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1.	Granfors, Michaela, et al. (författare) Iodine deficiency in a study population of pregnant women in Sweden 2015 Ingår i: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 94:11, s. 1168-1174 Tidskriftsartikel (refereegranskat)abstract IntroductionIodine deficiency in utero may impair neurological development of the fetus. In Sweden, iodine nutrition is considered to be adequate in the general population. The aim of this study was to evaluate iodine nutrition during pregnancy in Sweden. Material and methodsIn this cross-sectional study, the total study population (n=459) consisted of two cohorts (Varmland County, n=273, and Uppsala County, n=186) of pregnant non-smoking women without pre-gestational diabetes mellitus or known thyroid disease before or during pregnancy. Spot urine samples were collected in the third trimester of pregnancy for median urinary iodine concentration (UIC) analysis. ResultsThe median UIC in the total study population was 98g/L (interquartile range 57-148g/L). ConclusionsAccording to WHO/UNICEF/IGN criteria, population-based median UIC during pregnancy should be 150-249g/L. Thus, our results indicate insufficient iodine status in the pregnant population of Sweden. There is an urgent need for further assessments in order to optimize iodine nutrition during pregnancy.
2.	Gustin, Klara, et al. (författare) Assessment of Joint Impact of Iodine, Selenium, and Zinc Status on Women's Third-Trimester Plasma Thyroid Hormone Concentrations 2022 Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 152:7, s. 1737 -1746 Tidskriftsartikel (refereegranskat)abstract Background Iodine is essential for synthesizing thyroid hormones, but other micronutrients are also required for optimal thyroid function. However, there is a lack of data on combined micronutrient status in relation to thyroid hormones in pregnancy. Objectives We aimed to assess the joint associations of iodine, selenium, and zinc status with plasma concentrations of thyroid hormones and thyroid-stimulating hormone (TSH) in pregnancy. Methods We included 531 pregnant women (aged 22-40 y) participating in a Swedish birth cohort who provided blood and spot urine samples in gestational weeks 27-33 (mean: 29). Associations of urinary iodine concentration (UIC), plasma selenium concentration, and plasma zinc concentration (measured by inductively coupled plasma mass spectrometry) with plasma hormone concentrations [total and free thyroxine (tT4, fT4), total and free triiodothyronine (tT3, fT3), and TSH] were explored with Bayesian kernel machine regression (BKMR; n = 516; outliers excluded) and multivariable-adjusted linear regression (n = 531; splined for nonlinear associations). Results Median (IQR) micronutrient concentrations were 112 mu g/L (80-156 mu g/L) for UIC, 67 mu g/L (58-76 mu g/L) for plasma selenium, and 973 mu g/L (842-1127 mu g/L) for plasma zinc; the former 2 median values were below recommended concentrations (150 mu g/L and 70 mu g/L, respectively). Mean +/- SD TSH concentration was 1.7 +/- 0.87 mIU/L, with 98% < 4 mIU/L. BKMR showed a positive trend of joint micronutrient concentrations in relation to TSH. Plasma zinc was most influential for all hormones but tT3, for which plasma selenium was most influential. In adjusted linear regression models, zinc was positively associated with tT4, tT3, and TSH, and <1200 mu g/L also with fT4 and fT3. Selenium was inversely associated with fT3, and Conclusions Pregnant women's plasma TSH concentrations in the early third trimester increased with increasing joint status of iodine, selenium, and zinc. Zinc and selenium were more influential than iodine for the hormone concentrations. Multiple micronutrients need consideration in future studies of thyroid hormone status.
3.	Abraham-Nordling, Mirna, et al. (författare) Incidence of hyperthyroidism in Sweden 2011 Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 899-905 Tidskriftsartikel (refereegranskat)abstract Introduction: The incidence of hyperthyroidism has been reported in various countries to be 23-93/100000 inhabitants per year. This extended study has evaluated the incidence for similar to 40% of the Swedish population of 9 million inhabitants. Sweden is considered to be iodine sufficient country. Methods:All patients including children, who were newly diagnosed with overt hyperthyroidism in the years 2003-2005, were prospectively registered in a multicenter study. The inclusion criteria are as follows:clinical symptoms and/or signs of hyperthyroidism with plasma TSH concentration below 0.2 mIE/l and increased plasma levels of free/total triiodothyronine and/or free/total thyroxine. Patients with relapse of hyperthyroidism or thyroiditis were not included. The diagnosis of Graves' disease (GD), toxic multinodular goiter (TMNG) and solitary toxic adenoma (STA), smoking, initial treatment, occurrence of thyroid-associated eye symptoms/signs, and demographic data were registered. Results:A total of 2916 patients were diagnosed with de novo hyperthyroidism showing the total incidence of 27.6/100 000 inhabitants per year. The incidence of GD was 21.0/100 000 and toxic nodular goiter (TNG=STA+TMNG) occurred in 692 patients, corresponding to an annual incidence of 6.5/100 000. The incidence was higher in women compared with men (4.2:1). Seventy-five percent of the patients were diagnosed with GD, in whom thyroid-associated eye symptoms/signs occurred during diagnosis in every fifth patient. Geographical differences were observed. Conclusion:The incidence of hyperthyroidism in Sweden is in a lower range compared with international reports. Seventy-five percent of patients with hyperthyroidism had GD and 20% of them had thyroid-associated eye symptoms/signs during diagnosis. The observed geographical differences require further studies.
4.	Andersson, Maria, et al. (författare) A new national study suggests iodine intakes are adequate in Sweden 2008 Ingår i: IDD Newsletter. ; 29, s. 8-9 Tidskriftsartikel (refereegranskat)
5.	Andersson, M, et al. (författare) Adequate iodine nutrition in Sweden: a cross-sectional national study of urinary iodine concentration in school-age children. 2009 Ingår i: European journal of clinical nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 63:7, s. 828-34 Tidskriftsartikel (refereegranskat)abstract Background/Objectives:Sweden has a long-standing salt iodization program; however, its effects on iodine intake have never been monitored on a national level. The objective of this study was to evaluate iodine nutrition in the Swedish population by measuring the urinary iodine concentration (UIC) in a national sample of Swedish school-age (6-12 years of age) children.Subjects/Methods:A stratified probability proportionate to size cluster sampling method was used to obtain a representative national sample of school-age children from 30 clusters. Spot urine samples were collected for UIC analysis using a modified Sandell-Kolthoff method.Results:The median UIC of the children (n=857) was 125 mug/l (range 11-757 mug/l). The proportion of children with a UIC <100 mug/l was 30.0% and the proportion of children with a UIC <50 and >300 mug/l was 5.5 and 3.0%, respectively.Conclusions:The iodine nutritional status of the Swedish population is adequate. Iodized table salt remains the main dietary source of iodine in Swedish diet. Recommendations to reduce total salt intake in the population urge increased use of iodized salt in the production of processed foods. Pregnant and lactating women with high iodine requirements may still be at risk for low iodine intake. This study will serve as the basis for future monitoring of iodine nutritional status in Sweden.European Journal of Clinical Nutrition advance online publication, 10 September 2008; doi:10.1038/ejcn.2008.46.
6.	Barbosa, Edna J L, 1961, et al. (författare) Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study. 2014 Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8 Tidskriftsartikel (refereegranskat)abstract Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
7.	Barbosa, Edna J L, 1961, et al. (författare) Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy. 2012 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62 Tidskriftsartikel (refereegranskat)abstract bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
8.	Barbosa, Edna J L, 1961, et al. (författare) Influence of the Exon 3-deleted/full-length Growth Hormone Receptor Polymorphism on the Response to Growth Hormone Replacement Therapy in Adults with Severe Growth Hormone Deficiency. : d3-GHR isoform in GHD adults 2009 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:2, s. 639-644 Tidskriftsartikel (refereegranskat)abstract Context: There is considerable individual variation in the clinical response to growth hormone (GH) replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. Objective: To assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. Design, Patients: 124 adult GHD patients (79 men, median age 50 years) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (Group 1) and those bearing at least one d3-GHR allele (Group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). Intervention: GH dose was individually titrated to obtain normal serum IGF-I levels. Main Outcome Measures: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Results: Seventy-two (58%) patients had fl/fl genotype and were classified as Group 1, while 52 (42%) had at least one d3-GHR allele and were classified as Group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. Conclusion: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.
9.	Barbosa, Edna J L, 1961, et al. (författare) Models to predict changes in serum IGF1 and body composition in response to GH replacement therapy in GH-deficient adults. 2010 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 162:5, s. 869-78 Tidskriftsartikel (refereegranskat)abstract Clinical response to GH therapy in GH-deficient (GHD) adults varies widely. Good predictors of treatment response are lacking. The aim of the study was to develop mathematical models to predict changes in serum IGF1 and body composition (BC) in response to GH therapy in GHD adults.
