| 6551. |
- Kjellbom, Albin, et al.
(författare)
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Association Between Mortality and Levels of Autonomous Cortisol Secretion by Adrenal Incidentalomas : A Cohort Study
- 2021
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Ingår i: Annals of Internal Medicine. - 0003-4819. ; 174:8, s. 1041-1049
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autonomous cortisol secretion in patients with adrenal incidentalomas is associated with increased mortality, but detailed information about the risk associated with specific levels of autonomous cortisol secretion is not available.OBJECTIVE: To measure the association between mortality and levels of autonomous cortisol secretion in patients with adrenal incidentalomas.DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT03919734).SETTING: Two hospitals in southern Sweden.PATIENTS: Consecutive patients who had adrenal incidentalomas identified between 2005 and 2015 and were followed for up to 14 years. Outcome data were collected from national registers.MEASUREMENTS: Patients were grouped according to plasma cortisol level after a 1-mg dexamethasone suppression test (cortisolDST; <50, 50 to 82, 83 to 137, or ≥138 nmol/L).RESULTS: During a median follow-up of 6.4 years, 170 of 1048 patients died. Compared with a cortisolDST less than 50 nmol/L, a cortisolDST of 50 to 82 nmol/L was not associated with increased mortality (hazard ratio [HR], 1.15 [95% CI, 0.78 to 1.70]). However, a cortisolDST of 83 to 137 nmol/L (n = 119) had an HR of 2.30 (CI, 1.52 to 3.49), and a cortisolDST of 138 nmol/L or higher (n = 82) had an HR of 3.04 (CI, 1.86 to 4.98). Analyses using restricted cubic splines indicated that the association between cortisolDST and mortality was linear up to a cortisolDST of 200 nmol/L.LIMITATION: The results are not based on verified autonomous cortisol secretion; thus, the association may be underestimated.CONCLUSION: The association between mortality and cortisolDST increased linearly until cortisolDST reached 200 nmol/L. A cortisolDST of 83 to 137 nmol/L was associated with a 2-fold increase in mortality, and a cortisolDST of 138 nmol/L or higher was associated with a 3-fold increase in mortality. Additional studies should be done, and until those studies are completed some clinicians may consider these findings when deciding which patients to recommend for surgery.PRIMARY FUNDING SOURCE: Lisa and Johan Grönberg Foundation and Gyllenstiernska Krapperup Foundation.
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| 6552. |
- Kjellbom, Albin
(författare)
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Autonomous cortisol secretion – Mortality, morbidity and diagnostics
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- ContextUp to half of patients with adrenal adenomas found as incidentalomas show biochemical signs of subtle cortisol hypersecretion without having clinical signs or symptoms of Cushing’s syndrome. A condition called autonomous cortisol secretion (ACS). Previous studies have indicated that ACS might be associated with increased mortality.ObjectivesExplore if ACS is an independent risk factor for increased mortality. Evaluate low ACTH as a diagnostic marker of ACS. Investigate the prevalence of smoking in patients with adrenal adenomas.MethodsCohort and cross-sectional studies. Adult patients referred to two Swedish endocrine centres because of an adrenal adenoma, found as an incidentaloma, between 2005 and 2015 were enrolled. Mortality data were obtained from the Cause of Death Register. Patients were grouped according to predefined levels of cortisol after a 1-mg dexamethasone suppression test (cortisolDST); non-functional adrenal adenoma (NFAA), defined as cortisolDST Results1048 patients were followed for 6.4 years. Compared with NFAA mortality was not increased in cortisolDST 50-82 nmol/L, hazard ratio (HR) 1.17 (95% CI, 0.79-1.73)), while cortisolDST 83-137 and ≥138 nmol/L were associated with a significant increase in mortality, HR 2.33 (1.53-3.53) and 2.87 (1.74-4.74). Mortality did not differ significantly between 632 patients with NFAA and matched controls (3:1) when followed for 6.6 years, HR 1.13 (0.87-1.46). Studying 198 patients with unilateral adrenal adenomas and 100 healthy controls, low ACTH (ConclusionsACS is an independent risk factor for increased mortality, while NFAAs do not pose a relevant risk. The risk associated with ACS seems to become clinically relevant when the cortisolDST level is ≥83 nmol/L. Low ACTH is of limited value in diagnosing ACS, in part due to its high prevalence in patients with NFAA. Additionally, there appears to be a link between smoking, adrenal adenomas, and ACS.
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| 6553. |
- Kjellbom, Albin, et al.
