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  • 1
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 107, No. 9 ( 2022-08-18), p. e3699-e3704
    Abstract: Patients with pro-opiomelanocortin (POMC) defects generally present with early-onset obesity, hyperphagia, hypopigmentation and adrenocorticotropin (ACTH) deficiency. Rodent models suggest that adequate cleavage of ACTH to α-melanocortin–stimulating hormone (α-MSH) and desacetyl-α-melanocortin–stimulating hormone (d-α-MSH) by prohormone convertase 2 at the KKRR region is required for regulating food intake and energy balance. Methods We present 2 sisters with a novel POMC gene variant, leading to an ACTH defect at the prohormone convertase 2 cleavage site, and performed functional studies of this variant. Results The patients had obesity, hyperphagia and hypocortisolism, with markerly raised levels of ACTH but unaffected pigmentation. Their ACTH has reduced potency to stimulate the melanocortin (MC) 2 receptor, explaining their hypocortisolism. Conclusion The hyperphagia and obesity support evidence that adequate cleavage of ACTH to α-MSH and d-α-MSH is also required in humans for feeding control.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2022
    detail.hit.zdb_id: 2026217-6
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  • 2
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 183, No. 6 ( 2020-12), p. 669-676
    Abstract: Obesity and cardiometabolic diseases are associated with higher long-term glucocorticoid levels, measured as scalp hair cortisol (HairF) and cortisone (HairE). Cardiometabolic diseases have also been associated with copeptin, a stable surrogate marker for the arginine-vasopressin (AVP) system. Since AVP is, together with corticotropin-releasing hormone (CRH) an important regulator of the hypothalamic-pituitary adrenal axis (HPA axis), we hypothesize that AVP contributes to chronic hypercortisolism in obesity. Objective To investigate whether copeptin levels are associated with Higher HairF and HairE levels in obesity. Design A cross-sectional study in 51 adults with obesity (BMI ≥30 kg/m 2 ). Methods Associations and interactions between copeptin, HairF, HairE, and cardiometabolic parameters were cross-sectionally analyzed. Results Copeptin was strongly associated with BMI and waist circumference (WC) (rho = 0.364 and 0.530, P = 0.008 and 〈 0.001, respectively), also after correction for confounders. There were no associations between copeptin and HairF or HairE on a continuous or dichotomized scale, despite correction for confounders. Conclusion In patients with obesity, AVP seems not a major contributor to the frequently observed high cortisol levels. Other factors which stimulate the HPA axis or affect cortisol synthesis or breakdown may be more important than the influence of AVP on long-term glucocorticoid levels in obesity.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    RVK:
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 1485160-X
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  • 3
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A14-A14
    Abstract: Background: Long-term glucocorticoid levels measured in scalp hair (HairGC) are positively correlated to obesity in cross-sectional studies, however it is unclear whether this reflects a state of obesity or an actual maintaining or contributing factor to obesity. Objectives: To investigate whether hair cortisol (HairF) and hair cortisone (HairE) predict changes in body mass index (BMI) and waist circumference (WC) over time, and to assess whether HairGC are linked to immune parameters. Methods: We measured HairGC in 1604 participants of the Netherlands Study of Depression and Anxiety (NESDA), and correlated these to BMI, WC, and immune parameters (interleukin-6 (IL-6), high-sensitive C-reactive protein (CRP), total leukocyte, monocyte and lymphocyte counts and the neutrophil-to-lymphocyte ratio). Also, we assessed whether baseline HairGC predict