Citations

Abstract Disclosure: L. Rahimi: None. J. Saini: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) have higher prevalence of cardiovascular comorbidities including chronic kidney disease. However, considering that patients with MACS may have relative skeletal muscle atrophy, it is unclear whether the creatine-based assessment of kidney function is accurate in this population. Objective: To characterize the differences in assessing estimated glomerular filtration rate using cystatin (eGFRcys) versus creatinine (eGFRcre) in patients with MACS versus referent subjects. Methods: Cross-sectional single-center study, 2019-2022. MACS was defined as serum cortisol concentration >1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST). For each patient, eGFRcre, eGFRcys and eGFRcre/eGFRcys ratio were measured and compared between the two groups. Body composition was measured by DXA scan. The Kruskal-Wallis test was used to compare measurements between groups. Result: A total of 37 patients with MACS (median age 59 years (interquartile range, IQR 47-67), 25 (68%) women) and 45 referent subjects (median age 57 years (IQR 51-66), 30 (67%) women) were included. The distribution of BMI, total body fat mass and total body lean mass were similar between the two groups. In the MACS cohort, the median cortisol following 1-mg DST was 3.0 ug/dL (IQR, 2.2-4.0). While assessment of kidney function with eGFRcre showed no differences between patients with MACS and referent subjects (median 85.1 vs 87.0 ml/min/1.73m2, P=0.431), kidney function using eGFRcys was lower in MACS (median 78.0 vs 89.3 ml/min/1.73m2 in referents, P<0.014), resulting also in a higher eGFRcre/eGFRcys ratio (median 1.07 vs 0.97 in MACS vs referents, P=0.053). After adjusting for age, sex, and BMI, a higher 1 mg DST cortisol level in the MACS cohort was associated with a higher eGFRcre/eGFRcys ratio (Spearman correlation coefficient of 0.35, P = 0.042). Lower eGFRcys was associated with higher fat mass (Spearman correlation of -0.26, P = 0.023), and a higher eGFRcre/eGFRcys ratio showed a trend towards lower lean mass (Spearman correlation of -0.20, P = 0.081). Conclusion: Creatinine-based eGFR assessment in patients with MACS underestimates the degree of kidney dysfunction, likely due to underlying skeletal muscle atrophy. eGFRcys is a more accurate indicator of kidney function in patients with hypercortisolism. Presentation: 6/1/2024

The frequent concurrence of elevated blood pressure (BP) and type 2 diabetes markedly elevates the risk of cardiovascular disease and mortality. In this review, we discuss the evidence supporting the role of BP-lowering therapies in preventing cardiovascular events in people with type 2 diabetes and the most appropriate BP treatment target in these individuals. We outline possible reasons for the heterogeneous effect of BP lowering in patients with and without diabetes and consider several pathophysiological mechanisms that could potentially explain such differences. The review introduces a mediation model, delineating the intricate interplay between hypertension and diabetes and their joint contribution to cardiovascular and renal pathologies. Finally, we outline the role of lifestyle changes and other pharmacological options in attenuating cardiometabolic risks in patients with type 2 diabetes. We propose a comprehensive, patient-centred management strategy, integrating various antihypertensive therapeutic approaches and providing clinicians with a systematic framework for better decision-making.

Abstract Context Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. Objective We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. Methods A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Results Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P < .001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. Conclusion DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy.

