bluuebunny/crossref_metadata_2025 huggingface dataset:
RF12 | PSUN80 A Novel DXA Algorithm to Aid in the Diagnosis of Familial Partial Lipodystrophy
Authors: Harris Charles , Zheng Wenjun , Brown Rebecca
Published: November 2022

Familial partial lipodystrophy (FPLD) is a rare and heterogenous disease without gold-standard diagnostic criteria. The heterogeneity applies to fat distribution, symptomatology, metabolic complications, and genetic etiology. Disease heterogeneity has contributed to the lack of standardized diagnostic criteria, an obstacle to understanding both the natural history of the disease and response to therapies. We have assessed whether DXA data can aid in disease diagnosis.

DXA scans quantify fat and lean mass in the whole body, arms, legs, and trunk. An increased ratio of fat percentage in the trunk to the legs (termed "trunk-leg ratio", TLR) has been proposed as an objective method to detect FPLD. Using large sets of DXA data from control subjects, along with data from FPLD subjects, we sought to improve upon TLR. We hypothesized that TLR might change as a function of overall adiposity (total body fat, TF). Females were studied first because of the high female: male ratio of disease prevalence observed in FPLD. In 2713 control females with DXA measurements within the UKBiobank (UKB), TLR increased linearly as a function of TF until a TF of ∼36% and then the TLR plateaued with higher TF. We analyzed published DXA data of FPLD subjects from the USA (n=55).1 FPLD subjects had higher TLRs than controls at each level of adiposity. Due to the non-linear relationship between total adiposity and TLR, two linear fits were generated to best discriminate controls from FPLD subjects for a given adiposity. For females with body fat <36%, the algorithm predicts FPLD if TLR >TF*0.0311+0.232. For females with body fat ≥36%, the algorithm predicts FPLD if TLR >1.353. After training on this UKB data set, we tested the algorithm on independent data sets of control females from NHANES (n=2347) and FPLD subjects (n=37, from the NIH). The algorithm had a sensitivity of 92–97% and a specificity of 99.3%. This degree of specificity is still not sufficient for implementation of rare disease screening in the general population, but could be useful in a population with increased pre-test probability of having FPLD such as non-obese individuals with Type 2 diabetes and/or hypertriglyceridemia. Because race and ethnicity are possible modifiers of body fat distribution, we examined the relationship between TF and TLR across ethnic and racial groups in NHANES. Mexican-Americans (n=659), Hispanic-other (n=81), White (n=871), Black (n=612), and other/biracial (n=124) subjects from NHANES had a similar relationship between adiposity and TLR. Therefore, the same DXA criteria can be applied across these ethnicities. In summary, the relationship between adiposity and TLR may be used to aid in the diagnosis of FPLD in females.

Reference

Meral R, et al. Diabetes Care. 2018;41,2255–2258.

Presentation: Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
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

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<0.0001) after 7-days of LOR vs placebo. Serum insulin and HOMA-IR also decreased despite no WL during phase-1 (p<0.005).

After 6M of LOR, average WL was 6.9%, with 11/19 subjects achieving >5% and 7/19 >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 >10% WL. A CSF POMC cutoff of < 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

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

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

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 (<=21), plasma renin activity 3.0 ng/ml/h (<=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 (<=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

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

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 <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 >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

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 <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 <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 >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

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 < 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 (< 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.
PSAT051 Posterior Reversible Leukoencephalopathy Syndrome Associated With Cushing's Syndrome
Authors: Ferri-Guerra Juliana , Sacco Susana Barreiro , Manzano Alex J
Published: November 2022

