Citations

Abstract Disclosure: K.N. Grennan: None. S. Thota-Kammili: None. A.L. McKenna: None. C.G. Coyle: None. S.L. Samson: None. Introduction: Supplement misuse in the bodybuilding community is prevalent. With the availability of internet ordering and purchasing, patients have access to hormonal supplements without prescription or regulation. Here we present the case of a patient on self-administered hormonal supplements who presented in acute heart failure leading to cardiogenic shock in the setting of concurrent thyroid, adrenal, and gonadal axis dysfunction. Case Description: A 28-year-old male with no significant medical history was transferred to our hospital after presenting to an outside emergency room with dyspnea, cough, nausea, and a subjective fever. He developed acute hypoxic respiratory failure requiring intubation. Echocardiogram performed showed an ejection fraction (EF) of 10%. He was started on two vasopressors and methylprednisolone 1 g daily for two days, due to concern for myocarditis versus giant cell arteritis. Hormonal work-up showed TSH 0.02 mIU/L (normal range 0.3-4.2), free T4 0.4 ng/dL (0.9-1.7), total T3 48 ng/dL (80-200), FSH <0.3 IU/L (1.2-15.8), LH <0.2 IU/L (1.3-9.6), ACTH <5.0 pg/mL (7.2-63), cortisol 1.7 mcg/dL (2.5-12), estradiol 171 pg/mL (8.0-35), total testosterone 1730 ng/dL (240-950), and prolactin 47 ng/mL (4.0-15.2). He received 10 mg dexamethasone at the outside facility. A medication bag found by his family included online purchases of non-prescribed testosterone cypionate and enanthate, liothyronine, anastrozole, and clomiphene. None were medical grade. He was also taking the anabolic steroid clenbuterol for 3 days prior. Echocardiogram on day 3 of admission showed an improved EF of 36%. Cardiac magnetic resonance imaging (MRI) showed a papillary fibroelastoma and myocarditis. Patient was weaned off vasopressors and the ventilator. He was discharged on levothyroxine 50 mcg daily and hydrocortisone 10 mg twice daily for outpatient reassessment. Transesophageal echocardiogram confirmed diagnosis of papillary fibroelastoma. One month Endocrinology clinic follow-up showed no evidence of posterior pituitary, thyroid, or adrenal axis dysfunction or growth hormone excess, but he continued to have gonadal axis suppression with elevated prolactin and estradiol, the latter thought to be secondary to conversion from testosterone. Pituitary MRI showed no micro or macroadenoma. His EF recovered to 50%. He is pending surgical removal of the aortic valve fibroelastoma. Discussion: With hormonal supplements easily accessible online, it is important for physicians to counsel patients about the dangers of misuse. This case highlights a previously healthy 28-year-old man who presented in critical condition with cardiogenic shock and hypothalamic-pituitary axis dysfunction from supplements he purchased online. There should be targeted educational interventions regarding the harm of supplements aimed at the bodybuilding community to prevent similar cases. Presentation: 6/2/2024

Abstract Disclosure: P.L. castellanos: None. A.M. Chindris: None. S. Rao: None. J. Janus: None. R. Paz-Fumagalli: None. V.J. Bernet: None. Introduction: Limited information exists regarding the relationship between outcomes and decision-making based on results from Ultrasound-guided fine needle aspiration (USG-FNA) of cervical nodes/nodules suspicious for thyroid cancer metastases. Management options for positive findings include surgery, percutaneous ethanol ablation, radioactive iodine therapy, external beam radiation systemic therapy, or observation. This retrospective review is aimed at describing the management and associated outcomes of a cohort of thyroid cancer patients who underwent USG FNA for cervically metastases. Methods: Following our Clinic IRB review and approval, we performed a chart review and identified 163 patients with thyroid cancer patients who had undergone USG FNA of apparent cervical metastases at the Florida campus between 2012 and 2018. Cytology results and corresponding tumor marker washout from each sampled focus were recorded. The records review included recording anatomical and biochemical outcomes related to management decisions based on USG FNA results. Appropriate statistical plots were used to help visualize the data