| 1. |
- Bélteky, Malin, et al.
(författare)
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Maternal respiratory infections in early pregnancy increases the risk of type 1 diabetes
- 2020
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Ingår i: Pediatric Diabetes. - : Hindawi Publishing Corporation. - 1399-543X .- 1399-5448. ; 21:7, s. 1193-1201
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Tidskriftsartikel (refereegranskat)abstract
- Background/objective: Is exposure to maternal infections and use of antibiotics in the prenatal period associated with increased risk of T1D, regardless of genetic risk?Methods: Data on infections and use of antibiotics during pregnancy were collected from questionnaires at birth from parents to 16 292 children in the All Babies in Southeast Sweden (ABIS) cohort and validated against national diagnosis registers. As of November 2017, 137 ABIS children had developed T1D, 72 boys and 65 girls (0.8% of the original cohort).Results: More cases were born in spring and summer than fall and winter. However, onset of T1D appeared to be more common in either summer or winter. In univariate analyses, respiratory tract infection in the first trimester (P = .002) and gastroenteritis during pregnancy (P = .04) were associated with later risk of T1D in the offspring. Other types of infection or antibiotic treatment were not associated with an increased risk. In a multiple logistic regression model, a mother with an autoimmune disease (P < .001), father with T1D (P < .001) and respiratory tract infection during the first trimester (P = .005) remained as risk factors for T1D in the offspring. In children with neutral HLA alleles antibiotic treatment may increase the risk of T1D (P = .01, OR 3.46, 95% CI 1.25-9.55).Conclusions: In the general population there seems to be an association between seasonal maternal respiratory tract infection in the first trimester of pregnancy and later risk of T1D in the offspring. HLA may play a role for the effect of exposure to infections and antibiotics.
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| 2. |
- Bothou, Christina, et al.
(författare)
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Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency : Experience from a Multicenter Survey
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8
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Tidskriftsartikel (refereegranskat)abstract
- Context: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment.Objective: Multicenter survey on current clinical approaches in managing AI during pregnancy.Design: Retrospective anonymized data collection from 19 international centers from 2013 to 2019.Setting and patients: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%).Results: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes.Conclusions: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.
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| 3. |
- Bäcklund, Nils, et al.
(författare)
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Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing's syndrome
- 2020
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:6, s. 569-582
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST). Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves. Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h. Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better. © 2020 European Society of Endocrinology Printed in Great Britain.
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| 4. |
- Bäcklund, Nils, et al.
(författare)
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Reference intervals of salivary cortisol and cortisone and their diagnostic accuracy in Cushing’s syndrome
- 2020
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 182:6, s. 569-582
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The challenge of diagnosing Cushing's syndrome (CS) calls for high precision biochemical screening. This study aimed to establish robust reference intervals for, and compare the diagnostic accuracy of, salivary cortisol and cortisone in late-night samples and after a low-dose (1 mg) dexamethasone suppression test (DST).Design and methods: Saliva samples were collected at 08:00 and 23:00 h, and at 08:00 h, after a DST, from 22 patients with CS and from 155 adult reference subjects. We also collected samples at 20:00 and 22:00 h from 78 of the reference subjects. Salivary cortisol and cortisone were analysed with liquid chromatography-tandem mass spectrometry. The reference intervals were calculated as the 2.5th and 97.5th percentiles of the reference population measurements. Diagnostic accuracies of different tests were compared, based on areas under the receiver-operating characteristic curves.Results: The upper reference limits of salivary cortisol and cortisone at 23:00 h were 3.6 nmol/L and 13.5 nmol/L, respectively. Using these reference limits, CS was detected with a sensitivity (95% CI) of 90% (70-99%) and specificity of 96% (91-98%) for cortisol, and a 100% (84-100%) sensitivity and 95% (90-98%) specificity for cortisone. After DST, cortisol and cortisone upper reference limits were 0.79 nmol/L and 3.5 nmol/L, respectively. CS was detected with 95% (75-100%) sensitivity and 96% (92-99%) specificity with cortisol, and 100% (83-100%) sensitivity and 94% (89-97%) specificity with cortisone. No differences in salivary cortisol or cortisone levels were found between samples collected at 22:00 and 23:00 h.Conclusion: Salivary cortisol and cortisone in late-night samples and after DST showed high accuracy for diagnosing CS, salivary cortisone being slightly, but significantly better.
