| 1. |
- Abraham-Nordling, Mirna, et al.
(författare)
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Incidence of hyperthyroidism in Sweden
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 899-905
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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.
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| 2. |
- Abrahamsson, Niclas, et al.
(författare)
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GLP1 analogs as treatment of postprandial hypoglycemia following gastric bypass surgery : a potential new indication?
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 169:6, s. 885-889
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The number of morbidly obese subjects submitted to bariatric surgery is rising worldwide. In a fraction of patients undergoing gastric bypass (GBP), episodes with late postprandial hypoglycemia (PPHG) develop 1-3 years after surgery. The pathogenesis of this phenomenon is not fully understood; meal-induced rapid and exaggerated increases of circulating incretins and insulin appear to be at least partially responsible. Current treatments include low-carbohydrate diets, inhibition of glucose intestinal uptake, reduction of insulin secretion with calcium channel blockers, somatostatin analogs, or diazoxide, a KATP channel opener. Even partial pancreatectomy has been advocated. In type 2 diabetes, GLP1 analogs have a well-documented effect of stabilizing glucose levels without causing hypoglycemia. Design: We explored GLP1 analogs as open treatment in five consecutive GBP cases seeking medical attention because of late postprandial hypoglycemic symptoms. Results: Glucose measured in connection with the episodes in four of the cases had been 2.7, 2.5, 1.8, and 1.6 mmol/l respectively. The patients consistently described that the analogs eliminated their symptoms, which relapsed in four of the five patients when treatment was reduced/discontinued. The drug effect was further documented in one case by repeated 24-h continuous glucose measurements. Conclusion: These open, uncontrolled observations suggest that GLP1 analogs might provide a new treatment option in patients with problems of late PPHG.
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| 3. |
- Barbosa, Edna J L, 1961, et al.
(författare)
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Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
- 2012
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
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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.
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| 4. |
- Barner, C., et al.
(författare)
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Effects on insulin sensitivity and body composition of combination therapy with GH and IGF1 in GH deficient adults with type 2 diabetes
- 2012
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 167:5, s. 697-703
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this trial was to evaluate the effect on insulin sensitivity and body composition of combination therapy with GH and IGF1 in adults with GH deficiency (GHD) and diabetes. Design, patients and methods: A 6-month randomised placebo-controlled pilot study. Fourteen adults with GHD and type 2 diabetes were included. All received rhGH (0.15 mg/day for 1 month and 0.3 mg/day for 5 months) and were randomised to rhIGF1 (15 μg/kg per day for 1 month and 30 μg/kg per day for 5 months) or placebo. Insulin sensitivity was evaluated with euglycaemic hyperinsulinaemic clamp and body composition by computed tomography of abdominal and thigh fat, as well as bioimpedance. Results: Twelve patients completed the study. They were overweight and obese; at baseline, insulin sensitivity (M-value) was low. IGF1 and IGF1 SDS increased in both groups, with the highest increase in the GH and IGF1 group. Positive changes in M-value by +1.4 mg/kg per min, in subcutaneous abdominal fat by -60.5 ml and in fat-free mass by +4.4% were seen in the GH and IGF1 group. Corresponding values in the GH and placebo-treated group were -1.5 mg/kg per min, +23 ml and -0.04% respectively (P=0.02, P=0.04 and P=0.03 for delta values between groups). No safety issues occurred. Conclusions: Combined GH and IGF1 treatment resulted in positive, but rather small effects, and might be a treatment option in a few selected patients.
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| 5. |
- Chisalita, Ioana Simona, et al.
(författare)
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Increased IGF1 levels in relation to heart failure and cardiovascular mortality in an elderly population : impact of ACE inhibitors
- 2011
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Ingår i: European Journal of Endocrinology. - : European Society of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:6, s. 891-898
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Tidskriftsartikel (refereegranskat)abstract
- Objective: There are conflicting results regarding the association of circulating IGF1 with cardiovascular (CV) morbidity and mortality. We assessed the relationship between IGF1 levels and heart failure (HF), ischemic heart disease (IHD), and CV mortality in an elderly population taking into account the possible impact of angiotensin converting enzyme (ACE) inhibitors. Design and methods: A total of 851 persons aged 66-81 years, in a rural Swedish municipality, were subjected to medical history, clinical examination, electrocardiography, echocardiography, and fasting plasma samples. They were then followed for 8 years. Results and conclusion: Patients on ACE inhibitors had higher IGF1 levels compared with those without ACE inhibitors. In patients on ACE inhibitors, higher IGF1 values were found in patients with an ejection fraction (EF) less than40% compared with EF greater than= 40%, in patients with higher proBNP levels in quartile 4 vs 1, and in patients with IHD when compared to those without ACE inhibitors (P less than 0.001). In patients without ACE inhibitors, no relationship was found between IGF1 levels and HF or IHD. In multivariate regression, only ACE inhibitors, ECG changes characteristic for IHD, and gender had a significant impact on IGF1. Patients with higher IGF1 levels in quintiles 4 and 5 compared to quintiles 1 and 2 had a 50% higher risk for CV death (P=0.03). This was significant after adjustment for well-known CV risk factors and ACE inhibitors (P=0.03). Conclusions: Our results show that treatment with ACE inhibitors in an elderly population is associated with increased IGF1 levels, especially in patients with impaired cardiac function or IHD. High IGF1 levels tend to be associated with an increased risk for CV mortality.
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| 6. |
- Ciganoka, Darja, et al.
(författare)
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Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:4, s. 517-525
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics. Design and methods: The SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls. Results: In total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P<0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR) = 3.38; 95% confidence interval (CI), 1.78-6.42; P=0.00016 and OR=2.41; 95% CI, 1.41-4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P=0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient beta=-10.4; P=0.002), increased body mass index (beta=4.1; P=0.004), higher number of adenoma resection (P<0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014). Conclusions: Our results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.
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| 7. |
- Cui, Tao, et al.
(författare)
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Olfactory receptor 51E1 protein as a potential novel tissue biomarker for small intestine neuroendocrine carcinomas
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168:2, s. 253-261
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Late diagnosis hinders proper management of small intestine neuroendocrine carcinoma (SI-NEC) patients. The olfactory receptor, family 51, subfamily E, member 1 (OR51E1) has been reported as a potential novel SI-NEC marker, without protein expression recognition. Thus, we further studied whether the encoded protein may be a novel SI-NEC clinical biomarker.DESIGN: OR51E1 coding sequence was cloned using total RNA from SI-NEC patient specimens. Quantitative real-time PCR analysis explored OR51E1 expression in laser capture microdissected SI-NEC cells and adjacent microenvironment cells. Moreover, immunohistochemistry investigated OR51E1 protein expression on operation and biopsy material from primary SI-NECs, mesentery, and liver metastases from 70 patients. Furthermore, double immunofluorescence studies explored the potential co-localization of the vesicular monoamine transporter 1 (SLC18A1, generally referred to as VMAT1) and OR51E1 in the neoplastic cells and in the intestinal mucosa adjacent to the tumor.RESULTS: OR51E1 coding sequence analysis showed absence of mutation in SI-NEC patients at different stages of disease. OR51E1 expression was higher in microdissected SI-NEC cells than in the adjacent microenvironment cells. Furthermore, both membranous and cytoplasmic OR51E1 immunostaining patterns were detected in both primary SI-NECs and metastases. Briefly, 18/43 primary tumors, 7/28 mesentery metastases, and 6/18 liver metastases were 'positive' for OR51E1 in more than 50% of the tumor cells. In addition, co-localization studies showed that OR51E1 was expressed in >50% of the VMAT1 immunoreactive tumor cells and of the enterochromaffin cells in the intestinal mucosa adjacent to the tumor.CONCLUSION: OR51E1 protein is a potential novel clinical tissue biomarker for SI-NECs. Moreover, we suggest its potential therapeutic molecular target development using solid tumor radioimmunotherapy.