pattern. ResultsThe median age was 59 years 69.9% were female and 91.3% were Caucasian. Initial presentation typically consisted of the appearance of a neck nodule and thyroidectomy was the first line of therapy in 155 of 163 cases. Imaging post-thyroidectomy demonstrated evidence of cervical lymphadenopathy in 75.5% of cases with localization in the lateral neck in 65.2% and central in 19.2% respectively. Regarding USG-FNA outcomes, 46.2% yielded malignancy while 26% were benign. The most prevalent cytology was papillary thyroid cancer detected in 87.1%.Thyroglobulin washout was performed on all patients with a history of papillary variant thyroid carcinoma, with positive results reported in 8.3%. Ethanol ablation was the most used treatment for lymph node recurrence followed by neck surgery in 56.2%. During the follow-up, 14% of the patients who were TGAB+ remained so.Outcome trends were as follows: The combined anatomical and biochemical negative was 82.3%, while the combined anatomical and biochemical positive was 2.5%. The combined anatomical negative and biochemical positive was 7.6%, alongside the combined anatomical positive and biochemical negative was 7.6%. Conclusion: Of 163 thyroid cancer cases with cervical lymphadenopathy, 46% had cytology-proven presence of malignancy. These patients underwent either observation, PEA, or surgery.At follow up the majority of the patients were without anatomical and biochemical evidence of disease while about 7-8% were positive by one of the parameters and much fewer were positive for disease by both parameters. Presentation: 6/3/2024

Abstract Disclosure: J. Saini: None. V. Fell: None. B. Atkinson: None. S. Achenbach: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have a higher prevalence of frailty and reduced muscle strength as compared to patients with nonfunctioning adrenal adenomas or subjects without adrenal disorders. Objective: To determine the impact of adrenalectomy on frailty and parameters of functional strength in patients with MACS. Methods: We conducted a single-center prospective longitudinal study of adults with MACS scheduled for adrenalectomy and referent subjects evaluated between 2018 and 2023. MACS was defined as serum cortisol>1.8 mcg/dL after 1 mg dexamethasone suppression test in patients with adrenal adenomas and no features of overt hypercortisolism. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Patients and referent subjects had a baseline and a follow-up evaluation at least 10 months later. Differences were assessed using paired t-tests for (1) Frailty Index (FI)--calculated using a questionnaire containing 47 variables on comorbidities, symptoms, and daily living activities (frailty defined as FI>0.25) (2) physical function assessed using handgrip strength (Jamar Plus digital hand dynamometer), timed up-and-go test (time taken to rise from a chair, walk to and from 3 m, and sit down), gait speed, 6-minute walk test, and (3) Advanced Glycation End (AGE) Product (using AGE reader). Results: We evaluated 41 patients before and after adrenalectomy, and 31 referent subjects at baseline and follow-up visit, at a similar interval (median 1.6, IQR 1.2-2.0 vs 1.5 years, IQR 1.0-2.2, P=0.759). While sex distributions were no different between the 2 groups (women, 66% vs 84%, P=0.086), patients with MACS were older than the referent group (median age 57.3, IQR 48.8-66.9 vs 49.0, IQR 41.7-57.9 years, P=0.005). Post-adrenalectomy, FI decreased by a mean of 0.057 (SD 0.08), P<0.001 in patients, and remained unchanged in the referent group. AGE decreased in patients by 0.148 (SD 0.45), P=0.04 but not in referent subjects (-0.047, SD 0.242, P=0.5). Patients demonstrated no improvement in parameters of muscle strength: gait speed (mean change 0.305 m/s, P=0.453), 6-minute walk test (mean change 16.4 meters, P=0.201), dominant (mean Z score change -0.055, P=0.72) and nondominant (mean Z score change -0.199, P=0.192) hand grip muscle strength. At follow-up, both patients (mean change 1.897 seconds, P<0.001) and referent subjects (mean change=1.475 seconds, P<0.001) demonstrated a deterioration on the timed up-and-go test. Conclusions: While no improvement was seen in the parameters of muscle strength, adrenalectomy improved the frailty index in patients with MACS. In addition, AGE, a biomarker associated with cardiovascular morbidity, decreased after adrenalectomy, suggesting a beneficial cardiovascular impact of MACS reversal. Presentation: 6/1/2024

