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Sökning: WFRF:(Johannsson Gudmundur)

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1.
  • Agnarsson, Hjalmar Ragnar, et al. (författare)
  • The impact of glucocorticoid replacement on bone mineral density in patients with hypopituitarism before and after 2 years of growth hormone replacement therapy.
  • 2014
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:4, s. 1479-1485
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with hypopituitarism have reduced bone mineral density (BMD) and increased fracture risk. Objective: The aim of this study was to analyze the effects of glucocorticoid (GC) replacement on BMD before and after two years of growth hormone (GH) therapy in hypopituitary patients. The main hypothesis was that patients on GC replacement demonstrate greater improvement in BMD when treated with GH. Design: This was a post hoc analysis of data from a prospective single centre study. Patients: Data on 175 adult patients with hypopituitarism and verified GH deficiency due to non-functioning pituitary adenoma were analyzed. Ninety-eight (56%) were GC insufficient, receiving a mean±SD hydrocortisone equivalent dose of 20.9±5.0 mg/day. Main outcome measure: BMD before and after two years of GH replacement therapy, measured by using dual-energy X-ray absorptiometry. Results: BMD at baseline did not differ between GC sufficient and insufficient patients, neither at lumbar spine nor femur neck. After two years on GH replacement BMD increased in both groups. After adjustment for weight, age, gender, free T4 concentrations, change in IGF-I levels and sex hormone treatment, GC sufficiency was associated with greater increase in BMD at femur neck (ΔT-score in GC insufficient patients 0.09±0.46, in GC sufficient patients 0.19±0.43; P<0.05) but not at lumbar spine. Conclusions: GH replacement therapy for 2 years increased BMD in hypopituitary patients. In contrast to our hypothesis, GC insufficient patients receiving near physiological doses of hydrocortisone do not show a greater therapeutic response to GH therapy than their GC sufficient counterparts.
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2.
  • Allen, D. B., et al. (författare)
  • GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults
  • 2016
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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3.
  • Allen, David B, et al. (författare)
  • GH Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults.
  • 2016
  • Ingår i: European Journal of Endocrinology. - 1479-683X. ; 174:2, s. 1-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant human growth hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statement highlighted a number of areas for on-going surveillance of long-term safety including; cancer risk, impact on glucose homeostasis and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk and the need for longterm surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.
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4.
  • Allosso, Francesca, et al. (författare)
  • Mortality in patients with adrenal insufficiency: a protocol for a systematic review and meta-analysis.
  • 2024
  • Ingår i: BMJ open. - 2044-6055. ; 14:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Adrenal insufficiency (AI) is a rare disorder characterised by an impaired secretion of glucocorticoids from the adrenal glands. Treatment strategies for AI have developed over time with reduced glucocorticoid replacement doses and improved circadian exposure regimens, but whether this has resulted in better survival is unknown. The main purpose of this systematic review is to gather and synthesise available evidence on long-term mortality in patients with AI. The secondary aim is to study causes of death, with focus on cardiovascular and infectious diseases, in AI patients.Studies published from the inception of respective databases (Medline, Embase, Cochrane and Web of Science) until the end of May 2023 will be systematically synthetised. Observational studies with a reference population will be included, and their quality will be assessed using the Newcastle-Ottawa scale. Data collected will be narratively integrated and a meta-analysis will be performed to pool data from studies considered homogeneous. The systematic review will be reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. This will be the first systematic review assessing mortality and causes of death in AI patients. The findings of this systematic review will be of value for both patients and healthcare providers.This systematic review does not require ethical approval or informed consent because it will be based on previously published data only and does not implicate any direct contact with individual patients. The research results will be presented at scientific conferences and submitted for publication in an internationally recognised peer-reviewed scientific journal.CRD42023416253.
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5.
  • Andela, C. D., et al. (författare)
  • MECHANISMS IN ENDOCRINOLOGY Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies
  • 2015
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 173:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion: Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.
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6.
  • Andersson, Agnes, et al. (författare)
  • Headache Before and After Endoscopic Transsphenoidal Pituitary Tumor Surgery: A Prospective Study
  • 2022
  • Ingår i: Journal of Neurological Surgery Part B-Skull Base. - : Georg Thieme Verlag KG. - 2193-6331 .- 2193-634X. ; 83:suppl. 2
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective Headache is a common symptom among patients with pituitary tumors, as it is in the general population. The aim of the study was to investigate headache as a symptom in patients with pituitary tumors before and 6 months after endoscopic transsphenoidal surgery (TSS). Design This is a prospective observational cohort study. Setting This study was conducted at university tertiary referral hospital. Participants A total of 110 adult patients underwent endoscopic TSS for pituitary tumors. Main Outcome Measures The Migraine Disability Assessment (MIDAS) questionnaire was used before and 6 months after surgery for the assessment of headache. Clinical variables with potential influence on headache were analyzed. Results Sixty-eight (62%) patients experienced headaches at least once during the 3 months before surgery. Thirty (27%) patients reported disabling headache before surgery, with younger age being an independent associated factor ( p <0.001). In patients with disabling headache before surgery, the median (interquartile range) MIDAS score improved from 78 (27-168) to 16 (2-145; p =0.049), headache frequency decreased from 45 (20-81) to 14 (4-35) days ( p =0.009), and headache intensity decreased from 6 (5-8) to 5 (4-7) ( p =0.011) after surgery. In total, 16 of the 30 (53%) patients reported a clinically relevant improvement and five (17%) a clinically relevant worsening. Four (5%) patients developed new disabling headache. No predictor for postoperative improvement of headache was identified. Conclusion In this prospective study, the results show that disabling headache improves following endoscopic TSS in a subset of patients with pituitary tumors. However, no predictive factors for improvement could be identified.
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7.
  • Andersson, Björn, et al. (författare)
  • Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: a randomized clinical trial.
  • 2002
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 87:1, s. 122-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Little is known about the metabolic or cardiovascular effects of selective ER modulators (SERMs), such as raloxifene hydrochloride (RLX), in postmenopausal women with type 2 diabetes mellitus (DM). Therefore, the effect of RLX vs. placebo (PL) on glycemic control, insulin sensitivity, as well as effects on a number of hormone, lipid, coagulation, and safety factors were determined in 30 postmenopausal women with type 2 DM in a randomized, double blind, cross-over trial. All participants had a SHBG serum concentration below 60 nmol/liter at baseline and had stable diabetes controlled by either oral hypoglycemic agents or diet for 1 month. In the first treatment period, participants received 12 wk of either PL or RLX, followed by an 8-wk washout before the second treatment period. In the second treatment period, participants were crossed over to the other treatment. Compared with PL, RLX did not significantly affect fasting blood glucose, hemoglobin A(1c), lipids, fasting insulin, or insulin sensitivity (as measured by the euglycemic clamp technique). Compared with PL, RLX reduced fibrinogen levels by 0.77 g/liter (P < 0.001), IGF-I by 2.4 nmol/liter (P < 0.001), and free T by 0.73 pmol/liter (P = 0.038) and increased SHBG by 5.5 nmol/liter (P = 0.001) and IGF-binding protein-3 by 0.57 ng/ml (P = 0.007). Our results demonstrate that RLX does not significantly affect glycemic control and has favorable or neutral effects on selected surrogate markers of cardiovascular risk in postmenopausal women with type 2 diabetes mellitus while decreasing hyperandrogenicity in these patients.
