Cortisone Levels Research Articles

Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease: A systematic review and meta-analysis.

The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. We also performed a meta-analysis on the cross-sectional difference in HairF levels between individuals with versus without CVD. Seven studies were included regarding MetS, sixteen regarding CVD, and one regarding both. Most articles indicated a strong, consistent cross-sectional association of higher HairF and HairE levels with CVD, which was confirmed by our meta-analysis for HairF (eight studies, SMD=0.48, 95% confidence intervals [CIs]: 0.16-0.79, p=0.0095). Moreover, these relationships appear largely independent of standard risk factors. Age seems relevant as the effect seems stronger in younger individuals. Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.

Cushing Syndrome Caused by Pituitary and Adrenal Hybrid Tumor: A Rare Case Report

Introduction: Cushing syndrome is a rare endocrine disorder caused by a variety of underlying etiologies. It can be due to exogenous or endogenous high cortisone levels (ACTH-dependent or ACTH-independent). We herein report a case of ACTHdependent Cushing syndrome caused by pituitary and adrenal hybrid adenoma. Case report: A 42-year-old female presented with a complaint of hematemesis. She had hirsutism, central obesity and violaceous striae on her abdomen and thigh. On detailed clinical examination and relevant investigation, we found that the cause of hematemesis was esophagitis with necrotic gastric ulcer due to Cushing syndrome caused by the pituitary and adrenal hybrid adenoma. Discussion: Cushing syndrome is a rare endocrine disorder characterized by increased exogenous or endogenous serum cortisol levels, which lead to various clinical presentations. Early identification of the disease and its cause is critical. The entire clinical presentation must be considered for correct diagnosis, which is generally delayed due to the overlapping symptoms of the disease with various specialities. Conclusion: Diagnosis and management of Cushing’s syndrome continues to present considerable challenges and necessitates referral to higher centers. Its diverse presentation warrants a complete clinical, physical, radiological and endocrine examination.

Extremely and very preterm children who were born appropriate for gestational age show no differences in cortisol concentrations or diurnal rhythms compared to full-term children.

The objective of this study was to compare the diurnal variations in cortisol and cortisone concentrations in serum and saliva among extremely preterm (EPT), very preterm (VPT), and full-term (FT) children, all born appropriate for gestational age (AGA). EPT, VPT, and FT children, all born AGA, were recruited from two healthcare centers. Cortisol and cortisone concentrations in serum and saliva were measured by liquid chromatography-mass spectrometry (LC‒MS). Statistical analysis was performed using nonparametric tests. A total of 101 children (5.0-8.9 years old) were included in this study: EPT=18, VPT=43 and FT=40. All groups had similar distributions in terms of age, birth weight standard deviation score (SDS) and BMI (SDS), showing no differences in serum ACTH, cortisol, or cortisone levels. Additionally, salivary cortisol and cortisone concentrations decreased significantly throughout the day (p values<0.0001). Salivary cortisol concentrations were below the limit of detection (0.55 nmol/L) before dinner andbefore bedtime in approximately one-third and two-thirds of all children, respectively. Salivary cortisone was detectable in all but one sample. The diurnal cortisol rhythm was preserved in all preterm children, regardless of their gestational age, and no differences in cortisol concentrations among the groups were found. This may have significant implications for the clinical management and follow-up of preterm individuals.

OR35-05 Interaction of Cortisol with Testosterone Predicts Abdominal Fat Mass in Normal-weight Polycystic Ovary Syndrome Women with Normal Serum 11-Oxygenated Androgens