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| 8. |
- Cunningham, Janet L., et al.
(författare)
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Connective tissue growth factor expression in endocrine tumors is associated with high stromal expression of alpha-smooth muscle actin
- 2010
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:4, s. 691-697
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Complications due to fibrosis development are common in patients with well-differentiated endocrine carcinomas in the small intestine (ileal carcinoids). Connective tissue growth factor (CTGF) expression in ileal carcinoids may be related to this fibrosis development. This study aimed to examine CTGF expression in relation to local myofibroblast differentiation in a large series of ileal carcinoids and in different types of endocrine tumors. METHODS Immunoreactivity (IR) for CTGF and α-smooth muscle actin (α-SMA), a marker for myofibroblasts, was compared in serial tumor tissue sections from 42 patients with ileal carcinoids and from 80 patients with other endocrine tumors. Western blot was performed on an additional 21 patients with ileal carcinoids. RESULTS CTGF IR was present in >50% of tumor cells in all 42 ileal carcinoids and in 2 out of 14 endocrine pancreatic tumors, 4 out of 6 rectal carcinoids, and 1 out of 5 lung carcinoids. Tumors with abundant CTGF expression also displayed α-SMA IR in stromal fibroblast-like cells, whereas other endocrine tumors displayed less or no CTGF and α-SMA IR. Protein bands corresponding to full-length CTGF (36-42 kDa) were detected in protein lysates from ileal carcinoids. CONCLUSION CTGF is uniquely prevalent in ileal carcinoids when compared with most other endocrine tumor types. Immunoreactive cells are adjacent areas with increased fibrovascular stroma that express α-SMA. This supports a potential role for CTGF in myofibroblast-mediated fibrosis associated with ileal carcinoids, and indicates that CTGF should be investigated as a target for future therapy.
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| 9. |
- Elbornsson, Mariam, et al.
(författare)
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Fifteen years of GH replacement improves body composition and cardiovascular risk factors
- 2013
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 168:5, s. 745-753
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on body composition and cardiovascular risk factors. Design/patients: In this prospective, single-center, open-label study, the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults (93 men) with adult-onset GH deficiency (GHD). Mean age was 50.5 (range 22-74) years at study start. Body composition was measured using dual-energy X-ray absorptiometry. Results: The mean initial GH dose of 0.55 (S. E. M. 0.03) mg/day was gradually lowered to 0.40 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.53 (0.10) at baseline to 0.74 (0.13) at study end (P<0.001 vs baseline). Lean soft tissue (LST) increased to 3% above the baseline level at study end (P<0.001). After a 9% decrease during the first year of treatment (P<0.001 vs baseline), body fat (BF) started to increase and had returned to the baseline level after 15 years. Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased. Fasting plasma glucose increased from 4.4 (0.1) at baseline to 4.8 (0.1) mmol/l at study end (P<0.001). However, blood HbA1c decreased from 5.0 (0.1) to 4.6 (0.1) % (P<0.001). Conclusions: Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile. Fasting plasma glucose increased whereas blood HbA1c was reduced. European Journal of Endocrinology 168 745-753
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| 10. |
- Elbornsson, Mariam, et al.
(författare)
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Fifteen years of GH replacement increases bone mineral density in hypopituitary patients with adult-onset GH deficiency
- 2012
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 166:5, s. 787-795
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Few studies have determined the effects of more than 5-10 years of GH replacement in adults on bone mineral content (BMC) and bone mineral density (BMD). Design/patients: In this prospective, single-centre, open-label study, the effects of 15 years of GH replacement on BMC and BMD, measured using dual-energy X-ray absorptiometry, were determined in 126 hypopituitary adults (72 men) with adult-onset GH deficiency (GHD). Mean age was 49.4 (range 22-74) years at the initiation of the study. Results: The mean initial GH dose of 0.63 (S.E.M. 0.03) mg/day was gradually lowered to 0.41 (0.01) mg/day after 15 years. The mean serum IGF1 SDS increased from -1.69 (0.11) at baseline to 0.63 (0.16) at the study end (P < 0.001 vs baseline). The 15 years of GH replacement induced a sustained increase in total body BMC (+5%, P < 0.001) and BMD (+2%, P < 0.001). Lumbar (L2-L4) spine BMC increased by 9% (P < 0.001) and BMD by 5% (P < 0.001). In femur neck, a peak increase in BMC and BMD of 7 and 3%, respectively, was observed after 7 years (both P < 0.001). After 15 years, femur neck BMC was 5% above the baseline value (P < 0.01), whereas femur neck BMD had returned to the baseline level. In most variables, men had a more marked response to GH replacement than women. Conclusions: Fifteen-year GH replacement in GHD adults induced a sustained increase in total body and lumbar (L2-L4) spine BMC and BMD. In femur neck, BMC and BMD peaked at 7 years and then decreased towards baseline values.
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| 11. |
- Feldt-Rasmussen, Ulla, et al.
(författare)
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Response to GH treatment in adult GH deficiency is predicted by gender, age, and IGF1 SDS but not by stimulated GH-peak
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168:5, s. 733-743
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We studied whether the severity of GH deficiency (GHD) defined as i) GH-peak on stimulation tests (insulin tolerance test (ITT), arginine, and glucagon), ii) number of additional pituitary deficits, or iii) baseline IGF1 SDS could impact the response to GH treatment. We further explored whether iv) IGF1 SDS after 24 months of GH replacement or v) Delta IGF1 SDS from baseline to 24 months was related to the phenotypic response to GH treatment. Design, patients, and measurements: The patient cohort (n=1752; 50% women) was obtained from KIMS (Pfizer International Metabolic Database). The patients were divided into three groups of approximately equal size (tertiles) according to the stimulated GH-peak values and baseline IGF1 SDS and were studied at baseline, 12, and 24 months of GH therapy. Results: Lower baseline IGF1 SDS predicted better response in weight, BMI, total cholesterol, and triglycerides, while IGF1 SDS after 24 months was associated with reduction in waist/hip ratio, total cholesterol, and improved quality of life (QoL). Age-correlated negatively with the response in body weight, BMI, waist, IGF1 SDS, and total and LDL-cholesterol. Response in weight and BMI was greater in men than in women, whereas women showed greater improvement in QoL than men. Patients with more severe GHD as assessed by lower GH-peaks and more pituitary hormone deficiencies had a greater increase in IGF1 SDS. The increase in IGF1 SDS was associated with a reduction in waist/hip ratio and an increase in weight, BMI, and triglycerides. There was no correlation with other lipids, blood pressure, or glucose. Conclusion: Our findings indicate that baseline and 24 months, IGF1 and its degree of increase during GH replacement were more important than stimulated peak GH to predict the phenotypic response.
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| 12. |
- Gaillard, R. C., et al.
