Lower Baseline Cortisol Research Articles

Longitudinal associations of social jetlag with obesity indicators among adolescents - Shanghai adolescent cohort

ObjectiveTo explore the longitudinal association between social-jetlag (SJL) and obesity development among adolescents, sex-difference and related modifying factors in the association. MethodsBased on Shanghai-Adolescent-Cohort during 2017–2021, a total of 609 students were investigated. In grade 6, 7 and 9, the information on SJL was collected using questionnaires, and anthropometric measures were conducted. The fingernail cortisol and progesterone levels in grade 6 (using LC-MS/MS) and body composition in grade 9 (using Inbody-S10) were measured. By the latent-class-mixture-modeling, two trajectories for SJL (high-level vs. low-level) throughout 4 years were developed. The prospective associations of SJL trajectories and weight/fat gains were analyzed by sex and under different (high/moderate/low) cortisol/progesterone stratifications. ResultsIn grades 6–9, 39.00%–44.50 % of adolescents experienced at least 1 h of SJL. Compared with the low-level SJL trajectory, the high-level SJL trajectory was associated with greater differences in body-mass-index Z-scores and waist-to-height ratios across 4 years, higher levels of body-fat-percentage and fat-mass-index in grade 9 (P-values<0.05), and such associations were stronger among girls and under moderate-to-high (vs. low) baseline cortisol and progesterone levels. However, no significant associations among boys were observed. ConclusionsHigh-level SJL in adolescents may be associated with the development of obesity, especially among adolescent girls and under relatively high baseline cortisol and progesterone levels.

The Moderating Role of Cortisol and Negative Emotionality in the Effects of Classroom Size and Window View on Young Children's Executive Functions.

This study probed how baseline cortisol (BC), negative emotionality (NE), and environmental facets-classroom size and window view-interact to affect executive function (EF) in preschoolers using virtual reality (VR). In a cohort of 144 children aged 61-85 months, BC levels were measured by saliva assays and NE by parental surveys. Participants completed computerized EF assessments both pre- and post-exposure to one of four VR conditions, which varied by classroom size (large vs. small) and window view (natural vs. built). Due to missing data and outlier responses, three children were removed from the analyses. Regression analyses, accounting for initial EFs, revealed that higher BC was significantly associated with better Digit-span task scores in the nature view, while lower BC correlated with improved performance in the built view. With regard to classroom size, children with varying levels of NE benefitted from the large classroom environment, as evidenced by marginally significant improvements on the Corsi block task. However, higher NE children outperformed their lower NE peers in the large classroom, while a trend inverted in the small classroom context. The findings illuminate how the physical components of preschool environments may interact with children's physiological reactivity, potentially influencing the development of working memory.

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.

