bluuebunny/crossref_metadata_2025_split huggingface dataset:
RF24 | PSUN95 Defining Predictors of Weight Loss Response to Lorcaserin
Authors: Gugger Aristea Sideri , Dimino Cara , Panigrahi Sunil K , Mayer Laurel S , Smiley Richard M , Korner Judith , Wardlaw Sharon L 
Published: November 2022

Abstract

The need for personalized medicine in obesity is pressing, but we are currently unable to predict individual responses to weight loss (WL) medications. The melanocortin (MC) system consisting of proopiomelanocortin (POMC) and agouti related protein (AgRP) neurons and brain MC-Rs plays a critical role in regulating energy homeostasis and is targeted by lorcaserin (LOR), a 5HT2cR agonist previously FDA approved for WL. We therefore investigated the short and long-term effects of LOR on the MC system as assessed by cerebrospinal fluid (CSF) neuropeptide measurements and other parameters in order to identify potential biomarkers to predict WL response.

Methods
In phase-1 of our two-phase study, thirty subjects with obesity were randomized to receive placebo or LOR for 7-days and were then crossed over to 7-days of LOR or placebo after a 3-week washout period. Subjects then continued to phase-2 and were treated with LOR for 6-months. The study was terminated early as LOR was withdrawn from the market and only 19 subjects completed 6M. Anthropometrics, plasma and CSF were collected and test meals were administered after both placebo and LOR during phase-1 and at the end of phase-2. POMC prohormone and the POMC-derived peptide, β-endorphin (β-EP), were measured in CSF by in house ELISA and RIA. The MC-R antagonist, AgRP, was measured by ELISA in CSF and plasma as both may reflect brain AgRP.

Results
During phase-1 there was a decline in CSF POMC (p=0.001) and an increase in CSF β-EP (p=0.0017) resulting in an increase in the ratio of β-EP /POMC (processed peptide/prohormone) (p&lt;0.0001) after 7-days of LOR vs placebo. Serum insulin and HOMA-IR also decreased despite no WL during phase-1 (p&lt;0.005).
After 6M of LOR, average WL was 6.9%, with 11/19 subjects achieving &gt;5% and 7/19 &gt;10% WL. Leptin, insulin and HOMA-IR declined. CSF POMC remained lower and β-EP and β-EP/POMC remained higher after 6M vs 7-day placebo (baseline), whereas AgRP increased only at 6M. Anthropometrics and caloric intake during test meals were not significantly different between LOR and placebo in phase-1 and did not predict WL at 6M. Phase-1 changes in POMC or β-EP did not predict WL. However, baseline CSF POMC and POMC/AgRP ratio correlated negatively with WL and were significantly lower in subjects with &gt;10% WL. A CSF POMC cutoff of &lt; 220 fmol/ml at baseline was found to predict 10% WL at 6M (p=0.045 Fisher).

Conclusion
In this study we show that the melanocortin system is impacted after 1 week of LOR. Furthermore lower melanocortin activity at baseline predicted a better weight loss response to drug treatment. Assessment of melanocortin activity could thus provide a way to personalize the pharmacotherapy of obesity with possible future alternative selective 5HT2cR agonists.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.
RF28 | PSUN198 The Dramatic Fat Mass Loss Caused by Bimagrumab is Similar in Diabetic and Non-diabetic Patients.
Authors: Klickstein Lloyd , Flynt Amy , Edgerton Dawn , Dole Kiran , Nguyen Kevin 
Published: November 2022

