Intracranial hypertension and empty Sella from adrenal adenoma and excessive and prolonged steroid usage: a case report

Background There is only one documented case of intracranial hypertension (IH) and empty sella from cortisol-producing adrenal adenoma so far. And IH and empty sella caused by long-term exogenous hypercortisolism has never been reported before. The purpose of this case report is to alert clinicians to glucocorticoid-induced IH. Case presentation We present retrospectively a 50-year-old woman with cortisol-secreting adrenal adenoma, who progressed to intractable intracranial hypertension and a markedly expanded empty sella due to improper treatment. In 2011, the patient presented with hypertension, lack of cortisol circadian rhythm, low ACTH, a left adrenal adenoma and a partial empty sella, but did not receive low-dose dexamethasone suppression test (LDDST) and 24-h urinary cortisol. In 2014, she exhibited truncal obesity, raised cortisol, LDDST non-suppression, high urinary free cortisol and low ACTH, proving her cortisol-producing adrenal adenoma. She was simultaneously diagnosed with unexplained IH because of papilledema and elevated intracranial pressure, and her partial empty sella changed to a complete empty sella. In 2015, she underwent adrenal adenoma resection. From 2015 to 2018, she kept taking dexamethasone at least 2 mg daily without her doctors’ consent. During this period, she developed transient cerebrospinal fluid rhinorrhea, and her empty sella further worsened. After switching to low dose hydrocortisone, her papilledema disappeared completely, but optic atrophy has become irreversible. Conclusions The patient seems to be just an extreme case, but it may reveal and illustrate a general phenomenon: Both cortisol-producing adrenal adenoma and long-term exogenous hypercortisolism could cause varying degrees of elevated intracranial pressure and empty sella. Clinicians should remain vigilant for this phenomenon in patients with cortisol-producing adrenal adenoma or excessive and prolonged steroid usage and give them corresponding examinations to identify this complication.

Psychosocial stress and neuroendocrine biomarker concentrations among women living with or without HIV

Objective Women living with HIV (WLWH) experience psychosocial stress related to social-structural vulnerabilities. To investigate neuroendocrine pathways linking stress and increased cardiovascular disease risk among WLWH, we evaluated associations between psychosocial stress (i.e., perceived stress, posttraumatic stress, and experiences of race- and gender-based harassment) and a composite neuroendocrine biomarker index among WLWH and women without HIV. Methods In 2019–2020, Women’s Interagency HIV Study participants in Washington, DC completed a questionnaire and provided blood and 12-hour overnight urine samples for testing of serum dehydroepiandrosterone sulfate (DHEA-S) and urinary free cortisol, epinephrine, and norepinephrine. Psychosocial stress was measured using the Perceived Stress Scale, PTSD Checklist-Civilian Version, and Racialized Sexual Harassment Scale. Latent profile analysis was used to classify participants into low (38%), moderate (44%), and high (18%) stress groups. Composite biomarker index scores between 0–4 were assigned based on participants’ number of neuroendocrine biomarkers in high-risk quartiles (≥75th percentile for cortisol, epinephrine, and norepinephrine and ≤25th percentile for DHEA-S). We evaluated associations between latent profile and composite biomarker index values using multivariable linear regression, adjusting for socio-demographic, behavioral, metabolic, and HIV-related factors. Results Among 90 women, 62% were WLWH, 53% were non-Hispanic Black, and median age was 55 years. In full multivariable models, there was no statistically significant association between psychosocial stress and composite biomarker index values among all women independent of HIV status. High (vs. low) psychosocial stress was positively associated with higher mean composite biomarker index values among all monoracial Black women (adjusted β = 1.32; 95% CI: 0.20–2.43), Black WLWH (adjusted β = 1.93; 95% CI: 0.02–3.83) and Black HIV-negative women (adjusted β = 2.54; 95% CI: 0.41–4.67). Conclusions Despite a null association in the overall sample, greater psychosocial stress was positively associated with higher neuroendocrine biomarker concentrations among Black women, highlighting a plausible mechanism by which psychosocial stress could contribute to cardiovascular disease risk.