Abstract Disclosure: D.A. Dumesic: Consulting Fee; Self; Ferring Pharmaceuticals, Precede Biosciences, Inc, Spruce Biosciences, Inc. Grant Recipient; Self; National Institutes of Health. A.F. Turcu: None. H. Liu: None. T.R. Grogan: None. D.H. Abbott: None. G. Lu: None. D. Dharanipragada: None. G.D. Chazenbalk: None. Adrenal and ovarian steroidogenesis are interwoven with endocrine-metabolic dysfunction into polycystic ovary syndrome (PCOS). Women with PCOS and normal weight have androgen excess along with preferential abdominal adipose deposition (1,2), which is partially reversed by androgen receptor blockade (3). The role of adrenal steroids in this relationship, however, remains unclear. The present study examines whether serum levels of 11-oxygenated adrenal androgens, cortisol and/or cortisone differ between normal-weight PCOS women and body mass index (BMI)/age-matched normo-androgenic ovulatory women (controls) and whether adrenal steroids associate with abdominal adipose deposition. Twenty normal-weight PCOS women and 20 age- and BMI-matched controls underwent circulating hormone/metabolic determinations, intravenous glucose tolerance testing and total-body dual-energy x-ray absorptiometry. Clinical characteristics and hormonal values were compared between PCOS and control subjects. An unpaired Student’s t-test and Pearson correlation coefficients, adjusting for serum cortisol, were used as appropriate. Serum total/free testosterone (T) and androstenedione (A4) levels, and android/gynoid fat mass ratio, were greater in PCOS women with low-normal insulin sensitivity than in controls (all androgens P&amp;lt;0.001; android/gynoid fat mass ratio, P=0.026). A positive correlation of serum androgens with android/gynoid fat mass ratio was observed in all women combined (total T: R=+0.41, P=0.013; free T: R=+0.49, P=0.003; A4: R=+0.45, P=0.006). Serum 11ß-hydroxyA4 (11OHA4), 11-ketoA4 (11KA4), 11ß-hydroxyT (11OHT) and 11-ketoT (11KT), cortisol and cortisone levels were comparable between PCOS women and controls, and were unrelated to body fat distribution. Serum 11-oxygenated adrenal androgens correlated negatively with % total body fat (11OHA4: R=-0.42, P=0.011; 11KA4: R=-0.34, P=0.046; 11OHT: R=-0.36, P=0.031; 11KT: R=-0.37, P=0.027), but were no longer significant when adjusting for a concomitant negative relationship of serum cortisol with % total body fat (R=-0.45, P=0.006). Serum cortisol levels also correlated negatively with android fat mass in all women combined (R=-0.38, P=0.021) and were accompanied by a trend (P=0.075) towards reduced serum cortisol to cortisone ratio, as a marker of reduced 11β-hydroxysteroid dehydrogenase type 1 (HSD11ß1) conversion of cortisone to cortisol, in PCOS women versus controls (P=0.075). Ratios of 11KT/11KA4 and 11KT/11OHT as markers of AKR1C3and HSD11ß2 activities, respectively, did not differ by female type (both enzyme markers, P=nonsignificant). Conclusion: Reduced cortisol action, mediated in part through decreased HSD11ß1, interacts with an elevated androgens pathway to determine abdominal fat mass in normal-weight PCOS women with normal serum 11-oxygenated androgens.

SAT299 Comparison Of Plasma Cortisol-, Salivary Cortisol- And Salivary Cortisone-response To The Short Synacthen Test In Women Using Oral Contraceptives

Abstract Disclosure: N. Bäcklund: None. S. Lundstedt: None. T. Olsson: None. P.M. Dahlqvist: None. G. Brattsand: None. Introduction: The short Synacthen test (SST) is a cornerstone in the diagnosis of adrenal insufficiency (AI). However, cortisol levels in serum or plasma may be misleadingly elevated by estrogen containing oral contraceptives (OCs), due to increased levels of cortisol binding protein (CBG). This may falsely declare a woman with AI to be cortisol sufficient. Salivary cortisol and cortisone closely correlate with the unbound fraction of plasma cortisol and is thus less likely to be influenced by variations in CBG levels. Our hypothesis was that the salivary cortisol and cortisone response to SST would be similar in women with and without OC use. Materials and methods: A standard intravenous 250 µg SST was performed in 87 women without known diseases or medications affecting the cortisol axis, 41 using OCs containing ethinylestradiol and 46 controls. Plasma cortisol was analyzed by Roche Elecsys Cortisol II assay and salivary cortisol and cortisone by LC-MS/MS in samples collected at baseline (time 0), and 30 and 60 minutes after Synacthen injection. The effect of OCs upon plasma cortisol, salivary cortisol and salivary cortisone was assessed by a two-way ANOVA with sampling time after SST as repeated measure. Results: There was an overall effect of OCs on plasma cortisol, but not on salivary cortisol or cortisone. Plasma cortisol levels were considerably higher in the OC group vs. controls at all time points; +150% at 0 minutes; +90% at 30 minutes; and +86% at 60 minutes. There was a significant interaction between OC use and sample time point for both salivary cortisol and cortisone. Mean salivary cortisol in women using OCs was 37% higher vs. controls at 0 minutes but was instead lower in the OCs group at 30 and 60 minutes after SST (-13% and -11%, respectively). Similarly, mean salivary cortisone was also slightly higher in the OC group than controls at baseline (+13%) and somewhat lower at 30 and 60 minutes (-6% and -7%). Conclusion: Plasma cortisol levels during an SST were significantly elevated in women using OCs containing estrogen whereas OC effects upon salivary cortisol and cortisone levels were modest, especially for salivary cortisone. Analysis of salivary cortisone is a promising alternative to plasma cortisol for diagnosis of AI in women using OCs. Presentation: Saturday, June 17, 2023

SAT296 Ambulatory 24-hour Tissue Microdialysis Of Cortisol And Metabolites, A Tool For Precision Management In Addison’s Disease

