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This article is an editorial discussing the problem of childhood hypoglycemia. It highlights the lack of a clear definition for neonatal hypoglycemia and the challenges in diagnosing and treating the condition. The editorial also explores different aspects of childhood hypoglycemia, including genetic and non-genetic causes, as well as the role of glucose monitoring and potential therapeutic strategies. The authors emphasize the need for further research and a multidisciplinary approach to improve the understanding and management of childhood hypoglycemia. [Extracted from the article]

Background: Damage to the insula has been associated with various types of cardiovascular dysfunction, including arrhythmias and blood pressure imbalances. Acute neuroendocrine disturbances following insular damage have also been described. Case Presentation: A 50‐year‐old right‐handed man with a left insular ischemic lesion exhibited aphasia and right central VII nerve palsy. Five days after the stroke, the patient exhibited severe bradycardia and hypotension. He had been treated for ocular trauma with prednisone for the preceding 3 weeks. Cortisol and adrenocorticotropic hormone levels indicated secondary adrenal insufficiency. Despite adequate fluid intake, the patient's blood pressure dropped, requiring norepinephrine administration. Midodrine was also initiated, leading to clinical improvement. The therapy was gradually discontinued as vital signs normalized. By Day 24, electrocardiogram monitoring was unremarkable, hormonal levels normalized, and the neurological examination revealed only mild residual speech fluency impairment. Computed tomography scans confirmed a recovering ischemic lesion of the left insula. Conclusions: This case reveals the inhibitory effect exerted by a left‐sided insular stroke on the autonomic system. It also highlights the still largely unexplored neuroendocrine complications of damage to this brain region. [ABSTRACT FROM AUTHOR]

Adrenal insufficiency is a critical condition that can often present with non specific symptoms, posing a diagnostic challenge in the context of co-existing conditions. Authors hereby, report a complex case of secondary adrenal insufficiency revealed through persistent fever and hyponatremia in a 73-year-old female with a multifaceted medical history, including hypertension, diabetes, and Takotsubo cardiomyopathy. Her symptoms of intermittent fever and diarrhoea were refractory to treatment, leading to hospital readmission. Initial laboratory investigations highlighted hyponatremia, low haemoglobin, elevated inflammatory markers, and low cortisol levels. Although a urinary tract infection with multidrug-resistant Klebsiella was identified and treated, her febrile state persisted. Extensive serological testing for a broad range of infectious diseases yielded negative results, excluding infectious etiologies as the cause of her fever. Imaging studies, including chest X-ray, Electrocardiogram (ECG), echocardiogram, Positron Emission Tomography (PET) scan, Computed Tomography (CT), and transesophageal echocardiography, failed to identify a source of infection or malignancy. Notably, a low random cortisol level coupled with an inappropriately low Adrenocorticotropic Hormone (ACTH) level prompted further endocrine evaluation. Magnetic Resonance Imaging (MRI) revealed an empty sella turcica, confirming secondary adrenal insufficiency. This diagnosis was substantiated by the patient's positive response to steroid therapy, which led to clinical improvement and eventual discharge. The present case underlines the importance of considering adrenal insufficiency in patients presenting with unexplained hyponatremia and fever, particularly when other common aetiologies have been ruled out. It also illustrates the potential for critical endocrine disorders to mimic sepsis, underscoring the necessity of a comprehensive diagnostic approach in the face of complex presentations. [ABSTRACT FROM AUTHOR]

This article, published in Clinical Pediatric Endocrinology, discusses a case of adrenal crisis (AC) in a young child with septo-optic dysplasia (SOD) during a trip. The patient, a 16-month-old Japanese child with SOD and intellectual disability, developed AC after a long-distance trip. The authors suggest that prolonged periods in unfamiliar environments during trips may be a potential precipitating factor for AC in susceptible individuals. They recommend considering prophylactic administration of a stress dose of hydrocortisone during trips to prevent AC. However, further research is needed to determine the effectiveness of this approach. [Extracted from the article]

This article discusses the perioperative management of adrenal insufficiency in pediatric patients. Adrenal crises, which can be life-threatening, can occur in patients with adrenal insufficiency during periods of physiological stress. The primary management strategy is stress dosing of hydrocortisone, often combined with dextrose-containing intravenous fluids. The article presents a retrospective analysis of data on perioperative hydrocortisone dosing in pediatric patients with adrenal insufficiency, highlighting significant variability in dosing and a low incidence of adverse events. The findings emphasize the importance of institutional guideline development, education, and further research in this field to improve perioperative management of adrenal insufficiency in children. [Extracted from the article]

Budesonide is a 'non‐absorbable' corticosteroid often used for gut graft versus host disease. Systemic exposure is usually minimal because of metabolism by cytochrome (CYP) 3A4 in enterocytes and the liver. However, concomitant use of posaconazole and voriconazole, inhibitors of CYP3A4 commonly used as antifungal prophylaxis in allograft patients receiving immunosuppression, can lead to substantial systemic steroid exposure. This paper describes a case of severe iatrogenic Cushing syndrome and tertiary adrenal insufficiency because of this interaction, highlighting the necessity for improved awareness of this phenomenon. [ABSTRACT FROM AUTHOR]

Adrenal insufficiency is a disease characterized by insufficient secretion of adrenocortical hormones, usually treated with glucocorticoid replacement therapy. The routine drugs have two forms-short-acting and long-acting. The shorter one should be taken 2-3 times a day resulting hormone level of patients fluctuating greatly within a day. Although long-acting drugs reduce the frequency of administration, it is easy to lead to excessive replacement, resulting in adverse effects on metabolism. New alternative treatments for adult patients have emerged, including modified-release hydrocortisone and hydrocortisone subcutaneous infusion pumps. In this review, we briefly introduce these new therapies, emphasizing the pharmacodynamics and pharmacokinetics of the replacement, the effects on metabolism and drug safety, aiming at contributing to the future clinical practice.

