Metabolic syndrome in adults with autistic traits: associated psychological, behavioral, and biological factors in females and males - a PharmLines initiative.

Background: While cardiovascular diseases is highly prevalent and an important cause of mortality in autistic adults, knowledge on their increased cardiovascular risk is limited. Hence, this study aimed to investigate psychological, behavioral, and physical factors associated with metabolic syndrome (MetS) in adults with autistic traits. Methods: In total, 17,705 adults from the Lifelines Cohort were included and categorized using Autism Spectrum Quotient-10 sum-scores. The quartiles with highest (HQ-traits-group females: n = 2,635; males: n = 1803) and lowest levels of autistic traits (LQ-traits-group, n = idem) were analyzed. Using multivariable logistic regression, the associations between MetS and (self-reported and interviewed) psychological, behavioral, and physically measured factors in these stratified groups were investigated. Results: Among females, MetS was more common in the HQ-traits-group than in the LQ-traits-group (10.0% versus 7.5%, p < 0.01), while this was not the case among males (HQ-traits-group 13.8% versus LQ-traits-group 13.1%, p = 0.52). In both the female and male HQ-traits-group, the presence of MetS was associated with poorer self-reported health, less daily physical activity, and altered leukocyte counts. Conclusion: These findings underline the relevance of adequate cardiovascular prevention in adults with higher levels of autistic traits. Future research could gain more insight into the relationship between cardiovascular risk and autistic traits in females, and into tailored cardiovascular prevention.

[Intermittent fasting in science and practice; what are the effects on weight and cardiometabolic health?] / Intermitterend vasten in wetenschap en praktijk.

Intermittent fasting (IF) is a broad concept and covers several fasting regimes. Studies of 'early time restricted feeding' and 'alternate day fasting' with energy restriction show a greater effect on weight and cardiometabolic health in overweight people in the short term, compared to a continuous caloric restriction (CCR). 'Late time restricted feeding' seems to have no or unfavorable effects. Long-term studies (up to 2 years) suggest that IF regimens are not superior to continuous caloric restriction. The few studies available show a similar compliance and metabolic adaptation between IF and CCR. There is insufficient knowledge about long-term safety in various groups of people, the influence of dietary quality and the practical feasibility of IF regimes. As a result, no recommendations can yet be made on the use of IF in the treatment of overweight and related diseases.

[Pharmacotherapy for obesity]. / Farmacotherapie voor obesitas.

Obesity is a complex endocrine disease, mainly caused by environmental, behavioral and biological factors. Maintaining weight loss is extremely difficult due to the neuro-endocrine dysregulations that stimulate the body to return to the previous, increased, weight. Identifying underlying weight-gaining factors is needed, including medication-related, psychological and endocrine factors, as well as monogenic obesity. The cornerstone of treatment is optimization of lifestyle and all other contributing factors. Achieving at least 5% weight loss already has important health benefits. If combined lifestyle intervention (CLI) alone is not successful, pharmacotherapy or bariatric surgery can be added for patients with increased weight-related health risks. Recently, novel pharmacotherapy became available, among which, liraglutide 3 mg and the combination therapy naltrexone/bupropion, which leads to an additional 5-6% mean weight loss compared to CLI alone. For rare forms of obesity there are specific drugs that target defects in the regulation of hunger and satiety. Promising new pharmacotherapy for obesity is under development.

Spontaneous remission of unidentified Cushing's disease revealed by hair cortisol analysis.

Pituitary apoplexy is an infrequent but life-threatening complication of pituitary adenomas. When apoplexy occurs in a hormonally active adenoma, this may induce spontaneous remission of the clinical syndrome. In these cases, clinical suspicion of Cushing's disease or acromegaly may arise at presentation, but due to spontaneous remission of active hormone production, it is not possible to biochemically confirm this diagnosis in retrospect. Resolution of clinical symptoms during follow up retrospectively suggests the diagnosis. However, we describe a patient with Cushing's disease presenting with pituitary apoplexy, who was biochemically in remission at presentation. The diagnosis could be confirmed in retrospect using hair cortisol analysis, thereby enabling clinicians to adequately anticipate remission of Cushing's disease.

Hair cortisol in patients with a depressive episode treated with electroconvulsive therapy.

