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7204 An Unexpected Cause of Ga-68 Dotatate PET/CT Somatostatin Receptor Avidity in a Pediatric Patient with Hereditary Paraganglioma-Pheochromocytoma Syndrome due to an SDHA Mutation
Leopold, Kaitlin , Binkovitz, Larry A. , Casas, Luis Domingo Guerra, Lteif, Aida, Polites, Stephanie F. , Casas, Luis

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.1408 Get It

Abstract Disclosure: K. Leopold: None. S. Polites: None. L. Binkovitz: None. L. Casas: None. A.N. Lteif: None. Title: An Unexpected Cause of Ga-68 Dotatate PET/CT Somatostatin Receptor Avidity in a Pediatric Patient with Hereditary Paraganglioma-Pheochromocytoma Syndrome due to an SDHA Mutation. Introduction: Individuals with Succinate Dehydrogenase (SDHx) gene mutations have an increased risk of paragangliomas and pheochromocytomas beginning in childhood.Clinical Case: A 9 year old male with Cornelia de Lange syndrome and a paternally inherited SDHA pathogenic gene variant (c1534C>T) presented with worsening migraine headaches and skin pallor with activity. 24 hour urine fractionated metanephrines were mildly elevated, with metanephrine 122 mcg/24h (29-92 mcg/24 h), normetanephrine 187 mcg/24 h (34-169 mcg/24 h), and total metanephrine 309 mcg/24 h (47-223 mcg/24 h). Ga-68 DOTATATE PET/CT showed a focus of moderately increased radiotracer activity in the anterior aspect of the distal gastric antrum with a max SUV 8.2 corresponding to a 9x7 mm nodule on CT in the same area, suggestive of underlying somatostatin receptor positive lesion such as a paraganglioma. MRI with contrast completed to further characterize the lesion showed no visible mass corresponding to the focal area of radiotracer uptake on DOTATATE PET/CT. Repeat 24 h urine metanephrines continued to show mild elevation of metanephrine (138 mcg/24h), normetanephrine (200 mcg/24h), and total metanephrines (338 mcg/24h). 24 hour urine catecholamines, 5-Hydroxyindoleacetic acid, and homovanillic acid were normal. An upper endoscopic ultrasound was completed which confirmed the presence of a lesion near the stomach but not arising from the stomach wall and not consistent with a gastrointestinal stromal tumor. CT enterography with IV contrast showed a 6x6 mm enhancing mass within the distal right lateral gastric wall. Due to ongoing symptoms, mild elevations in urine fractionated metanephrines, and a clear mass on US and CT, the patient underwent laparoscopic abdominal exploration where a 14x14x13 mm mass with surrounding gastric and duodenal serosa was excised with primary closure of the bowel. Pathology showed ectopic pancreatic tissue in the wall of the small bowel and stomach. Repeat Ga-68 DOTATATE PET/CT 5 months following surgery showed resolution of the distal gastric somatostatin receptor avidity. Clinical Lesson: This is the first case of ectopic pancreatic tissue mimicking a paraganglioma in a pediatric patient with hereditary paraganglioma-pheochromocytoma syndrome. False positive imaging should be considered in patients with SDHx mutations when the uptake is atypical in location and when the elevation in urine metanephrines is mild. Presentation: 6/3/2024
7833 Gestational Diabetes Mellitus (GDM): A Weighted Spectrum of Clinical Outcomes
Moazzami, Mitra , Venkatesan, Nanditha , Rajagopalan, Kamalnath Sankaran, Vella, Adrian , Egan, Aoife M.

