Adrenal Insufficiency Patients Research Articles

Urine metabolomics signature reveals novel determinants of adrenal suppression in children taking inhaled corticosteroids to control asthma symptoms.

Asthma is routinely treated with inhaled corticosteroids (ICS). Asthma patients on ICS are at increased risk of adrenal suppression, a potentially serious effect of long-term glucocorticoid exposure; however, this relationship is poorly understood. Therefore, this study aims to identify metabolite biomarkers related to adrenal suppression in asthma patients taking ICS. A total of 571 urine metabolites from 200 children with asthma on ICS in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) cohort were profiled. Samples were grouped by peak plasma cortisol measurement as adrenal sufficient (>350 nmol/L) or insufficient (≤350 nmol/L) (outcome). Regression and discriminant-based statistical models combined with network analyses were utilized to assess relationships between metabolites and the outcome. Finally, prioritized metabolites were validated using data from an ancillary study of the Childhood Asthma Management (CAMP) cohort with similar characteristics to PASS. Ninety metabolites were significantly associated with adrenal suppression, of which 57 also could discriminate adrenal status. While 26 metabolites (primarily steroids) were present at lower levels in the adrenal insufficient patients, 14 were significantly elevated in this group; the top metabolite, mannitol/sorbitol, was previously associated with asthma exacerbations. Network analyses identified unique clusters of metabolites related to steroids, fatty acid oxidation, and nucleoside metabolism, respectively. Four metabolites including urocanic acid, acetylcarnitine, uracil, and sorbitol were validated in CAMP cohort for adrenal suppression. Urinary metabolites differ among asthma patients on ICS, by adrenal status. While steroid metabolites were reduced in patients with poor adrenal function, our findings also implicate previously unreported metabolites involved in amino acid, lipid, and nucleoside metabolism.

The study of serum cortisol in patients prescribed glucocorticoid in Hue University of Medicine and Pharmacy Hospital

Background: The adrenal disorders such as adrenal insufficiency and Cushing syndrome may be life-threatening unless patients are diagnosed and treated timely. Taking exogenous glucocorticoid (GC) interfered with the interpretation of the level of serum cortisol in either diagnosis of adrenal insufficiency or evaluation the function of hypothalamic-pituitary-adrenal axis. Objectives: 1) Evaluating the difference between the level of basal serum cortisol before and after taking GC. 2) Evaluating the level of basal serum cortisol in patients who were prescribed physiological dose of GC when withdrawn. Materials and method: This is a cross-sectional study that enrolled patients prescribed GC. It obtained the levels of basal serum cortisol before and after taking GC. In 2nd objective, the level of basal serum cortisol was measured in patients who were diagnosed with GC-induced adrenal insufficiency and prescribed physiological dose of GC when withdrawn temporarily. Results: The values of basal serum cortisol when taking hydrocortisone and prednisolone were higher than before prescribed (p < 0.05). In contrast, the values of basal serum cortisol when taking fluticasone were lower than before prescribed (p < 0.05). Even inhaled fluticasone could affect the level of basal serum cortisol. In GC-induced adrenal insufficiency patients prescribed physiological dose of GC, the group of patients with the values of cortisol when withdrawn < 100 nmol/L accounted for 61.9% while ones with the values 100 - 375 nmol/L accounted for 38.1%. The analysis of ROC curve shows that the duration of physiological-dose-GC prescription could predict the levels of basal serum cortisol when withdrawn and hypothalamic-pituitary-adrenal axis recovery with optimal cut-off of duration is 13 months (Sensitivity: 100%, specificity: 92.3%). Conclusion: Exogenous glucocorticoid could affect the results of basal serum cortisol. The duration of physiologic-dose-GC prescription could predict that hypothalamic-pituitary-adrenal axis recovery in patients with glucocorticoid-induced-adrenal insufficiency could be happened and who could achieve adequate response of Synacthen stimulation test. Key words: cortisol, glucocorticoid, hydrocortisone, methylprednisolone, fluticasone, dexamethasone, cross-reactivity.

