Low Serum Cortisol Levels Research Articles

12204 Role Of [18F]FDG-PET/CT In Detection Of Immunotherapy-induced Hypophysitis - A Case-control Study

Abstract Disclosure: A. Fischer: None. J.M. Martinez Gomez: None. J. Mangana: None. R. Dummer: None. Z. Erlic: None. S. Nölting: None. F. Beuschlein: None. A. Maurer: None. M. Messerli: None. M.W. Huellner: None. S. Skawran: None. Adverse events related to immune-checkpoint inhibitor (ICI) therapy frequently affect endocrine organs. Depending on the type of ICI therapy, 0.5% to 10% of patients develop hypophysitis. Diagnosis relies on unspecific clinical symptoms and low serum cortisol level. On MRI, the diagnosis of ICI-induced hypophysitis is supported by enlargement of the pituitary gland and its stalk. However, pituitary MRI is negative in up to 2/3 of patients with hypophysitis on anti-PD-1 monotherapy. A delayed diagnosis increases the risk for life-threatening adrenal crisis. Consequently, there is a need for diagnostic tools that facilitate the early detection of ICI-induced hypophysitis. In this retrospective, single-center case-control-study, we investigated the diagnostic efficacy of [[1]8F]FDG positron emission tomography/computed tomography (FDG-PET/CT) in detecting ICI-induced hypophysitis. Fourteen patients with metastatic melanoma and ICI-induced hypophysitis were compared to a control group of 14 metastatic melanoma patients undergoing ICI treatment without evidence of hypophysitis, matched for age and sex. FDG-PET/CT scans were acquired as part of routine clinical care between 79 days before to 8 days after hypophysitis diagnosis (mean 26+/-29 days before diagnosis) in the case group. In the control group, FDG-PET/CT scans were obtained at a mean of 78+/-31 days after initiating ICI therapy. To mitigate inter-individual differences in standardized uptake value (SUV), the ratio of maximum SUV of the pituitary gland to the mean SUV of the blood pool (SUV-ratio pituitary/bloodpool) was calculated. Hypophysitis was diagnosed at a median of 83 (range: 65 - 98) days after the first ICI treatment; 9/14 (64.3%) patients received ipilimumab/nivolumab. Isolated cortisol deficiency was observed in 6/14 patients (42.9%), while 7/14 (50.0%) patients also displayed secondary hypothyroidism. Visual assessment of the distribution of the SUV-ratio pituitary/bloodpool demonstrated a positive correlation with decreasing proximity to the time of diagnosis. To evaluate diagnostic performance, only patients within 50 days before and 8 days after diagnosis (12/14) were included. The SUV-ratio pituitary/bloodpool was significantly higher in the case group compared to the control group (mean 3.57+/-3.24 vs. 1.69+/-0.41 respectively; p = 0.034). By optimizing the Youden index through area under the receiver operating characteristics curve (AUC) analysis, a sensitivity of 72.7% and a specificity of 90.9% were achieved at a threshold of 2.41 for the SUV-ratio pituitary/bloodpool (AUC = 0.769). In conclusion, our findings indicate that in patients undergoing ICI treatment for metastatic melanoma, an pituitary SUV-ratio pituitary/bloodpool in FDG-PET/CT of approximately 2.5 might indicate impending ICI-induced hypophysitis and should trigger close clinical monitoring. Presentation: 6/3/2024

8191 Navigating The Maze Of Adrenal Insufficiency, A Complex Case Of Late Presentation

Abstract Disclosure: K.N. Pereira: None. V. Sundaram: None. V. Mehta: None. K. Desai: None. B. Agrawal: None. Adrenal insufficiency, a rare but potentially life-threatening endocrine disorder, arises from the inadequate production or ineffective response to adrenal hormones, particularly cortisol and aldosterone. It poses diagnostic challenges, especially in individuals with intricate medical histories and manifests as either primary (Addison's disease) or secondary. The subtlety of initial symptoms often leads to a delayed diagnosis, emphasizing the importance of a high index of suspicion among healthcare providers. Timely recognition and intervention are crucial to prevent adrenal crises, which includes severe hypotension, electrolyte imbalances and life-threatening complications. This case report delves into the presentation, diagnosis, and management of primary adrenal insufficiency in a 51-year-old female with a myriad of co-morbidities who presented with persistent low blood pressure, syncope episodes and dizziness both at rest and with exertion, despite being on midodrine with systolic blood pressure readings ranging from 60s to 80s mmHg. She was also noted to be bradycardic and laboratory results showed hyponatremia, hyperkalemia, hypoglycemia and anemia. She was given prompt fluid resuscitation, stress dose steroids and fludrocortisone, leading to a remarkable improvement in blood pressure and overall clinical status. Subsequent testing showed low serum cortisol level and elevated ACTH level, confirming the diagnosis of primary adrenal insufficiency. Continued steroids resulted in significant symptomatic improvement and with no further episodes of hypotension or syncope on ensuing follow ups. This case serves as a poignant illustration for the need for a heightened clinical suspicion, as the symptoms of adrenal insufficiency can often masquerade within the intricate tapestry of comorbidities. When the utilization of midodrine, aimed at managing orthostatic hypotension, did not abate symptoms, it prompted a thorough investigation into the possibility of underlying adrenal dysfunction. This case also highlights the collaborative, multidisciplinary approach in the management of adrenal insufficiency, with endocrinology playing a pivotal role. Presentation: 6/1/2024

Serum phosphate levels at diagnosis predict long-term risk for hypopituitarism in patients with acromegaly.

Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated. This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conductingcorrelation analysis and multivariable logistic regression. Sixty-one patients were followed for 4.5years (range 1-21). Patients with hyperphosphatemia (> 4.5mg/dl) at baseline had larger adenomas (15.0mm [8.0, 47.0] vs. 10.0mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0nmol/l [27.6, 516.0] vs. 294.0nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01). Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly.

SAT626 The Use Of Salivary Cortisol Measurement By Mass Spectrometry To Identify Low Serum Cortisol Values In Healthy Volunteers Receiving CRN04894, A Melanocortin 2 Receptor (MC2R) Antagonist

Abstract Disclosure: A. Ayala: Employee; Self; Crinetics Pharmaceuticals Inc. C. LaCerte: Employee; Self; Crinetics Pharmaceuticals Inc. R. Luo: Employee; Self; Crinetics Pharmaceuticals Inc. C. Davidson: Employee; Self; Crinetics Pharmaceuticals Inc. J. Wang: Employee; Self; Crinetics Pharmaceuticals Inc. P. Trainer: Employee; Self; Crinetics Pharmaceuticals Inc. A. Krasner: Employee; Self; Crinetics Pharmaceuticals Inc. Clinical trials of cortisol-lowering drug candidates would benefit from user-friendly methods to measure cortisol in an outpatient setting. CRN04894 is a potent, orally bioavailable, MC2R antagonist in development for the treatment of ACTH-dependent Cushing’s syndrome and congenital adrenal hyperplasia. We have previously reported results from a randomized, double-blinded, placebo-controlled (6 active:3 placebo/cohort), multiple (10-day) ascending dose (40 to 80 mg/day) study in healthy volunteers. Declines in basal and ACTH-stimulated serum cortisol levels and a median reduction of 75% in 24-hr urinary-free cortisol (UFC) were seen in the 80 mg cohort. Asymptomatic glucocorticoid deficiency (defined as 08:00 serum cortisol of <5 µg/dL) was the most commonly observed adverse event. Here we report the comparison of salivary cortisol measurements with serum cortisol day curves and 24-hr UFC observed in this study. We evaluated cortisol and ACTH data from the three cohorts dosed once daily (QD) at 22:00 with either 40, 60, or 80 mg. Cortisol (salivary & serum) and ACTH day curves (results reported as the mean of 4 or 5 available samples collected at 22:00, 08:00, 12:00, 16:00 & 20:00) studies were undertaken on days -1, 1, 4, and 9. Mean serum cortisol was moderately correlated with 24-hr UFC:creatinine ratio (ug/g) (r = 0.495) and strongly correlated (r = 0.734) with mean salivary cortisol. There was across all three doses of CRN04894 a consistent magnitude ranking change in measured cortisol analytes: serum (free plus bound) < saliva < urine, with substantial changes being seen within 24 hours of initiation of CRN04894 and no loss of cortisol suppression over 9 days despite median ACTH changes of >1000% from baseline (60 & 80 mg doses). Time-matched individual saliva and serum cortisol values were used (without timepoint or visit restrictions) to explore the relationship between low serum cortisol and salivary levels. A saliva cutoff for cortisol deficiency was optimized for diagnostic accuracy (92.2%) using a serum cortisol value of <5 µg/dL as the reference. Four subjects had 08:00 serum cortisol <5 µg/dL and saliva cortisol data. All four cases were correctly identified as cortisol-deficient using a simultaneous saliva cortisol cutoff of <0.0491 µg/dL. In conclusion, CRN04894 effectively lowered cortisol measured in serum, saliva, and urine in healthy volunteers. Salivary cortisol measured by tandem mass spectrometry correlated well with serum cortisol day curves and may be useful in the diagnosis of biochemical cortisol deficiency in outpatient studies. Future studies will explore the use of salivary glucocorticoid measurement in patients with Cushing’s disease receiving CRN04894. Presentation: Saturday, June 17, 2023

Depression symptoms and suicide risk of internal medicine residents before and after first year of the COVID-19 pandemic.

