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Sökning: WFRF:(Chantzichristos Dimitrios 1976 )

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  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • Overall and disease-specific mortality in patients with Cushing's disease: a Swedish nationwide study.
  • 2019
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 104:6
  • Tidskriftsartikel (refereegranskat)abstract
    • It is still a matter of debate whether patients with Cushing's disease (CD) in remission have increased mortality.To study overall and disease-specific mortality, and predictive factors, in an unselected nationwide cohort of patients with CD.A retrospective study on patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardised mortality ratios (SMRs) with 95% confidence intervals (CI) were calculated and Cox regression models were used to identify predictors of mortality.Five-hundred-and-two patients [387 women (77%)] with CD were identified, of whom 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 years (SD 16) and median follow-up time was 13 years (IQR 6-23). The observed number of deaths was 133 versus 54 expected, resulting in an overall SMR of 2.5 (95% CI 2.1-2.9). The commonest cause of death was cardiovascular diseases [SMR 3.3 (95% CI 2.6 -4.3)]. Excess mortality was also found due to infections and suicides. SMR in patients in remission was 1.9 (95% CI 1.5-2.3), where bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality whereas growth hormone replacement was associated with improved outcome.This large nationwide study shows that patients with CD have an excess mortality. The findings illustrate the importance of obtaining remission and continued active surveillance, along with adequate hormone replacement, and evaluation of cardiovascular risk and mental health.
  • Ragnarsson, Oskar, 1971-, et al. (författare)
  • The incidence of Cushing’s disease : : a nationwide Swedish study
  • 2019
  • Ingår i: Pituitary. - Springer. - 1386-341X. ; 22:2, s. 179-186
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Studies on the incidence of Cushing’s disease (CD) are few and usually limited by a small number of patients. The aim of this study was to assess the annual incidence in a nationwide cohort of patients with presumed CD in Sweden. Methods: Patients registered with a diagnostic code for Cushing’s syndrome (CS) or CD, between 1987 and 2013 were identified in the Swedish National Patient Registry. The CD diagnosis was validated by reviewing clinical, biochemical, imaging, and histopathological data. Results: Of 1317 patients identified, 534 (41%) had confirmed CD. One-hundred-and-fifty-six (12%) patients had other forms of CS, 41 (3%) had probable but unconfirmed CD, and 334 (25%) had diagnoses unrelated to CS. The mean (95% confidence interval) annual incidence between 1987 and 2013 of confirmed CD was 1.6 (1.4–1.8) cases per million. 1987–1995, 1996–2004, and 2005–2013, the mean annual incidence was 1.5 (1.1–1.8), 1.4 (1.0–1.7) and 2.0 (1.7–2.3) cases per million, respectively. During the last time period the incidence was higher than during the first and second time periods (P < 0.05). Conclusion: The incidence of CD in Sweden (1.6 cases per million) is in agreement with most previous reports. A higher incidence between 2005 and 2013 compared to 1987–2004 was noticed. Whether this reflects a truly increased incidence of the disease, or simply an increased awareness, earlier recognition, and earlier diagnosis can, however, not be answered. This study also illustrates the importance of validation of the diagnosis of CD in epidemiological research.
  • Chantzichristos, Dimitrios , 1976-, et al. (författare)
  • Early Clinical Indicators of Addison’s Disease in Adults with Type 1 Diabetes: a Nationwide, Observational, Cohort Study
  • 2019
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X. ; 104:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Patients with type 1 diabetes mellitus (T1DM) have an increased risk of Addison disease (AD) development, but prediction of those at risk is not possible. Objective To determine whether there are early clinical indicators that may denote the development of AD in adults with T1DM. Design Observational, matched-cohort study. Setting Patient data from Swedish national registries [National Diabetes Register (NDR), Inpatient Register, and Prescription Drug Register]. Participants All patients with T1DM diagnosed with concomitant AD (n = 66) among the 36,514 adult patients with T1DM in the NDR between 1998 and 2013. Each case was matched to five controls with T1DM alone (n = 330). Main Outcome Measures Clinical data and drug prescriptions were assessed prior to baseline (inclusion into the study) and prior to AD diagnosis. Analysis of covariance and estimated group proportions were used for comparisons. Results Prior to baseline, cases had a higher frequency of thyroid/antithyroid drug prescription than controls (9.1% vs 1.8%). Prior to AD diagnosis, cases had higher frequencies of diabetic retinopathy (12.1% vs 2.1%), infections requiring hospital admission (16.7% vs 2.1%), thyroid/antithyroid drug prescription (28.8% vs 7.0%), and glucagon prescription (18.2% vs 6.4%). There was no difference in glycated Hb between the groups prior to baseline or prior to AD diagnosis. Conclusions These data suggest that medical treatment of thyroid disease, a severe infection, and glucagon prescription for severe hypoglycemia should raise the suspicion of AD development in adults with T1DM. Development of diabetic retinopathy might also be associated with glucocorticoid deficiency and the development of AD among patients with T1DM.