Abstract Disclosure: I. Botusan: None. K. Berinder: None. P. Methlie: None. T. Upton: None. E. Zavala: None. K. Simunkova: None. D.A. Vassiliadi: None. I. Marinelli: None. G.M. Russell: None. M.A. Grytaas: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. O. Kampe: None. M. Oksnes: None. S. Bensing: None. Background: The autoimmune attack on the adrenals in AD (Addison’s disease) results in lack of the vital hormones cortisol and aldosterone, rendering AD patients dependent on life-long hormone replacement therapy. Current therapies cannot replicate the physiological well-tuned, circadian and ultradian hormonal oscillations properly, probably contributing to increased mortality, morbidity and reduced quality of life. No established biomarker for treatment monitoring exists hampering treatment optimization. Ambulatory 24-hour dynamic steroid profiling may represent a novel therapy-monitoring tool, providing new insights in different replacement therapy regimes. Aim: We aimed to assess 24-hour profiles of free cortisol and metabolites in patients with AD on different glucocorticoid replacement therapies (GRT) and compare the results with healthy volunteers (HV). Material and methods: The study includes 41 patients with AD on different GRT regimes (hydrocortisone, cortisone acetate, modified release hydrocortisone) and 214 healthy participants. Twenty minute microdialysis fractions were collected ambulatory from abdominal subcutaneous tissue over 24 hours using a novel and portable microdialysis fraction collector (U-RHYTHM). Steroid hormones were analyzed by ultrasensitive liquid chromatography tandem mass spectroscopy (LC-MS/MS). Dynamic biomarkers were used to define hormone parameters in both healthy and hormone-replaced participants, and to assess the “time in range” for patients on GRT compared with the profiles of healthy controls. Results: Free cortisol and cortisone levels were measurable in all AD patients, while 18- hydroxycortisol, and corticosterone were detected only in a few AD patients suggesting the persistence of residual adrenal function. Lower cortisol levels during night were observed in AD compared with controls. Ambulatory 24-hour dynamic steroid profiling revealed marked interindividual variations partially depending on the type of GRT and dosing-regime. Conclusions: The 24-hour profiles of free cortisol and cortisone differs between patients with AD and healthy volunteers. Ambulatory 24-hour microdialysis samplings may provide a novel dynamic tool to monitor GRT in AD providing opportunity for individual dose adjustment. Presentation: Saturday, June 17, 2023

FRI159 Syndrome of Apparent Mineralocorticoid Excess (AME) from Licorice Tea

Abstract Disclosure: P.C. Lambert: None. We report a patient who had Syndrome of Apparent Mineralocorticoid Excess (AME) from licorice tea. Pt is a 65 y/o man with past medical history of HLD, HTN who presented to clinic for routine follow up. BMP was normal. Six months later patient reported diarrhea, bloating and gas after visiting family. To alleviate symptoms, he tried apple cider vinegar, herbal teas and stopped coffee and caffeinated drinks. His BP was 162/92. BMP showed Na 145, K 3.1, CO 37 and 20 meq of potassium daily was started. Follow up in 5/2020 found persistent elevated BP of 160/102 with elevated BP on home monitor and leg edema. Lisinopril-HCTZ was changed to amlodipine 5 mg. BMP showed Na 146, K 2.2, CO 44. Potassium was increased to 40 meq bid. Two weeks later BP was 160/90. Amlodipine was increased to 10 mg daily. He reported resolution of his edema. BMP showed Na 131, K 3.1, CO 33. At this point, the renin/aldosterone axis was tested with aldosterone &amp;lt;1.0 ng/dL and PRA &amp;lt;0.167 ng/mL/hr. On subsequent discussion it was found pt was taking black licorice tea. After cessation, pt’s BP improved and pt was gradually titrated off potassium supplements and blood pressure meds entirely. Repeat lab testing on 6/2020 found aldosterone 2.4 ng/dL, PRA 0.455 ng/mL/hr, Na 142, K 4.8, CO 31. On return to clinic on 8/2020 BP was 124/72 off medication. His labs were Na 143, K 4.1, CO 30. Syndrome of Apparent Mineralocorticoid Excess (AME) is caused by a deficiency in the 11-beta-hydroxysteroid dehydrogenase enzyme type 2 isoform (11-beta-HSD2). The enzyme converts cortisol to cortisone which cannot bind to the mineralocorticoid receptor. Deficiency of this enzyme will lead to more cortisol binding to the mineralocorticoid receptor which binds just as avidly as aldosterone. This leads to increased mineralocorticoid activity without increased aldosterone. Causes of AME can be genetic or induced by the steroid glycyrrhetinic acid, in licorice, that inhibits 11-beta-HSD2. Licorice candy in the USA generally does not have licorice root. It can be found in many sources including chewing tobacco and flavored chewing gum besides tea. Pt can take as low as 50 g daily of confectionery licorice for two weeks to produce elevated blood pressure. Patients will present with hypokalemia hypertension, metabolic alkalosis, low plasma renin activity and low plasma aldosterone levels. Urinary free cortisone and cortisol levels can assist with diagnosis but as in this case review of history was enough to diagnose and treat the patient. Presentation Date: Friday, June 16, 2023