0731 Salivary Cortisol and Sleep in Grandparents Raising Grandchildren and Non-Caregiving Grandparents

Abstract Introduction Caregivers often exhibit unhealthy/dampened cortisol profiles and sleep problems due to high stress. Grandparent caregivers (GP-CG) may be particularly vulnerable with caregiving burden and age-related changes in sleep/health. Yet there is lack of empirical evidence examining baseline cortisol and reactivity in GP-CG and how they are associated with sleep. We examined differences between GP-CG and non-GP-CG in cortisol levels pre- and post-stress tasks and the moderating role of caregiving status in the relationship between cortisol and sleep. Methods 486 participants in the second wave of the 2009 MIDUS biomarkers project were characterized as GP-CG who cared for their grandchild for at least 1 year (n=63, Mage=61.80, 64% female) and non-GP-CG (n=423, Mage=62.98, 56.2% female). T-tests and multiple regressions (SPSS PROCESS) examined group differences and moderation by caregiving status in the associations between salivary cortisol (Salivette®; measured before and after Stroop and MATHTurner tasks) and sleep (work-day and non-work-day total sleep time-TST; frequency of Sleep Onset Latency problems-SOLfreq; 1-never to 5-always) over the past month. Analyses controlled for age, gender, cortisol collection time. Results GP-CG had lower baseline cortisol (M=10.35, SD=6.02) than non-GP-CG (M=12.15, SD=7.70; t(485)=2.03, p=.045). GP-CG had lower post-task cortisol reactivity (M=10.99, SD=5.83) than non-GP-CG (M=13.21, SD=7.73; t(485)=2.06, p=.040). Only non-GP-CG had a significant cortisol increase from baseline to post-task (t(1,422)=3.00, p=.001)). Caregiving status interacted with baseline cortisol (t(1, 484)=3.81, p=.04) in its association with SOLfreq (R2=.16, p=.03). Higher baseline cortisol was associated with less SOLfreq in GP-CG with no relationship in non-GP-CG. Additionally, caregiving status interacted with post-task cortisol (t(1,484)=7.79, p=.006) in its association with non-work-day TST (R2=.17, p=.04). Cortisol and TST had a positive relationship in GP-CG but a negative relationship in non-GP-CG. Conclusion GP-CG may have lower baseline cortisol and reactivity compared to non-GP-CG, consistent with previous literature examining individuals with prolonged stress compared to healthy controls. GP-CG’s reduced cortisol reactivity may be adaptive given that the positive relationship between cortisol and sleep in this group, contrary to the negative association found among healthy controls. Future research should utilize longitudinal data to determine the temporality of these relationships. Support (if any) NIA (P01AG020166, R37AG027343; McCrae, PI: R01AG061976)

Diagnosis and management of adrenal insufficiency

Adrenal insufficiency is the inadequate secretion of glucocorticoid and/or mineralocorticoid secretion from the adrenal cortex. Primary adrenal insufficiency is the result of failure of the adrenal gland and secondary adrenal insufficiency is due to a lack of stimulation via pituitary adrenocorticotropic hormone or hypothalamic corticotropin-releasing hormone. Adrenal insufficiency may cause non-specific symptoms. Early detection and testing based on clinical suspicion may prevent subsequent presentation with adrenal crisis. Once identified, a low baseline cortisol (often <100 nmol/L) alongside raised adrenocorticotropic hormone (ACTH) can be enough to diagnose primary adrenal insufficiency. However, confirmatory testing can be done using the cosyntopin (Synacthen®) stimulation test or the insulin tolerance test, which is the gold standard for secondary adrenal insufficiency. The underlying cause of adrenal insufficiency can often be identified via a strategic approach to investigation. Adrenal crisis is a life-threatening medical emergency which must be treated immediately if there is strong clinical suspicion with fluids and corticosteroids otherwise can be fatal. Patients must be educated and empowered to take control of their own medical management.

Low Baseline but Not Delta Cortisol Relates to 28-Day Transplant-Free Survival in Acute and Acute-on-Chronic Liver Failure.

The clinical, prognostic, and therapeutic impact of adrenal insufficiency in acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) remains controversial and exact diagnostic criteria are lacking. We sought to determine the diagnostic and therapeutic value of cortisol measurement and glucocorticoid (GC) treatment in ALF and ACLF. 28-day transplant-free survival (TFS) was studied in relation to absolute cortisol concentrations and to GC treatment in ALF (n= 30) and ACLF (n= 34) patients. Cortisol concentrations and short synacthen test were assessed by chemiluminescence immunoassay and liquid chromatography-mass spectrometry. Clinicians decided independently on GC treatment. In relation, phenotypic and functional characteristics of circulating monocytes were assessed. In ALF, baseline cortisol concentrations <387 nmol/L predicted TFS (sensitivity 83%, specificity 53%). In ACLF, baseline cortisol <392 nmol/L correlated with TFS (sensitivity 80%, specificity 61%). In both, ALF and ACLF, GC treatment did not influence 28-day TFS in patients with low baseline cortisol. However, in patients with baseline cortisol exceeding 387 and 392 nmol/L, respectively, TFS was higher if they had been treated with GC. High baseline cortisol was associated with low HLA-DR expression on monocytes. Our data suggest a prognostic value of baseline cortisol measurement in ALF and ACLF. Overall, strong activation of the hypothalamic-pituitary-adrenal axis indicated poor prognosis. Furthermore, baseline cortisol deserves prospective evaluation as a guide for GC treatment decision-making.