changes in BMI and WC at the follow-up visit, three years later, and whether immune parameters influenced this correlation. Results: In cross-sectional analyses, HairF and HairE were positively correlated to BMI (β=2.06 and β=2.84kg/m2 respectively) and WC (β=5.36 and β= 8.54cm respectively, all p & lt;0.001). HairF was related to IL-6 (adjusted β=0.15, p & lt;0.05) and leukocyte count (adjusted β=0.57, p & lt;0.01), and HairE to IL-6 (adjusted β=0.21, p & lt;0.05). In the adjusted longitudinal analyses, baseline HairF was associated with a yearly increase in BMI (β=0.58%, p=0.009) and baseline HairE with a yearly increase in WC (β=0.84%, p=0.049). Adjusting for baseline IL-6 or leukocytes did not affect the found associations between GC and WC or BMI change. Conclusions: HairGC levels are related to BMI, WC, IL-6 and leukocytes in cross-sectional analyses. Moreover, chronically higher HairGC may be a relevant risk factor for the development of obesity in the future, although causality is yet to be proven.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 4
    In: Journal of the Endocrine Society, The Endocrine Society, Vol. 5, No. Supplement_1 ( 2021-05-03), p. A30-A30
    Abstract: Introduction: Recently, cross-sectional studies report associations between long-term glucocorticoid levels in scalp hair (HairGC) and obesity. However, there is a wide variation in studied outcomes and associations, possibly caused by differences in population characteristics, e.g. age, sex, dispersion of adiposity, and used laboratory methods. The aim of this systematic review and meta-analysis was to investigate the relation between HairGC and anthropometrics and to explore possible moderators of this association. Methods: We searched the Medline, Embase, Cochrane, Web of Science, Scopus, Cinahl, PsycInfo, and Google Scholar databases for articles that relate HairGC to measures of adiposity (date 11-16-2020). Primary outcomes were correlations between hair cortisol (HairF) and cortisone (HairE), and anthropometrics: BMI, waist circumference (WC) and waist-hip-ratio (WHR). Authors were contacted to provide missing outcome information. Pooled correlation coefficients were calculated using random effects models. Assessment of heterogeneity was performed using the I2 statistic. Exploratory moderator analyses were performed with subgroup analyses and meta-regression. This systematic review was performed in accordance to the PRISMA guidelines. Results: Our systematic search identified 150 cohorts, comprising a total of 37,107 unique individuals, of which 15,033 sampled from population-based cohorts. For BMI, the pooled correlation for HairF was 0.121 (95% CI 0.083–0.158, n=26,941; I2 94.2%, p & lt;0.001) and for HairE 0.108 (95% CI 0.047–0.167, n=7,250; I2 52%, p & lt;0.01). For WC, the pooled correlation for HairF was 0.111 (95% CI 0.058–0.164, n=10,290; I2 63%, p & lt;0.01) and for HairE 0.200 (95% CI 0.137–0.264, n=2,198; I2 0%, p=0.42). For WHR, the pooled correlation for HairF was 0.102 (95% CI 0.040–0.163, n=6,865; I2 27%, p=0.14) and for HairE 0.261 (95% CI 0.195–0.330, n=1,314; I2 0%, p=0.40). A higher percentage of male participants was related to stronger correlations with WC (p & lt;0.001), but not with BMI and WHR. Mean age, mean BMI, and mean HairGC levels of the cohorts did not significantly moderate the pooled correlations, neither did the used laboratory techniques (immunoassays vs mass spectrometry-based assays). Conclusion: This unique, large meta-analysis demonstrates that long-term endogenous glucocorticoids as assessed by HairGC show small but consistent correlations to measures of obesity, despite a large heterogeneity between the included cohorts. The strongest associations were found between HairE and WC and between HairE and WHR. This suggests that glucocorticoid levels in the high-normal range, especially cortisone, may contribute to or reflect the state of specifically central adiposity, even within the general population.
