bluuebunny/crossref_metadata_2025 huggingface dataset:
PSUN113 Evaluating The Efficacy Of Anti-Obesity Medications In a Multidisciplinary Weight Management Clinic At a VA Medical Center
Authors: Goettemoeller Travis , Mazhar Hiba , Chippior Jessica , Rajpal Aman
Published: November 2022

Objective

Anti-obesity medications have been shown to be effective in multiple randomized clinical trials, but there is limited data on the efficacy of these medications in the veteran population. This study was aimed to evaluate the effectiveness of anti-obesity medications in a multidisciplinary weight management clinic at our VA medical center.

Methods

This was a retrospective, descriptive study of 98 patients seen in a multidisciplinary weight management clinic at our VA medical center between January 1, 2019 and October 31, 2021. General requirements to be seen in the clinic were a BMI >30 or BMI >27 with comorbid conditions. Patients seen at least twice in the clinic were included in the study. Patients who received anti-obesity medications (phentermine-topiramate, naltrexone-bupropion, or GLP-1 receptor agonist (liraglutide or semaglutide)) had weights recorded at medication start date and at 2-4 months, 4-8 months, 8-10 months, and 10-14 months intervals. Baseline BMI, HbA1c, LDL-C and triglycerides were recorded at the medication start and followed up at similar intervals.

Results

There were 98 participants (56% males) within this study, with mean age of 54.9 years, mean baseline weight of 127.3 kg, and BMI of 43.5. Of all 98 patients seen in the clinic (regardless of being on anti-obesity medicine), 85 experienced some weight loss with 39 losing at least 5% of their body weight. The average weight loss from first to last visit was 4.1%. There were 72 patients who received anti-obesity medications for at least 3 consecutive months, including 12 patients who were subsequently trialed on a second class of anti-obesity medication. There were 35 trials of Qsymia, 43 trials of GLP-1 receptor agonists, and 6 trials of naltrexone-bupropion. For those patients receiving medications, average weight loss at 2-4 months was 3.7% (N=73), 4-8 months was 4.9% (N=58), 8-10 months was 6.0% (N=32), and 10-14 months was 5.5% (N=29). The percentage of patients able to lose at least 5.0% of their weight was 30.1% at 2-4 months, 43.1% at 4-8 months, 68.8% at 8-10 months, and 51.7% at 10-14 months. There was a decrease noted in HbA1c and LDL-C at all time periods, while there was no change in triglycerides.

Conclusion

Our data shows the effectiveness of anti-obesity medications in a veteran population seen in a multidisciplinary weight management clinic, though to a lesser extent as compared to clinical trials. Given the higher prevalence of multiple chronic conditions seen in veterans when compared to the general population, these patients have additional challenges when trying to achieve their weight loss goals. Further study must be performed to determine the long-term effectiveness and tolerability of these medications in this population. The differential effects among the anti-obesity medications should also be investigated further.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN121 Nonalcoholic Steatohepatitis (NASH), Race/Ethnicity, and Gender in Adult US Population of NHANES 17-18
Authors: Friedman Theodore , Shaheen Magda , Schrode Katrina , Kermah Dulcie , Zarrinpar Ali , Puri Vishwajeet , Najjar Sonia
Published: November 2022

Nonalcoholic steatohepatitis (NASH) is a more severe form of non-alcoholic liver disease (NAFLD) that is characterized by inflammation and liver damage. Previous studies have identified a strong association between NAFLD and race/ethnicity, but there has been less investigation of a racial disparity specifically in NASH. We tested the association between NASH and race/ethnicity in the adult US population of NHANES 17-18 (n=5492). Hepatic steatosis (HS) was diagnosed by FibroScan® using controlled attenuation parameter (CAP) values (stages): S0 <238, S1 (mild)=238-259, S2 (moderate)=260-290, S3 (severe) >290. Participants with moderate/severe steatosis without the exclusion criteria (elevated transferrin level >50%, chronic hepatitis B, chronic hepatitis C, excessive alcohol use, or prescription medications that might cause HS) were considered to have NAFLD (n=3,292). Subjects with NAFLD and a HAIR score (defined by HOMA-IR, hypertension, and ALT) of ≥ 2 were considered to have NASH, as opposed to simple NAFLD. Data were analyzed using Chi square and multinomial regression adjusting for the other independent variables [demographics: (age, gender, education, poverty), physical activity, smoking, waist-hip ratio, body mass index, triglyceride, cholesterol, glucose, HbA1c, C-reactive protein (hsCRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and healthy eating index (HEI)] using SAS (Release V.9.1.3, 2002; SAS) and including sample weights and design. The overall prevalence of NASH was 7.6% and it varied by race/ethnicity. Mexican Americans had the highest prevalence (10.6%), followed by other Hispanics (9.1%); Non-Hispanic Whites had the lowest prevalence (6.8%) (p<0.05). Females had lower prevalence (4.8%) than males (10.4%) (p<0.05). Among males, Mexican Americans had the highest prevalence (14.3%), followed by Blacks (11.3%), and other race had the lowest prevalence (7.7%). In the overall adjusted model, Blacks had lower odds of NASH relative to Non-Hispanic Whites [Adjusted Odds Ratio (AOR)=0.4, 95% confidence interval (CI)=0.3-0.6, p<0.05)]. Although Mexican Americans had higher odds of NASH relative to Non-Hispanic Whites, it was not statistically significant (AOR=1.9, 95%CI=0.9-3.9, p=0.09). Among males and females, there was no statistical association between NASH and race/ethnicity (p>0.05). We concluded that the prevalence of NASH was highest among Mexican American males relative to the other groups. Targeted interventions for Mexican American males are needed to increase awareness, management and prevention related to NASH.