  • Chantzichristos, Dimitrios , 1976-, et al. (författare)
  • Incidence, prevalence and seasonal onset variation of Addison's disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies.
  • 2018
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 178:1, s. 115-122
  • Tidskriftsartikel (refereegranskat)abstract
    • We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies.Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model.Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years (P value = 0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5).The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern.
  • Chantzichristos, Dimitrios , 1976-, et al. (författare)
  • MANAGEMENT OF ENDOCRINE DISEASE: Disease burden and treatment challenges in patients with both Addison's disease and type 1 diabetes mellitus.
  • 2020
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 183:1, s. R1-R11
  • Forskningsöversikt (refereegranskat)abstract
    • Concurrent type 1 diabetes (T1D) and Addison's disease (AD) is a rare combination of diseases and, in approximately one third of these patients, it is also combined with an autoimmune thyroid disease. Recently, it was shown that patients with both T1D and AD have a higher risk of premature death compared to patients with T1D alone, the most common causes of death being due to diabetic complications and cardiovascular disease. These patients receiving replacement therapies with both insulin and glucocorticoids face an increased risk of hypo- and hyperglycemia, and diabetic ketoacidosis, and have a higher risk of adrenal crisis than patients with AD alone. Treatment challenges include the opposing effects of insulin and glucocorticoids on glucose homeostasis, and the need to balance and synchronize these two treatments. The rarity of this disease combination may explain the paucity of data on outcome and specific treatment strategies in this patient group. Based on this review, we suggest management strategies for their insulin and glucocorticoid replacement therapies and indicate future areas of research.
  • Chantzichristos, Dimitrios , 1976-, et al. (författare)
  • Mortality in patients with diabetes mellitus and Addison's disease: a nationwide, matched, observational cohort study.
  • 2017
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 176:1, s. 31-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Our hypothesis was that patients with diabetes mellitus obtain an additional risk of death if they develop Addison's disease (AD).Nationwide, matched, observational cohort study cross-referencing the Swedish National Diabetes Register with Inpatient, Cancer and Cause of Death Registers in patients with diabetes (type 1 and 2) and AD and matched controls with diabetes. Clinical characteristics at baseline, overall, and cause-specific mortality were assessed. The relative risk of death was assessed using a Cox proportional hazards regression model.Between January 1996 and December 2012, 226 patients with diabetes and AD were identified and matched with 1129 controls with diabetes. Median (interquartile range) follow-up was 5.9 (2.7-8.6) years. When patients with diabetes were diagnosed with AD, they had an increased frequency of diabetes complications, but both medical history of cancer and coronary heart disease did not differ compared with controls. Sixty-four of the 226 patients with diabetes and AD (28%) died, while 112 of the 1129 controls (10%) died. The estimated relative risk increase (hazard ratio) in overall mortality in the diabetes and AD group was 3.89 (95% confidence interval 2.84-5.32) compared with controls with diabetes. The most common cause of death was cardiovascular in both groups, but patients with diabetes and AD showed an increased death rate from diabetes complications, infectious diseases and unknown causes.Patients with the rare combination of diabetes and AD showed a markedly increased mortality and died more frequently from infections and unknown causes than patients with diabetes alone. Improved strategy for the management of this combination of metabolic disorders is needed.
