bluuebunny/crossref_metadata_2025 huggingface dataset:
OR10-3 Long-term Weight Loss Maintenance with Obesity Pharmacotherapy: a 5-Year Retrospective Study
Authors: Andre Clarissa , Aronne Louis , D’Angelo Debra , Shukla Alpana , Tchang Beverly , Weintraub Michael
Published: November 2022

Objective

To determine the association of anti-obesity medications (FDA-approved and off-label) with weight loss maintenance over 3-5 years.

Methods

We performed a retrospective observational study of adults 18-75 years treated for overweight/obesity at a tertiary academic weight management center with an initial visit between April 1st, 2014 and April 1st, 2016. We excluded patients who had a period of follow-up less than 2.5 years or a gap in follow-up of greater than 2 years. Patients who had bariatric surgery, pregnancy, or a medical condition predisposing them to weight loss during the study were also excluded. We extracted key demographic data, medical history, and weight at each visit. Anti-obesity medication (AOM) start date and end date was determined through chart review with attention to patient self-reporting of medication adherence to calculate total exposure to each AOM. We used the weight loss maintenance definition of weight regain ≤ 3% of the nadir weight.

Results

A total of 428 patients met inclusion criteria for the analysis and were followed for a mean of 4.4 years. The mean age was 50.9 years, 73% were female, and median initial BMI was 34.3 kg/m2. Weight categories were as follows: 19% overweight, 35% class 1, 25% class 2, and 20% class 3 obesity. In addition, 16% had diabetes and 36% had prediabetes.

The median nadir BMI was 25.6 with a median maximum weight loss of 14.7%. The median time to achieving nadir weight was 1.9 years. Average weight change from the initial to final visit was -10.6% (-10.9 kg), with a final visit median BMI of 27.4. The proportion of patients who achieved ≥5%, ≥10%, ≥15%, and ≥20% total weight loss was 70.8%, 48.1%, 30.1%, and 16.8%, respectively. During the 4.4 years the patients were followed, weight regain following the nadir weight was 6.3%. At the last observation, 40.2% of all patients had maintained their maximum weight loss.

The mean number of AOMs trialed throughout the duration of the study was 4.2. At the final visit, a mean of 2.5 AOMs were being taken. The most common medications observed at the final visit alone or in combination were metformin (76.2% of patients), phentermine (31.1%), topiramate (30.8%), bupropion (29.9%), and semaglutide (24.5%).

Conclusion

Long-term weight loss of 10.6% was observed over 3-5 years in adults with overweight/obesity who were managed with pharmacotherapy. This study demonstrates clinically significant long-term weight loss maintenance can be achieved with pharmacotherapy and lifestyle interventions.

Presentation: Sunday, June 12, 2022 11:30 a.m. - 11:45 a.m.
RF12 | PSUN118 Diet Quality and Energy Intake Mediate the Association of Food Insecurity with Adiposity
Authors: Morselli Lisa , James Roland , Kidambi Srividya
Published: November 2022

Food insecurity, the lack of consistent access to sufficient food for an active and healthy life, is associated with lower diet quality, higher BMI and adiposity, and poor metabolic health. Although lower diet quality is assumed to be responsible for the impact of food insecurity on adiposity, this hypothesis has not been previously investigated.

To test the hypothesis that diet quality mediates the association of food insecurity with adiposity, we used data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES, age ≥18 years, n=5821, weighted N=233,636,542). Anthropometrics included BMI, waist circumference and fat mass (measured by dual X-ray absorptiometry and expressed as percentage of total body weight). Food insecurity was assessed with the 10-item NHANES Food Security Survey Module and defined as ≥3 affirmative responses. Nutrition information was derived from 24h food recalls obtained on 2 separate occasions. Diet quality was estimated by the Healthy Eating Index-2015 (HEI), which includes a total score for overall diet quality, and sub-scores for several dietary components. Mediation analysis was conducted with the Baron and Kenny approach. A p-value <0.05 was considered statistically significant.

The cohort included 52% women, 11% non-Hispanic Black and 15% Hispanic participants. Eighteen percent were food insecure. They reported a lower energy intake compared to food secure participants, although the difference was not significant after adjusting for demographics and income (difference [95% confidence interval] -84 [-207.36, 38.91] kcal/day, p=0.15). Total HEI and fruit scores were lower in food insecure individuals, suggesting lower diet quality (adjusted difference -1.70 [-3.09, -0.32], p=0.03; and -0.28 [-0.53, -0.02], p=0.04, respectively). Obesity was 22% more prevalent in food insecure individuals (p<0.01). Fat mass and waist circumference were also higher in individuals with food insecurity (adjusted difference 0.95 [0.19, 1.7] %, p=0.02; and 3.81 [1.3, 6.31] cm, p=0.01, respectively). Mediation analysis revealed that total energy intake mediated the effect of food insecurity on fat mass but not BMI or waist circumference, while total HEI partially mediated the effect of food insecurity on waist circumference but not BMI or percent fat mass. No mediation of total fruit score on BMI or adiposity was observed.

In summary, our results confirm a greater prevalence of obesity and higher adiposity in food insecure individuals, despite a similar reported energy intake compared to food secure individuals. Energy intake and measures of diet quality appear to mediate some of the effect of food insecurity on overall and central adiposity, but not on BMI. This suggests that other factors, including the social determinants of health, may also play a role.

