| 1. |
- Chantzichristos, Dimitrios, 1976, et al.
(författare)
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Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.
- 2021
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Ingår i: eLife. - 2050-084X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.NCT02152553.
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| 2. |
- Demeke, T., et al.
(författare)
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Comorbidity and health-related quality of life in Somali women living in Sweden
- 2019
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 37:2, s. 174-181
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Tidskriftsartikel (refereegranskat)abstract
- - Objective: To explore the relationship between low serum vitamin D levels and comorbidity in Somali women, immigrants to Sweden. Design and setting: Cohort study in a Primary Health Care Center and a University Hospital. Subjects: Somali women skin type V, n = 114, aged 18–56 years, from latitude 0–10 ○ N, living in Sweden, latitude 57 ○ N > 2 years were compared with women from a population sample, skin type II-III, n = 69, aged 38–56 years, the WHO MONICA study, Gothenburg, Sweden. Main outcome measures: Serum (S)-25(OH)D, S-parathyroid hormone (PTH), comorbidity and Health-Related Quality of Life (HRQoL) using the Short Form-36 (SF-36) and part of the EQ-5D questionnaires. All calculations were corrected for age. Results: Vitamin D deficiency (S-25(OH)D < 25 nmol/l) was found in 73% of the Somali women and in 1% of the controls (p <.0001). S-PTH was elevated (>6.9 pmol/l) in 26% and 9%, respectively (p <.004). Somali women used less medication, 16% vs. 55%, p <.0001) but more allergy medication, 11% vs. 7% (p =.006), had fewer fractures, 2% vs. 28% (p <.0001) and lower HRQoL in 7 out of 9 scales (p <.05–.001), than native controls. There were no differences in the prevalence of diabetes mellitus, hypothyroidism, positive thyroid peroxidase antibodies, vitamin B12 deficiency, celiac disease or hypertension. Conclusions: Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity was low. Both mental, and especially physical HRQoL scores were lower in the Somali women. The effects of long-lasting deficiency are unknown.Key points The aim was to explore the relationship between vitamin D deficiency (S-25(OH)D < 25 nmol/l) and comorbidity in immigrants. Vitamin D deficiency was common in Somali women living in Sweden, 73%, but comorbidity of hypothyroidism, diabetes mellitus, hypertension, fractures and use of medications was low. Both mental, and especially physical, Health-Related Quality of Life were lower in the Somali women than in native Swedish women. The effects of long-lasting deficiency are unknown. © 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
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| 3. |
- Einarsdottir, Margret, et al.
(författare)
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High Mortality Rate in Oral Glucocorticoid Users: A Population-Based Matched Cohort Study
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe aim of the study was to investigate all-cause and disease-specific mortality in a large population-based cohort of oral glucocorticoid (GC) users. MethodsThis was a retrospective, matched cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. The cause of death was obtained from the Swedish Cause-of-Death Registry. Patients receiving prednisolone >= 5 mg/day (or equivalent dose of other GC) for >= 21 days between 2007-2014 were included. For each patient, one control subject matched for age and sex was included. The study period was divided into 3-month periods and patients were divided into groups according to a defined daily dose (DDD) of GC used per day. The groups were: Non-users (0 DDD per day), low-dose users (>0 but <0.5 DDD per day), medium-dose users (0.5-1.5 DDD per day) and high-dose users (>1.5 DDD per day). Hazard ratios (HRs), unadjusted and adjusted for age, sex and comorbidities, were calculated using a time-dependent Cox proportional hazard model. ResultsCases (n=223 211) had significantly higher all-cause mortality compared to controls (HR adjusted for age, sex and comorbidities 2.08, 95% confidence interval 2.04 to 2.13). After dividing the cases into subgroups, adjusted HR was 1.31 (1.28 to 1.34) in non-users, 3.64 (3.51 to 3.77) in low-dose users, 5.43 (5.27 to 5.60) in medium-dose users and, 5.12 (4.84 to 5.42) in high-dose users. The highest adjusted hazard ratio was observed in high-dose users for deaths from sepsis 6.71 (5.12 to 8.81) and pulmonary embolism 7.83 (5.71 to 10.74). ConclusionOral GC users have an increased mortality rate compared to the background population, even after adjustment for comorbidities. High-dose users have an increased risk of dying from sepsis, and pulmonary embolism compared to controls. Whether the relationship between GC exposure and the excess mortality is causal remains to be elucidated.
