Li, Dingfeng

Abstract Background: Adrenal tumors are reported in 5% of adults, with malignancy rates in 1–12%, and rates of overt hormonal excess in 1–15 %. However, most estimates originate from convenience samples. Our objective was to determine the incidence, prevalence and clinical presentation of adrenal tumors in a population-based setting. Methods: We used a centralized epidemiologic database to identify patients diagnosed with adrenal tumors in a local community 1995 to 2017. The database is a unique medical records linkage system that allows access to hospital and community medical records for local residents (population 137,000). We calculated incidence rates (IR) as the number of new patients diagnosed while living in the study area, and prevalence as the number of patients living in the study area on Dec 31 2017. IR and prevalence were sex- and age-adjusted to the 2010 US Census population. Results: Of 1,287 patients diagnosed with adrenal tumor, the median age of diagnosis was 62 years (IQR 52–72), 713 (55%) were women, and 13 (1%) were younger than 18 years at diagnosis. IR was highest in patients >65 YO, followed by patients 40–64 YO, 18–39 YO and <18 YO (142 vs 66 vs 9 vs 2 per 100,000 persons years). IR per 100,000 increased from 4.4 (CI95% 0.3–8.6) in 1995 to 47.8 (CI95% 36.9–58.7) in 2017. Overall prevalence in the population was 0.53% in 2017, ranging from 0.01% among 0–17 YO to 1.9% among +65 YO. Malignant adrenal mass was diagnosed in 8.7% patients (4 patients with adrenal cortical carcinoma (0.3%) and 108 (8.4%) patients with other malignant mass). Pheochromocytoma was diagnosed in 11 (1.1%) patients and benign adrenal mass was diagnosed in 1,175 (90.2%) patients (1,076 (83.6%) with adrenal adenoma and 85 (6.6%) with other benign mass). Median tumor size was 15 mm (range 5–255), and 184 (14%) of patients had bilateral tumors. Only 255 (20%) patients had dexamethasone suppression test, 93 (36%) with cortisol>1.8 mcg/dl. Of 1,076 adrenal adenomas, 53 (4.9%) had overt hormone excess, 140 (13%) had nonfunctioning adrenal adenomas, and 88 (8.2%) had mild autonomous cortisol secretion. Hormonal work up for was incomplete in 795 (73.9%) adenomas. Patients discovered incidentally (1,050, 81.6%) had a lower rate of malignancy and hormone excess (5.3% vs 52% of patients with non-incidental discovery, p <0.001). Rate of malignancy was highest in children (67% vs 8% >18YO, p<0.001), bilateral tumors (16% vs 8% unilateral, p<0.001), tumors ≥4 cm (33% vs 7% in < 4 cm, p<0.001). Conclusion: IR of adrenal tumors increased 10-fold since 1995, and was highest in patients >65 YO. 8.7% of tumors were malignant, with a majority represented by malignant adrenal tumors other than adrenal cortical carcinoma. The risk of malignancy was highest in non-incidental discovery, children, and tumors > 4 cm. Overt hormone excess was diagnosed in 4.5% of patients. The majority of patients with adrenal adenomas had a suboptimal work up for hormone excess.

