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- Ragnarsson, Oskar, 1971, et al.
(författare)
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Common genetic variants in the glucocorticoid receptor and the 11β-Hydroxysteroid dehydrogenase type 1 genes influence long-term cognitive impairments in patients with Cushing's syndrome in remission.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:9
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Tidskriftsartikel (refereegranskat)abstract
- Context: Cognitive function is impaired in patients with Cushing's syndrome (CS) in remission. Objective: To study the effects of polymorphisms in genes associated with glucocorticoid (GC) sensitivity on cognitive function in patients with CS in long-term remission. Design: A cross-sectional, case-controlled, single center study. Patients: Fifty-three patients with Cushing's syndrome in remission and 53 controls matched for age, gender and educational level. Main Outcome Measures: Cognitive function, studied using standardized neuropsychological testing, and polymorphisms in the GC receptor (NR3C1; Bcl1 and A3669G), mineralocorticoid receptor (NR3C2; I180V), 11β-Hydroxysteroid dehydrogenase type 1 (11βHSD1; rs11119328) and ATP binding cassette B1 (ABCB1; rs1045642) genes. The association between cognitive function and polymorphisms were analyzed using linear regression with adjustments for age and educational level. Results: The mean age in patients and controls was 53 ± 14 years. The median (interquartile range) duration of remission was 13 (5-18) years. In patients, SNP rs11119328 was associated with impairments in processing speed, auditory attention, auditory working memory and reading speed. This association was not seen in matched controls. The Bcl1 polymorphism was associated with fatigue and worse visual attention and working memory. The remaining SNPs were not associated with cognitive performance. Conclusion: In this study, polymorphisms in the 11βHSD1 and NR3C1 genes were associated with impaired cognitive function, indicating that GC sensitivity and pre-receptor regulation of GC action may play a role in the long-term consequences of CS. The study provides a novel insight into the etiology of cognitive dysfunction in patients with CS in remission.
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- Agnarsson, Hjalmar Ragnar, et al.
(författare)
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The impact of glucocorticoid replacement on bone mineral density in patients with hypopituitarism before and after 2 years of growth hormone replacement therapy.
- 2014
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:4
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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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- Johannsson, Gudmundur, 1960, et al.
(författare)
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Cardiovascular and metabolic impact of glucocorticoid replacement therapy.
- 2014
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Ingår i: Frontiers of hormone research. - : S. Karger AG. - 1662-3762. ; 43, s. 33-44
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Tidskriftsartikel (refereegranskat)abstract
- Cortisol in man is essential for life. Excess cortisol as in Cushing's syndrome and during pharmacological glucocorticoid (GC) therapy is associated with increased cardiovascular morbidity and mortality. Recent data from patients with adrenal insufficiency (AI) have demonstrated that currently used replacement regimens are associated with a poor cardiovascular outcome. In particular, a more than doubled vascular mortality rate has been observed in patients with primary AI. The unphysiological GC replacement, both in terms of the total daily dose and the pattern of delivery, may explain this poor outcome together with an inadequate treatment during an intercurrent illness. The mechanism may be both an induction of classical metabolic risk factors for vascular disease, such as obesity and hypertension, but also an unphysiological cortisol exposure to the vascular endothelium and the immune system that may induce an accelerated atherosclerotic process. This review summarizes some of the cardiovascular data associated with GC excess and outcome data in patients with AI. Studies that have compared various regimens for replacement therapy will be addressed and recent developments that may improve outcome in patients with AI will be discussed.
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- 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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- 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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