Adrenal Crisis - Definition, Prevention and Treatment: Results from a Delphi Survey.

Based on recent data, a total number of about 29 000 patients with adrenal insufficiency can be calculated for Germany, and about 1500 fatalities due to adrenal crises have to be expected within the next decade. Management of adrenal crises is still unsatisfactory. The objectives of this study were to establish consensus for diagnostic criteria, prevention strategies, and treatment recommendations for adrenal crises. The study was conducted from January 2022 to April 2023, using Delphi technique. Four rounds of questionnaires were sent to 45 experts, selected by a coordinating group on behalf of the adrenal section of the German Society of Endocrinology. The survey was implemented online using the REDCap web application. Responses were captured anonymously. During the Delphi process the expert panel developed diagnostic criteria to identify patients likely to have an adrenal crisis. Education about adrenal insufficiency among patients as well as non-endocrine medical personnel were regarded as highly important. It was suggested that recommendations for the management of adrenal insufficiency have to be simplified and made widely available. This study provides pragmatic strategies to identify and treat patients prone to adrenal crisis, thereby highlighting the need for an improved management of patients with adrenal insufficiency.

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.

Approach to the Patient: Preventing Adrenal Crisis Through Patient and Clinician Education.

Adrenal crisis continues to be an important cause of death despite being a preventable condition. Significant deficits in patient education in the prevention of adrenal crisis have been identified as a contributor to adrenal crisis risk, despite the importance of patient education being highlighted in international guidelines. Deficits in clinician education have also been identified as risk factors for adrenal crisis although they have not been addressed. We use 3 clinical cases to highlight the role of both patient and clinician education in the prevention of adrenal crisis, review what is known about education related to adrenal insufficiency and provide a possible approach to addressing education deficits with the aim of reducing the risk of adrenal crisis through both patient and clinician education.

Presumed adrenal insufficiency in neonates treated with corticosteroids for the prevention of bronchopulmonary dysplasia.

OBJECTIVE: To determine if extremely preterm (EPT) neonates receiving dexamethasone for the prevention of BPD have a higher incidence of presumed adrenal insufficiency (PAI). STUDY DESIGN: Retrospective cohort study of neonates <28 weeks gestation examining PAI after dexamethasone use and PAI after intratracheal budesonide with surfactant administration. RESULT: Of 332 neonates, 38% received dexamethasone. The incidence of PAI was higher in neonates who had received dexamethasone (20.8% vs 2.9%, p < 0.001). However, for intubated babies receiving surfactant, dexamethasone was not independently associated with increased PAI after adjusting for gestational age, birthweight, and race (aOR 2.92, 95% CI: 0.79-10.85). Dexamethasone was independently associated with increased PAI in infants previously receiving budesonide/surfactant treatment (aOR 5.38, 95% CI: 1.38-20.90). CONCLUSION: The use of dexamethasone alone was not associated with increased PAI, when adjusted for prematurity-related factors. The combination of budesonide with dexamethasone was significantly associated with increased PAI.

Immune checkpoint inhibitor combination therapies very frequently induce secondary adrenal insufficiency.

Immune checkpoint inhibitors (ICIs) are potent therapeutic options for many types of advanced cancer. The expansion of ICIs use however has led to an increase in immune-related adverse events (irAEs). Secondary adrenal insufficiency (AI) can be life-threatening especially in patients with delayed diagnosis. We retrospectively investigated secondary AI in ICI-treated patients. A total of 373 cancer patients treated with ICIs were included and evaluated. An adrenocorticotropic hormone (ACTH) deficiency was described in 13 patients. Among 24 patients with a combination of nivolumab and ipilimumab therapy, 7 patients (29%) developed secondary AI in a median time of 8 weeks during the combination therapy and 2 of 15 patients (13%) developed isolated ACTH deficiency during maintenance nivolumab monotherapy following the combination therapy. More than half of the patients (4/7) with a combination therapy-induced multiple anterior hormone deficiencies was diagnosed as secondary AI based on regular ACTH and cortisol tests with slight subjective symptoms. Secondary AI can arise frequently and rapidly in cancer patients receiving a combination ICI therapy, and thus we speculate active surveillance of AI using regular ACTH and cortisol tests during the combination therapy might be useful for avoiding life-threatening conditions due to secondary AI.

Frequently Asked Questions in Patients With Adrenal Insufficiency in the Time of COVID-19.