THU599 Serum And Urinary Free Cortisone As Novel Predictor Of Low-renin Arterial Hypertension

Abstract Disclosure: A. Tapia-Castillo: None. J. Perez: None. A. Sandoval: None. F. Allende: None. S. Solari: None. C.E. Fardella: None. C. Carvajal: None. A large proportion of low-renin hypertensive (LRH) patients correspond to primary aldosteronism (PA) caused by excessive MR activation mediated by excess of aldosterone. However, some of these LRH patients have low to normal serum aldosterone levels, where is thought the MR activation is aldosterone-independent and more likely due to glucocorticoid-mediated MR activation, as occurs in the nonclassical apparent mineralocorticoid excess (NCAME), which is characterized by high cortisol/cortisone ratio and low cortisone, affecting not only blood pressure (BP) control and urinary potassium excretion but also causing cardiac and renal damage, endothelial dysfunction and subclinical inflammation. Objective: To evaluate cortisone as a predictor of LRH and its association with parameters of kidney and vascular damage. Design: A cross-sectional study was carried out in 206 adult subjects. The subjects were classified according to low-renin phenotype (plasma renin activity (PRA) &amp;lt;1ng/ml*h) and low serum cortisone (&amp;lt;p25th). We measured clinical, biochemical, renal and vascular parameters. Statistical analyses as group comparisons were performed by Mann Whitney, and discriminatory analyses by ROC curves. Results: We identified 43% of subjects with low-renin phenotype. PRA was associated with serum aldosterone (r=0.36; p&amp;lt;0.001) and serum cortisone (r=0.22; p=0.001). A binary logistic regression analysis shows that cortisone predicts low-renin phenotype (OR=0.4 [95% CI, 0.21 – 0.78]). The ROC curves show an AUC for serum cortisone was 0.62 (95% CI: 0.54 to 0.69; p = 0.004) and urinary cortisone 0.6 (95% CI: 0.52 to 0.67; p = 0.02) to discriminate subjects with low-renin from controls. Subjects with low serum cortisone showed a higher albuminuria, PAI-1 and lower sodium renal excretion. Urinary free cortisone was also associated to blood pressure and serum potassium (p&amp;lt;0.05). Conclusion: These findings highlight the concept that the low-renin phenotype is dictated not only by serum aldosterone levels but also by low cortisone, suggesting it should be considered in endocrine arterial hypertension screening, complementary in the diagnosis of primary aldosteronism since it could generate false positives in the calculation of the aldosterone to renin ratio. Moreover, our study suggests that low cortisone levels could be associated with future occurrence of vascular and kidney damage. Presentation: Thursday, June 15, 2023

Diverse forage improves lipid metabolism and antioxidant capacity in goats, as revealed by metabolomics.

It is well established that promoting the balance of nutrients and plant secondary metabolites (PSM) by feeding diverse forage physiologically improves ruminant production. However, the underlying mechanism remains unclear. To investigate the physiological mechanism related to the improvement of physiological stress tolerance, ruminants were fed diverse forage. Oxidative stress markers were quantified, and serum metabolomics was performed. Six crossbred Shiba wethers (32.8±9.2kg BW) were arranged in a replicated 3×3 Latin square design. The treatments were feeding only Sudan grass hay (100% SDN); feeding a mixture of Sudan grass and alfalfa hay (70:30, SDN-ALF); and feeding a mixture of Sudan grass, timothy grass, and alfalfa hay (35:35:30; SDN-TMT-ALF). Each diet group was fed its specific diet for 21days with a 14-day adaptation period. Feed intake and digestibility, blood biochemistry, total antioxidant capacity (TAC), and superoxide dismutase (SOD) were analysed. In addition, blood serum metabolites were assessed by liquid chromatography-tandem mass spectrometry. The DM intake and DM, organic matter, and CP digestibility were higher (P<0.05) in the SDN-TMT-ALF group than in the SDN group. The TAC was higher (P<0.01) in the SDN-TMT-ALF and SDN-ALF groups (809.51 and 813.7µM, respectively) than the SDN group (720.69µM), while the SOD level was unchanged (P=0.06) among the treatments. Total serum cholesterol and NH3 levels were higher (P<0.05) in the SDN-TMT-ALF group (89.17mg/dL and 242.42µg/dL, respectively) than in the SDN group (71.00mg/dL and 89.17µg/dL). Additionally, the levels of nine metabolites in serum differed among the treatments (P<0.05). Linoleic acid (LA) and cortisone, which are related to LA metabolism and the steroid biosynthesis pathway, were upregulated by the SDN-ALF and SDN-TMT-ALF diets compared to the SDN diet, suggesting the contribution of ALF to altering the metabolites. The levels of hippuric acid, which is a metabolite of phenolic compounds, were higher (P<0.001) in the animals fed SDN, which contained higher phenolic and luteolin concentrations than the other diets. Pathway analysis suggested that the higher cortisone levels were derived from cholesterol due to upregulated glycolysis metabolism, which was positively related to increased ingestion, digestibility, and serum LA levels in animals given mixed forage. In conclusion, physiological stress tolerance in the animals was regulated by upregulation of LA and steroid hormone metabolism, which was associated with an increase in TAC rather than the ability of the animal to regulate its PSM intake.