BACKGROUND: There is substantial evidence showing changes in hypothalamic pituitary adrenal (HPA)-axis activity in patients with major depressive disorder (MDD). Also, there seem to be differences in HPA-axis functioning between MDD subgroups. It is however unclear whether hair cortisol concentrations (HCC), which are a stable marker of long-term cortisol levels, are suitable as a biomarker for identifying subgroups in MDD. METHODS: We were able to attain valid HCC from a scalp hair sample of sixty-two patients with a major depressive episode right before electroconvulsive therapy (ECT). HCC were our main biological outcome measure. We created subgroups using depression severity as defined by the Hamilton Depression Rating Scale, the presence/absence of psychotic symptoms, the presence of melancholia as defined by the CORE and catatonia as defined by the Bush-Francis Catatonia Rating Scale. RESULTS: Our analyses of the total group showed a median HCC of 4.4 pg/mg. We found patients with catatonia (N = 10) to have substantially higher median HCC (8.3 pg/mg) than patients without catatonia (3.8 pg/mg). Although presence of melancholia and depression severity were not significantly associated with HCC, more severe psychomotor agitation was associated with higher HCC. Pre-treatment HCC was not associated with ECT outcome. STRENGTHS AND LIMITATIONS: A complicating factor in interpretation of our results was the large variability in HCC. This could be related to potential confounders such as cardiometabolic and other comorbidities, that were however addressed to the extent possible. CONCLUSIONS: HCC is a potential biomarker for MDD patients with severe agitation and/or catatonia. CLINICALTRIALS.GOV: Identifier: NCT02562846.

Obesity-associated T-cell and macrophage activation improve partly after a lifestyle intervention.

BACKGROUND: The relation between low-grade inflammation and metabolic dysfunction in obesity is not fully explored. OBJECTIVE: To evaluate immune parameters in the obese state and after a lifestyle intervention program. METHODS: Patients with obesity (n = 87) from an academic obesity clinic were compared with controls with regard to macrophage and T-cell activation (reflected by serum levels of soluble CD163 (sCD163) and soluble IL-2 receptor (sIL-2R), respectively), and an array of cytokines, chemokines, and growth factors. In addition, these parameters and regulatory T-cells (Treg), were studied in 27 patients who followed a 75-week lifestyle intervention (dietary advice, exercise, and psychoeducation). RESULTS: Mean sIL-2R and sCD163 levels were higher in patients than controls (sIL-2R:2884 ± 936 pg/ml vs. 2207 ± 813 pg/ml, p = 0.001; sCD163:1279 ± 580 pg/ml vs. 661 ± 271 pg/ml, p < 0.0001 respectively). Patients with metabolic syndrome (MetS) had higher sCD163 than those without (1467 ± 656 pg/ml vs. 1103 ± 438 pg/ml). Patients had higher IL-1ß, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-8, IL-9, IL-10, IL-15, IL-17A, MCP-1/CCL2, MIP-1α/CCL3, MIP-1ß/CCL4, G-CSF, GM-CSF, FGF, IFN-γ, and TNF-α than controls, whereas VEGF-A, PDGF-BB, and eotaxin were lower. Upon intervention, sIL-2R decreased while peripheral Treg frequencies increased within the reference range (p = 0.042 and p = 0.005 respectively). The sIL-2R decrease correlated to a decrease in waist circumference (rho = 0.388, p = 0.045) and in trend to a decrease in MetS components (rho = 0.345, p = 0.078). The Treg increase was unrelated to weight loss or metabolic improvement. Mean sCD163 did not change significantly upon intervention, nor did the cytokines, chemokines, and growth factors (except IP-10/CXCL10). CONCLUSION: In obesity, T-cell homeostasis improves after a lifestyle intervention. Immunologic alterations can occur independently of metabolic improvement.

Scalp hair cortisol and testosterone levels in patients with sarcoidosis.

BACKGROUND: Patients with sarcoidosis often experience fatigue and psychological distress, but little is known about the etiology of these conditions. While serum and saliva steroid hormones are used to monitor acute steroid levels, scalp hair analysis is a relatively new method enabling measurement of long-term steroid levels, including hair cortisol reflecting chronic stress. We investigated whether scalp hair cortisol and testosterone levels differ between sarcoidosis patients both with and without fatigue and general population controls. Additionally, we studied if these hormones could serve as objective biomarkers for psychological distress in patients with sarcoidosis. METHODS: We measured hair steroid levels using liquid chromatography-tandem mass spectrometry in glucocorticoid naïve sarcoidosis patients. Patients completed the Perceived Stress Scale, Fatigue Assessment Scale, Hospital Anxiety and Depression Scale and Short Form 36 (SF-36). Hair steroid levels from 293 participants of the population-based Lifelines cohort study served as controls. RESULTS: Thirty-two patients (14 males) were included. Hair cortisol, but not testosterone, concentrations were significantly higher in patients with sarcoidosis than in general population controls (mean 6.6 versus 2.7 pg/mg, p<0.001). No differences were found in hair cortisol and testosterone levels between fatigued and non-fatigued patients with sarcoidosis. Hair cortisol of sarcoidosis patients correlated significantly with anxiety (r = 0.47, p = 0.01), depression (r = 0.46, p = 0.01), and SF-36 mental domain (r = -0.38, p = 0.03), but not with fatigue. CONCLUSIONS: Patients with sarcoidosis have chronically higher levels of the stress hormone cortisol than the normal population, while testosterone levels in hair did not differ. Hair cortisol levels were positively related to subjective measures of psychological distress, but not to fatigue. Our study shows that hair cortisol is a promising non-invasive biomarker for psychological distress in patients with sarcoidosis. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03108547. Registered 31 March 2017, retrospectively registered.