Objective: Patients with primary adrenal insufficiency (PAI) are thought to be particularly vulnerable to coronavirus disease 2019 (COVID-19); however, little is known about its true impact on this group. We assessed morbidity and health promotion attitudes during the pandemic amongst a large cohort of patients with PAI. Design: Cross-sectional, single-centre study. Methods: In May 2020, COVID-19 advice on social distancing and sick-day rules was distributed to all patients with PAI registered with a large secondary/tertiary care centre. A semi-structured questionnaire was used to survey patients in early 2021. Results: Of 207 contacted patients, 162 responded (82/111 with Addison’s disease, AD; 80/96 with congenital adrenal hyperplasia, CAH). Patients with AD were older than those with CAH (median age 51 vs 39 years; P < 0.001) and had more comorbidities (Charlson comorbidity index ≥2 47.6% vs 10.0%; P < 0.001). By the time of the survey, 47 patients (29.0%) had been diagnosed with COVID-19, the second commonest cause of sick-day dosing during the study and the leading trigger of adrenal crises (4/18 cases). Patients with CAH had a higher risk of COVID-19 compared to AD (adjusted odds ratio 2.53 (95% CI 1.07–6.16), P = 0.036), were less inclined to have the COVID-19 vaccine (80.0% vs 96.3%; P = 0.001), and were less likely to have undergone hydrocortisone self-injection training (80.0% vs 91.5%; P = 0.044) or wear medical alert jewellery (36.3% vs 64.6%; P = 0.001). Conclusions: COVID-19 was a principal trigger for adrenal crises and sick-day dosing in patients with PAI. Despite a higher risk of COVID-19, patients with CAH showed less engagement with self-protective attitudes. Significance statement: We conducted a cross-sectional study on a large and well-characterised group of patients with PAI and demonstrated that COVID-19 was a leading cause of morbidity during the early phases of the pandemic. Patients with AD were older and had a greater burden of comorbidity than those with CAH, including non-adrenal autoimmune disorders. However, patients with CAH were more likely to develop COVID-19 and demonstrated reduced engagement with healthcare services and health promotion strategies.

Background Immunotherapy-related endocrine adverse reactions are relatively common, which often lead to serious outcomes if not treated in time. However, the incidence of immunotherapy-related endocrine adverse reactions varies widely in previous literature reports without standard processing. Objective To investigate the occurrence and treatment process of endocrinologic adverse reactions caused by immune checkpoint inhibitors (ICIs) in the real world. Methods The clinical data of 204 patients with solid tumors treated with ICIs at the Third People's Hospital of Zhengzhou from January 2019 to March 2022 was retrospectively analyzed, the endocrinologic adverse reactions occured their treatment were observed and standardized management was conducted according to the adverse reactions grading. Results A total of 204 patients with solid tumors were included, involving 139 male patients and 65 female patients, with a median age of 65.4 (8.0, 88.4) years. The types of solid tumor were predominantly non-small cell lung cancer (43.1%) , the treatment drugs were mainly sindilizumab (47.1%) , and the treatment patterns were predominantly immunotherapy combined with targeted agents (57.4%) . 12 patients developed ICIs-related endocrinologic adverse reactions, including 9 cases (4.4%) of hypothyroidism (1 case of gradeⅠ, 7 cases of grade Ⅱ, 1 case of grade Ⅲ) with the median onset time of 7 (6, 10) weeks after the treatment of immunological drugs, 1 case (0.5%) of hyperthyroidism (gradeⅠ) occurred 9 weeks after the immunotherapy, 1 case (0.5%) of type 1 diabetes (gradeⅣ) occurred 6 weeks after auto-immunotherapy, 1 case (0.5%) of adrenal dysfunction (gradeⅢ) occurred 7 weeks after immunotherapy. All the 12 patients with endocrinologic adverse reactions were treated in time according to the hierarchical management process, and all their symptoms were improved or returned to normal, and continued to be treated with ICIs. Conclusion The risk of endocrinologic adverse reactions in the endocrine system is relatively high during the use of ICIs, especially abnormal thyroid function, which requires regular detection of endocrine indicators during treatment, timely intervention will not affect the subsequent treatment of ICIs.

Abstract Background Allgrove disease is a rare genetic syndrome characterized by adrenal insufficiency, alacrimia, achalasia and complex neurological involvement. Allgrove disease is due to recessive mutations in the AAAS gene, which encodes for the nucleoporin Aladin, implicated in the nucleocytoplasmic transport. The adrenal insufficiency has been suggested to rely on adrenal gland-ACTH resistance. However, the link between the molecular pathology affecting the nucleoporin Aladin and the glucocorticoid deficiency is still unknown. Results By analyzing postmortem patient’s adrenal gland, we identified a downregulation of Aladin transcript and protein. We found a downregulation of Scavenger receptor class B-1 (SCARB1), a key component of the steroidogenic pathway, and SCARB1 regulatory miRNAs (mir125a, mir455) in patient’s tissues. With the hypothesis of an impairment in the nucleocytoplasmic transport of the SCARB1 transcription enhancer cyclic AMP-dependent protein kinase (PKA), we detected a reduction of nuclear Phospho-PKA and a cytoplasmic mislocalization in patient’s samples. Conclusions These results shed a light on the possible mechanisms linking ACTH resistance, SCARB1 impairment, and defective nucleocytoplasmic transport.

Abstract Systemic corticosteroids (CSs), a keystone in pulmonology, are drugs with strong antiinflammatory activity. They are cheap, easily available, and accessible, but with common and serious side effects. Moreover, the use of exogenous CSs may suppress the hypothalamic–pituitary–adrenal (HPA) axis, predisposing to adrenal insufficiency. Safe CS treatment is a challenge of pharmacological research. This narrative review examined the indications of CSs in some respiratory diseases, analyzing what types, dosages, and length of treatment are required as the dosage and duration of CS treatments need to be minimized. Chronic maintenance treatments with CSs are associated with poor prognosis, but they are still prescribed in patients with severe asthma, Chronic obstructive pulmonary disease (COPD), and interstitial lung diseases. When CS discontinuation is not possible, all efforts should be made to achieve clinically meaningful reductions. Guidelines suggest the use of methylprednisolone at a dose of 20–40 mg/day or equivalent for up to 10 days in subjects with COVID-19 pneumonia (but not other respiratory viral diseases) and respiratory failure, exacerbations of asthma, and COPD. Some guidelines suggest that CS treatment shorter than 10–14 days can be abruptly stopped, strictly monitoring subjects with unexplained symptoms after CS withdrawal, who should promptly be tested for adrenal insufficiency (AI) and eventually treated. CSs are often used in severe community-acquired pneumonia associated with markedly increased serum inflammation markers, in acute respiratory distress syndrome (ARDS), in septic shock unresponsive to hydro-saline replenishment and vasopressors, and acute exacerbations of interstitial lung diseases. As these cases often require higher doses and longer duration of CS treatment, CS tapering should be gradual and, when useful, supported by an evaluation of HPA axis function.

