Frequency of stress dosing and adrenal crisis in paediatric and adult patients with congenital adrenal hyperplasia: a prospective study.

OBJECTIVE: Patients with congenital adrenal hyperplasia (CAH) require life-long glucocorticoid replacement, including stress dosing (SD). This study prospectively assessed adrenal crisis (AC) incidence, frequency, and details of SD and disease knowledge in adult and paediatric patients and their parents. DESIGN: Prospective, observational study. METHODS: Data on AC and SD were collected via a patient diary. In case of AC, medical records were reviewed and patient interviews conducted. Adherence to sick day rules of the German Society of Endocrinology (DGE) and disease knowledge using the German version of the CAH knowledge assessment questionnaire (CAHKAQ) were assessed. RESULTS: In 187 adult patients, the AC incidence was 8.4 per 100 patient years (py) and 5.1 in 100 py in 38 children. In adults, 195.4 SD episodes per 100 py were recorded, in children 169.7 per 100 py. In children 72.3% and in adults 34.8%, SD was performed according to the recommendations. Children scored higher on the CAHKAQ than adults (18.0 [1.0] vs 16.0 [4.0]; P = .001). In adults, there was a positive correlation of the frequency of SD and the incidence of AC (r = .235, P = .011) and CAHKAQ score (r = .233, P = .014), and between the incidence of AC and CAHKAQ (r = .193, P = .026). CONCLUSION: The AC incidence and frequency of SD in children and adults with CAH are high. In contrast to the paediatric cohort, the majority of SD in adults was not in accordance with the DGE recommendations, underlining the need for structured and repeated education of patients with particular focus on transition.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) After Pediatric Cardiac Surgery.

Although current studies do not support the routine use of corticosteroids after cardiopulmonary bypass in pediatric patients, there is incomplete understanding of the potential hemodynamic contribution of postoperative critical illness-related corticosteroid insufficiency in the intensive care unit. By reviewing the available studies and underlying pathophysiology of these phenomena in critically ill neonates, we can identify a subset of patients that may benefit from optimal diagnosis and treatment of receiving postoperative steroids. A suggested algorithm used at our institution is provided as a guideline for treatment of this high-risk population.

Increased risk of hospitalization, intensive care and death due to COVID-19 in patients with adrenal insufficiency: A Swedish nationwide study.

BACKGROUND: Patients with adrenal insufficiency (AI) have excess morbidity and mortality related to infectious disorders. Whether patients with AI have increased morbidity and mortality from COVID-19 is unknown. METHODS: In this linked Swedish national register-based cohort study, patients with primary and secondary AI diagnosis were identified and followed from 1 January 2020 to 28 February 2021. They were compared with a control cohort from the general population matched 10:1 for age and sex. The following COVID-19 outcomes were studied: incidence of COVID-19 infection, rates of hospitalization, intensive care admission and death. Hazard ratios (HR) with 95% confidence intervals (95% CI) adjusted for socioeconomic factors and comorbidities were estimated using Cox regression analysis. RESULTS: We identified 5430 patients with AI and 54,300 matched controls: There were 47.6% women, mean age was 57.1 (standard deviation 18.1) years, and the frequency of COVID-19 infection was similar, but the frequency of hospitalization (2.1% vs. 0.8%), intensive care (0.3% vs. 0.1%) and death (0.8% vs. 0.2%) for COVID-19 was higher in AI patients than matched controls. After adjustment for socioeconomic factors and comorbidities, the HR (95% CI) was increased for hospitalization (1.96, 1.59-2.43), intensive care admission (2.76, 1.49-5.09) and death (2.29, 1.60-3.28). CONCLUSION: Patients with AI have a similar incidence of COVID-19 infection to a matched control population, but a more than twofold increased risk of developing a severe infection or a fatal outcome. They should therefore be prioritized for vaccination, antiviral therapy and other appropriate treatment to mitigate hospitalization and death.

Spectrum of Adrenal Dysfunction in Hemoglobin E/Beta Thalassemia.