10.	Blomqvist, Lennart, 1947, et al. (författare) Preconceptual thyroid peroxidase antibody positivity in women with recurrent pregnancy losses may contribute to an increased risk for another miscarriage. 2023 Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 98:2, s. 259-269 Tidskriftsartikel (refereegranskat)abstract To investigate preconceptual thyroid peroxidase antibody (TPO-ab) positivity and/or thyroid stimulating hormone (TSH) levels in the upper range of normal as risk factors for recurrent unexplained first-trimester miscarriage.A post-hoc study of a randomized trial, in which acetylsalicylic acid did not affect the risk of a new miscarriage.Women (n=483) with at least three unexplained recurrent first-trimester miscarriages investigated at a Swedish secondary referral center.The levels of TPO-ab and TSH were determined before pregnancy. The occurrence of a new first-trimester miscarriage was analyzed by logistic regression with adjustments when applicable, for age, number of previous miscarriages, obesity and the investigated covariates levels of TPO-ab and TSH.Including all first trimester miscarriages, odds ratio (OR) according to presence of TPO-ab was 1.60 (95% confidence interval [CI]; 0.99-2.57), after adjustment 1.54 (95% CI; 0.94-2.53). Very early (biochemical) pregnancy losses occurred more often in women with than without preconceptual TPO-ab (6.8% vs. 2.0%), OR 3.51 (95% CI; 1.15-10.71), after adjustment 2.91 (95% CI; 0.91-9.29). There was no association between TSH in the upper range of normal and a new miscarriage, adjusted OR 0.76 (95% CI; 0.32-1.83). A prediction model for a new miscarriage included number of previous miscarriages, woman's age and presence of TPO-ab.In women with at least three recurrent unexplained pregnancy losses, the presence of TPO-ab may contribute to an increased risk of a first-trimester miscarriage, possibly more pronounced in very early pregnancy. TSH levels 2.5-4.0 mU/L do not seem to increase the miscarriage risk.
11.	Eriksson, Janna, 1992, et al. (författare) The effects of iron and selenium in iodine containing multivitamins on thyroid related compounds during pregnancy in Sweden: a randomized placebo cotrolled trial 2017 Ingår i: 87th Annual Meeting of the American Thyroid Association. Thyroid, 27(S1), poster 71. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract Multivitamins with iodine are advocated to pregnant women to avoid iodine deficiency, as iodine may be beneficial for brain development in the child. Multivitamins also contain iron and selenium that may affect thyroid hormone metabolism. Iron is included in the tyreoperoxidase enzyme promoting the coupling of iodine to thyroglobulin (Tg) and selenium is incorporated in deiodinases that regulates levels of thyroxine (T4) and triiodothyronine (T3). There is no previous studies on the effects of iodine containing multivitamins on iron and selenium levels in pregnant women and the relation to thyroid hormone levels. This was a randomized, double-blinded controlled trial of 200 pregnant women, who were randomized to multivitamins containing 150 lg iodine, 12 mg iron and 50 lg selenium/day or multivitamins without iodine, iron and selenium in pregnancy week 7–12 until delivery, besides iron supplements on usual routines. Thyroid hormones, Tg, selenium (ref 0.7– 1.2 lmol/L) and iron measurements (ferritin (ref 15–150 mg/L), transferrin saturation (ref 0.1–0.5)) were collected in the third trimester. Urinary iodine concentration confirmed mild ID in the control group with a Tg increase. In the third trimester, 139 patients were left for sampling. In the active group (n = 67) median (interquartile range (IQR)) selenium levels were 0.72 (0.16) vs 0.61 (0.14) in the control group (n = 72), p < 0.001. Low selenium values were noted in 70.0% of participants and it was more common in the control group (81.9%), p < 0.001. Median (IQR) Tg levels was higher in those with low selenium 30.0 (30.5) than in those with normal selenium 20.5 (21.5), p = 0.037. Thyroid hormones did not differ between active/control groups or low/normal selenium groups, but FT3/FT4 ratio was higher in the low selenium group than in the normal selenium group (0.35 (0.08) vs 0.33 (0.08)), p= 0.025. Ferritin in the active group was 22.0 (21.0) and 20.0 (21.5) in the control group, p = 0.393 and transferrin saturation 0.20 (0.11) and 0.18 (0.18), p = 0.802, respectively. Multivitamins used during pregnancy to increase iodine levels also increase selenium levels where effects on thyroid metabolism needs further evaluation.
12.	Eriksson, Janna, 1992, et al. (författare) Urinary iodine excretion and optimal time point for sampling when estimating 24-h urinary iodine 2023 Ingår i: British Journal of Nutrition. - : Cambridge University Press (CUP). - 0007-1145 .- 1475-2662. ; 130:8, s. 1289-97 Tidskriftsartikel (refereegranskat)abstract Iodine deficiency may cause thyroid dysfunction. The iodine intake in a population is measured by urinary iodine concentration (UIC) in spot samples or 24-h urinary iodine excretion (24UIE). 24UIE is considered the gold standard and may be estimated using an equation including UIC, urinary creatinine concentration, sex and age (e24UIE). The aims of this study were to evaluate the preferable timing of UIC when using this equation and assess the variability of UIE. Sixty healthy non-smoking women (n 31) and men (n 29) were included in Gothenburg, Sweden. Twelve urine samples were collected at six fixed times on two separate days. Variability was calculated for UIC, 24UIE, e24UIE, iodine excretion per hour (iHr) and UIC adjusted for creatinine and specific gravity. Median 24UIE was 156 mu g/24 h and the median UIC (all spot samples) was 104 mu g/l. UIC (P < 0 center dot 001), 24UIE (P = 0 center dot 001) and e24UIE (P < 0 center dot 001) were significantly higher in men. e24UIE was relatively similar to 24UIE. However, when e24UIE was calculated from UIC in the first void, it was about 15 % lower than 24UIE (P < 0 center dot 001). iHr was lowest in the morning and highest in the afternoon. Median iHr was higher in men (7 center dot 4 v. 5 center dot 3 mu g/h, P < 0 center dot 001). The variability of UIE was higher within individuals than between individuals. This study suggests that most time points for estimation of individual 24UIE are appropriate, but they should preferably not be collected in the first void.
13.	Falhammar, Henrik, et al. (författare) Bone Mineral Density, Bone Markers, and Fractures in Adult Males with Congenital Adrenal Hyperplasia. 2013 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 168, s. 331-341 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The aim of this study was to determine bone mineral density (BMD), markers of bone metabolism, fractures, and steroids reflecting hormonal control in adult males with congenital adrenal hyperplasia (CAH). SUBJECTS, METHODS AND DESIGN: We compared CAH males with 21-hydroxylase deficiency (n=30), 19-67 years old, with age- and sex-matched controls (n=32). Subgroups of CYP21A2 genotypes, age, glucocorticoid preparation, poor control versus overtreatment, and early versus late (>36 months) diagnosis were studied. Bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA) and markers of bone metabolism and androgens/17-hydroxyprogesterone levels were investigated. RESULTS: All, including older (>30 yrs), CAH patients had lower BMD in all measured sites compared to control subjects. The null group demonstrated lower BMD in more locations than the other groups. Osteoporosis/osteopenia was present in 81% of CAH patients compared to 32% in controls (≥30 yrs). Fracture frequency was similar, osteocalcin lower, and fewer patients than controls had vitamin D insufficiency. IGF-I was elevated in the milder genotypes. In patients, total body BMD was positively correlated to weight, BMI, total lean body mass, triglycerides, and negatively to prolactin. Patients on prednisolone had lower BMD and osteocalcin levels than those on hydrocortisone/cortisone acetate. Patients with poor control had higher femoral neck BMD. There were no differences in BMD between patients with an early versus late diagnosis. CONCLUSIONS: CAH males have low BMD and bone formation markers. BMD should be monitored, adequate prophylaxis and treatment established, and glucocorticoid doses optimized to minimize the risk of future fractures.
14.	Falhammar, Henrik, et al. (författare) Cardiovascular risk, Metabolic Profile, and Body Composition in Adult Males with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency. 2011 Ingår i: European journal of endocrinology. - 1479-683X. ; 164:1, s. 285-293 Tidskriftsartikel (refereegranskat)abstract Objective: Life-long glucocorticoid therapy in patients with congenital adrenal hyperplasia (CAH) or the disease per se may result in increased cardiovascular risk. We therefore investigated cardiovascular and metabolic risk profiles in adult CAH males. Subjects and Methods: We compared CAH males (n=30), 19-67 years old, with age- and sex-matched controls (n=32). Subgroups of different ages (<30 years or older) and CYP21A2 genotypes (null, I2splice and I172N as the mildest mutation) were studied. Anthropometry, fat and lean mass measured by dual-energy x-ray absorptiometry (DXA), lipids, liver function tests, homocysteine, lipoprotein(a), glucose and insulin during an oral glucose tolerance test (OGTT), urine albumin, adrenal hormones, and 24h ambulatory blood pressure measurements were studied. Results: CAH males were shorter. Waist/hip ratio and fat mass were higher in older patients and the I172N group. Heart rate was faster in older patients, the I2splice, and I172N groups. Insulin levels were increased during OGTT in all patients and in the I172N group. Gamma-glutamyl transpeptidase was increased in older patients and in the I172N group. Testosterone was lower in older patients. Homocysteine was lower in younger patients which may be cardioprotective. The cardiovascular risk seemed higher with hydrocortisone/cortisone acetate compared to prednisolone. Urinary epinephrine was lower in all groups of patients except in I172N. Conclusions: Indications of increased risk were found in CAH males ≥30 years old and in the I172N group. In contrast, younger CAH males did not differ from age-matched controls. This is likely to reflect a better management in recent years.