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| 5. |
- Casas, Rosaura, et al.
(författare)
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Glutamic Acid Decarboxylase Injection Into Lymph Nodes: Beta Cell Function and Immune Responses in Recent Onset Type 1 Diabetes Patients
- 2020
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Ingår i: Frontiers in Immunology. - : Frontiers Media S.A.. - 1664-3224. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- In spite of intensive treatment Type 1 diabetes leads to serious complications. Preservation of residual beta cell function makes the disease milder, facilitates treatment, prevents complications and increase survival. So far immune interventions have had limited effect, and some serious adverse events and risks. In an open pilot trial we aimed to improve efficacy of GAD-alum treatment using lymph-node administration in combination with oral vitamin D. Here we report the clinical effect and focus on biomarkers for response to treatment. Patients (n = 12) aged 12 to 24 years with recent onset of Type 1 diabetes received 4 μg GAD-alum into lymph-node at day 30, 60, and 90, and oral Vitamin D 2000 U/d, days 1 to 120. Beta cell function was estimated by Mixed Meal Tolerance Tests. GADA, GADA subclasses, GAD65-induced cytokines and proliferation, and T cells markers were analyzed. The treatment was tolerable with no adverse events. Fasting C-peptide and insulin requirement remained stable at 15 months, while HbA1c was lower than baseline. Stimulated C-peptide showed no change at 6 months but declined after 15 months (81% of baseline). Eleven patients remained in partial remission (IDAAC < 9). Patients (n = 9) with better clinical outcome had reduced proportion of IgG1 and increased IgG2, IgG3, and IgG4, increased IL-10 secretion, and reduction of proliferation and CD8+ T cells activation. Patients with poorer clinical response had higher baseline levels of GAD65-induced cytokines and T-cell activation, and an increased ratio of effector/central memory T cells. Intra-lymphatic GAD treatment combined with Vitamin D might preserve beta cell function and improve clinical course in T1D. Patients with less benefit have a different quality of immune response both before and after treatment.
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| 6. |
- Ewerman, Lea, et al.
(författare)
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Immunomodulating Effects Depend on Prolactin Levels in Patients with Hyperprolactinemia
- 2020
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Ingår i: Hormone and Metabolic Research. - Stuttgart : Thieme Medical Publishers. - 0018-5043 .- 1439-4286. ; 52:04, s. 228-235
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Tidskriftsartikel (refereegranskat)abstract
- Prolactin is known to have immune modulatory effects acting through the prolactin receptor, which is present on a variety of immune cells. Certain chemokines contribute to form the type of T helper (Th) preponderance in the immune response. The objective of this work was to assess if hyperprolactinemia not related to pregnancy is associated with changes in circulating levels of chemokines and other immunological markers. In this cross sectional study, 35 patients with hyperprolactinemia (5 men), and 102 healthy blood donors (19 men) were included. Serum levels of Th1- Th2- and Th17-associated chemokines, C-reactive protein, immunoglobulins, and the B cell attracting chemokine CXCL13 were assessed. The hyperprolactinemic group had significantly higher levels of Th2 associated CCL22 (p=0.022), Th17 associated CXCL1 (p=0.001), B cell attracting CXCL13 (p=0.003), and C-reactive protein (p<0.001) compared to controls, and these proteins were also positively correlated with prolactin levels. While differences in CCL22, CXCL1, CXCL13, and C-reactive protein were present in patients with low or moderate hyperprolactinemia, no differences were observed at high (>3600 mU/l) prolactin levels. To evaluate a possible dose-associated response to prolactin, an in vitro model was used, showing prolactin-induced increase in T-helper cell activation at moderate levels, while activation decreased at higher levels. Hyperprolactinemia seems to have several immunomodulatory effects and was associated with increased levels of chemokines associated with Th2 and Th17 responses and B cell attraction. However, patients with greatly increased prolactin had normal levels of chemokines, and in vitro, high levels of prolactin decreased T-helper cell activation.