Abstract Disclosure: M. Chinthapalli: None. P. Dogra: None. R. Sandooja: None. L. Rahimi: None. N.M. Iniguez Ariza: None. T. Foster: None. I. Bancos: None. Introduction: Adrenal glands are susceptible to hemorrhage due to their unique vasculature and physiological stress response. Scarce data are available on the presentation, etiology, and outcomes of adrenal hemorrhage (AH). Objective: To describe the presentation, etiological associations, and outcomes of patients with unilateral and bilateral AH. Methods: Single-center retrospective longitudinal study of consecutive patients reported to have AH on imaging performed between January 1st 2017-December 31st 2021. Clinical, baseline and follow up imaging, and laboratory data were reviewed. Subgroup analysis was performed based on the laterality (unilateral vs. bilateral) of AH. Results: Of 454 patients with AH (median age 62 years (IQR 50-70), 160 (35%) women), 383 (85%) had unilateral AH, 60 (13%) presented with synchronous bilateral AH, and 9 (2%) had unilateral AH followed by contralateral AH at a later time (metachronous bilateral AH). Only 93 (20%) patients had an evaluation by an endocrinologist. AH was discovered incidentally in 190 (42%) patients, and during evaluation for abdominal or back pain in 133 (29%), trauma in 104 (23%), sepsis in 19 (4%), and adrenal insufficiency in 8 (2%). Primary etiology of AH was a post-procedural complication in 154 (34%), trauma in 126 (28%), coagulopathy in 54 (12%), anticoagulant or antiplatelet therapy in 52 (12%), adrenal neoplasm in 29 (6%) and sepsis in 20 (4%). Metastasis (15, 50%) represented the most common adrenal neoplasm associated with AH. In 208 (46%) patients, diagnosis of AH occurred in the hospital setting, and in 246 (54%) during an outpatient evaluation. In the 393 patients with available baseline imaging, the median size of AH was 3.1 cm (IQR 2.2-4.0). During a median imaging follow-up of 6 months (IQR 3-12), AH reduced in size with a median decrease of -2.6 cm (IQR -1.8 to -3.7) on the right and -2.0 cm (IQR -1.0 to -4.8) on the left. Compared to patients with unilateral AH, those with bilateral AH were more likely to be diagnosed in the hospital setting (61 vs. 43%, P=0.006), have an underlying coagulopathy (50 vs. 4%, P<0.0001), or sepsis (13 vs. 3%, P<0.0001), be on anticoagulant or antiplatelet therapy (48 vs. 21%, P<0.0001), develop primary adrenal insufficiency (61 vs. 0%, P<0.0001) and have larger baseline AH size (4 cm vs. left 2.7 and right 3.1 cm, P=0.0002), but a similar rate of resolution. Conclusions: AH frequently presents as unilateral hemorrhage and can occur secondary to various etiologies, with trauma and postprocedural complication being the most common. Association with an underlying adrenal mass is uncommon, seen only in 6%. Bilateral AH carries a high risk for primary adrenal insufficiency and is more likely to occur in hospitalized patients, possibly due to an increased prevalence of underlying coagulopathy, sepsis and need for anticoagulation or antiplatelet therapy. Presentation: Friday, June 16, 2023

