Degree Of Excess Research Articles

7010 The Incidence Of Cushing Syndrome In Wisconsin Is More Common Than Population-Based Studies From Europe

Abstract Disclosure: T. Matoska: None. T.B. Carroll: Consulting Fee; Self; Corcept Therapeutics. Research Investigator; Self; Corcept Therapeutics. T.S. Wang: None. S. Dream: None. N. Zwagerman: None. J.W. Findling: Advisory Board Member; Self; Corcept Therapeutics, Recordati, Diurnal. Introduction: Endogenous neoplastic hypercortisolism [Cushing syndrome (CS)] is considered to be a rare disorder. Population-based studies from Europe estimate the incidence of CS to range from 1.8-3.2 cases/million patient-years, and there is limited data reporting the incidence of CS in the United States. All previous studies have shown that pituitary ACTH secreting tumors [Cushing disease (CD)] are the most common cause of CS. Based on our clinical experience, we speculated that the incidence of CS was more common than reported and that adrenal CS (ACS) was more common than CD. This study reports the incidence and etiology of CS from a single tertiary care center in Wisconsin (WI). Methods: Institutional clinic records between May 1, 2017, and December 31, 2022, were queried to identify WI residents treated for CS. Only patients diagnosed and treated at our institution during the study period were included. The diagnosis of CS was established with standard guideline-supported biochemical testing and appropriate imaging. Patients diagnosed with exogenous CS and those who did not undergo therapy for CS were excluded. Results: The query identified 185 patients who were diagnosed and treated for CS. These patients resided in 27 of the 72 WI counties representing a population of 4.5 million of the total WI population of 5.9 million. This suggests that, at a minimum, the incidence of CS in WI is 7.2 cases/million patient-years. Moreover, data from the WI Hospital Association show our institution treated <50% of all patients with CS discharged from WI hospitals from 2019-2023. Mean age at diagnosis was 52.4 years (SD 14.7) and 135 (73%) were female. Of the total cohort, 111 (60%) had ACS, 68 (36.8%) had CD, and 6 (3.2%) had ectopic ACTH syndrome (EAS). Patients with ACS had significantly lower LNSC, DST cortisol, and UFC when compared to those with CD and EAS. ACS had mean (SD) LNSC, DST cortisol, and UFC of 0.236 µg/dL (0.367), 6.5 µg/dL (8.7), and 64.2 µg/24h (92.8), respectively. CD had mean (SD) LNSC, DST cortisol, and UFC of 0.425 µg/dL (0.403), 11.7 µg/dL (7.5), and 151.1 µg/24h (287.4), respectively. EAS had mean (SD) LNSC, DST cortisol, and UFC of 3.189 µg/dL (0.931), 42.5 µg/dL (40.5), and 1514.2 µg/24h (1278.9), respectively. Overt physical features of CS were documented in the medical record of 117 (63.2%) patients at diagnosis ((ACS: 49 (44%); CD: 62 (91%); EAS: 6 (100%)). Conclusion: This study suggests that ACS is more common than CD as a cause of CS, and patients with ACS more frequently presented without physical features of hypercortisolism, probably due to the milder degree of cortisol excess. The incidence of CS in WI is at least 7.2 cases/million patient-years. As our institution cares for <50% of patients with CS in WI, the true incidence is likely far greater and may approach 14-15 cases/million patient-years. Presentation: 6/1/2024