(författare)
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Mortality not increased in patients with non-functional adrenal adenomas : a matched cohort study
- 2023
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 108:8, s. 536-541
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Tidskriftsartikel (refereegranskat)abstract
- CONTEXT: Mild autonomous cortisol secretion (MACS) is associated with increased mortality in patients with adrenal incidentalomas (AI), but little is known regarding the potential risk associated with non-functional adrenal adenomas (NFAA), which constitute the majority of AI.OBJECTIVE: Compare mortality risk in patients with NFAA, and different levels of MACS, to matched controls.METHOD: This was a retrospective matched cohort study. All patients referred to two endocrine centres in southern Sweden because of an AI between 2005 and 2015 were enrolled. Controls (3:1) matched for sex, age, and residency were included. Primary endpoint was all-cause mortality. Outcome data was obtained from the Cause of Death Register. Patients were grouped according to cortisol level post 1-mg dexamethasone suppression test (cortisolDST) (<50 (NFAA), 50-82, 83-137, and ≥138 nmol/L).RESULTS: 1154 patients and 3462 matched controls were included. During a median follow-up of 6.6 years, 210 patients and 505 controls died. There were no statistically significant differences in mortality between patients with NFAA and their controls (HR 1.13 (0.87-1.46)) whereas mortality was increased compared to controls in patients with cortisolDST 83-137 (HR 1.99 (1.38-2.88)) and ≥138 nmol/L (HR 4.09 (2.41-6.93)). Likewise, the mortality risk was increased inpatients younger than 65 years with cortisolDST 50-82 nmol/L compared to controls (HR 2.33 (1.30-4.17)).CONCLUSION: NFAA does not seem to pose a clinically relevant risk for increased mortality in patients with AI while patients with MACS, and especially younger patients and those with cortisolDST ≥83 nmol/L, have significantly increased mortality risk compared to matched controls.
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| 6554. |
- Kjellerås, Jennifer, et al.
(författare)
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Improved efficacy by using the pTnT-rhtTG plasmid for the detection of celiac disease specific tissue transglutaminase autoantibodies in radioligand binding assays.
- 2011
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 71, s. 701-704
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Tidskriftsartikel (refereegranskat)abstract
- Background. Tissue transglutaminase (tTG) autoantibodies are serological markers for celiac disease. The aim was to study the efficacy of the pTnT-rhtTG plasmid and subsequent diagnostic accuracy of tTG autoantibodies for childhood celiac disease using radioligand binding assays. Methods. Coupled in vitro transcription and translation of tTG were performed by pTnT-rhtTG as well as by the pGEMt Easy-rhtTG vectors using the TNT SP6 Coupled Reticulocyte Lysate System in the presence of [(35)S] methionine. Sera from 190 celiac disease children and 74 controls were measured for tTG autoantibodies in two separate radioligand binding assays using anti-human IgA agarose and protein A sepharose beads for the detection of IgA-tTG and IgG-tTG, respectively. Results. Median incorporation of [(35)S] methionine into the pTnT-rhtTG was 26% compared to 16% for the pGEMt Easy-rhtTG plasmid (p = 0.0016). Using pTnT-rhtTG (as compared to pGEMt Easy-rhtTG), sensitivities were IgA-tTG = 96.3% (95.7%) and IgG-tTG = 95.8% (97.3%) and specificities were IgA-tTG = 91.9% (90.5%) and IgG-tTG = 94.6% (98.4%). According to receiver operator characteristics for the pTnT (pGEMt Easy) assays, area under the curves were IgA-tTG = 98.4% (98.4%) and IgG-tTG = 97.7% (97.2%), respectively. Conclusion. The pTnT-rhtTG plasmid increased the efficacy of tTG antigen usage without reducing the diagnostic accuracy of IgA-tTG and IgG-tTG for childhood celiac disease. The pTnT-rhtTG plasmid is therefore recommended over the pGEMt Easy-rhtTG for the assessment of IgA-tTG and IgG-tTG using radioligand binding assays.
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| 6555. |
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| 6556. |
- Klannemark, Mia, et al.
(författare)
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Interaction between the Asn291Ser variant of the LPL gene and insulin resistance on dyslipidaemia in high risk individuals for Type 2 diabetes mellitus
- 2000
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 17:8, s. 599-605
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Lipoprotein lipase (LPL) is a major regulator of triglyceride clearance. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has previously been associated with dyslipidaemia and an increased frequency of cardiovascular disease as well as familial disorders of lipoprotein metabolism. The aim of this study was to test whether the phenotypic expression of the LPL Asn291Ser variant is dependent upon glucose tolerance and insulin resistance. Therefore, the Asn291Ser variant was examined in 192 patients with Type 2 diabetes, 278 subjects with normal glucose tolerance who are first degree relatives of patients with Type 2 diabetes and 226 healthy control spouses without family history of diabetes. METHODS: The subjects were genotyped with an allele-specific mini-sequencing method. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. RESULTS: The frequency of the Asn/Ser genotype was significantly increased in normoglycaemic subjects with hypertriglyceridaemia (> 1.7 mmol/1), and was associated with dyslipidaemia and increased systolic blood pressure. There was a significant interaction between Asn291Ser and insulin resistance in normoglycaemic subjects, indicating that dyslipidaemia is more severe in Asn/ Ser carriers with reduced insulin sensitivity. The frequency of the Asn/Ser genotype was not increased in diabetic subjects with hypertriglyceridaemia, but was associated with increased systolic blood pressure. CONCLUSIONS: The Asn/Ser genotype of the LPL gene is associated with dyslipidaemia in normoglycaemic subjects, and the dyslipidaemic phenotype is more severe in insulin-resistant subjects. This association is not seen in diabetic subjects.