Presentation: Saturday, June 11, 2022 1:18 p.m. - 1:23 p.m., Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF24 | PSUN116 Once-weekly semaglutide delays a late phase gastric emptying of solid meal measured by repeated scintigraphic imaging in obese women with PCOS
Authors: Jensterle Mojca , Ferjan Simona , Lezaic Luka , Socan Aljaz , Zaletel Katja , Janez Prof Andrej
Published: November 2022

Background

GLP-1 agonism have the potential to affect gastric emptying (GE), yet the reports for subcutaneous semaglutide, currently the most effective GLP-1 RA approved for weight management, remain inconclusive. It has been demonstrated that once-weekly semaglutide either had no effect on GE or it delayed GE only within the first hour, without late phase retention. Notably, those conclusions were made by an indirect method of estimation of GE through ingestion, absorption and determination of plasma level of paracetamol. Furthermore, in most previous studies with once weekly semaglutide, GE has been evaluated as a part of the composite outcome. The indirect method with paracetamol was shown to be appropriate for evaluation of kinetics of liquid meals, whereas it might lead to inaccurate estimation of late phase GE. Scintigraphic evaluation is considered as a reference method for the purpose.

Aim

This is the first study that evaluates the effect of once weekly subcutaneous semaglutide on late phase GE of a solid meal by scintigraphy in obese women with PCOS without other comorbidities as a primary outcome.

Materials and Methods

A single-blind, placebo-controlled trial was conducted in 20 women with PCOS and obesity, without diabetes and other comorbidities, randomized to once weekly subcutaneous semaglutide 1 .0 mg (S) or placebo (P) for 8 weeks. Gastric emptying was assessed by scintigraphy after ingestion of 99mTC colloid in pancake labelled with radiopharmaceutical that maintained a stable binding within gastric environment by scintigraphy using sequential static imaging and dynamic acquisition. Estimation of GE was obtained by repeated imaging of remaining 99mTC activity (RA) at fixed time intervals over 4 hours and the half time (T1/2) of gastric emptying had been calculated. Additionally, we evaluated anthropometric, metabolic, hormonal and appetite parameters.

Results

At 30 min after ingestion significant difference in RA was observed between semaglutide group and placebo (92.5% in S vs. 89% in P (p=0,05)) and persisted throughout the observation period up to 4 hour (37% in S vs. 0% in P (p=0,002)). T1/2 was significantly longer in S as compared to P (171 min vs 118 min, respectively (p<0.001)). In addition, semaglutide led to significant decrease in weight, waist and neck circumference, HbA1c and androgen levels. Subjective ratings of appetite suppression correlated with T1/2.

Conclusion

Once weekly semaglutide 1.0 mg resulted in a significant late-phase retention of solid meal measured by repeated scintigraphic imaging. This effect correlated with appetite suppression and likely contributed to weight loss.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 1:18 p.m. - 1:23 p.m.
RF36 | PSUN77 Female Dexras1 WT & KO Mice Fed a High Fat Diet Do Not Have Different Body Compositions nor Bone Densities
Authors: Gangavaram Anish , Thompson William , Fong Vincent
Published: November 2022

Glucocorticoids are a frequently prescribed class of medications, widely used for their anti-inflammatory and immunosuppressive effects. However, long term usage of glucocorticoids is associated with a variety of adverse effects, including adrenal suppression, increased adiposity, and decreased bone density. DEXRAS1, also known as RASD1, is a member of the Ras family of GTPases that is upregulated by glucocorticoids. In in vitro experiments, DEXRAS1 has been shown to promote differentiation of adipocytes and decrease differentiation of osteoblasts. Studies conducted in male Dexras1 knockout (KO) and wild type (WT) mice treated with dexamethasone found decreased body weight and visceral fat, and increased bone density in KO mice when compared to WT mice; together, these experiments suggest that the removal of the Dexras1 gene can prevent glucocorticoid-induced osteoporosis and fat-accumulation.A major limitation of the aforementioned studies is that they were performed using only male mice, despite well-known sex related differences in body composition and bone density. On average, females have a higher percentage of body fat and lower bone density. While obesity is prevalent across all sexes, osteoporosis is 4 times more common in females. Therefore, in order to better understand sex as a biological variable on the effects of the Dexras1 gene, we compared female Dexras1 KO and WT mice fed a high-fat diet (HFD) containing 45 kcal% fat over the course of 14 weeks. Body composition was assessed by quantitative magnetic resonance. Bone morphometry was analyzed with micro-CT, and bone density was analyzed with micro-CT and dual-energy x-ray absorptiometry (DXA) scans of female murine femurs. Interestingly, there were no differences in the overall body weight, fat mass, nor lean mass over this period between WT and KO female mice. Similarly, the female Dexras1 KO and WT mice mice showed no differences in their bone density, cortical thickness, and average trabecular separation. Since there was no difference in the fat mass, it is not surprising that there was also no difference in bone density, as they are often inversely related. These data in conjunction with previous experiments on male mice suggest that sex strongly impacts the phenotype observed as a result of knocking out the Dexras1 gene. The mechanisms underlying differential regulation between the sexes is unclear, and could include differences in sex hormones, the presence of estrus cycle in females, differences in stress response, or even differences in microbiome. Consequently, more studies are necessary to fully understand the function and regulation of Dexras1.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:36 p.m. - 12:41 p.m.
LBODP008 Gene Therapy For Congenital Adrenal Hyperplasia With AAV Vectors Into Fibroblasts, IPS Cells And Model Mice
Authors: Naiki Yasuhiro , Miyado Mami , Horikawa Reiko , Katsumata Noriyuki , Takada Shuji , Akutsu Hidenori , Onodera Masafumi , Fukami Maki
Published: November 2022