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8.
  • Arlien-Soborg, Mai C., et al. (författare)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • Ingår i: Clinical Endocrinology. - : WILEY. - 0300-0664 .- 1365-2265.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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9.
  • Arlien-Soborg, Mai C., et al. (författare)
  • Acromegaly management in the Nordic countries: A Delphi consensus survey
  • 2024
  • Ingår i: CLINICAL ENDOCRINOLOGY. - : WILEY. - 0300-0664 .- 1365-2265.
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveAcromegaly is associated with increased morbidity and mortality if left untreated. The therapeutic options include surgery, medical treatment, and radiotherapy. Several guidelines and recommendations on treatment algorithms and follow-up exist. However, not all recommendations are strictly evidence-based. To evaluate consensus on the treatment and follow-up of patients with acromegaly in the Nordic countries.MethodsA Delphi process was used to map the landscape of acromegaly management in Denmark, Sweden, Norway, Finland, and Iceland. An expert panel developed 37 statements on the treatment and follow-up of patients with acromegaly. Dedicated endocrinologists (n = 47) from the Nordic countries were invited to rate their extent of agreement with the statements, using a Likert-type scale (1-7). Consensus was defined as >= 80% of panelists rating their agreement as >= 5 or <= 3 on the Likert-type scale.ResultsConsensus was reached in 41% (15/37) of the statements. Panelists agreed that pituitary surgery remains first line treatment. There was general agreement to recommend first-generation somatostatin analog (SSA) treatment after failed surgery and to consider repeat surgery. In addition, there was agreement to recommend combination therapy with first-generation SSA and pegvisomant as second- or third-line treatment. In more than 50% of the statements, consensus was not achieved. Considerable disagreement existed regarding pegvisomant monotherapy, and treatment with pasireotide and dopamine agonists.ConclusionThis consensus exploration study on the management of patients with acromegaly in the Nordic countries revealed a relatively large degree of disagreement among experts, which mirrors the complexity of the disease and the shortage of evidence-based data.
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10.
  • Barbosa, Edna J L, 1961, et al. (författare)
  • Extracellular water and blood pressure in adults with growth hormone (GH) deficiency: a genotype-phenotype association study.
  • 2014
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth hormone deficiency (GHD) in adults is associated with decreased extracellular water volume (ECW). In response to GH replacement therapy (GHRT), ECW increases and blood pressure (BP) reduces or remains unchanged. Our primary aim was to study the association between polymorphisms in genes related to renal tubular function with ECW and BP before and 1 year after GHRT. The ECW measures using bioimpedance analysis (BIA) and bioimpedance spectroscopy (BIS) were validated against a reference method, the sodium bromide dilution method (Br(-)).
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11.
  • Barbosa, Edna J L, 1961, et al. (författare)
  • Genotypes associated with lipid metabolism contribute to differences in serum lipid profile of GH-deficient adults before and after GH replacement therapy.
  • 2012
  • Ingår i: European journal of endocrinology / European Federation of Endocrine Societies. - 1479-683X .- 0804-4643. ; 167:3, s. 353-62
  • Tidskriftsartikel (refereegranskat)abstract
    • bjective: GH deficiency (GHD) in adults is associated with an altered serum lipid profile that responds to GH replacement therapy (GHRT). This study evaluated the influence of polymorphisms in genes related to lipid metabolism on serum lipid profile before and after 1 year of GHRT in adults. Design and methods: In 318 GHD patients, total cholesterol (TC) serum concentrations, LDL-C, HDL-C, and triglycerides (TG) were assessed. Using a candidate gene approach, 20 single nucleotide polymorphisms (SNPs) were genotyped. GH dose was individually titrated to obtain normal serum IGF1 concentrations. Results: At baseline, the minor alleles of cholesteryl ester transfer protein (CETP) gene SNPs rs708272 and rs1800775 were associated with higher serum TC and apolipoprotein E (APOE) gene SNP rs7412 with lower TC concentrations; CETP SNPs rs708272, rs1800775, and rs3764261 and apolipoprotein B (APOB) gene SNP rs693 with higher serum HDL-C; APOE SNP rs7412, peroxisome proliferator-activated receptor gamma (PPARG) gene SNP rs10865710 with lower LDL-C, and CETP SNP rs1800775 with higher LDL-C; and APOE/C1/C4/C2 cluster SNP rs35136575 with lower serum TG. After treatment, APOB SNP rs676210 GG genotype was associated with larger reductions in TC and LDL-C and PPARG SNP rs10865710 CC genotype with greater TC reduction. All associations remained significant when adjusted for age, sex, and BMI. Conclusions: In GHD adults, multiple SNPs in genes related to lipid metabolism contributed to individual differences in baseline serum lipid profile. The GH treatment response in TC and LDL-C was influenced by polymorphisms in the APOB and PPARG genes.
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12.
  • Barbosa, Edna J L, 1961, et al. (författare)
  • Influence of the Exon 3-deleted/full-length Growth Hormone Receptor Polymorphism on the Response to Growth Hormone Replacement Therapy in Adults with Severe Growth Hormone Deficiency. : d3-GHR isoform in GHD adults
  • 2009
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 94:2, s. 639-644
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: There is considerable individual variation in the clinical response to growth hormone (GH) replacement therapy in GH deficient (GHD) adults. Useful predictors of treatment response are lacking. Objective: To assess the influence of the exon 3-deleted (d3-GHR) and full-length (fl-GHR) GH receptor isoforms on the response to GH replacement therapy in adults with severe GHD. Design, Patients: 124 adult GHD patients (79 men, median age 50 years) were studied before and after 12 months of GH therapy. GHD patients were divided into those bearing fl/fl alleles (Group 1) and those bearing at least one d3-GHR allele (Group 2), and the genotype was related to the effects of GH therapy on IGF-I levels and total body fat (BF). Intervention: GH dose was individually titrated to obtain normal serum IGF-I levels. Main Outcome Measures: GHR genotype was determined by PCR amplification, IGF-I levels by immunoassay, and BF by a four-compartment model. Results: Seventy-two (58%) patients had fl/fl genotype and were classified as Group 1, while 52 (42%) had at least one d3-GHR allele and were classified as Group 2 (40 were heterozygous and 12 were homozygous). At baseline, there were no significant differences in the study groups. Changes in IGF-I and BF after 12 months of GH treatment did not differ significantly between the two genotype groups. Conclusion: The presence of d3-GHR allele did not influence the response to GH replacement therapy in our cohort of adults with severe GHD.
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17.
  • Bengtsson, B A, et al. (författare)
  • Treatment of growth hormone deficiency in adults.
  • 2000
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 85:3, s. 933-42
  • Tidskriftsartikel (refereegranskat)abstract
    • In analogy with other hormonal replacement therapy GH treatment should be commenced with a low starting dose, independent of body weight or body surface area. Hormonal replacement should mimic the normal physiology to minimize the risk of side effects in the life-long replacement of adults. We should, therefore, consider individual responsiveness and also be aware of the difference between pattern of GH under normal condition and during s.c. administration. The safety and monitoring of GH replacement therapy in adults have been addressed in the Growth Hormone Research Society Consensus Guidelines for Diagnosis and Treatment of Adults with GH Deficiency from the Port Stephens Workshop, April 1997. Besides finding better and more accurate biochemical markers for choosing correct GH replacement dose, future research should address the long-term benefits and safety with GH replacement in adults, with special emphasize on incipient risks in terms of cardiovascular disease and of neoplasia, in particular.