[Obesity cannot be solved by meal replacements]. / Obesitas los je niet op met een kuurtje.

Finding new ways to reach sustainable weight reduction, which are suitable for daily practice, is important. In this commentary we discuss the article by Astbury et al. suggesting that a total diet replacement (TDR) programme in a primary care setting is safe and effective. We raise some important questions about the limited duration of the study, lack of clarity about additionally provided behavioural coaching and/or exercise in the intervention group vs the usual care control group, as well as the potential effects of low calorie dieting on muscle mass. Although other studies using meal replacements do not show an additional benefit compared to interventions based on a balanced diet with behavioural therapy, the results after this 52-week study are promising. However, longer-term follow-up and external validation is needed. Moreover, the large variation in results between participating centres shows that it is not a matter of "one size fits all" when it comes to successful dieting.

Prenatal maternal psychopathology and stress and offspring HPA axis function at 6 years.

OBJECTIVE: Intrauterine exposures such as maternal psychopathology and stress are known to influence the physical and mental health of the offspring. One of the proposed pathways underlying these associations is dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity in the offspring. This study examined the relation of perinatal maternal symptoms of psychopathology and stress with offspring HPA axis activity at 6 years as measured by hair cortisol and cortisone concentrations. METHODS: The study was part of the population-based Generation R Study, a prospective population-based cohort from fetal life onwards. 2546 children and their mothers formed the study population. Perinatal maternal psychopathology and stress were assessed by questionnaires in the second and third trimester. Principal components for both psychopathology and stress were created to reduce the number of explanatory variables. Child hair samples for cortisol and cortisone measurements were collected at the age of 6. Linear regression analysis, adjusted for covariates, was used to examine associations between maternal psychopathology and stress and child hair cortisol and cortisone levels. RESULTS: The maternal psychopathology principal component was associated with higher child hair cortisone (adjusted B = 0.24, 95%CI 0.08;0.40, p-value < 0.01). Effect estimates of the individual dimensions ranged from 0.97 (95%CI 0.21;1.73, p-value = 0.01) for interpersonal sensitivity to 1.67 (95%CI 0.86;2.47, p-value < 0.01) for paranoid ideation. In addition, children exposed to intrauterine stress, as measured by the principal component, had higher hair cortisone levels (adjusted B = 0.54, 95%CI 0.21;0.88, p-value < 0.01). Exposure to maternal psychopathology and stress was not associated with offspring hair cortisol. Stratification by child sex resulted in associations between maternal symptoms of psychopathology during pregnancy and child hair cortisone levels in boys and associations between maternal symptoms of stress during pregnancy and child hair cortisone levels in girls. CONCLUSION: Our results suggest that maternal psychopathology and stress during pregnancy are associated with long-term HPA axis activity of the offspring. The association of maternal psychopathology and stress during pregnancy with offspring hair cortisone levels is a novel finding. Future studies should examine whether these psychophysiological differences between exposed and non-exposed children underlie offspring morbidity associated with maternal psychopathology and stress during pregnancy.

[Obesity in the clinic room: diagnostics first, followed by effective treatment]. / Obesitas in de spreekkamer.

In clinical practice, relatively little attention is directed towards identifying underlying causes and contributing factors to weight gain in patients with obesity. However, recognising these "hidden fattening factors" is important as it can lead to more effective treatment strategies. In particular if underlying causes can be solved first, this could help to realise sustainable weight reduction. Besides the well-known lifestyle-related aspects, obesity may be caused or maintained by medication use, endocrine or hypothalamic disorders, monogenetic or syndromic diseases, and mental factors, which may require specific (medical) treatment. For lifestyle-related obesity, a combined lifestyle intervention (CLI) is a first step to combat obesity. This treatment comprises intensive guidance regarding healthy nutrition, physical activity, and behavioural psychology. In case of morbid obesity and insufficient effects of CLI after one year, weight-reducing medication or a bariatric intervention can be considered. This systematic strategy for diagnostics and treatment of obesity is illustrated by two clinical cases.

