Prevalence of lifestyle characteristics in glucocorticoid users and non-users: a Danish population-based cross-sectional study

OBJECTIVES Lifestyle may affect observed associations between glucocorticoid use and adverse events. This study aimed to investigate whether lifestyle differ according to use of systemic glucocorticoids. DESIGN Population-based cross-sectional study. SETTING The Central Denmark Region. PARTICIPANTS 30 245 adults (≥25 years of age) who participated in a questionnaire-based public health survey in 2010. OUTCOME MEASURES Systemic glucocorticoid use was categorised as never use, current use (prescription redemption ≤90 days before completing the questionnaire), recent use (prescription redemption 91–365 days before completing the questionnaire), former use (prescription redemption >365 days before completing the questionnaire) and according to cumulative dose expressed in prednisolone equivalents (<100, 100–499, 500–999, 1000–1999, 2000–4999, ≥5000 mg). We computed the prevalence of lifestyle factors (body mass index, smoking, alcohol intake, physical activity and dietary habits) according to glucocorticoid use. We then estimated age-adjusted prevalence ratios (aPRs) and 95% CIs, comparing the categories of glucocorticoid users versus never users. All analyses were stratified by sex. RESULTS Of the 30 245 participants (53% women, median age 53 years), 563 (1.9%) were current users, 885 (2.9%) were recent users, 3054 (10%) were former users and 25 743 (85%) were never users. Ever users of glucocorticoids had a slightly higher prevalence of obesity than never users (18% vs 14%, aPR=1.4, 95% CI 1.2 to 1.5 in women and 17% vs 15%, aPR=1.2, 95% CI 1.1 to 1.4 in men). In women, ever users of glucocorticoids had a slightly lower prevalence of high-risk alcohol consumption compared with never users (17% vs 20%, aPR=0.8, 95% CI 0.7 to 1.0). Smoking, diet and physical activity did not differ substantially according to use of glucocorticoids. CONCLUSION Our study provides a framework for quantifying potential uncontrolled confounding by lifestyle factors in studies of systemic glucocorticoids

Clinical indicators of adrenal insufficiency following discontinuation of oral glucocorticoid therapy: A Danish population-based self-controlled case series analysis

BACKGROUND: Biochemical adrenal insufficiency induced by glucocorticoid treatment is prevalent, but data on the clinical implications are sparse. We investigated clinical consequences of glucocorticoid-induced adrenal insufficiency after oral glucocorticoid cessation. METHODS: We conducted a Danish population-based self-controlled case series utilizing medical registries. In this design each individual serves as their own control allowing event rates to be compared as a function of time and treatment. Clinical indicators of adrenal insufficiency were defined as diagnoses of gastrointestinal symptoms, hypotension, cardiovascular collapse, syncope, hyponatremia, and hypoglycaemia. We included 286,680 persons who discontinued long-term (≥ 3 months) oral glucocorticoid treatment. We defined five risk periods and a reference period (before treatment): period 0 (on treatment), withdrawal period (1 month before and after cessation), followed by three consecutive 2 month-risk periods after withdrawal (periods 2–4). RESULTS: Median age at cessation was 69 years and 57% were female. Median treatment duration was 297 days and median cumulative dose was 3000 mg prednisolone equivalents. The incidence rates of hypotension, gastrointestinal symptoms, hypoglycemia and hyponatremia were increased in the withdrawal period compared to before treatment started (reference period). Incidence rate ratios comparing the withdrawal period with the reference period were 2.5 [95% confidence interval (CI): 1.4–4.3] for hypotension, 1.7 (95% CI: 1.6–1.9) for gastrointestinal symptoms, 2.2 (95% CI: 0.7–7.3) for hypoglycemia, and 1.5 (95% CI: 1.1–2.0) for hyponatremia. During 7 months of follow up, the rates of hypotension and gastrointestinal symptoms remained elevated compared to the reference period. Risk factors included use of antibiotics, increasing average daily dose of glucocorticoids, cumulative dose, and age. CONCLUSION: Oral glucocorticoid withdrawal was associated with adverse outcomes attributable to adrenal insufficiency. Our study underscores the need for future research to establish evidence-based clinical guidance on management of patients who discontinue oral glucocorticoids

Risk of cancer in patients with thyroid disease and venous thromboembolism

Diana H Christensen,1 Katalin Veres,1 Anne G Ording,1 Jens Otto L J&oslash;rgensen,2 Suzanne C Cannegieter,3 Reimar W Thomsen,1 Henrik T S&oslash;rensen1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark; 3Department of Clinical Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands Objective: Risk of venous thromboembolism (VTE) is increased in patients with hypo/hyperthyroidism. It is unknown whether VTE may be a presenting symptom of occult cancer in these patients. Design: Nationwide population-based cohort study based on Danish medical registry data. Methods: We identified all patients diagnosed with VTE during 1978&ndash;2013 who had a previous or concurrent diagnosis of hypothyroidism (N=1481) or hyperthyroidism (N=1788). We followed them until a first-time cancer diagnosis, death, emigration, or study end, whichever came first. We calculated 1-year absolute cancer risk and standardized incidence ratios (SIRs) for cancer incidence in the study population compared with national cancer incidence in the general population. Results: During the first year after a VTE diagnosis, the 1-year absolute cancer risk was 3.0% among patients with hypothyroidism and 3.9% among those with hyperthyroidism. During the first year of follow-up, SIRs for cancer in the study population compared with the general population were 1.96 (95% CI: 1.42&ndash;2.64) among patients with hypothyroidism and 2.67 (95% CI: 2.07&ndash;3.39) among those with hyperthyroidism. SIRs declined substantially after 1 year but remained increased during the remainder of the follow-up period (up to 36 years) (SIR for hypothyroidism=1.16 [95% CI: 0.97&ndash;1.39]; SIR for hyperthyroidism=1.26 [95% CI: 1.08&ndash;1.46]). Conclusion: VTE may be a marker of underlying occult cancer in patients with hypothyroidism or hyperthyroidism. Keywords: hyperthyroidism, hypothyroidism, venous thromboembolism, cancer, cohort stud