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19.
  • Bengtsson, Daniel, 1975-, et al. (författare)
  • Long-Term Outcome and MGMT as a Predictive Marker in 24 Patients With Atypical Pituitary Adenomas and Pituitary Carcinomas Given Treatment With Temozolomide
  • 2015
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:4, s. 1689-1698
  • Tidskriftsartikel (refereegranskat)abstract
    • Context/Objective: Locally aggressive pituitary tumors (LAPT) and pituitary carcinomas respond poorly to conventional therapy and cytotoxic drugs. Temozolomide (TMZ) is an oral alkylating drug with good tolerability, approved for treatment of malignant gliomas. The experience of its use in pituitary tumors is limited. Design and Setting: We report on 24 patients with aggressive pituitary tumors (16 LAPTs, 8 carcinomas) treated with TMZ for a median of 6 months (range 1-23). Follow-up ranged from 4 to 91 months with a median of 32.5 months. 19/24 tumors were hormone secreting (PRL 9, ACTH 4, GH 4, GH/PRL 2). Ki-67 was 2-50% in LAPTs, and 5-80% in carcinomas. Main Outcome: Response to TMZ and the association with tumor expression of O6-methylguanine DNA methyltransferase (MGMT), MLH1, MSH2, and MSH6, examined by immunohistochemistry. Results: Complete tumor regression occurred in two carcinomas and persisted at follow-up after 48 and 91 months, respectively. Partial regress of tumor mass ranging from 35% to 80% occurred in 5 LAPTs and 2 carcinomas. Another patient with LAPT had a 71% decrease in prolactin levels without change in tumor volume. Three LAPTs could not be evaluated. Median MGMT staining was 9% (5-20%) in responders vs 93% (50-100%) in nonresponders. Loss of MSH2 and MSH 6 was observed in a single patient who had a rapid development of resistance to TMZ. Conclusions: This study shows that TMZ is a valuable treatment option for patients with uncontrolled pituitary tumors. The data suggest that tumoral MGMT staining below 50% is associated with a high likelihood of treatment response.
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21.
  • Bergthorsdottir, Ragnhildur, 1971, et al. (författare)
  • Increased risk of hospitalization, intensive care and death due to covid-19 in patients with adrenal insufficiency : a Swedish nationwide study
  • 2024
  • Ingår i: Journal of Internal Medicine. - : John Wiley & Sons. - 0954-6820 .- 1365-2796. ; 295:3, s. 322-330
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown.Methods: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis.Results: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59–2.43), intensive care admission (2.76, 1.49–5.09) and death (2.29, 1.60–3.28).Conclusion: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.
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22.
  • Bergthorsdottir, Ragnhildur, 1971, et al. (författare)
  • Premature mortality in patients with Addison's disease: a population-based study.
  • 2006
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 91:12, s. 4849-53
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The survival rate of patients with primary adrenal insufficiency (Addison's disease) undergoing currently accepted replacement therapy is not known, although well-informed patients are considered to have a normal survival rate. In this study, we evaluated the mortality of patients with Addison's disease in Sweden. METHODS: A population-based, retrospective, observational study was performed, using the National Swedish Hospital and Cause of Death Registers, covering the period from 1987-2001. After a diagnosis of Addison's disease, each patient was followed until the end of follow-up or death. Mortality was compared with that of the Swedish background population. FINDINGS: We identified 1675 patients (995 women and 680 men) diagnosed with primary adrenal insufficiency. The average follow-up from initial diagnosis was 6.5 yr. Five hundred seven patients died during the study period compared with an expected 199. The risk ratio for all-cause mortality was 2.19 (confidence interval 1.91-2.51) for men and 2.86 (confidence interval 2.54-3.20) for women. The excess mortality in both men and women was attributed to cardiovascular, malignant, and infectious diseases. Concomitant diabetes mellitus was observed in 12% of the patients, but only contributed to the increased mortality to a minor extent. INTERPRETATION: Compared with the background population, we observed that the risk ratio for death was more than 2-fold higher in patients with Addison's disease. Cardiovascular, malignant, and infectious diseases were responsible for the higher mortality rate.
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23.
  • Bergthorsdottir, Ragnhildur, 1971, et al. (författare)
  • Visceral Fat and Novel Biomarkers of Cardiovascular Disease in Patients With Addison's Disease: A Case-Control Study
  • 2017
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:11, s. 4264-4272
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with Addison's disease (AD) have increased cardiovascular mortality. Objective: To study visceral fat and conventional and exploratory cardiovascular risk factors in patients with AD. Subjects: Patients (n = 76; n = 51 women) with AD and 76 healthy control subjects were matched for sex, age, body mass index (BMI), and smoking habits. Main outcome measures: The primary outcome variable was visceral abdominal adipose tissue (VAT) measured using computed tomography. Secondary outcome variables were prevalence of metabolic syndrome (MetS) and 92 biomarkers of cardiovascular disease. Results: The mean 6 standard deviation age of all subjects was 53 6 14 years; mean BMI, 25 6 4 kg/ m2; and mean duration of AD, 17 6 12 years. The median (range) daily hydrocortisone dose was 30 mg (10 to 50 mg). Median (interquartile range) 24-hour urinary free cortisol excretion was increased in patients vs controls [359 nmol (193 to 601 nmol) vs 175 nmol (140 to 244 nmol); P, 0.001]. VAT did not differ between groups. After correction for multiple testing, 17 of the 92 studied biomarkers differed significantly between patients and control subjects. Inflammatory, proinflammatory, and proatherogenic risk biomarkers were increased in patients [fold change (FC),.1] and vasodilatory protective marker was decreased (FC, < 1). Twenty-six patients (34%) vs 12 control subjects (16%) fulfilled the criteria for MetS (P = 0.01). Conclusion: Despite higher cortisol exposure, VAT was not increased in patients with AD. The prevalence of MetS was increased and several biomarkers of cardiovascular disease were adversely affected in patients with AD.
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24.
  • Berryman, Darlene E, et al. (författare)
  • Role of the GH/IGF-1 axis in lifespan and healthspan: Lessons from animal models.