Depression is a mental health disorder characterized by the presence of sadness or loss of the ability to feel pleasure, with a high incidence in patients with COVID 19. The investigations have focused on patient care and little on the care of health personnel, these being the ones with the highest mortality rate, so the objective of the study was to investigate the prevalence of depression symptoms and suicide risk and understand the association of depressive disorder and suicide risk with levels of serum cholesterol and low levels of serum cortisol among internal medicine fellows in a specialist medical hospital in Leon, Guanajuato, Mexico, before and after COVID-19. In this longitudinal study, internal medicine residents were initially monitored for 2months before starting to care for patients with COVID-19. Participants were asked to fill out depression symptoms and suicide risk surveys. We measured the serum cholesterol and cortisol of each participant, and again after 11months of treating COVID-19 patients. Depression symptoms and suicide risk were assessed; significant differences were found between the two time periods for depression (p < 0.01), and no difference was found for suicide risk (p = 0.182). We found a significant correlation between serum cholesterol levels and suicide risk (r = 0.366, p < 0.01); we also found differences in serum cortisol levels (p < 0.01) and cholesterol (p < 0.0001) before and after the pandemic. Caring for patients with COVID-19 in the hospital contributed to an increase in levels of depression symptoms and suicidal ideation, as well as differences in levels of cortisol and cholesterol in resident physicians of internal medicine; among the possible reasons for this change could be the conditions of personal protection while treating patients, the uncertainty in the first months of not knowing how the virus was transmitted and not having or knowing when vaccinations would be available, as well as the lack of a strategy of adequate mental health support from the institutions dedicated to their academic training.

Effect Modification of Cortisol on the Associations Between Obsessive-Compulsive Symptoms on Suicidality in Patients With Acute Coronary Syndrome.

Obsessive-compulsive symptoms (OCS) and suicidal ideation (SI) are common in patients with acute coronary syndrome (ACS). This study investigated the associations of OCS and serum cortisol levels with SI, and further evaluated the possible modifying effects of cortisol on the associations between OCS and SI in acute and chronic phases of ACS. In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of OCS (using the OCS dimension of the Symptom Checklist-90-Revised), serum cortisol levels, and SI (using the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI. Logistic regression analysis was performed with adjustment for covariates. Higher OCS was significantly associated with SI both at baseline and follow-up. Serum cortisol showed no such association, but modified the association between OCS and SI. That was the associations were significant only in the higher but not in the lower serum cortisol levels, with significant interaction terms after adjusted for relevant covariates. Evaluating OCS and serum cortisol levels at the acute phase could improve the accuracy of clinical predictions of SI both in the acute and chronic phases of ACS.

Effects of antenatal dexamethasone on postnatal serum cortisol levels in late preterm infants

Objectives To explore whether antenatal dexamethasone impacts postnatal serum cortisol levels in stable late preterm (LPT) infants. Secondary outcomes were to identify short-term hospital outcomes related to antenatal dexamethasone exposure. Methods A prospective cohort study of serial serum cortisol levels in LPT infants within 3 h of birth, and at 1, 3, and 14 postnatal days. Serum cortisol levels were compared between infants exposed to antenatal dexamethasone >3 h and <14 days prior to delivery (aDex) and those who either did not receive dexamethasone or were exposed < 3 h or >14 days prior to delivery (no-aDex). Results Thirty-two LPT infants (aDex) were compared with 29 infants (no-aDEX). Group demographic characteristics were similar. Serum cortisol levels were identical between the groups at all 4-time points. Cumulative antenatal dexamethasone exposure ranged from 0 to 12 doses. Post-hoc analysis of the 24-hour serum cortisol levels indicated a significant difference between 1 to 3 cumulative doses versus 4 or more doses (p = .01). Only 1 infant in the aDex group had a cortisol level <3rd percentile of the reference value. Rates of hypoglycemia (absolute difference [95% CI] − 1.0 [–16.0,15.0]; p = .90) and mechanical ventilation were similar in both groups (absolute difference [95%CI] − 0.3 [–9.3,8.7]; p = .94). No deaths occurred. Conclusion Antenatal dexamethasone administered 14 days prior to delivery did not affect serum cortisol levels and short-term hospital outcomes in stable LPT infants. Exposure to low cumulative doses of dexamethasone resulted in transient low serum cortisol levels compared to 4 or more doses only at 24-hours.