Grants: R01MD012579, R24DA017298, U54MD007598, S21MD000103, UL1TR001881

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF36 | PSUN79 Prolonged Stimulation of β-Adrenergic Receptors in Human Brown and White Adipocytes Increases and then Decreases Metabolic Activity
Authors: Katz Jacqueline M , Pierce Anne E , Zhu Alexander R , Cero Cheryl , Cypess Aaron M
Published: November 2022

Background

Obesity results from excess adipose triglyceride storage and leads to multiple life-threatening complications that may be amenable to novel pharmacological therapies. Both human white and brown adipocytes express β1-, β2-, and β3-adrenergic receptors (β-AR's), and stimulation of each activates converging signaling pathways that regulate essential metabolic and cellular functions. Clinical data indicate that acute and chronic stimulation of the β3-AR with the selective agonist mirabegron increases lipolysis and thermogenesis, thereby making β3-AR activation a promising target to improve obesity-related metabolic disease.

Purpose

In this study, we evaluated in vitro the short-term and prolonged activation of β3-ARs via mirabegron and compared the effects to the activation of β1- and β2-AR.

Methods

Functional cellular assays such as lipolysis and cellular respiration, were measured in immortalized human white (hWA) and brown (hBA) adipocytes derived from the superficial and deep neck depots, respectively. Cells were treated for 6 h (short-term) and 24 h (prolonged) with mirabegron (β3-AR agonist), dobutamine (β1-AR agonist), terbutaline (β2-AR agonist) and isoproterenol (non-selective β-AR agonist). One-way ANOVA was used for statistical analysis.

Findings

In hWA, only short-term activation of the β2-AR induced lipolysis (1.8-fold increase, P=0.0002), while in hBA, both the β2-AR (1.5-fold increase, P=0.04) and β3-AR (1.6 fold increase, P=0.002) increased lipolysis with 6h treatment, as compared to the vehicle. By 24h, lipolysis was blunted in both cell types, likely due to agonist-induced desensitization and downregulation. Distinct from the lipolytic effects ofβ-AR activation, the basal oxygen consumption rate (OCR) was not significantly different among hBA and hWA treated acutely and chronically with each of the three selective β-ARs and positive control isoproterenol. However, in hBA only, prolonged activation of all three β-AR's lowered maximal mitochondrial respiration (isoproterenol: 25% decrease, P=0.0004; dobutamine: 25% decrease, P=0.0003; terbutaline: 26% decrease, P=0.0004; mirabegron: 38% decrease, P<0.0001, respectively). No significant changes in OCR parameters were detected in hWA.

Conclusion

In hBA, acute stimulation of either the β2-AR or β3-AR induces lipolysis. Prolonged exposure to β-agonists comparably lowers maximal cellular respiration, suggesting that all β-AR's are subject to agonist-induced desensitization. Moreover, continuous activation of lipolysis may deplete the intracellular fatty acid pool necessary for mitochondrial oxidative respiration. These responses will need to be addressed before novel adrenergic activators can be utilized to reduce triglyceride stores and treat obesity-related metabolic disease.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:00 p.m. - 1:05 p.m.
PSAT038 A Case of Spontaneous Atraumatic Unilateral Adrenal Hemorrhage
Authors: Bilbatua Martha , Amori Renee
Published: November 2022

Background

Adrenal hemorrhage is a rare disorder with an incidence of 0.1 to 1% for which a cause is identified in most cases. It is usually classified as traumatic or atraumatic, unilateral or bilateral and can result in serious consequences such as adrenal crisis and death if not diagnosed and treated properly. We describe a patient with an atraumatic unilateral adrenal hemorrhage without a known coagulopathy Case presentation: A 51-year-old man with history of COPD and Reynaud's phenomenon presented to the hospital for severe right upper quadrant pain. CT of the abdomen demonstrated a right adrenal hemorrhage of 5.2×4.0×2.6 cm in size, for which Endocrinology was consulted. The patient denied recent trauma or anticoagulation use. Physical examination exhibited generalized abdominal tenderness, without hypotension, or symptoms of acute adrenal insufficiency. Biochemical evaluation showed an AM Cortisol level of 14.3 ug/dL (4.2 - 22.4 ug/dL) and ACTH 67.1 pg/mL (7.2 - 63.3 pg/mL). MRI abdomen showed a decrease in size of the hemorrhage measuring 3.1×1.7×5.2 cm. He was referred to Hematology/Oncology to evaluate for coagulopathy which was unrevealing. About one month from hospital discharge, the patient reported voice hoarseness and was diagnosed with moderately differentiated keratinizing squamous cell carcinoma of larynx. Ten months later PET-CT scan showed hypermetabolic laryngeal mass with bilateral cervical lymphadenopathy without evidence of adrenal gland metastasis with resolution of adrenal hemorrhage, indicative that the hemorrhagic episode is unrelated to this newly diagnosed malignancy.