Aim:Although the peak cortisol response in the low-dose test does not reach the generally accepted value of 18 μg/dL, there are many patients whose adrenal insufficiency diagnosis was ruled out by getting an adequate response with the standard-dose test. Thus, the standard-dose adrenocorticotropic hormone (ACTH) stimulation test is unnecessarily applied to many patients. This study aims to compare low- and standard-dose ACTH stimulation tests in diagnosing adrenal insufficiency and to determine a new optimal threshold level for low-dose ACTH stimulation tests to avoid unnecessary standard-dose ACTH tests.Methods:In this single-center cross-sectional study, patients with suspected adrenal insufficiency who underwent low-dose (1 mcg) and standard-dose (250 mcg) ACTH stimulation tests were evaluated. Cases were separated into two groups: (I) inadequate cortisol response (

Abstract Background In patients with adrenal insufficiency (AI), adrenal crisis (AC) represents a clinical emergency. Early recognition and prompt management of AC or AC-risk conditions in the Emergency Department (ED) can reduce critical episodes and AC-related outcomes. The aim of the study is to report the clinical and biochemical characteristics of AC presentation to improve their timely recognition and proper management in a ED setting. Methods Single-centre, retrospective, observational study on pediatric patients followed at the Department of Pediatric Endocrinology of Regina Margherita Children’s Hospital of Turin for primary AI (PAI) and central AI (CAI). Results Among the 89 children followed for AI (44 PAI, 45 CAI), 35 patients (21 PAI, 14 CAI) referred to the PED, for a total of 77 accesses (44 in patients with PAI and 33 with CAI). The main causes of admission to the PED were gastroenteritis (59.7%), fever, hyporexia or asthenia (45.5%), neurological signs and respiratory disorders (33.8%). The mean sodium value at PED admission was 137.2 ± 1.23 mmol/l and 133.3 ± 1.46 mmol/l in PAI and CAI, respectively (p = 0.05). Steroids administration in PED was faster in patients with CAI than in those with PAI (2.75 ± 0.61 and 3.09 ± 1.47 h from PED access, p = 0.83). Significant factors related to the development of AC were signs of dehydration at admission (p = 0.027) and lack of intake or increase of usual steroid therapy at home (p = 0.059). Endocrinological consulting was requested in 69.2% of patients with AC and 48.4% of subjects without AC (p = 0.032). Conclusion children with AI may refer to the PED with an acute life-threatening condition that needs prompt recognition and management. These preliminary data indicate how critical the education of children and families with AI is to improve the management at home, and how fundamental the collaboration of the pediatric endocrinologist with all PED personnel is in raising awareness of early symptoms and signs of AC to anticipate the proper treatment and prevent or reduce the correlated serious events.

The dramatic rise in opioid use over the last two decades has led to a surge in their harmful health effects. Lesser known among clinicians is the impact of opioids on the endocrine system, especially with regard to cortisol. Opioids can suppress the hypothalamus-pituitary-adrenal (HPA) axis and may result in clinically significant adrenal insufficiency, especially in those treated at higher doses and for a longer time. A high clinical suspicion is necessary in this population for early diagnosis of opioid-induced adrenal insufficiency (OAI). Diagnosis of OAI is challenging, as the symptoms are often vague and overlap with those due to opioid use or the underlying pain disorder. Traditional assays to diagnose adrenal insufficiency have not been widely studied in this population, and more investigation is needed to determine how opioids might affect assay results. Once a diagnosis of adrenal insufficiency has been made, glucocorticoid replacement in the form of hydrocortisone is likely the mainstay of treatment, and effort should be made to taper down opioids where possible. Cortisol levels should be retested periodically, with the goal of stopping glucocorticoid replacement once the HPA axis has recovered. In this review, we provide context for diagnostic challenges in OAI, suggest diagnostic tools for this population based on available data, and offer recommendations for the management of this disorder. There is a paucity of literature in this field; given the widespread use of opioids in the general population, more investigation into the effects of opioids on the HPA axis is sorely needed.

ContextPatients with primary adrenal insufficiency due to congenital adrenal hyperplasia (CAH) are at risk for adrenal crisis during infectious illnesses. Increased risk of infection including COVID-19 has been variably reported.ObjectiveTo evaluate COVID-19 illness outcomes and stress dose practices in a large cohort of patients with CAH during the first two years of the pandemic and compare observations of COVID-19 infection in patients with CAH to the general USA population.MethodsBetween March 2020 and November 2022, patients with CAH followed at the National Institutes of Health Clinical Center were queried about COVID-19 infection during their routine visits. Cases of COVID-19 were compared to controls. COVID-19 infection rates and symptoms were compared to general USA population data from the Centers for Disease Control and Prevention.ResultsOf 168 patient visits, there were 54 (32%) cases of COVID-19 infection, and 15 (28%) were pediatric. Overall an association was found between acquiring COVID-19 and obesity (p=0.018), and adults acquiring COVID-19 were on lower doses of fludrocortisone (p=0.008). Fewer cases of COVID-19 infection were reported in those receiving hydrocortisone or modified-release hydrocortisone compared to longer acting glucocorticoids (p=0.0018). In our CAH population, the pattern of COVID-19 infection rates and COVID-related symptomatology were similar to those observed in the general USA population. Most patients with the presumed alpha variant reported anosmia and ageusia, while gastrointestinal symptoms were commonly reported during the delta and omicron waves. Stress dosing occurred in 30/54 cases, and 7 received parenteral hydrocortisone. Two hospitalizations occurred; one pediatric and one adult, both with co-morbidities. There were 5 emergency room visits and no reported deaths.ConclusionPatients with CAH with close follow-up do not appear to be at increased risk of acquiring COVID-19 or to have a more severe course of COVID-19 compared to the general USA population. Obesity may increase risk of acquiring COVID-19 in patients with CAH, and overall infection risk may be lower in those receiving short-acting and circadian glucocorticoid replacement therapy. Established age-appropriate guidelines for stress dosing during infectious illnesses should be used for patients with CAH and COVID-19. COVID-19 specific guidelines are not indicated. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT00250159.

ABSTRACTObjective: Adrenocortical responsiveness is critical for maintaining glucocorticoids production and homeostasis during stress. We sought to investigate adrenocortical responsiveness during hypoxia in mice and the mechanisms responsible for the regulation of adrenal responsiveness.Methods: (1) Adult male WT mice were randomly divided into four groups: normoxia, hypoxia (24h), hypoxia (72h), hypoxia (72h) + GYY4137(hydrogen sulfide (H2S) donor, 133mmol/kg/day); (2) WT mice were randomly divided into four groups: sham, adrenalectomy (ADX), sham+hypoxia, ADX+hypoxia; (3) Cse-/- mice were randomly divided into two groups: Cse-/-, Cse-/- +GYY4137.Results: The circulatory level of corticosteroid induced by ACTH stimulation was significantly reduced in the mice with hypoxia compared with control mice. The mortality rate induced by lipopolysaccharide (LPS) increased during hypoxia. Cystathionine-γ-lyase (CSE) expression was significantly reduced in adrenal glands during hypoxia. GYY4137 treatment significantly increased adrenal responsiveness and attenuated NLRP3 inflammasome activation in mice treated by hypoxia and Cse-/- mice. Furthermore, The sulfhydrated level of PSMA7 in adrenal gland was decreased in the mice with hypoxia and Cse-/- mice. PSMA7 was S-sulfhydrated at cysteine 70. Blockage of S-sulfhydration of PSMA7 increased NLRP3 expression in adrenocortical cells.Conclusion: Reduced H2S production mediated hypo-adrenocortical responsiveness and NLRP3 inflammasome activation via PAMA7 S-sulfhydration during hypoxia.