Two cases of infantile-onset primary generalized glucocorticoid hypersensitivity and the effect of mifepristone

BackgroundPrimary generalized glucocorticoid hypersensitivity (PGGH) is a very rare disease caused by terminal organ hypersensitivity to glucocorticoids for which the aetiology is unknown. The incidence of PGGH is extremely rare, especially in children. To date, the literatures about the etiology, prognosis and treatment of PGGH are scarce. Aim of the study is describing the cases of two Chinese children with infantile-onset PGGH in one family, one of whom died and one who was treated with mifepristone. They are the two youngest children with PGGH reported in the literature.Case presentationTwo siblings with infantile-onset PGGH were affected in this family. The main manifestations of patient 1 were typical Cushing’s syndrome-like manifestations, significantly aggravated symptoms after physiological doses of glucocorticoids and very low levels of serum cortisol and adrenocorticotropin hormone (ACTH) during attacks. After being diagnosed with PGGH, he was given guidance to avoid glucocorticoids and took mifepristone therapy for 5 months, and his symptoms improved. Patient 2 was the younger brother of patient 1, with similar manifestations to his brother at the age of 4 months. Patient 2 ultimately died at the age of 9 months.ConclusionPGGH is a very rare disease that can lead to death if not diagnosed and treated in a timely manner. This article describes the cases of the two youngest children with PGGH reported in the literature, one of whom improved after mifepristone treatment, and increases the knowledge of the clinical manifestations of and the treatment experience in PGGH.

PSUN24 Adrenal Metastases Treated with Radiotherapy: Development of Adrenal Insufficiency

Abstract Introduction Adrenal metastases are the second most common neoplasms of the adrenal cortex. Adrenal insufficiency (AI) develops when more than 90% of the cortex is destroyed. In patients with adrenal metastases requiring local treatment, stereotactic ablative radiation therapy (SAbR) has been shown to be well tolerated. Yet, data on the development of AI following adrenal SAbR are scarce. Therefore, we aimed to assess the incidence, timing, and factors associated with the development of AI in patients undergoing SAbR for the treatment of adrenal metastases. Utilizing an IRB approved registry protocol, we conducted a retrospective longitudinal follow-up study to characterize 66 patients (73% men; median age 61 years) with adrenal metastases who underwent SabR, followed for median 3.8 years from the initial cancer diagnosis and 11.5 months from SAbR. The diagnosis of primary AI was based on low morning serum cortisol levels (&amp;lt;5 μg/dL) with &amp;gt;2-fold elevated plasma ACTH, or peak cortisol &amp;lt;18 μg/dL post cosyntropin. Primary carcinomas included renal cell (41%), lung (38%), colorectal (9%), melanoma (5%), and others (7%). Twenty-four (38%) patients had bilateral adrenal metastases. At the time of SAbR, 41 (62.1%) patients had uninvolved contralateral adrenal glands, 16 (24.2%) had bilateral adrenal metastases, and 9 (13.6%) had contralateral adrenalectomy prior to SAbR. Nine patients had bilateral SAbR and 9 had SAbR to one adrenal gland in the setting of contralateral adrenalectomy. Most patients (66.7%) underwent 5 SAbR fractions, with a median dose of 800 cGy/fraction. In our cohort, 39/66 (59%) patients underwent comprehensive assessment of adrenal function. Overall, 7 (10.6%) patients developed post-SAbR AI at median time of 4.3 months (range, 0.7-20.2). The incidence of post-SAbR AI was 22.2% (2/9) in patients with prior contralateral adrenalectomy, 18.8% (3/16) with bilateral adrenal metastases, and 0% (0/41) with normal contralateral adrenal gland. A 6-month-AI-free survival rate was 72.7% (95% CI, 37.0-90.3) in patients with bilateral metastases and 64.8% (1.6-73.7) in patients with contralateral adrenalectomy. Post-SAbR median progression-free survival (local disease) was 3.0 years, with 6-month and 1-year survival rates of 82.4% and 75.0%, respectively. Conclusions Our study shows thatpatients with a normal contralateral adrenal gland are unlikely to develop post-SAbR AI. In contrast, AI occurred in ∼ 20% of patients with prior contralateral adrenalectomy or bilateral adrenal metastases. In this high-risk cohort, only 60% of patients underwent assessment of adrenal function. It is crucial to monitor adrenal function in patients undergoing SAbR for adrenal metastasis, especially in those with affected or surgically absent contralateral gland. This study reinforces the importance of a team-based approach to the management of patients with adrenal metastasis to improve patient outcomes. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Isolated ACTH deficiency following immunization with the BNT162b2 SARS-CoV-2 vaccine: a case report