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| 4. |
- Einarsdottir, Margret, et al.
(författare)
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High prescription rate of oral glucocorticoids in children and adults: a retrospective cohort study from Western Sweden.
- 2020
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 92:1, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids (GCs) are a cornerstone in treating various common and uncommon diseases. The aim of this study was to estimate the prevalence of GC use in terms of doses associated with risk of tertiary adrenal insufficiency in adults and children, and treatment indications.This was a retrospective cohort study. Information on dispensed prescriptions was obtained from the Swedish Prescribed Drug Register. Patients with prescriptions of prednisolone (or equivalent dose of other GCs) ≥5 mg daily for ≥21 days between 2007-2014 were included. Information on concurrent diseases was obtained from the Swedish National Patient Register and the Västra Götaland Regional Healthcare Database.Of 1,585,335 inhabitants in Västra Götaland County, 223,211 were included in the study (women 55.6%). Mean age was 48 ± 24 years. Period prevalence of oral GC use during the 8-year study period was 14.1%. The highest prevalence (27.4%) was in men aged 80-89 years and lowest (7.5%) in men 10-19 years of age. The period prevalence in children 0-9 years of age was 10.6%. COPD and asthma were the most common indications for treatment (17.2%) followed by allergy (12.5%), and malignant neoplasms (11.5%). Allergy was the most frequent indication (20.5%) in children and adolescents.Between 2007-2014, every seventh inhabitant in western Sweden received a GC prescription at doses associated with risk of developing tertiary adrenal insufficiency. These findings illustrate the importance of awareness of the potential development of tertiary adrenal insufficiency in both pediatric and adult patients.
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| 5. |
- Einarsdottir, Margret, et al.
(författare)
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Topical clobetasol treatment for oral lichen planus can cause adrenal insufficiency.
- 2023
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Ingår i: Oral diseases. - 1601-0825.
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Tidskriftsartikel (refereegranskat)abstract
- Glucocorticoids suppress the hypothalamic-pituitary-adrenal axis, which may lead to glucocorticoid-induced adrenal insufficiency. The study aimed to investigate the prevalence of this state in patients with oral lichen planus treated with topical clobetasol propionate.In this cross-sectional study, 30 patients with oral lichen planus receiving long-term (>6 weeks) clobetasol propionate gel 0.025% were invited to participate. Adrenal function was assessed by measuring morning plasma cortisol after a 48-h withdrawal of clobetasol treatment. In patients with plasma cortisol <280 nmol/L, a cosyntropin stimulation test was performed.Twenty-seven patients were included. Twenty-one (78%) patients presented with plasma cortisol ≥280 nmol/L (range 280-570 nmol/L), and six (22%) <280 nmol/L (range 13-260 nmol/L). Five of these six patients underwent cosyntropin stimulation that revealed severe adrenal insufficiency in two patients (cortisol peak 150 nmol/L and 210 nmol/L) and mild adrenal insufficiency in three patients (cortisol peak 350-388 nmol/L).In this study, approximately 20% of patients receiving intermittent topical glucocorticoid treatment for oral lichen planus had glucocorticoid-induced adrenal insufficiency. It is essential for clinicians to be aware of this risk and to inform patients about the potential need for glucocorticoid stress doses during intercurrent illness.
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| 6. |
- Einarsdottir, Margret, et al.
(författare)
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Undiagnosed adrenal insufficiency as a cause of premature death in glucocorticoid users.
- 2024
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Ingår i: Endocrine connections. - 2049-3614. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users.Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency.Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30-99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients.GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.
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| 7. |
- Ellegård, Lotta, et al.