BACKGROUND: Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied. AIMS AND OBJECTIVES: In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements. METHODS: In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated. Among them, 57 and 47 were transfusion dependent and non-transfusion dependent. According to Mahidol criteria, patients were classified into mild (n = 39), moderate (n = 39), and severe (n = 26) disease. Early morning (8 Am) serum cortisol, plasma ACTH, and plasma aldosterone, renin were measured. Patients with baseline cortisol of 5 to 18 µg/dL underwent both 1 µg and 250 µg short Synacthen test. According to these results, patients were classified as having either normal, subclinical, or overt (primary/secondary) adrenal dysfunction. RESULTS: Adrenal insufficiency was found in 41% (n = 43). Among them 83.7% (n = 34) had primary AI and 16.3% (n = 9) had secondary AI. Thirty-three patients (31%) with normal or elevated ACTH and with low or normal aldosterone with high renin were diagnosed as having subclinical AI. There was no difference in prevalence of AI between transfusion dependent and non-transfusion dependent (P = .56) nor was there was any difference in prevalence of AI according to disease severity (P = .52). CONCLUSION: Adrenal insufficiency is common in HbE/beta thalassemia and is independent of transfusion dependency and disease severity.

Serum cortisol level to screen for significant hypothalamic-pituitary-adrenal axis suppression in patients receiving multiple steroid injections.

BACKGROUND: Morning serum cortisol level (mSCL) is a practical screening tool for hypothalamic-pituitary-adrenal (HPA) axis suppression and has been used to assess for duration of cortisol deficiency after epidural and peripheral glucocorticoid injections. More evidence is needed to establish the utility of mSCL in patients undergoing repeat injections with increasing cumulative glucocorticoid equivalent dose (CGED) that could place them at higher risk of HPA axis suppression. OBJECTIVES: To estimate the prevalence of spine injection candidates with significant HPA axis suppression (sigAS), to understand the correlation between 12 months of CGED and the presence of sigAS based on the timing of mSCL collection after the most recent glucocorticoid injection (within 6 weeks or between 6 weeks and 12 months), and to investigate demographic and clinical factors relating to sigAS. METHODS: Retrospective chart review of patients scheduled for spine injection who had an associated mSCL and documented histories of prior glucocorticoid injections. The steroid name, dose, type, and procedure location were recorded for each injection that occurred within 12 months before mSCL. CGED was calculated from standard glucocorticoid equivalent conversion factors. RESULTS: SigAS was present in 7.8% to 22% of the analysis cohorts. There was no association found between CGED and sigAS regardless of timing of mSCL. There was a trend toward lower mSCL and sigAS with increasing CGED. There were no significant relationships found between sigAS and overall demographic or clinical factors. CONCLUSIONS: A 3-fold reduction in the rate of sigAS was noted 6 weeks after the most recent steroid injection. Using mSCL provides a template to investigate the impact of CGED and the best timing for mSCL collection in order to define a more practical guideline to identify patients at higher risk of sigAS earlier and plan for future spine injections.

Postpartum acute adrenal insufficiency of early-onset Sheehan syndrome: A case series study in a single center.

AIM: To identify the symptoms and relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. METHODS: We retrospectively reviewed the charts of 125 women admitted to our intensive care unit because of postpartum hemorrhage between January 2011 and December 2021. Three women developed acute adrenal insufficiency. We investigated the total blood loss, shock status, consciousness level upon arrival, and intensive care provided to the women. We also analyzed the symptoms and laboratory data that led to the diagnosis of acute adrenal insufficiency. Continuous variables were presented by median (minimum-maximum). RESULTS: The medians and ranges of age, total blood loss, and shock index [heart rate/systolic blood pressure] on admission were 33.1 (17.2-45.3) years, 3351 (595-20 260) g, and 0.94 (0.55-2.94), respectively. Seven women were older than 40 years, 28 experienced >5000 g blood loss, 17 had shock index >1.5, 27 had impaired consciousness upon arrival, and 15 underwent hysterectomy. Women who developed acute adrenal insufficiency were <40 years old and had a bleeding volume of over 5000 g, impaired consciousness upon arrival, and had undergone hysterectomy. They had experienced lactation failure, presented with hyponatremia-related symptoms on postpartum days 8-9, experienced general malaise, headache, and impaired consciousness, and showed severe hyponatremia. CONCLUSIONS: Massive postpartum hemorrhage over 5000 g, impaired consciousness upon arrival, and hysterectomy as a hemostatic measure were relevant factors associated with acute adrenal insufficiency of early-onset Sheehan syndrome. Hyponatremia-related symptoms occurring after lactation failure are indicative of the onset of acute adrenal insufficiency.