Background

Congenital adrenal hyperplasia (CAH) is due to defects of steroid synthetic enzymes, which includes microsomal and mitochondrial P450s. Microsomal P450s include 21-hydroxylase and 17α-hydroxylase/17-lyase. 21-hydroxylase deficiency (21-OHD), in which CYP21A2 is mutated or deleted, is the most common cause of CAH and results in underproduction of glucocorticoids and mineralocorticoids, and overproduction of androgens. 11β-hydroxylase deficiency (11β-OHD), which is a defect of a mitochondrial P450, is the second common cause of CAH. Patients with CAH are treated with oral steroid supplementation, but optimal control of blood steroid levels remains difficult. Thus, new therapeutic approaches are still needed. Intravenous adeno-associated virus (AAV)-mediated administration of human CYP21A2 into adult 21-OHD patients has been reported at the ENDO 2021 meeting. In this study, we examined the effects of induction of causative genes with an AAV vector into fibroblasts from patients and iPS cells and adrenal glands of model mice.

Methods

Fibroblasts from CAH patients were subjected to primary culture. The cells were infected with a serotype-2 AAV vector (AAV2) containing defected genes and cultured in steroid substrate-containing medium for 24 hours. We measured steroid metabolites in the medium by liquid chromatography tandem mass spectrometry and evaluated gene expressions by RT-PCR. In addition, iPS cells were established from fibroblasts of 11β-OHD and differentiated into adrenocortical cells with retinoic acid and cAMP. They were infected with a serotype-9 AAV vector (AAV9) containing CYP11B1 cDNA. Steroid metabolites in the culture medium were measured and gene expressions were evaluated by RT-PCR. 11β-OHD model mice were made by a gene-editing method. We injected AAV9 containing Cyp11b1 cDNA into the adrenal gland and measured serum DOC and corticosterone levels before and every 4 weeks after injection.

Results

AAV2 infected fibroblasts from 21-OHD and 17α-hydroxylase/17-lyase deficiency can metabolite steroid precursors but failed to convert DOC to corticosterone in 11β-OHD. Differentiation into adrenocortical cells from iPS cells of 11β-OHD was confirmed by expression of CYP21A2. AAV9 gene induction of adrenal cortical cells successfully induced 11β-hydroxylase activity. 11β-OHD mice also showed improved steroid synthesis after AAV9 adrenal induction.

Conclusion

These results indicate that extra-adrenal induction of CYP21A2 may ameliorate steroid metabolism in 21-OHD patients. In contrast, 11β-OHD needs AAV9 adrenal induction to treat the steroid abnormality. Our results suggest that specific gene therapeutic strategies are needed to be adapted for each type of CAH.

Presentation: No date and time listed
PSAT037 The Unlikely Suspect - A New Diagnosis of Autoimmune Addison's Disease in an 80-year old Lady
Authors: Carroll Dylan , Sharma Pranjali
Published: November 2022

Introduction

Hyponatremia is a common cause of hospitalization in older adults. Addison's disease (AD), an uncommon cause of hyponatremia, is primary adrenal insufficiency (AI) caused by autoimmune adrenalitis, infections, adrenal hemorrhage, or infiltration. Autoimmune adrenalitis is an uncommon cause of AD after age 60 years. We report an 80 year old patient with hyponatremia who was ultimately diagnosed with autoimmune AD.

Case report

An 80 year-old lady with steroid-controlled asthma, presented to the ER with weakness, imbalance, nausea and vomiting two weeks after a urinary tract infection. Her blood pressure was 96/64 mm Hg with otherwise normal vital signs and unremarkable general examination. Laboratory evaluation revealed hyponatremia (Na 120 mmol/L), hyperkalemia (K 5.7 mmol/L) and acute kidney injury (creatinine 1.2 mg/dl, GFR 43 ml/min/m). Hyperkalemia resolved with intravenous fluids, insulin and dextrose therapy (K 4.7 mmol/L). However, hyponatremia persisted (Na 120-123 mmol/L) despite fluid restriction, normal saline, and salt tablets. Additionally, patient remained hypotensive with blood pressure between 90/40-120/60 mm Hg. Due to concern for AI from prior steroid use, morning cortisol was measured and was low (4.63 mcg/dl). Concurrent ACTH level was elevated (252 pg/ml, range 7.2-63.3 pg/ml). Cosyntropin stimulation test done during hospitalization was abnormal (4.5 mcg/d→6.7 mcg/dl→8 mcg/dl) confirming AD.

At outpatient consultation with endocrinology, patient reported nausea and vomiting for 18 months prior to hospitalization, 50 lbs weight loss, weakness, short-term memory loss, and dizziness attributed to vertigo. Symptoms worsened a month prior to patient's hospitalization. Repeat cosyntropin stimulation test remained abnormal (8.5 mcg/dl→9.6 mcg/dl→10 mcg/dl). CAT scan of the abdomen with adrenal protocol was unremarkable for adrenal masses, hemorrhage, infiltration, or metastasis. Surprisingly, 21-hydroxylase antibody testing was positive confirming autoimmune AD. The patient has been on hydrocortisone 15 mg in AM + 5 mg in PM and fludrocortisone 0.1 mg daily for one year now with improvement in symptoms.