    Type of Medium: Online Resource
    ISSN: 2472-1972
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2881023-5
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  • 5
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 2 ( 2021-01-23), p. e551-e561
    Abstract: Stress may lead to an adverse body fat distribution from childhood onwards. Objective To examine the associations of hair cortisol concentration (HCC) at 6 years with general and organ fat measures, risk of overweight, and nonalcoholic fatty liver disease (NAFLD) at 10 years and to assess whether these were independent of adiposity measures at 6 years. Design, Setting and participants HCCs were measured in hair of 6-year-old children (n = 2042) participating in the Generation R Study, a population-based prospective cohort study. Main Outcome Measures Body mass index (BMI), fat mass index measured by dual-energy X-ray absorptiometry scan, and visceral fat index, pericardial fat index, liver fat fraction measured by magnetic resonance imaging and risk of overweight and NAFLD were obtained at 10 years. Results The associations of higher HCC at 6 years, with higher BMI, fat mass index, and increased risk of overweight at age 10 years are explained by the relationships observed at 6 years. HCCs at 6 years were associated with a higher liver fat fraction (difference 0.11 liver fat fraction standard deviation score; 95% confidence interval [CI] 0.03, 0.18) and a higher risk of NAFLD at 10 years (odds ratio 1.95; 95% CI 1.06, 3.56), independent of fat mass index at 6 years. HCCs were not associated with pericardial or visceral fat indices. Conclusions Higher HCCs at 6 years were associated with higher BMI, fat mass index, liver fat fraction, and higher risks of overweight and NAFLD at 10 years. Only the associations for liver fat fraction and NAFLD were independent of fat mass index at 6 years.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 6
    Online Resource
    Online Resource
    The Endocrine Society ; 2021
    In:  The Journal of Clinical Endocrinology & Metabolism Vol. 106, No. 9 ( 2021-08-18), p. e3400-e3413
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 106, No. 9 ( 2021-08-18), p. e3400-e3413
    Abstract: Biological stress is related to cardiovascular disease in adults. The associations of stress with cardiovascular and metabolic diseases may originate in childhood. Objective This work aims to examine the associations of hair cortisol concentrations at age 6 years with cardiometabolic risk factors at ages 6 and 10 years. Methods Cortisol concentrations were measured in hair of 6-year-old children (n = 2598) participating in the Generation R Study, a population-based prospective cohort study in Rotterdam, the Netherlands. Main outcome measures included blood pressure, heart rate, concentrations of insulin, glucose, lipids, and C-reactive protein in blood at ages 6 and 10 years. Results Higher hair cortisol concentrations at age 6 years were associated with higher systolic blood pressure at age 10 years (difference 0.17 SD score; 95% CI, 0.03-0.31). The association attenuated into nonsignificance after adjustment for childhood body mass index (BMI) at age 6 years. Higher hair cortisol concentrations at age 6 years were associated with an increase in total and low-density lipoprotein cholesterol between ages 6 and 10 years but not with those measurements at age 6 or 10 years. Hair cortisol concentrations were not associated with other cardiometabolic risk factors at age 6 or 10 years. Conclusion Hair cortisol concentrations were not independent of BMI associated with cardiometabolic risk factors at 6 or 10 years. The associations of biological stress with cardiometabolic risk factors may develop at later ages.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2021
    detail.hit.zdb_id: 2026217-6
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  • 7
    In: The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, Vol. 104, No. 9 ( 2019-09-01), p. 3859-3867
    Abstract: Turner syndrome (TS) usually manifests in traits as short stature and premature ovarian failure. Many patients also have an increased risk of cardiometabolic disorders and psychological distress, which are features that overlap with those of a prolonged state of hypercortisolism. Objective To investigate whether TS is associated with increased long-term cortisol concentrations as measured in scalp hair and whether these are linked to cardiometabolic and psychological parameters. Design Prospective observational case-control study. Setting Academic outpatient TS expertise center. Participants Fifty-five patients with TS (53% 45,X karyotype), and 110 age-matched female community control subjects from the general population–based Lifelines cohort study. Main Outcome Measures Hair cortisol concentrations (HCC), anthropometrics, biochemical parameters, and psychological questionnaires for perceived stress (Perceived Stress Scale–14), fatigue (Checklist Individual Strength–20), and health-related quality of life (RAND-36). Results Compared with control subjects, patients with TS had higher HCC [geometric mean, 3.51 pg/mg (95% CI, 2.64 to 4.65) vs 2.39 pg/mg (2.13 to 2.68); P = 0.003] and a worse cardiometabolic profile in terms of fasting glucose, and triglycerides. HCC was only associated with total cholesterol levels (standardized β = 0.294; P = 0.047) and was not associated with the psychological outcomes. A higher HCC was inversely associated with height only in patients with TS (standardized β = −0.307; P = 0.023). Conclusion Patients with TS are chronically exposed to higher cortisol levels, which is associated with short stature and increased total cholesterol levels, and potentially contributes to the known elevated cardiovascular disease risk.