Discussion

Adrenal hemorrhage is a rare disorder that overall is associated with a 10-20% mortality rate, it is usually classified as traumatic and no traumatic. Most times it is caused by secondary disorders such as trauma, surgery, anticoagulants, infections, but in rare instances is idiopathic. Clinical manifestations of adrenal hemorrhages vary depending on extension of the hemorrhage and early diagnosis is crucial for better outcomes. As per current guidelines, assessment for adrenal insufficiency including hemodynamics, biochemical evaluation and imaging is paramount. To date, clear etiology of primary adrenal hemorrhage is lacking. This case demonstrated an unusual presentation of idiopathic unilateral adrenal hemorrhage without evidence of adrenal insufficiency.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF21 | PSAT78 The beta3-Adrenergic Receptor as a Target for the Prevention of Glucocorticoid-induced Adipose Tissue Dysfunction in Rodents
Authors: Gado Manuel , Heinrich Annett , Wiedersich Denise , Bornstein Stefan R , Rauner Martina , Hofbauer Lorenz C , Henneicke Holger
Published: November 2022

Glucocorticoids (GC) are an integral part of anti-inflammatory therapy. However, their therapeutic effectiveness is limited by their deleterious adverse effects such as the development of obesity, diabetes, and cardiometabolic disease. GC-induced obesity arises from excessive fat accumulation in white adipose tissue (WAT) as well as suppressed thermogenic function of brown adipose tissue (BAT). The sympathetic nervous system (SNS) plays a key role in the regulation of both WAT as well as BAT biology. As part of this project, we investigate the interaction between SNS and GC signaling in the adipose organ.

To that end, we modulated the SNS activity in adipose tissues of mice by altering the housing temperature of corticosterone-treated mice and respective controls to either 29°C, 22°C, or 13°C. Following the four-week treatment course, GC-treated mice housed at 29°C and 22°C gained more weight and accumulated more visceral and subcutaneous white fat than their temperature-matched controls. Interestingly, maintaining mice in the 13°C environment protected animals from GC-induced weight gain and obesity. Additionally, cold adaptation effectively prevented the development of GC-driven hyperglycemia, hyperinsulinemia and hyperleptinemia, all of which were readily observed at 29°C and 22°C. Furthermore, the sympathetic innervation as well as the thermogenic capacity of BAT were preserved in cold-acclimated mice in spite of corticosterone treatment, whereas mice housed at higher temperatures showed marked suppression of the thermogenic function in BAT following GC exposure. To further test whether sympathetic activation is responsible for the prevention of GC-induced dysmetabolism by prolonged adaption to cold, we investigated the effect of a pharmacological β3-AR agonist, CL316,243 during GC excess. Similar to cold exposure, selective activation of the β3-AR not only averted the development of GC-induced fat accumulation and hyperinsulinemia, but also preserved the thermogenic capacity in BAT despite exposure to supra-physiological levels of corticosterone.

Taken together, our data indicate that both cold-acclimation as well as β3-AR activation counteract GC-induced obesity, adipose tissues dysfunction, and related metabolic comorbidities. Thus, targeting the β3-AR may represent a potential therapeutic approach to alleviate GC-induced metabolic abnormalities.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 12:42 p.m. - 12:47 p.m.
LBODP022 A Rare Case Of Hypercalcemia: Mycobacterium Avium Complex Induced Hypercalcemia
Authors: Aluko Oluwatomisin A , Akinbamijo Kasopefoluwa , Malmberg Ifeoluwa , SYEED M E H M O O D A , Rather Manzoor
Published: November 2022

Background

Primary hyperparathyroidism and malignancy accounts for 90% of cases of hypercalcemia. Other causes of hypercalcemia are granulomatous diseases of which tuberculosis and sarcoidosis account for most. We report on a patient with acquired immunodeficiency syndrome (AIDS) presenting with new-onset hypercalcemia secondary to mycobacterium avium complex (MAC) infection.

Clinical Case

A 36-year-old man diagnosed with HIV-1/AIDS on ART presented to the hospital 3 months after initial diagnosis with worsening abdominal pain, nausea and vomiting, cough, weight loss and night sweats. He had presented to an outside facility with similar complaints, he had EGD done, was started on Augmentin and Azithromycin, and was awaiting biopsy results. On arrival he was afebrile and without palpable lymphadenopathy. He was found to have a high serum calcium (12.4 mg/dL, n 8.6-10.2 mg/dL) and acute kidney injury (AKI) (creatinine 1.7 mg/dL, n 0.6-1.3 mg/dL). His CD4 count had increased from 17 at time of diagnosis to 80 cells/μL (n 443-1,471 cells/μL). Workup for hypercalcemia revealed an elevated phosphorus (5.2 mg/dL, n 2.5-5. 0 mg/dL), low PTH (<1 pg/mL, n 12-88 pg/mL), elevated 1,25 Vit D level (112 pg/ml, n 20- 79 pg/ml), low PTHrP (8 pg/ml, n 14-27 pg/ml). TSH was mildly elevated (8 uIU/ml, n 0.35-5.50 uIU/ml) with normal free T4 levels. CT scan done on admission revealed bulky retroperitoneal and mesenteric root adenopathy with hepatosplenomegaly initially concerning for lymphoma. Patient was started on intravenous hydration and bisphosphonate was administered. He underwent laparoscopic lymph node biopsy and bronchoscopy with pathology report showing numerous acid-fast organisms, negative for malignancy. AFB culture was positive for MAC. Prednisone was started after biopsy with improvement in serum calcium (calcium 9.4 mg/dL). He was treated with Azithromycin and Ethambutol and discharged home a week after.

Conclusion

Granulomatous diseases like MAC, an AIDS-defining illness, cause hypercalcemia via activation of macrophages which express extrarenal 1- alpha -hydroxylase. It converts vitamin D to its active form 1,25(OH)2 vitamin D causing its excess, leading to hypercalcemia. Other potential causes of hypercalcemia such as malignancy must be ruled out as seen in our patient who had classic B symptoms with imaging suggestive of lymphoma. Treatment of hypercalcemia in granulomatous disease is aimed at treatment of the underlying disorder. It responds well to glucocorticoids and bisphosphonates.

