Citations

Autonomous cortisol secretion (ACS) affects up to 50% of patients with adrenal adenomas. Despite the limited evidence, clinical guidelines recommend measurement of serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S) and corticotropin (ACTH) to aid in the diagnosis of ACS. Our objective was to determine the accuracy of serum concentrations of DHEA-S and ACTH in diagnosing ACS. We conducted a retrospective single center study of adults with adrenal adenoma evaluated between 2000−2020. Main outcome measure was diagnostic accuracy of DHEA-S and ACTH. ACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. Of 468 patients, ACS was diagnosed in 256 (55%) patients with a median post-DST cortisol of 3.45 mcg/dL (range, 1.9–32.7). Patients with ACS demonstrated lower serum concentrations of DHEA-S (35 vs. 87.3 mcg/dL, p < 0.0001) and ACTH (8.3 vs. 16 pg/mL, p < 0.0001) compared to patients with non-functioning adrenal tumors (NFAT). Serum DHEA-S concentration <40 mcg/dL diagnosed ACS with 84% specificity and 81% PPV, while serum ACTH concentration <10 pg/mL diagnosed ACS with 75% specificity and 78% PPV. The combination of serum concentrations of DHEA-S <40 mcg/dL and ACTH <10 pg/mL diagnosed ACS with the highest accuracy with 92% specificity and 87% PPV. Serum concentrations of DHEA-S and ACTH provide additional value in diagnosing ACS.

AbstractContextThe COVID-19 pandemic has impacted healthcare environment.ObjectiveTo determine the impact of the pandemic on self-reported outcomes in patients with adrenal insufficiency (AI).Design and settingProspective longitudinal survey study at 2 tertiary centers.ParticipantsPatients with AI.InterventionPatient-centered questionnaire.Main outcome measuresDepression Anxiety Stress Scales-21, Short Form-36, and AI self-management.ResultsOf 342 patients, 157 (46%) had primary AI, 109 (32%) had secondary AI, and 76 (22%) had glucocorticoid-induced AI. When compared to prepandemic, daily glucocorticoid dose and number of adrenal crises did not change. However, patients reported a higher financial impact from AI (34% vs 23%, P = 0.006) and difficulty accessing medical care (31% vs 7%, P &lt; 0.0001) during the pandemic. A third of patients reported difficulty managing AI during the pandemic. After adjusting for duration and subtypes of AI, younger patients [odds ratio (OR) 2.3, CI 95% 1.3-4.1], women (OR 3.7, CI 95% 1.9-7.1), poor healthcare access(OR 4.2, CI 95% 2.3-7.7), lack of good insurance support (OR 2.8, CI 95% 1.3-5.9), and those with a higher financial impact (OR 2.3, CI 95% 1.3-4.3) reported greater difficulties managing AI. Patients were more likely to report a higher anxiety score (≥8) if they found managing AI challenging during the pandemic (OR 3.0, CI 95% 1.3-6.9), and had lower Physical Component Summary (OR 4.9, CI 95% 2.2-11.0) and Mental Component Summary (OR 4.1, CI 95% 1.8-9.5) scores prior to the pandemic.ConclusionsA third of patients with AI reported difficulties with management of AI during the pandemic, particularly in younger patients, women, and those with poor healthcare access.