Morbidity in Patients with Chronic Adrenal Insufficiency - Cardiovascular Risk Factors and Hospitalization Rate Compared to Population Based Controls.

Patients with adrenal insufficiency (AI) have been found to have increased cardiovascular morbidity, partly associated with nonphysiologic glucocorticoid replacement. We included two separate cohorts (cohort 1 n=384 patients, cohort 2 n=180 patients) of patients with chronic primary and secondary AI under standard replacement therapy and compared them to two age- and sex-matched population-based studies (SHIP-TREND/DEGS). Odds ratios with 95% CI for hypertension, hyperlipidemia/HLP, type 2 diabetes/T2DM, obesity, and hospitalization with adjustment for confounders were evaluated by logistic regression. Patient cohort 1 had significantly lower ORs for obesity [0.4 (0.3-0.6), p<0.001] and hypertension [0.5 (0.3-0.6), p<0.001] compared to SHIP-TREND and for obesity [0.7 (0.5-0.9), p=0.01], hypertension [0.4 (0.3-0.5), p<0.001] and HLP [0.4 (0.3-0.6), p<0.001] compared to DEGS. In cohort 2, ORs were significantly lower for HLP compared to both SHIP-TREND [0.4 (0.2-0.7), p=0.001] and DEGS [0.3 (0.2-0.5), p<0.001] and for hypertension [0.7 (0.4-0.9), p=0.04] compared to SHIP-TREND. In patients with SAI from cohort 2, ORs for DM2 [2.5 (1.3-4.9) p=0.009], hypertension [2.5 (1.4-4.5), p=0.002] and obesity [1.9 (1.1-3.1), p=0.02] were significantly higher compared to DEGS, whereas ORs for HLP were significantly lower compared to both SHIP [0.3 (0.1-0.6), p=0.002] and DEGS [0.3 (0.1-0.6), p<0.001]. In most of our AI patients treated with conventional glucocorticoid doses, the risk for T2DM, obesity, hypertension, and HLP was not increased. The number of hospitalizations was significantly higher in AI patients compared to controls, which might reflect increased susceptibility but also a more proactive management of concomitant diseases by physicians and patients.

Factors underlying a disproportionate increase in hospital admissions for adrenal insufficiency in women aged 20-29 years.

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.

Predisposing factors for adrenal crisis in chronic adrenal insufficiency: a case-control study.

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 11ß-hydroxysteroid dehydrogenase 1 (HSD11B1) and 11ß-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.

Statin treatment is not associated with an increased risk of adrenal insufficiency in real-world setting.

Introduction: Statins could reduce the synthesis of steroid hormones, thereby could cause adrenal insufficiency. We investigated this risk in a large nationwide database. Methods: We conducted a nested case-control study using a cohort of individuals affiliated to the French health insurance system in 2010, ≥18y and without adrenal insufficiency history. Each case had a first event of adrenal insufficiency between 2015 and 2017 and was matched to up to ten controls on age, sex, and prior treatment with corticosteroids. Statin exposure was measured over the five years preceding the index date, considering a six-month censoring lag-time. Association was estimated using a conditional logistic regression adjusted for confounders included in a disease risk score. Analyses were stratified on age, sex and corticosteroid history of use. Results: 4 492 cases of adrenal insufficiency were compared with 44 798 controls (median age 66y, 58% women), of which 39% vs. 33% were exposed to statins, respectively. No association between statin use and adrenal insufficiency was found when adjusting the model for confounders (adjusted odds ratio 0.98; 95% confidence interval 0.90-1.05). These results were consistent regardless of the exposure definition and stratifications considered. Conclusion: Statin-related adrenal insufficiency risk, if any, seems to be very limited and does not compromise the benefit of statin treatment.