Adrenal insufficiency (AI) is a life-threatening disorder, with increased morbidity and mortality, especially in case of an acute illness that can increase the requirement of cortisol. A novel infectious disease, termed Coronavirus Disease 2019 (COVID-19), appeared in 2020. Therefore, AI patients are experiencing a novel challenge: the risk of infection. In our experience, a prompt contact to the Endocrine center (with a telemedicine consultation) and a full awareness of diseases (cortisol deficiency, COVID-19 and the self-management of an adrenal crisis) are important to motivate patients. Vaccine is an effective treatment to prevent hospitalization and aggressive course of COVID-19. Some patients manifest challenges due to inequitable access and vaccine hesitancy, resulting in a delay in the acceptance of vaccines despite the availability of vaccination services. Therefore, an effort of all physicians must be conducted in order to advise patients with AI. In this short review, we try to answer some frequently asked questions regarding the management of patients with AI.

Guidance for the prevention and emergency management of adult patients with adrenal insufficiency.

Adrenal insufficiency (AI) is an often-unrecognised endocrine disorder, which can lead to adrenal crisis and death if not identified and treated. Omission of steroids in patients with AI, particularly during physiological stress such as an intercurrent illness or surgery, can also lead to an adrenal crisis. The National Reporting and Learning System (NRLS) identified 78 incidents including two deaths and six incidents of severe harm to patients in a recent 4-year period. This guidance will go through causes of adrenal insufficiency, groups at risk of an adrenal crisis, emergency management and management for surgical procedures. A new NHS Steroid Emergency Card has been developed to be carried by patients at risk of adrenal crisis. We hope the new emergency card and this guidance will increase awareness of the need to start steroids promptly in patients at risk of an adrenal crisis, particularly those presenting in the emergency department or to acute medicine teams and those undergoing surgery or invasive procedures.

Adrenal-sparing surgery: current concepts on a theme from the past.

Adrenal insufficiency represents a debilitating condition which mandates lifelong steroid replacement and which is associated with significant long-term morbidity, due to either inadequate or excessive replacement. The concept of preserving healthy cortical tissue by means of partial adrenalectomy has evolved as a means of avoiding the detrimental consequences of adrenal insufficiency. The advent of advanced technology in adrenal surgery has greatly facilitated the performance of partial adrenalectomy, enabling utilization of this method in an increasing number of endocrine diseases. Hereditary pheochromocytoma, Conn's syndrome, Cushing's syndrome, and non-functional adrenal masses represent the current indications for partial adrenalectomy, although the specific circumstances under which adrenal-sparing surgery should be proposed are still debatable. Partial adrenalectomy can be achieved by all types of minimally invasive surgery. In the absence of randomized, prospective, controlled studies designed to compare laparoscopic, retroperitoneoscopic, and robot-assisted partial adrenalectomy, none of these techniques has as yet been proven to be the gold standard for adrenal-sparing surgery. Apart from indications for surgery, results of surgery, and different types of partial adrenalectomy, controversial topics addressed in this review article include technical aspects such as the volume of residual adrenal tissue needed, ligation of adrenal vein, and means of tumor identification. Discussion of these controversial topics represents an attempt to define the role of partial adrenalectomy in modern adrenal surgery.

Guía para el manejo y la prevención de la insuficiencia suprarrenal aguda / SEEN guidelines for the management and prevention of acute adrenal insufficiency

La insuficiencia suprarrenal aguda (ISA) es una urgencia médica potencialmente letal cuya prevención y tratamiento deberían ser conocidos por todos los profesionales médicos. La ISA es una condición infradiagnosticada debido a la inespecificidad de los síntomas de presentación, pero su diagnóstico y tratamiento con glucocorticoides es vital. Puede ser desencadenada por una deficiencia de novo en la síntesis de cortisol o secundaria a la omisión del tratamiento hormonal sustitutivo con corticoides o al ajuste inadecuado de la dosis requerida en situaciones de estrés en el paciente ya diagnosticado. La prevención de la ISA disminuye de forma significativa la mortalidad cardiovascular y por infecciones de los pacientes con insuficiencia renal y mejora su calidad de vida. Por ello, es fundamental la adecuada educación del paciente, sus familiares y del personal sanitario. El Grupo de Trabajo de Patología Suprarrenal del Área de Conocimiento de Neuroendocrinología de la Sociedad Española de Endocrinología y Nutrición (SEEN) ha elaborado, a partir de una propuesta de la Junta Directiva de la SEEN, esta guía para el óptimo manejo de la insuficiencia suprarrenal en fase aguda. Esta guía tiene el objetivo de ser eminentemente práctica y dar recomendaciones orientadas a todos los profesionales sanitarios que pueden estar involucrados en el diagnóstico, tratamiento y la prevención de la ISA. Así mismo, pretende facilitar pautas de actuación para el paciente y sus familiares en su manejo y prevención