Abstract Disclosure: A. Kittithaworn: None. P. Dogra: None. L. Rahimi: None. R. Sandooja: None. I. Bancos: None. Background: Adrenal calcification is discovered incidentally on imaging performed for reasons other than adrenal pathology and represents <1% of benign adrenal lesions. Data on the etiology and morphology of adrenal calcifications are scarce. Objective: To determine the etiology and imaging characteristics of adrenal calcification. Methods: We conducted a single-center retrospective study of patients with adrenal calcification on abdominal computed tomography between January 1st,2017 and December 31st, 2021. Medical records were reviewed for demographics, discovery mode, etiology and morphology. Subgroup analysis of patients with calcification/s associated with an adrenal mass was performed. Results: Adrenal calcification was reported in 540 patients (245, 45% women, median age 65 years (IQR 54-74). Only a minority of patients with adrenal calcifications were evaluated by an endocrinologist (167, 31%). Adrenal calcifications were discovered incidentally in 472 (87%) patients, during cancer staging imaging in 66 (12%), and evaluation of other symptoms in 2 (<1%). The etiology of adrenal calcification was most commonly idiopathic (390, 72%), followed by adrenal mass (112, 21%), hemorrhage (20, 6%), and granulomatous disease (8, 1.5%). Adrenal calcifications were bilateral in 34 (6%) patients and unilateral in 506 (94%), with a similar left and right distribution. Unilateral calcifications were more frequently single (399, 79%) with punctate (60%), coarse (28%), linear/curvilinear (9%), or eggshell (3%) morphology. Bilateral adrenal calcifications presented more frequently with multiple lesions (53% vs 21% in unilateral calcifications, p <0.0001), and were coarse (59%), punctate (29%), or linear (9%). When associated with either unilateral or bilateral adrenal mass, calcifications were either central (50, 45%), peripheral (44, 39%), septal (10, 9%), or both central and peripheral (7, 7%) in relation to the adrenal mass. Adrenal masses associated with adrenal calcifications were: adrenal adenomas in 63 (56%), myelolipomas or cysts in 28 (23%), metastases in 12 (11%), adrenal carcinomas in 4 (4%), pheochromocytomas in 2 (2%), and other rare masses in 3 (3%) patients. Patients with adrenal calcifications associated with an adrenal mass were younger at the time of diagnosis (median of 63 vs 66 years, p=0.014), and had a higher proportion of women (61% vs. 41%, p=0.0002), and were more likely to be discovered during cancer staging imaging (21% vs. 10%, p=0.003). Adrenal mass-associated calcifications were more frequently multiple rather than single lesions (46% vs. 17%, p<0.0001). Conclusion: Adrenal calcifications are usually unilateral single punctate or coarse lesions of unclear etiology. The majority of the adrenal masses that demonstrated calcifications were benign, however adrenal malignancy or pheochromocytomas were diagnosed in 17% of cases. Presentation: Friday, June 16, 2023

Abstract Disclosure: L. Rahimi: None. A. Kittithaworn: None. R. Gregg Garcia: None. J. Saini: None. P. Dogra: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Objective: Patients with mild autonomous cortisol secretion (MACS) have been reported to have a higher prevalence of chronic kidney disease (CKD), possibly due to the direct effect of hypercortisolism on kidney function and indirect effect of MACS-associated cardiovascular comorbidities, such as diabetes, hypertension, obesity, and dyslipidemia. Limited studies suggest improvement of kidney function following adrenalectomy in patients with MACS. In this study, we aimed to assess the factors associated and the degree and timing of change in kidney function post adrenalectomy in patients with MACS or nonfunctioning adrenal adenoma (NFA). Methods: We conducted a retrospective single-center study and included adult patients with MACS or NFA diagnosed based on a post-dexamethasone cortisol cutoff of 1.8 mcg/dL, who underwent adrenalectomy between 1999-2022. The change in estimated glomerular filtration rate (eGFR) before and up to 3.5 years after adrenalectomy was defined as the primary outcome. Demographics and comorbidities were included in univariable and multivariable analyses. Results: We included 155 (76.0%) patients with MACS and 49 (24.0%) patients with NFA treated with adrenalectomy. The proportion of women was high in both MACS and NFA (71.6% vs 69.4%, p=0.77), however, patients with MACS were older (median age 59.2 vs 54.6 years in NFA, p=0.05). The prevalence of hypertension was higher in MACS vs NFA (71.0% vs 53.1%, p=0.02), while the prevalence of diabetes (25.2% vs 28.6%, p=0.89), dyslipidemia (47.7% vs 46.9%, p=0.92), smoking (74.2% vs 68.9%, p=0.49) and obesity (median BMI 30.4 vs 31.8 kg/m2, p=0.35) was similar between the two groups. Prior to adrenalectomy, patients with MACS had lower eGFR (median 84.4 vs 89.2 ml/min/1.73m2, p=0.09) and a higher prevalence of CKD stage ≥ 3 (16.1% vs 8.2%, p= 0.16). In patients with MACS, after an initial decline of eGFR within 6 months post adrenalectomy (mean decrease 5.3 ml/min/1.73m2), eGFR increased by a mean of 4.9 points at 18-30 months, and by a mean of 8.1 points at 30-42 months post-adrenalectomy (p<0.01). Patients with NFA followed a similar eGFR change trend (p=NS). When comparing post-adrenalectomy delta eGFR in patients with MACS vs NFA, no significant differences were found. After adjusting for age, sex, pre-adrenalectomy eGFR, patient group, hypertension, antihypertensive therapy, and diabetes, there were still significant changes in eGFR over time. In a multivariable analysis, younger age (est -031, p<0.001) and lower pre-adrenalectomy eGFR (est-0.27, p=0.001) were associated with kidney function improvement post-adrenalectomy. Conclusion: Patients with MACS and NFA demonstrate improvement of eGFR over the 3.5 years of follow up post-adrenalectomy. The factors that are associated with improvement of eGFR are lower eGFR before surgery, younger age at time of adrenalectomy and longer follow up post adrenalectomy. Presentation: Friday, June 16, 2023

