Gerard Noppe

Increased Scalp Hair Cortisol Concentrations in Obese Children

CONTEXT Pathologically increased cortisol exposure induces obesity, but it is not known whether relatively high cortisol within the physiological range is related to childhood obesity. OBJECTIVE The aim of the study was to compare hair cortisol concentrations between obese and normal-weight children. DESIGN We performed an observational case-control study. PARTICIPANTS Twenty obese children (body mass index-SD score [BMI-SDS]>2.3) and 20 age- and sex-matched normal-weight children (BMI-SDS<1.1) aged 8-12 years were recruited. MAIN OUTCOME MEASURES Scalp hair samples from the posterior vertex were collected, and hair cortisol concentrations were measured using ELISA. Body weight, height, and waist circumference were measured. From the obese children, additional data on blood pressure and blood lipid concentrations were collected. RESULTS In both groups, five boys and 15 girls were included; their mean age was 10.8±1.3 vs 10.8±1.2 years (obese vs normal weight; not significant). Body weight, BMI, BMI-SDS, and waist circumference were higher in the obese children compared with the normal-weight children (69.8±17.2 vs 35.5±7.2 kg; 29.6±4.9 vs 16.4±1.6 kg/m2; 3.4±0.5 vs -0.2±0.8 SDS; 94±13 vs 62±6 cm; P<.001 all). Hair cortisol concentration was higher in obese than normal-weight children (median [interquartile range], 25 [17, 32] vs 17 [13, 21] pg/mg; P<.05). CONCLUSIONS Hair cortisol concentration, a measure for long-term cortisol exposure, was higher in obese children than normal-weight children. This suggests long-term activation of the hypothalamus-pituitary-adrenal axis in obese children and may provide a novel target for treatment of obesity in children.

Children’s hair cortisol as a biomarker of stress at school entry

Abstract Quantification of cortisol in scalp hair seems a promising measurement for long-term cortisol levels, and thereby a biomarker for stress. We examined hair cortisol concentrations (HCC) in children when first entering elementary school. Participants were 42 children (45% boys) with a mean age of 4.2 years (SD = 0.42 months). Hair samples (≥5 cm) were collected 2 months after school entry. Hair analysis was conducted using two 2-cm long segments, reflecting the first 2 months of school attendance (the scalp-near segment) and 2 months prior to school entry. HCC were higher after school entry than before, especially for fearful children. Alterations in HCC were not moderated by experience in group daycare before school entry. Thus, HCC suggest that starting elementary school is accompanied by increased stress hormone levels in young (in particular fearful) children.

Splitting hair for cortisol? Associations of socio-economic status, ethnicity, hair color, gender and other child characteristics with hair cortisol and cortisone

The aim of this study was to examine associations of SES and ethnicity with hair cortisol and cortisone and to identify potential child and family characteristics that can assist in choosing covariates and potential confounders for analyses involving hair cortisol and cortisone concentrations. Hair samples were collected in 2484 6-year-old children from the Generation R Study, a prospective cohort in Rotterdam, the Netherlands. Measurements for cortisol and cortisone were used as the outcome in regression analyses. Predictors were SES, ethnicity, hair color and child characteristics such as birthweight, gestational age at birth, BMI, disease, allergy, and medication use. Lower family income, more children to be supported by this income, higher BMI and darker hair color were associated with higher hair cortisol and cortisone levels. Boys also showed higher levels. Ethnicity (Dutch and North European descent) was related to lower levels. High amounts of sun in the month of hair collection was related to higher levels of cortisone only. More recent hair washing was related to lower levels of cortisol and cortisone. Gestational age at birth, birth weight, age, medication use, hair washing frequency, educational level of the mother, marital status of the mother, disease and allergy were not associated with cortisol or cortisone levels. Our results serve as a starting point for choosing covariates and confounders in studies of substantive predictors or outcomes. Gender, BMI, income, the number of persons in a household, ethnicity, hair color and recency of hair washing are strongly suggested to take into account.