15.	Falhammar, Henrik, et al. (författare) Fertility, Sexuality and Testicular Adrenal Rest Tumors in Adult Males with Congenital Adrenal Hyperplasia. 2012 Ingår i: European journal of endocrinology. - 1479-683X. ; 166, s. 441-449 Tidskriftsartikel (refereegranskat)abstract Objective: Fertility in males with congenital adrenal hyperplasia (CAH) is reported from normal to severely impaired. We therefore investigated fertility/fecundity, social/sexual situation, and pituitary- gonadal function in CAH males.Subjects and methods: The patient cohort comprised 30 males with 21-hydroxylase deficiency, 19-67 yr. Their fertility was compared with age-matched national population data. For the evaluation of social/sexual factors and hormone status, age-matched controls were recruited (n=32). Subgroups of different ages (<30 years and older) and CYP21A2 genotypes: null (severe salt wasting), I2splice (milder salt wasting), and I172N (simple virilizing) were also studied. Patients underwent testicular ultrasound examination (n=21), and semen analysis (n=14).Results: Fertility was impaired in CAH males compared to national data (0.9±1.3 vs. 1.8±0.5 children/father, P<0.001). There were no major differences in social and sexual factors between patients and controls apart from more fecundity problems, particularly in the I172N group. The patients had lower testosterone/estradiol ratio and inhibin B, and higher FSH. The semen samples were pathological in 43% (6/14) of patients and sperm concentration correlated with inhibin B and FSH. Testicular adrenal rest tumours (TARTs) were found in 86% (18/21). Functional testicular volume correlated positively with the testosterone/estradiol ratio, sperm concentration and inhibin B. Patients with pathological semen had increased fat mass and indications of increased cardiometabolic risk.Conclusions: Fertility/fecundity was impaired in CAH males. The frequent occurrence of TARTs resulting in testicular insufficiency appears to be the major cause, but other factors such as elevated fat mass may contribute to a low semen quality.
16.	Falhammar, H, et al. (författare) Fractures and Bone Mineral Density in Adult Women with 21-Hydroxylase Deficiency. 2007 Ingår i: J Endocrinol Metab. - : The Endocrine Society. - 0021-972X .- 1945-7197. Tidskriftsartikel (refereegranskat)abstract Context: Patients with classic congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacologic doses of glucocorticoids are an established risk factor for osteoporosis. Objectives: To evaluate bone mineral density (BMD), fracture prevalence and markers of bone metabolism in adult females with CAH. Design: This was a cross-sectional observational study. Setting: Tertiary care referral centers. Participants: We studied 61 women, aged 18-63 years, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt-wasting (n = 27), simple virilising (n = 28) and non-classic 21-hydroxylase deficiency (n = 6). Sixty-one age-matched women were controls. Main outcome measures: History of fractures was recorded. Total body, lumbar spine and femoral neck BMD were measured by dual-energy X-ray absorptiometry. The WHO criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide (CTX) was studied. Results: The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m(2). Patients had lower BMD than controls at all measured sites (P < 0.001). In patients < 30 years old 48% were osteopenic vs 12% in controls (P < 0.009). In patients >/= 30 years old 73% were osteopenic or osteoporotic vs 21% in controls (P < 0.001). BMD was similar in the two classic forms and had no obvious relationship to genotypes. CTX was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058). Conclusion: Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.
17.	Falhammar, Henrik, et al. (författare) Increased liver enzymes in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 2009 Ingår i: Endocrine journal. - 1348-4540. ; 56:4, s. 601-8 Tidskriftsartikel (refereegranskat)abstract The aims were assessing liver function tests (LFT) in women with congenital adrenal hyperplasia (CAH) on glucocorticoids. Sixty-one women with genetically verified CAH due to 21-hydroxylase deficiency, aged 18-63 years were compared to 61 controls. Serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT), anthropometry and fat mass (dual energy X-ray absorptiometry) were measured. ALT and GGT were higher in the entire patient group (p=0.01 and 0.002); AST, GGT and ALP in patients > or =30 years (p=0.007-0.045); all LFT in salt-wasting (p<0.001-0.042); GGT in simple virilizing (p=0.008); ALT, GGT and ALP in Null/Null genotype (p=0.018-0.040); ALT and GGT in I2splice genotype (p<0.001 and 0.011). Using a recently proposed cut-off level for ALT (>0.317 microkat/L), 54% of patients vs 23% of controls had elevated levels (p=0.028). In patients, GGT and ALP correlated with waist circumference and with total body and trunk fat (r=0.274-0.406, p=0.001-0.043). However, ALT, GGT and ALP were increased even in non-obese patients (waist circumference < or =88 cm and body mass index <30 kg/m(2)) (p=0.012-0.045) mainly attributed to the patients > or =30 years who also demonstrated elevated insulin levels and HOMA-indices. In conclusion, compared with controls, women with CAH have higher LFT, in particular patients > or =30 years and those with severe forms, probably reflecting a higher lifetime glucocorticoid exposure. LFT were positively correlated to measurements of body fat. These women might have increased frequency of NAFLD. The finding of higher LFT also in non-obese patients suggests that not only central obesity but also glucocorticoids per se may influence.
18.	Falhammar, Henrik, et al. (författare) Metabolic profile and body composition in adult women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. 2007 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:1, s. 110-6 Tidskriftsartikel (refereegranskat)abstract CONTEXT: The chronic, often supraphysiological glucocorticoid doses used in congenital adrenal hyperplasia (CAH) might increase morbidity in cardiovascular disease and diabetes. OBJECTIVE: Our aim was to assess risk factors for cardiovascular disease and diabetes in CAH women. SUBJECTS, METHODS, AND DESIGN: We compared 61 women, 18-63 yr, with CAH due to 21-hydroxylase deficiency with 61 age- and sex- matched controls. Twenty-seven were younger than 30 yr, and 34 were 30 yr or older. Anthropometry, fat and lean mass measured by dual-energy x-ray absorptiometry, serum lipids, insulin, and adrenocortical steroids were studied. MAIN OUTCOME MEASURE: Body composition and cardiovascular risk factors were the main outcome measures. RESULTS: Younger patients and controls had similar waist to hip ratio, lean and fat mass, and insulin. Older patients had higher waist to hip ratio, lean mass, and insulin than controls. Fat mass was similar to controls but higher than in younger patients. Lipid profiles were slightly more favorable in older patients than controls. Gestational diabetes was more common in patients (21% of pregnancies vs. 0, P < 0.026). Few older patients had hypertension, cardiovascular disease, or diabetes. Despite moderate glucocorticoid doses, most patients had suppressed androgens. CONCLUSIONS: No clear evidence of unfavorable cardiovascular risk factors were found. Increased fat mass and higher insulin levels were, however, found in patients older than 30 yr. High frequency of gestational diabetes is a risk marker for future diabetes. Lifelong follow-up, lifestyle modifications, and attempts to adjust and reduce the glucocorticoid doses seem important.
19.	Falhammar, Henrik, et al. (författare) Quality of life, social situation, and sexual satisfaction, in adult males with congenital adrenal hyperplasia. 2014 Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1559-0100 .- 1355-008X. ; 47:1, s. 299-307 Tidskriftsartikel (refereegranskat)abstract To determine quality of life (QoL) in adult males with congenital adrenal hyperplasia (CAH). CAH males with 21-hydroxylase deficiency (n = 30), 19-67 years old, were compared with controls (n = 32). QoL was assessed using questionnaires on general living conditions and sexual issues, and the psychological well-being index (PGWB) form. Fewer CAH males than controls were students (3 vs. 25 %, P = 0.028) and more had blue-collar work (57 vs. 33 %, P = 0.023). Patients were less interested in sports (47 vs. 72 %, P = 0.034) and art/literature/film (10 vs. 47 %, P = 0.004). PGWB total score was 82.7 ± 13.7 versus 87.0 ± 11.1 (P = NS), but hydrocortisone/cortisone acetate treated scored lower than controls and prednisolone treated. Glucocorticoid over-treated had lower QoL than those with poor control (PGWB total score 77.1 ± 13.5 vs. 92.4 ± 11.1, P = 0.026) and controls (P = 0.025). Total PGWB score was positively correlated with adrenal androgens and steroid precursors. Subscale scores indicated that patients with late diagnosis were more depressive (12.1 ± 2.8 vs. 13.9 ± 1.4, P = 0.011) and had a lower self-control (11.3 ± 3.6 vs. 13.1 ± 1.0, P = 0.019) compared with controls. Sexual satisfaction was similar in spite of more patients being sexually inactive (27 vs. 6 %, P = 0.040). Adult CAH males differed from controls with respect to type of occupation and spare time interests but had similar QoL despite being less sexually active. Optimizing glucocorticoid therapy might further improve QoL. Some disadvantages found in patients diagnosed late will hopefully not be seen in patients diagnosed by neonatal screening, but this has yet to be studied.