Risk factors that are associated with adrenal insufficiency among patients with fever of unknown origin.

BACKGROUND: Adrenal insufficiency is one of the causes of fever of unknown origin (FUO). The purpose of this study is to find out risk factors that are associated with adrenal insufficiency in FUO patients. METHODS: This study was conducted retrospectively in a tertiary hospital with 846 beds in South Korea. All adult inpatients (age ≥19 years) who have requested a consult with the department of infectious disease for FUO between 1 July 20191 July 2019 and 30 June 202030 June 2020 were included in the study. Among them, those who underwent an adrenocorticotropic hormone (ACTH) stimulation test and had a fever of 37.8°C or higher within 48 hours of the ACTH stimulation test were finally included in the study subjects. RESULTS: A total of 202 FUO patients were enrolled and 61 (30.1%) were finally diagnosed with adrenal insufficiency. In a multivariate analysis, use of immunosuppressant within 3 months (OR 6.06, 95% CI 1.82-20.13, P = 0.003), use of corticosteroid within 3 months (OR 8.23, 95% CI 1.35-50.17, P = 0.022), sodium ≥ 136.7 (OR 3.43, 95% CI 1.49-7.88, P = 0.004), and calcium ≥ 8.4 (OR 0.31, 95% CI 0.14-0.71, P = 0.005) were proven to be factors associated with adrenal insufficiency in FUO patients. CONCLUSION: In conclusion, 30.1% of FUO patients were diagnosed with adrenal insufficiency. The risk factors that are associated with adrenal insufficiency in FUO patients were immunosuppressive prescription or systemic steroid prescription within 3 months, or with sodium ≥ 136.7 or calcium < 8.4.

COVID-19 pandemic and adrenals: deep insights and implications in patients with glucocorticoid disorders.

PURPOSE: Coronavirus disease-19 (COVID-19) has spread throughout the world. It was initially defined as a potentially severe syndrome affecting the respiratory tract, but it has since been shown to be a systemic disease with relevant extrapulmonary manifestations that increase mortality. The endocrine system has been found to be vulnerable to COVID-19 infection. The current review aims to evaluate the available data on the impact of COVID-19 infection and treatment, as well as COVID-19 vaccines, on adrenal gland function, particularly in patients with GC disorders. METHODS: A thorough search of published peer-reviewed studies in PubMed was performed using proper keywords. RESULTS: Adrenal viral tropism and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication in the adrenal glands have been demonstrated, and adrenal insufficiency (AI) is a rare, but potentially severe complication in COVID-19 disease, whose recognition can be difficult if only for the empirical treatments administered in the early stages. Glucocorticoid (GC) treatment have had a pivotal role in preventing clinical deterioration in patients with COVID-19, but long-term GC use may increase COVID-19-related mortality and the development of iatrogenic AI. Patients with GC disorders, especially AI and Cushing's syndrome, have been identified as being at high risk of COVID-19 infection and complications. Published evidence suggests that AI patient awareness and proper education may help adjust GC replacement therapy appropriately when necessary, thereby reducing COVID-19 severity. The COVID-19 pandemic has had an impact on AI management, particularly in terms of adherence to patients' care plans and self-perceived challenges. On the other hand, published evidence suggests that the clinical course of COVID-19 may be affected by the severity of hypercortisolism in patients with CS. Therefore, to ameliorate the risk profile in these patients, cortisol levels should be adequately controlled, along with careful monitoring of metabolic and cardiovascular comorbidities. To date, the COVID-19 vaccine remains the only available tool to face SARS-CoV-2, and it should not be treated differently in patients with AI and CS. CONCLUSION: SARS-CoV-2 infection has been linked to adrenal damage and AI is a rare complication in COVID-19 disease, requiring prompt recognition. Educational efforts and patient awareness may reduce COVID-19 severity in patients with AI. Control of cortisol levels and monitoring of complications may improve the clinical course of COVID-19 in patients with CS.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) Among Patients with COVID-19 at a Tertiary Hospital: Clinical Characteristics and Outcomes.