Preoperative serum cortisone levels are associated with cognition in preschool-aged children with tetralogy of Fallot after corrective surgery: new evidence from human populations and mice

BackgroundTetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Children with TOF would be confronted with neurological impairment across their lifetime. Our study aimed to identify the risk factors for cerebral morphology changes and cognition in postoperative preschool-aged children with TOF.MethodsWe used mass spectrometry (MS) technology to assess the levels of serum metabolites, Wechsler preschool and primary scale of intelligence-Fourth edition (WPPSI-IV) index scores to evaluate neurodevelopmental levels and multimodal magnetic resonance imaging (MRI) to detect cortical morphological changes.ResultsMultiple linear regression showed that preoperative levels of serum cortisone were positively correlated with the gyrification index of the left inferior parietal gyrus in children with TOF and negatively related to their lower visual spaces index and nonverbal index. Meanwhile, preoperative SpO2 was negatively correlated with levels of serum cortisone after adjusting for all covariates. Furthermore, after intervening levels of cortisone in chronic hypoxic model mice, total brain volumes were reduced at both postnatal (P) 11.5 and P30 days.ConclusionsOur results suggest that preoperative serum cortisone levels could be used as a biomarker of neurodevelopmental impairment in children with TOF. Our study findings emphasized that preoperative levels of cortisone could influence cerebral development and cognition abilities in children with TOF.

Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children

Despite the multiple benefits of vaccination, cardiac adverse Events Following COVID-19 Immunization (c-AEFI) have been reported. These events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. Herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. Overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event.

Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR)

The exact link between systemic and ocular endogenous corticoids (steroidome) is unclear and whether the ocular steroidome is altered in CSCR eyes is unknown. The aims of this study were to analyze the human steroidome in the aqueous humor as a function of age, sex and time of the day, to correlate systemic and ocular steroidome and to analyze the ocular steroidome in long lasting complex inactive CSCR. Based on our results, we present two CSCR cases treated by the combination of oral mineralocorticoid antagonist and glucocorticoids drops. In a cross-sectional study, aqueous humor (AH) was collected between 8am and 6 pm from 50 unaffected individuals (25 men and 25 women) and from 14 patients with chronic CSCR, during cataract surgery. In addition, simultaneous serum and AH were collected from 27 individuals undergoing cataract surgery and, simultaneous AH and vitreous were collected from 9 patients undergoing cataract and vitrectomy to estimate corticoids levels in the different compartments. The steroidome was determined using a LC–MS/MS method that quantifies 13 endogenous corticoids from the gluco, mineralocorticoid and androgen pathways. In AH and vitreous, the highest corticoid level is reached by cortisol (F), that represents less than 10% of F serum level. The cortisol levels in the serum did not correlate with ocular cortisol levels. Serum and ocular cortisone (E) levels correlate, although less than 5% of circulating E reaches the eye. The only mineralocorticoids measured in the AH were corticosterone (B) and its inactive form, the 11-desoxycorticosterone (A). There was no influence of circadian rhythm on cortisol ocular levels and there was no correlation between the age or the sex and the level of F, E, A, and B. In eyes with chronic inactive CSCR, the levels of the active glucocorticoid form F was lower than in control eyes and the F/E ratio was reduced by 50% but the B/A ratio was higher indicating imbalance towards active mineralocorticoids. Base on this observation, we propose to combine an antagonist of the mineralocorticoid receptor together with topical glucocorticoids in two CSCR patients, resistant to all other treatments, with favorable outcome. Our results indicate that the ocular psteroidome is highly regulated suggesting a local metabolism of ocular corticoids. In eyes with long-lasting complex inactive CSCR, the steroidome analysis shows lower active glucocorticoids and higher active mineralocorticoids.