  • 2008
  • Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1096-6374. ; 18:6, s. 455-71
  • Tidskriftsartikel (refereegranskat)abstract
    • Animal models are fundamentally important in our quest to understand the genetic, epigenetic, and environmental factors that contribute to human aging. In comparison to humans, relatively short-lived mammals are useful models as they allow for rapid assessment of both genetic manipulation and environmental intervention as related to longevity. These models also allow for the study of clinically relevant pathologies as a function of aging. Data associated with more distant species offers additional insight and critical consideration of the basic physiological processes and molecular mechanisms that influence lifespan. Consistently, two interventions, caloric restriction and repression of the growth hormone (GH)/insulin-like growth factor-1/insulin axis, have been shown to increase lifespan in both invertebrates and vertebrate animal model systems. Caloric restriction (CR) is a nutrition intervention that robustly extends lifespan whether it is started early or later in life. Likewise, genes involved in the GH/IGF-1 signaling pathways can lengthen lifespan in vertebrates and invertebrates, implying evolutionary conservation of the molecular mechanisms. Specifically, insulin and insulin-like growth factor-1 (IGF-1)-like signaling and its downstream intracellular signaling molecules have been shown to be associated with lifespan in fruit flies and nematodes. More recently, mammalian models with reduced growth hormone (GH) and/or IGF-1 signaling have also been shown to have extended lifespans as compared to control siblings. Importantly, this research has also shown that these genetic alterations can keep the animals healthy and disease-free for longer periods and can alleviate specific age-related pathologies similar to what is observed for CR individuals. Thus, these mutations may not only extend lifespan but may also improve healthspan, the general health and quality of life of an organism as it ages. In this review, we will provide an overview of how the manipulation of the GH/IGF axis influences lifespan, highlight the invertebrate and vertebrate animal models with altered lifespan due to modifications to the GH/IGF-1 signaling cascade or homologous pathways, and discuss the basic phenotypic characteristics and healthspan of these models.
  •  
25.
  • Berryman, Darlene E, et al. (författare)
  • The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations.
  • 2013
  • Ingår i: Nature reviews. Endocrinology. - : Springer Science and Business Media LLC. - 1759-5037 .- 1759-5029. ; 9:6, s. 346-56
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.
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26.
  • Birzniece, Vita, et al. (författare)
  • Modulatory effect of raloxifene and estrogen on the metabolic action of growth hormone in hypopituitary women.
  • 2010
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 95:5, s. 2099-106
  • Tidskriftsartikel (refereegranskat)abstract
    • The metabolic action of GH is attenuated by estrogens administered via the oral route. Selective estrogen receptor modulators lower IGF-I to a lesser degree than 17beta-estradiol in GH-deficient women, and their effect on fat and protein metabolism is unknown.
  •  
27.
  • Boguszewski, C L, et al. (författare)
  • 22-kD growth hormone exclusion assay: a new approach to measurement of non-22-kD growth hormone isoforms in human blood.
  • 1996
  • Ingår i: European journal of endocrinology. - 0804-4643. ; 135:5, s. 573-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Human growth hormone (GH) exists in a variety of isoforms. In the pituitary, the most abundant isoform is 22-kD GH (22 K GH), while other isoforms (non-22 K GH) are present in variable amounts. In human plasma, the GH heterogeneity contributes to the wide variability in GH levels measured by different immunoassays. The physiological role of the non-22 K GH isoforms is poorly understood, but they may represent a spectrum of agonists or antagonists of the GH receptor. It is possible that increased amounts of non-22 K GH isoforms in the circulation contribute to the growth failure observed in some short children and may be involved in the pathophysiology of acromegaly and other unrelated diseases. Currently, there is no method available to evaluate the ratio of non-22 K GH isoforms to total GH in large sets of serum samples. In this report, a novel assay procedure is described in which monomeric and dimeric isoforms of 22 K GH are removed from serum and non-22 K GH isoforms are quantitated. The 22 K GH exclusion assay (22 K GHEA) was established as a screening method to identify conditions in which the ratio of non-22 K GH isoforms to total GH in human blood is altered. A 22 K GH-specific monoclonal antibody (MCB) is used for binding to 22 K GH in serum. Magnetic beads coated with rat anti-mouse immunoglobulin G and a magnetic device are used to remove the 22K GH-MCB complexes from serum. The non-22 K GH isoforms are measured by a polyclonal antibody-based immunoradiometric assay (GH-IRMA). The assay procedure was optimized systematically by statistical experimental designs. In serum spiked with monomeric or dimeric 22 K GH, the 22 K GH extraction was efficient at GH levels up to 100 microg/l (range 96.3-100%). The intra- and interassay precision for non-22K GH levels of 3.9 microg/l were 2.6% and 8.7%, respectively, while for levels of 0.6 microg/l, which were very close to the detection limits of the assay, the coefficients were 17.0% and 21.6%, respectively. The percentage of non-22 K GH isoforms determined in serum samples from three different groups of subjects showed clearly distinctive values. The 22 K GHEA is a new method for evaluation of non-22 K GH isoforms in human blood under different physiological and pathophysiological conditions.
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28.
  • Boguszewski, C L, et al. (författare)
  • Circulating non-22-kilodalton growth hormone isoforms in acromegalic men before and after transsphenoidal surgery.
  • 1997
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 82:5, s. 1516-21
  • Tidskriftsartikel (refereegranskat)abstract
    • GH represents several molecular isoforms in addition to the main 22-kDa (22K) GH. There have been reports suggesting that circulating non-22K GH isoforms are increased in acromegaly, but the possible implications of such observations in the management of the disease have not been addressed. The aim of this study was to evaluate the proportion of circulating non-22K GH isoforms in acromegaly. In addition, the relationships between the amount of non-22K GH and tumor size, biochemical measurements, and body composition also were investigated. Samples with different GH levels were selected from 24-h GH profiles from 15 acromegalic men evaluated before and 1 yr after transsphenoidal surgery and from 13 healthy men. The serum non-22K GH levels, expressed as percentage of total GH concentration, were determined by the 22K GH exclusion assay, which is based on immunomagnetic extraction of 22K GH from serum and quantitation of non-22K GH using a polyclonal GH assay. The proportion of non-22K GH isoforms was fairly constant in different samples from the same patient, regardless of the GH level. However, a wide variation of values was observed among acromegalics, both before (14-51%) and after surgery (8-62%). The proportion of non-22K GH isoforms was increased in untreated patients, compared with controls (26.6 vs. 17.4%; P < 0.01), and the values correlated significantly to tumor size, mean 24-h GH concentration, serum PRL, and extracellular water. After surgery, patients not truly cured, with mean 24-h GH concentration of 1 microg/L or more, had an increased proportion of non-22K GH, compared with those with levels less than 1 microg/L (P < 0.01). In the former group, the median values were similar than those in untreated acromegalics (34 vs. 26.6%, respectively), whereas in the latter, they were comparable with those in the controls (15.2 vs. 17.4%, respectively). We conclude that acromegalics have an increased proportion of circulating non-22K GH isoforms. The values are fairly constant in different samples from an individual, regardless of GH level, but a large spectrum can be observed among patients. This variability suggests that different pituitary adenomas secrete GH isoforms in variable amounts. Our observation that a higher proportion of non-22K GH isoforms is present in patients not truly cured after surgery suggests that the evaluation of non-22K GH isoforms can be useful in the follow-up of acromegalic patients.
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29.