BackgroundThe global COVID-19 pandemic requires urgent development of new vaccines. Endocrinological adverse effects following the new mRNA vaccine against COVID-19 have been reported in several cases. Specific to the involvement of pituitary function; however, only a single case with hypophysis has been reported. This is the first case of isolated adrenocorticotropic hormone (ACTH) deficiency (IAD) following mRNA vaccination against COVID-19.Case presentationA healthy 31-year-old man received the BNT162b2 SARS-CoV-2 mRNA vaccine. The first injection was uneventful. One day after the second injection, he noticed general fatigue and fever. In the following several days, he additionally developed headaches, nausea, and diarrhea. Four days after the vaccine injection, he visited a hospital with worsening of these symptoms. Physical examination revealed slight disorientation but no other deficits. Laboratory tests revealed hyponatremia, hypoglycemia, and extremely low plasma ACTH and serum cortisol levels (ACTH < 1.5 pg/ml, cortisol 1.6 μg/dl). He was diagnosed with adrenal crisis and was emergently treated with hydrocortisone. The symptoms responded well and he recovered within a few days. Magnetic resonance images after the replacement with hydrocortisone revealed an atrophic pituitary gland. The patient was referred to our tertiary hospital for further endocrinological examination. Pituitary endocrine load tests revealed isolated adrenocortical response deficiency. After other clinical assessments, he was diagnosed as having isolated ACTH deficiency. After initiation of hydrocortisone replacement, there has been no recurrence of symptoms related to adrenocortical insufficiency nor involvement of other pituitary functions.ConclusionThis is the first reported case of IAD potentially associated with COVID-19 immunization. Recent reports have emphasized the importance of adjuvants in the mRNA vaccine that induce the endocrinological adverse effects through disturbance of the autoimmune system, but details are still unclear. Given the broad and rapid spread of vaccinations against COVID-19, it is clinically important to consider that there could be cases with a rare but emergent adrenal crisis even among those who present common symptoms of adverse effects following inactive SARS-CoV-2 mRNA vaccination.

Childhood Maltreatment, Low Serum Cortisol Levels, and Non-Suicidal Self-Injury in Young Adults With Major Depressive Disorders.

BackgroundNon-suicidal self-injury (NSSI) is a serious public health problem widely present among young adults and adolescents. While finding risk factors associated with NSSI among young patients with major depressive disorder (MDD) is challenging, the current study aims to measure childhood adversity and serum cortisol levels and elucidate their relationship in MDD patients with NSSI.MethodsIn this cross-sectional study, 126 young patients with MDD (aged 16 to 35 years) were recruited. The depressive symptoms were assessed by the Beck Depression Inventory (BDI-II), and the childhood adversity was evaluated by the Chinese version of the Childhood Trauma Questionnaire (CTQ) scale. Serum cortisol levels were determined by the kits in patients.ResultsRelative to MDD patients without NSSI, MDD patients with NSSI had a higher CTQ total score and its four subscores. Moreover, the cortisol levels in patients with MDD/NSSI were significantly decreased than in MDD patients without NSSI. For patients with MDD/NSSI, there is a negative association between cortisol levels and emotional neglect, but not for MDD patients without NSSI. Further regression analysis showed that low cortisol levels, BDI-II, and emotional neglect were risk factors for NSSI in young patients with MDD.ConclusionOur findings suggest that young MDD patients with NSSI experience more childhood adversity and have lower cortisol levels. Also, lower cortisol levels were associated with childhood adversity but not with depressive symptoms. Further, lower cortisol levels, depressive symptoms, and emotional neglect were risk factors for NSSI in young patients with MDD.

A Novel Homozygous MC2R Variant Leading to Type-1 Familial Glucocorticoid Deficiency.

ContextType 1 familial glucocorticoid deficiency (FGD) (OMIM #607397) is a rare autosomal recessive disorder due to mutations in melanocortin-2-receptor (MC2R) gene encoding the G protein-coupled adrenocorticotropic (ACTH) transmembrane receptor.ObjectiveThe aim of the study is to describe 2 siblings born to a healthy consanguineous family presenting with clinical and biochemical features of FGD, harboring a novel homozygous MC2R variant.MethodsBoth patients are siblings born at term via normal delivery with normal birth weights. The first sibling presented with symptoms of hypoglycemia, repeated episodes of infections starting from 2 days of age. At 18 months of age, low serum cortisol was found, and he was started on hydrocortisone replacement therapy. The second sibling developed hypoglycemia on day 1 after birth, investigations revealed low serum sodium and cortisol levels and was also commenced on hydrocortisone treatment. Whole exome sequencing (WES) and in vitro functional studies on cell line transfected with wild-type and mutant plasmid clones were undertaken.ResultsWES revealed a novel homozygous missense mutation c.326T>A, p.Leu109Gln in the MC2R gene. In-silico prediction tools predicted the effect of this mutation to be deleterious. In vitro study using HEK293 cells transfected with MC2R wild-type and mutant clones showed a defect in protein expression and cAMP generation when stimulated with ACTH.ConclusionHomozygous semiconserved p.Leu109Gln mutation disrupts cAMP production and MC2R protein expression leading to ACTH resistance. This study provides additional evidence that this novel pathogenic variant in MC2R results in FGD phenotypes.