(författare)
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Overall and cause-specific mortality in GH-deficient adults on GH replacement
- 2012
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 166:6, s. 1069-1077
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hypopituitarism is associated with an increased mortality rate but the reasons underlying this have not been fully elucidated. The purpose of this study was to evaluate mortality and associated factors within a large GH-replaced population of hypopituitary patients. Design: In KIMS (Pfizer International Metabolic Database) 13 983 GH-deficient patients with 69 056 patient-years of follow-up were available. Methods: This study analysed standardised mortality ratios (SMRs) by Poisson regression. IGF1 SDS was used as an indicator of adequacy of GH replacement. Statistical significance was set to P<0.05. Results: All-cause mortality was 13% higher compared with normal population rates (SMR, 1.13; 95% confidence interval, 1.04-1.24). Significant associations were female gender, younger age at follow-up, underlying diagnosis of Cushing's disease, craniopharyngioma and aggressive tumour and presence of diabetes insipidus. After controlling for confounding factors, there were statistically significant negative associations between IGF1 SDS after 1, 2 and 3 years of GH replacement and SMR. For cause-specific mortality there was a negative association between 1-year IGF1 SDS and SMR for deaths from cardiovascular diseases (P=0.017) and malignancies (P=0.044). Conclusions: GH-replaced patients with hypopituitarism demonstrated a modest increase in mortality rate; this appears lower than that previously published in GH-deficient patients. Factors associated with increased mortality included female gender, younger attained age, aetiology and lower IGF1 SDS during therapy. These data indicate that GH replacement in hypopituitary adults with GH deficiency may be considered a safe treatment.
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| 13. |
- Glad, Camilla A M, 1981, et al.
(författare)
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SNPs within the GH-signaling pathway are associated with the early IGF1 response to GH replacement therapy in GHD adults.
- 2014
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 170:1, s. 101-7
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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.
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| 14. |
- Gustafsson, Stefan, et al.
(författare)
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Adiponectin and cardiac geometry and function in elderly : results from two community-based cohort studies
- 2010
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 162:3, s. 543-550
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Several smaller studies have indicated that adiponectin might be associated with left ventricular (LV) mass and function, but community-based studies with adequate sample size and adjustment for potential confounders are lacking. Our objective was to investigate such associations in two large community-based studies of elderly. DESIGN: Cross-sectional. METHODS: We evaluated cross-sectional relations between serum adiponectin and echocardiographic measures of cardiac geometry and function (LV mass index, LV relative wall thickness, LV end-diastolic diameter, left atrial diameter, ejection fraction, LV isovolumic relaxation time, and E/A ratio) in 954 70-year-old participants (50% women) of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), and in 427 71-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM). RESULTS: In models adjusted for age, sex, body mass index, systolic blood pressure, antihypertensive treatment, antidiabetic treatment, lipid-lowering medication, fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, creatinine, and smoking, adiponectin was inversely associated with ejection fraction in men (beta, -1.62; 95% confidence interval (CI), -2.50, -0.75 in PIVUS; beta, -1.35; 95% CI, -2.41, -0.29 in ULSAM), but not in women. After additional adjustment for N-terminal pro-brain natriuretic peptide (NT-proBNP), the association between adiponectin and ejection fraction was attenuated (beta, -0.98; 95% CI, -1.86, -0.10 in PIVUS; beta, -0.75; 95% CI, -1.84, 0.35 in ULSAM). CONCLUSIONS: Serum adiponectin concentrations were associated with ejection fraction in men, and these associations were partially attenuated by NT-proBNP. Our results imply that adiponectin may be associated with systolic function through pathways that involve natriuretic peptides.
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| 15. |
- Holmer, Helene, et al.
(författare)
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Hypothalamic involvement and insufficient sex steroid supplementation are associated with low bone mineral density in women with childhood onset craniopharyngioma
- 2011
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Ingår i: European Journal of Endocrinology. - : Bio Scientifica. - 0804-4643 .- 1479-683X. ; 165:1, s. 25-31
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Tidskriftsartikel (refereegranskat)abstract
- Context: Data on bone mineral density (BMD) are lacking in adults with childhood onset (CO)-craniopharyngioma (CP) with hypothalamic damage from the tumor. In patients with CO GH deficiency, BMD increases during GH treatment. Objective: The aims were to evaluate BMD in adults with CO-CPs on complete hormone replacement, including long-term GH and to evaluate the impact of hypothalamic damage on these measures. Design and participants: BMD (dual-energy X-ray absorptiometry), markers of bone turn over, physical activity and calcium intake were assessed in 39 CO-CP adults (20 women), with a median age of 28 (17-57) years, in comparison with matched population controls. Results: Late puberty induction was recorded in both genders, but reduced androgen levels in females only. Only CP women had lower BMD (PZ0.03) at L2-L4, and reduced Z-scores at femoral neck (P=0.004) and L2-L4 (P=0.004). Both genders had increased serum leptin levels (P=0.001), which significantly correlated negatively with BMD at L2-L4 (P=0.003; r=-0.5) and 45% of CP women had Z-score levels less than= -2.0 S.D. Furthermore, 75% of those with a Z-score less than= -2.0 S.D. had hypothalamic involvement by the tumor. Calcium intake (P=0.008) and physical activity (P=0.007) levels were reduced in CP men only. Levels of ostecalcin and crossLaps were increased in CP men only. Conclusions: Despite continuous GH therapy, low BMD was recorded in CO-CP females. Insufficient estrogen and androgen supplementation during adolescence was the main cause, but hypothalamic involvement with consequent leptin resistance was also strongly associated with low BMD in both genders.
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| 16. |
- Jakob, F., et al.
(författare)
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Effects of teriparatide in postmenopausal women with osteoporosis pre-treated with bisphosphonates : 36-month results from the European Forsteo Observational Study
- 2012
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 166:1, s. 87-97
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To describe fracture rates, back pain, and health-related quality of life (HRQoL) in postmenopausal women with osteoporosis and prior bisphosphonate therapy, treated with teriparatide for up to 18 months and followed up for a further 18 months. Design: Prospective, multinational, and observational study. Methods: Data on prior bisphosphonate use, clinical fractures, back pain visual analog scale (VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed using a repeated measures model. Results: Of the 1581 enrolled patients with follow-up data, 1161 (73.4%) had a history of prior bisphosphonate use (median duration: 36 months). Of them, 169 (14.6%) sustained >= 1 fracture during 36-month follow-up. Adjusted odds of fracture were significantly decreased at each 6-month interval compared with the first 6 months of teriparatide treatment: 37% decrease in the 12 to ! 18 months period during teriparatide treatment (P=0.03) and a 76% decrease in the 12- to 18-month period after teriparatide was discontinued (P<0.001). Significant reductions in back pain and improvement in HRQoL were observed. Conclusions: Postmenopausal women with severe osteoporosis previously treated with bisphosphonates had a significant reduction in the incidence of fractures compared with the first 6 months of therapy, a reduction in back pain and an improvement in HRQoL during up to 18 months of teriparatide treatment. These outcomes were still evident for at least 18 months after teriparatide was discontinued. The results should be interpreted in the context of an uncontrolled, observational study in a routine clinical setting.
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| 17. |
- Lima, Kari, et al.