Acute adrenal insufficiency (AAI) is a potentially fatal medical emergency whose prevention and treatment should be known by all medical professionals. AAI is an underdiagnosed condition because of its non-specific symptoms, but its diagnosis and early treatment with glucocorticoids is vital. It may be triggered by a de novo deficiency in cortisol synthesis or occur secondarily to omission of hormone replacement therapy (corticosteroids) or inadequate adjustment of the dose required in stress situations in patients previously diagnosed with adrenal insufficiency. AAI prevention significantly decreases death from cardiovascular diseases and infections in patients with adrenal insufficiency, and also improves their quality of life. Adequate education of patients, relatives, and all healthcare professionals is therefore essential. Therefore, the Adrenal Disorders Group of the Neuroendocrinology Area of the Spanish Society of Endocrinology and Nutrition (SEEN) has prepared, at the proposal of the SEEN's board, a guideline for optimal management of acute adrenal insufficiency. The guideline is intended to provide practical recommendations for all healthcare professionals who may be involved in the diagnosis, treatment, and prevention of AAI. It is also intended to provide patients and their families with action guidelines for AAI management and prevention

SEEN guidelines for the management and prevention of acute adrenal insufficiency. / Guía para el manejo y la prevención de la insuficiencia suprarrenal aguda.

Acute adrenal insufficiency (AAI) is a potentially fatal medical emergency whose prevention and treatment should be known by all medical professionals. AAI is an underdiagnosed condition because of its non-specific symptoms, but its diagnosis and early treatment with glucocorticoids is vital. It may be triggered by a de novo deficiency in cortisol synthesis or occur secondarily to omission of hormone replacement therapy (corticosteroids) or inadequate adjustment of the dose required in stress situations in patients previously diagnosed with adrenal insufficiency. AAI prevention significantly decreases death from cardiovascular diseases and infections in patients with adrenal insufficiency, and also improves their quality of life. Adequate education of patients, relatives, and all healthcare professionals is therefore essential. Therefore, the Adrenal Disorders Group of the Neuroendocrinology Area of the Spanish Society of Endocrinology and Nutrition (SEEN) has prepared, at the proposal of the SEEN's board, a guideline for optimal management of acute adrenal insufficiency. The guideline is intended to provide practical recommendations for all healthcare professionals who may be involved in the diagnosis, treatment, and prevention of AAI. It is also intended to provide patients and their families with action guidelines for AAI management and prevention.

Utilizing health information technology to improve the recognition and management of life-threatening adrenal crisis in the pediatric emergency department: medical alert identification in the 21st century.

Background Many barriers exist to the appropriate recognition and management of life-threatening adrenal crisis in the emergency department (ED). Clinical decision support (CDS) is a health information technology (IT) component that provides useful information to providers as healthcare is being delivered. We hypothesized that CDS incorporated into the electronic health record (EHR) could improve the recognition and management of adrenal crisis within the pediatric ED. Methods We retrospectively analyzed the impact of electronic CDS on the management of patients with known adrenal insufficiency (AI) presenting to two pediatric ED locations over a 19-month period with symptoms suggestive of adrenal crisis. Outcome variables assessed included the frequency of hydrocortisone (HC) administration, appropriateness of HC dosing, and timing to HC order placement and administration. Results A total of 145 encounters were reviewed. When the electronic CDS was in place at the time of the ED visit, patients were nearly 3 times as likely to receive HC (p = 0.002). Among those patients who received HC, the presence of the CDS increased the likelihood of an appropriate 50-mg/m2 dose of HC being given from 20 to 53% (p = 0.02). However, the CDS did not significantly reduce the time from ED arrival to HC order placement (p = 0.36) or administration (p = 0.59). Conclusions The use of innovative health IT strategies, such as the electronic CDS, can improve the recognition and management of adrenal crisis among patients with AI presenting to the pediatric ED.