Abstract
Bimagrumab is a fully human, ligand-blocking antibody to activin receptors type IIA and type IIB that in obese diabetic patients has been shown to improve body composition dramatically. After 48 weeks of treatment (N=75, allocated 1: 1, bimagrumab intravenously (iv) 10 mg/kg/month: placebo), in the bimagrumab group total body fat mass decreased by 20.5% while at the same time, lean mass increased by 3.6%, both assessed by dual X-ray absorptiometry (DXA). At 24 weeks, fat mass loss was 16.5% in those treated with bimagrumab, while there was little effect on fat or lean mass in the placebo group at either timepoint. In a subset of patients who underwent magnetic resonance imaging, the fat loss effect was greatest for hepatic fat, with a 52% reduction from baseline to week 48, and for abdominal visceral fat, where a 34% decrease was observed over the same interval (Heymsfield SB et al. JAMA Open 2021;4: e2033457).
Most drugs for obesity are less effective in diabetics, so to evaluate the efficacy of bimagrumab on fat mass in non-diabetics, we undertook a pooled analysis of patient-level data from 6 clinical studies of bimagrumab previously conducted to assess muscle anabolic activity and/or clinical safety. Criteria for study selection included at least 24 weeks of therapeutic drug exposure, DXA performed at baseline and at least 2 additional time points. Studies that recruited patients with known, underlying primary diseases of adipose tissue or muscle were excluded. Of the 568 subjects in these 6 studies, 7 were identified as diabetic and excluded, leaving 561 subjects in 4 dose groups including placebo (N=204), 70 mg iv monthly (N=43), 210 mg iv monthly (N=75), or a top dose group comprising 700 mg iv once monthly or 10 mg/kg iv once monthly or 30 mg/kg iv q8w x 2 (total N=239). A dose- and time-dependent effect of bimagrumab on fat loss was observed and at the 24 week time point, the top dose group lost 14.6% (LS mean (95% CI) 13.2% - 16.0%) of total body fat mass, while the placebo group increased their fat mass by 2.4% (0.9% - 3.8%). Approximately 41% of the subjects in this pooled analysis were overweight or obese, which is a potential limitation of this study since all subjects in the diabetes study were overweight or obese, however this likely does not affect the conclusion since no effect of baseline BMI on % initial body fat lost at week 24 was seen. Thus, unlike most other drugs for obesity, the efficacy of bimagrumab is very similar in both diabetic patients and in non-diabetic patients.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:58 p.m. - 1:03 p.m.
LBODP007 Clinical Characteristics And Treatment Outcomes Of Adrenal Histoplasmosis And Tuberculosis In Thailand: A 15-year Retrospective Study In A Single Tertiary Center
Authors: Vorasayun Thanyaporn , Porntharukchareon Thachanun , Plongla Rongpong , Snabboon Thiti , Sunthornyothin Sarat , Parksook Wasita Warachit 
Published: November 2022

Abstract

Background
Adrenal histoplasmosis and tuberculosis (TB) are the most common adrenal infections. These conditions are widely reported in developing countries.

Methods
We performed a retrospective study of patients with adrenal histoplasmosis and TB at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from 2005 to 2020, and evaluated clinical characteristics, treatment, and outcomes. The diagnosis was made by proven microbiologic evidence of infection and morphologic adrenal abnormalities by cross-sectional imaging.

Results
Of all 27 patients, 20 had adrenal histoplasmosis, 6 had adrenal TB, and 1 had coinfection with both pathogens. The majority of the patients had bilateral adrenal involvement (93%). Most patients were males (81%), and the mean age was 62 years. Ninety-six percent of patients did not have HIV infection. The most frequent comorbidities were hypertension (50%) and diabetes mellitus (23%). Common presentations were weight loss and anorexia (77%), and fever (65%), in which the median time from the presentation to diagnosis was 3.5 months. The prevalence of adrenal insufficiency was 67%. All patients with adrenal insufficiency received steroid replacement, yet 17% had an adrenal crisis during the treatment course. Ninety-six percent of patients received medical treatment (antituberculosis or antifungal agents), while almost half needed additional surgery (44%). During a median follow-up period of 20.5 months, the mortality rates were 28.5%, in which all death was from patients with adrenal histoplasmosis or coinfection with histoplasmosis and TB.

Conclusion
There were high rates of adrenal insufficiency in patients with adrenal histoplasmosis and TB. High mortality rates were also observed, particularly in adrenal histoplasmosis. Appropriate management of these conditions is required from both infectious and hormonal perspectives.
Presentation: No date and time listed
PSAT028 Congenital Adrenal Hyperplasia with Adrenal Myelolipoma: Gender Identity and Choice of Therapy
Authors: Kasina Siva Kumar , Sivitz William , Correia Marcelo 
Published: November 2022

Abstract

Background
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder characterized by impaired glucocorticoid and mineralocorticoid synthesis with excessive adrenal androgen production. In affected females, most forms of CAH lead to virilization. Persons with CAH have a higher prevalence of adrenal myelolipomas compared with the general population.