High cortisol levels are associated with oxidative stress and mortality in maintenance hemodialysis patients

BackgroundChronic stimulation of the mineralocorticoid receptor has been suggested as one of the potential causes of cardiovascular events and death in patients with end-stage renal disease. This observational cohort study was performed to demonstrate that serum cortisol might be a predictive marker for patient mortality and to evaluate its association with oxidized low-density lipoprotein (oxLDL) in hemodialysis (HD) patients.MethodsPatients receiving HD three times a week were screened for enrollment at two institutions. Baseline cortisol levels were measured before each HD session, and the patients were divided into two groups according to the median value of serum cortisol before analysis. The baseline characteristics and laboratory values of the high and low cortisol groups were compared. Serum cortisol, adrenocorticotropic hormone, renin, aldosterone, and oxLDL were measured in 52 patients to evaluate the effect of oxidative stress on serum cortisol levels.ResultsA total of 133 HD patients were enrolled in this cohort study. Compared to the patients with low serum cortisol levels, the patients with high serum cortisol levels (baseline cortisol ≥ 10 μg/dL) showed higher rates of cardiovascular disease (59.7% vs. 39.4%, P=0.019) and left ventricular systolic dysfunction (LVSD) (25.9% vs. 8.0%, P=0.016). The patients in the high cortisol group demonstrated higher all-cause mortality than those in the low cortisol group. The serum cortisol level was an independent risk factor for patient mortality (hazard ratio 1.234, 95% confidence interval 1.022-1.49, P=0.029). Among the 52 patients with oxLDL measurements, oxLDL was an independent risk factor for elevated serum cortisol levels (Exp(B) 1.114, P=0.013) and LVSD (Exp(B) 12.308, P=0.045). However, plasma aldosterone levels did not affect serum cortisol levels.ConclusionsSerum cortisol is a useful predictive marker for all-cause death among patients receiving HD. OxLDL is an independent marker for elevated serum cortisol among HD patients.

Study of Effect of Whitening Creams on Serum Basal Cortisol level In Egyptian Females

Abstract Objective The aim of the present study is to evaluate the relationship between practice of whitening creams (Topical Corticosteroids) and serum cortisol level in a sample of healthy females at Ain- shams University Teaching hospital. Background Topical corticosteroids (TCs) are widely used as depigmenting agents alone or in combination with other fairness creams. Secondary adrenocortical insufficiency occurs due to deficiency of corticotropin (adrenocorticotropic hormone) [ACTH] in the pituitary gland. With low levels of corticotropin, cortex layer in the adrenal gland is not sufficiently stimulated to release adequate amount of cortisol. Excessive glucocorticoid therapy is the primary cause of adrenocortical insufficiency. Methods we recruited 45 subjects practice whitening creams (TCs) for three months or more; matched with a healthy control group consists of 45 participants. Early morning basal serum cortisol level (8:00 am) done by one-step competitive immunoassay using Beckman Coulter device. Cortisol ELISA Kit provided by CALBIOTECH, Inc (Co_103S). Results Early morning serum cortisol level was statistically insignificant among subjects practice whitening creams in combination with TCs vs. healthy controls (p value 0.307). However, there were 7 out of 45 participants in the study group (15.6%) had low serum cortisol level (&amp;lt;5ug/dl) with highly statistically significant difference regarding whitening creams usage methods. In comparison and data analysis between subjects of the study group regarding practice duration, used quantity, application frequency, and method of exposure, there was high statistically significant difference between subjects with normal cortisol level vs. subjects with low cortisol level (p value &amp;lt;0.001). There were, no significant difference found regarding BMI, and arterial blood pressure between study group and controls. Conclusion Whitening creams abuse especially high potency TCs is a common phenomenon that may induce several local and systemic complications including adrenal gland insufficiency.

The possibility of short-term hypothalamic-pituitary-adrenal axis suppression with high-volume, high-dose nasal mometasone irrigation in postsurgical patients with chronic rhinosinusitis.

Medically refractory chronic rhinosinusitis (CRS) is often treated with functional endoscopic sinus surgery (FESS) and high-volume steroid nasal irrigation. While budesonide is the most common steroid irrigation for this indication, mometasone has a superior pharmacokinetic profile, which may allow dose escalation. The safety and efficacy of mometasone at higher concentrations than previously used in treating CRS have not been explored. Patients were recruited from a tertiary level clinic between June 2018 and December 2019. Inclusion criteria included adults (>18 years); CRS diagnosis; previous FESS; pre-treatment morning cortisol within normal range; minimum of twice daily high-volume sinonasal mometasone irrigations (total dose of 4 mg) for 12 weeks; and post-treatment morning cortisol measured within 2 weeks following the study period. Patients with potential for endogenous or exogenous disruption of the HPA axis were excluded. 14 patients were enrolled in this prospective cohort study. In all but one patient, pre- and post-treatment morning cortisol levels were not significantly different and were within normal limits (6.7-25.4 μg/dL). Following an uninterrupted 12-week treatment course, no evidence of HPA axis suppression was found (P = 0.915). The single patient who was found to have a low (1.3 μg/dL) post-treatment morning serum cortisol level reportedly received an intraarticular steroid shot several days prior to the blood draw. She remained asymptomatic and her rechecked serum cortisol was within normal limits at 12.3 μg/dL. High-volume 2 mg twice daily sinonasal mometasone irrigations did not cause HPA axis suppression in a representative sample of patients with refractory CRS post-FESS with normal baseline cortisol levels.

