2. This case report shows an unusual presentation of pheochromocytoma in a patient with neurofibromatosis type 1.

Case Presentation
A 27-year-old normotensive woman with a past medical history significant for neurofibromatosis type 1 diagnosed at age 16 was involved in a single-vehicle rollover collision. She experienced a sudden episode of dizziness and presyncope associated with nausea while she was driving. She was found with altered mental status and a serum glucose level of 31 mg/dl (reference value 70-99mg/dL), indicating hypoglycemia which remained persistent after administering a glucose drip. The patient denied any recent febrile illness, previous episodes of dizziness, vertigo, syncope, or known hypoglycemia. Her CT abdomen with intravenous contrast showed a 4.8 cm lobulated heterogeneous mass involving the right adrenal glands concerning for pheochromocytoma. Her laboratory workup revealed HbA1C of 4.9%, serum-free insulin of 6 mcU/mL (reference range &lt;17mcU/mL), C-peptide of 1 ng/mL (reference value 0.5-2 ng/mL), insulin autoantibodies of &lt;0.4 nU/mL (reference value &lt;95 nU/mL), random cortisol of 38.4 mcg/dL (reference value 5-25 mcg/dL), ACTH of &lt;5 pmol/L (reference value 10-60 pmol/L), and a normal cosyntropin stimulation test. Further investigations showed high serum levels of normetanephrine of 8.02 nmol/L (reference range 0-0.89 nmol/L), metanephrines of 0.69 nmol/L (reference range 0-0.49 nmol/L), and chromogranin A of 300 ng/mL (reference range 0-95 ng/mL) which confirmed the diagnosis of pheochromocytoma.

Conclusion
Hypoglycemia is an unusual presentation of pheochromocytoma, which is usually associated with impaired glucose tolerance and hyperglycemia. Our case shows that pheochromocytoma associated with neurofibromatosis type 1 can present with persistent hypoglycemia.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN13 Transcriptional and epigenetic landscapes of adrenocortical tumors
Authors: Lerario Antonio , Mohan Dipika , Hammer Gary 
Published: November 2022

Abstract
Historically, our knowledge of adrenocortical tumorigenesis has been limited to clinical observations of genetic syndromes featuring benign and malignant adrenal disease. In the last two decades, the enormous boom in high-throughput approaches has transformed our understanding of adrenal pathophysiology. While benign adrenocortical tumors may be cured by surgery, adrenocortical carcinoma (ACC) continues to be associated with dismal clinical outcomes. Understanding the molecular pathogenesis of adrenocortical tumors and the programs that facilitate benign versus malignant trajectories is crucial for developing curative therapeutic approaches. Although numerous transcriptome, epigenome, and single cell datasets profiling physiologic adrenal cortex and adrenal tumors are publicly available, there is no analysis integrating the spectrum of physiologic to malignant disease. Through analysis of these datasets, including single center datasets and those published by ENCODE, ENSAT, and TCGA, we demonstrate that biologic processes involved in tissue differentiation are recurrently disrupted across tumorigenesis. While the dominant programs supporting benign tumors include intracellular signaling programs that stabilize steroidogenic identity, ACC is characterized by activation of proliferation, immune, and imprinting programs that restrict access to adrenocortical differentiation states. Taken together, these studies identify that loss of differentiation fidelity within the confines of putative cell of origin is the core determinant of benign versus malignant tumorigenesis in the adrenal cortex.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN22 Outcomes of Adrenalectomy for Adrenocortical Carcinoma at a Single Institution
Authors: Gurney Antonia , Kotwal Anupam , Patel Anery , Shank Jessica , Yuil-Valdes Ana , Pachigolla Srujana , Goldner Whitney , Fingeret Abbey 
Published: November 2022

Abstract

Background
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor overall prognosis. Complete surgical resection is the mainstay of therapy.

Methods
We performed a retrospective review of adult patients at a single institution undergoing index adrenalectomy for initial diagnosis of adrenocortical carcinoma from 2012 through 2021. Clinical and demographic variables were assessed.