Objectives: Among critically ill patients, there is usually impairment of the hypothalamic-pituitary-adrenal axis, leading to a condition known as critical illness-related corticosteroid insufficiency (CIRCI). This investigation aims to determine the incidence of and characterize CIRCI among patients with COVID-19 as well as to analyze the outcomes of these critically ill patients. Methodology: This is a single-center, retrospective cohort study that investigated the occurrence of CIRCI among critically ill patients infected with COVID-19. Results: In this cohort, there were 145 COVID-19-positive patients with refractory shock, which reflects that 22.94% of the COVID-19 admissions have probable CIRCI.Patients who were given corticosteroids were found to have statistically significant longer median days on a ventilator (p=0.001). However, those on the corticosteroid arm were at higher risk of morbidity and mortality and a greater proportion had organ dysfunction. Multivariable logistic regression analysis revealed that SOFA score was a significant predictor of mortality in CIRCI (p=0.013). Conclusion: CIRCI has a unique presentation among patients with COVID-19 because of the presence of a high level of inflammation in this life-threatening infection. It is possibly a harbinger of a markedly increased risk of mortality in these patients.

Canine hypoadrenocorticism: Insights into the Addisonian crisis.

Objective: Primary objectives of this study were to determine presenting complaints, physical examination, clinicopathologic findings, and hospitalization time of dogs with spontaneous hypoadrenocorticism presenting with critical disease; and to compare those end points to dogs with a more stable presentation. Secondary objectives were to evaluate the shock index and to identify precipitating stressors. Animals: Eighty-four dogs at the Western College of Veterinary Medicine between 1998 and 2018 were included. Procedure: Data were retrieved from the medical records. Results: Collapse and depression were more common among critically ill dogs. Hyperlactatemia was rare despite a diagnosis of hypovolemic shock, and a shock index was ineffective in this patient subset. Isosthenuria, total hypocalcemia, and more severe acidosis were more common (P < 0.05) in critical dogs. Owner separation was the most common precipitating stressor. Conclusion and clinical relevance: We concluded that the critical Addisonian dog has unique characteristics that may aid in early disease identification.

Hypoadrénocorticisme canin : aper ç u de la crise Addisonienne. Objectif: Les principaux objectifs de cette étude étaient de déterminer les motifs de présentation, l'examen physique, les résultats clinico-pathologiques et la durée d'hospitalisation des chiens atteints d'hypoadrénocorticisme spontané présentant une maladie critique; et de comparer ces paramètres aux chiens avec une présentation plus stable. Les objectifs secondaires étaient d'évaluer l'indice de choc et d'identifier les facteurs de stress déclencheurs. Animaux: Quatre-vingt-quatre chiens du Western College of Veterinary Medicine entre 1998 et 2018 ont été inclus. Procédure: Les données ont été extraites des dossiers médicaux. Résultats: L'effondrement et la dépression étaient plus fréquents chez les chiens gravement malades. L'hyperlactatémie était rare malgré un diagnostic de choc hypovolémique, et un indice de choc était inefficace dans ce sous-groupe de patients. L'isosthénurie, l'hypocalcémie totale et l'acidose plus grave étaient plus fréquentes (P < 0,05) chez les chiens critiques. La séparation du propriétaire était le facteur de stress déclencheur le plus courant. Conclusion et pertinence clinique: Nous avons conclu que le chien addisonien critique a des caractéristiques uniques qui peuvent aider à l'identification précoce de la maladie.(Traduit par Dr Serge Messier).

Early Detection of Adrenal Insufficiency: The Impact of Newborn Screening for Adrenoleukodystrophy.