  • Boguszewski, C. L., et al. (författare)
  • Mechanisms in endocrinology: Clinical and pharmacogenetic aspects of the growth hormone receptor polymorphism
  • 2017
  • Ingår i: European Journal of Endocrinology. - 0804-4643. ; 177:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Pharmacogenetics aims to maximize the beneficial effects of a medical therapy by identifying genetic finger prints from responders and non-responders and, thereby improving safety and efficacy profile of the drug. Most subjects who are deficient in growth hormone (GHD) are candidates for recombinant human GH (rhGH) therapy. To date, it is well established that even after adjustments for several clinical variables, such as age, gender, body composition and the age at onset of the GHD, response to rhGH treatment is highly variable among individuals, part of which is believed to be due to genetic factors within the GH system. As the first genetic variant to potentially influence the individual response to rhGH therapy in children with growth disorders, polymorphism in the GH receptor (GHR) has attracted a great interest as a target for pharmacogenetics. Studies have been conducted to compare the functional and molecular effects of the full-length GHR (fl-GHR) isoform with the exon 3 deleted (d3-GHR) isoform in children and adults treated with rhGH therapy. Additionally, the impact of the GHR polymorphism has been investigated in relation to the clinical status and response to medical treatment in acromegaly, especially to the GHR antagonist drug pegvisomant. We have performed a narrative review of the studies performed to date on the association of GHR polymorphism with rhGH response in children and adults, and its potential influence in the medical management of acromegaly. In addition, data from studies on the general population and in other chronic diseases examining a role of this genetic variant in the regulation of growth and metabolism are summarized. © 2017 European Society of Endocrinology.
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30.
  • Boguszewski, Margaret C S, 1964, et al. (författare)
  • Low birth size and final height predict high sympathetic nerve activity in adulthood.
  • 2004
  • Ingår i: Journal of hypertension. - 0263-6352. ; 22:6, s. 1157-63
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Being born small for gestational age (SGA) is associated with insulin resistance, hypertension and increased cardiovascular morbidity/mortality in adulthood. Sympathetic nerve hyperactivity is a well-known risk factor for cardiovascular disease mortality and is proposed to link insulin resistance with hypertension. The objective of this study was to test the hypothesis that sympathetic nerve activity is altered in individuals born SGA. DESIGN: A cross-sectional, comparative study of 20 healthy adults (21-25 years old) born SGA (birth weight < -2SD score for healthy newborns) with normal and short stature, and 12 age, gender and body mass index matched individuals, born appropriate for gestational age (AGA) with normal stature. METHODS: Direct recordings of resting sympathetic nerve activity to the muscle vascular bed (MSA) were obtained from the peroneal nerve posterior to the fibular head. Heart rate, respiration and blood pressure were recorded during the microneurographic session. RESULTS: MSA was increased in both groups of young adults born SGA as compared to those born AGA (P < 0.05 and P < 0.005, respectively). In the combined study group MSA was inversely correlated to birth weight, length (r = -0.59, P < 0.001 and r = -0.69, P < 0.0005, respectively) and final adult height (r = -0.58; P < 0.001). CONCLUSIONS: Being born SGA and achieving a short final height is associated with increased sympathetic nerve traffic. We suggest that the increase in sympathetic nerve traffic in young adults born SGA with normal and short stature may be the link between low birth size, hypertension and cardiovascular morbidity later in life.
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31.
  • Boguszewski, M. C. S., et al. (författare)
  • Safety of growth hormone (GH) treatment in GH deficient children and adults treated for cancer and non-malignant intracranial tumors-a review of research and clinical practice
  • 2021
  • Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 24:5, s. 810-827
  • Tidskriftsartikel (refereegranskat)abstract
    • Individuals surviving cancer and brain tumors may experience growth hormone (GH) deficiency as a result of tumor growth, surgical resection and/or radiotherapy involving the hypothalamic-pituitary region. Given the pro-mitogenic and anti-apoptotic properties of GH and insulin-like growth factor-I, the safety of GH replacement in this population has raised hypothetical safety concerns that have been debated for decades. Data from multicenter studies with extended follow-up have generally not found significant associations between GH replacement and cancer recurrence or mortality from cancer among childhood cancer survivors. Potential associations with secondary neoplasms, especially solid tumors, have been reported, although this risk appears to decline with longer follow-up. Data from survivors of pediatric or adult cancers who are treated with GH during adulthood are scarce, and the risk versus benefit profile of GH replacement of this population remains unclear. Studies pertaining to the safety of GH replacement in individuals treated for nonmalignant brain tumors, including craniopharyngioma and non-functioning pituitary adenoma, have generally been reassuring with regards to the risk of tumor recurrence. The present review offers a summary of the most current medical literature regarding GH treatment of patients who have survived cancer and brain tumors, with the emphasis on areas where active research is required and where consensus on clinical practice is lacking.
  •  
32.
  • Boguszewski, M. C. S., et al. (författare)
  • Safety of growth hormone replacement in survivors of cancer and intracranial and pituitary tumours: a consensus statement
  • 2022
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 186:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.
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33.
  • Bosaeus, Ingvar, 1950, et al. (författare)
  • Comparison of methods to estimate body fat in growth hormone deficient adults.
  • 1996
  • Ingår i: Clinical endocrinology. - 0300-0664. ; 44:4, s. 395-402
  • Tidskriftsartikel (refereegranskat)abstract
    • All of the presently used methods for in-vivo determination of body composition have inherent methodological errors and depend on various assumptions. We have therefore compared several different methods used to measure body fat in adult GH deficiency during GH treatment.Comparison of body composition data from a two-phase trial with an initial placebo-controlled, double-blind 6-month period, followed by open treatment with GH until all patients had received GH for 12 months.Twenty-five patients with known GH deficiency entered the study. Baseline examinations were complete in 23 patients, and 22 patients (16 males, 6 females) completed all examinations after treatment.Body fat calculated from total body potassium (TBK) by whole-body 40K counting, total body water (TBW) by tritium dilution, total body nitrogen (TBN) by neutron activation, and bioelectric impedance (BIA) measurements were compared to body fat determinations by dual-energy X-ray absorptiometry (DEXA) in two-compartment and multicompartment body composition models.At baseline, DEXA fat mass agreed well at group level with measurements based on TBW or TBK alone, in a four-compartment model based on TBK and TBW, and a multicompartment model based on bone mineral (by DEXA), TBN and TBW. Body fat by BIA agreed less well. After 12 months of GH treatment, body fat decreased by all methods used. This decrease was smaller by DEXA than by the other methods. The four-compartment model based on TBK and TBW, and TBW alone, showed the best agreement with changes in DEXA fat.All methods showed a decrease of body fat with GH treatment, but variation between methods was considerable.
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34.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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35.
  •  
36.
  • Buendia, Ruben, 1982, et al. (författare)
  • Estimation of body fluids with bioimpedance spectroscopy: state of the art methods and proposal of novel methods
  • 2015
  • Ingår i: Physiological Measurement. - : IOP Publishing. - 0967-3334 .- 1361-6579. ; 36:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Determination of body fluids is a useful common practice in determination of disease mechanisms and treatments. Bioimpedance spectroscopy (BIS) methods are non-invasive, inexpensive and rapid alternatives to reference methods such as tracer dilution. However, they are indirect and their robustness and validity are unclear. In this article, state of the art methods are reviewed, their drawbacks identified and new methods are proposed. All methods were tested on a clinical database of patients receiving growth hormone replacement therapy. Results indicated that most BIS methods are similarly accurate (e.g. < 0.5 +/- 3.0% mean percentage difference for total body water) for estimation of body fluids. A new model for calculation is proposed that performs equally well for all fluid compartments (total body water, extra-and intracellular water). It is suggested that the main source of error in extracellular water estimation is due to anisotropy, in total body water estimation to the uncertainty associated with intracellular resistivity and in determination of intracellular water a combination of both.
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37.
  • Buendia, Rubén, et al. (författare)
  • Robustness study of the different immittance spectra and frequency ranges in bioimpedance spectroscopy analysis for assessment of total body composition.