20.	Filipsson, Helena, 1966 (författare) Aspects of diagnosis and treatment of hypopituitarism in adult life 2009 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Management of adult patients with hypopituitarism can improve with better char¬ac¬terisation of idiopathic pituitary insufficiency (IPI) and clearer diagnosis of central hy¬pothy¬roidism (CH). Moreover, optimised treatment strategies for glucocorticoid (GC) re¬placement therapy and of long-term growth hormone (GH) in GH deficiency (GHD) are needed. This thesis contains four studies addressing these issues. By evaluating patients with IPI, mutations generating hypopituitarism were identified in an unselected adult IPI population. A new allel constellation in a compound PROP1 mutation was re¬vealed in two siblings, with a phenotype of very late onset ACTH-insufficiency. Those cases were only detected in patients with documented childhood onset disease. A pilot study investigated the response of the thyroid gland after stimulation with 0.9 mg re¬combinant human thyreotropin (rhTSH) in patients with newly diagnosed CH and healthy controls. The untreated CH patients had lower free thyroxine response than controls. A database study containing 2424 hypopituitary patients, di¬vided into ACTH-insufficient and ACTH-sufficient (AS) patients, demonstrated a clear GC dose-re¬sponse relation with metabolic outcome. Patients with hydrocortisone equivalent doses of <20 mg/day had a similar metabolic profile as AS patients. In a large study on GHD patients on long-term GH treatment quality of life (QoL), body composition, and metabolic outcome were evaluated during 4-month-GH-dis¬continuation in a dou¬ble blind, placebo controlled design. QoL deteriorated, body com¬position moved towards a GHD state and metabolic parameters were impaired during placebo treatment. These studies infer that genetic hypopituitarism should be searched for in IPI cases, especially in childhood onset disease and where there is a family history. The diag¬nosis of CH can be improved by an rhTSH test. In many cases, doses of GC can be reduced in ACTH-insufficient patients in order to improve their metabolic outcome and continuous long-term GH replacement is needed to maintain beneficial effects on QoL, body composition, and metabolism.
21.	Filipsson, Helena, 1966, et al. (författare) Exploring the use of recombinant human TSH in the diagnosis of central hypothyroidism. 2008 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 159:2, s. 153-60 Tidskriftsartikel (refereegranskat)abstract CONTEXT: The diagnosis of central hypothyroidism (CH) is often difficult to establish as serum TSH levels may be low, normal, or slightly increased. OBJECTIVE: To explore the use of recombinant human TSH (rhTSH) in the diagnosis of CH. DESIGN: Randomized single-blind clinical trial. SETTING: Outpatient clinic of a tertiary care referral center. INTERVENTION: A single intramuscular injection of 0.1 and 0.9 mg rhTSH in random order with 1-week interval. PARTICIPANTS: Eighteen adult patients with pituitary insufficiency and six healthy age-, sex-, and body mass index-matched controls. Six patients had untreated CH (newCH), six had treated CH (CH), and six patients were TSH sufficient (nonCH). Five weeks before TSH stimulation, levothyroxine was replaced with tri-iodothyronine (T(3)) for 4 weeks. One week before stimulation, treatment was withdrawn. MAIN OUTCOME MEASURES: Thyroid hormones and thyroglobulin (Tg) before and 2, 3(1/2), 7, 24, 48, and 72 h after each injection. RESULTS: In the newCH group, basal free thyroxine (FT(4)) levels were lower than in controls (P<0.05). After 0.9 mg rhTSH, the increases in FT(4) and reverse T(3) (rT(3)) were less marked in the newCH group than in controls (FT(4)+/-s.e.m. 9.2+/-0.5 to 19.7+/-1.2 vs 11.3+/-0.5 to 27.8.2+/-2.4 pmol/l, P<0.05). The CH group exhibited reduced basal and stimulated FT(4) compared with the TSH-sufficient groups. Tg increased similarly among all study groups after rhTSH injection. CONCLUSION: In this pilot study, patients with untreated CH had lower response to 0.9 mg rhTSH in FT(4) and rT(3) than controls. An rhTSH test may be useful in the diagnosis of CH, but further studies are required.
22.	Filipsson, Helena, 1966, et al. (författare) GH replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies. 2009 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X. ; 161 Suppl 1 Tidskriftsartikel (refereegranskat)abstract Severe GH deficiency (GHD) in adults has been described as a clinical entity. However, some of the features associated with GHD could be due to unphysiological and inadequate replacement of other pituitary hormone deficiencies. This may be true for glucocorticoid replacement that lacks a biomarker making dose titration and monitoring difficult. Moreover, oral estrogen replacement therapy decreases IGF1 levels compared with the transdermal route, which attenuates the responsiveness to GH replacement therapy in women. In addition, in untreated female hypogonadism, oral estrogen may augment the features associated with GHD in adult women. Important interactions between the hormones used for replacing pituitary hormone deficiency occur. Introducing GH replacement may unmask both an incipient adrenal insufficiency and central hypothyroidism. Therefore, awareness and proper monitoring of these hormonal interactions are important in order to reach an optimal replacement therapy. This review will focus on the complex hormonal interactions between GH and other pituitary hormones in GHD and in GH replacement.
23.	Filipsson, Helena, 1966, et al. (författare) The impact of glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients. 2006 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:10, s. 3954-61 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Hypopituitary patients with untreated GH deficiency and patients on inappropriately high doses of glucocorticoid (GC) share certain clinical features. OBJECTIVE: The aim of the study was to examine the influence of GC substitution on clinical characteristics in hypopituitary patients before and after GH replacement therapy. METHOD: A total of 2424 hypopituitary patients within the KIMS (Pfizer International Metabolic Database) were grouped according to ACTH status. Comparisons were performed between subjects on hydrocortisone (HC) (n = 1186), cortisone acetate (CA) (n = 487), and prednisolone/dexamethasone (n = 52), and ACTH-sufficient patients (AS) (n = 717) before and after 1 yr of GH treatment in terms of body mass index, waist and hip circumference, blood pressure, glucose, glycosylated hemoglobin (HbA1c), serum lipids, IGF-I, and comorbidity. Hydrocortisone equivalent (HCeq) doses were calculated, and measurements were adjusted for sex and age. RESULTS: At baseline, the HC group had increased total cholesterol, triglycerides, waist circumference, and HbA1c, and the prednisolone/dexamethasone group had increased waist/hip ratio as compared with AS. After HCeq dose adjustment, the HC group retained higher HbA1c than the CA group. GC-treated patients showed a dose-related increase in serum IGF-I, body mass index, triglycerides, low-density lipoprotein cholesterol and total cholesterol levels. Subjects with HCeq doses less than 20 mg/d (n = 328) at baseline did not differ from AS in metabolic endpoints. The 1-yr metabolic response to GH was similar in all GC groups and dose categories. All new cases of diabetes (n = 12), stroke (n = 8), and myocardial infarction (n = 3) during GH treatment occurred in GC-treated subjects. CONCLUSION: HCeq doses of at least 20 mg/d in adults with hypopituitarism are associated with an unfavorable metabolic profile. CA replacement may have metabolic advantages compared with other GCs.