Biomarker Response to Mindfulness Intervention in Veterans Diagnosed with Post-traumatic Stress Disorder.

This study evaluates the effects of treatment with mindfulness-based stress reduction (MBSR) compared to the active control, present-centered group therapy (PCGT), on morning plasma cortisol, interleukin-6 (IL-6), and C-reactive protein (CRP) in veterans diagnosed with post-traumatic stress disorder (PTSD). In a post hoc exploratory analysis, we pooled biomarkers and clinical outcomes of mindfulness, PTSD, and depression from two randomized controlled trials comparing MBSR (n = 104) to PCGT (n = 106) in U.S. military veterans diagnosed with PTSD. Linear mixed-effects modeling was used to evaluate associations between changes in biomarkers and clinical outcomes from baseline to 9-week primary endpoint and 16-week follow-up endpoint. Cortisol levels were inversely related to self-reported PTSD symptoms at baseline (p = 0.02). Cortisol increased from baseline to 9-week endpoint for both groups, but significantly less so in the MBSR group compared to PCGT group (mean difference 1.69 ± 0.8 SE; p = 0.035). Changes in IL-6 and CRP did not differ between groups at either baseline or week 9. From baseline to week 9, increased mindfulness was significantly associated with increased cortisol (p = 0.02) and decreased PTSD and depression severity (p < 0.01). Increased IL-6 and CRP were significantly associated with decreased PTSD severity (p < 0.05), but not depression. Pooled analysis corroborated earlier findings that MBSR is significantly better than PCGT in improving clinical outcomes. Increased mindfulness was strongly associated with improved symptoms. Increased mindfulness is associated with a recalibration of cortisol levels which may be indicative of therapeutic response, especially in patients with lower baseline cortisol. Furthermore, mindfulness-based practices improve symptoms of PTSD and depression in a significant correlation with self-reported levels of mindfulness. NCT01532999 and NCT01548742.

Relations among CRFR1 and FKBP5 genotype, cortisol, and cognitive function in aging humans: A Project FRONTIER study

Here we use the glucocorticoid cascade hypothesis framework to address the role of baseline cortisol on changes in cognitive function over a 3-year span in non-demented rural Americans. We also determine if genotype at 4 different single nucleotide polymorphisms (SNPs) relates to change in cognitive function. We predicted 1) over time, increases in baseline cortisol will be associated with decline in cognitive function, 2) individuals homozygous for 3 CRFR1 SNP rare alleles (AA rs110402, TT rs7209436, and TT rs242924 vs. others) will show less cognitive decline and this will be particularly pronounced in those with lower baseline cortisol, and 3) FKBP5 T carriers (TT or CT vs. CC homozygotes) will have decreased cognitive performance and this will be particularly pronounced in individuals with higher baseline cortisol. Collectively, our data do not robustly support the glucocorticoid cascade hypothesis. In several cases, higher baseline cortisol related to better cognitive performance over time, but within individuals, increased cortisol over time related to decreased performance on some cognitive domains over time. Contrary to our predictions, individuals with the rare CRFR1 haplotype (AA, TT, TT) performed worse than individuals with the common haplotype across multiple domains of cognitive function. FKBP5 genotype status had minimal impacts on cognitive outcomes. Genotype effects were largely not dependent on cortisol. The Project FRONTIER dataset is supported by Texas Tech University Health Sciences Center Garrison Institute on Aging.