  • 2014
  • Ingår i: Physiological measurement. - : IOP Publishing. - 1361-6579 .- 0967-3334. ; 35:7, s. 1373-95
  • Tidskriftsartikel (refereegranskat)abstract
    • The estimation of body fluids is a useful and common practice for assessment of disease status and therapy outcomes. Electrical bioimpedance spectroscopy (EBIS) methods are noninvasive, inexpensive and efficient alternatives for determination of body fluids. One of the main source of errors in EBIS measurements in the estimation of body fluids is capacitive coupling. In this paper an analysis of capacitive coupling in EBIS measurements was performed and the robustness of the different immittance spectra against it tested. On simulations the conductance (G) spectrum presented the smallest overall error, among all immittance spectra, in the estimation of the impedance parameters used to estimate body fluids. Afterwards the frequency range of 10-500kHz showed to be the most robust band of the G spectrum. The accuracy of body fluid estimations from the resulting parameters that utilized G spectrum and parameters provided by the measuring device were tested on EBIS clinical measurements from growth hormone replacement therapy patients against estimations performed with dilution methods. Regarding extracellular fluid, the correlation between each EBIS method and dilution was 0.93 with limits of agreement of 1.06 ± 2.95 l for the device, 1.10 ± 2.94 l for G [10-500kHz] and 1.04 ± 2.94 l for G [5-1000kHz]. Regarding intracellular fluid, the correlation between dilution and the device was 0.91, same as for G [10-500kHz] and 0.92 for G [5-1000kHz]. Limits of agreement were 0.12 ± 4.46 l for the device, 0.09 ± 4.45 for G [10-500kHz] and 0.04 ± 4.58 for G [5-1000kHz]. Such close results between the EBIS methods validate the proposed approach of using G spectrum for initial Cole characterization and posterior clinical estimation of body fluids status.
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38.
  • Burman, Pia, et al. (författare)
  • Deaths Among Adult Patients With Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo Malignant Brain Tumors Contribute to an Increased Mortality
  • 2013
  • Ingår i: Journal of Clinical Endocrinology & Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 98:4, s. 1466-1475
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Patients with hypopituitarism have an increased standardized mortality rate. The basis for Objective: To investigate in detail the cause of death in a large cohort of patients with hypopituitarism Design and Methods: All-cause and cause-specific mortality in 1286 Swedish patients with Main Outcome Measures: Standardized mortality ratios (SMR) were calculated, with stratification for Results: An excess mortality was found, 120 deaths vs 84.3 expected, SMR 1.42 (95% confidence Conclusion: Two important causes of excess mortality were identified: first, adrenal crisis in response
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39.
  • Burt, Morton G, et al. (författare)
  • Impact of acute and chronic low-dose glucocorticoids on protein metabolism.
  • 2007
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:10, s. 3923-9
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: High-dose glucocorticoids cause acute protein loss by increasing protein breakdown and oxidation. Whether lower glucocorticoid doses, typical of therapeutic use, induce sustained catabolism has not been studied. OBJECTIVE: Our objective was to assess the effect of acute and chronic therapeutic glucocorticoid doses on protein metabolism. DESIGN AND SETTING: We conducted an open longitudinal and a cross-sectional study at a clinical research facility. PATIENTS AND INTERVENTION: Ten healthy subjects were studied before and after a short course of prednisolone (5 and 10 mg/d sequentially for 7 d each). Twelve subjects with inactive polymyalgia rheumatica receiving chronic (>12 months) prednisone (mean = 5.0 +/- 0.8 mg/d) were compared with 12 age- and gender-matched normal subjects. MAIN OUTCOME MEASURE: Whole-body protein metabolism was assessed using a 3-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation (Lox, index of protein oxidation) and leucine incorporation into protein (LIP, index of protein synthesis) were estimated. RESULTS: Prednisolone induced an acute significant increase in Lox (P = 0.008) and a fall in LIP (P = 0.08) but did not affect leucine Ra. There was no significant difference between the effects of the 5- and 10-mg prednisolone doses on leucine metabolism. In subjects receiving chronic prednisone therapy, leucine Ra, Lox, and LIP were not significantly different from normal subjects. CONCLUSION: Glucocorticoids stimulate protein oxidation after acute but not chronic administration. This time-related change suggests that glucocorticoid-induced stimulation of protein oxidation does not persist but that a metabolic adaptation occurs to limit protein loss.
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40.
  • Burt, Morton G, et al. (författare)
  • Impact of growth hormone and dehydroepiandrosterone on protein metabolism in glucocorticoid-treated patients.
  • 2008
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 93:3, s. 688-95
  • Tidskriftsartikel (refereegranskat)abstract
    • CONTEXT: Chronic pharmacological glucocorticoid (GC) use causes substantial morbidity from protein wasting. GH and androgens are anabolic agents that may potentially reverse GC-induced protein loss. OBJECTIVE: Our objective was to assess the effect of GH and dehydroepiandrosterone (DHEA) on protein metabolism in subjects on long-term GC therapy. DESIGN: This was an open, stepwise GH dose-finding study (study 1), followed by a randomized cross-over intervention study (study 2). SETTING: The studies were performed at a clinical research facility. PATIENTS AND INTERVENTION: In study 1, six subjects (age 69+/-4 yr) treated with long-term (>6 months) GCs (prednisone dose 8.3+/-0.8 mg/d) were studied before and after two sequential GH doses (0.8 and 1.6 mg/d) for 2 wk each. In study 2, 10 women (age 71+/-3 yr) treated with long-term GCs (prednisone dose 5.4+/-0.5 mg/d) were studied at baseline and after 2-wk treatment with GH 0.8 mg/d, DHEA 50 mg/d, or GH and DHEA (combination treatment). MAIN OUTCOME MEASURE: Changes in whole body protein metabolism were assessed using a 3-h primed constant infusion of 1-[13C]leucine, from which rates of leucine appearance, leucine oxidation, and leucine incorporation into protein were estimated. RESULTS: In study 1, GH 0.8 and 1.6 mg/d significantly reduced leucine oxidation by 19% (P=0.03) and 31% (P=0.02), and increased leucine incorporation into protein by 10% (P=0.13) and 19% (P=0.04), respectively. The lower GH dose did not cause hyperglycemia, whereas GH 1.6 mg/d resulted in fasting hyperglycemia in two of six subjects. In study 2, DHEA did not significantly change leucine metabolism alone or when combined with GH. Blood glucose was not affected by DHEA. CONCLUSION: GH, at a modest supraphysiological dose of 0.8 mg/d, induces protein anabolism in chronic GC users without causing diabetes. DHEA 50 mg/d does not enhance the effect of GH. GH may safely prevent or reverse protein loss induced by chronic GC therapy.
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41.