The relationship between 63days of 24-h urinary free cortisol and hair cortisol levels in 10 healthy individuals.

BACKGROUND: Interest in measuring cortisol in scalp hair is increasing because of its assumed ability to provide a historical timeline of previous systemic levels of cortisol. Yet, it remains uncertain how well hair cortisol represents the total systemic secretion of cortisol over time. METHODS: Ten healthy individuals collected 24-h urine samples for 63 consecutive days and provided a hair sample at the end of the study period. 24-h urinary creatinine levels in every urine sample were determined to assess completeness of the samples. Cortisol levels in 24-h urine samples and in hair were measured with liquid chromatography tandem mass spectrometry. The correlations between urinary cortisol and hair cortisol were calculated using Kendall's tau. RESULTS: We found a nonsignificant moderate correlation between average urinary cortisol secretion and average hair cortisol concentration rт=0.422, p=0.089. CONCLUSIONS: Hair cortisol concentration correlates low to moderately with 24-h urinary cortisol concentration over a period of 63days.

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.

Glucocorticoid receptor polymorphisms modulate cardiometabolic risk factors in patients in long-term remission of Cushing's syndrome.

CONTEXT: Glucocorticoid receptor (GR) polymorphisms modulate glucocorticoid (GC) sensitivity and are associated with altered metabolic profiles. OBJECTIVE: To evaluate the presence of GR polymorphisms (BclI (rs41423247), N363S (rs56149945), ER22/23EK (rs6189/rs6190), and 9ß (rs6198) and investigate their associations with metabolic alterations in patients in long-term remission of Cushing's syndrome (CS). DESIGN AND SETTING: Cross-sectional case-control study. PATIENTS AND METHODS: Sixty patients in long-term remission of CS were genotyped. Associations between GR polymorphisms and multiple vascular, body composition and metabolic parameters were investigated. MAIN OUTCOME MEASURES: Allelic frequencies of the polymorphisms and their associations with several cardiometabolic risk factors. RESULTS: This study shows that carriers of the 9ß polymorphism have a higher systolic blood pressure and lower resistin levels. The GC sensitizing BclI polymorphism is associated with an adverse cardiometabolic risk factor profile: higher fat percentages of extremities and legs, higher serum leptin and E-selectin levels, and higher intima media thickness in carriers versus non-carriers. CONCLUSIONS: The 9ß and BclI polymorphisms of the GR adversely affect the cardiometabolic profile in patients who are in remission after the treatment of CS. This suggests that genetically altered GC sensitivity modulates the long-term adverse cardiometabolic effects resulting from (endogenous) hypercortisolism.

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 (ß=-0.103, p=0.007, 95%CI [-0.179, -0.028]) and hair cortisone (ß=-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.

Cortisol levels in scalp hair of patients with structural heart disease.

BACKGROUND: Stress is considered a modifiable risk factor for cardiovascular disease. Scalp hair analysis is a tool to assess long-term exposure to the stress hormone cortisol. We aimed to determine the association between hair cortisol concentrations (HCC) and clinical characteristics in patients with structural heart disease. Additionally, we investigated potential predictors for longitudinal change in HCC. METHODS: The study consisted of 261 patients with structural heart disease from a randomized controlled trial of mindfulness training. One sample of scalp hair was used to determine HCC both at baseline and at 12-week follow-up. In 151 patients, HCC was available (mean age: 41.3 years, range 18-65). We investigated the association between HCC at baseline and several physiological measures (BMI, blood pressure, heart rate, respiratory rate, 6-minute walk test), as well as psychological parameters (physical and mental component summary measures (SF-36), emotional distress (HADS), and perceived stress). Additionally, we used these clinical parameters to predict HCC change over time. RESULTS: The median HCC was 22.3 pg/mg of hair (23.5 interquartile range). In multivariable linear regression analyses, an association was observed between log-transformed HCC and BMI (ß 0.171, p=0.037), respiratory rate (ß 0.194, p=0.016), and the physical summary score (ß -0.163, p=0.054). Independent predictors of log-transformed HCC change after 12 weeks were mental summary score (ß -0.200, p=0.019) and diastolic blood pressure (ß -0.171, p=0.049). CONCLUSIONS: In patients with structural heart disease a positive association exists between HCC and BMI. Mental health status may predict a change in long-term cortisol over time.