X-linked adrenoleukodystrophy (X-ALD; OMIM:300100) is a progressive neurodegenerative disorder caused by a congenital defect in the ATP-binding cassette transporters sub-family D member 1 gene (ABCD1) producing adrenoleukodystrophy protein (ALDP). According to population studies, X-ALD has an estimated birth prevalence of 1 in 17.000 subjects (considering both hemizygous males and heterozygous females), and there is no evidence that this prevalence varies among regions or ethnic groups. ALDP deficiency results in a defective peroxisomal b-oxidation of very long chain fatty acids (VLCFA). As a consequence of this metabolic abnormality, VLCFAs accumulate in nervous system (brain white matter and spinal cord), testis and adrenal cortex. All XALD affected patients carry a mutation on the ABCD1 gene. Nevertheless, patients with a defect on the ABCD1 gene can have a dramatic difference in the clinical presentation of the disease. In fact, X-ALD can vary from the most severe cerebral paediatric form (CerALD), to adult adrenomyeloneuropathy (AMN), Addison-only and asymptomatic forms. Primary adrenal insufficiency (PAI) is one of the main features of X-ALD, with a prevalence of 70% in ALD/ AMN patients and 5% in female carriers. The pathogenesis of X-ALD related PAI is still unclear, even if a few published data suggests a defective adrenal response to ACTH, related to VLCFA accumulation with progressive disruption of adrenal cell membrane function and ACTH receptor activity. The reason why PAI develops only in a proportion of ALD/AMN patients remains incompletely understood. A growing consensus supports VLCFA assessment in all male children presenting with PAI, as early diagnosis and start of therapy may be essential for X-ALD patients. Children and adults with PAI require individualized glucocorticoid replacement therapy, while mineralocorticoid therapy is needed only in a few cases after consideration of hormonal and electrolytes status. Novel approaches, such as prolonged release glucocorticoids, offer potential benefit in optimizing hormonal replacement for X-ALD-related PAI. Although the association between PAI and X-ALD has been observed in clinical practice, the underlying mechanisms remain poorly understood. This paper aims to explore the multifaceted relationship between PAI and X-ALD, shedding light on shared pathophysiology, clinical manifestations, and potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Introduction: Patients with primary adrenal insufficiency (PAI) suffer from increased risk of infection, adrenal crises and have a higher mortality rate. Such dismal outcomes have been inferred to immune cell dysregulation because of unphysiological cortisol replacement. As the immune landscape of patients with different types of PAI has not been systematically explored, we set out to immunophenotype PAI patients with different causes of glucocorticoid (GC) deficiency. Methods: This cross-sectional single center study includes 28 patients with congenital adrenal hyperplasia (CAH), 27 after bilateral adrenalectomy due to Cushing’s syndrome (BADx), 21 with Addison’s disease (AD) and 52 healthy controls. All patients with PAI were on a stable GC replacement regimen with a median dose of 25 mg hydrocortisone per day. Peripheral blood mononuclear cells were isolated from heparinized blood samples. Immune cell subsets were analyzed using multicolor flow cytometry after four-hour stimulation with phorbol myristate acetate and ionomycin. Natural killer (NK-) cell cytotoxicity and clock gene expression were investigated. Results: The percentage of T helper cell subsets was downregulated in AD patients (Th1 p = 0.0024, Th2 p = 0.0157, Th17 p < 0.0001) compared to controls. Cytotoxic T cell subsets were reduced in AD (Tc1 p = 0.0075, Tc2 p = 0.0154) and CAH patients (Tc1 p = 0.0055, Tc2 p = 0.0012) compared to controls. NKCC was reduced in all subsets of PAI patients, with smallest changes in CAH. Degranulation marker CD107a expression was upregulated in BADx and AD, not in CAH patients compared to controls (BADx p < 0.0001; AD p = 0.0002). In contrast to NK cell activating receptors, NK cell inhibiting receptor CD94 was modulation in clock gene expression could be confirmed in our patient subgroups, major interindividual-intergroup dissimilarities were not detected. Discussion: In patients with different etiologies of PAI, distinct differences in T and NK cell-phenotypes became apparent despite the use of same GC preparation and dose. Our results highlight unsuspected differences in immune cell composition and function in PAI patients of different causes and suggest disease-specific alterations that might necessitate disease-specific treatment. [ABSTRACT FROM AUTHOR]

The adrenal glands are small endocrine glands located on top of each kidney, producing hormones regulating important functions in our body like metabolism and stress. There are several underlying causes for adrenal insufficiency, where an autoimmune attack by the immune system is the most common cause. A number of genes are known to confer early onset adrenal disease in monogenic inheritance patterns, usually genetic encoding enzymes of adrenal steroidogenesis. Autoimmune primary adrenal insufficiency is usually a polygenic disease where our information recently has increased due to genome association studies. In this review, we go through the physiology of the adrenals before explaining the different reasons for adrenal insufficiency with a particular focus on autoimmune primary adrenal insufficiency. We will give a clinical overview including diagnosis and current treatment, before giving an overview of the genetic causes including monogenetic reasons for adrenal insufficiency and the polygenic background and inheritance pattern in autoimmune adrenal insufficiency. We will then look at the autoimmune mechanisms underlying autoimmune adrenal insufficiency and how autoantibodies are important for diagnosis. We end with a discussion on how to move the field forward emphasizing on the clinical workup, early identification, and potential targeted treatment of autoimmune PAI. [ABSTRACT FROM AUTHOR]