Results
Fifteen patients were identified who underwent adrenalectomy for ACC during the study period with a mean age of 49.2 years (SD 17.8) with 6 (40%) male, 13 (87%) white, mean body mass index 29.5 kg/m2 (SD 7.5). On preoperative cross-sectional imaging nine (60%) were left sided tumors and the largest dimension was a mean of 11.1cm (SD 4.5), with pre-contrast density of 27.8 Hounsfield units (SD 9.6), five patients (36%) had evidence of local invasion and four patients (29%) had evidence of metastatic disease on imaging. Ten patients (67%) had biochemical evidence of hormone excess and eight had secretion of more than one cortical hormone, with overall ten (67%) glucocorticoid secretion, six (40%) androgen secretion, two (13%) mineralocorticoid secretion. Four patients (27%) had minimally invasive laparoscopic or robotic adrenalectomy. Three patients (20%) had a surgical complication including ileus, pancreatic leak and pleural effusion requiring intervention. Complications were not associated with hormone excess (p = 0.50). On final pathology, one patient (7%) was staged T0 who later presented with metastatic disease 18 months postoperatively, six (43%) were T2, 4 (29%) T3, and 3 (21%) T4. No patients had locoregional lymph node metastases. Ten patients (67%) had R0 resection with negative margins, 4 (27%) had microscopic positive margins, and 1 had grossly positive margins. Seven patients had Ki-67 assessed with a mean of 29% (SD 20.6). Ten patients (71%) received adjuvant mitotane, eight (53%) systemic chemotherapy, and 4 (27%) adjuvant radiation. Within the study period, nine patients (60%) had a recurrence and six patients died (40%) with a median survival of 24 months. Positive margin status was associated with mortality with mortality of one (10%) of patients with negative margins and 5 (100%) of those with positive margins (p = 0.002). Of the four patients who presented with initial evidence of metastatic disease on imaging, two died during the study period and the other two remain alive on therapy. Adjuvant treatment with mitotane, systemic chemotherapy, or radiation were not associated with survival.

Conclusions
In this cohort, complete surgical resection with negative margins was associated with improved survival compared with patients with microscopic or grossly positive margins. The overall median survival was 24 months. Differences in outcome by adjuvant therapy are limited by the sample size.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN26 Radiation For Adrenal Metastases: Should Patients be Monitored For Primary Adrenal Insufficiency?
Authors: Herndon Justine , Bancos Irina 
Published: November 2022

Abstract

Background
Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Risk of primary adrenal insufficiency (PAI) in bilateral metastases is 12%. Adrenal radiation is one of the options available to treat adrenal metastases. The risk of PAI after bilateral adrenal radiation is unclear.

Objective
We aimed to determine the incidence and the timeline of PAI in patients undergoing adrenal radiation for bilateral metastases.
Design, Setting, and Participants: Single center retrospective study of adult patients with adrenal metastases treated with adrenal radiation between 2010 and 2021.

Results
Of 55 patients with adrenal metastases treated with adrenal radiation, 7 (12.7%) had bilateral therapy, of whom 5 (all with lung adenocarcinoma) developed PAI. Another patient with history of unilateral adrenal radiation and previous contralateral adrenalectomy also developed PAI. Following the radiation therapy (median dose 50 Gy [range 20-65 Gy]), administered in a median of 5 fractions (range 5-18 fractions) in 6 patients who developed PAI, all treated metastases either decreased in size during imaging follow up or demonstrated a decrease in SUV uptake on PET scan. PAI developed at a median time of 6.1 months after radiation (range 0.5-20.4 months). PAI was diagnosed based on laboratory monitoring in 3 patients and based on treating endocrinologist's discretion (e.g., symptoms, clinical context) in the other 3 patients. Patients were initiated on hydrocortisone (median daily dose of 20 mg, range 15-80 mg) and fludrocortisone (median dose of 0.05 mg, range 0.05-0.1 mg)
At the end of the study period, daily replacement dose was higher for both for hydrocortisone (median of 35 mg, range 15-160 mg) and for fludrocortisone (median of 0.0625 mg, range 0.05-0.1 mg). All but one patient with PAI had passed away at the end of the study, at a median time of 19.7 months (range 6.1-55.8 months) since radiation and median time of 7.7 months (range 1.2-55.3 months) since the diagnosis of PAI. In the two patients with bilateral adrenal radiation who did not develop PAI, the follow up was short: 1 patient passed away six-months post-radiation and another patient had only 4 months of follow up.

Conclusion
Adrenal radiation is an effective therapy for patients with adrenal metastases. Risk of PAI is very high when bilateral adrenal radiation is administered, and patients need to be counseled about it. We observed that daily glucocorticoid replacement dose was excessive in some patients possibly reflecting the use of stress dosing due to underlying sickness. Both clinical and biochemical monitoring every 3-6 months should be instituted in patients undergoing bilateral adrenal radiation.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.