CONTEXT: Males with adrenoleukodystrophy (ALD) have an 80% lifetime risk of developing adrenal insufficiency (AI), which can be life-threatening when undetected. Newborn screening (NBS) for ALD has been implemented in 29 states, yet the impact of NBS upon clinical management has not been reported. OBJECTIVE: To investigate whether the implementation of NBS has altered the time to diagnosis of AI in children with ALD. DESIGN: We conducted a retrospective medical chart review of pediatric patients with ALD. SETTING: All patients were seen in a leukodystrophy clinic in an academic medical center. PATIENTS: We included all pediatric patients with ALD who were seen between May 2006 and January 2022. We identified 116 patients (94% boys). MAIN OUTCOME MEASURES: We extracted information about ALD diagnosis in all patients and AI surveillance, diagnosis, and treatment in boys with ALD. RESULTS: Thirty-one (27%) patients were diagnosed with ALD by NBS, and 85 (73%) were diagnosed outside the newborn period. The prevalence of AI among boys in our patient population was 74%. AI diagnosis was made significantly earlier in boys diagnosed with ALD by NBS than in boys diagnosed outside the newborn period (median [IQR] age of diagnosis = 6.7 [3.9, 12.12] months vs 6.05 [3.74, 8.35] years) (P < .001). When maintenance dose of glucocorticoids were initiated, there were significant differences in ACTH and peak cortisol levels in patients diagnosed by NBS and outside the newborn period. CONCLUSIONS: Our results suggest that implementing NBS for ALD leads to significantly earlier detection of AI and earlier initiation of glucocorticoid supplementation in boys affected by ALD.

Epidemiology and Causes of Primary Adrenal Insufficiency in Children: A Population-Based Study.

CONTEXT: Incidence and causes of primary adrenal insufficiency (PAI) have not been comprehensively studied in children. OBJECTIVE: Our objective was to describe the epidemiology and to assess causes of PAI in Finnish children. METHODS: A population-based descriptive study of PAI in Finnish patients aged 0-20 years.Diagnoses referring to adrenal insufficiency in children born in 1996-2016 were collected from the Finnish National Care Register for Health Care. Patients with PAI were identified by studying patient records. Incidence rates were calculated in relation to person-years in the Finnish population of same age. RESULTS: Of the 97 patients with PAI, 36% were female. The incidence of PAI was highest during the first year of life (in females 2.7 and in males 4.0/100 000 person-years). At 1-15 years of age, the incidence of PAI in females was 0.3/100 000 and in males 0.6/100 000 person-years. Cumulative incidence was 10/100 000 persons at age of 15 years and 13/100 000 at 20 years. Congenital adrenal hyperplasia was the cause in 57% of all patients and in 88% of patients diagnosed before age of 1 year. Other causes among the 97 patients included autoimmune disease (29%), adrenoleukodystrophy (6%), and other genetic causes (6%). From the age of 5 years, most of the new cases of PAI were due to autoimmune disease. CONCLUSION: After the first-year peak, the incidence of PAI is relatively constant through ages 1-15 years, and 1 out of 10 000 children are diagnosed with PAI before the age of 15 years.

Adrenal crisis in infants and young children with adrenal insufficiency: Management and prevention.

Background: Despite the optimization of replacement therapy, adrenal crises still represent life-threatening emergencies in many children with adrenal insufficiency. Objective: We summarized current standards of clinical practice for adrenal crisis and investigated the prevalence of suspected/incipient adrenal crisis, in relation to different treatment modalities, in a group of children with adrenal insufficiency. Results: Fifty-one children were investigated. Forty-one patients (32 patients <4 yrs and 9 patients >4 yrs) used quartered non-diluted 10 mg tablets. Two patients <4 yrs used a micronized weighted formulation obtained from 10 mg tablets. Two patients <4 yrs used a liquid formulation. Six patients >4 yrs used crushed non-diluted 10 mg tablets. The overall number of episodes of adrenal crisis was 7.3/patient/yr in patients <4yrs and 4.9/patient/yr in patients >4 yrs. The mean number of hospital admissions was 0.5/patient/yr in children <4 yrs and 0.53/patient/yr in children >4 yrs. There was a wide variability in the individual number of events reported. Both children on therapy with a micronized weighted formulation reported no episode of suspected adrenal crisis during the 6-month observation period. Conclusion: Parental education on oral stress dosing and switching to parenteral hydrocortisone when necessary are the essential approaches to prevent adrenal crisis in children.

Radiation of bilateral adrenal metastases is associated with a high risk of primary adrenal insufficiency.