Background

Corticosteroids can induce hypertension through a variety of mechanisms such as vasoconstriction, increased hepatic production of angiotensinogen, sympathetic activity, and possible direct cardiotoxic effect. Posterior reversible leukoencephalopathy syndrome (PRES), a syndrome with unclear pathogenesis, can be the consequence of blood pressure elevation in these patients, which can present with headaches, altered consciousness, visual disturbances, or seizures. CASE REPORTA 57-year-old African American woman with a history of hypertension on Lisinopril 40mg as an outpatient, who was brought to the emergency department (ED) by family members due to altered mental status (AMS). Daughter reports that a day prior to the admission the patient has complained of feeling unwell, with mild shortness of breath and anxiety. On admission, she was found to be on sinus tachycardia with heart rate between 100-140bpm and severely hypertensive at 203/107mmHg. Toxicology screen was positive for cannabinoids, which the patient admitted to vapping the night prior. At the ED, Stroke alert was called due to altered mentation and weakness, however CT brain showed no large infarct or hemorrhage. MRI was obtained and showed patchy t2/flair hyperintense signal abnormality predominantly of the subcortical white matter in the bilateral frontoparietal lobes, most conspicuous at the vertex. Findings could reflect acute hypertensive encephalopathy (PRES). The patient had a Cushingoid appearance, with truncal obesity, moon face and reported easy bruising. Given the clinical findings and severe hypertension, serum cortisol was obtained at night and was found to be elevated at 34. 08UG/DL (3.44 - 16.76 ug/dl). ACTH was mildly low at 5 pg/mL (6-50pg/mL). 24-hour urine cortisol was then ordered and also found to be elevated at 818mcg/24h (4-50mcg/24h). Blood pressure was controlled with antihypertensive medications (nifedipine 60mg and carvedilol 12.5mg), AMS resolved and patient was discharged home with follow up with endocrinology for further Cushing's workup.

Conclusion

Cushing Syndrome is a known cause of secondary hypertension that should not be neglected. Patients that present with severe or resistant hypertension regardless of age should be worked up for possible secondary cases. Patients with Cushing syndrome are at elevated cardiovascular risk and the sooner the diagnosis is made, the better, so they can receive appropriate treatment. Hypertensive crisis can present as PRES syndrome and patients with clinical suspicion for Cushing should be worked up for the condition.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT052 Iatrogenic Cushing's Syndrome With a Remote History of Synthetic Glucocorticoid Use in the Setting of a CYP3A4 Inhibitor – Location Matters
Authors: Hand Jane , Shah Kajal , Chang Alan
Published: November 2022

Introduction

The most common cause of Cushing's syndrome is iatrogenic due to the exogenous administration of glucocorticoids (GCs). Exogenous GCs disrupt the hypothalamic-pituitary-adrenal (HPA) axis by reducing ACTH production, thereby suppressing cortisol production by the adrenal gland. The degree of HPA axis suppression and recovery varies by the formulation, dose, duration, frequency, timing, and location of GC administration. It is also well known that the clearance of GCs is delayed by inhibitors of cytochrome P450 (CYP) 3A4 isoenzyme. Here we report a case in which a patient on cobicistat developed iatrogenic Cushing's syndrome (ICS) even with a remote history of GC use.

Clinical Case

A 34-year-old male with Human Immunodeficiency Virus (HIV) on cobicistat and a history of a motor vehicle accident was referred for evaluation of ICS. The patient was started on triamcinolone epidural injections after the accident and developed a ruddy face, weight gain, posterior neck fat redistribution, and purple abdominal striae. He received a total of nine injections over three months at an unknown dose with the last injection being given two years ago. His symptoms improved after stopping the regimen. He received no GCs again until four months prior to presentation when he completed a 4 mg methylprednisolone taper and the cushingoid phenotype returned. Biochemical workup was consistent with HPA axis suppression: morning cortisol <0.5 mcg/dL (4-22 mcg/dL), ACTH <5 pg/mL (6-50 pg/mL), and DHEAS 18 mcg/dL (106-464 mcg/dL). Synthetic glucocorticoid screen was positive for methylprednisolone 5.3 mcg/dL (n <0.10 mcg/dL) and triamcinolone 0.29 mcg/dL (n <0.1 mcg/dL). The patient denied any surreptitious GC use. We concluded the patient still had unmetabolized triamcinolone even after two years due to drug interactions from cobicistat, which is a CYP3A4 inhibitor. Moreover, epidural triamcinolone has the longest half-life, 523 hours, compared to oral or intraarticular injections.