Presentation: No date and time listed
LBODP023 Popular Supplements Containing Plant Extracts With High Biotin Content Can Severely Impact Parathyroid Hormone (PTH) Measurements Leading To A False Suspicion Of Primary Hyperparathyroidism (PHP).
Authors: Wozniak Zofia , Seroczynska Barbara
Published: November 2022

Introduction

Biotin interference has been recognised as an important factor to take into consideration when analysing discrepancies in laboratory test results of hormone measurements in a 2020 AACC guideline. 1 Little attention has been given yet to possible interference with compound supplements including plant extracts with high biotin content.

Clinical Case

A 64 year old woman has been observed in the outpatient clinic for hypothyroidism and Cushing syndrome resolved with adrenalectomy. Routine laboratory check monitoring vitamine D supplementation revealed parathyroid hormone (PTH) elevation- 138 pg/ml with slightly depressed vitamin D level- 24 ng/ml and calcium and phosphorus within normal limits (Ca- 9.3 mg/dl, Pi-2.88 mg/dl). Vitamin D supplementation has been elevated to 4000 IU per day and the PTH and vitamin D levels re-checked after 3 months. Vitamin D was still deficient- 27 ng/ml, PTH was 129 pg/ml. Two months later the patient was hospitalised to evaluate her post-cushing status and the results of Ca, Pi, PTH and vitamin D were reported to be within the normal ranges. Suspecting biotin interference the patient was advised to re- check the PTH levels in two different laboratories and the results differed significantly and were: 72 pg/ml checked with ECLIA method and 137 pg/ml for CMIA method. Suspecting biotin interference patient's history was re-evaluated for supplements and a compound supplement has been identified containing high quantities of pumpkin seed extract (260 mg/capsule) which contains substantial quantities of biotin. Identification of this confounding factor spared the patient further diagnostic procedures.

Conclusion

It is useful to consider other non-obvious sources of biotin in the form of compound supplements and plant extracts when encountering conflicting results of hormone measurements.1. AAC Guidance Document on Biotin Interference in Laboratory Tests. Journal of Applied Laboratory Medicine, 2020 May 1;5(3): 575-587.

Presentation: No date and time listed
LBSAT145 Localizing The "Difficult" Parathyroid Tumor
Authors: Graf Akua , Cochran Craig , Abijo Tomilowo , Sadowski Samira Mercedes , Nilubol Naris , Simonds William F , Weinstein Lee Scott , Chang Richard , Jha Smita
Published: November 2022

Background

The identification of parathyroid tumor(s) in patients with persistent/recurrent primary hyperparathyroidism (PHPT) is critical for a successful re-operative surgery. We describe our experience with invasive studies for parathyroid tumor localization and provide follow-up data regarding our experience with selective arterial hypocalcemic stimulation with central venous sampling (SAHSCVS).

Methods

We identified patients who underwent pre-operative invasive testing for localization of parathyroid tumor at our center. At our center, only PHPT patients with history of prior neck surgery without definitive findings on non-invasive testing (sestamibi, ultrasound, CT, MRI) proceed to invasive studies. The result of each invasive localization study (arteriogram, SAHSCVS and selective venous sampling (SVS)) was categorized as true-positive (TP), false-positive (FP) and false-negative (FN) based on biochemical outcome.

Results

Ninety-five patients with 98 tumors underwent invasive testing for parathyroid tumor localization. All but one had recurrent disease. Sixty-two patients (65%) had "apparently sporadic" PHPT, 19/95 (20%) had MEN1, three had parathyroid cancer (PC) and the remaining had other heritable forms of PHPT. Median age of index PHPT presentation was 47 [34-58] years. Of 87 tumors with available operative details, 66 (76%) were in the neck, 20 in the mediastinum (23%), and one in the forearm at site of prior autograft. Seventy-two (83%) showed hyperplasia or hypercellularity on histology. Median tumor size was 5 mm. Arteriogram, SAHSCVS and SVS accurately localized the tumor in 47/90 (52%), 54/90 (60%) and 49/61 (80%) tumors respectively. Positive Predictive Value of arteriogram, SAHSCVS and SVS was 47/50 (94%), 55/64 (86%) and 49/59 (83%) respectively. Both sensitivity and PPV showed no significant difference between patients with MEN1+PC vs. others. Among the 54 tumors accurately localized by SAHSCVS, SVS was performed in 29/54 with complete concordance. Twenty-seven tumors (30%) were missed (FN) on SAHSCVS, of these 14/25 (56%) were also missed on arteriogram. Nevertheless, 16/20 (80%) localized accurately on subsequent SVS. SAHSCVS was FP in localizing nine tumors - seven (78%) of these did not show a blush on arteriogram. All pre-operative localizing studies were unrevealing in 9/98 presentations (10%).

Conclusion

Patients with difficult to localize parathyroid tumors have clinical features suspicious for germline-predisposition forms of PHPT indicated by recurrent disease, hyperplastic glands, and age of index presentation. SAHSCVS can be a useful adjunct in patients who require invasive localization. 90% of these tumors are localized with combination of current non-invasive and invasive testing. AcknowledgementThis research is supported by the Intramural Research Program of NIDDK, NCI and NIH Clinical Center.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
LBSAT229 Extended-release Calcifediol Effectively Raised 25-hydroxyvitamin D In CKD Despite Obesity
Authors: Strugnell Stephen A , Ashfaq Akhtar , Bishop Charles W
Published: November 2022