Clinical case
A 38-year-old Spanish speaking individual who identified as male presented with headache and chest pain. Imaging revealed diffuse nodular thickening and enlargement of the right adrenal gland consistent with hyperplasia as well as 11 cm multilobulated left adrenal lesion containing macroscopic fat and soft tissue consistent with myelolipoma. A small uterus posterior to the bladder and presumed ovaries were also visualized with no visualization of prostate, spermatic cord or testicles. He reported a brother with a childhood hormone condition leading to an attempt to raise as female, resulting in subjective distress and unhappiness. Our patient never had breast development, menstrual cycles, or recurrent abdominal pain. There was no history of adrenal crisis, lightheadedness, or syncope and no hyperpigmentation on exam. He recalled salt craving as a child. Genital exam was refused by the patient. Labs demonstrated plasma cortisol 4.5 mcg/dl (6-18.4), ACTH 123 pg/ml (7-63), serum aldosterone 30 ng/dl (&lt;=21), plasma renin activity 3.0 ng/ml/h (&lt;=0.6-4.3), sodium 139 mEq/l (135-145) and potassium 4.2 mEq/l (3.5-5). The 17-hydroxyprogesterone concentration was 16,713 ng/dl (&lt;=138), androstenedione was 36.52 ng/ml (0.33-1.34), and total testosterone was 621 ng/dl (male reference range 249-836). Based on the above findings and clinical history, his biologic sex was strongly felt to be female. A decision had to made regarding the need for glucocorticoid therapy and for possible adrenalectomy for the large myelolipoma. Because he had no symptoms of adrenal insufficiency and quite content with his gender identity, neither hormone therapy nor surgical intervention were performed. As of 8 months after presentation, he reported on going health and well-being. We recommended follow-up adrenal imaging and discussed glucocorticoid coverage for possible future stress conditions and educated him for this potential need.

Discussion
This case is unusual in that he was asymptomatic for adrenal insufficiency yet maintained male gender identity into adulthood. His adrenal myelolipoma likely developed from untreated CAH. We felt that treating with steroids and/or resecting his adrenal gland might well suppress ACTH and adrenal androgen production which would be detrimental to his gender identity and quality of life.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT029 Acute Presentations of 4 Patients with Spontaneous Adrenal Hemorrhage
Authors: Issa Basil , Ganawa Shawg , Keevil Brian , Hanna Fahmy , Fryer Anthony , Ahmed Gasim , Ensah Grace 
Published: November 2022

Abstract

Case 1
A 19 year old primigravida, 35 weeks gestation, presented with acute severe right flank pain and vomiting. She underwent a MR cholangiopancreatography following advice from the gastroenterologists. This revealed a right adrenal gland haemorrhage 46×24×40 mm. CRP was raised at 151mg/l. Random cortisol, potassium and plasma metanephrines (pMET) were normal. She was delivered by Caesarian Section at term with 100 mg IV hydrocortisone cover and with no complications to either mother or baby. CT adrenals performed 8 weeks postpartum was entirely normal with no evidence of residual haemorrhage or adrenal mass.

Case 2
A 63 man with hypertension presented with acute severe left flank pain. CT renal and CT angiogram showed a large left adrenal and perinephric haemorrhage. This was treated with coil embolization of the left suprarenal artery. Initial biochemistry showed mildly raised plasma normetanephines at 2211 pmol/l which subsequently normalised. Overnight dexamethasone suppression test (ONDST) and aldosterone/plasma renin activity were normal. Serial CT scan showed gradual resolution of the adrenal haemorrhage with no underlying adrenal lesion.

Case 3
A 56 year old man presented with a 3 day history of epigastric and left sided abdominal pain with nausea and fever. CT scan of the abdomen revealed a 5 cm adrenal haemorrhage which was contained within the gland. ONDST, pMET and aldosterone/plasma renin activity were normal. Serial scans showed resolution of the adrenal haemorrhage and a residual 14×13 mm adrenal nodule with a density of 20 Hounsfield Units but which remained unchanged in size.

Case 4
A 72 year old man with generalised abdominal pain a week after hip replacement surgery. He developed a fever and his inflammatory markers were raised. CT abdomen showed non-enhancing bilateral adrenal lesions consistent with adrenal haemorrhage. He was taking Apixaban for thromboprophylaxis following hip replacement. A short synacthen test performed to rule out adrenal insufficiency showed a suboptimal cortisol response and treatment with hydrocortisone was commenced.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT042 Adrenal Insufficiency Associated to Immune Checkpoint Inhibitors
Authors: Barreto Brigida Colon , Oktaei Hooman 
Published: November 2022

Abstract

Background
Innovations in management of multiple malignancies have developed throughout the years. Despite benefits in immune checkpoint inhibitors there is an incidence of approximately 9.4% to 10.4% in endocrine immune related disorders. The challenge advocates to promptly recognize the clinical manifestations related to adverse effects.