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.783 Get It

Abstract Disclosure: M. Moazzami: None. N. Venkatesan: None. K.S. Rajagopalan: None. A.V. Vella: None. A. Egan: None. Gestational diabetes mellitus (GDM) affects approximately 10% of pregnancies, with rates almost doubling in minority subgroups. Higher body mass index (BMI) is a significant GDM risk factor, and BMI ≥ 25kg/m2 is often used as a criterion in risk factor-based screening programs. However, up to 60% of individuals with GDM have a normal BMI, and it is unclear if this offers protection against associated adverse outcomes. Furthermore, many prior studies fail to address the fact that those of Asian descent require a lower BMI cut-off, given their different distribution of body fat. Our study evaluated GDM pregnancy outcomes using BMI as a risk indicator. We compared individuals with BMIs < 25 kg/m2, 25-30 kg/m2, and > 30 kg/m2. For individuals that self-identified as Asian, we adjusted BMI categories: <23 kg/m2 for normal weight, 23-30 kg/m2 for overweight, and >30 kg/m2 for obese. We identified 2212 subjects diagnosed with GDM via universal screening and Carpenter and Coustan criteria at our institution from 2018 - 22. In total, 508 (23.0%) were normal weight, 611 (27.6%) overweight, and 1093 (49.4%) obese. The average maternal age was 31 years. Higher proportions identified as Hispanic and non-White race in overweight and obese categories. Maternal adverse outcomes were higher in obese compared to overweight or normal BMI categories (cesarian delivery: normal 26.7 v overweight 28.3 v obese 22.7%, p<0.001; hypertensive disorders: normal 13.2 v overweight 12.5 v obese 22.7%, p <0.001). Pharmacological therapy was required in 50% with obesity versus 24.8% in normal, and 28.7% in overweight categories (p<0.001). While there were no differences in live birth rates across categories, infants born to mothers with obesity had a higher birthweight (normal 3.30 v overweight 3.38 v obese 3.45kg, p<0.001) and were more likely to have neonatal hypoglycemia (normal 28.7 v overweight 25.5 v obese 43.8%, p<0.001) and require intensive care unit admission (normal 8.4 v overweight 5.5 v obese 12.7%, p<0.001). Attendance at postpartum glucose testing varied across BMI categories with lower attendance in mothers with obesity followed by normal weight BMI (normal 40.75 v overweight 45.99 v obese 36.2%, p<0.001). Compared to overweight individuals, those with normal weight exhibited higher rates of postpartum glucose intolerance (12.4 v 6.9%, p =0.002). However, those with obesity had the highest rates of glucose intolerance (20.7%, p<0.0002). Individuals with normal weight had the highest rates of breastfeeding (normal 95.9 v overweight 92.8 v obese 91.4% p=0.006). This study highlights the nuanced relationship between BMI and pregnancy outcomes in GDM. While maternal obesity was associated with the poorest outcomes, those with normal BMI were not protected compared to overweight individuals, and experience higher rates of postpartum glucose intolerance. Presentation: 6/2/2024
6422 Identifying Predictive Symptoms Of Adrenal Insufficiency
Han, Ashley J , Achenbach, Sara J., Atkinson, Beth, Bancos, Irina