Inadequate levels of serum total 25-hydroxyvitamin D (25D) in chronic kidney disease (CKD) are associated with an increased risk of secondary hyperparathyroidism (SHPT). Serum 25D can be difficult to raise sufficiently with vitamin D supplements (cholecalciferol or ergocalciferol) to effectively lower elevated parathyroid hormone (PTH) levels especially in overweight patients. Obesity is common in CKD and requires attention when vitamin D repletion is considered. Vitamin D supplements are fat-soluble molecules which accumulate in adipose tissue. They have low affinity for serum vitamin D binding protein and are poorly mobilized from adipose tissue into circulation for hepatic activation. Recent studies suggest that serum 25D levels of ≥50 ng/mL are necessary to produce significant PTH reductions in nondialysis patients. Data were analyzed from two identical randomized clinical trials investigating the efficacy and safety of treating adult nondialysis patients with extended-release calcifediol (ERC; n=285) or placebo (n=144) to see if ERC raised 25D to at least 50 ng/mL in all body weight categories, with subgroup analyses by race, gender and age. On enrollment, subjects had eGFR of ≥15 and <60 mL/min/1.73 m2, PTH ≥85 and <500 pg/mL, serum 25D ≥10 and <30 ng/mL, corrected serum calcium ≥8.4 and <9.8, serum phosphorus ≥2. 0 and <5. 0, absence of nephrotic range proteinuria (>3 mg/mg creatinine) and no history of parathyroidectomy or renal transplantation. These subjects had mean (SD) age of 65.4 (10.9) years, serum 25D at baseline of 19.6 (5.4) ng/mL, body weight of 97.8 (24.3) kg and BMI of 34.7 (7.9) kg/m2. Fifty percent were male, 64. 0% White, 32.9% African-American or Black, and 3.1% Other, and 20% were Hispanic. A total of 356 subjects completed a 20- to 26-week treatment period per-protocol and were included in the analysis. Enrolled subjects ingested a 30 mcg capsule of ERC (OPKO Pharmaceuticals, Miami) daily for 12 weeks followed by one or two capsules (30 or 60 mcg) daily for a 14 more weeks. Control subjects received matching placebo. Mean (SD) serum 25D remained unchanged with placebo treatment but rose progressively with ERC treatment to 67.1 (21.6) ng/mL (mean of weeks 20-26). The observed increases in serum 25D were inversely related to body weight but exceeded 50 ng/mL in all body weight categories, irrespective of race (White vs. African-American or black), gender or age (<70 vs. ≥70 years). Side effects observed at these levels were similar to placebo. These data showed that ERC successfully raised mean serum 25D to at least 50 ng/mL irrespective of body weight, race, gender or age.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP125 Soft Bones in Crohn's: Tumor-induced osteomalacia and inflammatory bowel disease
Authors: Habbsa Samima , Farhan Hisham , Thomas Afton , George Lauren , Hu Yinin , Whitlatch Hilary
Published: November 2022

Introduction

Bone loss is common in patients with inflammatory bowel disease (IBD) and is usually attributed to Vitamin D malabsorption, treatment with glucocorticoids or chronic inflammation. We report a case of bone loss, hypophosphatemia, and atypical fractures in a patient with IBD who was ultimately diagnosed with tumor-induced osteomalacia (TIO), a rare paraneoplastic syndrome of chronic hypophosphatemia and impaired vitamin D metabolism.

Clinical Case

A 39-year-old male presented for evaluation of low bone density, hypophosphatemia, and multiple stress fractures. His medical history includes Crohn's disease in biochemical remission on adalimumab and bilateral hip avascular necrosis. There was no history of significant steroid use or known family history of metabolic bone disease. He was previously highly active as a modern dancer. Over the course of 3 years, he developed progressive diffuse bony pain and he became wheelchair-bound. A whole body bone scan visualized multiple age-indeterminate atraumatic fractures, including bilateral metatarsal fractures and numerous rib fractures. Dual energy x-ray absorptiometry showed significantly low bone mass for age (Z-scores –3.4, -3.1, -3.7 at the L1-L4 spine, total right femur and right femoral neck, respectively). Physical exam was notable for a soft, subcutaneous 8 cm mass posterior to the left paraspinal muscle at the level of T12, which had previously been diagnosed as a lipoma. Laboratory evaluation revealed phosphorus 1 mg/dL (2.5-4.5 mg/dL), calcium 9.1 mg/dL (8.6-10.2 mg/dL), PTH 35 pg/mL (15-65 pg/mL), c-telopeptide 592 pg/mL (38-724 pg/mL), bone specific alkaline phosphatase 114.5 mcg/L (4-27 mcg/L), vitamin D-1,25 8.9 pg/mL (19.9-79.3 pg/mL), and vitamin D-25 34 ng/mL (normal >30 ng/mL). Fibroblast growth factor-23 (FGF-23) level was 1200 RU/mL (44-215 RU/mL), consistent with TIO. Thyroid function, dexamethasone suppression test, testosterone and IGF-1 were normal. Ga-DOTATATE PET scan demonstrated that the paraspinal soft tissue mass was strongly somatostatin avid. The patient was treated with oral calcitriol and phosphate replacement. He underwent a biopsy of the left paraspinal mass, which was consistent with a bland epithelioid and spindle cell neoplasm, most suggestive of a phosphaturic mesenchymal tumor. He is scheduled for a radical resection of the soft tissue mass.

Conclusion

To date, there are no published case reports of TIO with coexisting IBD. Inflammatory cytokines, such as tumor necrosis factor alpha, have been shown to positively correlate with FGF-23 levels, and FGF-23 has been documented to be elevated during IBD flares. Given this, the presence of IBD may portend a worsened metabolic bone prognosis in patients who simultaneously develop FGF-23 secreting tumors.