Factitious Cushing's syndrome, hypopituitarism, and self-provoked skin lesions: when the skin mirrors the soul.

SummaryFactitious Cushing’s syndrome (CS) is a very rare form of Münchausen syndrome. Its presentation and course are extremely heterogeneous, and diagnosis is generally challenging. We report the case of a 52-year-old woman who was initially investigated because of the occurrence of cushingoid features. Nevertheless, endocrine work-up showed very low morning plasma ACTH and serum cortisol levels. In addition, it also demonstrated central hypopituitarism and hypogonadotropic hypogonadism. Head MRI showed a small pituitary mass. Based on these results, and probably overlooking the initial clinical suspicion, general practitioner (GP) referred the patient to our Endocrine Unit for hypopituitarism. At inspection, moon face, central obesity, and bruising were evident. Multiple ulcerative skin lesions were also concentrated in the right arm and leg. Dermatology evaluation suggested that the lesions were self-provoked. For several days, the patient denied the assumption of corticosteroids, but we finally discovered that the GP’ nurse had prescribed betamethasone without the GP’s knowledge for about 2 years. In conclusion, the surreptitious assumption of corticosteroids is very rare, but the physicians should be aware that pituitary function could be impaired by high doses of corticosteroids, mimicking hypopituitarism. In these patients, a multidisciplinary approach and environmental investigation can be useful to diagnose factitious CS.Learning pointsSurreptitious assumption of corticosteroids can cause heterogeneous presentation, ranging from Cushing’s syndrome to multiple hypopituitarism.Suppression of ACTH and cortisol levels in a patient with cushingoid features firstly suggests surreptitious assumption of corticosteroids.A multidisciplinary approach can be extremely useful in patients with suspected factitious Cushing’s syndrome.Sometimes, to prove surreptitious assumption of corticosteroids needs environmental investigation.

The Association of Low Blood Glucose and Low Serum Cortisol Levels in Severely Ill Children Admitted to Tertiary Referral Hospitals in Malawi: A Case-Control Study

ABSTRACT.Low blood glucose concentrations < 5 mmol/L in severely ill children presenting to hospitals in low-income countries are associated with mortality. Adrenal insufficiency with low cortisol levels may contribute to low blood glucose concentrations. Understanding the association between low cortisol and low blood glucose may assist in improving guidelines for management of severely ill children. The study aimed to determine the association between low serum cortisol and low blood glucose in severely ill children. A matched case-control study of children aged 1 month to 15 years was conducted at two tertiary hospitals in Malawi. Cases were children with blood glucose < 5 mmol/L. Two age-matched controls with blood glucose of ≥ 5–15 mmol/L were enrolled per case. Low cortisol was defined as serum cortisol of < 25 µg/dL (690 nmol/L) and adrenal insufficiency as serum cortisol of < 10 µg/dL (276 nmol/L). A total of 54 cases and 108 controls were enrolled with, median age of 2.8 years (interquartile range [IQR]: 1.7–4.4). The median cortisol level was 58.7 µg/dL (IQR: 42.3–61.8) in cases and 40.9 µg/dL (IQR: 33.7–51.2) in controls (P = 0.911). The proportion of low cortisol was 4/54 (7.4%) in cases and 9/108 (8.3%) in controls. Logistic regression shows no association between low cortisol and low blood glucose (adjusted odds ratio: 0.33; 95% confidence interval, 0.04–3.02). Results suggest that there is no association between low cortisol and low blood glucose among severely ill children presenting to hospitals in Malawi. The reason for low blood glucose needs further investigation.

Occurrence of Adrenal Suppression in Patients Having Sepsis in Indian Population and Impact of Corticosteroid Supplementation on Its Overall Survival

Abstract Objective Our aim was to estimate the occurrence of adrenal suppression in critically ill patients with septic shock who have got admission in intensive care unit and to evaluate the effectiveness of hydrocortisone in these patients in relation to mortality of patient, development of septic shock, and effect on total leucocyte count. Methods Serum cortisol was measured in 120 patients with sepsis. Patients with decreased cortisol level were split in to two groups (group A and B). Group A received 50 mg of hydrocortisone 6 hourly and group B was given matching placebo. At day 7, serum cortisol level was estimated for both A and B groups. The results were calculated and compared with relation to incidence of adrenal insufficiency, development of septic shock, effect on total leucocyte count, and survival at 28 days. Results The occurrence of adrenal suppression in patients having sepsis in our study was 44 out of 120 patients, that is, 36.6%. After supplementation of corticosteroid for 7 days the mean value of serum cortisol of group A was 40.38 ± 8.44 µg/dL and group B was 24.30 ± 6.47 µg/dL (p &lt; 0.001). At day 7, in group A, 22.7% developed septic shock, whereas in group B, 36.4% developed septic shock (p &lt; 0.001). In group A and B, mortality rate of the patients at 28 days was 18.2 and 22.7%, respectively. Conclusion Hydrocortisone supplementation in critically ill patients with low random basal serum cortisol level with sepsis does not significantly improve the overall survival.