The cost burden of hospitalisation for adrenal insufficiency patients in the NHS in england

The cost burden of hospitalisation for adrenal insufficiency patients in the NHS in england

The usefulness of saliva cortisol as a marker for replacement therapy in adrenal insufficiency patients treated with hydrocortisone in tablet versus capsule forms: A randomized crossover trial

The usefulness of saliva cortisol as a marker for replacement therapy in adrenal insufficiency patients treated with hydrocortisone in tablet versus capsule forms: A randomized crossover trial

Serological Evidence and Self-reported Outcomes in Patients with Adrenal Insufficiency during the first waves of COVID-19 in the North-East Italy.

COVID-19 is a potentially serious new infection firstly broken out in the North East Italy during Spring 2020. Patients with adrenal insufficiency (AI) have a known increased risk of infections, that could precipitate to adrenal crisis. Even COVID-19-related psycho-social impact could affect their health, requiring a dynamic adaptation of daily glucocorticoid (GC) therapy. The aim of this study was to evaluate the incidence of COVID-19 infection and self-reported outcomes in AI patients after the first pandemic waves. Open-label, cross-sectional monocentric study on 84 (65 primary, 19 secondary) AI patients, resident in Veneto and followed-up in our out clinical of Endocrine Unit. All patients underwent serological investigation of anti-SARS-CoV2 IgG and purpose-built "ADDI-COVID" questionnaire by August 2020 and were recontacted to reevaluate COVID-19 infection occurrence in March-April 2021. All patients resulted negative to the serological test for anti-SARS-CoV2 IgG at the end of the first pandemic wave. After the third wave, COVID-19 infection occurred in 8 patients without need of hospitalization. Half patients felt an increased risk of COVID-19 infection, significantly associated with increased stress and GC stress-dose. Only one patient reported adrenal crisis stress-correlated. The majority of AI workers changed working habits, significantly reducing COVID-19-related stress. AI patients did not show an increased incidence of COVID-19, but the perception of increased COVID-19 infection risk significantly impacts their psychological well-being, working habits and GC daily doses. Therapeutic patient education is crucial especially for AI workers to prevent and treat situations that could lead to an adrenal crisis.

Monitoring adrenal insufficiency through salivary steroids: a pilot study.

Various glucocorticoid replacement therapies (GRTs) are available for adrenal insufficiency (AI). However, their effectiveness in restoring glucocorticoid rhythm and exposure lacks adequate biochemical markers. We described the diurnal salivary cortisol (SalF) and cortisone (SalE) rhythm among different GRTs and analysed the associations between saliva-derived parameters and life quality questionnaires. Control subjects (CSs, n = 28) and AI patients receiving hydrocortisone (HC, n = 9), cortisone acetate (CA, n = 23), and dual-release hydrocortisone once (DRHC-od, n = 10) and twice a day (DRHC-td, n = 6) collected 9 saliva samples from 07:00 to 23:00. Patients compiled Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, and Addison disease-specific quality-of-life questionnaires. SalE and SalF were measured by liquid chromatography-mass spectrometry. Exposure was monitored using SalE for HC and DRHC and SalF for CA. Area under the curve (AUC) was computed. Different GRTs were compared by Z-scores calculated from saliva-derived parameters. Questionnaire results predictors were evaluated with multiple regression analysis. Compared with controls, all GRTs resulted in glucocorticoid overexposure in the morning. Hydrocortisone, CA, and DRHC-td caused overexposure also in afternoon and evening. Compared with other treatments, CA determined increased Z-score-07:00 (P < .001), DRHC-td determined increased Z-score-AUC07:00→14:00 (P = .007), and DRHC-od induced lower Z-score-AUC14:00→23:00 (P = .015). Z-scores-AUC14:00→16:00 ≥ .619 best predicted questionnaire scores. None of the GRTs mimics normal glucocorticoid rhythmicity and exposure. SalE, SalF, and Z-score may be useful markers for monitoring and comparing different GRTs. Excess glucocorticoid in early afternoon best associated with depressive symptoms and worse life and sleep quality.

Exploring sexual function in adrenal insufficiency: findings from the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent therapy in hypocortisolism (DREAM) trial.