BACKGROUND: Adrenal metastasis is the most common adrenal malignancy and can be bilateral in up to 43% of patients. Radiotherapy (RT) is one option available to treat adrenal metastases. The risk of primary adrenal insufficiency (PAI) after adrenal RT is unclear. OBJECTIVE: Determine the incidence and the timeline of PAI in patients undergoing adrenal RT. DESIGN, SETTING AND PARTICIPANTS: Single-centre longitudinal retrospective cohort study of adult patients with adrenal metastases treated with RT between 2010 and 2021. RESULTS: Of 56 patients with adrenal metastases treated with adrenal RT, eight (14.3%) patients developed PAI at a median of 6.1 months (interquartile range [IQR]: 3.9-13.8) after RT All patients developing PAI had either unilateral RT in the setting of contralateral adrenalectomy or bilateral adrenal RT. Patients who developed PAI received a median RT dose of 50 Gy (IQR: 44-50 Gy), administered in a median of five fractions (IQR: 5-6). Treated metastases decreased in size and/or metabolic activity on positron emission tomography in seven patients (87.5%). Patients were initiated on hydrocortisone (median daily dose of 20 mg, IQR: 18-40) and fludrocortisone (median daily dose of 0.05 mg, IQR: 0.05-0.05 mg). At the end of the study period, five patients died, all due to extra-adrenal malignancy, at a median time of 19.7 months (IQR: 16-21.1 months) since RT and median time of 7.7 months (IQR: 2.9-12.5 months) since the diagnosis of PAI. CONCLUSION: Patients receiving unilateral adrenal RT with two intact adrenal glands have a low risk of PAI. Patients receiving bilateral adrenal RT have a high risk of PAI and require close monitoring.

Is Preoperative Adrenal Insufficiency Screening Necessary for Cardiovascular Thoracic Surgery Patients?

Background: The association between adrenal insufficiency (AI) and the treatment outcomes of cardiothoracic surgery patients has been little reported. The aims of this study were to investigate the incidence of AI and to compare the post-surgical outcomes of patients with perioperatively treated AI and patients with a normal adrenal response. Methods: A 1.5-year prospective study was conducted in 98 patients scheduled for cardiothoracic surgery. Patients were categorized as either AI or normal-adrenal-response patients. Those with AI were treated with stress doses of glucocorticoid perioperatively. The post-surgical outcomes of patients with AI and of those with a normal adrenaline response were analyzed using multivariable analysis. Results: The overall incidence of AI was 34.7%. There were no statistically significant differences in post-surgical outcomes, including prolonged hospital stay, postoperative infection, prolonged inotropic drug use and relative AI, between the two groups. Only the rate of hyperglycemia requiring insulin infusion was significantly higher in the AI group than in the non-AI group (OR = 14.15, 95% CI = 1.44-138.60, p = 0.02). Conclusions: The proper diagnosis and management of AI can result in surgical outcomes in AI patients comparable to those of normal-adrenal-response patients. Non-life-threatening hyperglycemia requiring insulin infusion was found only in the AI group.

Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America.

OBJECTIVES: Adrenal insufficiency (AI) is a life-threatening condition where an accurate diagnosis is critical. While the ACTH stimulation test is the diagnostic test of choice, there remains uncertainty around its protocols and interpretation of results. In this context, the objective of this study was to understand practices of North American pediatric endocrinology providers on the diagnosis of AI in children. METHODS: An anonymous electronic survey was sent to members of the Pediatric Endocrine Society. RESULTS: A total of 221 participants were included. The majority practiced in academic centers (78%). All respondents ordered ACTH stimulation tests. While 85% used high-dose ACTH stimulation tests (HDST) to diagnose primary AI, there was less consistency in the choice of tests (HDST vs. low-dose ACTH stimulation test; LDST) when diagnosing secondary AI. When interpreting results, 95% used peak cortisol levels, 70% considered the clinical picture, and 49% used relative increase in cortisol levels. Median (IQR) cortisol cutoff level after ACTH stimulation test that was considered sufficient was 18 (15.5-18) µg/L [496 (428-496) nmol/L]; 17% used different cutoffs for LDST, and 18% used different cutoffs for newborns. Finally, 47% were unaware of the assay that was used in their institution for cortisol measurements. CONCLUSIONS: Pediatric endocrinology providers use ACTH stimulation tests variably, including in the choice between HDST vs. LDST, test protocols, and interpretation of results.