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.209 Get It

Abstract Disclosure: A.J. Han: None. S.J. Achenbach: None. B.J. Atkinson: None. I. Bancos: None. Background: Diagnosis of adrenal insufficiency (AI) is often delayed due to its vague and non-specific symptomatology. As classic symptoms of AI such as fatigue and nausea are prevalent in the general population, identifying clinical features that are more specific to AI may help clinicians determine which patients require additional testing. Methods: A single-center retrospective study was performed of patients who underwent outpatient Cosyntropin stimulation testing (CST) between 2005-2018. Patients with oral glucocorticoid or estrogen use within 2 months of CST, and patients without available Current Visit Information (CVI) form at the time of CST were excluded. Presence of symptoms was obtained from CVI, and laboratory findings were electronically extracted. Adrenal insufficiency was defined as post-CST peak cortisol <18 mcg/dL. Morbidity was assessed using the Elixhauser index. Variables for multivariable analysis were defined a priori and included fatigue, dizziness, muscle pain, joint pain, weight loss >10 pounds, abdominal pain, nausea/vomiting, and hyponatremia. Results: Among 5347 patients who underwent CST, 376 (7.0%) of patients were found to have AI. There were no sex differences between patients with and without AI, however patients with AI were slightly older (median age 48.9 vs 47.1 years, p=0.026), and had a higher median BMI (26.5 vs 25.6 kg/m2, p=0.002). Prevalence of comorbidities was similar between the two groups, with a median Elixhauser index of 1 (IQR 1-3), however, patients with AI were more likely to report difficulties with activities of daily living (69% vs 57%, p<0.001). Hyponatremia was diagnosed in 4% of patients with AI and 3% of those without AI, p=0.208. Although patients in our cohort reported a high prevalence of fatigue (79%), dizziness (50%), joint pain (50%), muscle pain (48%), nausea (40%), abdominal pain (39%), and weight loss in the past 6 months (29%), there were no statistically significant differences in reported symptoms between patients with and without AI with the exception of joint pain (59% vs 49%, p<0.001) and muscle pain (54% vs 47%, p=0.009). Based on multivariable analysis, only joint pain (OR 1.51, 95% CI 1.14-1.99) and weight loss >10 pounds in the past 6 months (OR 1.31, 95% CI 1.02-1.68) were associated with higher odds of AI diagnosis. Interestingly, patients who reported fatigue had lower odds of AI diagnosis on CST (OR 0.66, 95% CI 0.49-0.88). Conclusions: Commonly associated symptoms of AI such as fatigue, dizziness, nausea, and abdominal pain were poor predictors of AI diagnosis based on CST. Consequently, the presence of these symptoms alone may not warrant additional testing. Notably, clinical features such as myalgia, arthralgia, and weight loss >10 pounds in the past 6 months were found to be more predictive of AI. Presentation: 6/1/2024
7590 Bone Mineral Content In Women With Functional Hypothalamic Amenorrhea Compared To Eumenorrheic Controls And Recently Menopausal Women
Safwan, Nancy , Uddenberg, Erin R, Hurtado, M D, Saadedine, Mariam , Obrutu, Okezi, Berga, Sarah L. , Pisarska, Margareta D. , Faubion, Stephanie S. , Merz, C. Noel Bairey , Shufelt, Chrisandra

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.368 Get It

Abstract Disclosure: N. Safwan: None. E.R. Uddenberg: None. M.D. Hurtado: None. M. Saadedine: None. S.S. Faubion: None. O. Obrutu: None. S.L. Berga: None. M.D. Pisarska: None. C. Bairey Merz: None. C.L. Shufelt: None. Background: Functional hypothalamic amenorrhea (FHA) accounts for 30% of secondary amenorrhea due to suppression of GnRH associated hypercortisolemia resulting in chronic hypoestrogenemia. FHA occurs as a result of varying combinations of psychosocial stress, excessive exercise, and/or disordered eating. FHA is associated with decreased bone mineralization; however, it is unknown how bone health compares to older, menopausal women who also experience bone loss. We compared dual-energy x-ray absorptiometry (DXA) bone health parameters among women with FHA, eumenorrheic controls, and recently menopausal women and evaluated if previous oral contraceptive (OC) use among FHA women has an impact on bone mineral density (BMD). Methods: This cross-sectional study included 20 women with FHA, 9 eumenorrheic controls, and 12 recently menopausal women who underwent hip and spine DXA. All participants were not on hormone therapy. FHA was defined as amenorrhea >3 consecutive months, estradiol <50 pg/ml, FSH <10 mIU/L, and LH <10 mIU/L, excluding other etiologies including PCOS, prolactinoma, thyroid dysfunction, and pregnancy. Eumenorrheic controls had self-reported monthly menses confirmed with day 22-24 progesterone >3 ng/ml. Recently menopausal women had natural menopause <3 years of final menstrual period, and FSH >30 mIU/L. DXA bone health parameters were measured using Lunar iDXA (GE) including BMD from the lumbar spine (L1-L4) and hip. Statistical analysis included nonparametric testing with pairwise Wilcoxon rank sum and Kruskal Wallis, reported as median [interquartile ranges]. Results: By design, the mean age of FHA was 28 ± 6 yr, 29 ± 3 yr for controls, and 54 ± 2 yr for recently menopausal women (p<0.0001). There were no differences in weight or BMI among the groups (p=0.27, p=0.30, respectively). BMD L1-L4 differed among the three groups with 1.10 g/cm2 [1.00, 1.24] for FHA, 1.18 [1.15, 1.29] for eumenorrheic controls, and 1.02 [0.96, 1.08] for menopausal women (p=0.002). Pairwise analysis revealed a significant difference in BMD L1-L4 between FHA and controls (p=0.04) and menopausal women and controls (p=0.009, age-adjusted). However, there was no difference in BMD L1-L4 between FHA and menopausal women (p=0.08, age-adjusted). In FHA women with previous OC use, BMD L1-L4 was not different from eumenorrheic controls (p=0.20), while BMD L1-L4 differed from that of recently menopausal women (p=0.004). These differences were not observed at the hip. Conclusion: Compared to eumenorrheic controls, lumbar spine BMD in young women with FHA (mean age 28 yr) was similar to recently menopausal women (mean age 54 yr) emphasizing the profound bone impact of FHA. Previous OC use seems to mitigate FHA bone mineralization changes. Future studies should investigate if bone health differs among women with FHA based on underlying cause and if previous OC use plays a role in maintaining bone health. Presentation: 6/3/2024
9336 Bone Pain Caused By Computer Cleaners Huffing
Sokrab, M, Rao, Veitla, Shah, Pinak , Shaker, Joseph , Shah, P