Presentation: No date and time listed
ODP129 Variation in 25(OH)D Levels, Measurement Methods and Prevalence of Vitamin D Deficiency: a Systematic Review and Meta-analysis
Authors: Premaor Melissa , Fernandes Maira , Campos Fernanda , Brondani Juliana , Comim Fabio
Published: November 2022

Vitamin D deficiency is a common disease with high morbidity. Although, there are several studies evaluating its prevalence in different Brazilian regions, its actual prevalence it not known. Furthermore, some research suggests that serum levels of 25-hydroxyvitamin D [25(OH)D] may vary according to the measurement technique. This variation may affect the results of the prevalence of vitamin D deficiency in Brazil, given that its diagnosis is made by measuring 25(OH)D, regardless of the technique used. Our study aimed to investigate whether 25(OH)D values vary according to the 25(OH)D measurement technique in Brazil. Therefore, a systematic review including controlled clinical trials, cohort studies, cross-sectional studies, and case-control studies was performed. Studies that included all participants with some underlying pathology were excluded. The bibliographic search was carried out in PubMed, BIREME, and EMBASE databases. Two protocol members independently performed the selection and extraction of data from the studies. A third member reviewed this selection and extraction. In total, 1,166 studies were found, of which 122 had their full texts evaluated, 34 studies evaluated the serum levels of 25(OH)D, and described the technique used to measure this hormone. A total of 356,565 participants with a mean age between 18 and 80 years were included in the analysis. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] and vitamin D insufficiency [25(OH)D < 30 ng/mL] in Brazil were, respectively, 29.7% (95%CI 25 .6 to 34.1%) and 65.2% (95%CI 62.5 to 87. 0%). Mean serum levels of 25(OH)D varied according to the technique and brand used to measure this hormone. The mean 25(OH)D values according to the technique used: chemiluminescence 25.5 ng/mL (95%CI 24. 0 to 27. 0 ng/mL); ELISA 41 (95%CI 37. 0 to 46.1 ng/ml); HPLC 28.7 ng/ml (95%CI 23.9 to 33.6 ng/ml) and radioimmunoassay 24.5 ng/ml (95%CI 20.2 to 28.8 ng/ml); p<0. 0001. This variation is associated with the heterogeneity of the pooled results of vitamin D prevalence in Brazil. In conclusion, these findings suggest that the prevalence of vitamin D in Brazil may vary according to the measurement technique used. Better standardization of the results of the 25(OH)D measurement assays becomes urgent that we can have a more precise estimate of this problem.

Presentation: No date and time listed
OR13-2 Characterizing the Impact of Burosumab on Bone Health in Children with X-Linked Hypophosphatemia: Results from Year 1 of the Disease Monitoring Program
Authors: Carpenter Thomas , Cassinelli Hamilton , Glorieux Francis , Hetzer Joel , Merritt II J Lawrence , Moreira Carolina A , Portale Anthony , Ward Leanne , Woo Claudine , Imel Erik
Published: November 2022

X-linked hypophosphatemia (XLH) is a rare, heritable disorder wherein excess FGF23 leads to renal phosphate wasting and impaired activation of vitamin D. XLH is characterized by rickets and osteomalacia leading to bone pain, skeletal deformities, and short stature. The XLH Disease Monitoring Program (DMP; NCT03651505) is a prospective, multinational outcomes study of the longitudinal progression of clinical, radiographic, and biochemical features of XLH in children and adults. We assessed the impact of the recombinant human IgG1 monoclonal antibody to FGF23, burosumab, on measures of bone health in children with XLH at Year 1 of the DMP.

As of March 2021, 287 children (<18 years) had completed the Year 1 visit. Participants were grouped by when they first received burosumab: Group 1, prior to DMP enrollment (N=68; mean (SD) age 9.5 (3.6) years); Group 2, during the DMP (N=150; 8.7 (5.0) years); Group 3, never, but receiving conventional therapy (N=69; 8.8 (5.3) years).

Before receiving burosumab, serum phosphorus levels were below normal; after burosumab initiation, serum phosphorus in Groups 1 and 2 rapidly normalized, with sustained improvements up to 3 years of treatment. Serum phosphorus remained low in Group 3. Before burosumab, serum alkaline phosphatase levels were above normal; with continued burosumab therapy, mean levels gradually declined towards normal and were maintained for up to 4 years.

The Radiographic Global Impression of Change (RGI-C) assessed rickets and lower limb deformity from DMP baseline to Year 1, with positive values denoting improvement. Mean (SD) RGI-C rickets global scores were +1.0 (0.9) for Group 1 (n=44), +1.5 (0.7) for Group 2 (n=39), and +0.3 (1.2) for Group 3 (n=3). Lower limb deformity RGI-C scores were +0.3 (0.6) for Group 1 (n=42), +0.4 (0.8) for Group 2 (n=39), and +0.8 (1.1) for Group 3 (n=3). Height Z-score change from DMP baseline at Year 1 was 0.1 (0.3) for Group 1 (n=58), 0.1 (0.4) for Group 2 (n=90), and -0.8 (3.1) for Group 3 (n=18). There were no new safety concerns or reports of hyperphosphatemia.

These real-world data affirm that normalization of serum phosphorus is rapid and sustained following burosumab initiation, resulting in improved serum alkaline phosphatase levels which positively impact bone mineralization. Improvements in rickets, growth, and lower limb deformity occur in the first year of burosumab treatment and continue in those who started burosumab prior to entering the DMP. The absence of new safety concerns or reports of hyperphosphatemia up to 4 years after burosumab initiation is also notable. The 10-year DMP study design will provide understanding of long-term effects in these patients with continued burosumab therapy.

Presentation: Sunday, June 12, 2022 11:15 a.m. - 11:30 a.m.
OR13-4 Bone Mineral Density in Transgender Youth on Gender Affirming Therapies
Authors: Ma Nina , Moreau Kerrie , Nadeau Kristen , Rothman Micol , Nokoff Natalie
Published: November 2022

Background

2% of youth identify as transgender. Many have puberty blocked with gonadotropin-releasing hormone analogues (GnRHa), followed by testosterone (T) or estradiol (E2). Bone mineral density (BMD) effects of these therapies are understudied.