Data on sexual function in patients with adrenal insufficiency are scarce and largely controversial. To investigate sexual dysfunction in patients with primary and secondary adrenal insufficiency and the effects of switching to once-daily dual-release hydrocortisone on sexual function in outcome assessors blinded, randomized, multicenter, active comparator clinical trial. Eighty-nine adrenal insufficiency patients on conventional, multiple daily doses of glucocorticoid replacement, enrolled in the Dual RElease hydrocortisone versus conventionAl glucocorticoid replaceMent in hypocortisolism (DREAM) trial, were randomly assigned to continue their therapy or to switch to an equivalent dose of dual-release hydrocortisone. Sixty-three patients (34 women) consented to sex steroid measurements and questionnaires completion for quality of life (Addison's disease-specific quality-of-life questionnaire) and sexual function evaluation (female sexual function index for women, International Index of Erectile Function-Erectile Function for men) at baseline and 24weeks after randomization. At baseline, sexual dysfunction was observed in 41% of women and 59% of men with adrenal insufficiency. In both sexes, no associations were found between sexual function and hormone levels, whereas Addison's disease-specific quality-of-life questionnaire total and fatigue domain scores positively correlated with total female sexual function index and International Index of Erectile Function-Erectile Function scores. At 24weeks, there was no significant difference either in sexual function or sex steroid levels between study groups. In the dual-release hydrocortisone group, the variation in the female sexual function index desire domain score was positively associated with the change in Addison's disease-specific quality-of-life questionnaire's symptom domain score (ρ=0.478, p=0.045). Sexual dysfunction is common in adrenal insufficiency patients and is likely explained by multiple factors. dual-release hydrocortisone treatment is not directly associated with sexual function improvement, but an indirect effect mediated by quality-of-life amelioration cannot be excluded.

Salivary Cortisol Measurement Contamination After Oral Hydrocortisone: A Randomized Crossover Trial.

The study aimed to evaluate salivary cortisol (SC) contamination and determine the associated factors in secondary adrenal insufficiency (SAI) patients treated with hydrocortisone (Hc). A randomized crossover trial involved SAI patients. SC was measured before the morning Hc dose, then at one, two, and four hours after. The procedure was performed twice on two days of a week: one day while taking Hc in tablet form (tablet set) and one day while taking Hc in capsule form (capsule set). Area under the curve (AUC) of SC levels over time was calculated in each participant for the two sets. SC contamination was defined as AUCtablet above the 95th percentile of AUCcapsule. Thirty-four patients (24 females and 10 males) with a median age of 48 years were enrolled. Post-Hc dose SC levels were higher in tablet than in capsule set, particularly at one hour. Prevalence and extent of SC contamination were estimated to 32% and 88%, respectively. In capsule set, SC measured two hours after Hc intake showed the strongest correlation with AUC (r=0.88, p<0.001). In multivariate analysis, serum potassium≥3.9 mEq/l was the only predictor for SC contamination [multi-adjusted OR (95% CI): 7.1 (1.4-36.1); p=0.018]. SC measured during the two hours after Hc intake is inaccurate for glucocorticoid replacement therapy assessment in SAI patients treated with Hc in tablet form.

Morbidity in Patients with Chronic Adrenal Insufficiency - Cardiovascular Risk Factors and Hospitalization Rate Compared to Population Based Controls.

Patients with adrenal insufficiency (AI) have been found to have increased cardiovascular morbidity, partly associated with nonphysiologic glucocorticoid replacement. We included two separate cohorts (cohort 1 n=384 patients, cohort 2 n=180 patients) of patients with chronic primary and secondary AI under standard replacement therapy and compared them to two age- and sex-matched population-based studies (SHIP-TREND/DEGS). Odds ratios with 95% CI for hypertension, hyperlipidemia/HLP, type 2 diabetes/T2DM, obesity, and hospitalization with adjustment for confounders were evaluated by logistic regression. Patient cohort 1 had significantly lower ORs for obesity [0.4 (0.3-0.6), p<0.001] and hypertension [0.5 (0.3-0.6), p<0.001] compared to SHIP-TREND and for obesity [0.7 (0.5-0.9), p=0.01], hypertension [0.4 (0.3-0.5), p<0.001] and HLP [0.4 (0.3-0.6), p<0.001] compared to DEGS. In cohort 2, ORs were significantly lower for HLP compared to both SHIP-TREND [0.4 (0.2-0.7), p=0.001] and DEGS [0.3 (0.2-0.5), p<0.001] and for hypertension [0.7 (0.4-0.9), p=0.04] compared to SHIP-TREND. In patients with SAI from cohort 2, ORs for DM2 [2.5 (1.3-4.9) p=0.009], hypertension [2.5 (1.4-4.5), p=0.002] and obesity [1.9 (1.1-3.1), p=0.02] were significantly higher compared to DEGS, whereas ORs for HLP were significantly lower compared to both SHIP [0.3 (0.1-0.6), p=0.002] and DEGS [0.3 (0.1-0.6), p<0.001]. In most of our AI patients treated with conventional glucocorticoid doses, the risk for T2DM, obesity, hypertension, and HLP was not increased. The number of hospitalizations was significantly higher in AI patients compared to controls, which might reflect increased susceptibility but also a more proactive management of concomitant diseases by physicians and patients.