Discussion

Medications, poor diet, and diabetes are common causes of hyponatremia in the elderly. AD, an uncommon cause of hyponatremia, should be considered in a hospitalized hyponatremic elderly patient. Non-specificity of AD symptoms makes the diagnosis in this age group difficult, often causing delay in appropriate management.

Autoimmune AD is characterized by the presence of 21-hydroxylase antibodies. Data on autoimmune AD incidence in the elderly is limited due to rarity. Our patient's autoimmune AD was likely masked due to steroid use for asthma. During COVID-19 pandemic, masking, and social distancing decreased the patient's steroid needs and unmasked AD after the UTI. Our case highlights the importance of considering autoimmune AD as a cause of AI even in the elderly.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT041 A Rare Case of Severe Cyclical Cushing Syndrome Due to Ectopic ACTH Secretion by Appendiceal Carcinoid
Authors: Sidra Fnu , Hamidi Oksana , Nwariaku Ohwofiemu , Mirfakhraee Sasan , Jia Liwei , Polanco Patricio
Published: November 2022

Cushing syndrome (CS) secondary to ectopic ACTH secretion (EAS) is rare and accounts for 10% of CS with majority being bronchial or gut neuroendocrine tumors (NETs) and squamous cell lung cancer. There are only a few case reports of EAS due to appendiceal carcinoid.

A 24-year-old woman was referred to endocrinology for 60-pound weight gain, acne, hirsutism, generalized weakness, heat intolerance, and hot flashes. She had secondary amenorrhea for 6 months prior to presentation. Family history was significant for bronchial carcinoid in mother. On examination, she had moon facies, wide purple striae on abdomen, hirsutism, dorsocervical and supraclavicular fat pads. She had normal blood pressure. Her laboratory workup showed potassium 3.2 mmol/L (N, 3.5-5.3), urine free cortisol (UFC) 539 mcg/24 hours (N<50), ACTH 54 pg/ml (N, 6-50) and post 1-mg dexamethasone suppression test cortisol 8.8 mcg/dL. CT abdomen revealed a 3-cm enhancing appendiceal mass, enlarged periappendiceal mesenteric lymph nodes and a 4-cm enhancing right hepatic lobe lesion. Ga-68 Dotatate PET/CT confirmed increased radiotracer uptake in appendiceal mass, lymph nodes and hepatic mass. On liver biopsy, pathology showed well differentiated NET Grade 1 and positive ACTH stain. Repeat UFC was 65 mcg/24 hrs and serum cortisol went down to <1 mcg/dL indicating severe cyclical CS. She was referred to surgical oncology for opinion on debulking surgery. Her genetic testing was negative. She was started on Lanreotide. Given severe cyclical CS with extensive tumor burden, she underwent robotic bilateral adrenalectomy with a plan for cytoreductive surgery once she is on physiologic doses of steroids.

Appendiceal NET causing Ectopic CS is exceedingly rare. In 20 years’ experience at NIH, there was only one case of appendiceal NET reported. First reported case was in 1971, when CS was cured by resection of an appendiceal carcinoid incidentally detected on laparotomy for adrenalectomy. There are 3 additional case reports in literature of appendiceal carcinoid with ectopic CS. Management can be challenging particularly in patients with metastatic disease. Medical therapy should be individualized, and adrenalectomy should be considered early in patients with uncontrolled CS due to EAS.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT045 Spontaneous Adrenal Hemorrhage with Partial Adrenal Insufficiency in a Patient Anticoagulated with Apixaban for Antiphospholipid Syndrome
Authors: Hu Jiun-Ruey , Tan Jiawei
Published: November 2022

Background

Addison's disease secondary to adrenal hemorrhage is a rare complication of antiphospholipid syndrome (APLS). Anticoagulation with a direct oral anticoagulant (DOAC) might increase the risk of adrenal hemorrhage. We report a patient who developed bilateral adrenal hemorrhage after starting apixaban for deep venous thrombosis (DVT) and pulmonary embolism (PE) in the setting of latent APLS.

Clinical Case

A 45-year-old man without significant past medical history presented with a left lower extremity DVT and PE. He had no personal or family history of previous trauma, bleeding or clotting events. He was discharged on apixaban. Three days later he was readmitted with bilateral flank pain. Computerized tomography (CT) imaging showed bilateral adrenal gland edema. He was hemodynamically stable. Due to persistent right flank pain and concern for ileus, CT was repeated and revealed findings concerning for adrenal hemorrhage. He subsequently complained of asthenia. Further testing revealed a reduced morning cortisol of 1.4 ug/dL (reference: 6.0 - 18.4 ug/dL) and an elevated morning ACTH of 149 pg/mL (7.2-63.3 pg/mL). Plasma dehydroepiandrosterone sulphate (DHEA-S) was reduced at 39 mcg/dL (70 - 495 mcg/dL), and epinephrine and norepinephrine were undetectable. Morning plasma aldosterone was undetectable and renin activity was 0.76 ng/mL/h (0.25 - 5.82 ng/mL/h). He was started on stress dose steroids and discharged on maintenance hydrocortisone without reinitiating anticoagulation.