6998 Giant Pheochromocytoma: A Retrospective Single-Center Study

Abstract Disclosure: B. Bahrani Fard: None. N. Nikravangolsefid: None. J. Maroun: None. A. Cross: None. T. Foster: None. T. McKenzie: None. W. Young Jr: None. B.M. Dy: None. M. Lyden: None. I. Bancos: None. Background: Giant pheochromocytomas (PHEO), defined based on size > 10 cm, are rare. Data on clinical presentation, management, and prognosis of giant PHEOs are scarce. Objectives: to determine prevalence of giant PHEO and compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. Methods: We conducted a single-center retrospective cohort study of consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at 6:1 ratio, evaluated between 2000-2023. All variables were extracted from the electronic medical record. Results: Of 828 patients with PHEO evaluated between 2000 and 2023, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO were similar in age (median age 53 vs 55 years, P=.55), more frequently discovered based on symptoms (52% vs 32%, P=.04), and less likely to be bilateral (3% vs 12%, P=.31). Genetic testing was performed in 103 (48%) of patients, without group differences, however, patients with giant PHEO were less likely to have an associated germline mutation detected (7% vs 47%, P=.004). Patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe metanephrine excess >10 times above upper normal range (76% vs 30%, P<.0001). Adrenalectomy was performed in 94% of patients with giant PHEOs and in 100% referents, with higher rates of open adrenalectomy in giant PHEO (86% vs 14%, P<.0001). In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a longer hospital length of stay (laparoscopic: median 5 vs 2 days, P<.0001; open: median 6 vs 5 days, P=.24), and a higher complication rate (31% vs 10%, P=.006).Median follow up was 3 years (IQR 1-8) years, similar in patients and referents. Metastases developed at a much higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease specific mortality was 7% in patients with giant PHEOs and 0% in referents. Conclusion: Patients with giant PHEO were more symptomatic, had a higher degree of catecholamine excess, and a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up. Presentation: 6/2/2024

Presentation, Management, and Outcomes of Patients with Giant Pheochromocytoma: Retrospective Cohort Study.

Data on giant pheochromocytomas (PHEO), defined based on size ≥ 10 cm, are scarce. to compare presentation, management, and outcomes of patients with giant vs non-giant PHEOs. retrospective cohort study, 2000-2023. referral center. consecutive patients with giant PHEO and randomly chosen patients with non-giant PHEO (referents) at a 1:6 ratio. perioperative complications, metastases, mortality. Of 828 patients with PHEO, 31 (3.7%) had giant PHEO (median size 12 cm, IQR 10.0-13.5). In comparison to referents (n=186, median size 4 cm, IQR, 2.9-5.0), patients with giant PHEO had more symptoms of catecholamine excess (median of 2 vs 1, P=.04) and presented with a higher prevalence of severe catecholamine excess (76% vs 30%, P<.0001).Adrenalectomy was performed in 94% of patients with giant PHEOs and 100% referents. In addition to preoperative alpha-adrenergic blockade (89%), metyrosine was used in 14 (7%) patients, mostly in patients with giant PHEO (26% vs 3%, P<.0001). Patients with giant PHEO had a higher perioperative complication rate (31% vs 10%, P=.004).During a median follow-up of 3 years, metastases developed at a higher rate in patients with giant PHEOs (45% vs 4% in referents, P<.0001). Disease-specific mortality was 7% in patients with giant PHEOs and 0% in referents (P=.02). Patients with giant PHEO as compared to referents were more symptomatic, had a higher degree of catecholamine excess, and had a higher rate of perioperative complications. Almost half of patients with giant PHEO developed metastases, warranting a close follow-up.

Verification of thermodynamic parameters of a mixture of generator gas on oxygen-hydrogen fuel with an excess of one of the fuel components