24.	Frisén, Lars, et al. (författare) Gender role behavior, sexuality, and psychosocial adaptation in women with congenital adrenal hyperplasia due to CYP21A2 deficiency 2009 Ingår i: J Clin Endocrinol Metab. - : The Endocrine Society. ; 94:9, s. 3432-9 Tidskriftsartikel (refereegranskat)abstract CONTEXT: Gender-atypical behavior has been described in young girls as well as in women with congenital adrenal hyperplasia (CAH) due to a CYP21A2 deficiency. OBJECTIVE: The aim of the study was to assess health-related, psychosexual, and psychosocial parameters and correlate the results to CYP21A2 genotype. DESIGN AND PARTICIPANTS: Sixty-two Swedish women with CAH and age-matched controls completed a 120-item questionnaire and a validated quality of life instrument [psychological general well-being (PGWB) formula] to identify psychosexual and psychosocial parameters. The patients were divided into four CYP21A2 genotype groups. RESULTS: The women with CAH held more male-dominant occupations (30%) compared to controls (13%) (P = 0.04), especially those in the null genotype group (55%) (P = 0.006). They also reported a greater interest in rough sports (74%) compared to controls (50%) (P = 0.007). Eight women with CAH (14%) reported a prime interest in motor vehicles, compared to none of the controls (P = 0.002). Non-heterosexual orientation was reported by 19% of women with CAH (P = 0.005), 50% in the null genotype group (P = 0.0001), 30% in I2 splice (NS), and 5% in I172N (NS). PGWB total score did not differ between patients and controls. CONCLUSION: We identified increased gender-atypical behavior in women with CAH that could be correlated to the CYP21A2 genotype. This speaks in favor of dose-dependent effects of prenatal androgens on the development of higher brain functions. The impact of the disease on upbringing and interpersonal relationships did not correlate with disease severity, indicating that other factors, such as coping strategies, are important for psychosocial adaptation. This illustrates the need for psychological support to parents and patients.
25.	Fryk, Emanuel, et al. (författare) Microdialysis and proteomics of subcutaneous interstitial fluid reveals increased galectin-1 in type 2 diabetes patients 2016 Ingår i: Metabolism-Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 65:7, s. 998-1006 Tidskriftsartikel (refereegranskat)abstract Objective. To identify a potential therapeutic target for type 2 diabetes by comparing the subcutaneous interstitial fluid from type 2 diabetes patients and healthy men. Methods. Proteomics was performed on the interstitial fluid of subcutaneous adipose tissue obtained by microdialysis from 7 type 2 diabetes patients and 8 healthy participants. 851 proteins were detected, of which 36 (including galectin-1) showed significantly altered expression in type 2 diabetes. We also measured galectin-1 expression in: (1) adipocytes isolated from adipose tissue biopsies from these participants; (2) subcutaneous adipose tissue of 24 obese participants before, during and after 16 weeks on a very low calorie diet (VLCD); and (3) adipocytes isolated from 6 healthy young participants after 4 weeks on a diet and lifestyle intervention to promote weight gain. We also determined the effect of galectin-1 on glucose uptake in human adipose tissue. Results. Galectin-1 protein levels were elevated in subcutaneous dialysates from type 2 diabetes compared with healthy controls (p < 0.05). In agreement, galectin-1 mRNA expression was increased in adipocytes from the type 2 diabetes patients (p < 0.05). Furthermore, galectin-1 mRNA expression was decreased in adipose tissue after VLCD (p < 0.05) and increased by overfeeding (p < 0.05). Co-incubation of isolated human adipocytes with galectin-1 reduced glucose uptake (p < 0.05) but this was independent of the insulin signal. Conclusion. Proteomics of the interstitial fluid in subcutaneous adipose tissue in vivo identified a novel adipokine, galectin-1, with a potential role in the pathophysiology of type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.
26.	Glad, Camilla A M, 1981, et al. (författare) SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults. 2014 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 170:1, s. 101-7 Tidskriftsartikel (refereegranskat)abstract GH-deficient (GHD) adults have reduced serum concentrations of IGF1. GH replacement therapy increases serum IGF1 concentrations, but the interindividual variation in treatment response is large and likely influenced by genetic factors. This study was designed to test the hypothesis that single-nucleotide polymorphisms (SNPs) in genes within the GH signaling pathway influence the serum IGF1 response to GH replacement.
27.	Hagenfeldt, K., et al. (författare) Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency 2008 Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 23:7, s. 1607-1613 Tidskriftsartikel (refereegranskat)
28.	Hansson, Marie, 1979, et al. (författare) Iodine Content and Distribution in Thyroid Specimens from Two Patients with Graves' Disease Pretreated with Either Propylthiouracil or Stable Iodine: Analysis Using X-Ray Fluorescence and Time-of-Flight Secondary Ion Mass Spectrometry. 2012 Ingår i: Case reports in endocrinology. - : Hindawi Limited. - 2090-651X .- 2090-6501. ; 2012 Tidskriftsartikel (refereegranskat)abstract Patients with Graves' disease can be medically prepared before surgery in different ways, which may have various effects on iodine stores. Thyroid specimens were collected at surgery from two patients pretreated with propylthiouracil (PTU) and stable iodine, respectively. A quantitative analysis of iodine content was performed using X-ray fluorescence (XRF) in frozen tissue and a qualitative analysis of aldehyde-fixed material with Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS). Iodine concentrations were 0.9mg/mL and 0.5mg/mL in the thyroid tissue from the patients treated with PTU and stable iodine respectively. TOF-SIMS showed iodine in the follicle lumina in both. However, in the PTU case, iodine was also seen within the thyrocytes indicating accumulation of iodinated compounds from uninhibited hormone release. XRF and TOF-SIMS can be used to follow iodine distribution within the thyroid and the intricate processes following the different medical treatment alternatives in Graves' disease.
29.	Harland, Rex, et al. (författare) Dinoflagellate cysts and hydrographical change in Gullmar Fjord, west coast of Sweden. 2006 Ingår i: The Science of the total environment. - : Elsevier BV. - 0048-9697. ; 355:1-3, s. 204-31 Tidskriftsartikel (refereegranskat)abstract This high-resolution study of the latest Holocene dinoflagellate cyst record from Gullmar Fjord, on the west coast of Sweden, provides evidence for the recognition of two major dinoflagellate communities within the fjord over the last 85 years. These communities may have their origins with the history of cultural eutrophication within the region, but are more likely to be associated with the wider phenomenon of the North Atlantic Oscillation and/or the complex hydrographical response of the fjord to various changing climatic environments between 1915 and 1999. The changing dinoflagellate cyst populations are compared in detail with the many hydrographical parameters available from this well studied fjord with its long instrumental records. Indeed the dinoflagellate cysts fail to demonstrate a convincing ongoing eutrophication record for the fjord but do show a major change in the cyst assemblages at about 1969/1970 at a time when the NAO was changing from a negative phase to the present-day positive phase. Gullmar Fjord is important in the history of dinoflagellate cyst studies, being the site of the 1954 study by Erdtman in which viable cysts, produced within the phytoplankton, were first documented within the water column.
30.	Holmberg, Mats, 1958, et al. (författare) A Longitudinal Study of Medial Temporal Lobe Volumes in Graves Disease 2022 Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 107:4, s. 1040-1052 Tidskriftsartikel (refereegranskat)abstract Context: Neuropsychiatric symptoms are common features of Graves disease (GD) in hyperthyroidism and after treatment. The mechanism behind these symptoms is unknown, but reduced hippocampal volumes have been observed in association with increased thyroid hormone levels. Objective: This work aimed at investigating GD influence on regional medial temporal lobe (MTL) volumes. Methods: Sixty-two women with newly diagnosed GD underwent assessment including magnetic resonance (MR) imaging in hyperthyroidism and 48 of them were followed up after a mean of 16.4±4.2 SD months of treatment. Matched thyroid-healthy controls were also assessed twice at a 15-month interval. MR images were automatically segmented using multiatlas propagation with enhanced registration. Regional medial temporal lobe (MTL) volumes for amygdalae and hippocampi were compared with clinical data and data from symptom questionnaires and neuropsychological tests. Results: Patients had smaller MTL regions than controls at inclusion. At follow-up, all 4 MTL regions had increased volumes and only the volume of the left amygdala remained reduced compared to controls. There were significant correlations between the level of thyrotropin receptor antibodies (TRAb) and MTL volumes at inclusion and also between the longitudinal difference in the levels of free 3,5,3′-triiodothyronine and TRAb and the difference in MTL volumes. There were no significant correlations between symptoms or test scores and any of the 4 MTL volumes. Conclusion: Dynamic alterations in the amygdalae and hippocampi in GD reflect a previously unknown level of brain involvement both in the hyperthyroid state of the condition and after treatment. The clinical significance, as well as the mechanisms behind these novel findings, warrant further study of the neurological consequences of GD.
