| 11. |
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| 12. |
- Lobell, Anna, et al.
(författare)
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Association of Autoimmune Addison's Disease with Alleles of STAT4 and GATA3 in European Cohorts
- 2014
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Gene variants known to contribute to Autoimmune Addison's disease (AAD) susceptibility include those at the MHC, MICA, CIITA, CTLA4, PTPN22, CYP27B1, NLRP-1 and CD274 loci. The majority of the genetic component to disease susceptibility has yet to be accounted for. Aim: To investigate the role of 19 candidate genes in AAD susceptibility in six European case-control cohorts. Methods: A sequential association study design was employed with genotyping using Sequenom iPlex technology. In phase one, 85 SNPs in 19 genes were genotyped in UK and Norwegian AAD cohorts (691 AAD, 715 controls). In phase two, 21 SNPs in 11 genes were genotyped in German, Swedish, Italian and Polish cohorts (1264 AAD, 1221 controls). In phase three, to explore association of GATA3 polymorphisms with AAD and to determine if this association extended to other autoimmune conditions, 15 SNPs in GATA3 were studied in UK and Norwegian AAD cohorts, 1195 type 1 diabetes patients from Norway, 650 rheumatoid arthritis patients from New Zealand and in 283 UK Graves' disease patients. Meta-analysis was used to compare genotype frequencies between the participating centres, allowing for heterogeneity. Results: We report significant association with alleles of two STAT4 markers in AAD cohorts (rs4274624: P = 0.00016; rs10931481: P = 0.0007). In addition, nominal association of AAD with alleles at GATA3 was found in 3 patient cohorts and supported by meta-analysis. Association of AAD with CYP27B1 alleles was also confirmed, which replicates previous published data. Finally, nominal association was found at SNPs in both the NF-kappa B1 and IL23A genes in the UK and Italian cohorts respectively. Conclusions: Variants in the STAT4 gene, previously associated with other autoimmune conditions, confer susceptibility to AAD. Additionally, we report association of GATA3 variants with AAD: this adds to the recent report of association of GATA3 variants with rheumatoid arthritis.
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| 13. |
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| 14. |
- Onnestam, Lisa, et al.
(författare)
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National Incidence and Prevalence of TSH-Secreting Pituitary Adenomas in Sweden
- 2013
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 98:2, s. 626-635
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Tidskriftsartikel (refereegranskat)abstract
- Context: TSH-secreting pituitary adenomas (TSHomas) are rare. Epidemiological data are scant and there are no reports on national incidence. less thanbrgreater than less thanbrgreater thanObjective: The objective of the study was to estimate the national Swedish incidence and prevalence of TSHomas. less thanbrgreater than less thanbrgreater thanDesign: This was an observational study. less thanbrgreater than less thanbrgreater thanSetting: The study was conducted at tertiary referral centers. less thanbrgreater than less thanbrgreater thanPatients: The Swedish Pituitary Registry and World Health Organization International Statistical Classification of Diseases and Related Health Problems coding at all university hospitals were used to identify patients diagnosed with TSHomas 1990-2010. The identified patients medical records were studied until the latest follow-up [median 5.0 years (range andlt; 1-20 years)]. less thanbrgreater than less thanbrgreater thanMain Outcome Measurements: Incidence, prevalence, demographics, tumor characteristics, treatment outcome, and thyroid hormone level at diagnosis were measured. less thanbrgreater than less thanbrgreater thanResults: The age-standardized national incidence of 28 TSHoma patients was 0.15 per 1 million inhabitants per year, with an increasing incidence over time (0.05 per 1 million per year in 1990-1994 to 0.26 per 1 million per year in 2005-2009). The national prevalence in 2010 was 2.8 per 1 million inhabitants, in which 0.85 per 1 million had active disease. Most patients (n = 22) underwent pituitary surgery, 5 had radiotherapy, and 6 had somatostatin analogues. Eighteen patients were considered cured at the latest follow-up; 25% remained uncontrolled. Subjects treated for putative primary hyperthyroidism prior to diagnosis had TSH levels more than double those with intact thyroid at diagnosis (P = .013). The median time to diagnosis was longer for women than men (4 vs andlt; 1 year, P = .026). More women than men were treated surgically (94.1% vs 54.5%, P = .022). less thanbrgreater than less thanbrgreater thanConclusion: This is the first estimate of a national incidence of TSHoma. Additional epidemiological studies are needed to compare these results with other geographical areas. This study suggests an increased incidence of TSHomas, in agreement with reports on other pituitary adenomas. (J Clin Endocrinol Metab 98: 626-635, 2013)
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| 15. |
- Wahlberg, Jeanette, 1969-, et al.