Abstract Introduction: Optimal initial antithyroid drugs (ATD) dosing may achieve rapid improvement in thyroid hormone levels while minimizing risk of adverse events. As ATD have become the most common first line therapy for the treatment of Graves’ disease (GD), we examined trends over time in initial ATD dosing, and the association between guideline-based ATD dosing with time to normalization of FT4 and frequency of adverse events. Methods: This is a single cohort retrospective study in Mayo Clinic, Rochester, MN. We identified adults (≥18 years old) diagnosed with new onset GD between January 1, 2002-December 31, 2019 treated with at least 14 days of ATD and with available initial follow up data within 3 months prior to a dose change. Propylthiouracil (PTU) doses were converted to Methimazole (MMI) equivalents at 10:1 ratio. Guideline concordant care was defined as initial ATD dosed based on 2016 American Thyroid Association guidelines (i.e. 5-10 mg for presenting FT4 between &gt;1.7-2.55 ng/dL, 10-20 mg for 2.56-3.40 ng/dL, and 30-40 mg for 3.41 ng/dL and above). Based on the first follow up FT4 values, patients were grouped into categories of: normal range (FT4 0.9-1.7 ng/dL) and under treated (FT4 &gt;1.7 ng/dL). Results: 398 patients were included; mean (SD) age was 49 years (16.6), and 75% were women. Mean initial (SD) Free T4 value was 3.9 ng/dL (2.8), with patients treated with ATD at mean (SD) starting dose of 21.9 mg (13.3) MMI equivalent. Over time there was a decrease in the starting ATD dose from 30 mg MMI equivalent in 2002-2004 to 20 mg in 2017-2019, despite steady presenting FT4 values (2.7 ng/dL in 2002-2005 and 3.1 ng/dL in 2017-2019). In the subset of 340 patients with overt hyperthyroidism, 181 (53%) received guideline concordant (GC) dosing. Patients receiving GC care had a higher initial FT4 (4.9 vs. 3.6 ng/dL, p=0.002), larger goiters (40 vs. 30 g, p&lt;0.001) and higher initial ATD mean dose (SD) 25 mg (15.7) vs. 21.3 mg (9.9), p= 0.05. However at follow up (median 32 days vs 35 days respectively), both groups had similar proportion of patients with normal FT4 values (43% vs. 42%, p=0.79); undertreated patients (45% vs. 45%, p=0.99) and frequency of adverse events (4% vs. 6%, p=0.40). Conclusion: The initial dose of ATD for the treatment of GD has decreased over the past 2 decades. Most clinicians initiate ATD at a dose concordant to guidelines. Despite this, a significant proportion of patients have persistent hyperthyroidism on initial follow up. In light of evidence of risks associated with duration of hyperthyroidism, strategies to improve optimization of initial dosing are needed. Pending further subgroup analysis by presenting FT4 severity, these preliminary results suggest and approach factoring other variables apart from guideline based initial ATD dose is needed to optimize response. Our data will be utilized to pilot an individualized, patient specific predictive model to guide initial dosing to this end.

Abstract Background: Adrenal adenomas have been linked with cardiovascular morbidity in selected patient populations from specialized referral centers. Population-based data examining the association of adrenal adenomas with cardiometabolic outcomes are lacking. Aim: To determine the incidence of cardiometabolic outcomes in a population-based cohort of patients with adrenal adenomas. Methods: We conducted a population-based cohort study of patients diagnosed with adrenal adenomas while living in a defined community from 1995–2017. Eligible patients were retrospectively identified by a medical records linkage system and confirmed on chart review. Adenomas were classified as mild autonomous cortisol secretion (MACS) if the serum cortisol concentration was &gt;1.8 mcg/dL after 1 mg overnight dexamethasone suppression test (DST), nonfunctioning adrenal tumor (NFAT) if serum cortisol after DST was ≤1.8 mcg/dL, and adenoma with unknown cortisol secretion (AUCS) if DST was not performed. Patients with overt hormone excess were excluded. Cardiometabolic outcomes were assessed at the time of adrenal adenoma diagnosis. Patients were then followed until death, migration out of the community, or through December 31, 2017. Incident outcomes were assessed starting at 1 year following the diagnosis and excluded those with the outcome of interest at baseline, except for myocardial infarction (MI) and coronary intervention, which were adjusted for in the analysis. Results: were compared to 1:1 age and sex-matched referent subjects without adrenal adenomas from the same community. Results: Adrenal adenomas were diagnosed in 1004 patients with 141 (14%) NFAT, 81 (8%) MACS, and 782 (78%) AUCS. The median age of diagnosis was 63 years (range, 20–96), and 582 (58%) were women. The baseline data was previously presented and showed higher prevalence of hypertension, diabetes, peripheral vascular disease (PVD), and heart failure (HF) in the adenoma group, after adjusting for BMI and tobacco use. During a median follow-up of 6.8 years (range, 0–22), patients with adrenal adenomas were more likely than referent subjects to develop new-onset dyslipidemia (HR 1.31, 95% CI 1.03–1.67), diabetes (HR 1.68, 95% CI 1.28–2.22), chronic kidney disease (HR 1.77, 95% CI 1.39–2.25), atrial fibrillation (HR 1.32 (1.03–1.70), PVD (HR 1.61, 95% CI 1.24–2.09), and HF (HR 1.46, 95% CI 1.15–1.85). In addition, the adenoma group had higher risk for incident MI (HR 1.62, 95% CI 1.16–2.25) and coronary intervention (HR 1.70, 95% CI 1.25–2.31). Conclusions: Adrenal adenomas are associated with increased incidence of adverse cardiometabolic outcomes in this population-based cohort study. While these results are potentially explained by different degrees of cortisol excess, the majority of patients received suboptimal hormone evaluation, suggesting a knowledge gap in the workup of adrenal adenomas in the broader medical community.