31.	Holmberg, Mats, 1958, et al. (författare) Is thyroid autoimmunity involved in structural brain changes seen during hyperthyroidism in patients with Graves’ disease? 2018 Ingår i: Annual Meeting of the American Thyroid Association in Washington, DC. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
32.	Holmberg, Mats, 1958, et al. (författare) Structural brain changes in hyperthyroid Graves' disease: protocol for an ongoing longitudinal, case-controlled study in Göteborg, Sweden-the CogThy project. 2019 Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 9:11 Tidskriftsartikel (refereegranskat)abstract Cognitive impairment and reduced well-being are common manifestations of Graves' disease (GD). These symptoms are not only prevalent during the active phase of the disease but also often prevail for a long time after hyperthyroidism is considered cured. The pathogenic mechanisms involved in these brain-derived symptoms are currently unknown. The overall aim of the CogThy study is to identify the mechanism behind cognitive impairment to be able to recognise GD patients at risk.The study is a longitudinal, single-centre, case-controlled study conducted in Göteborg, Sweden on premenopausal women with newly diagnosed GD. The subjects are examined: at referral, at inclusion and then every 3.25 months until 15 months. Examinations include: laboratory measurements; eye evaluation; neuropsychiatric and neuropsychological testing; structural MRI of the whole brain, orbits and medial temporal lobe structures; functional near-infrared spectroscopy of the cerebral prefrontal cortex and self-assessed quality of life questionnaires. The primary outcome measure is the change in medial temporal lobe structure volume. Secondary outcome measures include neuropsychological, neuropsychiatric, hormonal and autoantibody variables. The study opened for inclusion in September 2012 and close for inclusion in October 2019. It will provide novel information on the effect of GD on medial temporal lobe structures and cerebral cortex functionality as well as whether these changes are associated with cognitive and affective impairment, hormonal levels and/or autoantibody levels. It should lead to a broader understanding of the underlying pathogenesis and future treatment perspectives.The study has been reviewed and approved by the Regional Ethical Review Board in Göteborg, Sweden. The results will be actively disseminated through peer-reviewed journals, national and international conference presentations and among patient organisations after an appropriate embargo time.44321 at the public project database for research and development in Västra Götaland County, Sweden (https://www.researchweb.org/is/vgr/project/44321).
33.	Ittermann, T., et al. (författare) Standardized Map of Iodine Status in Europe 2020 Ingår i: Thyroid. - : Mary Ann Liebert Inc. - 1050-7256 .- 1557-9077. ; 30:9 Tidskriftsartikel (refereegranskat)abstract Background:Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods:We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results:In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 mu g/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 mu g/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC Conclusions:We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.
34.	Johannsson, Gudmundur, 1960, et al. (författare) Long-acting hydrocortisone for glucocorticoid replacement therapy. 2007 Ingår i: Hormone research. - : S. Karger AG. - 1423-0046 .- 0301-0163. ; 68 Suppl 5, s. 182-8 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Glucocorticoid (GC) deficiency is a consequence of various disorders that are by themselves rare. Because of this low prevalence, the low cost of GC replacement therapy and the belief that existing outcomes are good, there has been little interest in development of new and improved pharmaceutical products for treatment of GC deficiency. However, GC replacement therapy is complex: diurnal variation of endogenous cortisol must be replicated, GC needs may change during times of physical and psychological stress and there is no biomarker of its action that can be used to monitor individual dose response. CURRENT LIMITATIONS: Recent data suggest that the outcome of established long-term GC replacement therapy may not be as good as previously believed. Short-acting GCs such as hydrocortisone (HC) and cortisone acetate for replacement therapy require 2 to 3 administrations per day. DEVELOPING ALTERNATIVES: Drug delivery system technologies are now available that could permit design and manufacture of a formulation that could accommodate once-daily administration of HC. Such a formulation would enable more physiological serum cortisol-time profiles than are possible with currently available formulations. This short review provides some background on GC replacement therapy, along with recent data on the outcome of patient groups with GC insufficiency, and briefly discusses some general principles for a controlled-release ('long-acting') HC formulation.
35.	Johansson, Birgitta, 1957, et al. (författare) The relationship between mental fatigue, depression, and cognition in Graves' disease. 2023 Ingår i: European thyroid journal. - 2235-0640 .- 2235-0802. ; 12:4 Tidskriftsartikel (refereegranskat)abstract Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves' disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism.A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment.During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies.Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.
36.	Khamisi, Selwan, et al. (författare) Fracture Incidence in Graves' Disease: A Population-Based Study. 2023 Ingår i: Thyroid : official journal of the American Thyroid Association. - : Mary Ann Liebert. - 1557-9077 .- 1050-7256. ; 33:11, s. 1349-1357 Tidskriftsartikel (refereegranskat)abstract Background: Population-based studies have indicated an increase in bone turnover in hyperthyroidism with a subsequent decrease in bone mineral density and an increased risk of fractures, especially in postmenopausal women. However, heterogeneity between studies prevents a definitive conclusion. Graves' disease (GD) is an autoimmune disease, and it is the most common cause of hyperthyroidism. The aim of this study was to investigate fracture risk in patients with GD. Methods: A total of 2134 patients with incident GD and 21,261 age, sex- and county-matched controls were included 16-18 years after diagnosis in a retrospective cohort study. Drug and patient national registries in Sweden were used to assess the risk of developing skeletal complications. Up to 10 years of age, sex- and county-matched controls per patient were selected from databases from the National Board of Health and Welfare and Statistics Sweden. Cox proportional hazards models were fitted to estimate hazard ratios (HR) and confidence intervals [CI]. Results: There were no significant differences in fracture rates between GD and controls but after adjustment for comorbidities, the data showed higher vertebral fracture rates in male GD patients aged >52 years compared to male controls, HR=2.83 [CI 1.05-7.64]. The rates of osteoporosis treatments as well as treatment with corticosteroids were higher in patients with GD. However, HR for the association between GD and fractures remained largely unchanged after adjustment for osteoporosis treatments and treatments with corticosteroids. Conclusions: There were no significant differences in total fracture rate between GD and the general population. However, men older than 52 years had a higher vertebral fracture rate. This study also shows that patients with treated GD receive more osteoporosis treatments compared to the general population.
37.	Lindo, Agneta, et al. (författare) Patient needs and care: moves toward person-centered care for Graves' disease in Sweden. 2023 Ingår i: European thyroid journal. - 2235-0640 .- 2235-0802. ; 12:3 Tidskriftsartikel (refereegranskat)abstract Patients with Graves' disease (GD) not only need appropriate medical care, but they also need to be cared for. The aim of this review is to examine the literature on GD patient needs, expectations, perceptions, and quality of life. We will also present methods for patient care, define gaps in knowledge, and suggest factors that can be introduced into the regular care of GD patients. Patient information, teamwork with thyroid/contact nurses, education of personnel and patients, quality of life measurements, and the formation of a rehabilitation program have enough evidence to be implemented into regular care. However, visualizing patient needs through person-centered care requires further evaluation in GD patients before being implemented in routine care. We conclude that considerable improvement in nursing can be achieved in relation to GD.
38.	Manousou, Sofia, 1979, et al. (författare) A Paleolithic-type diet results in iodine deficiency: a 2-year randomized trial in postmenopausal obese women. 2018 Ingår i: European journal of clinical nutrition. - : Springer Science and Business Media LLC. - 1476-5640 .- 0954-3007. ; 72:1, s. 124-129 Tidskriftsartikel (refereegranskat)abstract Different diets are used for weight loss. A Paleolithic-type diet (PD) has beneficial metabolic effects, but two of the largest iodine sources, table salt and dairy products, are excluded. The objectives of this study were to compare 24-h urinary iodine concentration (24-UIC) in subjects on PD with 24-UIC in subjects on a diet according to the Nordic Nutrition Recommendations (NNR) and to study if PD results in a higher risk of developing iodine deficiency (ID), than NNR diet.A 2-year prospective randomized trial in a tertiary referral center where healthy postmenopausal overweight or obese women were randomized to either PD (n=35) or NNR diet (n=35). Dietary iodine intake, 24-UIC, 24-h urinary iodine excretion (24-UIE), free thyroxin (FT4), free triiodothyronine (FT3) and thyrotropin (TSH) were measured at baseline, 6 and 24 months. Completeness of urine sampling was monitored by para-aminobenzoic acid and salt intake by urinary sodium.At baseline, median 24-UIC (71.0μg/l) and 24-UIE (134.0μg/d) were similar in the PD and NNR groups. After 6 months, 24-UIC had decreased to 36.0μg/l (P=0.001) and 24-UIE to 77.0μg/d (P=0.001) in the PD group; in the NNR group, levels were unaltered. FT4, TSH and FT3 were similar in both groups, except for FT3 at 6 months being lower in PD than in NNR group.A PD results in a higher risk of developing ID, than a diet according to the NNR. Therefore, we suggest iodine supplementation should be considered when on a PD.European Journal of Clinical Nutrition advance online publication, 13 September 2017; doi:10.1038/ejcn.2017.134.