Associations of psychoactive substances and steroid hormones in hair: Findings relevant to stress research from a large cohort of young adults

ObjectiveEpidemiological studies increasingly use hair samples to assess people’s cumulative exposure to steroid hormones, but how the use of different psychoactive substances may affect steroid hormone levels in hair is, so far, largely unknown. The current study addresses this gap by establishing the substance exposure correlates of cortisol, cortisone, and testosterone in hair, while also accounting for a number of relevant covariates. MethodData came from a large urban community-sample of young adults with a high prevalence of substance use (N = 1002, mean age=20.6 years, 50.2% female), who provided 3 cm of hair samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified cortisol, cortisone, and testosterone, as well as delta-9-tetrahydrocannabinol (THC), 3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”), cocaine, several opioids, and their respective metabolites. Multiple linear regression models with covariates were used to predict steroid hormone levels from substance exposure in a four-step approach: In the full sample, low and high substance hair concentrations (median split) were first tested against no use for each substance individually (step 1) and for all substances together (step 2). Then, within the participants with any substance in hair only, the continuous hair concentration of each substance in pg/mg (step 3) and finally of all substances together, were regressed (step 4). ResultsLow, high, and continuous levels of THC in hair were robustly associated with higher levels of cortisol (sig. in step 1 low THC: β = 0.29, p = .021; high THC: β = 0.42, p = .001; step 2: low THC: β = 0.27, p = 0.036, and high THC: β = 0.40, p = .004, and step 4: β = 0.12, p = .041). Participants with high MDMA levels had higher levels of cortisone without adjusting for other substances (step 1: β = 0.34, p = .026), but this effect was not significant in the other models. While high THC levels were associated with lower levels of testosterone in step 2 (β = −0.35, p = .018), MDMA concentration was positively related to testosterone concentration with and without adjusting for other substances (step 3: β = 0.24, p = .041; step 4: β = 0.17, 95%, p = .015) in male participants. ConclusionThe use of psychoactive substances, especially of cannabis and ecstasy, should be considered in studies investigating steroid hormones in hair.

Psychological prediction of stress-related hair steroid hormone levels in young men: a person-centered approach

The aim was to: (1) identify individual profiles in young men regarding personality and cognitive appraisal style employing easy-to-use instruments, and (2) to explore how such profiles relate to biological stress indicators. The sample consisted of 173 male Lithuanian conscripts. An assessment was made after one month into their basic military training. Levels of cortisol, cortisone and testosterone were established through analysis of hair samples. Psychological assessments included the Big Five model of personality as well as cognitive appraisal style and perceived stress during the previous month of service. Four unique personality profiles were identified in a cluster analysis that differed significantly as theoretically expected on the Perceived Stress Scale. Statistically significant between-profile differences were found on cortisol and cortisone but not on testosterone. The personality profile with the highest scores on all three biological markers was characterized by high scores on Extraversion and Openness and low scores on Agreeableness. Second, three distinct cognitive appraisal style profiles emerged. They were related as theoretically expected to perceived stress, but they were unrelated to the hair steroid hormone concentration levels. Third, the combination of the most psychologically vulnerable personality profile, which included low scores on Emotional stability, and the most stressed cognitive appraisal style profile, yielded the clearest result and showed that it was possible to detect individuals with significantly higher stress-related hair steroid hormone levels using psychological instruments. Practical potential implications include identification of individuals who are most psychologically vulnerable and in need of close monitoring.

Determination of nicotine and cotinine in human hair using online solid phase extraction coupled with liquid chromatography-tandem mass spectrometry and their relation to hair cortisol and cortisone

Tobacco smoking is one of the critical public health threats all over the world. Since nicotine and its metabolite cotinine have been routinely used as the biomarkers to estimate the exposure to tobacco smoking, hair nicotine and cotinine analyses can provide of a retrospective index of nicotine and cotinine integrated over extended periods of several months prior to hair sampling to estimate the long-term exposure to tobacco smoking. Since the relationship between tobacco smoking and hypothalamic-pituitary-adrenal (HPA) axis is implicated in both stress response and nicotine addiction, better understanding of the association between hair nicotine, cotinine levels and hair cortisol, cortisone levels is an important prerequisite toward more adequate use of this method in future research. We here presented an online solid phase extraction (SPE) coupled with liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for quantification of long-term integrated nicotine and cotinine in human hair. This method was applied to the analysis of hair nicotine and cotinine in 40 participants of smokers and nonsmokers (mean ± SD age: 46.25 ± 11.92 years; 40 % male) and the investigation of their association with hair cortisol and cortisone. Methanol together with glass tube was used for hair nicotine and cotinine extraction during the incubation time of 18-h. The limits of quantification were 1 pg/mg for nicotine as well as 0.1 pg/mg for cotinine. The inter- and intra-day coefficients of variation were below 15 %. The method recovery ranged between 90 % and 104 %. Group-level analyses revealed that smokers exhibited higher hair nicotine and cotinine levels compared to nonsmokers. Hair nicotine and cotinine levels showed significant positive associations with hair cortisol and cortisone levels in smokers (nicotine and cortisol: Spearman's ρ = 0.619, p = 0.005; cotinine and cortisol: Spearman's ρ = 0.468, p = 0.043; nicotine and cortisone: Spearman's ρ = 0.773, p = 0.000; cotinine and cortisone: Spearman's ρ = 0.531, p = 0.016), but not in nonsmokers. The presented online SPE LC-MS/MS method provides a simply and highly specific analytical strategy for the detection of nicotine and cotinine concentrations in human hair for the retrospective assessment of cumulative long-term nicotine and cotinine exposure. Furthermore, hair nicotine, cotinine levels correlate with hair cortisol, cortisone levels in smokers other than nonsmokers.