Liquid gas generators (LGG) are additional firing units in the power system of liquid rocket engines (LPRE). The LGG ensure the operation of the power units of the turbopump unit (TPU) of the engine by feeding combustion products (CP) to the turbine drive. The main criteria for the efficiency of the generator gas is the complex (RT)gg and the thermodynamic properties of the mixture, depending on temperature, pressure, the degree of excess of the oxidizer and the enthalpy of the fuel, attributed to the conditions of supply to the nozzles of the GG. Changing the parameters of the generator gas leads to a change in the turbine power parameters due to its effect on the adiabatic operation of the Lad turbine. Depending on the engine circuit under consideration, CP GG can perform work in other units and elements of the engine, as well as influence many parameters of the LPRE. Among the main ones can be noted: the power of the booster gas turbine of the booster turbopump unit (BTPU) in the case of the selection of the generator gas after the GG or turbogas after the main turbine; the temperature of heating the refrigerant in the heat exchanger introduced in the GG; specific impulse of a liquid rocket propulsion system (LRPS), depending on the quantity and properties of the turbogas entering the exhaust pipe of the engine (for the engine circuit without afterburning the generator gas); mixing in the combustion chamber (CC) due to afterburning of turbogas entering the engine chamber after the turbine (for the engine circuit with afterburning of generator gas); parameters of the firing wall of the engine in the case of using a high-temperature gas curtain by blowing generator gas into the supersonic part of the nozzle. For many pairs of fuel during combustion in GG, the nonequilibrium of combustion products is characteristic (especially in hydrocarbon fuels).Due to the fact that the combustion products (CP) during the combustion of an oxygen-hydrogen mixture, due to the simplicity of the reaction, have time to form while staying in the GG (i.e., the time of chemical equilibrium of the CP is less than or equal to the time of stay in the GG), their thermodynamic parameters can be reliably determined using programs that simulate chemical equilibrium reactions. In this article, the issue of obtaining reliable results of thermodynamic calculations of generator gas at low and high coefficients of oxidant excess is investigated. Verification of parameters obtained in the programs “Astra” and “Rocket Propulsion Analysis” with calculated values was carried out. The most suitable program for performing engineering calculations and modeling the thermodynamics of liquid gas generators has been determined.

Greenness transformation, environmental awareness, and green product policy in spatial markets

AbstractThis paper examines the transformation towards greenness, focusing on consumer environmental awareness within a circular city model characterized by elastic demand. Our findings reveal that the equilibrium investment in environmentally friendly initiatives falls short of the socially optimal level for a given market structure. The degree of excess or insufficient market entry is influenced by the level of environmental awareness. Further, we delve into the role of environmental delegation, demonstrating that heightened environmental awareness can mitigate underinvestment in the environment and reduce inefficiency in market entry. From a policy perspective, we expand our analysis to include the “Green Product Policy.” This extension aims to explore the impact of such a policy on environmental awareness and assess the applicability of the “excess entry theorem” in this context.

Surgical Technique Selection in the Management of Pediatric Gynecomastia.

Although the majority of pubertal onset gynecomastia is self-resolving in nature, persistent deformity may require surgical intervention. This study aims to identify patient factors associated with surgical technique selection and proposes an algorithm for the surgical management of pediatric gynecomastia. A retrospective analysis was performed of all surgically managed pediatric gynecomastia patients operated on at a single institution from 2012 to 2022. Charts and patient photos were analyzed for patient and operative demographics, endocrinologic comorbidities, complications, and outcomes. Data were analyzed using bivariate and logistic regression analysis. Fifty-six surgically managed gynecomastia patients less than 18 years of age were included. The average age at surgery was 16.1 years old, with a mean BMI of 26.9. Most patients were overweight or obese (54.8%) and had Simon grade IIb or greater gynecomastia (55.4%) at presentation. All patients underwent 1 of 4 mastectomy techniques with or without liposuction: inferior periareolar (n=25, 44.6%), circumareolar (n=13, 23.1%), transverse with pedicled nipple (n=4, 7.1%), or free nipple graft (n=14, 25.0%). Bivariate and logistic regression analysis revealed significant differences in sternal notch-to-nipple distance, nipple-to-inframammary fold distance, breast resection weight, and gynecomastia grade between the 4 surgical techniques used in this study. An algorithm incorporating these factors was devised to guide surgical decision-making. The proposed algorithm guides surgical technique selection for pediatric gynecomastia and is contingent upon the degree of ptosis and skin excess, anticipated resection weight, and skin quality.

Prospective, longitudinal study of cancer predictors and rates in a New York City cohort of 598 patients with acromegaly.