Fertility and pregnancy in adrenal insufficiency.

Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

Increased risk of hospitalization, intensive care and death due to COVID-19 in patients with adrenal insufficiency: A Swedish nationwide study.

Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

THU611 Circadian Misalignment Of Melatonin Secretion In Adrenal Insufficiency (AI)

Abstract Disclosure: M. Darji: None. S. Pannain: None. S. Sam: None. E. Van Cauter: None. E.C. Hanlon: None. Background: Despite glucocorticoid replacement, the mortality risk of AI remains markedly elevated. Under normal conditions, the circadian rhythm of endogenous cortisol levels is a major internal synchronizing signal between central and peripheral circadian clocks. There is increasing evidence indicating that circadian misalignment has a host of adverse effects, including increased cardio-metabolic risk. The present study aimed to assess circadian function in AI patients, as compared to individually-matched healthy subjects, under controlled laboratory conditions. The 24-h profile of melatonin, normally secreted exclusively at night, was used as the marker of central circadian timing. The 24-h profile of leptin was used as a marker of peripheral circadian function. Methods: Plasma cortisol, melatonin, and leptin were measured over a 24-h period every 30-60 minutes under controlled light-dark, sleep-wake and dietary conditions. A best-fit curve was calculated for each individual hormonal profile using a locally weighted nonlinear regression procedure with a window of 4 hours. The peak and the nadir were defined as the maximum and minimum of the best-fit curve, respectively. The amplitude was defined as half of the difference between the peak and the nadir. Sleep was polygraphically recorded. During daytime hours, the participants completed validated questionnaires assessing Vigor, Mood and Sleepiness. Results: Complete data sets were obtained in 15 AI patients (12 women; age: 47.9 ±12.5 years, BMI: 26.6 ± 12.5 kg/m2; mean ± SD). Twelve AI patients were on hydrocortisone treatment (total dose range: 20 to 40mg/day, number of doses: 1-5 /day) and 3 were on prednisone treatment. Controls (n=15, 12 women) were aged 48.5 ±14.5 years with BMI of 26.5 ± 5.4 kg/m2. The amplitude of the cortisol profile was wider in AI patients, relative to controls, with a higher morning peak and an extended and lower nocturnal nadir. Unexpectedly, we observed a marked difference in the melatonin profile in AI patients as compared to controls. A daytime phase of elevated melatonin levels, culminating prior to lights off while the patients were awake, was detected in 9 of the 15 AI patients. The nocturnal elevation persisted with a similar amplitude to that observed in controls but was advanced by 1-2 hours. The 24-h leptin profile was similar in the two groups. The presence of a daytime melatonin peak in AI patients was associated with lower ratings of vigor and mood, and higher ratings of sleepiness. Conclusion: Glucocorticoid treatment to replace the endogenous levels and circadian rhythmicity of cortisol in AI may impact central circadian timing, resulting in daytime, in addition to nighttime, release of melatonin. This finding suggests that exogenous cortisol replacement that does not mimic a normal 24-h rhythm, may cause central circadian dysfunction and contribute to alterations in mood, vigor and sleepiness. Presentation: Thursday, June 15, 2023

SAT301 Patient-centered Outcomes Measures To Assess Quality Of Life In Adrenal Insufficiency Treatment