Abstract Background: Adrenal adenomas are incidentally diagnosed in 7% of adults undergoing abdominal imaging. Mild autonomous cortisol secretion is present in 50% of adrenal adenomas, and even “nonfunctioning” adrenal adenomas demonstrate abnormal steroid profile. We aimed to 1) investigate the prevalence of mental and sleep disorders in patients with adrenal adenomas and to 2) determine the risk of mental and sleep disorders after the diagnosis of adrenal adenoma in patients compared to the referent subjects from the same population Methods: Using a medical records linkage system, we identified adult patients living in the Olmsted County, MN diagnosed with an adrenal adenoma during 1995–2017. Patients with overt hormone excess were excluded. Every patient with adenoma was matched by sex and age to a referent subject from the same population. Subjects were followed until death or end of the study. Mental health related comorbidities and sleep disorders were assessed at baseline and during follow up. Results: Our cohort included 1004 patients with adrenal adenomas and 1004 referent subjects (58% women, median age of 63 years). Patients were more likely to smoke (70% vs 54%, p &lt;0.001) and had a higher BMI (30 kg/m2 vs 28 kg/m2, p &lt; 0.001). Within 5 years prior to the index date (diagnosis of adenoma), and after adjusting for BMI and smoking, patients demonstrated a higher prevalence of depression (Odds ratio, OR of 1.3 (CI95% 1.1–1.6), p=0.02), anxiety (OR of 1.4 (CI95% 1.1–1.8, p=0.003), substance abuse disorders (OR of 2.4 (CI 95% 1.7–3.4), p&lt;0.001), but not insomnia (OR of 1.2 (CI95% 0.9–1.7) and sleep related breathing disorders (OR of 1.3 (CI 95% 0.9–1.7). During follow-up, starting 1 year after the diagnosis, patients demonstrated a higher risk of new onset depression (HR of 1.9, CI95%1.5–2.4), anxiety (HR of 1.5,CI95% 1.2–1.9), schizophrenia (HR of 1.7, CI95% 1.2–2.4), and substance abuse disorders (HR of 1.6, CI95% 1.2–2.0). Risk of sleep disorders 1 year after diagnosis was also high for insomnia (HR of 1.4, CI95% 1.1–1.9), sleep-related breathing disorders (HR of 1.8, CI95% 1.4–2.3), hypersomnias of central origin (HR of 2.0, CI95%1.04–3.96), parasomnias (HR of 2.4, CI95%1.2–4.7), and sleep-related movement disorders(HR of 1.9, CI95%1.3–2.6). Conclusion: Patients with adenomas are at increased risk for mental and sleep disorders, possibly explained by the underlying subtle cortisol secretion. Further prospective studies with an in-depth characterization of both hormonal secretion and mental/sleep disorders are needed. Reversibility or improvement of mental health and sleep disorders with adrenalectomy should be investigated.