Long-term GH/IGF-1 excess could increase risk of cancer in acromegaly, but individual levels of these hormones do not relate to this risk. Therefore, we newly investigated longitudinally-measured IGF-1 levels as a potential predictor of cancer in a large NYC acromegaly cohort. We conducted a prospective, longitudinal study of 598 acromegaly (309 men, 289 women) and 292 clinically nonfunctioning pituitary adenoma (CNFPA)(140 women, 152 men) patients from the same underlying population. GH and IGF-1 levels were measured longitudinally and outcomes were observed during long-term follow-up. Cumulative exposure to IGF-1 excess was tested as a predictor of cancer. We compared cancer prevalence in acromegaly and CNFPA cohorts and incidence in each to that expected from SEER data. Cancer prevalence by last follow up was 22.6% in acromegaly and 12.7% in CNFPAs (OR = 1.99 (95% CI, 1.34, 2.97)(P=0.0005). Overall SIR for cancer was 1.78 (1.51, 1.81) in the acromegaly and 1.26 (0.89, 1.70) in the CNFPA cohorts. Cumulative exposure to IGF-1 excess, OR=1.278 (1.060, 1.541)(P = 0.01), years from acromegaly diagnosis to cancer or last follow up, OR= 1.03 (1.004, 1.057)(P=0.024), and age at follow up, OR =1.064 (1.047, 1.082)(P<0.001), were predictors of cancer. Cancer risk is increased in acromegaly, but not in CNFPA patients. Cumulative exposure to IGF-1 excess is a predictor of cancer in acromegaly. Our data suggest that cancer risk in acromegaly relates to the degree and duration of IGF-1 excess and that full appreciation of this risk requires long-term follow up.

Bilateral Adrenocortical Nodular Disease and Cushing's Syndrome.

Primary pigmented nodular adrenocortical disease (PPNAD) and bilateral macronodular adrenocortical disease (BMAD) are 2 forms of adrenocortical nodular diseases causing Cushing's syndrome but are 2 very distinct conditions. PPNAD, affecting mostly young patients with an almost constant severe Cushing's syndrome, is characterized by pigmented micronodules, usually less than 1 cm, not always visible on imaging. On the contrary, BMAD is predominantly diagnosed in the fifth and sixth decades, with highly variable degrees of cortisol excess, from mild autonomous cortisol secretion to overt Cushing's syndrome. BMAD presents as large bilateral adrenal macronodules, easily observed on imaging. Both diseases are often genetically determined: frequently PPNAD is observed in a multiple neoplasia syndrome, Carney complex, and a germline genetic defect is identified in around 80% of index cases, always affecting key actors of the cAMP/protein kinase A (PKA) pathway: mostly PRKAR1A, encoding the PKA 1-alpha regulatory subunit. On the other hand, BMAD appears mostly isolated, and 2 predisposing genes are known at present: ARMC5, accounting for around 20% of index cases, and the recently identified KDM1A, causing the rare presentation with food-dependent Cushing's syndrome, mediated by the ectopic expression of the glucose-dependent insulinotropic polypeptide receptor (GIPR) in adrenal nodules. GIPR was the first demonstrated receptor to illegitimately regulate cortisol secretion in nodular adrenocortical diseases, and a myriad of other receptors and paracrine signals were discovered afterward. The last 30 years were pivotal in the understanding of the genetics and pathophysiology of bilateral adrenocortical nodular diseases, leading to a personalized approach of these fascinating conditions.

Study of thyroid functions in transfusion dependent thalassemia patients of pediatric age group with reference to serum ferritin level in a tertiary care centre

Hypothyroidism is one of the most common endocrine complication in transfusion dependent thalassemia patients. Its prevalence and severity is variable and the natural history is poorly described. The frequency of hypothyroidism in Beta Thalassemia Major (BTM) children ranges from 6 to 30%. To determine the levels of serum TSH and FT4 in patients with transfusion-dependent thalassemia (TDT), as well as their relationship to the degree of iron excess indicated by serum ferritin levels. This observational descriptive study was undertaken on 200 patients (5 to15 yrs of age) in the department of Pediatrics in SCB Medical College, Cuttack, Odisha, India from to after obtaining clearance from institutional ethical committee. Out of total 200 TDT children, 141(70.50%) were euthyroid and 59(29.50%) were hypothyroid. Among hypothyroid children, 9(4.5%) had overt hypothyroidism and 50(25%) children had subclinical hypothyroidism. In children &amp;#60;10 years of age group there was a positive correlation between serum ferritin and rise in serum TSH (p &amp;#60; 0.05, r= .553). The rise in serum ferritin was statistically not significant with fall in serum FT4 (p &amp;#60; 0.05, r= .122). In children &amp;#62;10 years of age group, there was positive correlation between serum TSH and serum ferritin (p &amp;#60; 0.05,r=.845). There was an inverse relation between rise in serum ferritin and fall in serum FT4 (p &amp;#60; 0.05, r= -.406). Hypothyroidism was associated in significant number of transfusion dependent thalassemia patients. Adequate iron chelation therapy to keep serum ferritin level within normal limit and early detection of hypothyroidism preferably below 10 years of age will prevent hypothyroidism and its complications in transfusion dependent thalassemia.