Clinical Lesson: GCs are primarily metabolized in the liver by CYP3A4. Very few cases have been reported with the use of cobicistat and the cushingoid phenotype typically appears within 3-6 months of the GC use. However, our patient had detectable triamcinolone and return of ICS two years after epidural injections. It is not enough to know whether a patient received GCs; it is also essential to know how it was given and the location of the injection as the half-lives vary depending on said location. This case reinforces the importance of pharmacovigilance and performing a thorough medication reconciliation, as even a remote history of steroid use in the setting of CYP3A4 inhibitors could lead to ICS.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT072 Clinical Features of Patients with 21-Hydroxylase Deficiency and Testicular Adrenal Rest Tumors
Authors: Bachega Tânia A S S , Costa Fernanda C , Madureira Guiomar , Mendonca Berenice B , Miranda Mirela C
Published: November 2022

Testicular adrenal rest tumors (TARTs) are one of the most frequent comorbidities in males with 21-hydroxylase deficiency (CAH) and different prevalence rates have been reported. TART still present difficult control and frequently lead to infertility. Since it is also observed in patients with adequate hormonal control, its predictors factors are not yet well-known.

Objective

To evaluate TARTs prevalence in a significant CAH male cohort and to correlate with the long-term predictors and their impact on patients’ gonadal function. Patients and methods: Data of 53 males (24 salt wasters, 10 non-classical) were retrospectively evaluated. Hormonal control quality, assessed through long-term (last 5 years) mean ACTH, 17OHP, androstenedione (D4), testosterone (T), FSH, LH, inhibin B and renin levels were analyzed as well as sperm analysis. Mean glucocorticoid doses were evaluated and converted into cortisol equivalent. Genotypes, determined through entire CYP21A2 sequencing, were classified according to predicted impairment on residual enzymatic activity: null and severe groups. Data of patients with/without TARTs by scrotal ultrasound (US) were compared. Student's t and Chi-square tests were used.

Results

TARTs were observed in 18 (42%) of classical patients, all of them presented with bilateral lesions. None of the non-classical males presented with TART. The mean age of TART diagnosis was 21.32±5.2 years, the youngest patient with TART was 12y6mo old. Ten patients with TART underwent sperm analysis and all of them presented with altered results, while 3/10 patients without TART presented with abnormal sperm count. On the other hand, only 4 (22%) TART patients developed hypergonadotropic hypogonadism. Despite late diagnosis of the SV form in our cohort, the frequency of TARTs was significantly higher in SW patients (54% vs 37%); interestingly, similar frequencies of genotype groups were observed in patient with/without TARTs. Mean glucocorticoid doses did not differ in patients with and without TARTs as well as fludrocortisone doses in SW patients with and without TARTs (p>0.05 for both). Mean 17OHP, D4 and T levels did not differ in both patient groups; mean ACTH levels were 305.3+/-282 vs. 103.2+/-81.9pg/ml in patients with and without TART, respectively (p>0.05). Mean renin levels were significantly higher in patients with TARTs than in those without (152.4+/-116.8 vs. 93.8+/-96.4mIU/ml). Testicular function parameters (mean inhibin B, FSH, LH levels and frequency of abnormal sperm analysis) were worse in the TART group vs without TART (p<0.05).

Conclusion

in our series, a high frequency of TARTs was observed, leading to male fertility impairment. An additive renin stimulatory effect, instead of long-term hormonal control or genotype, seemed to be the major role in TARTs development.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT096 Development and Validation of Mitotane Determination in Plasma Samples by LC-DAD
Authors: Lima-Valassi Helena P , Marques Anna Sylvia Ferrari , Alves Atecla Nunciata Lopes , Mendonca Berenice B
Published: November 2022

Introduction

Mitotane (o,p'–DDD) is the drug of choice for adrenocortical carcinomas (ACC) and its measurement in plasma is essential to control drug administration.