Two weeks later, he re-presented with a right lower extremity DVT. An APLS panel revealed elevated anti-beta2 glycoprotein 1 IgG and anti-cardiolipin IgG. Laboratory work-up for other causes of thrombosis, including inherited and acquired thrombophilias, anatomical vascular obstruction, paroxysmal nocturnal hemoglobinuria (PNH), heparin-induced thrombocytopenia (HIT), and myeloproliferative neoplasms (MPN), was unrevealing. Warfarin was started with an international normalized ratio (INR) target range of 2-3. Hydrocortisone was continued at a total daily dose of 30mg. Since discharge, his morning cortisol levels have been low at 4.4-4.9 ug/dL and ACTH has remained high at 92-137 pg/mL, but aldosterone has been variable at <1 to 9 ng/dL, and renin has been normal at 0.35 ng/mL/h. This suggests what transpired had been microthrombi-associated intra-adrenal hemorrhage involving the zona fasciculata with sparing of the glomerulosa.

Conclusion

This case highlights DOAC-associated adrenal hemorrhage in a patient with underlying APLS, an under-appreciated complication. The extent to which the various layers of the adrenal gland are affected may vary. Since guidelines on the management of patients with partial adrenal insufficiency are lacking, further reporting is needed on long term outcomes and adrenal function of these patients.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT055 ACTH-Dependent or ACTH-Independent: The Importance of a Reliable ACTH Assay in Solving a Case of Cushing Syndrome
Authors: Duro Teodor , Lovato Christina
Published: November 2022

Background

Reliable laboratory assays are of paramount importance in the field of endocrinology, as our ability to make diagnoses and recommend the appropriate treatment, rely heavily on them.

Clinical Case

A 36-year-old woman presented to our clinic with a history of a 30-pound weight gain over the course of a year and hypertension that was sub-optimally controlled on two antihypertensive medications. On physical exam she exhibited facial plethora, moon facies, central obesity, dorsocervical fat pad, and reddish abdominal striae. Laboratory data revealed a 24 hr urine free cortisol 277 mcg/24 h (n ≤ 45 mcg/24 h), 8 am cortisol after 1 mg dexamethasone suppression test 19.2 mcg/dL (cut-off <1.8 mcg/dL) with a dexamethasone level 179 ng/dL (n 140-295 ng/dL). Serum DHEAS <15 mcg/dL (n 35-430 mcg/dL) which was suggestive of an adrenal source of cortisol. CT scan of the adrenals revealed a 3.0×2.3 cm right adrenal nodule, 14 HU, relative washout of 58%, absolute washout of 68%, consistent with an adenoma. However, plasma ACTH was 20 pg/mL (n 0-46 pg/mL) which was suggestive of an ACTH-dependent etiology. Repeat ACTH levels through our local lab ranged between 17-27 pg/mL. An MRI of the brain was obtained which showed a normal pituitary gland without evidence of an adenoma.

Due to the discrepancy between the clinical picture and the ACTH levels, the patient's case was discussed with the medical director of our local lab. It was decided to obtain another sample for ACTH which was tested for heterophile antibodies but did not yield any meaningful results. The patient denied being on any supplements that could interfere with the ACTH assay. The sample was then sent out to an outside lab with a plasma ACTH level <1 pg/mL (n 7.2-63 pg/mL), which was consistent with the patient's clinical presentation of an adrenal source of cortisol excess. Further investigation revealed that our local lab used a Siemens Immulite assay which was likely detecting interference, whereas the outside lab used the Roche Elecsys assay. In previous studies, the Roche assay has highly correlated with intact ACTH that has been measured by HPLC-MS/MS. The patient was started on ketoconazole and has been referred for right adrenalectomy.

Clinical Lessons

Heterophile antibodies and ACTH fragments are common culprits of ACTH immunoassay interference, but they can be difficult to detect if there is not a high index of suspicion. Erroneous laboratory results can lead clinicians to perform unnecessary procedures and delay patient care. This case highlights the importance of a reliable plasma ACTH assay to inform clinical judgment.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT085 Monoclonal Cortisol Immunoassay Cut Off Point to Diagnose Adrenal Insufficiency (AI)
Authors: Cortez Samuel , McNerney Kyle , Arbelaez Ana Maria
Published: November 2022

Objective

Adrenal Insufficiency (AI) is diagnosed when the peak cortisol level after a cosyntropin stimulation test is <18 mg/dL using a standard reference (e.g. polyclonal antibody (pAb) immunoassay). However, in most laboratories the polyclonal assay is being replaced by a specific monoclonal antibody (mAb) immunoassay which yields lower cortisol levels, leading to the over diagnosis of AI and unnecessary steroid use.

Methods/Study Population

We obtained blood samples from 36 patients undergoing 1 mcg cosyntropin stimulation tests for diagnosis of AI. Samples were analyzed using pAb immunoassay (Abbott Architect Cortisol), mAb immunoassay (Roche Elecsys Cortisol II), and mass spectrometry (MS). AI was diagnosed if serum cortisol level was <18 using the pAb immunoassay. Measurements by MS and mAb immunoassay were individually used in simple logistic regression models to predict AI. For each model, we calculated a cortisol level corresponding to a 50% probability (median) of AI and used the delta method to determine the standard error and 95% confidence interval of the median. We used receiver operator characteristic (ROC) curve, area under the curve, sensitivity, and specificity to evaluate the potential of the median values as thresholds for each predictor.

Results

The ROC curve model indicated an area under the curve of 0.997 with a median value of 11.2 mcg/dL for the mAb immunoassay. This provides a sensitivity of 95%, specificity of 95%, positive predictive value of 95%, and negative predictive value of 94%. This new value has a Kappa coefficient of 0.89 when compared to the pAb immunoassay. When using all the data points throughout the stimulation test, data showed a mean difference in cortisol level between the mAb immunoassay and the pAb immunoassay of 5.12 mcg/dL (p-value <0.01) at any point during the test.