Association of hair glucocorticoid levels with sleep quality indicators: a pilot study in apparently healthy perimenopausal and menopausal women.

Poor sleep quality is associated with different physical and mental health diseases. It is proposed that increased hypothalamic-pituitary-adrenal axis activity is a potential contributor affecting sleep pattern and quality. We aimed to analyze the relationship between subjective sleep quality indicators and hair glucocorticoid levels among relatively healthy perimenopausal and postmenopausal women. A total of 145 women aged 50-64 y.o. were enrolled in the cross-sectional pilot study. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index, while stress level was measured using the Perceived Stress Scale. Hair cortisol and cortisone levels were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. Statistically significant positive relationship was found between hair cortisol concentration and Pittsburgh sleep quality index score. Similarly, statistically significant positive associations were observed between hair total glucocorticoid level and Pittsburgh sleep quality index, sleep disturbance, and Perceived Stress Scale scores. Subjects with prolonged sleep latency had significantly higher hair cortisol and total hair glucocorticoid concentrations compared with individuals whose sleep latency is not disturbed. Additionally, Chi-squared test indicated that lower hair cortisol concentration was significantly related to better sleep efficiency. Increased hair glucocorticoid (cortisol, cortisone) levels were found to be related with worse sleep quality measured by Pittsburgh sleep quality index score.

Association of serum cortisol and cortisone levels and risk of recurrence after endocrine treatment in breast cancer

Metabolic reprogramming in breast cancer involves changes in steroid hormone synthesis and metabolism. Alterations in estrogen levels in both breast tissue and blood may influence carcinogenesis, breast cancer growth, and response to therapy. Our aim was to examine whether serum steroid hormone concentrations could predict the risk of recurrence and treatment-related fatigue in patients with breast cancer. This study included 66 postmenopausal patients with estrogen receptor-positive breast cancer who underwent surgery, radiotherapy, and adjuvant endocrine treatment. Serum samples were collected at six different time points [before the start of radiotherapy (as baseline), immediately after radiotherapy, and then 3, 6, 12 months, and 7–12 years after radiotherapy]. Serum concentrations of eight steroid hormones (cortisol, cortisone, 17α-hydroxyprogesterone, 17β-estradiol, estrone, androstenedione, testosterone, and progesterone) were measured using a liquid chromatography–tandem mass spectrometry-based method. Breast cancer recurrence was defined as clinically proven relapse/metastatic breast cancer or breast cancer-related death. Fatigue was assessed with the QLQ-C30 questionnaire. Serum steroid hormone concentrations measured before and immediately after radiotherapy differed between relapse and relapse-free patients [(accuracy 68.1%, p = 0.02, and 63.2%, p = 0.03, respectively, partial least squares discriminant analysis (PLS-DA)]. Baseline cortisol levels were lower in patients who relapsed than in those who did not (p < 0.05). The Kaplan–Meier analysis showed that patients with high baseline concentrations of cortisol (≥ median) had a significantly lower risk of breast cancer recurrence than patients with low cortisol levels (<median) (p = 0.02). During follow-up, there was a decrease in cortisol and cortisone concentrations in relapse-free patients, whereas these steroid hormones increased in patients who relapsed. In addition, steroid hormone concentrations immediately after radiotherapy were associated with treatment-related fatigue (accuracy of 62.7%, p = 0.03, PLS-DA). However, baseline steroid hormone levels did not predict fatigue at 1 year or at 7–12 years. In conclusion, breast cancer patients with low baseline cortisol levels were more likely to experience recurrence. During follow-up, cortisol and cortisone levels decreased in relapse-free patients but increased in patients with recurrence. Thus, cortisol and cortisone may act as potential biomarkers indicating individual risk of recurrence.

Elevated follicular cortisone level is a negative predictor of clinical pregnancy in women undergoing fresh embryo transfer