Abstract Disclosure: M. Vahidi Rad: None. S. Ahmed: None. A. Kumar: None. Introduction: Granulomatous disease can cause hypercalcemia due to increased production of 1,25 dihydroxyvitamin-D. Mycobacterium avium complex (MAC) infection is an AIDS (acquired immunodeficiency syndrome)-defining illness and a granulomatous disease that can lead to hypercalcemia. We report a case of severe hypercalcemia from Immune Reconstitution Inflammatory Syndrome (IRIS) in a patient with AIDS and disseminated MAC which developed several months after initiation of appropriate antibiotic and antiviral therapy. Clinical Case: A 30-year-old female with HIV on anti-retroviral therapy and disseminated MAC infection on antibiotics developed PTH independent mild hypercalcemia in the 10.9-11.5 mg/dL range about 4 months after initiation of antiviral and antibiotic therapy. 1,25 dihydroxyvitamin D level was normal at 50 pg/mL (reference range 18-78 pg/mL). The hypercalcemia worsened and about 8 months after initiation of antimicrobial therapy, she had a hospitalization for severe hypercalcemia with corrected calcium of 15.2 mg/dL and acute kidney injury. PTH was suppressed at 6.9 pg/mL and repeat 1,25 dihydroxyvitamin D level was elevated at 129 pg/mL (reference range 18-78 pg/mL). Other testing for PTH independent hypercalcemia including PTH- Related Peptide, serum protein electrophoresis (SPEP) and TSH were normal. She was diagnosed with hypercalcemia from increased calcitriol production in the setting of IRIS secondary to disseminated MAC. Hypercalcemia secondary to increased production of calcitriol in patients with MAC and HIV infection might happen or worsen months after starting the antimicrobial treatments and has been reported as a potential manifestation of immune reconstitution. MAC-associated IRIS has been reported to be associated with a T-helper cell response with increased number of interferon-gamma-producing T-cells and Th1-cytokines that can potentially cause a granulomatous reaction. These granulomas will have increased macrophage 1-alpha-hydroxylase activity that can further result in more production of 1,25 dihydroxyvitamin D3 and cause more hypercalcemia. Prednisone was started with resultant improvement in hypercalcemia. Conclusion: Severe hypercalcemia due to worsening of subclinical granulomatous infections such as MAC can be a manifestation of IRIS in patients with HIV infection or AIDS who are on antiretroviral treatments. This responds to glucocorticoids. Presentation: 6/2/2024

Abstract Disclosure: M. Salama: None. R. Basmaci: None. T. Rajjo: None. O. Chuzhyk: None. A.N. Lteif: None. A. Al Nofal: None. Objective: Heightened societal acceptance of transgender youth and increased awareness of their unmet medical needs have led to a rise in referrals for hormonal therapy. There is limited literature available on the metabolic outcomes of hormone therapy on transgender youth. We investigated how the different metabolic markers of cardiovascular disease change after the initiation of gender-affirming hormonal therapy in transgender adolescents. Methods: A Retrospective, observational cohort study based on chart review of all children with gender dysphoria (under 18 years of age) who were evaluated in the Pediatric Endocrinology Clinic in a tertiary care center between January 2015 and December 2022. Children's demographic information, baseline weight, height, BMI, hematocrit, lipid profile, ALT, prolactin, and HbA1C levels were obtained before and after the initiation of gender-affirming hormonal therapy. The Wilcoxon signed-rank test was employed for paired analysis, while the chi-square test was used as appropriate. Results: We identified 106 transgender youth who were included in the analysis, with a median age at the start of hormonal therapy of 16 years (IQR: 15-17); comprising 68 trans-males (64%) and 38 trans-females (36%). The median treatment duration was 34 months (IQR: 18-54). Among trans-males, ALT levels increased post-treatment (mean difference 6.851 U/L, p < 0.001), as did BMI Z scores (mean difference 0.257, p < 0.001) and LDL-C (mean difference 12.734 mg/dl, p = 0.002), triglycerides (mean difference 10.18 mg/dl, p = 0.009), non-HDL-C (mean difference 12.8 mg/dl, p = 0.002), and total cholesterol (mean difference 10.18 mg/dl, p = 0.02). No significant differences were observed in HbA1C and HDL-C post-treatment. Among transfemales, BMI Z-scores were higher post-treatment (mean difference 0.27, p = 0.007), with increased total cholesterol (mean difference 19.88 mg/dl, p = 0.008), LDL-C (mean difference 12.6 mg/dl, p = 0.02), and HDL-C (mean difference 11.38 mg/dl, p < 0.001). Other variables did not significantly differ pre-and post-treatment. Ten transfemales with measured prolactin levels pre- and post-treatment showed no statistically significant differences. Conclusion: This pilot study revealed increased BMI Z scores following the commencement of hormone therapy in both trans-male and trans-female youths. Moreover, masculinizing treatment led to increased ALT levels. Furthermore, the cardiometabolic profile exhibited diverse alterations, particularly higher LDL-C levels in both cohorts. These findings underscore the necessity for close monitoring of these parameters during the treatment of transgender youth. Larger prospective randomized controlled trials are essential to comprehensively assess the impact of gender-affirming therapy on transgender youth. Presentation: 6/2/2024

Abstract Disclosure: J. Herndon: None. W.G. Breen: None. N. Laack: None. W.S. Harmsen: None. D.Z. Erickson: None. Background: Treatment of chordomas and parasellar meningiomas includes surgical resection and/or various forms of radiotherapy. Proton beam therapy (PBT) is able to provide higher doses of radiation to the targeted tissues while better sparing surrounding structures, potentially facilitating decreased toxicity. While proton utilization has increased, there is a paucity of data regarding short- and long-term endocrinologic outcomes in these patients. Objective: Determine rate of hypopituitarism in patients with chordomas and parasellar meningiomas undergoing PBT. Methods: A prospectively maintained radiation database including adult patients treated with PBT since 2015 at a tertiary referral center for chordomas and parasellar meningiomas was reviewed. Data collected at baseline included demographic data, tumor diagnosis and pathology, prior history of surgery/radiation, radiation treatment, biochemical hormonal data, and incidence of pituitary insufficiencies (PI). Biochemical pituitary hormonal data and incidence of new PI was recorded at 6 months, 1 year, 2 years, 3 years, 4 years, 5 years, and up to two additional time points up to 10 years post-PBT. Statistical analysis includes descriptive statistics presented as number (%) and median [IQR]. Results: Of 177 patients with sellar/parasellar masses with sufficient endocrine data who underwent PBT, a total of 64 patients (36.2%) were included; 40 (62.5%) with parasellar meningioma and 24 (37.5%) with chordoma. Median age of patients was 49.5 years old [37.7, 63.2], and 44 (68.8%) were female. Median follow-up was 24 months [12, 36]. Prior to PBT, 52 patients (81.3%) were treated surgically, 5 (7.8%) had prior fractionated photon or gamma-knife radiation therapy. At baseline 10 patients (15.6%) exhibited PI in at least one pituitary axis, most commonly secondary hypogonadism (7, 70%). Median PBT total prescribed dose was 54 Gy [50.4, 70.0] in a median of 30 [28, 35] fractions. Cumulative incidence of newly diagnosed PI at follow-up was 4.7% at 6 months, 9.4% at 1 year, 14.1% at 2 years, and 17.2% at 3+ years. No patients with PI at baseline developed new deficiencies. Among the 11 patients (17.2%) who developed new PI, 17 various deficiencies were recorded (range 1-3 per patient), including hypogonadism (8, 47.1%), hypothyroidism (6, 35.3%), and adrenal insufficiency (4, 23.5%). No growth hormone deficiency was clinically diagnosed, however IGF-1 levels decreased from baseline at the follow-up (when available) by a median of -11.8 ng/mL at 6 months (n = 12), -3.0 at 1 year (n = 12), -17.0 at 2 years (n = 7), -30.5 at 3 years (n = 4), -55.0 at 4 years (n = 3), and -37.5 at 5 years (n = 2). Conclusion: Incidence of newly developed PI in chordomas and parasellar meningiomas following PBT for adult patients after median initial follow up of 2 years was low, however extended follow up data are necessary. Presentation: 6/1/2024