[When is a perioperative glucocorticoid stress-dose regime indicated?]. / Wanneer is een perioperatief glucocorticoïdstressschema geïndiceerd?

To avoid a life-threatening crisis due to adrenal insufficiency during or after surgery, extra glucocorticoids are often administered perioperatively to patients already taking them. However, this type of supplementation also has a downside, e.g. complications such as fluid retention, hyperglycaemia, psychiatric disturbances, infection and delayed wound healing. In patients with primary or central adrenal insufficiency their daily hydrocortisone substitution should be supplemented perioperatively depending on the type of surgery. Also, suppression of the pituitary-adrenal function may occur in patients being treated with exogenous glucocorticoids for other diseases and this may justify perioperative supplemental glucocorticoid administration. However, the extent of adrenal suppression in response to exogenous glucocorticoids is heterogeneous. This can be explained by differences in glucocorticoid type and dosage, treatment duration, mode of administration, as well as an individual's glucocorticoid sensitivity and metabolism of glucocorticoids. In this article we provide suggestions as to which patients should or should not be perioperatively supplemented with glucocorticoids.

[New insights into ways of determining cortisol exposure in patients with bipolar disorder]. / Nieuwe inzichten in de evaluatie van cortisolblootstelling bij patiënten met een bipolaire stoornis.

BACKGROUND: Previous research has shown a relationship between the stress hormone cortisol and bipolar disorder. The level of cortisol exposure is usually examined by means of measurements that provide a snapshot of cortisol exposure or by means of dynamic testing. Recently, a new technique has been introduced which can measure, retrospectively, the cortisol level in scalp hair over longer periods of time. AIM: To provide insight into various methods used in psychiatry for measuring the hypothalamus-pituitary-adrenal (HPA)-axis activity and also to highlight recent research into measurements of cortisol in scalp hair of patients with bipolar disorder. METHOD: We give a brief overview of the literature relating to HPA-axis testing in psychiatric patients. As a result of our recent studies with 100 patients suffering from bipolar disorder, we are now able to determine the levels of cortisol in scalp hair. RESULTS: Tests that measure hpa activity can be divided into three categories: point measurements, stimulation tests and inhibition tests. In our recent study of bipolar patients we found that a raised level of cortisol in scalp hair was related to a later onset of bipolar disorder (in patients over 30) or to multiple psychiatric diagnoses. Lower levels of cortisol level in scalp hair of bipolar patients were observed in bipolar patients with comorbid panic disorder. CONCLUSION: The use of hair analysis to measure mean cortisol levels over long periods seems to give added value to the hpa-axis tests currently used for measuring cortisol exposure. The technique may make it easier to differentiate between various subtypes of bipolar disorder.

Elevated hair cortisol concentrations in children with adrenal insufficiency on hydrocortisone replacement therapy.

BACKGROUND: Glucocorticoid replacement therapy in patients with adrenal insufficiency needs to be tailored to the individual patient based on body composition and clinical signs and symptoms as no objective method for assessment of treatment adequacy is available. Current treatment regimens are often not satisfactory, which is shown by the adverse metabolic profile and doubled mortality rates in treated adrenal insufficiency patients. Measurement of cortisol concentrations in hair reflect the long-term systemic cortisol exposure and may be of use in refinement of hydrocortisone treatment. OBJECTIVE: We aimed to study whether long-term cortisol (hydrocortisone) levels, as measured in scalp hair, are similar in children with adrenal insufficiency and healthy children. MATERIAL AND METHODS: We set up a case control study, measuring anthropometric characteristics and hair cortisol concentrations (HCC) in 54 hydrocortisone substituted children with adrenal insufficiency (AI patients) in the age of 4-18 years and 54 healthy children matched for gender and age. RESULTS: Mean HCC were significantly higher in AI patients compared with healthy controls (mean 13·3 vs 8·2 pg/mg, P = 0·02). AI patients also had a higher BMI (P < 0·001) and waist circumference (WC) (P = 0·02). HCC was significantly associated with BMI (P = 0·002) and WC (P = 0·002). HCC explained 13% of the difference in BMI and 29% of the difference in WC between AI patients and controls. CONCLUSION: Hydrocortisone-treated AI patients have increased HCC and adverse anthropometric characteristics compared with healthy controls. HCC measurement may be of value in identifying overtreatment and thereby improve hydrocortisone replacement therapy.