BackgroundAlthough numerous studies have investigated the potential correlation between follicular fluid (FF) steroid concentrations and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes, few have accounted for the effect of controlled ovarian hyperstimulation regimes on FF steroid concentrations. ObjectiveTo comprehensively compare follicular steroid concentrations between women stimulated with gonadotropin-releasing hormone agonist (GnRHa) and antagonist (GnRHant) protocols and to explore the associations between FF steroid concentrations and IVF/ICSI outcomes. MethodsA total of 295 infertile women undergoing IVF/ICSI from January 2018 to May 2020 were enrolled. Eighty-four and 211 women received GnRHa and GnRHant protocols, respectively. Seventeen steroids in FF were quantified by liquid chromatography tandem mass spectrometry (LC–MS/MS), and the correlation of follicular steroids with clinical pregnancy was explored. ResultsFollicular steroid concentrations were similar between the GnRHa and GnRHant groups. Follicular cortisone levels were adversely associated with clinical pregnancy in fresh embryo transfers. Receiver operating characteristic (ROC) analysis revealed an area under the ROC curve (AUC) of 0.639 (95% confidence interval = 0.527–0.751, p = 0.025) for predicting non-pregnancy, with an optimal cutoff value of 15.81 ng/mL (sensitivity = 33.3%, specificity = 94.1%). Women with FF cortisone concentrations ≥15.81 ng/mL were fifty times less likely to achieve clinical pregnancy in fresh embryo transfers than those with FF cortisone levels below this threshold (adjusted OR = 0.019, 95% confidence interval = 0.002–0.207, p = 0.001) after adjusting for age, body mass index, baseline serum progesterone levels, serum levels of luteinizing hormone, estradiol and progesterone on human chorionic gonadotropin day, ovarian stimulation protocols, and the number of transferred embryos. ConclusionsThere was no significant difference in intrafollicular steroid levels between GnRHa and GnRHant protocols, and intrafollicular cortisone level ≥15.81 ng/mL was found to be a strong negative predictor of clinical pregnancy in fresh embryo transfers with high specificity.

Associations between hair cortisol, cortisone and DHEA levels and Covid19 related stressors among family members during the first outbreak of COVID19 within the FinnBrain Cohort Study in Finland

Some studies have associated COVID-19-pandemic-related stress with elevated hair cortisol concentrations among health care workers and mother-child pairs. We investigated, whether parent-reported pandemic-related stressors predicted hair cortisol, cortisone and DHEA levels among parents and 5-to-8-year-old children in general population. Hair samples utilized to define cortisol, cortisone and DHEA concentrations were collected at homes in June 2020 covering the cumulative hormone output during the first wave of the COVID-19 pandemic in Spring in Finland. Parents reported pandemic-related stressors (e.g. lifestyle restrictions, economic difficulties, health events related to self and others) by responding to an online questionnaire in May-June 2020. This study consists of 150 mothers, 25 fathers and 165 children from FinnBrain Birth Cohort Study who had complete data available. According to the preliminary results, hair cortisone concentrations associated with health events related to self among fathers (β = 0.29, p =.057) when adjusted for depressive symptoms (Edinburgh Postnatal Depression Scale) (β = 0.089, p =.007), age and education. In parents, we found no other associations between hair hormone concentrations (HHC) and pandemic-related stressors. Analyses in children will be presented in the conference. We found no strong evidence for the associations between pandemic-related stressors and HHC among parents. Finding concerning cortisone could point the possible role of cortisol metabolism in the biological response to pandemic, suggesting that not just cortisol should be studied in related studies.

Interplay of Cortisol, Testosterone, and Abdominal Fat Mass in Normal-weight Women With Polycystic Ovary Syndrome.

Ovarian and adrenal steroidogenesis underlie endocrine-metabolic dysfunction in polycystic ovary syndrome (PCOS). Adipocytes express aldo-keto reductase 1C3 and type 1 11β-hydroxysteroid dehydrogenase, which modulate peripheral androgen and cortisol production. To compare serum adrenal steroids, including 11-oxygenated androgens (11-oxyandrogens), cortisol, and cortisone between normal-weight women with PCOS and body mass index- and age-matched ovulatory women with normal-androgenic profiles (controls), and assess whether adrenal steroids associate with abdominal adipose deposition. Prospective, cross-sectional, cohort study. Academic medical center. Twenty normal-weight women with PCOS and 20 body mass index-/age-matched controls. Blood sampling, IV glucose tolerance testing, and total-body dual-energy x-ray absorptiometry. Clinical characteristics, hormonal concentrations, and body fat distribution. Women with PCOS had higher serum total/free testosterone (T) and androstenedione (A4) levels and a greater android/gynoid fat mass than controls (androgens P < .001; android/gynoid fat mass ratio, P = .026). Serum total/free T and A4 levels correlated positively with android/gynoid fat mass ratio in all women combined (P < .025, all values). Serum 11ß-hydroxyA4, 11-ketoA4, 11ß-hydroxyT, 11-ketoT, cortisol, and cortisone levels were comparable between female types and unrelated to body fat distribution. Serum 11-oxyandrogens correlated negatively with % total body fat, but lost significance adjusting for cortisol. Serum cortisol levels, however, correlated inversely with android fat mass (P = .021), with a trend toward reduced serum cortisol to cortisone ratio in women with PCOS vs controls (P = .075), suggesting diminished 11β-hydroxysteroid dehydrogenase activity. Reduced cortisol may protect against preferential abdominal fat mass in normal-weight PCOS women with normal serum 11-oxyandrogens.