Abstract Disclosure: V. Adedara: None. M. Chinthapalli: None. A. Parisapogu: None. G. Potluri: None. K. Markandu: None. K. Maddineni: None. H. Desai: None. Introduction: Thyroid cancer (TC) is an increasingly pressing health issue worldwide, particularly within the Organisation for Economic Co-operation and Development (OECD) countries, which account for 36.57% of all global TC cases. This study focuses on the impact of high Body Mass Index (h-BMI), paralleling rising obesity rates, on the burden of TC across 38 OECD countries. Method: Employing the Global Burden of Disease framework, we analyzed the trends in deaths, Disability Adjusted Life Years (DALYs), and Years Lived with Disabilities (YLDs) attributable to TC attributable to h-BMI, considering variables such as age, sex, year, and location over the past three decades. Results: Our findings show a significant increase in the total number of TC deaths attributable to h-BMI, rising from 873 (95%UI: 422-1471) in 1990 to 1646 (95%UI: 819-2703) in 2019. Similarly, DALYs escalated from 22041 (95%UI: 10576-37075) in 1990 to 39485 (95%UI: 19952-63534) in 2019, with YLDs increasing from 2360 (95%UI: 1082-4179) to 6170 (95%UI: 3036-10416). The age-standardized rate (ASR) showed an annual percentage change (APC) in the death rate of 5% (95%UI: -0.07-20%), and a 10% increase (95%UI: 2-10) in DALYs rate over three decades. The United States reported the highest number of deaths at 449 (95%UI: 233-703) in 2019. Regarding ASR, Iceland had the highest death rate of 0.16 per 100,000, followed by Mexico (0.13), Estonia (0.11), and Latvia (0.11). Males exhibited a higher APC in deaths (131% vs. 60%) and DALYs (112% vs. 52%) compared to females over the last three decades. Additionally, an increase in deaths was observed with advancing age, with the highest DALYs noted in the 75-79 year age group. Conclusion: To effectively address the rising thyroid cancer rates linked to high BMI, a unified approach is essential: public health policies must focus on obesity prevention, clinicians should integrate BMI management in thyroid cancer care, collaboration between policymakers and healthcare providers needs strengthening, and public awareness about the risks of high BMI must be increased to promote early screening and lifestyle changes. Presentation: 6/3/2024

Abstract Disclosure: E. Tama: None. R. Rivera: None. S. Fansa: None. D. Anazco: None. W. Ghusn: None. S. Faubion: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. M.D. Hurtado: None. Introduction: Midlife women (ages 40 to 65) experience age-related weight gain (0.4-0.7 kg/year) due to physiologic and psychosocial changes. Evidence supports that age-related decrease in lean mass and its subsequent effect on energy expenditure are key physiologic factors. To date, the are no data describing if changes in the main regulators of energy intake (i.e., hunger, satiation, and satiety) across women’s lifespan play a role in weight gain during midlife. The aim of this study is to characterize measurements of satiation, satiety, and appetite sensations through early adulthood and midlife in women with obesity. Methods: This is a cross sectional study of women aged 19-65 with overweight or obesity who have undergone measurements of (i) body composition by DXA scan; (ii) resting energy expenditure (REE) by indirect calorimetry; (iii) satiation by calories consumed to satiation (CTS) during an ad libitum meal test; (iv) satiety by time needed to empty 50% of the stomach content (GEt1/2) in a gastric emptying study and plasma satiety hormone levels (PYY, GLP-1, and CCK); and (v) appetite sensations by visual analog scales (VAS) for hunger and fullness. We present data as mean ± standard deviation. We performed simple correlations between these variables and age. We performed multiple regression analyses to adjust for body composition and REE. Results: Our cohort included 552 mostly white (93%) women, with a mean age of 41±11 years and a mean BMI of 37±7 kg/m2. Increased age significantly correlated with higher waist circumference (r=0.1, p=0.006), waist/hip ratio (r=0.1, p=0.01), and total fat mass % (r=0.1, p=0.04); and with lower lean mass % (r=-0.1, p=0.04) and REE (r=-0.3, p<0.0001). Increased age was associated with decreased hunger sensation (i.e., lower