Objective

To develop and validate a simple, reliable and straightforward method for Mitotane determination in plasma samples.

Method

Drug free plasma samples were collected in potassium-ethylenediamine tetraacetate (K-EDTA) tubes and spiked with 1.0, 2.5, 10.0, 25.0 and 50.0 µg/mL of DDD. p,p´-DDD was used as internal standard and was added at 25.0 µg /mL to each sample, standards and controls. Samples were submitted to protein precipitation with acetonitrile and than centrifuged and 50 uL sobrenadant was injecting into a 1260 Infinity II liquid chromatography system (Agilent Technologies) and DDD and IS were detected at 230 nm by diodo array detector (DAD) in a 12 minutes isocratic mode with a solvent mixture of 60% acetonitrile and 40% formic acid in water 0.1% pump mixed, at 0.6 mL/min flow rate. Chromatography column Waters Acquity HSS T3 was kept at 28°C. We evaluated sensitivity, precision, presence of carry-over, recovery, linearity and the accuracy of this method.

Results

Our method resulted in a symmetrical peak shape and good baseline resolution for DDD (mitotane) and 4,4´-DDD (internal standard) with retention times of 6.0min, 6.4mim, respectively, with resolution higher than 1.5. Endogenous plasma compounds did not interfere with the evaluated peaks when blank plasma and spiked plasma with standards were compared. Linearity was assessed over the range of 1.0 to 50.0 µg/mL for DDD (R2 > 0.9987 and a 97.8% - 105.5% extraction efficiency). Analytical sensitivity was 0.98 µg/mL, functional sensitivity was 1.00 µg/mL, intra-assay and inter-assay coefficient of variation were less than 9. 98%, carry-over was not detected, recovery ranged from 98% to 117% and high accuracy was observed (89.4% to 105.9%) with no matrix effects for mitotane measurements. Patient's samples results were compared with previous measurement by GC-MS method with a high correlation (r=0.88 and bias=-10.2%) showed that our method is usefull for routine mitotane measurement.

Conclusion

DDD determination in plasma samples by our developed and validated method is simple, robust, efficient and sensitive for therapeutic drug monitoring and dose management in order to achieve therapeutic index of mitotane in patients with adrenocortical cancer.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN12 Change of Computed Tomography-Based Body Composition After Adrenalectomy in Patients with Pheochromocytoma: Importance of Sympathetic Activity on Human Fat Metabolism
Authors: Kim Beom-Jun , Kim Kyung Won , Ko Yousun
Published: November 2022

Context

Despite potential biological importance of sympathetic nervous system on fat and skeletal muscle metabolism in animal and in vitro experiments, its impact in humans remains questionable.

Objective

To clarify the influence of catecholamine excess on human body composition

Design

Retrospective longitudinal cohort study

Patients

313 consecutive patients with histologically confirmed pheochromocytoma who underwent repeat abdomen computed tomography (CT) scans before and after adrenalectomy were included.

Measurements: Changes in CT-determined visceral fat area (VFA), subcutaneous fat area (SFA), skeletal muscle area (SMA), and skeletal muscle index (SMI) measured at the level of third lumbar vertebra

Results

The mean age was 50.6X ± 13.6 years and 171 (54.6%) were women. A median follow-up duration of repeat CT was 25.0 months. VFA and SFA were 14.5% and 15.8% higher, respectively, after adrenalectomy, whereas SMA and SMI remain unchanged. Consistently, patients with visceral obesity significantly increased from 103 (32.9%) at baseline to 138 (44.1%) following surgery; however, the prevalence of sarcopenia was equivalent. Furthermore, higher baseline levels of blood metanephrine and urine normetanephrine were related to greater increases in SFA, but not in muscle parameters, after adrenalectomy.