Discussion/Significance

New and highly specific mAb immunoassays are being used more widely but yield lower cortisol results. This reflects the need for further studies to determine new cut off points for highly specific cortisol immunoassays. A cut off level of 11.2 mcg/dL for the mAb immunoassay would provide a sensitivity of 95% and specificity of 95%.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF33 | PSUN02 Presentation, Management, and Outcomes of Urinary Bladder Paraganglioma: Results from a Multi-center Study
Authors: Yu Kai , Yu Kai , Ebbehoj Andreas Ladefoged , Obeid Hiba , Vaidya Anand , Else Tobias , Wachtel Heather , Main Ailsa Maria , Sondergaard Esben , Christensen Louise Lehmann , Juhlin Christofer , Calissendorff Jan , Cohen Debbie , Bennett Bonita , Andersen Marianne Skovsager , Larsson Catharina , Almeida Madson Q , Boorjian Stephen A , Young William F , Bancos Irina
Published: November 2022

Context and Objectives

Urinary bladder paraganglioma (UBPGL) is rare. We aimed to characterize the presentation and outcomes of patients diagnosed with UBPGL.

Methods

We conducted a multi-center study of consecutive patients with pathologically-confirmed UBPGL evaluated between 1971 and 2021. Outcomes included repeat bladder surgery, metastases, and disease-specific mortality.

Results

110 patients (56, 51% women) were diagnosed with UBPGL at a median age of 50 years (IQR, 36-61 years). Median tumor size was 2 cm (IQR, 1-4 cm). UBPGL was diagnosed prior to biopsy in only 37 (34%), and only 69 (63%) patients had evaluation for catecholamine excess. In addition to the initial bladder surgery, 26 (25%) required multiple therapies, including repeat surgery in 10 (9%). Synchronous metastases were present in 9 (8%) patients, and 24 (22%) other patients with UBPGL developed metachronous metastases at a median of 4 years (IQR, 2-10 years) after initial diagnosis. Development of metachronous metastases was associated with younger age (Hazard ratio, HR 0.97, 95%CI 0.94-0.99), UBPGL size (HR of 1.69, 95%CI of 1.31-2.17), and a higher degree of catecholamine excess (HR of 5.48, 95%CI of 1.40-21.39). Disease-specific mortality was higher in patients with synchronous metastases (HR of 20.80, 95%CI, 1.30-332.91). Choice of initial surgery, genetic association, sex, or presence of muscular involvement on pathology were not associated with development of metastases or mortality.

Conclusions

Only a minority of patients were diagnosed before biopsy/surgery, reflecting the need of better diagnostic strategies. All patients with UBPGL should be monitored life-long for development of recurrence and metastases.

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.
LBSAT230 Daily Variation In Serum Calcifediol In Japanese And Non-japanese Adults
Authors: Ashfaq Akhtar , Strugnell Stephen A , Tabash Samir , Bishop Charles W
Published: November 2022

Circadian rhythm and 24-hour intra-subject variation in serum calcifediol (25-hydroxyvitamin D3) in the absence of vitamin D supplementation or treatment are poorly studied in healthy adults of any race. To address this dearth of information, a single-center, open-label study was completed in the US to evaluate both of these parameters in 67 male and female (balanced for gender) first generation Japanese (n=35) and non-Japanese (n=32) subjects, aged between 18 and 55 years. "First generation" was defined as: born in Japan; had 2 Japanese biological parents and 4 Japanese biological grandparents; had lived outside of Japan for less than 5 years; and, had made no significant changes in lifestyle, including diet, since leaving Japan. "Non-Japanese" was defined as: not of Japanese or Asian descent; and, parents and grandparents were not born in Japan or in any Asian countries. Enrolled subjects had a body mass index within 18. 0 to 30. 0 kg/m2 (inclusive) and body weight not less than 50 kg. The body weight for non-Japanese subjects was 9% to 17% higher than that of Japanese subjects (60.3 to 92.9 kg versus 51.2 to 84.9 kg). Exclusion criteria included consumption of a vitamin D supplement within the previous 28 days, consumption of grapefruit or oranges, alcohol, medications or tobacco within the previous 72 hours, and participation in strenuous physical activity within the previous 72 hours. Subjects were housed in a Phase 1 unit for 2 days where they received only standardized diets. Blood samples were collected on the second day at 0, 2, 4, 6, 8, 10, 12, 16 and 24 hours for determination of serum calcifediol by LC/MS/MS (mean accuracy: 0.37%; mean precision: 3. 07%) at Syneos Laboratories (Quebec, Canada). For all subjects, mean serum calcifediol levels ranged from 20.90 to 22.24 ng/mL over the 24-hour collection period with an average inter-subject variation (SD) of 6.79 ng/mL. A circadian rhythm was not evident either in the total population or in the racial subgroups. Mean intra-subject variation over 24 hours was 1. 08 ng/mL (SD; range: 0.27-3.22) or 5. 05% (CV; range: 2.36-14.81). Differences in 24-hour intra-subject variation between races were not significant (P>0. 05). These data support the conclusions that: (1) clinically meaningful circadian rhythms in serum calcifediol are absent in healthy first generation Japanese and non-Japanese adults living in the US; (2) the mean diurnal variation in serum calcifediol is small (approximately 5%); and (3) vitamin D therapies may appropriately be considered "physiological" if they raise serum total 25-hydroxyvitamin D after each dose only within the bounds of normal diurnal variation thereby allowing gradual adaptation to repletion.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP068 A Case Report of Nivolumab Associated Hypercalcemia
Authors: Sherpa Chheki , Shrestha Bishow , Singh Vinita
Published: November 2022