Abstract Context: Quality of life (QoL) is impaired in patients with chronic adrenal insufficiency (AI) despite standard glucocorticoid (GC) replacement therapy. Current evidence on the determinants of QoL is scarce and limited in very few European countries, and how it relates to AI subtypes remains underexplored. Objective: We conducted the first survey study in patients with AI in the USA to determine the correlations between clinical parameters, adverse outcomes, patient education, socioeconomic factors, and QoL in different subtypes of AI. Design, Setting and Participants: Cross-sectional survey study of 529 patients with AI between 2015 and 2020, at three tertiary centers in the USA. Intervention: Patient-centered questionnaires. Main Outcome Measures: QoL scores using Short-Form 36. Results: Of 529 participants, 223 (42.2%) had primary AI (PAI), 190 (35.9%) had secondary AI (SAI), and 116 (21.9%) had glucocorticoid induced AI (GIAI). Median age at the time of survey was 58 years (IQR: 43–68), 342 (64.8%) were women and 483 (91.3%) were Caucasians. Median duration of AI was 6 years (IQR: 3–14.5), longest in patients with PAI (11 vs 4 years in SAI and GIAI, p=0.0001). Overall, Physical Composite Summary (PCS) score was lower than the Mental Composite Summary (MCS) (38.1±12.9 vs 46.5±11.8). Across the eight dimensions, each individual decade- and sex-adjusted Z-score (using the normative data of USA population) in patients with PAI was significantly higher than that of the other two AI subtypes (all p&lt;0.05), although all Z-scores were still below 0. In multivariate analyses, patients were more likely to report a worse PCS score (&lt;40) if they were women (OR: 3.3, CI 95%: 1.8–6.0), had SAI or GIAI (OR: 2.5, CI 95%: 1.4–4.3), had shorter duration of AI (&lt;6 years) (OR: 2.0, CI 95%: 1.1–3.6), were treated with &gt;25 mg hydrocortisone equivalent daily (OR: 2.3, CI 95%: 1.2–4.6), had more comorbidities related to GC excess (OR: 2.3, CI 95%: 1.3–4.0), reported higher financial burden due to AI (OR: 2.1, CI 95%: 1.3–3.6), and reported difficulties with AI management (OR: 2.5, CI 95%: 1.2–5.2). Women (OR: 2.1, CI 95%: 1.08–4.0), shorter duration of AI (OR: 2.4, CI 95%: 1.4–4.3), higher financial burden due to AI (OR: 2.3, CI 95%: 1.3–4.0), reporting difficulties with AI management (OR: 2.6, CI 95%: 1.4–4.9), and lack of family support during adrenal crisis (OR: 9.1, CI 95%: 2.3–33.3), were predictors of a worse MCS score (&lt;40). Conclusions: Patients with AI have substantially impaired QoL despite GC replacement therapy. Certain determinants of QoL are modifiable and achievable, such as avoiding GC over-replacement, offering detailed hands-on education in self-management, more comprehensive insurance coverage, and more robust domestic support. Our study calls for a multidimensional effort from patients, clinicians, and society to improve QoL in this vulnerable patient population.

Objective Several small studies reported increased prevalence and incidence of asymptomatic vertebral fractures in patients with non-functioning adrenal adenomas and adenomas with mild autonomous cortisol secretion. However, the risk of symptomatic fractures at vertebrae, and at other sites remains unknown. Our objective was to determine the prevalence and incidence of symptomatic site-specific fractures in patients with adrenal adenomas. Design Population-based cohort study, Olmsted County, Minnesota, USA, 1995–2017. Methods Participants were the patients with adrenal adenoma and age/sex-matched referent subjects. Patients with overt hormone excess were excluded. Main outcomes measures were prevalence and incidence of bone fractures. Results Of 1004 patients with adrenal adenomas, 582 (58%) were women, and median age at diagnosis was 63 years (20–96). At the time of diagnosis, patients had a higher prevalence of previous fractures than referent subjects (any fracture: 47.9% vs 41.3%, P = 0.003, vertebral fracture: 6.4% vs 3.6%, P = 0.004, combined osteoporotic sites: 16.6% vs 13.3%, P = 0.04). Median duration of follow-up was 6.8 years (range: 0–21.9 years). After adjusting for age, sex, BMI, tobacco use, prior history of fracture, and common causes of secondary osteoporosis, patients with adenoma had hazard ratio of 1.27 (95% CI: 1.07–1.52) for developing a new fracture during follow up when compared to referent subjects. Conclusions Patients with adrenal adenomas have higher prevalence of fractures at the time of diagnosis and increased risk to develop new fractures when compared to referent subjects.