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.371 Get It

Abstract Disclosure: M. Sokrab: None. V.S. Rao: None. P. Shah: None. J.L. Shaker: None. A 47 year-old woman was evaluated 2/2024 for bone pain especially in the forearms and lower legs. The symptoms were worse since about 4/2023. Initial evaluation 11/2023 revealed elevated alkaline phosphatase levels and markers of bone remodeling (P1NP 396 ug/dl, normal; 20-101 and C-telopeptide 4389, normal; 177-1015. The plasma fluoride level was 17.1 mcmol/L (normal; < 4.1). There was no history of excess exposure to fluoride from dental products. She did not drink powdered iced tea or use green tea capsules. There was no industrial fluoride exposure and she consumed city water. She used inhaled fluticasone twice weekly but was not taking other fluoride containing medications, particularly voriconazole. She reported huffing computer cleaner containing difluoroethane between mid 2023 and early 2024. On examination, she had diffuse skeletal tenderness especially over her forearms and lower legs. Lab data revealed calcium 9.2 mg/dl (normal, 8.6-10.2), albumin 4 g/dl, phosphorus 3.6 mg/dl (normal, 2.5-4.5), creatinine 1.08 mg/dl (normal, 0.5-1.1), ionized calcium 1.33 mmol/l (normal, 1.18-1.33), pH normalized ionized calcium 1.25 mmol/l (normal, 1.18-1.33), PTH 126 pg/ml (normal, 15-72), 25(OH)vitamin D 29.5 ng/ml (normal, 20-50), and alkaline phosphatase 287 u/l (normal, 40-120) with a predominant elevation of the bone isoenzyme. The bone specific alkaline phosphatase was 93.4 mcg/l (normal, 7.0-22.4). The SPEP revealed a biclonal IgG Kappa monoclonal protein too small to quantify. The repeat fluoride level was 1.2 mg/l (normal, <0.05). Imaging included diffuse uptake on bone scan as well as periostitis/periosteal thickening involving legs, arms, and hands. There was axial osteosclerosis. Our patient appears to have skeletal fluorosis. Although the time-line of reported huffing and symptoms is not completely consistent, we could find no other exposure to fluoride and speculate she may have been huffing before she recalls. Skeletal fluorosis (SF) is endemic in some countries generally related to drinking water or tea that is high in fluoride, In the US, SF is caused by abnormal use of fluoride-containing dental products, excessive consumption of powdered iced tea containing fluoride, chronic use of the antifungal agent voriconazole and now more often huffing abuse of computer cleaners containing difluoroethane. The number of reported cases of huffing-related SF appears to be increasing and greater awareness of this problem is needed. Presentation: 6/1/2024
6590 Androgen Derived Hepatocellular Adenoma And Reinitiation Of Gender Affirming Hormone Therapy
McKenna, Amanda L. , Loo, Nicole , Ritchie, Charles , Metcalfe, Allie M., Nakhleh, Raouf E. , Krishna, Murli , Thota-Kammili, Sanjana , Eleazer, Jacob , Chang, Alice Y. , Eleazer, Jacob R , Huang, Yuting , Yang, Liu