Inflammation-based scores in benign adrenocortical tumours are linked to the degree of cortisol excess: a retrospective single-centre study.

Benign adrenocortical tumours are diagnosed in ∼5% of adults and are associated with cortisol excess in 30%-50% of cases. Adrenal Cushing's syndrome (CS) is rare and leads to multiple haematological alterations. However, little is known about the effects of the much more frequent mild autonomous cortisol secretion (MACS) on immune function. The aim of this study was to evaluate the haematological alterations in benign adrenocortical tumours with different degrees of cortisol excess. We investigated 375 patients: 215 with non-functioning adrenal tumours (NFAT), 138 with MACS, and 22 with CS. We evaluated the relationship between the degree of cortisol excess and full blood count as well as multiple inflammation-based scores, including the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), and the systemic immune-inflammation index (SII). We observed a gradual and significant increase of leucocytes, neutrophils, and monocytes across the spectrum of cortisol excess, from NFAT over MACS to CS. Neutrophil-to-lymphocyte ratio and SII were significantly higher in both MACS and CS when compared to NFAT (P < .001 and P = .002 for NLR and P = .006 and P = .021 for SII, respectively). Conversely, LMR was lower in MACS and CS than in NFAT (P = .01 and <.001, respectively) but also significantly lower in CS compared to MACS (P = .007). Neutrophil-to-lymphocyte ratio, SII, and LMR correlated with the degree of cortisol excess in benign adrenocortical tumours and were altered in patients with CS and MACS. These findings suggest that, similar to clinically overt CS, MACS also affects the immune function, potentially contributing to the MACS-associated comorbidities.

High-Definition Abdominal Body Scale

Introduction: High-definition liposuction (HDL) has been coined to identify liposuction results that are superior to traditional liposuction. The HDL Body scale has been previously described to help objectify changes required to achieve HDL results (that range from 2 to 10 score) with the ultimate goal of achieving a near perfect 9 or 10 body score. Materials/Methods: We present the High-Definition (HD) Abdominal Body Scale that is intended to assist with attaining HD abdominal contouring outcomes. High-definition abdominal contouring outcomes require comprehensive correction of abdominal contour concerns as well as creation of abdominal muscle highlights and natural shadows. HD Abdominal Body Scale assigns scores ranging from 2 to 10 with the ultimate goal of achieving a near perfect 9 or 10 body score indicative of HD outcomes. Results: The HD Abdominal Body Scale and subsequent surgical algorithm for HD abdominal contouring and case studies are presented. Discussion: Considerations for achieving HD abdominal contouring outcomes include assessing degree of fat excess, integrity of abdominal muscles, amount of skin redundancy, as well as quality and extent of skin texture changes. Evaluation of these factors provides the premise for determining HD abdominal contouring scores. HD abdominal contouring scores are used to establish proper patient selection, appropriate surgical design, and objective assessment of outcomes. Conclusion: This article presents an abdominal HDL Body Scale that helps expand patient populations who are candidates for HD body contouring. Surgeons’ outcomes may be improved using the HDL body scale and surgical algorithm presented.