Abstract Background: Adrenal adenoma is reported in around 5% of adults undergoing cross-sectional imaging. Although most adenomas are considered non-functioning (NFAT), up to 48% present with mild autonomous cortisol secretion (MACS). Several studies reported increased prevalence and incidence of vertebral fractures in MACS; however conclusions are limited by small sample size, selection bias, inadequate reference population and length of follow up. Objective: To determine the prevalence and incidence of site-specific fragility fractures in a population-based cohort of patients with adrenal adenomas. Methods: Residents of local community with a radiographic diagnosis of adrenal adenoma between 1995 and 2017 were identified using a centralized epidemiologic database and matched with reference subjects for sex and age. All subjects were followed through 2017, until death or migration from the community. MACS was diagnosed based on cortisol level ≥1.8 mcg/dl after overnight 1mg dexamethasone suppression, NFAT based on cortisol level <1.8 mcg/dl, and patients not tested with dexamethasone were considered as adenoma with unknown cortisol secretion (AUCS). Results: Of 1003 patients with adrenal adenomas (581 women (58%), median age of diagnosis 63 years (20–96)), 136 (14%) were diagnosed with NFAT, 86 (9%) with MACS, and 781(78%) with AUCS. At the time of diagnosis, patients had higher BMI (median 30 vs 28 kg/m2, p<0.001), and higher prevalence of tobacco use (70% vs 54%, p<0.001) than reference subjects. Of 154 patients and 113 reference subjects with BMD available at baseline, patients had a higher median BMD at the total hips (0.93 vs 0.89, p=0.02) but similar median BMD at lumbar spine (1.05 vs 1.03, p=0.49) when compared to reference subjects. However, patients had a higher prevalence of fractures than reference subjects (any fracture: 50% vs 42%, p<0.001, vertebral fracture: 6.5% vs 3.7%, P=0.004). When adjusted for age, sex, and prior history of fracture, patients with adenoma had HR of 1.24 (CI 95% 1.04–1.48) for developing a new fracture and HR of 1.18 (CI 95% 0.97–1.44) when also adjusted for BMI and smoking. Subgroup analysis demonstrated that the prevalence of fractures at the time of diagnosis was higher in all 3 subgroups at any fragility fracture site when compared to reference subjects (NFAT: 44% vs 37%, MACS: 48% vs 43%, AUCS: 51% vs 43%); patients with MACS had the highest incidence of new fracture after 5 years of follow up when compared to AUCS and NFAT (cumulative incidence: MACS 25% vs NFAT 19% vs AUCS 16%), though the differences were not significant. Conclusions: Patients with adrenal adenomas have higher prevalence of fractures at the time of diagnosis. During follow up, patients with adenoma have a higher incidence of fractures even when adjusted for sex, age, and prior history of fracture, possibly due to underlying undiagnosed abnormal cortisol secretion.

Abstract Background: Adrenal insufficiency (AI) is a chronic disorder necessitating life-long replacement. Patients’ quality of life and health outcomes depend on knowledge and comfort level with self-management. Objective: To determine patients’ knowledge in regards to diagnosis and management, estimate burden of disease and to identify predictors of adverse outcomes in patients with AI Methods: Survey study of patients with AI evaluated at two tertiary medical centers between 2015 and 2019. Collected variables included data on circumstances of AI diagnosis, symptoms, management, burden of disease, and overall well-being. Results: Among 785 patients (mean age at diagnosis 44.2 ± 18.0, 64% women, and 92% Caucasian), 310 (40%) had primary AI (PAI), 255 (33%) had secondary AI (SAI) not related to glucocorticoid use, and 211 (27%) had steroid-induced AI (SIAI). Patients were diagnosed with AI after presenting with symptoms for a median of 1 year (0-6), 28% with symptoms lasting >2 years, 44% visiting emergency room (ER) at least once prior to diagnosis. A third of patients reported a discordant diagnosis from their medical record. Baseline glucocorticoid replacement therapy included hydrocortisone (HC) in 447 (59%), median of 20 mg (IQR 15 - 25mg), prednisone in 190 (25%), median of 5 mg (IQR 4 - 7.5mg), other regimens in 38 (5%), and no steroids in the remainder (85, 11%); 197 (26%) patients reported daily equivalent HC dose of >25 mg. Overall, 549 (73%) of patients reported use of stress dose steroids at least once per year, higher in patients taking HC >25 mg/day (3.2 vs 2.7 times per year if HC<25mg/day, p=0.01). Improper use of stress steroids was reported in 193, 25% patients. Patients taking HC>25 mg /day reported a higher number of adrenal crises (1.6 vs 1.3 in patients on HC<25 mg/day, p=0.04). Among 314 (41%) patients who reported ER visits due to adrenal crisis, only a third received prompt glucocorticoids. One third of patients described their general health as fair or poor. Predictors of negative perceptions of overall health included SIAI (OR 6.2 and 2.5, vs PAI and SAI respectively), poor understanding of diagnosis (OR 2.6), daily HC>25 mg (OR 2.1), and presence of at least one adrenal crisis (OR 2.3) (p<0.001 for all). Conclusion: Patients with AI experience delay in diagnosis, and a third do not fully understand their diagnosis. In addition to patient education, interventions to improve general health and outcomes may include selecting a physiological glucocorticoid replacement therapy, prevention of adrenal crisis, and improving ER care.