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.1031 Get It

Abstract Disclosure: A.L. McKenna: None. Y. Huang: None. L. Yang: None. N. Loo: None. C. Ritchie: None. A. Metcalfe: None. R. Nakhleh: None. M. Krishna: None. S. Thota-Kammili: None. J. Eleazer: None. A.Y. Chang: None. Hepatocellular adenomas (HCA) are uncommon, benign epithelial tumors of the liver. Risk factors include exogenous estrogen or androgen use, and genetic and metabolic syndromes. Management of HCA is delineated by sex assigned at birth; Observation is recommended in an HCA less than 5 cm in an individual assigned female at birth, while resection of an HCA in an individual assigned male at birth is recommended no matter the size due to risk of malignant transformation. What is not known is whether risk is different for individuals with gender incongruence on gender affirming hormone therapy (GAHT). There is limited data on the risk of HCA in this population. One case report of a transgender man who continued GAHT after diagnosis of an HCA though no follow-up information was available. We present follow-up on a transgender man assigned female at birth with multiple hemorrhagic HCA that was re-initiated on GAHT after stabilization of adenomas off GAHT. Unlike prior cases, the molecular profile showed ß-catenin negative, estrogen and androgen receptors positive. This is the first case report to our knowledge reporting detailed follow-up after restarting masculinizing GAHT after diagnosis of HCA. A 24-year-old transgender man presented to the emergency department with right upper quadrant pain. Initial labs were notable for ALT of 239 units per liter (U/L) and AST 165 U/L. Magnetic resonance imaging (MRI) of the abdomen and liver elastogram revealed multiple bilobar hepatic masses, the largest measuring 9.9 cm concerning for hemorrhagic HCA which was subsequently confirmed on liver biopsy. Immunostains were positive for estrogen and androgen receptors. The patient had no history of alcohol or illicit drug use, tattoos, or family history of liver disease. The patient had been treated with 100 mg of intramuscular testosterone cypionate weekly for the past six years for gender incongruence locally. No testosterone concentrations were available from prior to or during acute presentation. Discontinuation of hormone therapy was recommended along with conservative management with frequent MRI. Over the next 19 months, monitoring revealed improvement/resolution of the auto infarcting adenomas with the last MRI noting two stable HCA measuring 2.1 cm and 0.8 cm without new or enlarging liver lesions. Due to gender dysphoria off GAHT, reinitiation of hormone therapy with low dose AndroGel 1.62% topically was prescribed at 18 months after presentation. The patient has been monitored with labs monthly and plans to obtain MRI abdomen every three months. To date, the patient has tolerated reinitiation of therapy. This case demonstrates that patients on masculinizing GAHT who develop HCA can be conservatively managed and monitored based on pathology and that testosterone does not necessarily explain sex differences in the presentation/malignant transformation of HCA cisgender men as opposed to cisgender women. Presentation: 6/3/2024
6855 Nationwide Analysis Of Mentorship In Endocrinology Fellowship
Toro-Tobón, David , Billings, Heather , Toro-Tobon, David , Bancos, Irina