(författare)
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Health-related quality of life in hypothyroidism-A population-based study, the WHO MONICA Project
- 2021
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Ingår i: Clinical Endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 95:1, s. 197-208
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Tidskriftsartikel (refereegranskat)abstract
- Objective To explore health-related quality of life (HRQoL) among subjects with hypothyroidism compared to subjects without hypothyroidism in the general population. HRQoL is important in clinical practice. Hypothyroidism is prevalent, mainly found in women, and increasing with age. Design Cohort study of random population sample. Patients Women and men, n = 414 (39-78 years) from the WHO MONICA project, Gothenburg, Sweden, participated. Hypothyroidism was defined as subjects having levothyroxine supplementation or serum thyroid-stimulating hormone (S-TSH) >4.2 mU/L. Measurements Health-related quality of life was measured with Psychological General Well-Being Index (PGWB), Nottingham Health Profile (NHP), Short Form 36 Health Survey (SF-36) and a single item self-rated health scale (0-100), and stress was rated 1-6. The results were adjusted for age, sex and comorbidity using analysis of covariance (ANCOVA). Results Hypothyroidism was found in 70 subjects (17%). They scored worse HRQoL than controls regarding Sleep (p < .001), Social isolation (p = .01) and Total NHP (p < .05), and had more medication in general 2.7 +/- 2.5 vs. 1.8 +/- 2.1, p < .05. Subjects with levothyroxine (n = 40) showed similar results as the total hypothyroid group. Subjects unaware of their newly detected elevated STSH (n = 30) showed lower HRQoL in Sleep (p < .01) and Pain (p < .05) in NHP. HRQoL was similar in subjects with and without positive thyroperoxidase antibodies (TPO-Ab) either in those with hypothyroidism (44% TPO-Ab) or controls (9% TPO-Ab). Conclusion Men and women with hypothyroidism in the general population reported having more issues with Sleep and Social isolation than those without hypothyroidism irrespective of TPO-Ab. Scores were similar in all of the other HRQoL domains measuredAQ5.
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| 8. |
- Esposito, Daniela, et al.
(författare)
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Pituitary dysfunction in granulomatosis with polyangiitis
- 2017
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Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20:5, s. 594-601
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Tidskriftsartikel (refereegranskat)abstract
- Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment.
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| 9. |
- Forslund, Maria, 1978, et al.
(författare)
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Health-Related Quality of Life in perimenopausal women with PCOS
- 2022
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Ingår i: Clinical and Experimental Obstetrics and Gynecology. - : IMR Press. - 0390-6663. ; 49:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have shown that younger women with polycystic ovary syndrome (PCOS) have decreased Health-Related Quality of Life (HRQoL) compared with women in general. Method: In this study peri- and postmenopausal women previously diagnosed with PCOS (n = 27) were compared with randomly selected, age-matched controls (n = 94). Mean age of the study participants was 52 years. Structured interviews and Short Form (SF)-36 questionnaires were used. Results: No differences in SF-36 scores were found, median for the physical summary score was 54 vs. 57, for women with PCOS and controls, respectively; and 53 vs. 53 for the mental summary score, with no differences in any of the eight dimensions of HRQoL. There were no significant difference in prevalence of depression and/or anxiety. The use of drugs for mood disorders was 22% in both groups. Conclusion: PCOS women of peri- and postmenopausal ages had similar HRQoL compared with age-matched controls.
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| 10. |
- Forslund, Maria, 1978, et al.
(författare)
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Higher menopausal age but no differences in parity in women with polycystic ovary syndrome compared with controls.
- 2019
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Ingår i: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 1600-0412 .- 0001-6349. ; 98:3, s. 320-326
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Tidskriftsartikel (refereegranskat)abstract
- To address the question of whether women with polycystic ovary syndrome (PCOS) reach menopause later than age-matched controls, we conducted a follow-up cohort study of women with well-characterized PCOS that was diagnosed 24 years ago. The hypothesis was that women with PCOS would reach menopause later than non-PCOS women. Parity during these 24 years was also studied.Twenty-seven women diagnosed with PCOS in 1992 (mean age 29.5 years) were re-examined in 2016 (mean age 52.4 years). Randomly selected women, n = 94 (mean age 52.4 years), from the same geographic area included in the World Health Organization MONICA study, Gothenburg, Sweden, served as controls.The mean menopausal age in women with PCOS was higher than in controls (53.3 ± 2.2 years vs 49.3 ± 3.5 years, P < 0.01). Serum-follicle stimulating hormone levels were lower in the PCOS women than in controls (31.0 ± 28.1 IU/L vs 52.3 ± 37.7 IU/L, P = 0.01). There was no difference in parity between women with PCOS (1.9 ± 1.3 children, range 0-4) and controls (1.7 ± 1.0, range 0-4 children).Women with PCOS reached menopause 4 years later and had lower serum-follicle stimulating hormone compared with age-matched controls. Neither parity nor nulliparity differed between women with PCOS and controls.
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