(författare)
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Asthma and allergic symptoms and type 1 diabetes-related autoantibodies in 2.5-yr-old children
- 2011
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Ingår i: Pediatric Diabetes. - : John Wiley & Sons. - 1399-543X .- 1399-5448. ; 12:7, s. 604-610
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Tidskriftsartikel (refereegranskat)abstract
- A dominance of Th2 cytokine pattern is associated with allergic diseases, whereas a Th1 pattern has been reported in autoimmune type 1 diabetes (T1D). The Th1/Th2 paradigm has led to the interest in the relationship between these diseases. To investigate the association between atopic diseases, asthma and occurrence of T1D-related β-cell autoantibodies in children, we studied 7208 unselected 2.5-yr-old children from the All Babies in Southeast Sweden (ABIS) cohort. The ABIS cohort includes 17 055 (78.3% out of all 21 700) children born from October 1997 to October 1999, and followed prospectively with regular biological samples and questionnaires, at birth, at 1 and 2.5 yr. Risk factors for development of β-cell autoantibodies at the age of 2.5 yr were type of domiciliary, domestic animals (cat and dog) and getting a new brother/sister during first year of life. Maternal smoking during pregnancy [odds ratio (OR) 1.6] and heavy smoking at home (>10 vs. ≤10 cigarettes) implied risk for tyrosine phosphatase autoantibodies (IA-2A) (OR 2.9). Wheezing during the first year of life implied risk for glutamic acid decarboxylase autoantibodies (GADA) (OR 1.9) and double positivity for GADA and IA-2A (OR 9.1). Rash on several locations (at least three times during 12 months) (OR 1.7) as well as allergic symptoms related to fur-bearing animals (OR 2.7) implied risk for IA-2A. Food allergy against egg, cow-milk, fish, nuts/almonds (one or in combination) implied risk for GADA and IA-2A (OR 4.5). In a regression model wheezing during first year of life remained as a risk factor for GADA [OR 2.0, confidence interval (CI) 1.1–3.8; p = 0.031] and both GADA and IA-2A (OR 10.7, CI 3.9–29.4; p = 0.000). We conclude that allergic symptoms are associated with the development of T1D-related autoantibodies during the first years of life.
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| 16. |
- Wahlberg, Jeanette, et al.
(författare)
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Atypical or typical adrenocorticotropic hormone-producing pulmonary carcinoids and the usefulness of 11C-5-hydroxytryptophan positron emission tomography : two case reports
- 2013
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Ingår i: Journal of Medical Case Reports. - : BioMed Central (BMC). - 1752-1947. ; 7, s. 80-
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionPulmonary carcinoids associated with ectopic adrenocorticotropic hormone secretion have a good prognosis if histological examination shows typical pulmonary carcinoid and low proliferation, whereas a poor outcome is linked to atypical pulmonary carcinoid and high proliferation. Here we describe the diagnostic challenges to find the tumor in Cushing’s syndrome secondary to ectopic adrenocorticotropic hormone secretion in two cases with an atypical and a typical pulmonary carcinoid, respectively. Case presentationA 63-year-old Caucasian woman presented with aggressive clinical features related to Cushing’s syndrome, having very high levels of urinary cortisol and circulating adrenocorticotropic hormone and cortisol. Magnetic resonance imaging showed no pituitary tumor, and bilateral inferior petrosal sinus sampling revealed no central peripheral ratio of adrenocorticotropic hormone. Computed tomography and 111Indium-pentetreoide somatostatin receptor scintigraphy could not visualize any ectopic tumor. The patient was referred for an 11C-5-hydroxytryptophan positron emission tomography, and a small 8mm nodule in her left lung was found. The tumor was removed via a lateral thoracic incision and wedge excision. The histological examination showed an atypical carcinoid with Ki-67 index of 9 to 10%, and an additional lobectomy was performed. The second patient, a 22-year-old Caucasian man, also presented with aggressive Cushing’s syndrome, with very high urinary cortisol levels and increased circulating cortisol as well as adrenocorticotropic hormone levels. A magnetic resonance imaging scan of the pituitary showed no tumor, whereas a 12×9×14mm tumor was detected in the right lung on the primary computed tomography scan and no further investigation was performed. The tumor was removed via a lateral thoracic incision and wedge excision. A typical carcinoid with Ki-67 index of 1 to 2% was found and no further surgery was performed. After surgical removal, the biochemical disturbances resolved and significant clinical improvement were achieved in both patients after 24 months of follow up. ConclusionsDiagnostic evaluation time is limited due to the aggressive course in ectopic adrenocorticotropic hormone-dependent Cushing’s syndrome. We suggest that 11C-5-hydroxytryptophan positron emission tomography could be considered early as a secondary diagnostic tool when primary computed tomography and/or magnetic resonance imaging scans fail to show any tumor.