Abstract Sparse data are available on the etiology, morphology, clinical presentation, and outcomes of adrenal calcification. In this single-center retrospective study of 540 consecutive patients (median age 65 years, 45% women) with adrenal calcification on computed tomography (December 2017 to January 2021), most were discovered incidentally (472, 87%). The commonest etiology was idiopathic (389, 72%), followed by the adrenal tumor (113, 21%), hemorrhage (29, 5%), and infiltrative disease (7, 1%). Calcified adrenal tumors were predominantly benign (92, 81%) and primarily adenomas (63, 69%), whereas the most common calcified adrenal malignancy (16, 18%) was metastasis (12, 67%). Calcification (unilateral 94%, bilateral 6%) morphology varied from punctate (313, 58%) to coarse (165, 30%), linear/curvilinear (46, 9%), and rim-like (16, 3%). In summary, adrenal calcifications are usually incidentally discovered unilateral, punctate, or coarse lesions of unclear etiology. Most calcified adrenal tumors are benign and <20% malignant or pheochromocytomas.

AbstractThe current study was aimed to investigate the beneficial effect of sumatriptan, a 5‐hydroxytryptamine 1B/1D (5HT1B/1D) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro‐inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR‐127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J‐score), ELISA analysis of tumour necrosis factor‐alpha (TNF‐α) and interleukin‐1beta (IL‐1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J‐score, TNF‐α, IL‐1β and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J‐score, TNF‐α, IL‐1β and microscopic lesions. Concurrent administration of GR‐127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin‐, WRS‐ and ethanol‐induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

Abstract: The COVID-19 pandemic, caused by the coronavirus, SARS-CoV-2, has claimed millions of lives worldwide in the past two years. Fatalities among the elderly with underlying cardiovascular disease, lung disease, and diabetes have particularly been high. A biometrics analysis on author’s keywords was carried out, and searched for possible links between various coronavirus studies over the past 50 years, and integrated them. We found keywords like immune system, immunity, nutrition, malnutrition, micronutrients, exercise, inflammation, and hyperinflammation were highly related to each other. Based on these findings, we hypothesized that the human immune system is a multilevel super complex system, which employs multiple strategies to contain microorganism infections and restore homeostasis. It was also found that the behavior of the immune system is not able to be described by a single immunological theory. However, one main strategy is “self-destroy and rebuild”, which consists of a series of inflammatory responses: 1) active self-destruction of damaged/dysfunctional somatic cells; 2) removal of debris and cells; 3) rebuilding tissues. Thus, invading microorganisms’ clearance could be only a passive bystander response to this destroy–rebuild process. Microbial infections could be self-limiting and promoted as an indispensable essential nutrition for the vast number of genes existing in the microorganisms. The transient nutrition surge resulting from the degradation of the self-destroyed cell debris coupled with the existing nutrition state in the patient may play an important role in the pathogenesis of COVID-19. Finally, a possible coping strategies to mitigate COVID-19, including vaccination is also discussed.