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| 7. |
- Iliadis, Stavros I., 1983-, et al.
(författare)
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Psychometric properties and concurrent validity of the Transgender Congruence Scale (TCS) in the Swedish setting
- 2020
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The Transgender Congruence Scale (TCS) is a non-binary tool used in Sweden for gender dysphoria (GD) assessment; however, its Swedish version has not been validated. To investigate the psychometric properties of the TCS, its capacity to distinguish individuals with GD and its concurrent validity compared to other scales. Patients with GD (n=135) and controls (n=443) filled in a questionnaire containing sociodemographic questions, the TCS, the Utrecht Gender Dysphoria Scale (UGDS), and the Gender Identity/Gender Dysphoria Questionnaire for Adolescents and Adults (GIDYQ-AA). TCS had good discriminatory validity and internal consistency. Patients with GD, stratified by birth-assigned sex, had lower TCS scores compared to controls. Confirmatory factor analysis (CFA) supported the two-factor model of the TCS. Multiple-group CFA suggested measurement invariance between birth-assigned sexes and configural invariance between patients with GD and controls. Area under the ROC curve for birth-assigned males was 0.991 and for females 0.994. A TCS mean value of three provided sensitivity 94.3% and 95.1% as well as specificity 98.6% and 98% for aM and aF, respectively. The TCS was significantly correlated to UGDS and GIDYQ-AA. The TCS may be a valuable tool in the clinical assessment of individuals with GD.
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| 8. |
- Papakokkinou, Eleni, et al.
(författare)
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Excess Morbidity Persists in Patients With Cushing’s Disease During Long-term Remission : A Swedish Nationwide Study
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:8, s. 2616-2624
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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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| 9. |
- Sævik, Åse Bjorvatn, et al.
(författare)
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Residual Corticosteroid Production in Autoimmune Addison Disease
- 2020
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - Washington : Oxford University Press. - 0021-972X .- 1945-7197. ; 105:7, s. 2430-2441
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Tidskriftsartikel (refereegranskat)abstract
- Context: Contrary to current dogma, growing evidence suggests that some patients with autoimmune Addison disease (AAD) produce corticosteroids even years after diagnosis.Objective: To determine frequencies and clinical features of residual corticosteroid production in patients with AAD.Design: Two-staged, cross-sectional clinical study in 17 centers (Norway, Sweden, and Germany). Residual glucocorticoid (GC) production was defined as quantifiable serum cortisol and 11-deoxycortisol and residual mineralocorticoid (MC) production as quantifiable serum aldosterone and corticosterone after > 18 hours of medication fasting. Corticosteroids were analyzed by liquid chromatography-tandem mass spectrometry. Clinical variables included frequency of adrenal crises and quality of life. Peak cortisol response was evaluated by a standard 250 µg cosyntropin test.Results: Fifty-eight (30.2%) of 192 patients had residual GC production, more common in men (n = 33; P < 0.002) and in shorter disease duration (median 6 [0-44] vs 13 [0-53] years; P < 0.001). Residual MC production was found in 26 (13.5%) patients and associated with shorter disease duration (median 5.5 [0.5-26.0] vs 13 [0-53] years; P < 0.004), lower fludrocortisone replacement dosage (median 0.075 [0.050-0.120] vs 0.100 [0.028-0.300] mg; P < 0.005), and higher plasma renin concentration (median 179 [22-915] vs 47.5 [0.6-658.0] mU/L; P < 0.001). There was no significant association between residual production and frequency of adrenal crises or quality of life. None had a normal cosyntropin response, but peak cortisol strongly correlated with unstimulated cortisol (r = 0.989; P < 0.001) and plasma adrenocorticotropic hormone (ACTH; r = -0.487; P < 0.001).Conclusion: In established AAD, one-third of the patients still produce GCs even decades after diagnosis. Residual production is more common in men and in patients with shorter disease duration but is not associated with adrenal crises or quality of life.
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