  • Bärebring, Linnea, et al. (författare)
  • Serum cortisol and vitamin D status are independently associated with blood pressure in pregnancy
  • 2019
  • Ingår i: Journal of Steroid Biochemistry and Molecular Biology. - : Elsevier BV. - 0960-0760. ; 189:May, s. 259-264
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim was to study if serum cortisol during pregnancy was associated with blood pressure and development of gestational hypertensive disorders. Additionally, associations between 25-hydroxyvitamin D (25OHD) and cortisol, including confounding effects and interactions in their relation to blood pressure were investigated. In total, 1413 pregnant women from the prospective Swedish GraviD cohort were included. Serum was collected in the first (T1) and third trimester (T3) and analyzed for 25OHD by liquid chromatography mass spectrometry and cortisol using an electro-chemiluminescence immunoassay. The main outcome measures were T1 blood pressure and development of gestational hypertensive disorders (gestational hypertension or preeclampsia). Gestational hypertensive disorders were defined as new onset hypertension, with or without proteinuria, after gestational week 20. Mean ± SD cortisol increased significantly from T1 to T3 (312 ± 123 vs. 659 ± 201 nmol/L, p < 0.001) and this increase was influenced by ethnicity. Serum concentrations of cortisol and 25OHD correlated in both T1 (B = 0.35, p < 0.001) and T3 (B = 0.30, p < 0.001). Cortisol and 25OHD were positively associated with T1 blood pressure, and there were non-significant trends for associations with gestational hypertensive disorders. Cortisol and 25OHD did not display any confounding effect or effect modification in their relationships with blood pressure. In conclusion, there was a positive correlation between serum cortisol and 25OHD in both early and late pregnancy. Both cortisol and 25OHD were positively associated with early pregnancy blood pressure. These results imply that the two hormones might be on different paths in their relationship with blood pressure. © 2019
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42.
  • Casanueva, Felipe F., et al. (författare)
  • Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement
  • 2017
  • Ingår i: Pituitary. - : Springer Science and Business Media LLC. - 1386-341X .- 1573-7403. ; 20, s. 489-498
  • Forskningsöversikt (refereegranskat)abstract
    • © 2017, The Author(s). Introduction: With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods: To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results: After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions: Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country.
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43.
  • Chantzichristos, Dimitrios, 1976, et al. (författare)
  • Early Clinical Indicators of Addison’s Disease in Adults with Type 1 Diabetes: a Nationwide, Observational, Cohort Study
  • 2019
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 104:4, s. 1148-1157
  • Tidskriftsartikel (refereegranskat)abstract
    • Context Patients with type 1 diabetes mellitus (T1DM) have an increased risk of Addison disease (AD) development, but prediction of those at risk is not possible. Objective To determine whether there are early clinical indicators that may denote the development of AD in adults with T1DM. Design Observational, matched-cohort study. Setting Patient data from Swedish national registries [National Diabetes Register (NDR), Inpatient Register, and Prescription Drug Register]. Participants All patients with T1DM diagnosed with concomitant AD (n = 66) among the 36,514 adult patients with T1DM in the NDR between 1998 and 2013. Each case was matched to five controls with T1DM alone (n = 330). Main Outcome Measures Clinical data and drug prescriptions were assessed prior to baseline (inclusion into the study) and prior to AD diagnosis. Analysis of covariance and estimated group proportions were used for comparisons. Results Prior to baseline, cases had a higher frequency of thyroid/antithyroid drug prescription than controls (9.1% vs 1.8%). Prior to AD diagnosis, cases had higher frequencies of diabetic retinopathy (12.1% vs 2.1%), infections requiring hospital admission (16.7% vs 2.1%), thyroid/antithyroid drug prescription (28.8% vs 7.0%), and glucagon prescription (18.2% vs 6.4%). There was no difference in glycated Hb between the groups prior to baseline or prior to AD diagnosis. Conclusions These data suggest that medical treatment of thyroid disease, a severe infection, and glucagon prescription for severe hypoglycemia should raise the suspicion of AD development in adults with T1DM. Development of diabetic retinopathy might also be associated with glucocorticoid deficiency and the development of AD among patients with T1DM.
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44.
  • Chantzichristos, Dimitrios, 1976, et al. (författare)
  • Identification of human glucocorticoid response markers using integrated multi-omic analysis from a randomized crossover trial.
  • 2021
  • Ingår i: eLife. - 2050-084X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucocorticoids are among the most commonly prescribed drugs, but there is no biomarker that can quantify their action. The aim of the study was to identify and validate circulating biomarkers of glucocorticoid action.In a randomized, crossover, single-blind, discovery study, 10 subjects with primary adrenal insufficiency (and no other endocrinopathies) were admitted at the in-patient clinic and studied during physiological glucocorticoid exposure and withdrawal. A randomization plan before the first intervention was used. Besides mild physical and/or mental fatigue and salt craving, no serious adverse events were observed. The transcriptome in peripheral blood mononuclear cells and adipose tissue, plasma miRNAomic, and serum metabolomics were compared between the interventions using integrated multi-omic analysis.We identified a transcriptomic profile derived from two tissues and a multi-omic cluster, both predictive of glucocorticoid exposure. A microRNA (miR-122-5p) that was correlated with genes and metabolites regulated by glucocorticoid exposure was identified (p=0.009) and replicated in independent studies with varying glucocorticoid exposure (0.01 ≤ p≤0.05).We have generated results that construct the basis for successful discovery of biomarker(s) to measure effects of glucocorticoids, allowing strategies to individualize and optimize glucocorticoid therapy, and shedding light on disease etiology related to unphysiological glucocorticoid exposure, such as in cardiovascular disease and obesity.The Swedish Research Council (Grant 2015-02561 and 2019-01112); The Swedish federal government under the LUA/ALF agreement (Grant ALFGBG-719531); The Swedish Endocrinology Association; The Gothenburg Medical Society; Wellcome Trust; The Medical Research Council, UK; The Chief Scientist Office, UK; The Eva Madura's Foundation; The Research Foundation of Copenhagen University Hospital; and The Danish Rheumatism Association.NCT02152553.
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45.
  • Chantzichristos, Dimitrios, 1976, et al. (författare)
  • Incidence, prevalence and seasonal onset variation of Addison's disease among persons with type 1 diabetes mellitus: nationwide, matched cohort studies.
  • 2018
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 178:1, s. 115-122
  • Tidskriftsartikel (refereegranskat)abstract
    • We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies.Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model.Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years (P value=0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5).The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern.
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46.
  • Chantzichristos, Dimitrios, 1976, et al. (författare)
  • MANAGEMENT OF ENDOCRINE DISEASE: Disease burden and treatment challenges in patients with both Addison's disease and type 1 diabetes mellitus.
  • 2020
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 183:1
  • Forskningsöversikt (refereegranskat)abstract
    • Concurrent type 1 diabetes (T1D) and Addison's disease (AD) is a rare combination of diseases and, in approximately one third of these patients, it is also combined with an autoimmune thyroid disease. Recently, it was shown that patients with both T1D and AD have a higher risk of premature death compared to patients with T1D alone, the most common causes of death being due to diabetic complications and cardiovascular disease. These patients receiving replacement therapies with both insulin and glucocorticoids face an increased risk of hypo- and hyperglycemia, and diabetic ketoacidosis, and have a higher risk of adrenal crisis than patients with AD alone. Treatment challenges include the opposing effects of insulin and glucocorticoids on glucose homeostasis, and the need to balance and synchronize these two treatments. The rarity of this disease combination may explain the paucity of data on outcome and specific treatment strategies in this patient group. Based on this review, we suggest management strategies for their insulin and glucocorticoid replacement therapies and indicate future areas of research.
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47.
  • Chantzichristos, Dimitrios, 1976, et al. (författare)
  • Mortality in patients with diabetes mellitus and Addison's disease: a nationwide, matched, observational cohort study.