Introduction

Nivolumab is a human immunoglobulin G4 (IgG4) antibody which binds to programmed cell death receptor-1 (PD-1) and blocks the binding of PD-1 to either the PD-ligand 1 (PD-L1) or PD-L2 expressed on the surface of cancer cells. It has been approved for the treatment of melanoma, non-small cell lung cancer, renal cell carcinoma etc. Various endocrine immune-related adverse events including thyroiditis, hyper- and hypothyroidism, hypophysitis and type 1 diabetes has been described. We report a case of Nivolumab associated hypercalcemia.

Case presentation

67-year-old female with history of CKD stage 3 with secondary hyperparathyroidism, melanoma of right ankle was admitted after one month of receiving the first dose of Nivolumab for her melanoma. She had altered mentation with elevated corrected calcium of 15.94(8.4-10.2) mg/dl. Prior calcium levels were in low to normal range, eGFR was 13, creatinine elevated at 3.4 (0.57-1.11) mg/dl, PTH 84 (10-65) pg/ml, 25 OH vitamin D 54 (30-74) ng/ml, Phosphorus normal, Magnesium normal, 1,25-OH vitamin D was elevated at 103(18-72) pg/ml, PTHrp normal, normal SPEP, normal TSH, no history of fractures, normal DXA, no history of kidney stones, not on any calcium supplements, not on thiazide or lithium. Chest x ray and NM full body PET CT did not show any evidence of granulomatous disease except for recurrence and metastasis of melanoma in right thigh, calf, and ankle. No family history of kidney stones or hypercalcemia. Patient was treated with IV fluids and Calcitonin. Her calcium quickly improved to 9.9 within 48 hours. Within 3 weeks of discharge, she was readmitted for elevated calcium of 14.4 mg/dl, creatinine 2.29 mg/dl, eGFR 21, PTH 96 pg/ml, Mg 1.8 (1.6-2.6) mg/dl. She was treated with IV fluids and calcitonin and calcium normalized within 48 hours. Parathyroid scan did not show any parathyroid adenoma. She was started on prednisone for possible Nivolumab associated immune adverse reaction. She was also briefly treated with cinacalcet which was discontinued. Prednisone was tapered and then stopped over the course of 6 weeks. Calcium remains normal. PTH remains slightly elevated which is thought to be due to secondary hyperparathyroidism from CKD. Normal cortisol level.

Discussion

This is likely a case of Nivolumab associated hypercalcemia given the onset soon after immunotherapy initiation and improvement with glucocorticoid therapy. Immunotherapy was not resumed after the first dose due to recurrent severe hypercalcemia. The patient is currently under surveillance for melanoma. Calcium level remains normal. Although it is rare, a few cases of Nivolumab associated hypercalcemia have been reported previously. Exact mechanism is not known but it has been speculated that macrophage activation by Nivolumab can cause increased level of 25(OH) D-hydroxylase with increased conversion of 25-OH vitamin D to 1,25-OH vitamin D resulting in calcitriol mediated hypercalcemia.

Presentation: No date and time listed
ODP117 Pseudohypoparathyroidism Type IB: A Rare Cause of Hypocalcemia
Authors: Encarnacion Dionardo Medina , Sharma Brihant , Malik Maham , Sood Aayushi , Syed Omar , Khattar Khyati
Published: November 2022

Introduction

Pseudohypoparathyroidism (PHP) describes disorders of hypoparathyroidism that are the result of resistance of target tissues to the actions of parathyroid hormone (PTH). Studies have estimated the prevalence of PHP to be 0.34 in 100,000 in Japan and 1.1 in 100,000 in Denmark. The first biochemical abnormalities to become apparent are elevated serum levels of PTH and elevated serum levels of phosphorus, followed by hypocalcaemia. We present a patient diagnosed with PHP Type 1B (PHP1B), which was presented to us many years after her initial diagnosis, with other major comorbidities now present.

Case description

This patient is an 81 year old female presenting to the clinic to discuss her previously diagnosed PHP1B. Her past medical history revealed she began having symptoms of intermittent muscle cramping at the age of 22, followed by carpopedal spasms and periorbital paresthesia a year later. She has also had a physical examination significant for a positive Trousseau sign, but no phenotypical signs of Albright hereditary Osteodystrophy (AHO). Lab evidence from 1977 was recovered showing urinary cyclic AMP level <20 nmol/mg after administration of PTH, consistent with PHP1B. The family history in her parents and children has revealed no similar genetic history so far. Other comorbidities she has developed since her diagnosis are hypokalemia, hypothyroidism, osteoporosis with a femur fracture, obesity, chronic kidney disease and nephrolithiasis. She has been continuing treatment throughout her life with calcium, calcitriol and vitamin D supplementation for hypocalcemia. She has been mostly eucalcemic since then, and complains of occasional carpopedal spasms and perioral numbness.