Conclusion

This study provides important clinical evidence that sympathetic hyperactivity can contribute to lipolysis in both visceral and subcutaneous adipose tissues, while its impact on human skeletal muscle is less clear.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN15 Recurrence of Benign Pheochromocytoma
Authors: Manas F N U , Jagan Suchetha , Mols-Kowalczewski Barbara
Published: November 2022

INTRODUCTION: Pheochromocytoma is a rare, usually benign, tumor of adrenal medulla. The prevalence is about 4.5-6.5%. The common presenting symptoms are headache, palpitations, diaphoresis, flushing, hypertension, and tachycardia. The high catecholamine levels can also result in arrhythmias, cardiomyopathy, stroke, and even death. It can also be asymptomatic and diagnosed as an adrenal incidentaloma on routine imaging. Due to its diverse and non-specific presentation, it is often called a great mimic in medicine. It is diagnosed both biochemically with plasma or urine metanephrines and by imaging (CT or MRI). The first line treatment is surgical resection of adrenal gland, adrenalectomy. Resected tumors should be pathologically confirmed for absence of malignancy. The recurrence of benign pheochromocytoma after adrenalectomy is rare. Recurrence rate following adrenalectomy is 6.5-16.5%. There are no identified predictors of recurrence but usually it occurs after 2-3 years. Annual imaging and biochemical testing for plasma and urinary metanephrines is recommended for early diagnosis of recurrence. CASE PRESENTATION: A middle aged female with past medical history of uncontrolled hypertension and uncontrolled diabetes mellitus underwent CT scan for abdominal pain, fatigue, and unintentional weight loss. She also complained of intermittent palpitations, chest heaviness, sweating, facial flushing, and headaches. Family history was negative for endocrinopathies or endocrine malignancies. CT showed 12 cm right adrenal mass. Plasma metanephrines were ordered given the imaging findings and they were elevated at more than 13000 pg/nl (normal < 60 pg/ml). All other adrenal hormones were within normal range. She was diagnosed with pheochromocytoma and underwent right adrenalectomy. The tumor was confirmed to be benign by histopathology. Post-surgery her symptoms resolved, and biochemical tests normalized with plasma metanephrine at 35 pg/ml. She presented again 4 years later with similar symptoms. Patient experienced palpitation and noted to have high blood pressure at home. She had also been experiencing flushing and having a sense of impending doom. On examination the patient was diaphoretic and review of systems was positive for heat intolerance, polydipsia and polyuria. EKG revealed sinus tachycardia and blood glucose was elevated. Labs revealed elevated plasma metanephrine and normetanephrine levels. Renin activity and plasma aldosterone levels were normal. CT scan confirmed soft tissue masses, 2. 0 x4. 0 cm posteriorly and 2. 0 x3.2cm laterally, in the pararenal space surrounding the right kidney, suggestive of local recurrence of pheochromocytoma. CONCLUSION: Even though rare, the recurrence of pheochromocytoma can occur, usually after 2-3 years. Annual imaging and biochemical testing is recommended to diagnose recurrent pheochromocytoma, especially in patients with large tumors (>5cm).

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN16 Sublethal Hyperthermia Decreases Cellular Proliferation and Transiently Disrupts Steroidogenesis in Adrenal Cells
Authors: Mullen Nathan , Donlon Padraig T , Duffy Katen , Feely Sarah , Warde Kate M , Prakash Punit , Dennedy Michael Conall , O’Halloran Martin
Published: November 2022

Introduction

Primary Aldosteronism is the most common cause of secondary hypertension. First-line treatment; adrenalectomy resects adrenal nodules and adjacent normal tissue, limiting suitability to those who present with unilateral disease. Use of thermal ablation represents an emerging approach as a possible minimally invasive therapy for unilateral and bilateral disease, to target and disrupt hypersecreting aldosterone producing adenomas, while preserving adjacent normal adrenal cortex. Ablation involves heating tissue >50°C to induce cellular necrosis. Outside the core ablation zone, the transitional zone is an area exposed to variable temperatures between 37°C – 50°C. To understand the feasibility of precision ablation in the adrenal gland, we examined the effect of applying these temperatures to adrenocortical cells to identify i) the required temperature to effectively ablate adrenal cells ii) the extent of damage that may occur to surrounding healthy adrenal cells with exposure to transitional zone temperatures.