Adrenal insufficiency is common amongst kidney transplant recipients receiving maintenance prednisolone and can be predicted using morning cortisol.

Long-term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTRs), leading to significant cumulative glucocorticoid exposure. The aims of this study are to investigate the prevalence of adrenal insufficiency (AI) in KTRs taking prednisolone and to develop a screening algorithm to identify patients at the highest risk of AI. In this cross-sectional cohort study, 67 KTRs receiving prednisolone underwent a short synacthen test (SST) and measurement of cumulative glucocorticoid exposure. A total of 72% (n=48) of participants failed the SST. Participants with AI had a higher daily prednisolone dose (4.9versus 4.2 mg/day; P=.002)andgreatercumulative glucocorticoid exposure (289versus 111 mg/kg; P=.03)than those with intact adrenal function. Participants with AI had lower baseline cortisol than participants with intact adrenal function (143 versus 303 nmol/L; P<.001).Morning cortisol of>288 nmol/L predicted a normal SST with 100% specificity [95% confidence interval (CI) 92-100] and 70% sensitivity (95% CI 56-78%), therefore excluding AI. Our results suggest KTRs are at a higher risk for AI than previously reported. A morning serum cortisol measurement is a useful screening tool in this cohort, reducing the need for stimulatory testing by 44%. KTRs with AI need education regarding glucocorticoid sick rules, similar to patients with other forms of AI.

Type 4 Renal Tubular Acidosis (RTA) Induced by Spironolactone Use in Secondary Adrenal Insufficiency

Type 4 RTA is caused by either decreased aldosterone production or resistance. Primary adrenal insufficiency results in decreased aldosterone whereas spironolactone can cause aldosterone resistance1. We present a case of spironolactone-induced type 4 RTA in a patient with suspected primary adrenal insufficiency.A 70-year-old female with liver cirrhosis on spironolactone and chronic bronchitis on inhaled steroids (ICS) presented for altered mental status. Laboratories showed hyponatremia 131 mmol/L (135–145 mmol/L) and hyperammonemia 113 µmol/L (11–51 µmol/L). She was successfully treated with oral lactulose for hepatic encephalopathy. However, on day 3, she developed worsening hyponatremia (126 mmol/L) and hyperkalemia 5.8 mmol/L (3.5–5.4 mmol/L). Spironolactone was discontinued, and hyperkalemia improved after medical treatment. Nonetheless, hyperkalemia recurred with worsening hyponatremia (125 mmol/L), hypoglycemia (57 mg/dL), and mild non-anion gap metabolic acidosis without other signs or symptoms of adrenal insufficiency. On day 5, her morning cortisol was 1.5 µg/dL (5–20 µg/dL), with ACTH 11 pg/mL (6–70 pg/mL). Her hyperkalemia persisted (6.3–6.8 mmol/L), and she was started on oral patiromer. Due to suspected adrenal insufficiency, she received dexamethasone 10 mg daily, and endocrinology was consulted. On day 7, an ACTH stimulation test (250 µg IV) showed a baseline ACTH <3 pg/mL, baseline cortisol 0.7 µg/dL (3–15 µg/dL), cortisol 30 minutes 9.9 µg/dL, and 60 minutes 12.2 µg/dL, consistent with incomplete response attributed to the supraphysiologic dexamethasone versus chronic ICS. On day 8, endocrinology discontinued dexamethasone and enoxaparin, and started hydrocortisone 10 mg orally in AM and 5 mg in PM. Aldosterone (measured at day 6) was 7.2 ng/dL (<= 31.0 ng/dL), renin activity 3.1 ng/mL/hr (0.5–4.0 ng/mL/hr), and aldosterone/renin ratio 2.3 (<= 25) consistent with hyporeninemic hypoaldosteronism since aldosterone and renin were inappropriately normal for the hyperkalemia. Repeat cosyntropin test on day 11 showed low ACTH (3 pg/mL), low baseline cortisol 1.1 µg/dL, cortisol 30 minutes 7.9 µg/dL, and 60 minutes 11.2 µg/dL, consistent with secondary adrenal insufficiency, ascribed to chronic ICS. Potassium level normalized seven days after spironolactone discontinuation, related to its approximate duration of action1. The patient was discharged with hydrocortisone 10 mg daily, and spironolactone was permanently discontinued.Spironolactone use can result in type 4 RTA due to aldosterone resistance and mimic mineralocorticoid deficits characteristic of primary adrenal insufficiency.1. O’Connell JE, Colledge NR. Type IV renal tubular acidosis and spironolactone therapy in the elderly. Postgrad Med J. 1993;69(817):887–889.