Objective: Hypothalamic-pituitary axis dysfunction is a common complication in post-operative craniopharyngioma(CP) patients, and it greatly impacts the longterm quality of life of such patients. To better understand the effects of postoperative hypothalamic-pituitary dysfunction and long-term hormone replacement therapy in patients with childhood CP, we assessed approximately 200 patients with childhood-onset CP postoperatively. Methods: Clinical details of patients with childhood-onset CP who underwent sellar tumor resection in Beijing Children’s Hospital and Beijing Tiantan Hospital from 2018 to 2019 were retrieved retrospectively. The participants were followed up to assess the effects of post-operative long-term hormone replacement therapy and assess the tumor recurrence rate. Results: The median age of admission was 8.1 (1.8, 14.3) years. Headache (45.5%), visual impairment (39.5%), and nausea (33.0%) were the most common clinical manifestations. ACP accounted for 95% of all CP cases. The incidence of central adrenal insufficiency and central hypothyroidism within the first week after surgery was 56.2% and 70.3%, respectively. At the same time 85.5% of the patients required at least one dose of desmopressin to control urine output. Total survival and tumor recurrence rates were 98.6% and 26.1%, respectively, with a median follow-up time of 29.7 (19.0, 40.3) months. During the follow-up period, 28.1% patients met the diagnostic criteria for short stature, while 54.4% fit the criteria for obesity. In addition, 94.4% of the patients were taking at least one kind of hormone substitution, and 74.7% were taking three or more. The prevalence of levothyroxine, glucocorticoid, desmopressin, and growth hormone replacement therapy was 87.3%, 77.5%, 78.9% and 31.0%, respectively. The proportion of patients treated with the substitutive combination of levothyroxine, hydrocortisone, and desmopressin was 54.9%. Conclusion: This study is a large-sample systematic postoperative endocrine function evaluation of patients with childhood-onset CP. Due to the high prevalence of post-operative hypothalamic-pituitary dysfunction, patients with CP usually require long-term multiple hormone substitution therapy. Individualized management and accurate hormone replacement dosage for postoperative childhood-onset CP patients are of great importance. [ABSTRACT FROM AUTHOR]

Since the year 2000, admissions for adrenal insufficiency (AI) and adrenal crises (AC) have shown a particular increase in young adult females. We examined data on acute non-surgical hospitalisations for AI/AC from New South Wales, Australia, to determine relevant factors that may have contributed to this increase. Data were analysed to ascertain associations between various comorbid psychosocial issues, identified by relevant ICD-10-AM codes in each record, and ACs. From 2005 to 2021. There were 877 admissions for an acute non-surgical illness in this age group. The average admission rate for females [63.5/million/year] was almost twice that for males [34.0/million/year] (p<0.01), as was the average female AC admission rate [14.7/million/year] relative to that in males [6.75/million/year] (p=NS). Infection was present in 41.6% (n=365) of the admissions and Type 1 diabetes mellitus was present in 12.2% (n=107). Overall, psychosocial factors were considered by the senior clinician to have contributed to the illness episode in 22.1% of all admissions and 29.0% of AC admissions. Having one or more psychosocial problems was associated with an AC in females (37.4%, n=49, in those having an AC, p<0.001) but not males. Females with an AC also had a higher mean composite psychosocial, psychiatric and drug/alcohol score [0.47 (0.67)] than females without an AC [0.32 (0.62) p<0.05]. No comparable associations were found in male patients. An increase in the rates of hospitalisations that included a code for at least one psychosocial problem was highly correlated with increases in admission rates for both ACs (r=0.82, p<0.001) and all AI (r=0.98, p<0.001) in females but there was no such relationship in males. This new evidence suggests that psychosocial factors may play an important role in ongoing rates of ACs in treated AI (incidence approximately 6-8 ACs/100PY) particularly in young adult females. In order to minimize AC episodes, all barriers to self-management need exploration on an individual patient basis and with regard to the patient population as a whole. [ABSTRACT FROM AUTHOR]

Adrenal hemorrhage is a rare, but important, diagnosis to recognize, in particular when there is involvement of both adrenal glands. Bilateral adrenal hemorrhage can in fact lead to adrenal insufficiency, with dramatic consequences if not promptly recognized and treated. It is normally caused by systemic conditions that lead to the vasoconstriction and thrombosis of the adrenal vein. Oftentimes, the clinical diagnosis of this condition can be very challenging, as its signs and symptoms are generalized and nonspecific (abdominal pain, nausea, and fatigue). Here, we present the cases of two patients admitted to the Emergency Department in 2016 and 2022 with acute abdominal pain, having recently undergone surgery and subsequently prescribed low-molecular-weight heparin. In both cases, laboratory results revealed neutrophilic leukocytosis and an unexplained anemia. Due to the persistence of abdominal pain despite medication, a CT scan was performed, showing an enlargement of both adrenal glands suggestive of bilateral adrenal hemorrhage. Adrenal function was tested that correlated with a diagnosis of adrenal insufficiency, and both patients were promptly treated with parenteral hydrocortisone as a result. On 5 years' follow-up from the acute event, the second patient's adrenal function had returned to normal, and he has not needed further adrenal replacement therapy; the first patient however demonstrated persistence of adrenal failure requiring replacement therapy. In this paper, through our experience and a literature analysis, we will aim to outline some clues to identify patients at potential risk of bilateral adrenal hemorrhage. [ABSTRACT FROM AUTHOR]

Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ damage observed mainly in patients with β-thalassemia and rarely in SCD. Iron overload, oxidative stress-induced cellular damage, chronic anemia, and HCV infection contribute to the development of endocrinopathies in β-thalassemia. The above factors, combined with vaso-occlusive events and microcirculation defects, are crucial for endocrine dysfunction in SCD patients. These endocrinopathies include diabetes mellitus, hypothyroidism, parathyroid dysfunction, gonadal and growth failure, osteoporosis, and adrenal insufficiency, affecting the quality of life of these patients. Thus, we aim to provide current knowledge and data about the epidemiology, pathogenesis, diagnosis, and management of endocrine disorders in β-thalassemia and SCD. We conducted a comprehensive review of the literature and examined the available data, mostly using the PubMed and Medline search engines for original articles. In the era of precision medicine, more studies investigating the potential role of genetic modifiers in the development of endocrinopathies in hemoglobinopathies are essential. [ABSTRACT FROM AUTHOR]

Purpose: Immune checkpoint inhibitors (ICIs) are of great success in cancer therapy. This study aimed to identify adrenal insufficiency (AI) associated with immune checkpoint inhibitor (ICI) treatment in cancer patients receiving steroid replacement therapy and report the clinical characteristics of ICI-associated AI and concurrent immune-associated adverse events (irAEs). Methods: Patients prescribed cortisone acetate between January 2020 and March 2022 were reviewed to identify AI associated with ICI treatment. Data collected included indication of ICI (cancer type), drug characteristics, and outcomes. Results: A total of 101 patients were diagnosed with AI following treatment with ICIs. The median age was 64 years (range 22-83 years); 73.3% of the patients were male. Median time to develop primary AI and secondary AI after starting ICI therapy was 200.5 (35-280) days and 178 (16-562) days, respectively. Concurrent irAEs occurred in 67 (66.3%) patients and included 63 (62.4%) endocrine irAEs. Log-rank test showed that there was a trend toward higher likelihood of death at 120-day follow-up in patients initially receiving intravenous hydrocortisone compared with those receiving oral cortisone acetate after diagnosis of AI (p = 0.029). Conclusion: This retrospective study comprehensively documented the clinical characterization of ICI-associated AI. Those initially receiving intravenous hydrocortisone after diagnosis of AI were associated with higher likelihood of death. Physicians should be aware of the variability of ICI-associated irAEs early in the treatment, early diagnoses, and timely management should be made. [ABSTRACT FROM AUTHOR]