Methods

Steroidogenic adrenocortical cell lines, H295R and HAC15, were treated with hyperthermia (high precision water bath) at temperatures of 37, 42, 45, 48 and 50°C and steroidogenesis was subsequently stimulated using forskolin (10µM) and angiotensin II (10nM). Cell death (Propidium iodide staining by flow cytometry), proliferation (xCELLigence real-time cell analysis), protein expression (Western blot/qRT-PCR), and steroid secretion (HPLC-Mass spectrometry) were analysed immediately and 7-days post-treatment.

Results

Cell death occurred at 48°C and 50°C (p<0.05 vs 37°C control), but not 45°C, or 42°C. Sublethal hyperthermia (42°C and 45°C for 30 minutes) induced a heat shock response demonstrated by upregulation of HSP70 and HSP90. Proliferation was subsequently reduced over 7-days alongside a decrease in aldosterone and cortisol secretion (p<0.05), and reduced expression of steroidogenic enzymes (CYP11B1, CYP11B2, CYP11A1) 18-hours post treatment (p<0.05). Following 7-days sublethal hyperthermia, steroid secretion and steroidogenic enzymatic expression returned to baseline levels.

Conclusion

Hyperthermia at 48°C and 50°C for 15 minutes is required for sustained cell death at 7-days post treatment. Sublethal hyperthermia, equivalent to that produced in the transitional zone during thermal ablation, produces a short-lived unsustained inhibition of steroidogenesis that recovers 7-days post treatment. Therefore, segmental adrenal sparing ablation is possible with recovery of transitional zone following ablation. This underlines the potential for precision technology development for bilateral adrenal ablation as definitive measure to treat PA caused by APA or Micronodular disease.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN21 Adrenal Incidentaloma: Is Interval Scanning Warranted?
Authors: Fryer Antony , Issa Basil , Lea Simon , Powner Gill , Sathiavageeswaran Mahesh , Waldron Julian , Hanna Prof Fahmy , Wachira Lianne , George Cherian , Clark Alex , Golash Anurag , Kempson Wayne , Accreditation Clinical Audit
Published: November 2022

Background

Adrenal incidentaloma (AI) is an increasingly recognised finding, with pressure on healthcare systems. Earlier guidelines recommended interval scanning and testing to ensure stability. However, the recent European guidelines do not recommend the need for repeat scanning if initial assessment is reassuring.

Aim

To explore the utility of this guidance on need for interval scanning of benign AI.

Methods

A retrospective unselected review of AI cases seen in our unit before the launch of the European guidelines was conducted. At that time, a local protocol was in use to characterise scan and test adrenal functions at baseline, and at two years, the scan and endocrine tests were repeated. We compared the baseline scan results with those at two-years.

Results

We collected data on 54 patients initially identified between 2011 and 2016. Of these, 31 had left-sided lesions, 15 had right-sided lesions and 8 bilateral. Of the left-sided lesions, 16 increased in size over the 2.2-year follow-up period, 4 decreased in size and 17 remained the same. Of the right-sided lesions, 3 increased in size over the follow-up period, 6 decreased in size and 13 remained the same. Of those that increased (left- or right-sided), the largest increase was 5mm. Taking 2 mm as the cut-off for a significant change: on the left, 32/37 (86%) had a change ≤2mm (P<0. 001 for no increase). On the right, 21/22 (95%) had a change ≤2mm (P<0. 001). Using a ≤5% increase as cut-off: 28/37 on the left (P=0. 028) and 20/22 on the right (p<. 001) showed ≤5% increase. There was no statistical difference in change in lesion size in terms of laterality, being indeterminate on initial scanning, gender, age or initial size on presentation.

Conclusion

We found that there was no significant change in size after two years. Therefore, our data support the European guidelines that repeat scanning is unnecessary. This should be reassuring to patients and provide a more cost-effective service.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.