Clinical Case
We report a case of a 61-year-old caucasian woman with Metastatic Lung Squamous Cell Carcinoma Stage IV on immunotherapy and radiotherapy who presented to ED with nausea and vomiting for the last 2 weeks. The review of the system pertinent for weight loss 18 pounds in the last 2 months, fatigue and decreased appetite. Medication history pertinent for active Pembrolizumab (started 6 months prior to presentation; cycle every 3 weeks); Radiotherapy (3 cycles) and steroid injections (last dose 1 month prior for bilateral knee pain). Upon arrival vital signs T 36.9C, HR 110/min, RR 18/min, BP 80/60mmHg, and StO2 98%. The physical examination pertinent for an acutely ill patient with tachycardia. Initial laboratory studies showed peripheral eosinophilia 14% (n &lt;6%); high anion gap metabolic acidosis (AG 18), hypokalemia 2.8 mmol/L (n 3.5-5.0mmol/L). The patient was hospitalized with sepsis and intractable vomiting. Gastroenterology evaluated with EGD showed erosive gastritis and reflux esophagitis. CT abdomen with IV contrast showed numerous sclerotic bone lesions and single hepatic lesion suggestive of metastatic disease; unremarkable adrenal glands. Poor response to initial hydration and antibiotics as blood pressure remained fluctuant borderline low prompted evaluation. Random cortisol at 6: 50am showed hypocortisolism (1.6mcg/dl) and TSH 1.290 mcIU/mL (n 0.358- 3.74mcIU/mL); patient was started on stress dose steroids and endocrinology was consulted for suspected adrenal insufficiency. Cosyntropin stimulation test (n &gt;18 mcg/dL) with baseline cortisol levels 1.6mcg/dl and ACTH less than 5mcg/dl; cortisol levels at 30 minutes after 250 mcg of Cosyntropin was 4.3mcg/dl and at 1 hour 6.8mcg/dl, confirming most likely secondary vs primary adrenal insufficiency. Within 24-48 hour stress dose steroids were weaned and the patient was then discharged home with hydrocortisone 20 mg am and 10mg pm for further outpatient management.

Conclusion
Pembrolizumab is a human programmed death receptor-1-blocking antibody that on October 2015 was FDA approved for treatment of non-small cell lung cancer. Adrenal Insufficiency can cause a broad nonspecific clinical scenario with reported incidence of 0.6-0.7% pembrolizumab-induced AI. This rare clinical entity adrenal insufficiency immune mediated endocrinopathy by pembrolizumab constitutes an emergency that prompts attention for early identification and initial management. Nevertheless increased morbidity and mortality is associated with acute adrenal crisis encouraging physicians to be aware of this particular risk.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT044 Management of Severe Cushing's Syndrome in a Patient with Cyclical Ectopic ACTH Production Treated with Osilodrostat.
Authors: Obeid Hiba , Sandouk Zahrae , Spencer-Segal Joanna 
Published: November 2022

Abstract

Introduction
We are presenting a case of severe Cushing's syndrome with multiple complications treated medically with osilodrostat.