preprandial VAShunger after an overnight fast, r=-0.1, p=0.04; and lower postprandial VAShunger 4hr after a standardized 320-kcal breakfast, r=-0.1, p=0.001), stronger satiation (i.e., lower CTS, r=-0.1, p=0.001), and more prolonged satiety (i.e., higher GEt1/2, r=0.1, p=0.02; higher postprandial GLP-1 levels, r=0.1, p=0.03; and higher postprandial VASfullness after and ad libitum meal, p=0.1, p=0.008). After adjusting for lean mass % and REE, the correlations between age and hunger sensations and satiation measurement, but not satiety measurements, were maintained. Conclusion: Our results show that older women have lower lean mass % and REE. After adjusting for these variables, older women experience decreased hunger sensation and achieve satiation with a lower number of calories. As these changes in theory would protect against midlife weight gain, the differences in body composition and REE remain the most likely culprit. Further research is necessary to investigate if there are other key factors that may contribute to weight gain such as the hedonic or emotional components of food intake. Presentation: 6/2/2024

Abstract Disclosure: R. Kennedy: None. D.A. D'Alessio: None. A.V. Vella: None. Introduction: Selective arterial calcium stimulation testing (SACST) can be utilized in patients to localize solitary insulinomas when imaging is non diagnostic. While a heterogenous stimulation pattern suggests NIPHS, or multiple insulinomas this case uniquely demonstrates such a pattern with a solitary insulinoma. Clinical Case: The patient is a 48 year old female who presented to the emergency department (ED) for bizarre behavior which resolved with a sweetened drink. Serum glucose was 62 mg/dL, she was treated with IV dextrose and was discharged from the ED. She was referred to outpatient endocrinology for further evaluation where continuous glucose monitoring confirmed predominantly fasting hypoglycemia. Adrenal insufficiency was excluded. She was admitted for a 72 hour inpatient fast where the patient achieved hypoglycemia within 24 hours, with glucose 46 mg/dL (associated with neuroglycopenic symptoms), beta hydroxybutyrate < 0.18 mmol/L, insulin 3.9 mcIU/mL, proinsulin 157pmol/L, c-peptide 1.4 ng/mL and a glucose rise greater than 25mg/dL after glucagon administration. Sulfonylurea screen and insulin antibodies were negative; IGF1 within normal limits. These labs were consistent with hyperinsulinemic hypoglycemia. An MRI pancreas however did not reveal an insulinoma. The patient therefore underwent a SACST, demonstrating a 10 fold response in the territory of the gastroduodenal artery and splenic artery, as well as a 3 fold response in the superior mesenteric artery. This heterogenous pattern in addition to the marked response in each arterial territory raised the possibility of multiple insulinomas. However as there were no tumors present on imaging, medical management was initiated with close follow up. She was trialed with months of somatostatin analogs and diazoxide with minimal improvement in the frequency and severity of her hypoglycemia. About a year after her initial diagnosis, repeat abdominal imaging (CT and MRI) revealed an 8 mm arterial hyper-enhancing lesion in the body of the pancreas concerning for neuroendocrine tumor. Repeat SACST was performed, this time showing a greater than 10 fold response in all three arterial territories. Angiography showed a tumor blush that was visible when each of the three major arteries were injected sequentially. She underwent laparoscopic pancreatic enucleation. The lesion was located on the body of the pancreas, with histology confirming an insulinoma. The patient responded promptly post operatively; her symptoms resolved without further need of medical management. Conclusion: Our case shows that the interpretation of an SACST should take into account the arterial anatomy before ascribing a non-focal response to multiple territories of insulin hypersecretion. Presentation: 6/1/2024