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| 6557. |
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| 6558. |
- Klein Hazebroek, Marlou, et al.
(författare)
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Adapting to the Cold : A Role for Endogenous Fibroblast Growth Factor 21 in Thermoregulation?
- 2020
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 11
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Forskningsöversikt (refereegranskat)abstract
- Fibroblast growth factor 21 (FGF21) is in biomedical focus as a treatment option for metabolic diseases, given that administration improves metabolism in mice and humans. The metabolic effects of exogenous FGF21 administration are well-characterized, but the physiological role of endogenous FGF21 has not been fully understood yet. Despite cold-induced FGF21 expression and increased circulating levels in some studies, which co-occur with brown fat thermogenesis, recent studies in cold-acclimated mice demonstrate the dispensability of FGF21 for maintenance of body temperature, thereby questioning FGF21's role for thermogenesis. Here we discuss the evidence either supporting or opposing the role of endogenous FGF21 for thermogenesis based on the current literature. FGF21, secreted by brown fat or liver, is likely not required for energy homeostasis in the cold, but the nutritional conditions could modulate the interaction between FGF21, energy metabolism, and thermoregulation.
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| 6559. |
- Klein Hazebroek, Marlou, et al.
(författare)
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Obesity-resistance of UCP1-deficient mice associates with sustained FGF21 sensitivity in inguinal adipose tissue
- 2022
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Ingår i: Frontiers in Endocrinology. - : Frontiers Media SA. - 1664-2392. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Metabolic diseases represent the major health burden of our modern society. With the need of novel therapeutic approaches, fibroblast growth factor 21 (FGF21) is a promising target, based on metabolic improvements upon FGF21 administration in mice and humans. Endogenous FGF21 serum levels, however, are increased during obesity-related diseases, suggesting the development of FGF21 resistance during obesity and thereby lowering FGF21 efficacy. In uncoupling protein 1 knockout (UCP1 KO) mice, however, elevated endogenous FGF21 levels mediate resistance against diet-induced obesity. Here, we show that after long-term high fat diet feeding (HFD), circulating FGF21 levels become similarly high in obese wildtype and obesity-resistant UCP1 KO mice, suggesting improved FGF21 sensitivity in UCP1 KO mice. To test this hypothesis, we injected FGF21 after long-term HFD and assessed the metabolic and molecular effects. The UCP1 KO mice lost weight directly upon FGF21 administration, whereas body weights of WT mice resisted weight loss in the initial phase of the treatment. The FGF21 treatment induced expression of liver Pck1, a typical FGF21-responsive gene, in both genotypes. In iWAT, FGF21-responsive genes were selectively induced in UCP1 KO mice, strongly associating FGF21-sensitivity in iWAT with healthy body weights. Thus, these data support the concept that FGF21-sensitivity in adipose tissue is key for metabolic improvements during obesogenic diets.
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| 6560. |
- Klingberg, Eva, et al.
(författare)
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Seasonal variations in serum 25-hydroxy vitamin D levels in a Swedish cohort
- 2015
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Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 49:3, s. 800-808
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Tidskriftsartikel (refereegranskat)abstract
- To study seasonal inter-individual and intra-individual variations in serum 25-hydroxy vitamin D (25(OH)D) and to explore parameters associated with 25(OH)D in a healthy Swedish adult population. 540 blood donors (60 % men; mean age 41 +/- A 13 years) and 75 thrombocyte donors (92 % men, aged 46 +/- A 11 years) were included. Serum was collected during 12 months and analyzed for 25(OH)D and parathyroid hormone (S-iPTH). The blood donors answered questionnaires concerning vitamin D supplements, smoking, physical activity, sunbed use and sun holidays. Repeated serum samples were collected from the thrombocyte donors to study the intra-individual variations in S-25(OH)D. S-25(OH)D varied greatly over the year correlating with the intensity of the UV-B irradiation (r (S) = 0.326; p < 0.001). During January-March, a S-25(OH)D level below the thresholds of 50 and 75 nmol/L was observed in 58 and 88 %, respectively, and during July-September in 11 and 50 % (p < 0.001). S-25(OH)D was negatively correlated with body mass index and S-iPTH, but was significantly higher in holiday makers in sunny destinations, sunbed users, non-smokers, and in the physically active. The intra-individual analyses showed a mean increase in S-25(OH)D by 8 nmol/L/month between April and August. Approximately 75 % had serum 25(OH)D values < 75 nmol/L during 75 % of the year and 50 % had serum 25(OH)D < 50 nmol/L during 50 % of the year. Serum 25(OH)D was strongly associated with parameters related to sun exposure, but only weakly with intake of vitamin D supplements.
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