(författare)
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Hypoparathyroidism and autoimmunity in the 22q11.2 deletion syndrome
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 165:2, s. 345-352
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterize the endocrine and autoimmune disturbances with emphasis on parathyroid dysfunction in patients with 22q11.2 deletion syndrome (22q11.2 DS). Design: In this nationwide survey; 59 patients (age 1-54 years) out of 86 invited with a 22q11.2 DS were recruited through all the genetic institutes in Norway. Methods: Data was collected from blood tests, medical records, a physical examination and a semi-structured interview. We registered autoimmune diseases and measured autoantibodies, hormone levels and HLA types. Results: Twenty-eight (47%) patients had hypoparathyroidism or a history of neonatal or transient hypocalcemia. Fifteen patients had neonatal hypocalcemia. Fourteen patients had permanent hypoparathyroidism including seven (54%) of those above age 15 years. A history of neonatal hypocalcemia did not predict later occurring hypoparathyroidism. Parathyroid hormone levels were generally low indicating a low reserve capacity. Twenty-eight patients were positive for autoantibodies. Six (10%) persons had developed an autoimmune disease, and all were females (P<0.02). Hypoparathyroidism correlated with autoimmune diseases (P<0.05), however, no antibodies were detected against the parathyroid glands. Conclusions: Hypoparathyroidism and autoimmunity occur frequently in the 22q11.2 DS. Neonatal hypocalcemia is not associated with later development of permanent hypoparathyroidism. Hypoparathyroidism may present at any age, also in adults, and warrants regular measurement of calcium levels. Hypoparathyroidism and autoimmunity occur frequently together. Our findings of autoimmune diseases in 10% of the patients highlight the importance of stringent screening and follow-up routines.
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| 18. |
- Lindahl, Katarina, et al.
(författare)
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Therapy of Endocrine Disease : Treatment of osteogenesis imperfecta in adults
- 2014
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:2, s. R79-R90
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Forskningsöversikt (refereegranskat)abstract
- Background: Osteogenesis imperfecta (OI) is a heterogeneous rare connective tissue disorder commonly caused by mutations in the collagen type I genes. Pharmacological treatment has been most extensively studied in children, and there are only few studies comprising adult OI patients. Objectives: i) To review the literature on the current medical management of OI in children and adults, and thereby identify unmet medical needs and ii) to present an overview of possible future treatment options. Results: Individualization and optimization of OI treatment in adults remain a challenge, because available treatments do not target the underlying collagen defect, and available literature gives weak support for treatment decisions for adult patients. Conclusions: Bisphosphonates are still the most widely used pharmacological treatment for adult OI, but the current evidence supporting this is sparse and investigations on indications for choice and duration of treatment are needed.
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| 19. |
- Melin, Eva, et al.
(författare)
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Depression, obesity, and smoking were independently associated with inadequate glycemic control in patients with type 1 diabetes
- 2013
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 168:6, s. 861-869
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to explore the associations between inadequate glycemic control of diabetes and psychological, anthropometric, and lifestyle variables in a population-based cohort of type 1 diabetes patients. Design: Cross-sectional study. Methods: In this study, 292 patients with type 1 diabetes, aged 18-59 years, participated. Psychological data were assessed by self-report instruments: Hospital Anxiety and Depression Scale and Toronto Alexithymia Scale-20. Anthropometrics, blood analyses, data from medical records, and data from the Swedish National Diabetes Registry were collected. Results: Self-reported depression (adjusted odds ratio (AOR) 4.8), obesity (AOR 4.3), and smoking (AOR 3.0) were independently associated with inadequate glycemic control of diabetes (HbA1c>8.6%). Gender-stratified analyses showed that self-reported depression (AOR 19.8) and obesity (AOR 7.0) in women and smoking in men (AOR 4.2) were associated with HbA1c>8.6%. Alexithymia, antidepressant medication, and physical inactivity were associated with HbA1c>8.6% only in bivariate analyses. Alexithymia, self-rated anxiety, physical inactivity, and absence of abdominal obesity were associated with self-reported depression. Conclusions: Depression was the only psychological factor independently associated with HbA1c>8.6%. The association was of comparable importance as obesity and smoking, well-known risk factors for inadequate glycemic control and diabetes complications. The association between depression and HbA1c>8.6% was particularly strong for women. Alexithymia, which is a relatively stable personality trait, was associated with depression. In the future care of patients with diabetes, psychological aspects should be considered alongside anthropometrics and lifestyle factors in order to achieve the goals for HbA1c.
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| 20. |
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| 21. |
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| 22. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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Comorbidity and cardiocascular risk factors in adult GH deficiency following treatment for Cushing´s disease or non-functioning pituitary adenomas during childhood.
- 2012
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Ingår i: European journal of endocrinology. - 0804-4643. ; 166:4, s. 593-600
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cushing's disease (CD) and non-functioning pituitary adenoma (NFPA) are rare in paediatric patients. The aim of this study was to describe long-term consequences in adults with GH deficiency (GHD) treated for CD or NFPA during childhood. Design, patients and methods This was a retrospective analysis of data from KIMS (Pfizer International Metabolic Database). Background characteristics, anthropometry and comorbidity were studied in 47 patients diagnosed with childhood-onset (CO)-CD and 62 patients with CO-NFPA. Data from 100 ACTH-sufficient patients with CO-idiopathic hypopituitarism (CO-Idio) were used for comparison. Cardiovascular risk profile was analysed at baseline and at 1 year on GH treatment in a subgroup of patients (17 CO-CD, 24 CO-NFPA and 55 CO-Idio) not receiving GH treatment at study entry. Results The median age at diagnosis of pituitary tumour was 14.0 years (range 10–17) in patients with CO-CD and 13.7 years (range 8–17) in CO-NFPA. In addition to GHD, 41% of patients with CO-CD had three or four other pituitary hormone deficiencies compared with 78% of patients with CO-NFPA (P<0.001). Eighty-nine per cent of patients with CO-CD had height SDS lower than 0 compared with 61% of patients with CO-NFPA (P=0.002). Hypertension was more common in CO-CD compared with CO-Idio (23 vs 9%, P=0.018). At 1 year on GH treatment, total- and low-density lipoprotein-cholesterol decreased significantly in CO-CD but not in CO-NFPA. Conclusion Adult patients with GHD following treatment for paediatric CD and NFPA have long-term adverse consequences. Despite more severe hypopituitarism in CO-NFPA, patients with CO-CD have more frequently compromised final stature.
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| 23. |
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| 24. |
- Ragnarsson, Oskar, 1971, et al.
(författare)
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The relationship between glucocorticoid replacement and quality of life in 2737 hypopituitary patients.
- 2014
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Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 171:5, s. 571-9
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Tidskriftsartikel (refereegranskat)abstract
- Quality of life (QoL) is impaired in hypopituitary patients and patients with primary adrenal insufficiency. The aim of this study was to analyse the impact of glucocorticoid (GC) replacement on QoL. The main hypothesis was that ACTH-insufficient patients experience a dose-dependent deterioration in QoL.
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| 25. |
- Rasouli, Bahareh, et al.
(författare)
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Alcohol and the risk for latent autoimmune diabetes in adults : results based on Swedish ESTRID study
- 2014
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:5, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design: A population-based case-control study was carried out to investigate the association of alcohol consumption and the risk of LADA. Methods: We used data from the ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged >= 35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results: Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Conclusions: Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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| 26. |
- Rehman, Javaid-ur, et al.