This article provides information on the use of glucocorticoids in medicine and the potential risks associated with their long-term use. It emphasizes the importance of gradually reducing the dosage of glucocorticoids to minimize withdrawal reactions, the risk of adrenal insufficiency, and disease reactivation. The article offers guidance to healthcare professionals on safe and effective ways to wean patients off long-term glucocorticoids. It also discusses the potential risks of adrenal suppression and adrenal crisis and provides advice on how to minimize these risks. The article highlights that the risk of adrenal insufficiency is influenced by factors such as the dose and duration of glucocorticoid use, the route of administration, and the underlying disease. It also mentions that there is variability in how individuals respond to glucocorticoids due to differences in absorption, metabolism, receptor expression, and gene activation. The article suggests various tests that can assess cortisol secretion and glucocorticoid suppression, with morning plasma cortisol and the short synacthen test being commonly used. It concludes by stating that individualized weaning plans can help reduce side effects and restore adrenal function, taking into account the risks of disease reactivation, hormone withdrawal syndrome, and adrenal insufficiency or crisis. [Extracted from the article]

Background/Objective. Chronic glucocorticoid (GCS) therapy is associated with increased risk of organ damage in systemic lupus erythematosus (SLE). However, discontinuation of low-dose GCS might cause withdrawal symptoms. This study is aimed at identifying GCS withdrawal symptoms and health-related quality of life (HRQoL) among SLE patients. Methods. SLE patients whose prednisolone had been previously withdrawn or taken <5 mg/day were enrolled. Serum morning cortisol levels were collected after 72-hour GCS discontinuation, and low-dose ACTH stimulation test (LDST) was performed. Patient report outcomes (PROs) included SLE-specific quality of life questionnaire (SLEQoL), functional assessment of chronic illness therapy (FACIT), patient health questionnaire (PHQ-9), and Pittsburgh's sleep quality index (PSQI). Results. Serum morning cortisol of 100 SLE patients was tested. Most patients were female (88%). Seventy-four patients showed remission. The mean ± SD of prednisolone was 0.73 ± 1.08 mg/day. Total SLEQoL and FACIT (mean ± SD) of all patients were 67.05 ± 26.15 and 13.7 ± 8.87 , respectively. Eighteen percent of patients had moderate-severe depressive symptoms, and 49% were poor sleepers. Adrenal function was determined by LDST in only 39 patients; 5 patients (12.8%) were adrenal insufficiency (AI), and 34 patients were normal adrenal function. Compared to normal adrenal function patients, SLE patients with AI had higher proportion of moderate-severe depressive symptom (PHQ − 9 > 9), but not statistically significant (40% vs. 20.6%, p = 0.34). PROs were comparable between groups. Independent factors associated with SLEQoL were FACIT (adjusted β 1.31, 95% CI 0.76, 1.86, p < 0.001), PHQ-9 (adjusted β 5.21, 95% CI 4.32, 6.09, p < 0.001), and PSQI (adjusted β 4.23, 95% CI 3.01, 5.45, p < 0.001), but not with AI (adjusted β -5.2, 95% CI -33.26, 22.93, 0.71, p = 0.71). Conclusion. SLE patients with previous GCS exposure could experience AI and withdrawal symptoms such as sleep disturbance and depression during discontinuation of low-dose GCS. Fatigue, depression, and poor sleeper were significantly associated with poor SLEQoL. [ABSTRACT FROM AUTHOR]

Background: Adrenal function tests (Synacthen test) in chronic hemodialysis (HD) patients are currently performed off dialysis. The study aimed to demonstrate equivalence of serum cortisol concentrations pre- and during HD, each for standard-dose (250 µg) and low-dose (1 µg) Synacthen test. Methods: In a single-center cross-over diagnostic equivalence study, Synacthen tests were performed in four settings, in standard- and low-dose as well as pre- and during HD. Serum cortisol concentration was measured at 30 and 60 min after Synacthen administration, and additionally at 20 min in low dose test. Based on a multivariable linear mixed model the means of cortisol concentration on log-scale were estimated in each dose and test time combination. Differences in means were calculated and the TOST approach was applied to test for equivalence. Equivalence was proven if the 90% confidence interval of the difference of two cortisol means was entirely between − 0.22 and 0.22. Results: In 28 chronic HD patients, serum cortisol concentrations at 30 and 60 min after Synacthen administration in both standard- and low-dose were shown to be equivalent pre- and during HD. In 10 of 56 low-dose tests, the cortisol peak was already reached after 20 min. However, cortisol concentrations at 20 and 30 min after low-dose Synacthen test pre- and during HD showed no significant difference. Conclusion: These results suggest that the adrenal function test may be carried out during an ongoing HD session, leading to a more patient-friendly performance of the test, less organizational effort and potentially earlier diagnosis of adrenal insufficiency. [ABSTRACT FROM AUTHOR]

A 41-year-old woman presented with a headache, diplopia, weight gain, moon face, and central obesity. Her plasma adrenocorticotropin (ACTH) level was 25.5 pmol/L (116 pg/mL) (normal range, 1.6-13.9 pmol/L [7.2-63.3 pg/mL]), serum cortisol level was 397.3 nmol/L (14.4 µg/dL) (normal range, 195.1-540.7 nmol/L [7.1-19.6 µg/dL]), and urinary free cortisol was 413.9 nmol/day (150.3 µg/day) (normal range, <221.5 mmol/day [<80.3 µg/day]). ACTH-dependent hypercortisolism was present, with cortisol suppression using a high-dose dexamethasone suppression test. Cushing disease was diagnosed and a contrast-enhanced magnetic resonance imaging scan demonstrated a 36-mm pituitary tumor with right cavernous sinus invasion. Before surgery, 20 mg pasireotide long-acting-release was initiated, and her symptoms rapidly improved. After 1 month, obvious tumor shrinkage was observed, ACTH and cortisol levels decreased, and diplopia resolved; therefore, we continued medical therapy. After 11 months, her ACTH and cortisol levels normalized, and most of the tumor had disappeared. The clinical course in this case suggests that pasireotide may be useful for preoperative treatment and primary medical therapy, at least in some patients with Cushing disease caused by a large tumor predicted to have difficulty achieving remission by surgery. [ABSTRACT FROM AUTHOR]