Serum cortisol as a predictor for posttraumatic stress disorder symptoms in post-myocardial infarction patients

BackgroundAfter an acute myocardial infarction (MI22MI: myocardial infarction), patients may develop posttraumatic stress disorder (PTSD33PTSD: posttraumatic stress disorder). There is evidence for alterations in the hypothalamic–pituitary–adrenal axis in PTSD. An association between patients` cortisol level after experiencing an MI and subsequent PTSD symptoms has not been investigated yet. Therefore, the aim of this study was to examine whether serum cortisol measured in patients admitted to hospital for acute coronary care after MI is predictive of PTSD symptoms at three and 12 months post-MI, respectively. MethodsPatients (N=106) with a verified MI and high risk for the development of MI-induced PTSD symptoms were included in the study within 48 hours of hospital admission for acute coronary intervention. Serum cortisol was measured from fasting venous blood samples the next morning. Hierarchical regression analysis was used to test for an independent contribution of cortisol levels from admission to the Clinician-Administered PTSD Scale sum score three and 12 months after discharge from the coronary care unit. ResultsHierarchical regression analysis showed that lower serum cortisol levels were significantly associated with more severe PTSD symptoms three months (B=-0.002, p=0.042) and 12 months (B=-0.002, p=0.043) post-MI. LimitationsThe generalizability of the findings is limited to patients with high acute peri-traumatic distress and without an acute severe depressive episode. The study does not provide any information about the diurnal cortisol pattern. ConclusionLower serum cortisol measured during MI hospitalization may predict more severe MI-induced PTSD symptoms three and 12 months after hospital discharge.

Acute Kidney Injury in a Previously Healthy 15-Year-Old Patient: A Subtle Presentation of Addison’s Disease

Introduction: Primary adrenal insufficiency (PAI), also known as Addison’s disease, is a disorder of the adrenal glands characterized by decreased levels of glucocorticoids and mineralocorticoids. It is a rare condition with a prevalence of 120 cases per million and is less frequently seen in the pediatric population. Here, we report a previously healthy 15-year-old patient with acute kidney injury (AKI) and PAI. Case Presentation: The patient was admitted to the hospital after findings of abnormal laboratory studies, which included an elevated BUN (53 mg/dL), creatinine (1.39 mg/dL), calcium (11.3 mg/dL), potassium (5.6 mmol/L), and hyponatremia (126 mmol/L). These were performed at an outpatient visit due to three-week history of back pain, fatigue and emesis. On admission, he had stable vital signs. Physical examination revealed generalized darkening of skin, more noticeable on the knuckles and palmar creases, with hyperpigmented patches in oral mucosa and both upper extremities. Although his renal function, serum potassium and calcium levels normalized after intravenous hydration with normal saline, hyponatremia (128 mmol/L) continued. His urine analysis and renal ultrasound were normal. Due to his hyperpigmentation and persistent hyponatremia, PAI was suspected. An ACTH stimulation test revealed that basal and stimulated serum cortisol levels were low, 2.6 mcg/dL and 2.9 mcg/dL, respectively. His plasma ACTH level was elevated at 1,625 pg/mL and serum aldosterone level was low at <4.0 ng/dL. These results were consistent with PAI. The patient’s hyponatremia resolved after receiving stress dose hydrocortisone. He was discharged home on hydrocortisone and fludrocortisone with endocrinology follow up. Discussion: PAI is well described in the literature, though reports in pediatrics vary. Patients may present with nonspecific symptoms such as unexplained weight loss, fatigue, diffuse abdominal pain, nausea, vomiting and muscular weakness. These symptoms may be of insidious onset, which often leads to delayed diagnosis. Physical signs include hypotension and hyperpigmentation. Characteristic biochemical findings are hyponatremia, hyperkalemia and hypoglycemia. Despite the electrolyte derangements, AKI is not a common presentation of PAI. There are only a few case reports associating these two diseases. In this case, his symptoms and abnormal electrolytes were initially considered to be the result of AKI of unknown origin. PAI only became a suspicion after a careful physical exam and persistent hyponatremia despite improvement of his AKI with fluid resuscitation. His low serum cortisol and aldosterone levels with elevated plasma ACTH confirmed the diagnosis of PAI. Conclusion: This case highlights a unique presentation of PAI in an adolescent. A timely diagnosis reduces the risk of unwanted and potentially life-threatening complications such as an Addisonian crisis.