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.1062 Get It

Abstract Disclosure: D. Toro-Tobon: None. H. Billings: None. I. Bancos: None. Background: Mentorship is crucial for training physicians' career development, yet evidence of its impact on endocrinology trainees is lacking. We assessed the current state of mentorship in endocrine fellowship training in the United States. Methods: We conducted a cross-sectional study between June and September 2023. Endocrine fellows were invited to complete an online questionnaire describing their mentorship experience and its influence on burnout, satisfaction, and scholarly productivity. Results: Of 153 participants (mean age 34, 69% women, 47% White, 20% Hispanic/Latino), 73% had a mentor. Having a mentor was not associated with age, gender identity, race, or ethnicity. Those without mentors were more commonly in two-year fellowships (63% vs. 81%, p=0.04), had less access to formal mentorship programs (48% vs. 21%, p<0.01), cited insufficient faculty availability for mentoring (11% vs. 26%, p=0.01), and encountered more challenges finding mentors in their training programs (11% vs. 38%, p<0.001). Mentored participants exhibited increased post-fellowship interest in academic practice (69% vs. 50%, p<0.01), higher involvement in clinical research (65% vs. 49%, p=0.01), more fellowship-dedicated scholarly time (36% vs. 22%, <0.001), a greater median number of publications (4.6 vs. 1.8, p<0.01) and abstracts (7 vs. 3.7, p<0.01), were more likely to have submitted a grant (29% vs. 5%, p=0.03) and had higher satisfaction with training (92% vs. 64%, p<0.001). Mentors were mostly chosen by mentees (70%) and shared gender identity (61%) but often had a different race or ethnicity (71.8%). The majority found mentorship relationships satisfactory (87%), contributing to increased academic productivity (84%) and reduced mentee burnout and stress levels (60%). In bivariate analysis, all mentor attributes significantly influenced higher academic productivity and mentee satisfaction. The most divergent for academic productivity were improved communication, alignment with expectations, inspiration for goal attainment, and effective networking. For mentorship satisfaction, distinctions were found in communication enhancement, goal-oriented assistance, knowledge/skill enrichment, and personalized career path development. Traits like active listening and adapting communication styles were not linked to decreased burnout, but actively supporting work-life balance independently correlated with reduced burnout. Conclusion: Mentorship positively affects endocrine fellows' scholarly productivity and career development. Yet, a significant number lack mentors or access to programs. Mentor attributes, like effective communication, goal alignment, and networking support boost productivity and satisfaction. However, reducing mentee burnout hinges on actively fostering work-life balance. Presentation: 6/3/2024
12542 Results Of The Foresight Trial Support The Efficacy And Safety Of Once-weekly Lonapegsomatropin In Adults With Growth Hormone Deficiency (ghd)
Gilis‐Januszewska, Aleksandra , Doknić, Mirjana , Silverstein, Julie , Huang, Eric A., Kang, Jennifer , Domrzalski, Laurie, Yuen, Kevin C.J. , Biller, Beverly M. K. , Picó, Antonio , Fleseriu, Maria , Raverot, Gérald , Isidori, Andrea M. , Takahashi, Yutaka , Garcia, José M. , Bancos, Irina , Komirenko, Allison S , Shu, Aimee D