Crooke cell adenoma (CCA) is a rare and aggressive subtype of a corticotroph adenoma, which requires lifetime surveillance. There have been 106 cases of CCAs reported in the English literature. We describe 2 cases of CCA, a 48-year-old man and an 84-year-old woman who both presented with binocular diplopia and temple pain. Neither case had clinical Cushing syndrome. Laboratory values for the 48-year-old man revealed, adrenocorticotropin (ACTH) 103 pg/mL (22 pmol/L) (RR: 7-63 pg/mL) and evening cortisol 14 µg/dL (386 nmol/L) (RR: 2.7-10.5 µg/dL). Computed tomography imaging demonstrated a mass adjacent to the right cavernous sinus extending into the sphenoid sinus. He underwent tumor resection with adjuvant radiation and has had a stable residual tumor for 4 years. Preoperative laboratory values for the 84-year-old woman revealed, ACTH 69 pg/mL (15 pmol/L) (RR: 7-63 pg/mL) and evening cortisol 16.2 µg/dL (447 nmol/L) (RR: 2.7-10.5 µg/dL). Brain magnetic resonance imaging revealed, a mass compressing the optic chiasm. She underwent resection and has had a stable residual tumor for 2 years. Surgical pathology in both cases revealed cytoplasmic hyaline deposits of more than 50% of the tumor cells, consistent with CCA. The CCA although rare, should be considered when evaluating cases with subclinical Cushing disease and visual symptoms. [ABSTRACT FROM AUTHOR]

Addison's disease (AD) entails a chronic insufficient production of gluco- and mineralocorticoids. Fatigue and decreased quality of life are frequently reported symptoms, but little is known about its effects on cognition. This study aims to explore the existence of cognitive impairment in patients with AD and the influence of treatment regimens. We conducted a systematic review. Inclusion criteria were met by 10 articles, most of them ranked as intermediate quality. Three studies analyzed the relationship between AD and cognitive impairment; one explored the effect of delaying treatment showing no effect on cognitive performance, and another one studied the effect of fludrocortisone treatment. Episodic memory was the most frequent cognitive domain impaired across studies, in comparison to healthy controls. Two papers investigated the relationship between impaired sleep quality and poor cognitive performance. Two studies related cognitive impairments with hypocortisolism-derived brain neuroglycopenia. Two studies investigated the effect of DHEA substitution. In conclusion, patients exhibit a moderately reduced performance in verbal learning. The pathophysiology of this impairment is likely multifactorial. Future studies should include larger sample sizes, the use of comprehensive and multi-domain neuropsychological and behavioral protocols, and neuroimaging. [ABSTRACT FROM AUTHOR]

In sepsis, dysregulation of the hypothalamic–pituitary–adrenal axis, alterations in cortisol metabolism, and tissue resistance to glucocorticoids can all result in relative adrenal insufficiency or critical illness-related corticosteroid insufficiency (CIRCI). The symptoms and signs of CIRCI during sepsis are nonspecific, generally including decreased mental status, unexplained fever, or hypotension refractory to fluids, and the requirement of vasopressor therapy to maintain adequate blood pressure. While we have been aware of this syndrome for over a decade, it remains a poorly understood condition, challenging to diagnose, and associated with significantly diverging practices among clinicians, particularly regarding the optimal dosing and duration of corticosteroid therapy. The existing literature on corticosteroid use in patients with sepsis and septic shock is vast with dozens of randomized controlled trials conducted across the past 4 decades. These studies have universally demonstrated reduced duration of shock, though the effects of corticosteroids on mortality have been inconsistent, and their use has been associated with adverse effects including hyperglycemia, neuromuscular weakness, and an increased risk of infection. In this article, we aim to provide a thorough, evidence-based, and practical review of the current recommendations for the diagnosis and management of patients with sepsis who develop CIRCI, explore the controversies surrounding this topic, and highlight what lies on the horizon as new evidence continues to shape our practice. [ABSTRACT FROM AUTHOR]

The potential of artificial intelligence (AI) in diagnosing and managing sexually transmitted infections (STIs), nonvenereal genital diseases, and overall sexual health is immense. AI shows promise in STI screening and diagnosis through image recognition and patient data analysis, potentially increasing diagnostic accuracy while ensuring inclusivity. AI can fuel the transformation of e-health and direct-to-consumer services, enhancing targeted screening and personalized interventions while improving the user-friendliness of services. There is a significant role for AI in sexual education, particularly its use in interactive, empathetic chatbots. AI's integration into health care as a decision support tool for primary health-care providers can boost real-time diagnostic accuracy. Furthermore, AI's use in big data can enhance real-time epidemiology, predictive analysis, and directed interventions at population levels. However, challenges such as real-world diagnostic accuracy, liability, privacy concerns, and ethical dilemmas persist. Future directions include an emphasis on inclusivity, language accommodation, and swift research-to-practice transitions. Collaboration among policymakers, researchers, and health-care providers is needed to leverage AI's transformative potential in sexual health. [ABSTRACT FROM AUTHOR]