The Prevalence of Adrenal Insufficiency in Kidney Transplant Recipients

Abstract Long term glucocorticoid therapy is a key component of immunosuppression for kidney transplant recipients (KTR), leading to a significant cumulative glucocorticoid exposure in this cohort. However, assessment of adrenal function and steroid education do not feature in clinical practice guidelines for KTR. This study aims to investigate the prevalence of adrenal insufficiency (AI) in KTR on maintenance prednisolone and develop a simple screening algorithm to identify patients at highest risk of AI. 67 KTR receiving prednisolone were recruited, with a median age of 52 yrs (IQR 39–64) and median time since transplantation of 79 months (IQR 46–146). Patients with known hypothalamic-pituitary-adrenal axis pathology, exposure to oral oestrogens or impaired graft function (creatinine &amp;gt;170 umol/l) were excluded. Participants underwent a short synacthen test [SST, Roche Elecsys II immunoassay, pass cortisol &amp;gt; 430 nmol/l, CV assay 1.8-2,1%)], assessment of lifetime glucocorticoid exposure and an assessment of metabolic health.72% (n=48) of participants failed the SST(30 min cortisol &amp;lt; 430nmol/l). Participants with AI had a higher daily prednisolone dose (4.9 vs 4.2mg/day, p=0.002), a greater cumulative glucocorticoid exposure (289 vs 111 mg/kg, p=0.03) and lower estimated glomerular filtration rate (63 vs 81 ml/min/1.73m2, p=0.03) than those with intact adrenal function. There was no difference in duration of glucocorticoids post transplantation, previous transplant history, pre-transplant glucocorticoid exposure, immunosuppression regime, exposure to other glucocorticoid preparations, BMI and cortisol binding globulin concentration between those who passed or failed a SST. Participants with AI had a lower baseline cortisol (143 vs 303 nmol/l, p&amp;lt;0.001), lower baseline serum ACTH (14 vs 20 pg/ml), a lower peak stimulated cortisol (325 vs 490 nmol/l, p&amp;lt; 0.001) and lower cortisol response (139 vs 189 nmol/l, p=0.013) to synacthen testing than those with normal adrenal function. A morning cortisol of &amp;lt;294 nmol/l predicted AI result with 100% sensitivity (95% CI 92–100%, p&amp;lt; 0.001) and 63% specificity, therefore AI could be excluded if morning cortisol &amp;gt;300nmol/l, reducing the need for stimulatory testing. Our results suggest KTR are at higher risk for AI than previously reported, highlighting a need for greater patient and physician awareness regarding AI. We suggest that KTR with a morning cortisol &amp;lt; 300nmol/l are at high risk of AI, and dynamic testing should be considered for these patients.