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.1321 Get It

Abstract Disclosure: B.M. Biller: Consulting Fee; Self; HRA Pharmaceuticals, Novartis Pharmaceuticals, Sparrow, Strongbridge Biopharma. Grant Recipient; Self; Strongbridge Biopharma. A. Gilis-Januszewska: Speaker; Self; Ipsen, Novartis Pharmaceuticals, Novo Nordisk, Recordati, Teva Pharmaceutical Industries Ltd.. M. Doknic: None. A.M. Pico: None. M. Fleseriu: Consulting Fee; Self; Ascendis, GlaxoSmithKline, Johnson &Johnson, Karyopharm, Novo Nordisk, Pfizer, Inc., Pharmacosmos. Research Investigator; Self; Ascendis. G. Raverot: None. A.M. Isidori: None. Y. Takahashi: None. J.M. Garcia: None. J.M. Silverstein: None. I. Bancos: None. E. Huang: Employee; Self; Ascendis Pharma, Inc. J. Kang: Employee; Self; Ascendis Pharma, Inc. A.S. Komirenko: Employee; Self; Ascendis Pharma, Inc. L. Domrzalski: Employee; Self; Ascendis Pharma, Inc. A. Shu: Employee; Self; Ascendis Pharma, Inc. K. Yuen: Advisory Board Member; Self; Amryt, Ascendis, Corcept, Crinetics, Novo Nordisk, Recordati, Strongbridge, Xeris. Grant Recipient; Self; Amryt, Ascendis, Corcept, Crinetics. Speaker; Self; Corcept, Novo Nordisk, Recordati. Background: Adult GHD (aGHD) is characterized by metabolic abnormalities due to insufficient growth hormone (GH) production. Lonapegsomatropin was designed to provide sustained release of unmodified somatropin, with the identical amino acid sequence as endogenous GH, and once-weekly injection reduces the burden of daily GH replacement therapy. MethodsForesiGHt was a randomized, parallel-3-arm, placebo(PL)-controlled (double-blind) and active-controlled (open-label) trial designed to establish the efficacy and safety of lonapegsomatropin in aGHD. It evaluated 259 adults with GHD across 21 countries who were GH treatment-naïve or not treated with GH in the prior year, randomized 1:1:1 to receive lonapegsomatropin, once-weekly PL, or daily somatropin (dGH). Fixed dosing was based on age and oral estrogen intake, and designed to be comparable across lonapegsomatropin and dGH arms. Following a 12-week (w) titration period to target maintenance dose, fixed doses were administered for 26w. ResultsBaseline (BL) characteristics were similar between arms. Lonapegsomatropin demonstrated superiority on the primary efficacy endpoint of change from BL in trunk percent fat at Week 38 vs PL (lonapegsomatropin -1.7% vs PL 0.4%, LS mean difference -2.0%, p < 0.0001) and on the key secondary efficacy endpoints of change from BL in total body lean mass (lonapegsomatropin 1.6 kg vs PL -0.1 kg, LS mean difference 1.7 kg, p < 0.0001) and change from BL in trunk fat mass (lonapegsomatropin -0.5 kg vs PL 0.2 kg, LS mean difference -0.7 kg, p = 0.0053). Mean total exposure and maintenance doses were similar for lonapegsomatropin and dGH arms, with larger changes from BL in average IGF-I SDS mean at Week 38 in the lonapegsomatropin arm (1.4) vs dGH arm (0.5). To assess outcomes at comparable weekly IGF-I exposure, a post-hoc analysis was performed in a subset of participants with average IGF-I SDS ≤1.75 SDS at Week 38. Mean IGF-I SDS for these subsets were similar (lonapegsomatropin -0.1, dGH -0.5), and comparable effects in fat and lean tissue compartments were demonstrated (change from BL in trunk percent fat mean -2.4% and -2.6% respectively; change from BL in total body lean mass mean 1.7 kg and 1.4 kg respectively). In the safety population, the incidence of severe AEs was low (lonapegsomatropin, 3.4%; placebo, 1.2%; dGH, 2.3%) and the incidence of treatment-related AEs was similar (lonapegsomatropin 24.7%, dGH 22.1%). Injection site reaction incidence was low and similar for lonapegsomatropin (4.5%), dGH (5.8%) and placebo (4.8%), and A1c levels remained stable in all treatment arms. ConclusionsThe results of the foresiGHt trial indicate that lonapegsomatropin is a safe, efficacious, and tolerable replacement for endogenous GH. Once-weekly dosing may be impactful for adults with GHD who typically manage multiple other medical therapies. Presentation: 6/3/2024
8702 Age-Sex Differences in Global Burden of Ischemic Heart Disease Attributable to High LDL in the Last 3 Decades:Global, Regional, National Variations, Age Dynamics, and Implications for Global Health
Adedara, Victor O. , Maddineni, Kavya, Dekhne, Anushka, Chinthapalli, Mrunal Teja, Potluri, Geethika, Parisapogu, Anusha, Markandu, Keethanshan, Desai, H. R. , Desai, H