Effects of Ketoconazole On Clinical Recovery In Central Serous Chorioretinopathy

Background: Hypercortisolism has long been correlated with choroidal vasorelaxation in central serous chorioretinopathy (CSCR). This may explain the inconsistency of therapeutic responses of the mineralocorticoid receptor (MR) antagonist since hyperaldosteronism has rarely been detected in such cases. Hence, an early treatment using ketoconazole, the first line cortisol inhibitor that also blocks the MR ligand, appears to be rational. This study aimed to evaluate the effects of ketoconazole on CSCR, and to analyze correlations between choroidal thickness and steroid hormones.Method: In this three-center retrospective cohort, forty-one naïve CSCR eyes of 41 patients were categorized into control (20 eyes) and treatment group (21 eyes). Patients in the treatment group were given oral ketoconazole at a daily dose of 400 or 600 mg for three to six weeks. At week 12, rescue laser therapy was applied to patients exhibiting persistent subretinal fluid (SRF). We performed a survival analysis to determine the time interval from presentation to clinical resolution of SRF. The secondary outcomes consisted of proportion of eyes with persistent SRF, and factors affecting therapeutic response.Results: Mean 24-hour urinary free cortisol (UFC) were elevated at 181 ± 70 and 150 ± 68 µg/day (range = 20-150) in the treatment and control group (p = 0.21). After controlling for age and gender, baseline UFC levels demonstrated a positive correlation with choroidal thickness in both eyes (p < 0.05). Ketoconazole significantly accelerated the resolution of CSCR with the median time to resolution of 7 versus 16 weeks (p < 0.01), and reduced the proportion of eyes receiving rescue therapy at 12 weeks (23.8% versus 50%, p = 0.01). Prolonged CSCR durations were likely found in elderly patients who had thick choroid in fellow eyes.Conclusions: Elevated glucocorticoids are likely responsible for the pathogenesis of CSCR. Therefore, a temporary decrease in choroidal hyperpermeability using the cortisol blocker could reduce the persistency of CSCR.

Cortisol Levels in Infants with Central Coordination Disorders during Vojta Therapy

Background: Due to the decrease in the percentage of perinatal mortality, which is one of the Millennium Development Goals, the number of children with a central coordination disorder (CCD) has increased, present in up to 40% of premature babies. Neurodevelopmental disorders detected in the diagnostic process require early interventions that will eliminate or overcome existing dysfunctions. These treatments often cause discomfort in the infant, which induces insecurity and activation of basic defense mechanisms. The aim of the work is to assess changes in cortisol concentration in infants treated with the Vojta method. Methods and findings: The study included 35 children with CCD aged between three and nine months. The participants had no comorbidities that could have affected the obtained results. The activities were planned to occur in three stages: 1. Collection of a saliva sample directly before the physiotherapy appointment. 2. Collection of saliva immediately after rehabilitation. 3. Collection of saliva 20 min after the end of rehabilitation. The physiotherapeutic intervention included the assessment of seven reactions of the body position in space according to Vojta and the conduct of a therapeutic session consisting of the first phase of rotation and creeping reflex according to Vojta. The concentration of free cortisol in saliva was assessed with LC-MS/MS. In the first measurement, none of the children presented an excess of the normative concentration of cortisol. The cortisol measurement performed directly after rehabilitation showed above-normative values in three children. In the third measurement, all of the children presented a decreased concentration of free cortisol. The analysis (paired two-tailed t-test, p < 0.05) showed statistically significant differences between particular stages of the measurements. The analysis of the scores obtained in the second measurement showed the concentration of scores in the area of “normal” at a level of 0.83 (normal concentration) and the area “above normal” at the level of 0.005 (very weak concentration). Based on the analysis of significance of the obtained scores, it was found that the result was not accidental, and the Vojta method used in the treatment of children with CCD was suitable. Conclusions: Here, for the first time, we presented how Vojta therapy was correlated with cortisol levels among children with a central coordination disorder.

Clinical Characteristics for the Improvement of Cushing's Syndrome Complicated With Cardiomyopathy After Treatment With a Literature Review