Revealing the peculiarities of asymmetry and kurtosis coefficients of gas medium parameters in premises during fire

The object of the study is the coefficients of asymmetry and excess of the selective distribution of hazardous parameters of the gas environment during material fires. The practical importance of the research lies in the use of measures of asymmetry and kurtosis for early detection of fires. The measures of asymmetry and kurtosis for sampling the final size of an arbitrary dangerous parameter of the gas environment are substantiated. The proposed measures make it possible to investigate the peculiarities of the coefficients of asymmetry and kurtosis in relation to the selective distribution of an arbitrary dangerous parameter of the gas environment. At the same time, it becomes possible to numerically determine the degree of difference of the sample distributions of dangerous parameters from the Gaussian, as well as the features of such measures. Experiments were conducted to determine the degree of asymmetry and excess of dangerous parameters of the gas environment in the laboratory chamber at the intervals of the absence and presence of ignition of the test materials. The obtained results indicate that on the intervals of absence and presence of fires, the selective distributions of dangerous parameters of the gas environment differ from the Gaussian distribution. Distributions are complex and individual in nature. Features of measures of asymmetry and kurtosis depend on the type of ignition material. It was established that the maximum values of the modulus of increase in the degree of asymmetry are characteristic for the carbon monoxide concentration (2.939) during the ignition of paper, for the smoke density (3.098) during the ignition of textiles, as well as for the temperature during the ignition of alcohol (7.163) and wood (1.06). It was determined that the maximum values of the modulus of excess measure increase are characteristic for smoke density (4.678) when paper, wood (1.652) and textiles (28.932) ignite, as well as for temperature (49.377) when alcohol ignites

European Society of Endocrinology Clinical Practice Guidelines on the management of adrenal incidentalomas, in collaboration with the European Network for the Study of Adrenal Tumors.

Adrenal incidentalomas are adrenal masses detected on imaging performed for reasons other than suspected adrenal disease. In most cases, adrenal incidentalomas are non-functioning adrenocortical adenomas, but may also require therapeutic intervention including that for adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastases. Here, we provide a revision of the first international, interdisciplinary guidelines on incidentalomas. We followed the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system and updated systematic reviews on four predefined clinical questions crucial for the management of incidentalomas: A) How to assess risk of malignancy? ; B) How to define and manage mild autonomous cortisol secretion? ; C) Who should have surgical treatment and how should it be performed? ; D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? Selected Recommendations: 1) Each adrenal mass requires dedicated adrenal imaging. Recent advances now allow discrimination between risk categories: Homogeneous lesions with HU ≤ 10 on unenhanced CT are benign and do not require any additional imaging independent of size. All other patients should be discussed in a multidisciplinary expert meeting, but only lesions >4 cm that are inhomogeneous or have HU >20 have sufficiently high risk of malignancy that surgery will be the usual management of choice. 2) Every patient needs a thorough clinical and endocrine work-up to exclude hormone excess including the measurement of plasma or urinary metanephrines and a 1-mg overnight dexamethasone suppression test (applying a cutoff value of serum cortisol ≤50 nmol/l (≤1.8 µg/dl)). Recent studies have provided evidence that most patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post dexamethasone >50 nmol/l (>1.8 µg/dl) harbor increased risk of morbidity and mortality. For this condition, we propose the term 'mild autonomous cortisol secretion' (MACS). 3) All patients with MACS should be screened for potential cortisol-related comorbidities that are potentially attributably to cortisol (e.g. hypertension and type 2 diabetes mellitus), to ensure these are appropriately treated. 4) In patients with MACS who also have relevant comorbidities surgical treatment should be considered in an individualized approach. 5) The appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. 6) Surgery is not usually indicated in patients with an asymptomatic, non-functioning unilateral adrenal mass and obvious benign features on imaging studies. Furthermore, we offer recommendations for the follow-up of non-operated patients, management of patients with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses, and for young and elderly patients with adrenal incidentalomas. Finally, we suggest ten important research questions for the future.

Onestep Footwear Public relations Campaign Planning as an Eco-Friendly Brand

This article aims to find out how to plan a public relations campaign to increase public awareness of shoe sole waste. Problems are focused on the degree of excess, disadvantages, opportunities and threats over shoe sole litter. In order to approach this problem, theoretical references from persuasive communication, public relations, campaigns and environmentally friendly products are used. The data was collected through input from the SWOT matrix in the form of questionnaire results that had been filled out by Onestep Footwear and analyzed qualitatively. This study concluded that overall, the shoe campaign for Bumi collaborated with one of the local shoe Brands from Bandung called Onestep Footwear. With this campaign, it is hoped that there will be an increase in public awareness of environmental pollution caused by shoe sole waste, and the emergence of a sense to continue to protect the environment by using environmentally friendly shoes, such as Onestep Footwear.