  • 2017
  • Ingår i: European journal of endocrinology. - 1479-683X. ; 176:1, s. 31-39
  • Tidskriftsartikel (refereegranskat)abstract
    • Our hypothesis was that patients with diabetes mellitus obtain an additional risk of death if they develop Addison's disease (AD).Nationwide, matched, observational cohort study cross-referencing the Swedish National Diabetes Register with Inpatient, Cancer and Cause of Death Registers in patients with diabetes (type 1 and 2) and AD and matched controls with diabetes. Clinical characteristics at baseline, overall, and cause-specific mortality were assessed. The relative risk of death was assessed using a Cox proportional hazards regression model.Between January 1996 and December 2012, 226 patients with diabetes and AD were identified and matched with 1129 controls with diabetes. Median (interquartile range) follow-up was 5.9 (2.7-8.6) years. When patients with diabetes were diagnosed with AD, they had an increased frequency of diabetes complications, but both medical history of cancer and coronary heart disease did not differ compared with controls. Sixty-four of the 226 patients with diabetes and AD (28%) died, while 112 of the 1129 controls (10%) died. The estimated relative risk increase (hazard ratio) in overall mortality in the diabetes and AD group was 3.89 (95% confidence interval 2.84-5.32) compared with controls with diabetes. The most common cause of death was cardiovascular in both groups, but patients with diabetes and AD showed an increased death rate from diabetes complications, infectious diseases and unknown causes.Patients with the rare combination of diabetes and AD showed a markedly increased mortality and died more frequently from infections and unknown causes than patients with diabetes alone. Improved strategy for the management of this combination of metabolic disorders is needed.
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48.
  • Chen, S. C., et al. (författare)
  • Development of A Minimum Dataset for the Monitoring of Recombinant Human Growth Hormone (rhGH) Therapy Use in Children with Growth Hormone Deficiency (GHD) - A GloBE-Reg Initiative
  • 2023
  • Ingår i: Hormone Research in Paediatrics. - 1663-2818 .- 1663-2826.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction Although there are some recommendations in the literature on the assessments that should be performed in children on recombinant human growth hormone (rhGH) therapy, the level of consensus on these measurements is not clear. The objective of the current study was to identify the minimum dataset (MDS) that could be measured in a routine clinical setting across the world, aiming to minimise burden on clinicians and improve quality of data collection. Methods This study was undertaken by the GH Scientific Study Group (SSG) in GloBE-Reg, a new project that has developed a common registry platform that can support long-term safety and effectiveness studies of drugs. Twelve clinical experts from 7 international endocrine organisations identified by the GloBE-Reg Steering Committee, 2 patient representatives and representatives from 2 pharmaceutical companies with previous GH registry expertise collaborated to develop this recommendation. A comprehensive list of data fields routinely collected by each of the clinical and industry experts for children with GHD was compiled. Each member was asked to determine the: (1) Importance of the data field and (2) Ease of data collection. Data fields that achieved 70% consensus in terms of importance qualified for the MDS, provided <50% deemed the item difficult to collect.Results A total of 246 items were compiled and 27 removed due to redundancies, with 219 items subjected to the grading system. Of the 219 items, 111 achieved at least 70% consensus as important data to collect when monitoring children with GH deficiency (GHD) on rhGH treatment. Sixty-nine of the 219 items were deemed easy to collect. Combining the criteria of importance and ease of data collection, 63 met the criteria for the MDS. Several anomalies to the MDS rule were identified and highlighted for discussion, including whether the patients were involved in current or previous clinical trials, need for HbA1c monitoring, other past medical history, and adherence, enabling formulation of the final MDS recommendation of 43 items; 20 to be completed once, 14 every 6 months and 9 every 12 months.Conclusion In summary, this exercise performed through the GloBE-Reg initiative provides a recommendation of the minimum dataset requirement, collected through real-world data, for the monitoring of safety and effectiveness of rhGH in children with GHD, both for the current daily preparations and the newer long-acting growth hormone.
  •  
49.
  • Christiansen, J. S., et al. (författare)
  • Growth Hormone Research Society perspective on the development of long-acting growth hormone preparations
  • 2016
  • Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 174:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: The Growth Hormone (GH) Research Society (GRS) convened a workshop to address important issues regarding trial design, efficacy, and safety of long-acting growth hormone preparations (LAGH). Participants: A closed meeting of 55 international scientists with expertise in GH, including pediatric and adult endocrinologists, basic scientists, regulatory scientists, and participants from the pharmaceutical industry. Evidence: Current literature was reviewed for gaps in knowledge. Expert opinion was used to suggest studies required to address potential safety and efficacy issues. Consensus process: Following plenary presentations summarizing the literature, breakout groups discussed questions framed by the planning committee. Attendees reconvened after each breakout session to share group reports. A writing team compiled the breakout session reports into a draft document that was discussed and revised in an open forum on the concluding day. This was edited further and then circulated to attendees from academic institutions for review after the meeting. Participants from pharmaceutical companies did not participate in the planning, writing, or in the discussions and text revision on the final day of the workshop. Scientists from industry and regulatory agencies reviewed the manuscript to identify any factual errors. Conclusions: LAGH compounds may represent an advance over daily GH injections because of increased convenience and differing phamacodynamic properties, providing the potential for improved adherence and outcomes. Better methods to assess adherence must be developed and validated. Long-term surveillance registries that include assessment of efficacy, cost-benefit, disease burden, quality of life, and safety are essential for understanding the impact of sustained exposure to LAGH preparations.
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50.
  • Clayton, P E, et al. (författare)
  • Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society.
  • 2007
  • Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 92:3, s. 804-10
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Low birth weight remains a major cause of morbidity and mortality in early infancy and childhood. It is associated with an increased risk of health problems later in life, particularly coronary heart disease and stroke. A meeting was convened to identify the key health issues facing a child born small for gestational age (SGA) and to propose management strategies. PARTICIPANTS: There were 42 participants chosen for their expertise in obstetrics, peri- and neonatal medicine, pediatrics, pediatric and adult endocrinology, epidemiology, and pharmacology. EVIDENCE: Written materials were exchanged, reviewed, revised, and then made available to all. This formed the basis for discussions at the meeting. Where published data were not available or adequate, discussion was based on expert clinical opinions. CONSENSUS PROCESS: Each set of questions was considered by all and then discussed in plenary sessions with consensus and unresolved issues identified. The consensus statement was prepared in plenary sessions and then edited by the group chairs and shared with all participants. CONCLUSIONS: The diagnosis of SGA should be based on accurate anthropometry at birth including weight, length, and head circumference. We recommend early surveillance in a growth clinic for those without catch-up. Early neurodevelopment evaluation and interventions are warranted in at-risk children. Endocrine and metabolic disturbances in the SGA child are recognized but infrequent. For the 10% who lack catch-up, GH treatment can increase linear growth. Early intervention with GH for those with severe growth retardation (height sd score, <-2.5; age, 2-4 yr) should be considered at a dose of 35-70 microg/kg x d. Long-term surveillance of treated patients is essential. The associations at a population level between low birth weight, including SGA, and coronary heart disease and stroke in later life are recognized, but there is inadequate evidence to recommend routine health surveillance of all adults born SGA outside of normal clinical practice.
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