Background: Endogenous Cushing's syndrome (CS), also called hypercortisolism, leads to a significant increase in mortality due to excessive cortisol production, which is mainly due to cardiovascular disease. CS complicated with cardiomyopathies, which is a rare and severe condition, has rarely been reported in the literature.Objective: To investigate the clinical characteristics of CS complicated with cardiomyopathies, we retrospectively reviewed the clinical manifestations, laboratory results, cardiac imaging results and prognosis to further understand the diagnosis, treatment, and management of these cases.Methods: The clinical data of patients diagnosed with CS complicated with cardiomyopathies obtained from discharge sheets from Peking Union Medical College Hospital from January 1986 to August 2021 were collected. Case reports of CS complicated with cardiomyopathies were retrieved from PubMed. In addition, Cushing's disease (CD) patients without cardiomyopathies were collected as controls to compare the clinical features.Results: A total of 19 cases of CS complicated with cardiomyopathies and cases of CD without cardiomyopathies (n = 242) were collected. The causes of CS included pituitary adenoma (n = 8, 42.11%), adrenal adenoma (n = 7, 36.84%), ectopic adrenocorticotropic hormone (ACTH) tumor (n = 2, 10.53%) and unclear causes (n = 2, 10.53%) in the CS complicated with cardiomyopathies group. The types of cardiomyopathies were dilated cardiomyopathies (n = 15, 78.94%) and hypertrophic cardiomyopathies (n = 4, 21.05%). The serum sodium concentration was significantly higher [145.50 (140.50–148.00) mmol/L vs. 141.00 (140.00–143.00) mmol/L], while the serum potassium concentration was significantly lower [2.70 (2.40–3.60) mmol/L] vs. 3.90 (3.50–4.20 mmol/L)] in the CS complicated with cardiomyopathies group compared to the CD patients without cardiomyopathies. There were no significant differences between the CS complicated with cardiomyopathies group and the CD patients without cardiomyopathies in the serum cortisol concentration and 24-h urine free cortisol, but a significant difference in the adrenocorticotropic hormone level [109.00 (91.78–170.30) pg/ml vs. 68.60 (47.85–110.00) pg/ml]. Twelve/16 (75.0%) patients showed significant improvement or even a complete healing of the heart structure and function after remission of hypercortisolemia after treatment with CS.Conclusions: CS complicated with cardiomyopathies is a very rare clinical entity, in which cortisol plays an important role and it can be greatly improved after remission of hypercortisolemia.

Assessment of Vitamin D Metabolism in Patients with Cushing’s Disease in Response to 150,000 IU Cholecalciferol Treatment

In this study we aimed to assess vitamin D metabolism in patients with Cushing’s disease (CD) compared to healthy individuals in the setting of bolus cholecalciferol treatment. The study group included 30 adults with active CD and the control group included 30 apparently healthy adults with similar age, sex and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 3-epi-25(OH)D3 and 24,25(OH)2D3), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3 and 7 after the administration. All data were analyzed with non-parametric statistics. Patients with CD had similar to healthy controls 25(OH)D3 levels (p > 0.05) and higher 25(OH)D3/24,25(OH)2D3 ratios (p < 0.05) throughout the study. They also had lower baseline free 25(OH)D levels (p < 0.05) despite similar DBP levels (p > 0.05) and lower albumin levels (p < 0.05); 24-h urinary free cortisol showed significant correlation with baseline 25(OH)D3/24,25(OH)2D3 ratio (r = 0.36, p < 0.05). The increase in 25(OH)D3 after cholecalciferol intake was similar in obese and non-obese states and lacked correlation with BMI (p > 0.05) among patients with CD, as opposed to the control group. Overall, patients with CD have a consistently lower 25(OH)D3/24,25(OH)2D3 ratio, which is indicative of a decrease in 24-hydroxylase activity. This altered activity of the principal vitamin D catabolism might influence the effectiveness of cholecalciferol treatment. The observed difference in baseline free 25(OH)D levels is not entirely clear and requires further study.

Does Experience Make Hucul Horses More Resistant to Stress? A Pilot Study

The aim of the study was to determine whether experience related to horse age and number of starts in championships influences stress level, measured by salivary cortisol concentration. The study involved 18 clinically healthy Hucul mares who participated in the Polish Championships for Hucul Horses. Evaluation of performance value was carried out in accordance with the guidelines specified in the breeding and genetic resources conservation program for this breed. The championship lasted two days, consisting of conformation evaluation, endurance, and Hucul path. Saliva was collected at baseline (T1), after arena assessment (T2), after endurance (T3), and on the second day after the Hucul path (T4). Cortisol levels increased from an average of 2.73 ± 1.18 ng/mL (T1) to 10.46 ± 8.03 ng/mL after T3. Significantly lower levels of free cortisol were detected in the saliva of the younger mares, up to 9 years old, and mares who participated in only one qualifying path after each element of the championship. The highest levels of cortisol (T3) were found in mares competing repeatedly on the qualifying path. No correlation was found between cortisol levels and the championship results. Participation of mares in the championship was associated with stress, which was reflected in the increase in cortisol levels in saliva.