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| 17. |
- Wahlberg, Jeanette, 1969-, et al.
(författare)
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Impaired Postural Balance in Turner Syndrom
- 2013
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Ingår i: Hormone and Metabolic Research. - : Georg Thieme Verlag KG. - 0018-5043 .- 1439-4286. ; 45:7, s. 537-540
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Tidskriftsartikel (refereegranskat)abstract
- An impaired body balance has been found in Turner syndrome (TS) in clinical tests like Rombergs’s test and walking on a balance beam. The aim of the study was to assess postural balance in TS subjects with specific balance testing using dynamic posturography and relate to body composition. Nineteen TS subjects (20–57 years) were included. Balance was measured with dynamic posturography (Equitest) and compared with 19 sex and age-matched controls (22–59 years). Equitest, visual, vestibular, and somatosensory systems were provoked with increasing difficulty (6 tests, SO1–SO6) and body sway was measured with a dual forceplate. Body composition was measured with DXA. No difference was found between the TS subjects and the controls on fixed platform with open eyes (SO1), with closed eyes (SO2), with stable platform and visual disorientation (SO3), or on unstable platform with open eyes (SO4). In the difficult tests on unstable platform the TS subjects did worse compared with controls both in the test with eyes closed (SO5), p<0.01, and in the test with visual disorientation (SO6), p<0.05. Composite (a merge of all six recordings) was significantly lower in the TS-group, p<0.05. In the TS group high total body weight was related to worse outcome on tests SO5, SO6, and composite, while total bone mass, age, height, or waist showed no significant association with balance scores. Our findings indicate that TS could have an increased risk for falling due to impaired ability to manage complex coordination tasks.
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| 18. |
- Wahlberg Topp, Jeanette, et al.
(författare)
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Effects of prolactin on platelet activation and blood clotting
- 2013
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa Healthcare. - 0036-5513 .- 1502-7686. ; 73:3, s. 221-228
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Tidskriftsartikel (refereegranskat)abstract
- Increased levels of prolactin often coincide with an increased risk for thromboembolic events, but it is unclear whether a direct causal relation exists. Our aim was to examine the effect of prolactin on platelet function. In addition to using recombinant prolactin for experiments in vitro, we analyzed platelet function by flow cytometry in a group of 13 females with hyperprolactinaemia and 18 healthy female controls. Platelet activation was measured by P-selectin expression and by the amount of platelet-bound fibrinogen after stimulation with adenosine diphosphate (ADP), collagen-related peptide and the protease activated receptor (thrombin receptor) (PAR)-activating peptides PAR4-AP and PAR1-AP. Free oscillation rheometry was used to measure clotting time in whole blood. No significant effect on platelet activation or clotting time could be seen in in vitro experiments by adding recombinant prolactin. However, significantly lower P-selectin expression was found in the hyperprolactinemic group when platelets were activated by ADP (5 and 10 mu M) or PAR4-AP. The expression of fibrinogen did not differ between the two groups for any of the activators used. For all samples, inverse significant correlations between P-selectin expression and prolactin concentration were found for both 5 mu M ADP (r = 0.61, p andlt; 0.01), 10 mu M ADP (r = -0.62, p andlt; 0.001) and PAR4-AP (r = -0.69, p andlt; 0.001). Thrombin cleavage of recombinant prolactin resulting in a 16 kDa C-terminal fragment did not alter the P-selectin expression upon activation. We found an indirect inhibitory effect of prolactin on platelets in hyperprolactinemic patients, suggesting that prolactin might have a protective role in thromboembolic disease.
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