Inflammation-based scores in benign adrenocortical tumours are related to the degree of cortisol excess

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Case Report: Management of Mild Autonomous Cortisol Secretion

Mild autonomous cortisol secretion is a term used to describe biochemical evidence of abnormal cortisol secretion in patients with ACA, but without the classical external manifestations of overt CS, such as central muscle weakness, adipose tissue redistribution, and skin fragility. Materials and methods: In this study, we report a case of patient who presents mild autonomous cortisol secretion among incidentally discovered adrenal masses; followed in unit of the endocrinology, diabetology, metabolic diseases and nutrition department of the Mohammed VI University Hospital of Marrakesh. Case report: A 68-year-old woman with a history of well-controlled hypertension and diabete presents to our department for etiological assessment of an adrenal incidentaloma. adrenal scan confirms a diagnosis of an incidental right adrenal nodule measuring 27x26mm is also identified having an density of 33UH and washout &gt; 50%, the patient’s physical examination is unremarkable and she does not have any overt Cushingoid features or midline back pain or paroxysmal attacks. Biochemical investigations revealed a morning cortisol following 1 mg of dexamethasone is 2 ug/dL. A normal serum potassium and methoxylated derivatives in urine are normal. A diagnosis of a mild autonomous cortisol secretion was made and given the relatively mild degree of cortisol excess and well-controlled Comorbidities a conservative management is chosen, she should undergo annual clinical reassessments. If she develops new or worsening cortisol-related comorbidities, she should undergo further biochemical testing and reconsideration of adrenalectomy. Conclusion: Future studies with adequate randomization and follow-up to assess adverse clinical endpoints are needed to determine the optimal management and follow-up of patients with MACS.

Seeing Pink

Seeing Pink

Manganese(I)-catalyzed asymmetric (transfer) hydrogenation of ketones: An insight into the effect of chiral PNN and NN ligands

A new type of (RC,SP)-1-(2-diphenylphosphino)ferrocenylethylamine N-substituted with a (RC)-5,6,7,8-tetrahydroquinolinyl group (LPNN-1) was successfully employed as a chiral chelating ligand in both Mn-catalyzed asymmetric transfer hydrogenation (ATH) and asymmetric hydrogenation (AH) of a broad range of ketonic substrates (39 examples), leading to high conversions and excellent enantioselectivities for their product alcohols. In particular, PNN-pincer complex Mn-1 and its NN-bidentate analogue Mn-2 have been isolated and their comparative performance as catalysts studied with Mn-1 proving more effective in both ATH and AH. Moreover, Mn-1 generally imparted higher degrees of enantiomeric excess (ee) in both hydrogenation processes which can reach up to 99% in ATH and 93% in AH for propiophenone-type substrates. DFT calculations highlight the importance of π-π interactions and steric hindrance between catalyst and substrate which manifests itself in enhancements in ee for propiophenone over acetophenone substrates. Furthermore, a possible mechanism for the Mn-catalyzed ATH has been proposed on the basis of a joint DFT and experimental investigation.

ODP046 Initial Lessons from a Prescreening Protocol to Identify Participants with Classic CAH Potentially Eligible for Gene Therapy Treatment with BBP-631, an Adeno-associated Virus (AAV) Serotype 5-Based Recombinant Vector Encoding the Human CYP21A2 Gene