Salivary Biomarkers (Opiorphin, Cortisol, Amylase, and IgA) Related to Age, Sex, and Stress Perception in a Prospective Cohort of Healthy Schoolchildren

Background. The use of easily accessible biomarkers for assessing young patients’ health is weighty. This cohort study is aimed at measuring stress/immune biomarkers in the saliva of healthy school-age children and comparing subgroups according to age, sex, and stress perception. Material and Methods. 503 children under 12 years old ( 8.7 ± 1.3 ) were included with anthropometric evaluation (height, waist, hip circumference, body weight, and body mass index (BMI)). Levels of opiorphin (OPI), free cortisol, alpha-amylase (sAA), and secreted immunoglobulin (sIgA) were determined by quantitative assays (ELISA) in unstimulated saliva. Unpaired t -test, Welch test, and Mann–Whitney U test were applied for appropriate group comparisons, and the correlation between variables was analyzed with Spearman’s rank coefficient. Results were considered significant at p < 0.05 . Results. sIgA and sAA exhibited significant differences depending on age and sex: IgA (ng/mL): 86 ± 68.6 vs. 104.9 ± 72.1 for (6-7 y.o.) and (8-11 y.o.), respectively, and 108.1 ± 80.1 vs. 94.6 ± 62.2 for male and females, respectively; sAA (U/mL): 78.9 ± 54.4 vs. 100.5 ± 81.2 for (6-7 y.o.) and (8-11 y.o.). No difference related to age or sex between groups was observed for cortisol and OPI. However, OPI levels were higher and correlated to prior stress exposure in children ( 0.31 ± 0.4 vs. 0.26 ± 0.5 ng / mL , p = 0.031 ). sAA was negatively correlated to low mood self-declaration in children in the last two weeks ( r = − 0.10 , p = 0.045 ). Conclusions. sIgA and sAA can be used as sex- and age-related biomarkers in children 6-12 y.o., which is not the case for free cortisol and opiorphin. However, OPI reflected previous exposure to stress, suggesting its use for evaluating stress-related changes in children

Assessment of Plasma-Free Cortisol Concentrations by LC-MS/MS in Patients with Autonomous Cortisol Secretion

Autonomous cortisol secretion (ACS) of an adrenal incidentaloma (AI) is associated with mild cortisol excess that could result in poor metabolic and cardiovascular outcomes. The biological activity of glucocorticoids depends on the unbound, free fraction. We aimed to evaluate plasma free cortisol (FC) concentrations in patients with ACS in this cross-sectional study. One hundred and ten AI patients in 3 groups; non-functioning (NFA, n=33), possible ACS (n=65), ACS (n=12) were enrolled. Following measurements were conducted: Clinical data and total serum cortisol (TC), plasma corticotrophin (ACTH), serum dehydroepiandrosterone sulfate (DHEA-S), cortisol after 1 mg dexamethasone by both immunoassay and LC-MS/MS (DexF), serum corticosteroid binding globulin (CBG), plasma dexamethasone concentration [DEX] and plasma FC by LC-MS/MS. Patients with ACS featured an unfavorable metabolic profile. Plasma [DEX] and serum CBG levels were similar between groups. Plasma FC was significantly higher in ACS when compared to NFA and possible ACS groups p<0.05 and p<0.01, respectively. In multiple regression analysis DexF (beta=0.402, p<0.001) and CBG (beta=−0.257, p=0.03) remained as the independent predictors of plasma FC while age, sex, BMI, smoking habit, and existing cardiovascular disease did not make a significant contribution to the regression model. In conclusion, the magnitude of cortisol excess in ACS could lead to increased plasma FC concentrations. Further studies in AI patients are needed to demonstrate whether any alterations of cortisol affinity for CBG exist and to establish whether plasma FC concentrations predict the unfavorable metabolic profile in ACS.

Cushing’s syndrome in pregnancy caused by an adrenal adenoma

Objective: The description of a rare case of Cushing’s syndrome caused by an adrenal adenoma in pregnancy with successful treatment. Case presentation: 30-ear-old Gravida 3 female was admitted to our hospital with hypertension at the 18th week of gestation. Hormonal analyses revealed primary Cushing’s syndrome with high plasma cortisol levels and low levels of adrenocorticotropic hormone. Magnetic resonance imaging demonstrated a mass on the right-side of the adrenal gland. Adrenalectomy was performed in the 28th week of gestation and the following histopathology revealed an adrenocortical adenoma. Pregnancy continued until the 38th week of gestation with glucocorticoid replacement therapy and the patient gave birth vaginally to a healthy boy in the 38th week of gestation. Conclusion: Cushing’s syndrome in pregnancy rarely occurs; dia gnosis may be dismissed or determined after birth in most cases. Misdia gnosis of Cushing’s syndrome is common because of physiological increase of corticotropin hormones and cortisol levels and overlapping symptoms that can occur even during physiological pregnancy. Cushing’s syndrome should have a place in the diff erential dia gnosis of hypertension in pregnancy (especially before the 20th week of gestation). Analysis of the urinary free cortisol level and circadian rhythm blood cortisol can provide a reasonable strategy to diagnose Cushing’s syndrome in pregnant women. Early dia gnosis and surgical treatment can signifi cantly reduce maternal and fetal complications. Key words: adenoma – Cushing’s syndrome – pregnancy – hypertension