Background: The rapid reduction in tumor burden by the oral B-cell lymphoma-2 inhibitor venetoclax (Ven) poses a risk of tumor lysis syndrome (TLS) for patients (pts) with chronic lymphocytic leukemia (CLL). The approved 5-week Ven dose ramp-up, along with prophylaxis and monitoring, effectively mitigate this risk of TLS but also introduce some logistical challenges to starting the drug. Moreover, the long ramp-up period may lead to clinical deterioration while pts are receiving lower doses, particularly for those with rapid disease progression after B-cell receptor pathway inhibitor (BCRi) therapy. Accelerated Ven dose ramp-up has been explored in a limited number of prior studies, including the prospective M14-032 trial (Jones et al. Lancet Oncol 2018) and a single-center retrospective study (Koenig et al. ASH 2019); these studies had conflicting results with regard to the risk of TLS. We conducted a multicenter study to systematically characterize the safety profile and feasibility of an accelerated Ven ramp-up schedule in pts with previously treated CLL. Methods: This is a retrospective chart review from 4 large academic US medical centers of 36 pts with relapsed/refractory CLL and a documented ramp-up period of &lt;5 weeks (duration at treating physician's discretion). The study period was defined from 1 month before to 1 month after ramp-up. TLS risk before Ven initiation was assessed per the label. Safety endpoints included the proportion of pts who experienced Grade ≥3 adverse events (AEs), TLS per Howard criteria (laboratory, clinical, or any reported TLS), and/or metabolic abnormalities observed during ramp-up. Feasibility of accelerated ramp-up was measured by assessing the proportion of pts who reached the target 400-mg dose or an alternative stable dose, defined as continuous/stable Ven dosing for ≥1 month after ramp-up. Descriptive statistics were calculated. Results: The median age at Ven initiation was 67.5 years (range 53-84) and 58.3% of pts had deletion 17p or TP53 mutation (Table 1). Pts were heavily pretreated (median of 3 lines of prior therapy [range 1-7]) and 88.9% had prior BCRi therapy; 27 pts (75.0%) had BCRi as immediate prior line of therapy before Ven. Before Ven initiation, 7 pts (19.4%) were at high risk of TLS, 13 (36.1%) at medium risk of TLS, and 15 (41.7%) at low risk of TLS; 1 unknown. Last line of therapy was discontinued in 30 pts (83.3%). Twenty-one pts (58.3%) received Ven monotherapy, 11 (30.6%) received Ven plus rituximab, 1 (2.8%) received Ven plus obinutuzumab, and 3 (8.3%) received Ven plus other (including ibrutinib, duvelisib, or idelalisib). Thirty-three pts (91.7%) underwent accelerated ramp-up as an inpatient, with a median hospital stay of 11 days (range 3-28). A stable dose of Ven was reached by 34 pts (94.4%), with median time of 15 days (range 3-66) to stable dose. Twenty-eight of these 34 pts (82.4%) reached the full 400 mg as their stable dose, with median time of 19.5 days (range 11-66). Overall, 15 pts (41.7%) experienced Grade ≥3 AEs and 4 (11.1%) discontinued Ven during ramp-up (2 pts due to clinical TLS, and 1 patient each due to persistent cytopenias and enrollment in hospice care). Seven pts (19.4%) had TLS (5 [13.9%] laboratory, 2 [5.6%] clinical), and 9 pts (25.0%) developed a metabolic abnormality only that did not meet Howard criteria for TLS (Table 2). Both pts with clinical TLS received Ven ramp-up while hospitalized; 1 high risk and 1 medium risk at baseline. Life-threatening (Grade 4) acute kidney injury and hypovolemic shock were reported for both. Of those pts with TLS, 4 (57.1%) required supportive medications. All AEs of TLS (including clinical events) resolved. Conclusion: In this multicenter study exploring accelerated Ven ramp-up, 82% of pts reached a stable dose of Ven 400 mg. TLS was observed in 19% of pts, including 2 pts with clinical TLS, which in both cases was reversible. Our data suggest that although the risk of TLS with an accelerated ramp-up appears to be greater than with 5-week Ven ramp-up per label, an accelerated Ven ramp-up schedule appears feasible at experienced academic centers with close inpatient monitoring. This dosing regimen may be beneficial for relapsed CLL pts with aggressive disease, particularly those progressing immediately after BCRi therapy. While promising, the approach cannot be routinely recommended until results are validated in a prospective clinical trial. Disclosures Davids: BeiGene: Consultancy; AstraZeneca: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Ascentage Pharma: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; AbbVie: Consultancy; Eli Lilly: Consultancy; MEI Pharma: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding; Sunesis: Consultancy; Gilead Sciences: Consultancy; Zentalis: Consultancy; Syros Pharmaceuticals: Consultancy; Research to Practice: Honoraria; Merck: Consultancy; Surface Oncology: Research Funding. Shadman:TG therapeutics: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Meyers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cellectar: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mustang Bio: Research Funding; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Sunesis: Research Funding; Gilead: Research Funding; MophoSys: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sound Biologics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta Pharma: Ended employment in the past 24 months. Parikh:GlaxoSmithKline: Honoraria; AbbVie: Honoraria, Research Funding; Ascentage Pharma: Research Funding; Genentech: Honoraria; Verastem Oncology: Honoraria; Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; TG Therapeutics: Research Funding; Merck: Research Funding; Pharmacyclics: Honoraria, Research Funding; MorphoSys: Research Funding. Ujjani:MorphoSys: Consultancy; Genentech: Consultancy, Honoraria; Atara: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Verastem Oncology: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding. Chen:AbbVie: Other: Institutional research grants, Research Funding. Johnson:AbbVie: Other: Institutional research grants, Research Funding. Jiang:AbbVie: Current Employment, Other: may hold stock or options. Llamas:AbbVie: Current Employment, Other: may hold stock or options. Feng:AbbVie: Current Employment, Other: may hold stock or options. Khan:ICON plc: Current Employment, Other: a company contracted by AbbVie for this study. Lamanna:MingSight: Other: Institutional research grants, Research Funding; Oncternal, Verastem, TG Therapeutics: Other: Institutional research grants, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Columbia University Medical Center: Current Employment; Juno: Other: Institutional research grants, Research Funding; Octapharma: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bei-Gene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Loxo: Research Funding. OffLabel Disclosure: "Venetoclax is a BCL-2 inhibitor indicated: for treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); in combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy. CLL/SLL: Dosing with venetoclax begins with a 5-week ramp-up."

Abstract Context Current evidence on determinants of adverse health outcomes in patients with adrenal insufficiency (AI) is scarce, especially in regards to AI subtypes. Objective To determine predictors of adverse outcomes in different subtypes of AI. Design and Setting Cross-sectional survey study at 2 tertiary centers. Participants A total of 696 patients with AI: primary AI (PAI, 42%), secondary AI (SAI, 32%), and glucocorticoid-induced AI (GIAI, 26%). Intervention Patient-centered questionnaire. Main Outcome Measures Patients’ knowledge, self-management of AI, self-perceived health, and adverse outcomes. Results The incidence rate of adrenal crisis was 24/100 patient-years with 44% experiencing at least 1 adrenal crisis since diagnosis (59% in PAI vs 31% in SAI vs 37% in GIAI, P &lt; .0001). All patients described high degrees of discomfort with self-management and receiving prompt treatment. Patients with PAI were most likely to develop adrenal crises (adjusted OR 2.8, 95% CI 1.9-4.0) despite reporting better self-perceived health (adjusted OR 3.3, 95% CI 2.1-5.3), understanding of their diagnosis (89% vs 74-81% in other subtypes, P = .002), higher comfort with self-management (62% vs 52-61% in other sub types, P = .005), and higher likelihood to receive prompt treatment for adrenal crises in the emergency department (42% vs 19-30% in other subtypes, P &lt; .0001). Conclusions Patients with AI reported high degrees of discomfort with self-management and treatment delays when presenting with adrenal crises. Despite better self-perceived health and understanding of diagnosis, patients with PAI experienced the highest frequency of adrenal crises. A multidimensional educational effort is needed for patients and providers to improve the outcomes of all subtypes of AI.