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.551 Get It

Abstract Disclosure: V. Adedara: None. K. Maddineni: None. A. Dekhne: None. M. Chinthapalli: None. G. Potluri: None. A. Parisapogu: None. K. Markandu: None. H. Desai: None. Background: Ischemic Heart Disease (IHD) stands as the foremost cause of mortality globally, contributing to 9.6 million deaths. Elevated levels of low-density lipoprotein cholesterol (LDL-C) consistently feature among the risk factors associated with IHD. Methods: Employing the Global Burden of Disease framework, we computed mortality and DALYs linked to IHD attributable to LDL-C, stratified by age-sex, year, and covering 204 countries and territories during the period from 1990 to 2019. Non-fatal health outcomes were estimated using DISMOD MR 2.1, Bayesian meta-regression tool for epidemiological modelling. Results were expressed in absolute counts and age-standardized rates (ASR) per 100,000 person-years. Results: The total number of deaths attributed to IHD due to elevated LDL-C increased from 2.5 million (95% Uncertainty Interval: 2-3.1 million) in 1990 to 3.7 million (95% UI: 2.8-4.8 million) in 2019. Concurrently, DALYs increased from 60.4 million (95% UI: 50.4-70.7 million) in 1990 to 84.9 million (95% UI: 69.5-101.3 million) in 2019. In terms of ASR, the annual percentage change (APC) in death rates decreased by 36%, and DALY rates decreased by 32% from 1990 to 2019. Regionally, East Asia exhibited the highest increase in APC in death counts by 191%, followed by Commonwealth Low-Income countries at 164%, and Oceania at 160% during the same period. Conversely, the Commonwealth High-Income region experienced the highest decrease at 41%. Males displayed higher APC in death (48% vs. 44%) and DALYs (42% vs. 38%) compared to females over the last three decades. In terms of ASR, males observed a higher decrease compared to females. In 2019, the age group 80-84 years had the highest number of deaths at 534,079 (264,177-813,898), while DALYs were most pronounced in the 55-59 year age group, reaching 10.6 million (8.9-12.3 million). Conclusion: IHD remains a significant global health challenge, with high LDL-C levels being a crucial modifiable risk factor. Age-sex disparities in the burden of IHD are evident, driven by variations in LDL-C metabolism, hormonal changes, and lifestyle factors. Recognizing and addressing these disparities is essential for developing effective prevention and treatment strategies tailored to different populations and age groups. Presentation: 6/2/2024
9255 Use of Race and Ethnicity in Endocrine Clinical Practice Guidelines
Torres, Danny Segura, Raygoza, Karina, García, Mariano López, Ospina, Naykky Maruquel Singh, Garcia, Mariano, Brito, Juan P. , McDonnell, Marie E. , Corrigan, Maureen D. , McCartney, Christopher R. , Dhaliwal, Ruban

Journal of the Endocrine Society | October 5, 2024 | Volume: 8 | Issue: Supplement_1 | Pages: No page available

10.1210/jendso/bvae163.1078 Get It

Abstract Disclosure: D. Segura Torres: None. K. Raygoza: None. M. Garcia: None. J.P. Brito: None. M.E. McDonnell: None. M. Corrigan: None. C.R. McCartney: None. R. Dhaliwal: None. N.M. Singh Ospina: None. Clinical practice guidelines (CPG) improve healthcare quality by guiding decision making. Recent trends in CPG development emphasize incorporating race/ethnicity terms and health equity considerations. However, the appropriateness of how race/ethnicity is utilized remains uncertain. Objective This study seeks to evaluate the use of race/ethnicity in published Endocrine Society (ES) CPG and elucidate the context in which race and ethnicity terms are used. Methods: We identified 30 active clinical practice guidelines from ES up to January 2023. Two reviewers independently and in duplicate: a) located statements addressing race/ethnicity using an electronic search with 24 keywords, b) determined the statements' location within guidelines, and c) classified them based on content using frameworks by Cerdena and Gilliam. Disagreements were resolved by consensus. Exclusions were made for statements not addressing race and ethnicity terms in the appropriate context (e.g., “minority” of the panel disagreed), as well as for those in references or duplicates. Results: We reviewed 30 clinical practice guidelines, with 19 of them containing statements related to race or ethnicity. After applying exclusion criteria, we identified a final analytic sample of 114 statements. The majority of these statements were found in the body of the clinical guidelines (79%), followed by the evidence-to-decision framework (14%), and clinical recommendations (7%).The predominant classification were statements in which there was biologization of race/ethnicity 55% (n=63). Discussions on racial/ethnic disparities accounted for 23% (n=26) of the statements, with 31% (n=8) of these including explicit considerations of social context. Additionally, there were descriptions of race-specific treatment or diagnosis/screening in 14% (n=16) and 9% (n=10) of the statements, respectively.Less commonly statements of race/ethnicity reflected the consideration of ancestry as a code for race/ethnicity (n=7, 6%), identified ancestry as a risk factor for disease (n=19, 6%), highlighted racial/ethnic groups as understudied n=6, 5%), normalized findings to the majority group (White centeredness) (n=7, 6%), and other categories (7%). None of the statements employed race/ethnicity terms to emphasize cultural humility or the value of inclusivity in guideline committees. Conclusion: We systematically analyzed how race and ethnicity terms are used in ES CPGs. Our findings align with prior assessments made in non-ES CPG, highlighting the prevalent biologization of race and ethnicity constructs. Addressing this trend and incorporating socio-structural context considerations could bolster the impact of clinical guidelines in promoting health equity. Presentation: 6/1/2024