(författare)
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Sleeping during the day : effects on the 24-h patterns of IGF-binding protein 1, insulin, glucose, cortisol, and growth hormone.
- 2010
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 163:3, s. 383-90
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Disturbed sleep is a major risk factor for metabolic disturbances, including type 2 diabetes, but the involved mechanisms are still poorly understood. We investigated how an acute shift of sleep to the daytime affected IGF-binding protein 1 (IGFBP1), which is a risk factor for diabetes. METHODS: Seven healthy men (age, 22-32 years) participated in a night sleep condition (sleep 2300-0700 h) and a day sleep condition (0700-1500 h) with hourly blood samples taken for 25 h (starting at 1900 h) and isocaloric meals every 4th hour awake. The blood samples were analyzed for IGFBP1, insulin, GH, glucose, and cortisol. RESULT: The acute shift of sleep and meal timing (to 8 h) shifted the 24-h patterns of IGFBP1, glucose, insulin, and GH to a similar degree. However, the day sleep condition also resulted in elevated levels of IGFBP1 (area under curve (AUC)+22%, P<0.05), and reduced glucose levels (AUC-7%, P<0.05) compared with nocturnal sleep. Sleeping during the day resulted in elevated cortisol levels during early sleep and reduced levels in late sleep, but also in increased levels the subsequent evening (P's<0.05). CONCLUSION: Sleep-fasting seems to be the primary cause for the elevation of IGFBP1, irrespective of sleep timing. However, sleeping during the day resulted in higher levels of IGFBP1 than nocturnal sleep, suggesting altered metabolism among healthy individuals, which may have implications for other groups with altered sleep/eating habits such as shift workers. Moreover, sleep and meal times should be accounted for while interpreting IGFBP1 samples.
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| 27. |
- Ross, I. L., et al.
(författare)
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Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168, s. 403-412
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Tidskriftsartikel (refereegranskat)abstract
- Background Uncertainty exists whether glucocorticoid receptor (GCR) polymorphisms play a role in steroid-related side effects in Addison's disease (AD) patients on hydrocortisone. The polymorphisms Bcll and N363S appear to increase sensitivity to cortisol, while the ER22/23EK polymorphism has been associated with resistance to cortisol. Method One hundred and forty seven AD patients, and gender, and ethnicity-matched controls were recruited in South Africa. Three polymorphisms in the GCR were studied, using PCR followed by restriction fragment length analysis. Associations with BMI, lipids, glucose and inflammatory markers were investigated. Results In both patients and controls, the Bcll polymorphism occurred more frequently in whites than in other ethnic groups studied but was not associated with any of the metabolic parameters tested. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs 24.7kg/m2) and control subjects (26.3 vs 24.2kg/m2). The ER22/23EK polymorphism was also associated with lower LDL cholesterol in control subjects (3.46 vs 3.93mmol/l) and in patients (3.52 vs 4.10mmol/l). N363S was associated with increased BMI in controls 29.9kg/m2 vs wild type 24.8kg/m2. Median hydrocortisone doses were greater in patients heterozygous for either ER22/23EK 30.0mg or N363S 25.0mg polymorphisms than in wild type patients 20.0mg (both comparisons). Conclusion Alterations in lipids, BMI and hydrocortisone dose were associated with two polymorphisms. Further larger studies are warranted to corroborate these findings.
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| 28. |
- Samefors, Maria, et al.
(författare)
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Vitamin D deficiency in elderly people in Swedish nursing homes is associated with increased mortality
- 2014
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Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 170:5, s. 667-675
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:Institutionalised elderly people at northern latitudes may be at elevated risk for vitamin D deficiency. In addition to osteoporosis-related disorders, vitamin D deficiency may influence several medical conditions conferring an increased mortality risk. The aim of this study was to explore the prevalence of vitamin D deficiency and its association with mortality.DESIGN:The Study of Health and Drugs in the Elderly (SHADES) is a prospective cohort study among elderly people (>65 years) in 11 nursing homes in Sweden.METHODS:We analysed the levels of 25-hydroxyvitamin D₃ (25(OH)D₃) at baseline. Vital status of the subjects was ascertained and hazard ratios (HRs) for mortality according to 25(OH)D₃ quartiles were calculated.RESULTS:We examined 333 study participants with a mean follow-up of 3 years. A total of 147 (44%) patients died within this period. Compared with the subjects in Q4 (25(OH)D₃ >48 nmol/l), HR (with 95% CI) for mortality was 2.02 (1.31-3.12) in Q1 (25(OH)D₃ <29 nmol/l) (P<0.05); 2.03 (1.32-3.14) in Q2 (25(OH)D₃ 30-37 nmol/l) (P<0.05) and 1.6 (1.03-2.48) in Q3 (25(OH)D₃ 38-47 nmol/l) (P<0.05). The mean 25(OH)D₃ concentration was 40.2 nmol/l (S.D. 16.0) and 80% had 25(OH)D₃ below 50 nmol/l. The vitamin D levels decreased from baseline to the second and third measurements.CONCLUSIONS:Vitamin D deficiency was highly prevalent and associated with increased mortality among the elderly in Swedish nursing homes. Strategies are needed to prevent, and maybe treat, vitamin D deficiency in the elderly in nursing homes and the benefit of vitamin D supplementation should be evaluated in randomised clinical trials.
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| 29. |
- Smith, Casey Jo Anne, et al.
(författare)
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Identification of TPIT and other novel autoantigens in lymphocytic hypophysitis : immunoscreening of a pituitary cDNA library and development of immunoprecipitation assays
- 2012
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 166:3, s. 391-398
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lymphocytic hypophysitis is an organ-specific autoimmune disease of the pituitary gland. A specific and sensitive serological test currently does not exist to aid in the diagnosis. Objective: To identify target autoantigens in lymphocytic hypophysitis and develop a diagnostic assay for these proteins. Design/methods: A pituitary cDNA expression library was immunoscreened using sera from four patients with lymphocytic hypophysitis. Relevant cDNA clones from screening, along with previously identified autoantigens pituitary gland-specific factor 1a and 2 (PGSF1a and PGSF2) and neuron-specific enolase (NSE) were tested in an in vitro transcription and translation immunoprecipitation assay. The corticotroph-specific transcription factor, TPIT, was investigated separately as a candidate autoantigen. Results: Significantly positive autoantibody reactivity against TPIT was found in 9/86 hypophysitis patients vs 1/90 controls (P = 0.018). The reactivity against TPIT was not specific for lymphocytic hypophysitis with autoantibodies detectable in the sera from patients with other autoimmune endocrine diseases. Autoantibodies were also detected against chromodomain-helicase-DNA binding protein 8, presynaptic cytomatrix protein (piccolo), Ca2+-dependent secretion activator, PGSF2 and NSE in serum samples from patients with lymphocytic hypophysitis, but at a frequency that did not differ from healthy controls. Importantly, 8/86 patients with lymphocytic hypophysitis had autoantibodies against any two autoantigens in comparison with 0/90 controls (P = 0.0093). Conclusions: TPIT, a corticotroph-specific transcription factor, was identified as a target autoantigen in 10.5% of patients with lymphocytic hypophysitis. Further autoantigens related to vesicle processing were also identified as potential autoantigens with different immunoreactivity patterns in patients and controls.
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| 30. |
- Sofiadis, Anastasios, et al.