Socioeconomic status in children is associated with hair cortisol levels as a biological measure of chronic stress

INTRODUCTION Low socioeconomic status (SES) may be associated with a high risk of lifestyle-related diseases such as cardiovascular diseases. There is a strong association between parental SES, stress and indicators of child health and adult health outcome. The exact mechanisms underlying this association have not yet been fully clarified. Low SES may be associated with chronic stress, which may lead to activation of the hypothalamic-pituitary-adrenal (HPA)-axis, resulting in a higher circulating level of the stress hormone cortisol. Therefore, chronic stress may mediate the association between low SES and elevated cortisol levels and its adverse outcomes. AIM We investigated whether SES was associated with a chronic measure of cortisol exposure in a child population. METHODS Cortisol and cortisone were measured in scalp hair in 270 children and adolescents, aged 4-18 years, enrolled through school visits. Neighborhood level SES was based on a score developed by the Netherlands Institute for Social Research using postal codes, and this includes neighborhood measures of income education and unemployment. Maternal and paternal education level were used as indicators of family SES. RESULTS Neighborhood level socioeconomic status score was significantly associated with hair cortisol (β=-0.103, p=0.007, 95%CI [-0.179, -0.028]) and hair cortisone (β=-0.091, p=0.023, 95%CI [-0.167, -0.015]), adjusted for age and sex. Additionally, hair cortisol was significantly correlated with maternal education level and hair cortisone was significantly correlated with paternal education level. CONCLUSION The results of our study suggest that the widely shown association between low family SES and adverse child health outcomes may be mediated by chronic stress, given the chronically higher levels of cortisol in children and adolescents in families with low SES. It is especially notable that the association between SES and cortisol was already found in children of young age as this can have major consequences, such as increased risk of cardio metabolic diseases in later life.

LC‐MS/MS‐based method for long‐term steroid profiling in human scalp hair

Liquid chromatography–tandem mass spectrometry (LC‐MS/MS) is the method of choice for quantification of steroids. Human scalp hair provides the possibility to measure long‐term retrospective steroid concentrations, which is especially useful for steroids with large time‐dependent fluctuations in concentration, such as the glucocorticoid cortisol.

Validation and Reference Ranges of Hair Cortisol Measurement in Healthy Children

Background: Cortisol is produced in a circadian rhythm controlled by the hypothalamus-pituitary-adrenal axis, making it cumbersome to measure long-term cortisol exposure. Hair has proven to be a reliable matrix for long-term cortisol measurement in adults and can be used as diagnostic tool for (cyclic) Cushings syndrome. The diagnostic applicability in children has not been studied, nor have the effects of development and hair care been evaluated in children. We aimed to establish reference ranges of hair cortisol concentrations (HCC) in healthy children and to evaluate the effects of age, gender, puberty and characteristics of hair care. Methods: In 128 healthy children aged 4-14 years, HCC were measured in a small 3-cm hair lock from the back of the head. Results: HCC increased with age (p = 0.04) up to age 10 years, with a mean of 5.0, 5.8, 6.8 and 8.5 pg/mg at age 4-5, 6-7, 8-9 and 10-14 years, respectively. Children aged 4-7 years had significantly lower HCC compared to healthy adults (p = 0.007). We did not find any influence of gender, puberty or hair care characteristics on hair cortisol. Conclusion: HCC can be reliably measured in childhood, and reference ranges increase with age. HCC in children are not dependent on hair care or hair characteristics.

Long-term glucocorticoid concentrations as a risk factor for childhood obesity and adverse body-fat distribution