Abstract Disclosure: W.J. Hover: None. K.E. Lowe: None. M.E. Lowe: None. J.G. Kallet: None. M.F. Slovick: None. S.L. Majka: None. M.T. McDermott: None. E.A. Regan: None. Individuals with adrenal insufficiency (AI) have been shown to have reduced quality of life in spite of hormone replacement. Although late-stage insufficiency and adrenal crisis may show signs including hypotension and electrolyte abnormalities, patient-reported symptoms may predict outcomes in AI and can be a key factor in understanding poor quality of life in adrenal insufficiency. The SF-36, a generic quality of life (QoL) survey has been reported in adrenal insufficiency but may lack disease-specific domains to define QoL deficits in AI. An AI disease-specific QoL survey, the AddiQoL has also been validated. We evaluated the AddiQol and SF-36 for distinguishing the health status of AI patients in terms of diagnosis, medication use and risk of crisis using a patient registry. Methods: We identified 344 individuals from the MyAI patient registry who had provided responses to both the AddiQoL and SF-36. We compared the AddiQoL overall score with three domains of the SF-36: physical function, role physical, vitality, and the physical and mental component scores (PCS and MCS). Results: Respondents were from all 50 US states with 83% female and mean (SD) age of 50 (15) years. AI diagnosis was Primary 63%, Central 32% and congenital adrenal hyperplasia 5% based on self-report and confirmation with medical records. Both the SF-36 and AddiQoL identified reduced QoL in the AI participants and were significantly correlated: PCS to AddiQoL 0.73 and MCS to AddiQoL 0.63. Role Physical, Vitality and General Health were the most reduced domains with mean values of 38.4 (43.5), 35.6 (24.5) and 40.8 (24.7) respectively. Primary AI showed significantly better QoL than Central AI by both SF-36 and AddiQol [80.3(15.1) vs 69.9 (14.2), p&amp;lt;0.001]. Respondents who reported an adrenal crisis within the past year had significantly lower AddiQol [72.8(15.4) vs 82.3 (15.4), p&amp;lt;0.001] and SF-36 scores. Respondents who were currently treated with hydrocortisone (HC) had better QoL than those on Prednisone [HC 78.1 (15.2), Prednisone 74.1 (15.9), p=0.02 adjusted for diagnosis group]. Conclusions: In a geographically broad cohort of US AI patients, we confirm significant reductions in QoL in spite of treatment. Both the SF-36 and AddiQoL were able to distinguish differences in QoL by diagnosis, risk of adrenal crisis and medication. Further work to define specific patterns of high-risk symptoms may improve early diagnosis of impending crisis. Presentation: Saturday, June 17, 2023

OR30-06 Hospitalisation, Intensive Care And Death Due To COVID-19 In Swedish Patients With Adrenal Insufficiency

Abstract Disclosure: R. Bergthorsdottir: None. D. Esposito: None. G. Johannsson: None. O. Ragnarsson: None. P. Dahlqvist: None. S. Bensing: None. J. Nåtman: None. F. Nyberg: None. Background: Patients with adrenal insufficiency (AI) have increased risk for morbidity and mortality related to infectious disorders. Whether patients with AI have an increased risk for infection with Coronavirus disease 2019 (COVID-19), need of hospitalisation, intensive care or death in COVID-19 disease is still unknown. Methods: Swedish national register-based cohort study. Patients with primary and secondary AI were identified in linked Swedish national healthcare registers and followed from 2020-01-01 until 2021-02-28, and were compared to controls from the general population, matched 10:1 for age and sex. The following COVID-19 outcomes were studied: hospitalisation, intensive care and death. Findings: We identified 5430 patients with AI, and 54300 controls; 47.6% females, with a mean (±SD) age of 57.1 (±18.1) years. The prevalence of positive COVID-19 testing and diagnosis were similar in patients with AI and controls. The rate of hospitalisation (2.1% vs 0.8%), intensive care (0.3% vs 0.1%) and death (0.8% vs 0.2%) for COVID-19 were higher in AI patients than controls, respectively. After adjustment for socioeconomic factors and comorbidities, the hazard ratio (95% confidence interval) for hospitalisation was 1.96 (1.59-2.43), for intensive care admission it was 2.76 (1.49-5.09) and for death 2.29 (1.60-3.28). Interpretation: Patients with AI have an increased risk for severe and fatal COVID-19 infection and should therefore be prioritised for vaccination, early antiviral and supportive treatment to prevent hospitalisation and death. Presentation: Sunday, June 18, 2023