(författare)
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Proteomic profiling of follicular and papillary thyroid tumors
- 2012
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 166:4, s. 657-667
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Thyroid proteomics is a new direction in thyroid cancer research aiming at etiological understanding and biomarker identification for improved diagnosis. Methods: Two-dimensional electrophoresis was applied to cytosolic protein extracts from frozen thyroid samples (ten follicular adenomas, nine follicular carcinomas, ten papillary carcinomas, and ten reference thyroids). Spots with differential expression were revealed by image and multivariate statistical analyses, and identified by mass spectrometry. Results: A set of 25 protein spots significant for discriminating between the sample groups was identified. Proteins identified for nine of these spots were studied further including 14-3-3 protein beta/alpha, epsilon, and zeta/delta, peroxiredoxin 6, selenium-binding protein 1, protein disulfide-isomerase precursor, annexin A5 (ANXA5), tubulin alpha-1B chain, and alpha 1-antitrypsin precursor. This subset of protein spots carried the same predictive power in differentiating between follicular carcinoma and adenoma or between follicular and papillary carcinoma, as compared with the larger set of 25 spots. Protein expression in the sample groups was demonstrated by western blot analyses. For ANXA5 and the 14-3-3 proteins, expression in tumor cell cytoplasm was demonstrated by immunohistochemistry both in the sample groups and an independent series of papillary thyroid carcinomas. Conclusion: The proteins identified confirm previous findings in thyroid proteomics, and suggest additional proteins as dysregulated in thyroid tumors.
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| 31. |
- Thomas, Dimitrios, et al.
(författare)
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Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors : Data from a multicenter study
- 2013
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168:2, s. 185-193
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE:To study the clinical presentation, diagnostic approach, response to treatment and the presence of other pathologies in patients with gastric carcinoid type-1 tumors (GC-1).DESIGN AND METHODS:Retrospective analysis of 111 patients from 4 institutions and a mean follow-up of 76 months.RESULTS:The main indications for gastroscopy were upper gastrointestinal tract symptoms. The mean number of lesions, maximum tumoral diameter and percentage of cells expressing Κi-67 labeling index were 3.6±3.8, 8±12.1mm and 1.9±2.4%, respectively. Serum gastrin and chromogranin A (CgA) levels were elevated in 100/101 and 85/90 patients, respectively. Conventional imaging studies demonstrated pathology in 9/111 patients. Scintigraphy with radiolabelled octreotide was positive in 6/60 without revealing any additional lesions. From the 59 patients who had been followed-up without any intervention 5 developed tumor progression. Thirty-two patients were treated with long acting somatostatin analogues (SSAs), leading to a significant reduction of gastrin and CgA levels, number of visible tumors and CgA immune reactive tumor cells in 28, 19, 27, and 23 treated patients respectively. Antrectomy and/or gastrectomy was initially performed in 20 patients and a complete response was achieved in 13 patients. The most common co-morbidities were vitamin B12 deficiency, thyroiditis and parathyroid adenomas.CONCLUSIONS:Most GCs-1 are grade 1 (82.72%) tumors presenting with stage I (73.87%) disease with no mortality after prolonged follow-up. Ocreoscan did not provide further information compared to conventional imaging techniques. Treatment with SSAs proved to be effective for the duration of administration.
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| 32. |
- Tjörnstrand, Axel, et al.
(författare)
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The incidence rate of pituitary adenomas in western Sweden for the period 2001-2011
- 2014
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:4, s. 519-526
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Tidskriftsartikel (refereegranskat)abstract
- © 2014 European Society of Endocrinology. Objective: The number of studies on the incidence of pituitary adenomas (PAs) is limited. The aim of this study was to evaluate the standardised incidence rate (SIR) of PAs in western Sweden.Design, subjects and methods: Data from adult patients diagnosed with PAs in 2001-2011, living in the Vä stra Götaland County, were collected from the Swedish Pituitary Registry (SPR). In addition, medical records on all patients diagnosed with PAs at the six hospitals in the region were reviewed. In total, 592 patients were included in the study.Age-SIR, given as rate/100 000 inhabitants (95% CI), was calculated using the WHO 2000 standard population as a reference.Results: The total SIRfor PAswas 3.9/100 000 (3.6-4.3); 3.3/100 000 (2.9-3.7) formen and 4.7/100 000 (4.1-5.3) forwomen. Inmen, SIR increasedwith age, while inwomen SIR peaked at 25-34 years, mainly due to prolactinomas. Non-functioning PA (NFPA)was the most common PA (54%, 1.8/100 000 (1.6-2.0)) followed by prolactinomas (32%, 1.6/100 000 (1.3-1.9)), acromegaly (9%, 0.35/100 000 (0.25-0.45)), Cushing'sdisease (4%, 0.18/100 000 (0.11-0.25)) andTSH-producingPA(0.7%, 0.03/100 000 (0.00-0.05)). The proportion of macroadenomas for NFPA was 82%, prolactinomas 37%, GH-producing PA 77%, ACTH-producing PA 28% and TSH-producing PA 100%. The lifetime risk for PAs was 0.27% (0.24-0.31) in men and 0.29% (0.26-0.33) in women.Conclusion: This study provides a reliable estimate on the overall incidence of PAs and confirms an increased incidence of PAs compared with studies conducted in the pre-magnetic resonance imaging era. The lower proportion of prolactinomas compared with previous studies is probably explained by the different criteria used.
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| 33. |
- Trimpou, Penelope, 1973, et al.
(författare)
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Secular trends in sex hormones and fractures in men and women
- 2012
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 166:5, s. 887-895
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To study secular trends in sex hormones, anthropometry, bone measures and fractures. Design: A random population sample was studied twice and subjects of similar age group were compared 13 years apart. Methods: X-ray-verified fractures were retrieved from a random population sample of 2400 men and women (participants 1616=67%) aged 25-64 years from the WHO, MONICA Project in Gothenburg, Sweden, in 1995 and 2008. Fasting serum hormones and calcaneal ultrasound were measured in every fourth subject. In fertile women, measurements were performed on cycle day interval 7-9. Results: In 2008, men had lower serum free testosterone than men of similar age in 1995 (P < 0.001). Body composition, physical activity and fracture incidence were similar. In women, hormone replacement therapy (HRT) was lower in 2008, 7 vs 28% (P < 0.0001), as was serum oestradiol, although use of tranquilisers and leisure time physical activity were higher. In 2008, the fracture incidence was higher in postmenopausal women, 29 vs 17% (P < 0.001), and vertebral crush had increased from 8 to 19% of all fractures (P=0.031). Serum cholesterol and triglycerides were lower in all subjects in 2008 compared with that in 1995. Conclusions: Secular trends were observed with lower serum testosterone in men in 2008, but no effect was seen on the fracture incidence of these fairly young men. In postmenopausal women in 2008, there was a higher fracture incidence along with more vertebral compressions. Lower HRT use, lower serum oestradiol and higher fall risk exposure due with more tranquilisers and leisure time physical activity in 2008 may explain the results.
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| 34. |
- Vandenput, Liesbeth, et al.