Background:Childhood obesity is an important risk factor for premature development of the metabolic syndrome (MetS) at adulthood. There is need for understanding of the mechanisms underlying the MetS and obesity. Patients with Cushing’s disease suffer from similar metabolic complications, leading to the hypothesis that inter-individual cortisol variation may contribute to the onset of obesity. In addition, glucocorticoid receptor (GR)-gene polymorphisms resulting in differential glucocorticoid (GC) sensitivity, have been associated with an adverse metabolic profile.Aim:To study associations of GC levels in scalp hair, as a marker of long-term systemic GC concentrations, and genetically determined GC sensitivity with obesity and body-fat distribution in children.Methods:We performed a cross-sectional study of cortisol and cortisone concentrations over a 3-month period, measured by LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in hair of 3019 6-year-old children participating in the Generation R study. Genotyping of GR-gene polymorphisms was performed.Results:Of all children, 4.3% was obese and 13.4% overweight. Cortisol was significantly associated with risk of obesity (odd ratio (OR): 9.4 (3.3–26.9)) and overweight (OR: 1.4 (1.0–2.0)). Cortisone was associated with risk of obesity (OR: 1.9 (1.0–3.5)). Cortisol and cortisone were significantly positively associated with body mass index, fat mass (FM) index and android/gynecoid FM ratio. GR polymorphisms were not associated with adiposity parameters.Conclusion:Long-term cortisol concentrations are strongly associated with an increased risk of childhood obesity and adverse body-fat distribution. Future research may reveal whether these are causal relations and may be a target for therapy.

Predicting hair cortisol levels with hair pigmentation genes: a possible hair pigmentation bias

Cortisol concentrations in hair are used to create hormone profiles spanning months. This method allows assessment of chronic cortisol exposure, but might be biased by hair pigmentation: dark hair was previously related to higher concentrations. It is unclear whether this association arises from local effects, such as increased hormone extractability, or whether the association represents systemic differences arising from population stratification. We tested the hypothesis that hair pigmentation gene variants are associated with varying cortisol levels independent of genetic ancestry. Hormone concentrations and genotype were measured in 1674 children from the Generation R cohort at age 6. We computed a polygenic score of hair color based on 9 single nucleotide polymorphisms. This score was used to predict hair cortisol concentrations, adjusted for genetic ancestry, sex, age and corticosteroid use. A 1-standard deviation (SD) higher polygenic score (darker hair) was associated with 0.08 SD higher cortisol levels (SE = 0.03, p = 0.002). This suggests that variation in hair cortisol concentrations is partly explained by local hair effects. In multi-ancestry studies this hair pigmentation bias can reduce power and confound results. Researchers should therefore consider adjusting analyses by reported hair color, by polygenic scores, or by both.

Hair analysis reveals subtle HPA axis suppression associated with use of local corticosteroids: The Lifelines cohort study

BACKGROUND AND AIMS Scalp hair is increasingly used to measure the long-term exposure to endogenous glucocorticoids hormones. Long-term cortisone (HairE) and cortisol (HairF) have been associated with obesity, metabolic syndrome, cardiovascular disease and psychopathology. However, little is known about the influence of the use of local corticosteroids and major stressful life events on hair glucocorticoids. MATERIALS AND METHODS We determined HairE and HairF using liquid chromatography - tandem mass spectrometry in 295 adult participants of the population-based Lifelines cohort study (75% females, median age 42). We collected anthropometry and fasting metabolic laboratory values, questionnaires on hair characteristics, recent use of corticosteroids, and recent major stressful life events. RESULTS After adjustment for covariates, hair glucocorticoids increased with age, male sex, black or brown hair color, and frequency of sweating on the scalp, and decreased with higher hair washing frequency (P<0.05). HairE was decreased in participants who used systemic corticosteroids (5.4 vs. 8.5pg/mg hair, P=0.041), and in participants who only used local agents such as inhaled, topical and nasal corticosteroids (6.8 vs. 8.5pg/mg, P=0.005). Recent life events were positively associated with HairF after adjustment for age and sex (P=0.026), but this association lost significance after adjustment for hair related characteristics (P>0.05). CONCLUSIONS HairE can be a useful marker to detect mild adrenal suppression due to corticosteroid use in the general population, even when only inhaled, nasal or topical corticosteroids are used, which suggests that these commonly used agents induce systemic effects.

Scalp hair 17-hydroxyprogesterone and androstenedione as a long-term therapy monitoring tool in congenital adrenal hyperplasia

Glucocorticoid replacement therapy in congenital adrenal hyperplasia (CAH) is challenging, especially in children, because both over‐ and under‐dosing may have profound and long‐lasting adverse effects. Clinical follow‐up parameters are largely nonspecific and slow to develop. Steroid concentrations in scalp hair may be a useful monitoring tool, as it provides information on both long‐term steroid precursor and glucocorticoid exposure.