Abstract Here we present the design and early findings from CAH-300 /NCT05101902, a prescreening protocol to identify participants who are potentially eligible for the CAH-301 Phase 1/2 treatment trial with BBP-631, an AAV5-based gene therapy for classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). The CYP21A2 gene encodes the 21-hydroxylase enzyme that plays a critical role in glucocorticoid and mineralocorticoid synthesis by the adrenal cortex. CYP21A2pathogenic variants cause 21OHD, the most common form of CAH, characterized by variable degrees of adrenal insufficiency and androgen excess. Standard treatment of classic CAH due to 21OHD usually consists of daily replacement doses of glucocorticoid (GC) and mineralocorticoid. However, supraphysiologic GC doses are often required to mitigate the androgen excess and it is difficult to dose exogenous GCs in a manner that provides adequate disease control while avoiding overtreatment. A gene therapy approach offers the potential to restore cortisol and aldosterone production from the adrenal glands in a physiologically regulated manner. To assess potential eligibility for the gene therapy trial CAH-301, participants in the prescreening protocol CAH-300 undergo initial assessments for the presence of exclusionary anti-21OH antibodies and anti-AAV5 antibodies, as well as for characterization of CYP21A2 genotype. After the participant meets initial eligibility criteria, referral to a treatment trial center may be arranged. To address the challenges in recruiting participants with this rare disorder, prescreening assessments are performed at the participant's home allowing for recruitment from broad geographic areas including those without proximity to a tertiary care center. Home assessments have also provided flexibility for participants during the COVID pandemic. Additional assessments during prescreening that further impact eligibility for the gene therapy trial include review of participant medical history and collection of hormonal biomarkers including 17-hydroxyprogestone, androstenedione, cortisol, and ACTH. Preliminary laboratory data show the expected presence of low cortisol (measured by both gas chromatography-mass spectrometry and immunoassay) with concomitant elevated ACTH, confirming the potential to detect meaningful changes in endogenous cortisol production after BBP-631 dosing. In summary, our prescreening approach with home assessments has enabled the efficient identification of participants potentially eligible for the CAH-301 gene therapy trial. Preliminary data have confirmed the presence of low cortisol and thus potential for detecting meaningful increases in endogenous cortisol production after gene therapy with BBP-631. Presentation: No date and time listed

ODP650 Impaired Cognition in Patients with Mild Autonomous Cortisol Secretion

Abstract Background Limited data describe cognitive deficits in patients with Cushing syndrome (CS). The impact of mild autonomous cortisol secretion (MACS) on cognition is unknown. Objective To determine the impact of MACS on cognitive function. Methods Single-center cross-sectional study of adults with MACS and age and sex-matched volunteers. MACS was defined as cortisol &amp;gt;1.8 mcg/dL following the dexamethasone suppression test (DST) in patients with an adrenal incidentaloma and no features of CS. We measured cognitive function through the NIH toolbox cognition battery (7 standardized tests of attention, episodic and working memory, language, executive function, and processing speed). T-scores corrected for age, sex, education, and race were used for analysis. All patients completed the SF-36 questionnaire. The frailty index was calculated as previously reported (Singh S. JCEM 2020). Results Participants included 50 patients with MACS (median age 61, range 54-68) and 50 volunteers (median age 60 years, range 54-68), with 60% women in both groups. In patients with MACS, median post-DST morning cortisol was 3.6 (range, 2.4-6.2), and median corticotropin was 8.5 (range, 5.9-13) pg/mL (normal 6-60). Patients with MACS had a higher median frailty index (median of 0.26 vs. 0. 05 in volunteers, p&amp;lt;0. 001) and lower quality of life scores on the SF-36 survey (median of 47 vs. 91, p&amp;lt;0. 001). Compared to volunteers, patients with MACS performed worse in the domains of attention and executive function (effective allocation of one's limited capabilities in an abundance of stimuli) (median T-score of 50 vs. 46, p=0. 03), cognitive flexibility (tested as the capacity to plan and monitor goal-directed activities) (median T-score of 61 vs. 55, p=0. 01). The fluid composite score (includes executive function, episodic memory, working memory, and processing speed) was lower in patients with MACS (mean of 53.2 vs. 48.9, p=0. 03). The total composite score was lower in patients with MACS when compared to volunteers (median T score of 50 vs. 54, p=0. 06). The total composite cognitive scores in patients of MACS were associated with the Frailty Index (R2 = 0.13, p = 0. 025) and SF-36 scores (R2 = 0. 08, p = 0. 05), but not post-DST cortisol. Conclusion Compared to volunteers, patients with MACS demonstrate cognitive impairment, particularly in the executive domain, which closely mimics changes observed with aging. These deficits do not correlate with the degree of cortisol excess. Presentation: No date and time listed