Discussion

PHP1B is isolated resistance to PTH in the kidney and normal PTH response in bone without features of AHO. PHP1A and 1C have PTH resistance in bone, and both express AHO. These various forms of PHP are due to defects in the GNAS gene that lead to decreased expression of the alpha-subunit of G protein (Gsa). In the absence of molecular analysis, the clinical and biochemical overlap between PHP and related disorders can lead to challenges in diagnostic classification. There are 2 types of PHP1B cases- autosomal dominant (AD) and sporadic. However, the majority of Patients with PHP1B do not have mutations within the GNAS but they have methylation and imprinting defects that result in absence of maternal Gsa. To emphasize, epimutation study rather than sequencing of the coding region in GNAS should be performed for genetic investigation, which has now become standard practice. Although there is no difference in clinical presentation between AD PHP1B and sporadic PHP1B, their differentiation early during the disease onset can help providers give patients more reliable genetic and reproductive counseling and provide optimal medical management of complications such as hypocalcemia.

Presentation: No date and time listed
ODP126 THE PREVALENCE OF LATENT IRON DEFICIENCY AND SARCOPENIA IN FREESTYLE WRESTLERS OF THE NATIONAL TEAM OF THE REPUBLIC OF SAKHA (YAKUTIA), RUSSIA
Authors: Grigoriev Nikolay , Kalinchenko Svetlana , Vorslov Leonid , Savvina Nadezhda , Petrova Milana N
Published: November 2022

The assessment of the quantity and quality of muscle mass is extremely important for assessing the current state of the athlete's somatic health. Decreased muscle mass and strength - sarcopenia - is a common cause of reduced athletic performance. The most common cause of sarcopenia, along with decreased levels of N-3 fatty acids and vitamin D, is iron deficiency, which has become a pandemic in the 21st century.

Purpose

To assess the prevalence of latent iron deficiency (LID) in the leading freestyle wrestlers in Yakutia, as well as the strength and endurance of the muscular system, using a questionnaire, available laboratory and instrumental studies.

Materials and Methods

The study included 13 freestyle wrestlers aged 18 to 34 years, members of the national team of the Republic of Sakha (Yakutia) and pupils of the Yakut wrestling school, now competing for other countries. All of them underwent anthropometric studies, measurements of isometric strength using a DK-50 hand dynamometer, questionnaires according to the questionnaire "SMART-diagnosis of iron deficiency", laboratory research: a complete clinical blood test and determination of the ferritin level.

Conclusions

In all 13 studied athletes, the result of "SMART-diagnosis of iron deficiency" score was more than 10 points, which is a clinical manifestation of iron deficiency, confirmed by laboratory examination (impaired erythrocyte quality (MCV, MCH, MCHC) and low ferritin levels). A decrease in the iron reserve in athletes leads to a decrease in physical performance, the gas gradients of oxygen and carbon dioxide in the blood change, and these, in turn, leads to "overtraining" and overstrain, and limits the athlete's ability to achieve high sports results and recovery. LID negatively affects the quality of muscle tissue. This is expressed by a decrease in muscle strength and endurance with carpal dynamometry. Changes of the traditional nutrition among the peoples of the North, strenuous exercise among freestyle wrestlers, as well as periodic dietary restrictions for weight loss before competitions and the lack of adequate correction and control of the iron status lead to the development of iron deficiency and a decrease of physical strength

Presentation: No date and time listed
ODP127 Trabecular Bone Score and Advanced Glycation End Products In Adults with Type 1 Diabetes
Authors: Coll Julie-Catherine , Garceau Élodie , Leslie William D , Michou Laëtitia , John Weisnagel S , Mac-Way Fabrice , Morin Suzanne N , Rabasa-Lhoret Rémi , Gagnon Claudia
Published: November 2022

Background

Individuals with type 1 diabetes (T1D) have a two- to threefold increase in fracture risk at any site, and up to a sevenfold increase in hip fracture risk compared to those without diabetes. Reduced bone quality appears to contribute to the increased fracture risk observed in this population. Advanced glycation end products (AGEs) tissue accumulation, which reflects long-term glycemic control, may influence bone quality in T1D.

Objective

We aimed to determine if skin AGEs, as a surrogate marker for bone AGEs, are associated with vertebral trabecular bone score (TBS),anindex of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images and evaluating bone quality.

Methods

We present preliminary data from subjects with T1D who participated in a cross-sectional study aiming at comparing the prevalence of vertebral fractures between adult subjects with T1D from two tertiary care centers and age-, sex- and BMI-matched controls without diabetes. TBS and bone mineral density (BMD) were assessed using DXA. Skin AGEs were measured by skin autofluorescence. Simple and multiple linear regression analyses were used to explore the factors associated with TBS.

Results

One hundred and six subjects with T1D (52.8% women; mean age 42.7±14.7 years; mean BMI 26.9±5.6 kg/m 2; mean diabetes duration 27.6±12.3 years; 48.1% with a microvascular complication; mean HbA 1C in the preceding 3 years 7.5±0.9%; mean skin AGEs 2.15±0.54 units; mean TBS 1.428±0.113) were included. Higher skin AGEs were associated with a lower TBS in simple regression analysis (p=0. 012). In multiple linear regression, older age, male sex, higher BMI, current smoking, higher serum calcium, lower lumbar spine and femoral neck BMD, but not skin AGEs, were significantly associated with a lower TBS (model adjusted R 2 =0.65).

Conclusion

In this population with relatively well-controlled T1D, skin AGEs were not independently associated with TBS.

Presentation: No date and time listed