(författare)
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Serum estradiol is associated with lean mass in elderly Swedish men
- 2010
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 162:4, s. 737-745
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Association studies in men have shown that androgens are inversely related to fat measures, while the relation between sex steroids and lean mass remains unclear. We, therefore, investigated the associations between serum sex steroid levels and body composition in elderly men with a main focus on lean mass measures. DESIGN AND METHODS: A cross-sectional survey of a population-based cohort of 3014 elderly men, aged 69-80 years (Osteoporotic Fractures in Men study, Sweden). Serum levels of testosterone and estradiol (E(2)) were measured by mass spectrometry, sex hormone-binding globulin (SHBG) levels were measured by IRMA, and measures of body composition were obtained by dual-energy X-ray absorptiometry. RESULTS: Total as well as free serum testosterone associated independently inversely (P<0.001), while total as well as free serum E(2) associated independently directly (P<0.001) with total body fat mass and trunk fat mass. Serum SHBG associated independently inversely with central fat distribution. Serum E(2) and free E(2) but not serum testosterone or free testosterone levels associated positively with lean mass (P<0.01). Elderly men within the lowest quartile of free E(2) had 0.5 kg less lean mass in the legs than subjects within the highest quartile, while the subjects in the different quartiles of free testosterone did not differ in lean mass. CONCLUSIONS: Serum E(2), but not serum testosterone, is directly associated with lean mass in this large study of elderly Swedish men. In addition, serum SHBG is associated with central fat distribution and we confirmed that serum testosterone is inversely associated with fat mass.
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| 35. |
- Åstrand, Olov, et al.
(författare)
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Weight gain by hyperalimentation elevates C-reactive protein levels but does not affect circulating levels of adiponectin or resistin in healthy subjects
- 2010
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Ingår i: European Journal of Endocrinology. - Bristol : BioScientifica. - 0804-4643 .- 1479-683X. ; 163:6, s. 879-885
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Increase of resistin and/or reduction of adiponectin have beenimplicated in the development of insulin resistance followingweight gain. We aimed to study this prospectively in humans.Design: Prospective and interventional with parallel control group.Methods: Twelve healthy men and six healthy women (age 26±6.6years) and an age-matched control group were recruited. Subjectsin the intervention group aimed for a bodyweight increase of5–15% by doubling the baseline caloric intake by eatingat least two fast food-based meals a day in combination withadoption of a sedentary lifestyle for 4 weeks.Results: Bodyweight increased from 67.6±9.1 to 74.0±11kg, P<0.001, by the intervention. Insulin levels increased(before: 27.4±12 pmol/l, after: 53.0±22 pmol/l,P=0.004), while plasma levels of adiponectin (before: 5038±3736ng/ml, after: 6739±7949 ng/ml, P=0.18) and resistin (before:21.8±19 ng/ml, after: 14.4±6.8 ng/ml, P=0.074)remained unchanged by the weight gain and were similar as incontrols. On the other hand, leptin levels increased about threefoldfollowing the intervention (before: 5.7±7.4, after: 16±20ng/ml, P=0.008), and also the inflammatory marker C-reactiveprotein (CRP) increased from 0.34±0.44 to 0.71±0.87mg/l, P=0.03, when two outliers >10 mg/l were disregarded.Conclusions: Hyperalimentation reduces insulin sensitivity when weight gainof 9% was combined with reduction of exercise. However, thelevels of resistin and adiponectin were unaffected by the intervention,while CRP levels increased within this short time period suggestingthat low-grade inflammation can occur early in the process ofdeveloping a metabolic syndrome.
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| 36. |
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| 37. |
- Abs, Roger, et al.
(författare)
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Prevalence of diabetes mellitus in 6050 hypopituitary patients with adult-onset GH deficiency before GH replacement: a KIMS analysis
- 2013
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 168:3, s. 297-305
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH deficiency (GHD) in adults is characterized by a tendency toward obesity and an adverse body composition with visceral fat deposit and may thus predispose to the development of type 2 diabetes mellitus. The aim of this study was to assess the observed prevalence proportion (PP) and observed PP over expected PP ratio (standardized prevalence proportion ratio, SPR) of diabetes according to International Diabetes Federation criteria in a large cohort of GH-untreated adult-onset GHD patients. Design and methods: Associations between baseline variables and diabetes prevalence in 6050 GHD patients from KIMS (Pfizer International Metabolic Database) were studied and robust Poisson-regression analyses were performed. Comparisons between baseline status and HbA1c categories in the nondiabetic patients were done with covariance analysis. P values < 0.05 were considered statistically significant. Results: PP was 9.3% compared with the expected 8.2%. SPR was 1.13 (95% confidence intervals (95% CIs), 1.04-1.23), which was significantly increased in females (1.23; 95% CI, 1.09-1.38%) but not in males (SPR 1.04; 95% CI, 0.92-1.17%). PP increased significantly by age, familial diabetes, country selection, BMI, waist circumference, number of pituitary deficiencies, and GHD etiology. SPR decreased significantly by age and increased significantly by BMI, waist circumference, and IGF1 SDS. Multiple regression model showed that the most important impact on SPR was from age and BMI. HbA1c values of 6.0-6.5% were found in 9.5% of nondiabetic patients and were associated with higher BMI and waist circumference. Conclusions: GHD is associated with an increased prevalence of diabetes, largely to be explained by the adverse body composition. These data urge toward early initiation of lifestyle modification measures. European Journal of Endocrinology 168 297-305
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| 38. |
- Andersen, Mette K., et al.
(författare)
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Association of variants in HLA-DQA1-DQB1, PTPN22, INS, and CTLA4 with GAD autoantibodies and insulin secretion in nondiabetic adults of the Botnia Prospective Study
- 2012
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 167:1, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Previously, we observed an association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. The aims of this study were to assess whether type 1 diabetes susceptibility gene variants explain this association and investigate the effect of the variants on insulin secretion and presence of glutamic acid decarboxylase autoantibodies (GADA) in nondiabetic adults. Design and methods: Polymorphisms in INS (rs689), PTPN22 (rs2476601), CTLA4 (rs3087243), and the HLA-DQA1-DQB1 regions (rs2187668 and rs7454108 tagging HLA-DQ2.5 and HLA-DQ8 respectively) were genotyped in the Botnia Prospective Study (n=2764), in which initially nondiabetic participants were followed for a mean of 8.1 years. Results: The variants did not explain the association between family history of type 1 diabetes and development of non-insulin-dependent diabetes. In these nondiabetic adults, HLA-DQ and PTPN22 risk genotypes were associated with GADA (HLA-DQ2.5/HLA-DQ8 or HLA-DQ8: OR (95% CI): 1.7 (1.3-2.3), P=0.0004; PTPN22 CT/TT: OR: 1.6 (1.2-2.2), P=0.003; P values were adjusted for sex, age, BMI, and follow-up time). A higher genetic risk score was associated with lower insulin secretion (insulinogenic index: 13.27 (16.27) vs 12.69 (15.27) vs 10.98 (13.06), P=0.02) and better insulin sensitivity index (risk score of 0-1 vs 2-3 vs 4-6: 142 (111) vs 144 (118) vs 157 (127), P=0.01) at baseline and a poorer capacity to compensate for the increased insulin demand after follow-up. Conclusions: In nondiabetic adults, HLA-DQ2.5/HLA-DQ8 and PTPN22 CT/TT genotypes were associated with GADA.
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| 39. |
- Ankarberg-Lindgren, Carina, 1963, et al.