The brain houses vital hormonal regulatory structures such as the hypothalamus and pituitary gland, which may confer unique susceptibilities to critical illness-related corticosteroid insufficiency (CIRCI) in patients with neurological disorders. In addition, the frequent use of steroids for therapeutic purposes in various neurological conditions may lead to the development of steroid insufficiency. This abstract aims to highlight the significance of understanding these relationships in the context of patient care and management for physicians. Neurological disorders may predispose patients to CIRCI due to the role of the brain in hormonal regulation. Early recognition of CIRCI in the context of neurological diseases is essential to ensure prompt and appropriate intervention. Moreover, the frequent use of steroids for treating neurological conditions can contribute to the development of steroid insufficiency, further complicating the clinical picture. Physicians must be aware of these unique interactions and be prepared to evaluate and manage patients with CIRCI and steroid insufficiency in the context of neurological disorders. This includes timely diagnosis, appropriate steroid administration, and careful monitoring for potential adverse effects. A comprehensive understanding of the interplay between neurological disease, CIRCI, and steroid insufficiency is critical for optimizing patient care and outcomes in this complex patient population. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) predominantly involves the lungs, albeit many other organ systems, including the hypothalamic-pituitary-adrenal (HPA) axis, can be affected due to the expression of the angiotensin-converting enzyme 2 (ACE2) binding receptor. Few studies have reported the involvement of adrenal gland and the HPA axis during the acute phase of COVID-19; however, the data on the long-term effect of COVID-19 on the HPA axis after acute infection is scarce. To assess and compare the changes in HPA axis in mild, moderate and severe COVID-19 categories at ≥ 3 months after acute infection. A prospective, observational study was conducted to assess the HPA axis status among COVID-19 subjects at least 3 months after recovery from acute infection. The study was conducted from June 2021 to May 2022. Subjects visited the hospital in the fasting state (8.00–9.00am), serum cortisol levels were measured at baseline, 30 and 60 minutes after a 1-μg short Synacthen test (SST). A total of 66 subjects ≥ 18 years of age were included in the study. The mean age (SD) was 49.13 ± 11.9 years, 45(68.18%) were male and 21 (31.81%) were female subjects. The mean BMI in the study was 25.91 ± 4.26 kg/m2. Seventeen (25.8%) subjects had mild, twelve (18.2%) had moderate and thirty-seven (56.1%) subjects had severe COVID-19 infection. Out of the sixty-six subjects with COVID-19, nine subjects (9/66, 13.63%) had peak serum cortisol < 496.62 nmol/L suggestive of adrenal insufficiency (AI). SST peak serum cortisol levels did not differ significantly across the disease severity [Mild, (628.50 ± 214.65 nmol/L) vs moderate, [603.39 ± 161.95 nmol/L) vs severe, (597.59 ± 163.05 nmol/L), P = 0.617]. Six subjects with AI came for follow-up at 12 months, and all had normal HPA axis. HPA axis is affected in 13.63% (9/66) of subjects at least 3 months after recovery from COVID-19 infection. AI in COVID-19 might be transient and would recover spontaneously. These findings have important implications for the clinical care and long-term follow-up of subjects after COVID-19 infection. [ABSTRACT FROM AUTHOR]

Purpose: Analyze the surgical management strategy and the current effects on Quality of Life of diagnosed Esophageal Achalasia (EA) patients in our department, with an assessment of the incidence, clinical course, and related disorders. Methods: Data was based on a retrospective review of all children who received achalasia treatment at our department between 2008 and 2022. Using the Pediatric Quality of Life Inventory Generic Core (PedsQL) Scales and the Pediatric-QL Gastrointestinal Symptoms Module (GI-PedsQL), we evaluated the long-term effects of this diagnosis on our patients' quality of life. Results: Esophageal achalasia (EA) was identified in a total of 13 cases (F: 7; M: 6). The mean patient delay was 27.90 months, and the median age was 6.5 years at diagnosis (2 months to 15 years). Regurgitation was the most frequently observed symptom, and the median follow-up was 7.32 (3- 30.7) months. There were descriptions of associations with Allgrove syndrome (n=7) and Down syndrome (n=1). All patients were treated by Open Heller myotomy (OHM) with one patient (n=1) initially treated by pneumatic dilatation (PD). In all 13 laparotomy myotomies, simultaneous fundoplication was performed using the DOR (n=12) and THAL (n=1) techniques. At follow-up, 12 patients had complete symptom relief with 1 patient exhibiting a persistence of symptoms. All 13 patients were prospectively contacted with a median time from latest check-up to date of inclusion of 2.9 (0.3-8.8) years. In comparison to data from a control group of EA patients, the overall PedsQL score of our patients was 72/100 (±17), with higher established scores in physical and emotional functioning but lower scores in social and school settings. On the other hand, when compared to a control group presenting with a gastroesophageal reflux disease (GERD), the GI-PedsQL overall score in our patients was higher with a 76/100 (±14.9), but they scored significantly lower in the dimensions: Foods and drinks limitations, difficulty swallowing, heartburn and vomiting. Discussion: Our study group's characteristics join most of the published literature with 54% of our patients presenting with Allgrove syndrome but it also joins the much rarer descriptions of Achalasia and Down's syndrome association with a singular case. The clinical course of our diagnosis process mainly consisted of timed esophagram and UGI endoscopy, lacking significantly in HREM evaluations but was efficient enough in guiding the surgical management. Our findings confirm the safety and effectiveness of Open Heller's myotomy with a success rate of 92.3% However, we concede that a laparoscopic approach should be further adopted if no contradiction is found. Moreover, we presented insight on long term QoL of patients posteriori to HM which was in concordance with other global experiences where patients reported dissatisfaction with their health and limited lifestyle. This significant negative impact was prominently present in comparison to healthy control groups as well as patients with inflammatory bowel diseases and compels a much needed discussion on the major chronic repercussions of Esophageal Achalasia in children. Conclusion: Even when managed by interdisciplinary teams of professionals, managing esophageal achalasia in specialized institutions is still a subject of debate. Early pediatric diagnosis is best achieved with routine physiological function tests and HREM. Moreover, more research is required to assess long-term Quality of Life. Standardized lifelong follow-up and qualified resources, both human and technological, are required to improve postoperative outcomes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to identify susceptibility markers for adrenal crises (AC) in educated patients with chronic adrenal insufficiency (AI). Design: A case–control study involving 66 patients with AI analyzing the impact of glucocorticoid and mineralocorticoid exposure, adrenomedullary function, inflammatory parameters, and educational status on AC frequency. Patients were categorized into low (n = 32) and high (n = 34) AC frequency groups based on AC occurrence (below or 2 times above the average of the reported AC frequency of 8.3 AC/100 patient-years in a previous prospective study). Methods: Parameters, including cortisol plasma profile and urinary steroid excretion after administration of the morning glucocorticoid dose, 24-h urinary steroid profiling, salivary cortisol profiling, and hair cortisol, estimated cortisol exposure. Polymorphisms (single nucleotide polymorphism [SNP]) of the glucocorticoid receptor (NR3C1) and mineralocorticoid receptor (NR3C2) associated with individual steroid sensitivity were assessed together with SNPs for 11β-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11β-hydroxysteroid dehydrogenase 2 (HSD11B2). Mineralocorticoid replacement was evaluated by serum and urinary electrolytes and osmolality, plasma–renin concentration, and ambulatory blood pressure levels. We additionally measured plasma and urinary catecholamines, serum levels of IL6 and hsCRP, and SNPs of IL6 and TNF-alpha. Patient knowledge of AC prevention was assessed by questionnaires. Results: Frequent AC patients had higher daily glucocorticoid doses and hair cortisol levels, with no significant differences in other parameters investigated. AC frequency is inversely correlated with the frequency of self-reported adjustments of the glucocorticoid replacement. Conclusion: Higher glucocorticoid dosages in high-risk patients, despite unaffected cortisol metabolism, may be linked to decreased cortisol sensitivity or impaired glucocorticoid absorption. Proactive dose adjustments show a protective effect against AC, regardless of biological vulnerability. [ABSTRACT FROM AUTHOR]