Objective

For youth on GnRHa alone or T or E2 +/- GnRHa, to evaluate: (1) BMD z-scores; (2) BMD z-score differences for those +/-GnRHa; and (3) associations between GnRHa duration and BMD z-score.

Methods

Cross-sectional study of transgender youth (n=56 age 10.4-19.8 years, 53% female sex assigned at birth) undergoing total body dual-energy X-ray absorptiometry (Hologic Discovery A). Data are presented as median and interquartile range, group differences evaluated with Mann Whitney U tests and associations with Spearman correlations.

Results

BMD z-scores on GnRHa alone (n=19) were -0.5 (-1.4, 0.3) using male norms and -0.8 (-1.7, 0.3) using female norms. BMD z-score for transgender males (TM) on T (n=21, 5 with past GnRHa): -0.2 (-0.6, 0.0) using male norms, 0.4 (-0.3, 0.8) using female norms. BMD z-score for transgender females (TF) on E2 (n=16, 6 on current/past GnRHa): -0.4 (-1.2, 0.3) using male norms, -0.2 (-1.0, 0.7) using female norms. TM on T with prior GnRHa had significantly lower BMD z-scores than TM on T alone (p=0.004); but no differences for TF on E2 +/- GnRHa. GnRHa duration was inversely correlated with BMD z-score (male norms: r=-0.5, p=0.005, female norms: r=-0.4, p=0.029). BMD z-score was unrelated to length of T/E2 therapy or sex steroid concentrations.

Conclusions

Longer durations of GnRHa therapy were associated with worse BMD z-scores.

Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.
RF32 | PSUN49 To Repeat or Not to Repeat: The Question of Aldosterone and Renin Variability
Authors: Ng Elisabeth , Gwini StellaMay , Libianto Renata , Choy Kay Weng , Fuller Peter , Shen Jimmy , Yang Jun
Published: November 2022

Plasma aldosterone concentration (PAC), renin levels and aldosterone-renin ratio (ARR) are used to screen for primary aldosteronism (PA). A recent study (Yozamp et al. Hypertension 2021) reported substantial intraindividual variability of PAC and ARR (using plasma renin activity) in the context of usual antihypertensive therapy. The intraindividual variability of PAC and direct renin concentration (DRC), a more widely used measurement of renin, in the absence of interfering medications is unknown but important where a single ARR is used to screen for PA.

The aim of this study was to evaluate the intraindividual variability of PAC, DRC and ARR in a cohort of patients with and without PA. Patients who attended an Endocrine Hypertension Service from May 2017 to July 2021 with at least two ARR measurements off interfering medications were retrospectively evaluated. While the measurements were performed at several hospital and community laboratories, the same analyser was used. PA was confirmed using the seated saline suppression test following an abnormal ARR >70 pmol/L: mU/L. PAC and DRC variability was calculated as coefficient of variation (CV=standard deviation/mean×100) and percent difference (PD=difference between highest and lowest values/mean×100).

A total of 223 patients were analysed (55% female, median age 52 years), including 162 with PA (25% with unilateral disease). Significant variability in both PAC and DRC was observed in the PA group (CV: 24%, 41%; PD: 46%, 76% respectively) and non-PA group (CV: 22%, 40%; PD: 38%, 65% respectively), which was higher than the assays’ analytical variability. The ARR was also highly variable within individuals, in both the PA group (CV: 42%; PD: 74%) and non-PA group (CV: 37%; PD: 61%). Variability was not significantly different between PA subtypes, and persisted irrespective of age, gender and degree of hypertension. Sixty-two patients (39%) with PA could have had a missed diagnosis if the ARR had not been repeated, i.e., had at least one ARR <70 pmol/L: mU/L, while 28 (46%) without PA had at least one abnormal ARR > 70.

Intraindividual variability in PAC, DRC and ARR occurs in a significant number of patients being investigated for PA. These results support the need for at least two ARR on separate occasions before PA is excluded or further investigated.

Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.
LBODP036 A Case of Euglycemic Diabetic Ketoacidosis After Distal Pancreatectomy
Authors: Turner James , Steinberg Helmut O
Published: November 2022

The patient is a 68-year-old female with a past medical history of type 2 diabetes mellitus, pancreatic mass, hypertension, hyperlipidemia, and coronary artery disease who presented to the hospital for elective surgical resection of her pancreatic mass. She underwent robotic-assisted laparoscopic distal pancreatectomy, splenectomy, and gastric wedge resection. Her hospital course was complicated by post-operative bleeding with hemoperitoneum the day after her initial surgery. She returned to the operative room for exploratory laparotomy during which the source of bleeding was identified and repaired. She was transferred to the intensive-care unit for post-operative monitoring. On the fourth day of admission, the patient became markedly acidotic. Her labs revealed a bicarbonate level of 12 mmol/L and a pH of 7.24. Her anion gap was elevated to 17. Endocrinology was consulted for suspected euglycemic diabetic ketoacidosis. Beta-hydroxybutyrate was elevated to 5.10 mmol/L (0 - 0.29 mmol/L). The patient's blood glucose was 159 mg/dL. Of note, the patient does take Empagliflozin at home. This medication has been associated with euglycemic diabetic ketoacidosis; however, she had not received this medication for five days prior to the onset of diabetic ketoacidosis. Glucosuria is expected to return to baseline after discontinuation of Empagliflozin within approximately three days. A urinalysis was checked at the time of consultation, and the patient did have a large amount of glucose in her urine which suggests that Empagliflozin was still acting to produce glucosuria. The patient was treated with intravenous insulin and fluids per the institution's protocol for the management of diabetic ketoacidosis. Her acidosis rapidly improved, and she was transitioned to subcutaneous insulin to manage her diabetes prior to discharge. This is an interesting case of euglycemic diabetic ketoacidosis due to the multifactorial precipitants: the dwindling effect of Empagliflozin five days after discontinuation, the loss pancreatic beta cell mass after distal pancreatectomy, and the stress of multiple surgeries complicated by life-threatening post-operative bleeding.