39.	Manousou, Sofia, 1979, et al. (författare) A randomized, double-blind study of iodine supplementation during pregnancy in Sweden: pilot evaluation of maternal iodine status and thyroid function. 2021 Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 60, s. 3411-3422 Tidskriftsartikel (refereegranskat)abstract Pregnant women in Sweden are mildly iodine deficient. We investigated the effect of daily iodine supplementation on the iodine and thyroid status of pregnant women.In this pilot, randomized, double-blind trial, 200 thyroid-healthy pregnant women were recruited at mean (standard deviation) pregnancy week 8.85 (1.62) and assigned (1:1) to daily intake of a multivitamin tablet with or without 150μg of iodine. Urine and serum samples were collected at baseline and once during the second and third trimesters. Urinary iodine concentration (UIC), serum thyroglobulin (Tg), thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOabs) were analyzed. Neonatal TSH data were collected. UIC and Tg were also analyzed in a group of 89 thyroid-healthy non-pregnant women of reproductive age (WRA).At baseline, the intervention and the control groups had similar median UIC (interquartile range (IQR)): 110μg/L (74-119) and 111μg/L (66-168), respectively. The intervention group reached iodine sufficiency with median UIC (IQR) 139μg/L (89-234) and 136μg/L (91-211) in the second and third trimester, respectively, without significant difference from the lower limit of the recommended range, i.e. 150-250μg/L (p=0.42 and p=0.87, respectively). The intervention group had higher median UIC and lower median Tg compared to the control group during the second (p<0.001 and p=0.019, respectively) and third trimester (p<0.001 and p=0.003, respectively), whereas thyroid hormones, serum TPOabs, and neonatal TSH were similar. The WRA group presented median UIC (IQR) 65μg/L (30-98) and median Tg (IQR) 18μg/L (13-27).A daily supplement containing 150μg of iodine to a group of pregnant women with mild iodine deficiency improved the iodine status from mild ID to iodine sufficiency. This improvement seems to have had a positive impact on maternal thyroglobulin. This study is now under extension to investigate the children's neuropsychological development.ClinicalTrials.gov Identifier NCT02378246, May 3, 2015, retrospectively registered.
40.	Manousou, Sofia, 1979, et al. (författare) Correlations of water iodine concentration to earlier goitre frequency in Sweden-an iodine sufficient country with long-term iodination of table salt. 2019 Ingår i: Environmental health and preventive medicine. - : Springer Science and Business Media LLC. - 1347-4715 .- 1342-078X. ; 24:1 Tidskriftsartikel (refereegranskat)abstract Before iodination of Swedish table salt in 1936, iodine deficiency resulting in goitre and hypothyroidism was common. Sweden has become iodine sufficient, as shown in a national survey in 2007, proving its iodination fortification programme effective for the general population. The objective of this study was to collect drinking water from water treatment plants nationally and test if water iodine concentration (WIC) correlated to urinary iodine concentration (UIC) of school-aged children in a national survey 2007 to former goitre frequency in 1929 and to thyroid volume data in 2007.In 2012, 166 treatment plants, located in 57% (166 of 290) of all Swedish municipalities, were asked to collect drinking water samples of approximately 10 ml. In 2007, tap water samples of the same volume were collected from 30 randomly selected schools for the national survey. Analysis of WIC was done in both treatment plants in 2012 (n = 166) and tap water in 2007 (n = 30). The correlation of WIC to the children's UIC and thyroid volume after iodination was tested based on data from the national survey in 2007. The association of WIC to former goitre frequency was tested based on pre-iodination data, derived from a map of goitre frequency drawn in 1929.The median WIC from water treatment plants was 4.0 μg/L (range 0-27 μg/L). WIC was similar in coastal and inland areas, for both ground and surface water. WIC correlated with historical goitre areas and was lower in the goitre areas than in non-goitre areas (p < 0.001). WIC in the same municipalities as the schools correlated with the UIC of children (p < 0.01), but not with their thyroid volume.WIC still contributes to iodine nutrition in Sweden, but iodination overrides the goitre effect.
41.	Manousou, Sofia, 1979, et al. (författare) Inadequate iodine intake in lactating women in Sweden: A pilot 1-year, prospective, observational study 2021 Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 100:1, s. 48-57 Tidskriftsartikel (refereegranskat)abstract Introduction Breastfed infants depend on breast-milk iodine for growth and brain development, as iodine is a trace element important for thyroid hormone production. Iodine need is higher during lactation; hence, mothers and children are at risk of iodine deficiency. We aimed to explore maternal iodine and thyroidal status during lactation. Material and methods Pregnant women were recruited in Goteborg, southwest Sweden. Maternal urine and serum were collected at pregnancy week 35-37 (n = 84) and 0.5, 4, and 12 months postpartum. Seventy mothers provided breast milk at 0.5 months. Results Median (interquartile range) breast-milk iodine concentration was 90 (66-116) mu g/L. About 58% had breast-milk iodine concentration <100 mu g/L. Iodine supplement users (n = 13) had higher breast-milk iodine concentration than non-users (n = 49) (140 mu g/L vs 71 mu g/L,P = .001). Exclusively breastfeeding women at 4 months postpartum (n = 57) had lower median urinary iodine concentration (85 mu g/L vs 133 mu g/L,P = .004) and higher thyroglobulin serum concentration (22.3 mu g/L vs 11.8 mu g/L,P = .032) than non-exclusively breastfeeding women (n = 25). Concentrations of thyroid hormones were unaffected. Conclusions This pilot study suggests that lactating women in southwest Sweden present mildly inadequate iodine intake, mainly among non-iodine supplement users and exclusively breastfeeding mothers. Studies on the coverage of the iodine fortification program in breastfeeding women are warranted.
42.	Manousou, Sofia, 1979, et al. (författare) Iodine deficiency and nutrition in Scandinavia. 2017 Ingår i: Minerva medica. - 1827-1669. ; 108:2, s. 147-158 Tidskriftsartikel (refereegranskat)abstract Iodine nutrition is a result of geological conditions, iodine fortification and monitoring strategies within a country together with the dietary habits of the population. This review summarizes the basis for the current iodine situation in the Scandinavian countries in order to identify gaps in knowledge, determine necessary future steps, highlight landmarks in Scandinavian iodine research and consider ongoing studies in Scandinavian countries with high international impact. Historically, iodine deficiency disorders such as goiter were common in Norway and Sweden, but not in Denmark. Different strategies have been used in Scandinavia to improve iodine nutrition. The major source of iodine is iodized salt in Sweden and from milk and dairy products in Norway. In Denmark, drinking water, milk, dairy products and iodized salt used in commercial production of bread are the important sources of iodine. The current iodine status in Scandinavia is not optimal and action is ongoing to increase iodination in Denmark, where there is mild iodine deficiency in the general population. Data from all three countries indicate insufficient iodine nutrition during pregnancy and there is a need for data from children, adolescents and young women. Monitoring a population's iodine status and dietary iodine sources is necessary to secure iodine nutrition in Scandinavia. Ongoing studies in Scandinavia will contribute significantly to the knowledge about the effects of mild to moderate iodine deficiency.
43.	Manousou, Sofia, 1979, et al. (författare) Iodine deficiency emerges among pregnant women in Sweden despite salt iodine fortification at 50 ppm-a national, cross-sectional study 2017 Ingår i: 87th Annual Meeting of the American Thyroid Association, October 18-22, 2017, Victoria, BC, Canada. - : Mary Ann Liebert Inc. Konferensbidrag (övrigt vetenskapligt/konstnärligt)
44.	Manousou, Sofia, 1979, et al. (författare) Iodine deficiency in pregnant women in Sweden: a national cross-sectional study. 2020 Ingår i: European journal of nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 59:6, s. 2535-2545 Tidskriftsartikel (refereegranskat)abstract Voluntary salt iodization at 50mg/kg salt ensures adequate iodine nutrition in Swedish school-aged children, but iodine status in pregnant women is uncertain.We conducted a cross-sectional national study of 743 pregnant women, at median gestational age of 23weeks (IQR 9, 38), recruited from maternal health care centers. We measured: urinary iodine concentration (UIC) and urinary creatinine concentration in spot urine samples; thyroglobulin (Tg), thyroid-stimulating hormone (TSH), and total thyroxine (tT4) on dried blood spots (DBS); and thyreoperoxidase antibodies in serum samples. Data on dietary supplement use were obtained, and women were classified as supplement users (consuming multivitamins containing≥150µg iodine/day) and non-supplement users (no supplements or<150µg iodine/day from supplements).Overall median UIC [bootstrapped 95% confidence interval (CI)] was 101µg/L (95, 108; n=737): 149µg/L (132, 164) in supplement users (n=253) and 85µg/L (79, 92) in non-supplement users (n=440) (p<0.001). Overall geometric mean DBS-Tg (95% CI) was 22.1μg/L (20.8, 23.5; n=675) and the prevalence of elevated DBS-Tg was 19%. DBS-Tg was lower in supplement users (n=229) than in non-supplement users (n=405) (19.1 vs 24.4μg/L, p<0.001). DBS-TSH, DBS-tT4, and S-TPOab positivity did not differ between the two groups.Pregnant women in Sweden have inadequate iodine nutrition. Women not taking iodine supplements containing≥150µg iodine/day are affected by mild iodine deficiency and are at higher risk for increased thyroid activity, while maintaining euthyroidism. Iodine intake should be improved in women both before and after conception by promotion of iodized salt instead of non-iodized salt. We urge regular monitoring of iodine status in the general Swedish population, as well as in risk groups.