Differential stress response to psychological and physical stressors in children using spatial versus response-dependent navigation strategies

Previous work from our lab has shown that basal cortisol levels are different between healthy young adults who spontaneously use caudate nucleus-dependent response strategies compared to young adults who use hippocampus-dependent spatial navigation strategies. Young adults who use caudate nucleus dependent strategies display lower basal cortisol levels compared to those who use hippocampus-dependent strategies. In the current study, we assessed navigation strategies in children using a virtual navigation task and measured cortisol at baseline as well as cortisol reactivity to both a psychological and to a physical stressor. Replicating what is observed in adults, we found that children who used caudate nucleus-dependent navigation strategies displayed lower cortisol levels at baseline compared to those who used hippocampus-dependent strategies. The psychological stressor, knowledge that a blood draw would be performed by a nurse, caused a significant increase in cortisol uniquely in response learners. The physical stressor, the actual blood draw, produced a significant increase in cortisol amongst spatial learners that was then comparable to levels observed in response learners. Lower baseline cortisol and higher cortisol psychological stress response observed amongst children who used response strategies may therefore reflect early biological changes during development which may have an impact later in life when considering risk for neuropsychiatric disorders.

SUN-308 Central Adrenal Insufficiency Is Rare in Adults with Prader-Willi Syndrome

Introduction: Prader-Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. This is partly due to the variable results of the synacthen test, compared with the more robust metyrapone test (MTP) and insulin tolerance test (ITT). In some countries, patients with PWS receive stress-dose corticosteroids during physical or psychological stress. Side effects of frequent corticosteroids use are weight gain, osteoporosis, diabetes mellitus and hypertension, already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity or even mortality. To prevent over- and undertreatment with corticosteroids, we assessed the prevalence of CAI in a large international cohort of adults with this rare disorder. Methods: The hypothalamic-pituitary-adrenal axis was tested in 81 adult subjects (55 Dutch, 10 British, 10 French, 6 Swedish) with genetically confirmed PWS. For multiple-dose MTP, 11-deoxycortisol >230 nmol/L (7.6 g/dL) was considered sufficient. For Dutch, French and Swedish patients who underwent ITT, cortisol >500 nmol/L (18.1 μg/dL) was considered sufficient. For British patients cortisol >450 nmol/L (16.3 μg/dL) was considered sufficient, as this center used a different assay. Additionally, we reviewed medical files of 645 adults with PWS from Italy (240), France (110), the Netherlands (110), Australia (60), Spain (45), Sweden (38) and the United Kingdom (42) for symptoms of hypocortisolism/adrenal crisis during surgery. Results: Data on 81 adult subjects (46 males and 35 females), median age (range) 25.2 yr (18.0 – 55.5), median BMI (range) 29.1 kg/m2 (20.0 – 62.0), with genetically confirmed PWS were collected. 33 subjects (41%) were using GH treatment since childhood. Multiple-dose MTP was performed in 45 subjects and ITT in 36 subjects. Both tests were well tolerated by all individuals. CAI was excluded in 80 of 81 patients. One patient with a peak cortisol level of 494 nmol/L (just below cut-off level of 500 nmol/L) was prescribed hydrocortisone for use during physical stress. There was no relation between baseline cortisol and ITT/multiple-dose MTP results. Even patients with a low baseline cortisol level (lowest: 102.0 nmol/L) had normal responses. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative corticosteroids treatment. None of them displayed any features of hypocortisolism/adrenal crisis. Conclusions: CAI is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing corticosteroids stress-doses in adults with PWS. Funding: CZ foundation.

New causes of old diseases. are we ready?