OR30-05 Impact Of Adrenal Insufficiency On Outcomes Among Patients Admitted With COVID-19

Abstract Disclosure: E. Krishnaraju: None. V. Deenadayalan: None. S. Maharjan: None. U.A. Ogar: None. A.G. Olafimihan: None. Background: Patients with adrenal insufficiency (AI) are more susceptible to infections including COVID-19 and are more likely to develop adverse complications from adrenal crisis. There is a paucity of data using a national sample size to demonstrate the effect of AI on the hospital course of patients admitted with COVID-19. In this study, we aim to compare the outcomes in patients admitted with COVID-19, with and without a secondary diagnosis of Adrenal insufficiency (AI). Methods: This is a retrospective study of the 2020 National Inpatient Sample (NIS) database, utilizing ICD-10 codes to identify patients admitted for COVID-19 with and without AI. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included a diagnosis of shock, myocardial infarction (MI), deep venous thrombosis (DVT), Urinary Tract Infection (UTI), sepsis, and blood transfusion. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total of 1,058,815 patients with COVID-19 were hospitalized, of which 4,170 (0.4%) had a secondary diagnosis of adrenal insufficiency. There was no significant difference between the average age between the two groups, however, the COVID-AI group had a higher proportion of females (51.44% females; P=0.016). This group also had a higher odds of having a Charlson comorbidity index of 5 or more (38.73% vs 27.79%, P&amp;lt;0.001) and having concomitant comorbidities like congestive heart failure (20.38% vs 15.55%; P&amp;lt;0.001), chronic kidney disease (24.7% vs 19.65%; P&amp;lt;0.001), COPD (18.11% vs 14.69%; P=0.004), and anemia (32.85% vs 19.91%; P&amp;lt;0.001) compared to group without AI. Most notably, COVID-AI patients had significantly higher odds of mortality (AOR 2.45, p&amp;lt;0.001), and prolonged hospital stay (AOR 6.82 days, p&amp;lt;0.001) after adjusting for confounders. Among the secondary outcomes, the COVID-AI group had significantly higher odds of having sepsis (AOR 4.14, p&amp;lt;0.001), shock (AOR 4.40, p&amp;lt;0.001), MI (AOR 2.11, p=0.001 ), AKI (AOR 1.84, p&amp;lt;0.001), DVT (AOR 2.45, p&amp;lt;0.001), need for intubation (AOR 3.42, p&amp;lt;0.001), pressor use (AOR 3.57, p&amp;lt;0.001 ), and blood transfusion (AOR 2.33, p&amp;lt;0.001 ). Conclusion: Patients who are adrenal insufficient are routinely educated to increase their steroid replacement therapy during illness. Previous studies have shown AI patients who are adequately treated and trained display the same incidence of COVID-19 symptoms and disease severity as Non-AI patients. Our study has shown any patient with a history of AI have an overall higher odds of mortality, prolonged hospital stay, and complications requiring ICU admission such as shock, need for pressors, and intubation. Therefore, emphasis on COVID preventative measures is vital for this subset of patients. Presentation: Sunday, June 18, 2023

Long-Term Usage of Oral Glucocorticoids Leading to Adrenal Insufficiency: A Comprehensive Review of the Literature.

Systemic glucocorticoid therapy is used worldwide by one to three percent of the general population and0.5-1.8% on long-term oral glucocorticoid use. It iswidely used inconditions such as inflammation, autoimmune diseases, and cancer to inhibit inflammatory responses. One of the possible undesirable side effects of exogenous corticosteroid treatment is adrenal suppression upon discontinuation of the medicationand adrenal insufficiency afterutilizing the supraphysiologic doses for more than one month. To prevent patients fromthe unwanted signs and symptoms ofadrenal insufficiency, includingfatigue, gastrointestinal upset,anorexia/weight loss, etc., better management of the quantity and frequency of exogenous corticosteroiduse, as well as better education before starting its use, is needed. For patients actively on exogenous corticosteroids, a close follow-up must be in place to avoid adrenal suppression after the eventual discontinuation of their use. This review article summarizes the important studies to date on this subject, especiallyoral glucocorticoid use,and analyzes risks such as dose, duration of exposure, and comorbidities of adrenal insufficiency associated with oral glucocorticoid use. We comprehensively include information on those with primary adrenal insufficiency and pediatric patients, hoping to provide better insight and clinical reference.