    Type of Medium: Online Resource
    ISSN: 0021-972X , 1945-7197
    RVK:
    Language: English
    Publisher: The Endocrine Society
    Publication Date: 2019
    detail.hit.zdb_id: 2026217-6
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  • 8
    In: European Journal of Endocrinology, Oxford University Press (OUP), Vol. 176, No. 6 ( 2017-06), p. 695-703
    Abstract: Current first-line screening tests for Cushing’s syndrome (CS) only measure time-point or short-term cortisol. Hair cortisol content (HCC) offers a non-invasive way to measure long-term cortisol exposure over several months of time. We aimed to evaluate HCC as a screening tool for CS. Design Case-control study in two academic referral centers for CS. Methods Between 2009 and 2016, we collected scalp hair from patients suspected of CS and healthy controls. HCC was measured using ELISA. HCC was available in 43 confirmed CS patients, 35 patients in whom the diagnosis CS was rejected during diagnostic work-up and follow-up (patient controls), and 174 healthy controls. Additionally, we created HCC timelines in two patients with ectopic CS. Results CS patients had higher HCC than patient controls and healthy controls (geometric mean 106.9 vs 12.7 and 8.4 pg/mg respectively, P   〈  0.001). At a cut-off of 31.1 pg/mg, HCC could differentiate between CS patients and healthy controls with a sensitivity of 93% and a specificity of 90%. With patient controls as a reference, specificity remained the same (91%). Within CS patients, HCC correlated significantly with urinary free cortisol ( r  = 0.691, P   〈  0.001). In two ectopic CS patients, HCC timelines indicated that cortisol was increased 3 and 6 months before CS became clinically apparent. Conclusions Analysis of cortisol in a single scalp hair sample offers diagnostic accuracy for CS similar to currently used first-line tests, and can be used to investigate cortisol exposure in CS patients months to years back in time, enabling the estimation of disease onset.
    Type of Medium: Online Resource
    ISSN: 0804-4643 , 1479-683X
    RVK:
    Language: Unknown
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
    detail.hit.zdb_id: 1485160-X
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  • 9
    In: RMD Open, BMJ, Vol. 5, No. 1 ( 2019-01), p. e000852-
    Abstract: To identify whether children with antenatal prednisone exposure have chronically elevated cortisol and cortisone concentrations, an altered body composition or higher blood pressure. In addition, to identify whether maternal rheumatoid arthritis disease (RA) activity is associated with these alterations. Methods In this prospective study, 56 children (mean age=10.0 years) with and 61 children (mean age=9.6 years) without antenatal prednisone exposure, born to women with RA, were included. Hair cortisol and cortisone were analysed using liquid chromatography–tandem mass spectrometry. Linear regression models were built to analyse differences between the two groups, corrected for relevant covariates. Hair cortisol concentrations were also compared between the study population and an age-matched healthy reference group(n=150 children, mean age=9.8 years). Results Hair cortisol and cortisone concentrations were similar in children with and without antenatal prednisone exposure (median cortisol 1.14 pg/mg (IQR 0.67–1.75) and 1.15 pg/mg (IQR 0.65–2.21) and median cortisone 6.76 pg/mg (IQR 5.42–8.86) and 7.40 pg/mg (IQR 5.39–10.73), respectively). Antenatal prednisone exposure and maternal RA disease activity were also not associated with body composition or blood pressure. Hair cortisol concentrations were not different in children born to mothers with RA compared with children from the reference group. Conclusion This, in its kind, large and unique long-term prospective study demonstrates that low-dose antenatal prednisone exposure and maternal RA disease activity are not associated with negative consequences in prepubertal childhood. The findings of this study are reassuring and support the assumption that low-dose maternal prednisone use during pregnancy is safe for the offspring, at least until the age of approximately 10 years.
    Type of Medium: Online Resource
    ISSN: 2056-5933
    Language: English
    Publisher: BMJ
    Publication Date: 2019
    detail.hit.zdb_id: 2812592-7
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