  • Melvin, Audrey, et al. (författare)
  • GDF15 Is Elevated in Conditions of Glucocorticoid Deficiency and Is Modulated by Glucocorticoid Replacement.
  • 2020
  • Ingår i: The Journal of clinical endocrinology and metabolism. - 1945-7197. ; 105:5
  • Tidskriftsartikel (refereegranskat)abstract
    • GDF15 is a stress-induced hormone acting in the hindbrain that activates neural circuitry involved in establishing aversive responses and reducing food intake and body weight in animal models. Anorexia, weight loss, nausea and vomiting are common manifestations of glucocorticoid deficiency, and we hypothesized that glucocorticoid deficiency may be associated with elevated levels of GDF15.To determine the impact of primary adrenal insufficiency (PAI) and glucocorticoid replacement on circulating GDF15 levels.We measured circulating concentrations of GDF15 in a cohort of healthy volunteers and Addison's disease patients following steroid withdrawal. Significantly higher GDF15 (mean ± standard deviation [SD]) was observed in the Addison's cohort, 739.1 ± 225.8 pg/mL compared to healthy controls, 497.9 ± 167.7 pg/mL (P = 0.01). The effect of hydrocortisone replacement on GDF15 was assessed in 3 independent PAI cohorts with classical congenital adrenal hyperplasia or Addison's disease; intravenous hydrocortisone replacement reduced GDF15 in all groups. We examined the response of GDF15 to increasing doses of glucocorticoid replacement in healthy volunteers with pharmacologically mediated cortisol deficiency. A dose-dependent difference in GDF15 (mean ± SD) was observed between the groups with values of 491.0 ± 157.7 pg/mL, 427.0 ± 152.1 pg/mL and 360 ± 143.1 pg/mL, in the low, medium and high glucocorticoid replacement groups, respectively, P < .0001.GDF15 is increased in states of glucocorticoid deficiency and restored by glucocorticoid replacement. Given the site of action of GDF15 in the hindbrain and its effects on appetite, further study is required to determine the effect of GDF15 in mediating the anorexia and nausea that is a common feature of glucocorticoid deficiency.
  • Papakokkinou, Eleni, et al. (författare)
  • Excess Morbidity Persists in Patients With Cushing's Disease During Long-term Remission : A Swedish Nationwide Study
  • 2020
  • Ingår i: The Journal of clinical endocrinology and metabolism. - Oxford University Press. - 1945-7197. ; 105:8
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Whether multisystem morbidity in Cushing's disease (CD) remains elevated during long-term remission is still undetermined. OBJECTIVE: To investigate comorbidities in patients with CD. DESIGN, SETTING, AND PATIENTS: A retrospective, nationwide study of patients with CD identified in the Swedish National Patient Register between 1987 and 2013. Individual medical records were reviewed to verify diagnosis and remission status. MAIN OUTCOMES: Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated by using the Swedish general population as reference. Comorbidities were investigated during three different time periods: (i) during the 3 years before diagnosis, (ii) from diagnosis to 1 year after remission, and (iii) during long-term remission. RESULTS: We included 502 patients with confirmed CD, of whom 419 were in remission for a median of 10 (interquartile range 4 to 21) years. SIRs (95% CI) for myocardial infarction (4.4; 1.2 to 11.4), fractures (4.9; 2.7 to 8.3), and deep vein thrombosis (13.8; 3.8 to 35.3) were increased during the 3-year period before diagnosis. From diagnosis until 1 year after remission, SIRs (95% CI were increased for thromboembolism (18.3; 7.9 to 36.0), stroke (4.9; 1.3 to 12.5), and sepsis (13.6; 3.7 to 34.8). SIRs for thromboembolism (4.9; 2.6 to 8.4), stroke (3.1; 1.8 to 4.9), and sepsis (6.0; 3.1 to 10.6) remained increased during long-term remission. CONCLUSION: Patients with CD have an increased incidence of stroke, thromboembolism, and sepsis even after remission, emphasizing the importance of early identification and management of risk factors for these comorbidities during long-term follow-up.
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