(författare)
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Testicular size development and reproductive hormones in boys and adult males with Noonan syndrome: a longitudinal study
- 2011
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Ingår i: European Journal of Endocrinology. - 0804-4643. ; 165:1, s. 137-44
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Tidskriftsartikel (refereegranskat)abstract
- Objective To characterise changes in testicular size and reproductive hormones and to investigate the aetiology of delayed puberty and impaired fertility in males with Noonan syndrome (NS). Design In this study, 12 males with NS were longitudinally followed from pre/early puberty until adulthood. Of the 12 males, ten had no medical history other than NS and were divided into two groups, undescended testes (UT), and descended testes (DT) and compared with a reference population. Methods Hormone concentrations in serum were determined by immunoassays and testicular volume was measured using an orchidometer. Results Before puberty, reproductive hormone levels were within the expected range in almost all cases. In some cases, LH, FSH and testosterone and oestradiol (E(2)) concentrations started to increase during puberty and inhibin B and anti-Mullerian hormone (AMH) declined to subnormal levels. Most of the boys studied had small testes that, in the majority of cases, progressed to normal size in adulthood. No difference in reproductive hormones was observed between the UT and DT groups either during puberty or at adulthood. However, as adults, males with NS had higher LH (5.7 vs 4.0 U/l, P<0.01), FSH (7.1 vs 2.5 U/l, P<0.001), testosterone (18.7 vs 15.6 nmol/l, P<0.01) and E(2) (66 vs 46 pmol/l, P<0.001) levels and lower AMH (33 vs 65 pmol/l, P<0.01) and inhibin B (median 108 vs 187 pg/ml, P<0.01) levels than the reference population. Conclusions In NS males, both Sertoli and Leydig cell dysfunction is common with reproductive hormone levels deteriorating progressively to adulthood.
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| 44. |
- Boonen, Steven, et al.
(författare)
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Influence of bone remodelling rate on quantitative ultrasound parameters at the calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European men: the European Male Ageing Study (EMAS)
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 165:6, s. 977-986
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the influence of sex hormones on markers of bone turnover and to explore the association between these markers and bone health in middle-aged and elderly European men. Design: A cross-sectional population-based survey. Methods: Men aged 40-79 years were recruited from population registers in eight European centres. Subjects completed a postal questionnaire which included questions concerning lifestyle and were invited to undergo quantitative ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP) and crosslinks (beta C-terminal cross-linked telopeptide (beta-cTX)), total testosterone, total oestradiol (E-2), sex hormone-binding globulin (SHBG) and insulin-like growth factor 1 (IGF1) were measured. Dualenergy X-ray absorptiometry (DXA) of the hip and lumbar spine was performed in two centres. Results: A total of 3120, mean age 59.9 years (S.D. = 11.0) were included. After adjustment for centre, age, height, weight, lifestyle factors, season and other hormones, total and free E-2 were negatively associated with beta-cTX but not P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated with both beta-cTX and P1NP. Total or free testosterone was not independently associated with either bone marker. After the same adjustments, higher levels of both bone markers were significantly associated with lower QUS parameters and lower DXA-assessed bone density at the total hip and lumbar spine. Conclusions: E-2, SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone turnover in middle-aged and older European men. Higher rates of bone remodelling are negatively associated with male bone health.
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| 45. |
- Camacho, E. M., et al.
(författare)
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Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study
- 2013
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 168:3, s. 445-455
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. Design: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (+/- S.D.) 4.4 +/- 0.3 years later. Results: Paired testosterone results were available for 2395 men. Mean (+/- S.D.) annualised hormone changes were as follows: testosterone -0.1 +/- 0.95 nmol/l; free testosterone (FT) -3.83 +/- 16.8 pmol/l; sex hormone-binding globulin (SHBG) 0.56 +/- 2.5 nmol/l and LH 0.08 +/- 0.57 U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost >= 15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. Conclusions: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction. European Journal of Endocrinology 168 445-455
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| 46. |
- Child, Christopher J., et al.
(författare)
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Assessment of primary cancers in GH-treated adult hypopituitary patients: an analysis from the Hypopituitary Control and Complications Study
- 2011
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 165:2, s. 217-223
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Tidskriftsartikel (refereegranskat)abstract
- Objective: GH and IGFs have mitogenic properties, causing speculation that GH treatment could increase risk of malignancy. While studies in GH-treated childhood cancer survivors have suggested a slight increase in second neoplasms, studies in GH-treated adults have been equivocal. Design: Incidence of de novo and second cancers was evaluated in 6840 GH-treated and 940 non GH-treated adult patients in the Hypopituitary Control and Complications Study pharmacoepidemiological database. Methods: Evident cancer cases were evaluated in the main analysis, with sensitivity analyses including probable and possible cancers. Standardized incidence ratios (SIRs) for cancers were calculated using Surveillance, Epidemiology and End Results for the USA and GLOBOCAN for all other countries. Results: During the mean follow-up of 3.7 years/GH-treated patient, 142 evident cancer cases were identified, giving an overall SIR of 0.88 (95% confidence interval (CI) 0.74-1.04); 95% CIs included the value of 1.0 for each country examined. The SIR for GH-treated patients from the USA (71 cases) was 0.94 (95% CI 0.73-1.18), and for non GH-treated patients from the USA (27 cases) was 1.16 (95% CI 0.76-1.69). For GH-treated patients from the USA aged < 35 years, the SIR (six cases) was 3.79 (1.39-8.26), with SIR not elevated for all other age categories; SIR for patients from the USA with childhood onset (CO) GH deficiency (GHD) was 2.74 (95% CI 1.18-5.41). The SIR for colorectal cancer in GH-treated patients (11 cases) was 0.60 (95% CI 0.30-1.08). Conclusions: With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs were found for subgroups in the USA cohort defined by age < 35 years or CO GHD.
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| 49. |
- Delgrange, Etienne, et al.
(författare)
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Giant prolactinomas in women
- 2014
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 170:1, s. 31-38
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To characterise distinctive clinical features of giant prolactinomas in women. Design: A multicentre, retrospective case series and literature review. Methods: We collected data from 15 female patients with a pituitary tumour larger than 4 cm and prolactin levels above 1000 mu g/l and identified 19 similar cases from the literature; a gender-based comparison of the frequency and age distribution was obtained from a literature review. Results: The initial PubMed search using the term 'giant prolactinomas' identified 125 patients (13 women) responding to the inclusion criteria. The female: male ratio was 1:9. Another six female patients were found by extending the literature search, while our own series added 15 patients. The median age at diagnosis was 44 years in women compared with 35 years in men (P<0.05). All cases diagnosed before the age of 15 years were boys. In women (n=34), we observed a minor peak incidence during the third decade of life and a major peak during the fifth decade. Amenorrhoea was a constant feature with seven cases of primary amenorrhoea. In eight women with onset of secondary amenorrhoea before the age of 40 years, the diagnosis was made 2-31 years later (median 9 years) and in all but one because of tumour pressure symptoms. The prolactin levels were above 10 000 mu g/l in 15/34 and misdiagnosis due to 'hook effect' occurred in two of them. Eighteen patients were treated with cabergoline; standard doses (<2.0 mg/week) were able to normalise prolactin in only 4/18 patients, and 7/18 patients were resistant to weekly doses ranging from 3.0 to 7.0 mg. Conclusion: Giant prolactinomas are rare in women, often resistant to dopamine agonists and seem to be distributed in two age groups, with a larger late-onset peak.
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