Presentation: No date and time listed
LBODP038 Metformin-Associated Severe Lactic Acidosis: A Case Study Of The Perfect Storm
Authors: Maki Marwa K , Manivannan Niveditha
Published: November 2022

Background

Metformin carries a rare risk of lactic acidosis. Medications that can increase the concentration of metformin in the serum can increase the risk of lactic acidosis. Similarly, kidney dysfunction leads to decreased clearance of the drug, hence potentiating its adverse effects.

Clinical Case

A 62-year-old male with HIV (undetectable viral load) on dolutegravir, atazanavir/cobicistat, rilpivrine, type 2 DM (A1C 7.2%) on metformin and dulaglutide presented with 1 day history of dyspnea. He had a respiratory rate of 28 and heart rate of 131. Blood glucose was 43 mg/dL (nl 74-99 mg/dL). Labs were also notable for lactate 23.6 mmol/L (nl 0.4-2 mmol/L), severe anion gap metabolic acidosis with pH <6.8, bicarbonate 5 mmol/L (nl 21-32 mmol/L). Creatinine was 2.29 mg/dL (nl 0.5-1.3 mg/dL) with a normal baseline kidney function. Beta-hydroxybutyrate was elevated at 0.73 mmol/L (nl 0. 02-0.27 mmol/L). Osmolar gap was 17.3 mOsm, ethanol level was 22 mg/dL (nl <10 mg/dL), ethylene glycol was not detected. Patient reported drinking four beers daily but endorsed binge drinking the previous night with associated emesis. Review of records showed that the patient was started on dulaglutide recently and he endorsed nausea and diarrhea with initiation of the medication. He otherwise had no changes in his metformin dose or antiretroviral regimen. He was admitted to the ICU for further management of his severe lactic acidosis. Patient's antiretroviral regimen, dulaglutide, and metformin were held on admission. Medical toxicology was consulted, and metformin associated lactic acidosis was suspected. He was initiated on dialysis and his lactic acidosis resolved within 24 hours. His antiretroviral regimen was resumed prior to discharge when his creatinine improved to 1.38 mg/dL. Metformin was discontinued and he was discharged on dulaglutide with endocrinology follow up.

Conclusion

This case demonstrates how multiple factors such as alcohol use, kidney injury, and other medications can increase the, otherwise rare, risk of lactic acidosis in patients taking metformin. The patient had experienced GI losses due to emesis from his increased alcohol intake as well as diarrhea with the initiation of dulaglutide leading to dehydration and acute kidney injury. The latter can give rise to decreased metformin clearance. In addition, dolutegravir increases metformin plasma exposure. Together, the constellation of factors had likely led to increased metformin plasma levels and associated severe lactic acidosis. Patients should be counseled on the use of alcohol while taking metformin. Additionally, drug interactions should be monitored, and dose reductions of metformin should be considered in patients taking dolutegravir.

Presentation: No date and time listed
LBODP045 Correlation Of Acetone Breathing Level In Serum Ketone Bodies Level Of Diabetes Ketoacidosis By Non-invasive Acetone Gas Analysis Device (g-breath) Multicenter Study
Authors: Niramitmahapanya Sathit
Published: November 2022

Background

Diagnosis of ketosis associated with DKA can be difficult due to variability in the metabolic state of DKA patients beta–hydroxybutyrate (BHB) are the main forms of ketone and followed by acetoacetic acid (AcAc) and acetone.

Objective

Find the correlation between breath acetone and serum BHB, AcAc and acetone during treatment duration of DKA.

Materials and Methods

We use metal Oxide Semiconductor (MOS) methods called G-Breath for measurement of exhaled acetone compared with serum BHB, AcAc and acetone level during treatment of DKA, in patients with hyperglycemia and suspected DKA. Exhaled acetone concentration will be represent as two electrical signal parameters breath acetone breath (ppmv) and total volatile organic compound (VOC).

Results

Serum parameters to diagnostic DKA especially ketone metabolites were significant higher in DKA group when compared with hyperglycemic group; serum acetone in DKA group was 67.65±79.52 vs 4.20±4.12 mg/L in hyperglycemic group by p value=0. 004, serum BHB in DKA group was11.19±12.96 vs 1.73±1.34 mg/dL in hyperglycemic group by p value=0. 007, serum AcAc was 31.90±16.98 vs 5.87±7.58 µg/mL in hyperglycemic group by p value<0. 001. In breath analytic parameters we found acetone in breath was significant higher DKA group 5.20±1.34 vs 1.18±1.77 in hyperglycemic group with p-value 0. 040. The correlation study acetone in breath was significant to all ketone metabolite of DKA such as serum acetone, The cut of point, sensitivity, specificity and Area under the Curve (AUC) we found serum acetone was the best test for diagnosis DKA with 100% sensitivity, 99.93% specificity AUC=0.987 with p<0. 001. The breath acetone for diagnosis of DKA at cut of point 2.15, sensitivity 100%, specificity 71.4% (AUC=0.847, p=0. 003) Conclusions: This study shown that acetone measurement in exhale with non-invasive device call G-breath can be used in part of DKA diagnosis with comfortable and can be warning diabetes for serious emergency condition. Keywords: Breath biomarkers, Breath acetone, Diabetic ketoacidosis, correlation

Presentation: No date and time listed