Effects of the therapy shift from cortisone acetate to modified-release hydrocortisone in a group of patients with adrenal insufficiency.

Patients with adrenal insufficiency (AI) may be exposed to supraphysiological glucocorticoids levels during standard treatment with cortisone acetate (CA) or immediate-release hydrocortisone (IR-HC). Recent studies, predominantly including patients in IR-HC treatment, suggested that modified-release hydrocortisone (MRH) provide a more physiological cortisol rhythm, improving metabolic control and quality of life. Our primary aim was to assess clinical and biochemical modifications in patients shifted from CA to MRH. We designed a retrospective longitudinal study, enrolling 45 AI patients (22 primary and 23 secondary AI) treated exclusively with CA thrice daily, shifted to MRH once daily; 29/45 patients concluded at least 18-months follow-up (MRH-group). We recruited 35 AI patients continuing CA as a control group (CA-group). Biochemical and clinical data, including metabolic parameters, bone quality, and symptoms of under- or overtreatment were collected. In 24 patients, a daily salivary cortisol curve (SCC) performed before and one month after shifting to MRH was compared to healthy subjects (HS). No significant changes in glycometabolic and bone parameters were observed both in MRH and CA-groups during a median follow-up of 35 months. A more frequent decrease in blood pressure values (23.1% vs 2.8%, p=0.04) and improvement of under- or overtreatment symptoms were observed in MRH vs CA-group. The SCC showed a significant steroid overexposure in both CA and MRH-groups compared to HS [AUC (area under the curve) = 74.4 ± 38.1 nmol×hr/L and 94.6 ± 62.5 nmol×hr/L respectively, vs 44.1 ± 8.4 nmol×hr/L, p<0.01 for both comparisons], although SCC profile was more similar to HS in MRH-group. In our experience, patients shifted from CA to equivalent doses of MRH do not show significant glycometabolic modifications but blood pressure control and symptoms of over-or undertreatment may improve. The lack of amelioration in glucose metabolism and total cortisol daily exposure could suggest the need for a dose reduction when shifting from CA to MRH, due to their different pharmacokinetics.

Is Preoperative Adrenal Insufficiency Screening Necessary for Cardiovascular Thoracic Surgery Patients?

Background: The association between adrenal insufficiency (AI) and the treatment outcomes of cardiothoracic surgery patients has been little reported. The aims of this study were to investigate the incidence of AI and to compare the post-surgical outcomes of patients with perioperatively treated AI and patients with a normal adrenal response. Methods: A 1.5-year prospective study was conducted in 98 patients scheduled for cardiothoracic surgery. Patients were categorized as either AI or normal-adrenal-response patients. Those with AI were treated with stress doses of glucocorticoid perioperatively. The post-surgical outcomes of patients with AI and of those with a normal adrenaline response were analyzed using multivariable analysis. Results: The overall incidence of AI was 34.7%. There were no statistically significant differences in post-surgical outcomes, including prolonged hospital stay, postoperative infection, prolonged inotropic drug use and relative AI, between the two groups. Only the rate of hyperglycemia requiring insulin infusion was significantly higher in the AI group than in the non-AI group (OR = 14.15, 95% CI = 1.44-138.60, p = 0.02). Conclusions: The proper diagnosis and management of AI can result in surgical outcomes in AI patients comparable to those of normal-adrenal-response patients. Non-life-threatening hyperglycemia requiring insulin infusion was found only in the AI group.

Doctors, teach your adrenal insufficiency patients well: provide them with a European Emergency Card!

Adrenal insufficiency is a life-threatening condition requiring chronic glucocorticoid replacement therapy, as well as stress adaptation to prevent adrenal crises. To increase patients' self-sustainability, education on how to tackle an adrenal crisis is crucial. All patients should carry the European Emergency Card.

Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey.

To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40-59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2-42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.