A 67-year-old male with metastatic cholangiocarcinoma presented with dehydration and delirium approximately 6 weeks after participating into a Rare Cancer Trial utilising combination of immune checkpoint inhibitors (ICIs), i.e., ipilimumab and nivolumab. His electrolytes were normal but cortisol was 36 nmol/L (185-625) and ACTH was 2 pmol/L (<10). Sixty-minute post-Synacthen cortisol was 153 nmol/L (>530). Secondary hypoadrenalism was diagnosed on the basis of low ACTH and baseline cortisol with poor response to Synacthen. Thyroid function tests revealed thyrotoxicosis, while TPO, thyroglobulin and TSH receptor antibodies were all negative. ICIs have been increasingly implicated in autoimmune endocrinopathies. Combination of ipilimumab and nivolumab can give rise to hypopituitarism or hypophysitis, and thyroid dysfunction. In healthy individuals, immune checkpoints maintain immunological tolerance to self-antigens. By inhibiting these immune checkpoints, ICIs cause auto-immune like manifestations against multiple organs. Typically, complications develop in susceptible patients 6–15 weeks after introduction of ICIs. The preferred screening test for hypophysitis is morning cortisol and ACTH, followed by Synacthen test.1 In oncology, ICIs are the most rapidly expanding class of drugs alternatives to traditional chemotherapy. Therefore, oncologists, endocrinologists and pathologists need to understand their mechanism of action, side effects, importance of monitoring ICI usage to detect and investigate the associated endocrine disorders. Reference1.Barroso-Sousa R, Ott PA, Hodi FS, et al. Endocrine dysfunction induced by immune checkpoint inhibitors: practical recommendations for diagnosis and clinical management. Cancer 2018; 124: 1111–21.

Neurodevelopmental outcomes in patients with mucopolysaccharidosis type I (MPS I)

Previous work from our lab has shown that basal cortisol levels are different between healthy young adults who spontaneously use caudate nucleus-dependent response strategies compared to young adults who use hippocampus-dependent spatial navigation strategies. Young adults who use caudate nucleus dependent strategies display lower basal cortisol levels compared to those who use hippocampus-dependent strategies. In the current study, we assessed navigation strategies in children using a virtual navigation task and measured cortisol at baseline as well as cortisol reactivity to both a psychological and to a physical stressor. Replicating what is observed in adults, we found that children who used caudate nucleus-dependent navigation strategies displayed lower cortisol levels at baseline compared to those who used hippocampus-dependent strategies. The psychological stressor, knowledge that a blood draw would be performed by a nurse, caused a significant increase in cortisol uniquely in response learners. The physical stressor, the actual blood draw, produced a significant increase in cortisol amongst spatial learners that was then comparable to levels observed in response learners. Lower baseline cortisol and higher cortisol psychological stress response observed amongst children who used response strategies may therefore reflect early biological changes during development which may have an impact later in life when considering risk for neuropsychiatric disorders.

Can short Synacthen tests (SST) be rationalised by establishing a lower baseline cortisol level which will predict SST outcome?

Can short Synacthen tests (SST) be rationalised by establishing a lower baseline cortisol level which will predict SST outcome?

Food deprived largemouth bass (Micropterus salmoides) are inactive and stressed, but do not show changes in lure inspections

Coping style traits, including physiology and behavior, can be used to predict if fish are vulnerable to capture by hook-and-line angling. Typically, fish with proactive coping styles are selectively captured, but effects of environmental influences, such as food availability, on the completion of each step leading to a successful angling capture (i.e., activity rates, encountering a lure, lure inspection, lure-striking, and ingestion) have not been quantified. Therefore, the objective of this study was to quantify the effects among activity behavior, stress (cortisol) responsiveness, and food availability on lure inspection behaviors of largemouth bass. No relationships were found between activity, stress responsiveness, and food availability to determine lure inspections. However, food deprivation decreased activity rates and increased baseline cortisol concentrations of largemouth bass. Additionally, after feeding treatments, fish with low baseline cortisol concentrations were more likely to inspect lures in both the fed and food deprived treatments. Results further discuss the implications of study findings to help fisheries managers predict the evolutionary impacts of angling.

Adrenal insufficiency in neonates undergoing cardiopulmonary bypass and postoperative hypothalamic-pituitary-adrenal function after prophylactic glucocorticoids.