45.	Manousou, Sofia, 1979, et al. (författare) Iodine Status After Bariatric Surgery-a Prospective 10-Year Report from the Swedish Obese Subjects (SOS) Study. 2018 Ingår i: Obesity surgery. - : Springer Science and Business Media LLC. - 1708-0428 .- 0960-8923. ; 28:2, s. 349-357 Tidskriftsartikel (refereegranskat)abstract Bariatric surgery can lead to nutrient deficiencies. Gastric by-pass (GBP) entails restriction and malabsorption, whereas, vertical banded gastroplasty (VBG) is only restrictive.The objective of this study is to study whether GBP-patients develop iodine deficiency from malabsorption, and if GBP- and VBG-patients develop lower 24-h urinary iodine excretion (24-UIE) than obese non-operated controls (OB-controls) due to lower iodine intake.The Swedish Obese Subjects (SOS) study is a prospective, non-randomized study of 4047 obese patients included 1987-2001, who chose bariatric surgery or non-surgical treatment. SOS-groups were compared at baseline, after 2 and 10years and with population-based subsamples (MONICA-controls).One hundred eighty-eight GBP-patients were matched with 188 VBG-patients and 188 OB-controls and with three subgroups from 412 MONICA-controls.Primary outcome was 24-UIE. Secondary outcomes were iodine intake, iodine supplementation, TSH, FT4, and thyroid morbidity.At baseline, median 24-UIE was higher in GBP-patients, VBG-patients and OB-controls than in MONICA-controls (214, 201, 203 and 137μg/day, p<0.001). At 10years, 24-UIE in GBP-patients (161μg/day) and VBG-patients (149μg/day) was lower compared with baseline (p<0.01) and OB-controls (189μg/day, p<0.01), but similar to 24-UIE in MONICA-controls (137μg/day). The 10-year-dietary iodine intake was similar in GPB-patients and OB-controls, but higher in VBG-patients. Iodine supplementation was taken by 0-9% in SOS-groups.After surgery, GBP- and VBG-patients did not suffer from iodine deficiency, but both groups had lower iodine status than OB-controls. Dietary supplements recommended after bariatric surgery do not need to include iodine, in iodine sufficient countries.clinicaltrials.gov : NCT01479452.
46.	Manousou, Sofia, 1979, et al. (författare) Role of iodine-containing multivitamins during pregnancy for children's brain function: protocol of an ongoing randomised controlled trial: the SWIDDICH study. 2018 Ingår i: BMJ open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:4 Tidskriftsartikel (refereegranskat)abstract Iodine is essential for normal brain development. Moderate and severe fetal iodine deficiency results in substantial to serious developmental delay in children. Mild iodine deficiency in pregnancy is associated with neurodevelopmental deficits in the offspring, but evidence from randomised trials is lacking. The aim of the Swedish Iodine in Pregnancy and Development in Children study is to determine the effect of daily supplementation with 150µg iodine during pregnancy on the offspring's neuropsychological development up to 14 years of age.Thyroid healthy pregnant women (n=1275: age range 18-40 years) at ≤12 weeks gestation will be randomly assigned to receive multivitamin supplements containing 150µg iodine or non-iodine-containing multivitamin daily throughout pregnancy. As a primary outcome, IQ will be measured in the offspring at 7 years (Wechsler Intelligence Scale for Children-V). As secondary outcomes, IQ will be measured at 3.5 and 14 years, psychomotor development at 18 months and 7 years, and behaviour at 3.5, 7 and 14 years. Iodine status (urinary iodine concentration) will be measured during pregnancy and in the offspring at 3.5, 7 and 14 years. Thyroid function (thyroid hormones, thyroglobulin), and deiodinase type 2 polymorphisms will be measured during pregnancy and in the offspring at 7 and 14 years. Structural MRI or other relevant structural or functional brain imaging procedures will be performed in a subgroup of children at 7 and 14 years. Background and socioeconomic information will be collected at all follow-up times.This study is approved by the Ethics Committee in Göteborg, Sweden (Diary numbers: 431-12 approved 18 June 2012 (pregnancy part) and 1089-16 approved 8 February 2017 (children follow-up)). According to Swedish regulations, dietary supplements are governed by the National Food Agency and not by the Medical Product Agency. Therefore, there is no requirement for a monitoring committee and the National Food Agency does not perform any audits of trial conduct. The trial will be conducted in accordance with the Declaration of Helsinki. The participating sites will be contacted regarding important protocol changes, both orally and in writing, and the trial registry database will be updated accordingly. Study results will be presented at relevant conferences, and submitted to peer-reviewed journals with open access in the fields of endocrinology, paediatrics and nutrition. After the appropriate embargo period, the results will be communicated to participants, healthcare professionals at the maternal healthcare centres, the public and other relevant groups, such as the national guideline group for thyroid and pregnancy and the National Food Agency.NCT02378246; Pre-results.
47.	Mohlin, Eric, et al. (författare) Long-term prognosis after medical treatment of Graves' disease in a northern Swedish population 2000-2010. 2014 Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 170:3, s. 419-27 Tidskriftsartikel (refereegranskat)abstract To investigate the long-term prognosis of patients with Graves' disease (GD) after antithyroid drug (ATD) treatment and follow-up outside of highly specialised care.
48.	Mollehave, L. T., et al. (författare) Register-based information on thyroid diseases in Europe: lessons and results from the EUthyroid collaboration 2022 Ingår i: Endocrine Connections. - : Bioscientifica. - 2049-3614. ; 11:3 Tidskriftsartikel (refereegranskat)abstract ObjectiveRegisters of diagnoses and treatments exist in different forms in the European countries and are potential sources to answer important research questions. Prevalence and incidence of thyroid diseases are highly dependent on iodine intake and, thus, iodine deficiency disease prevention programs. We aimed to collect European register data on thyroid outcomes to compare the rates between countries/regions with different iodine status and prevention programs. DesignRegister-based cross-sectional study. MethodsNational register data on thyroid diagnoses and treatments were requested from 23 European countries/regions. The provided data were critically assessed for suitability for comparison between countries/regions. Sex- and age-standardized rates were calculated. ResultsRegister data on >= 1 thyroid diagnoses or treatments were available from 22 countries/regions. After critical assessment, data on medication, surgery, and cancer were found suitable for comparison between 9, 10, and 13 countries/regions, respectively. Higher rates of antithyroid medication and thyroid surgery for benign disease and lower rates of thyroid hormone therapy were found for countries with iodine insufficiency before approx. 2001, and no relationship was observed with recent iodine intake or prevention programs. ConclusionsThe collation of register data on thyroid outcomes from European countries is impeded by a high degree of heterogeneity in the availability and quality of data between countries. Nevertheless, a relationship between historic iodine intake and rates of treatments for hyper- and hypothyroid disorders is indicated. This study illustrates both the challenges and the potential for the application of register data of thyroid outcomes across Europe.
49.	Nordberg, Kjell, 1955, et al. (författare) Climate and hydrography variations and marine benthic hypoxia in Koljö Fjord, Sweden. 2001 Ingår i: Journal of Sea Research. - 1385-1101. ; 46, s. 187-200 Tidskriftsartikel (refereegranskat)
50.	Nordenskjöld, Agneta, et al. (författare) Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia. 2008 Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:2, s. 380-6 Tidskriftsartikel (refereegranskat)abstract CONTEXT: In congenital adrenal hyperplasia (CAH) caused by different mutations, feminizing surgery is mostly performed in childhood, and many patients are lost to follow-up. OBJECTIVE/PATIENTS: A follow-up study on 62 CAH women aged 18-63 yr and 62 age-matched controls to correlate findings of both operative method and mutation was performed. DESIGN: Semistructured interviews were performed in cases and controls, as well as a gynecological examination in the cases. The results were correlated with disease-causing mutations and earlier surgical procedures if performed. SETTING: The study was conducted at university hospital referral clinics. MAIN OUTCOME MEASURES: Gynecological examination in all cases correlated to previous surgery (n = 49), type of mutation, and questionnaire responses. RESULTS: Half of the CAH women claimed that the disease affected their sex life. The women were less satisfied with their genitals, whether operated or not. Clitoris size and functions were affected by the surgical method. Five women had a clinically evident vaginal stenosis on examination. However, almost half of patients experienced a narrow vagina. The overall psychosexual aspects of life were affected in these patients with later sexual debut, fewer pregnancies and children, and an increased incidence of homosexuality. These quality of life factors were correlated to the severity of the mutations. CONCLUSIONS: The overall quality of life in adult women with CAH is affected both by the type of mutation and operative procedure. Indications for clitoroplasty should be restrictive. Medical, surgical, and psychological treatment should be centralized.

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