Clinical Case
A 71-year- old female with severe chronic obstructive pulmonary disease was noted to have episodes of hypokalemia, hyperglycemia, and hypertension lasting for several weeks.
At the time of presentation to the clinic, she had normal vital signs and no physical exam findings suggestive of hypercortisolism except for mild proximal muscle weakness.
Between 2019 and 2021, she had multiple episodes of the presenting symptoms along with elevated morning serum cortisol of 57 to 119 mcg/dl (normal 7-22 mcg/dl), 24-hour urine free cortisol 1343 to 2464 mcg/24 hours (normal 4.5-45 mcg/24 hours), midnight saliva cortisol 509 to 8870 ng/dl (normal &lt;100 ng/dl), and ACTH 105 to 150 pg/ml (normal 5-52 pg/ml). Between episodes labs were normal. A diagnosis of cyclic ACTH-dependent Cushing's syndrome was made.
Pituitary MRI was normal, with no evidence of pituitary adenoma.
Inferior petrosal sinus sampling was done while cortisol level was elevated, and it showed petrosal sinus to peripheral ACTH ratio of 1.2 following stimulation, a ratio &lt;3.0 suggests ectopic ACTH-dependent Cushing's syndrome.
A Ga-65 DOTATATE scan did not localize the tumor.
As she was considered a poor surgical candidate for bilateral adrenalectomy, she was started on osilodrostat 10 mg twice daily and hydrocortisone 10 mg twice daily for a block and replace strategy. She was admitted to the hospital 5 days later for increasing fatigue and severe hyperglycemia. Potassium level was 2.2 mmol/L (normal 3.5-5 mmol/L), blood glucose &gt;500 mg/dl, Hemoglobin A1c 8.2%, and random cortisol level was 96 mcg/dl. She was hypertensive and had new acute rib fractures, right lower lobe pulmonary embolism, and deep vein thrombosis.
She was given potassium supplements, insulin, anticoagulation, and spironolactone 100 mg bid. The dose of Osilodrostat was increased to 20 mg twice daily. Over 12 days, her cortisol level decreased gradually to 6.3 mcg/dl on the day of discharge. Spironolactone, insulin, and potassium were discontinued and hydrocortisone was prescribed for physiologic replacement.
As an outpatient, she continues both osilodrostat and hydrocortisone and is doing quite well.

Conclusion
Osilodrostat can rapidly and effectively decrease cortisol levels in patients with severe Cushing's syndrome.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT046 Herbal Supplement Causing Cushing's Syndrome in a Patient With Severe Tophaecous Gout
Authors: Fadanelli Margaret , Santos Claudia Villatoro 
Published: November 2022

Abstract
Previous reports describe self-prescribed prolonged use of steroids resulting in Cushing Syndrome to treat tophaceous gout1,2. We present a case of Chinese herbal supplements used for severe tophaceous gout causing Cushing's syndrome.
The patient is a 29-year-old male with prior history of severe tophaceous gout since age 18y, who presented to the hospital for fatigue and episodes of lightheadedness associated with shortness of breath and melena over the past four months. On physical examination, he had moon facies, central obesity, purple striae in the abdominal wall and axillary region, and large, deforming tophi in bilateral elbows and toes. He reported using a Chinese herbal supplement of unknown contents for the past year to maintain his gout attacks under minimal control. Admission hemoglobin was 4.2 mg/dL with severe iron deficiency. Due to suspected gastrointestinal bleed, he underwent work-up with EGD and colonoscopy, which did not reveal a bleeding source. His hemoglobin stabilized after four red blood cell transfusions with plans to do a video capsule outpatient. His celiac disease work-up was negative. Due to persistent fever and tachycardia, infection was ruled out with negative COVID PCR, viral panel, and QuantiFERON test. Work-up for suspected Cushing's syndrome showed ACTH level &lt; 3 pg/mL (7-84 pg/mL), morning cortisol 10 mg/dL (5-20 mg/dL), and DHEA sulfate 21.6mg/dL (160-449 mg/dL). Subsequent 24-hour urine collection showed elevated free cortisol at 127 µg/24hr (£60 µg/24hr) with ratio 101 µg/g Cr (&lt; 32 µg/g Cr). It was suspected that the Chinese herbal supplement had high contents of synthetic steroids as previously reported in literature2 with resultant development of exogenous Cushing syndrome. He reported not taking his herbal supplement for a couple of days before admission; therefore, he was treated with high-dose steroids for suspected acute gout flare with resolution of his tachycardia and fever after completing testing for Cushing Syndrome. No further episodes of melena were reported, and his hemoglobin remained stable. He was discharged with steroid taper over eight weeks and planned a Cortrosyn test when the steroid dose is 5 mg before discontinuing treatment.
Chinese herbal supplements can contain synthetic steroids, and unsupervised use can lead to adverse effects like Cushing's syndrome, as reported in our patient.
1. Lo TEN, Racaza GZ, Penserga EG. "Golden Kernels within the skin": disseminated cutaneous gout. Case Reports 2013; 2013.
2. Edwards CJ, Lian TY, Chng HH. Cushing's syndrome caused by treatment of gout with traditional Chinese medicine. QJM 2002; 95: 705–705.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.