Determine incidence of preoperative adrenal insufficiency in neonates >35 weeks gestation with congenital heart disease undergoing cardiothoracic surgery with bypass and effects of prophylactic methylprednisolone on postoperative hypothalamic-pituitary-adrenal function and hemodynamic stability. Prospective observational study in 36 neonates with preoperative adrenocorticotrophic hormone stimulation tests and serial total cortisol and adrenocorticotrophic hormone measurements before and after surgery. Data analyses: analysis of variance and regression. Baseline circulating adrenocorticotrophic hormone and cortisol were unchanged 4-20 days postnatal (P > 0.1); however, cortisol levels rose with increasing adrenocorticotrophic hormone, P = 0.02. Ten neonates (29%) demonstrated preoperative adrenal insufficiency (∆cortisol ≤9 µg/dl); one had postoperative hemodynamic instability. Growth-restricted neonates had lower baseline cortisol, but normal stimulation tests and responded well to surgical stresses. Seventy-five percent of neonates receiving perioperative methylprednisolone demonstrated postoperative hypothalamic-pituitary-adrenal inhibition. Adrenal insufficiency appears common in neonates >35 weeks gestation with congenital heart disease, but did not contribute to postoperative hemodynamic instability despite hypothalamic-pituitary-adrenal inhibition.

Socioeconomic risk moderates the association between caregiver cortisol levels and infant cortisol reactivity to emotion induction at 24 months.

Relations between maternal baseline cortisol and infant cortisol reactivity to an emotion induction procedure at child ages 7, 15, and 24months were analyzed using data from the Family Life Project (N=1,292). The emotion induction consisted of a series of standardized and validated tasks, including an arm restraint, toy removal, and mask presentation, intended to elicit responses of fear and frustration. Results revealed that at 7 and 15months, maternal baseline cortisol was negatively related to child cortisol reactivity, such that children of mothers with lower cortisol exhibited steeper cortisol increases in response to the emotion induction. At 24months, the association between mother and infant cortisol was moderated by socioeconomic risk, such that maternal baseline cortisol was associated with child cortisol reactivity only in dyads characterized by low socioeconomic risk. Furthermore, at 24 months, children of mothers with low baseline cortisol and low socioeconomic risk exhibited decreasing cortisol responses, whereas children of mothers with low baseline cortisol but high risk exhibited flat cortisol responses. Children in dyads characterized by high baseline maternal cortisol also exhibited flat cortisol responses regardless of socioeconomic risk. The role of caregiver physiology in the regulation of the child's stress response in the context of adversity is discussed.

FAAH genotype, CRFR1 genotype, and cortisol interact to predict anxiety in an aging, rural Hispanic population: A Project FRONTIER study

The neurophysiological underpinnings involved in susceptibility to and maintenance of anxiety are not entirely known. However, two stress-responsive systems, the hypothalamic-pituitary-adrenal axis and the endocannabinoid system, may interact in anxiety. Here, we examine the relationship between FAAH genotype, CRFR1 genotype, baseline cortisol, and state anxiety in a rural adult population using data from Project FRONTIER. We predicted that FAAH A (AA and AC vs CC; rs324420) and three CRFR1 SNP minor alleles (rs7209436 C→ T [minor allele]; rs110402, G → A [minor]; and rs242924 G→ T [minor]), would interact to predict low baseline cortisol and low state anxiety scores. We found partial support for our prediction. In CRFR1 minor carriers, the FAAH AA or AC (vs. CC) genotype was associated with higher cortisol and with lower anxiety. In CRFR1 non-minors, those with FAAH AA or AC (vs. CC) showed decreased cortisol and higher anxiety. These results suggest that FAAH CC genotype only conveys risk for anxiety in individuals who are also carriers of the CRFR1 minor combination. FAAH genotype was significantly associated with baseline cortisol but was not independently associated with anxiety. Contrary to our predictions, baseline cortisol was negatively associated with anxiety. Lastly, we did not find any independent relationships between any of our SNPs and baseline cortisol or anxiety. These data suggest FAAH and cortisol interact to predict state anxiety, but that the relationship depends on CRFR1 genotype. The Project FRONTIER dataset is supported by Texas Tech University Health Sciences Center Garrison Institute on Aging.