Abstract Disclosure: I. Bancos: Advisory Board Member; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Consulting Fee; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. Grant Recipient; Self; Recordati, HRA Pharmaceuticals. Other; Self; Adrenas, Diurnal, Neurocrine, Spruce, HRA Pharmaceuticals, Sparrow, Recordati Rare Diseases, Xeris, Novo Nordisk, AstraZeneca, Corcept. E.B. Geer: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Xeris Pharmaceuticals (Strongbridge), Corcept, Recordati Rare Diseases, Sparrow. F. Castinetti: Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; HRA Pharmaceuticals, Recordati. R. Feelders: Advisory Board Member; Self; Recordati. Consulting Fee; Self; HRA Pharmaceuticals, Recordati. Grant Recipient; Self; Corcept Therapeutics. M. Fleseriu: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Grant Recipient; Self; Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). R. Pivonello: Consulting Fee; Self; Corcept Therapeutics, Recordati, Crinetics Pharmaceuticals, H Lundbeck. Grant Recipient; Self; Recordati, Corcept Therapeutics, Xeris Pharmaceuticals (Strongbridge), Neurocrine Biosciences. M. Reincke: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Grant Recipient; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. Speaker; Self; Recordati Rare Diseases, HRA Pharmaceuticals, Lundbeck, Crinetics. A. Tabarin: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Crinetics, HRA Pharmaceuticals, Recordati Rare Diseases. J. Le Mouhaër: Employee; Self; Recordati. J. Stermenska: Employee; Self; Recordati. M. Maldonado: Employee; Self; Recordati. B.M. Biller: Advisory Board Member; Self; Recordati Rare Diseases. Consulting Fee; Self; H Lundbeck, Recordati Rare Diseases, Sparrow, Xeris Pharmaceuticals (Strongbridge). Introduction: Osilodrostat, a potent oral 11β-hydroxylase inhibitor, provides control of cortisol production and improves outcomes in patients (pts), as shown by the clinical development program of Cushing’s disease (CD; Fleseriu M et al. Lancet Diabetes Endocrinol 2021;9:847-75) leading to EMA approval for Cushing’s syndrome (CS) and FDA approval for CD. The prospective LINC 6 study (NCT05382156) evaluates long-term safety and efficacy of osilodrostat in routine clinical practice over a 3-­year follow-up of CS pts. Here, we report 1-year interim data. Methods: Pts aged ≥18 years with endogenous CS are being enrolled in countries where osilodrostat is approved and available (including USA and Europe), irrespective of prior osilodrostat use. Treatment decisions and follow-up are at investigator discretion. The primary endpoint is incidence of osilodrostat-related adverse events (AEs) and serious AEs, focusing on AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement. Secondary endpoints include change in mean urinary free cortisol (mUFC), serum cortisol and late-night salivary cortisol (LNSC). Evaluation of biochemical parameters is recommended at baseline, months 1 and 3, and every 3 months thereafter, as available. AEs are recorded at baseline and each visit. Analyses are descriptive. We report change for pts with assessments at baseline and every 3 months. Results: Of 106 pts enrolled at the 1-year interim analysis, 94 were included in the safety population: CD, n=78; non-CD CS, n=16 (adrenal adenoma, n=3; adrenal hyperplasia, n=3; ectopic, n=9; other, n=1). Mean (SD) age was 53.2 years (12.7); 70.2% (n=66) were female. Median (min-max) osilodrostat exposure and dose were 5.5 months (0.1-13.9) and 5.0 mg/day (1.0-60.0). 29 pts reported 109 AEs; 12 pts reported 44 AEs that were considered treatment related. Overall, the most common (≥5%) AEs were asthenia and vomiting (both n=6/109; 5.5%); treatment-related AEs with highest frequency were vomiting and dizziness (both n=4/44; 9.1%). 7 AEs led to discontinuation in 4 pts; 5 AEs were considered osilodrostat related (nausea and vomiting in 1 pt; worsening hypertension, uncontrolled blood pressure and dizziness in another) and 2 were not (pituitary tumor surgery and right adrenalectomy). AEs related to hypocortisolism, accumulation of adrenal hormone precursors, QT prolongation and pituitary tumor enlargement occurred in 7 (7.4%), 4 (4.3%), 2 (2.1%) and 0 pts, respectively. At month 3, mUFC, serum cortisol and LNSC were normalized in 71.4% (n=10/14), 69.2% (n=18/26) and 50.0% (n=7/14) of pts. Conclusions: Results from this real-world clinical setting show that osilodrostat is generally well tolerated and provides early improvements in mUFC and LNSC in pts with endogenous CS, building on evidence from the previous randomized, controlled trials LINC 3 and LINC 4. Presentation: 6/3/2024