Iatrogenic adrenal insufficiency in adults.

Iatrogenic adrenal insufficiency (IAI) is the most common form of adrenal insufficiency in adult patients, although its overall exact prevalence remains unclear. IAI is associated with adverse clinical outcomes, including adrenal crisis, impaired quality of life and increased mortality; therefore, it is imperative that clinicians maintain a high index of suspicion in patients at risk of IAI to facilitate timely diagnosis and appropriate management. Herein, we review the major causes, clinical consequences, diagnosis and care of patients with IAI. The management of IAI, particularly glucocorticoid-induced (or tertiary) adrenal insufficiency, can be particularly challenging, and the provision of adequate glucocorticoid replacement must be balanced against minimizing the cardiometabolic effects of excess glucocorticoid exposure and optimizing recovery of the hypothalamic-pituitary-adrenal axis. We review current treatment strategies and their limitations and discuss developments in optimizing treatment of IAI. This comprehensive Review aims to aid clinicians in identifying who is at risk of IAI, how to approach screening of at-risk populations and how to treat patients with IAI, with a focus on emergency management and prevention of an adrenal crisis.

Autoimmune primary adrenal insufficiency -current diagnostic approaches and future perspectives.

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.

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.

Using the behaviour change wheel and person-based approach to develop a digital self-management intervention for patients with adrenal insufficiency: the Support AI study protocol.

Introduction: Most patients with Adrenal insufficiency (AI) require lifelong glucocorticoid replacement. They need to increase glucocorticoids during physical illness or major stressful situations and require parenteral hydrocortisone in the event of an adrenal crisis. Patients with AI have impaired quality of life and high mortality; approximately 1 in 6-12 patients are hospitalised at least once/year from a potentially preventable adrenal crisis. Adoption of self-management behaviours are crucial; these include adherence to medication, following "sick day rules" and associated behaviours that aid prevention and treatment of adrenal crisis such as symptom monitoring, having extra tablets, carrying a medical-alert ID and injection kit, and self-injecting when necessary. Current patient education is ineffective at supporting self-management behaviour change or reducing adrenal crisis-related hospitalisations. This research study aims to gain an in-depth understanding of the barriers and enablers to self-management for patients with AI and to develop an evidence-based digital self-management behaviour change intervention. Methods: The study is conducted in accordance with the MRC Framework for developing complex interventions. Underpinned by the Behaviour Change Wheel (BCW), the Theoretical Domains Framework (TDF), and the Person-Based Approach, this research will be conducted in two phases: Phase 1 will involve a sequential qualitative/quantitative mixed-methods study involving focus group interviews followed by a cross-sectional survey with patients with AI recruited from patient advocacy groups and endocrine clinics in the UK. Phase 2 will develop the Support AI, a website-based digital behaviour change intervention (DBCI) informed by Phase 1 findings to support self-management for patients with AI. The most appropriate behaviour change techniques (BCTs) will be selected utilising a nominal group technique with an Expert Panel of 10-15 key stakeholders. The design of the Support AI website will be guided by the Person-Based Approach using an Agile iterative "think-aloud" technique with 12-15 participants over 3 usability testing iterations. Conclusion: A theory- and evidence-based digital behaviour change intervention will be developed which will be tested in a feasibility randomised trial following completion of this study. The projected benefit includes cost-effective health care service (reduced hospitalisations and demand for specialist services) and improved health outcomes and quality of life for patients with AI.

Adrenal insufficiency management in the pediatric emergency setting and risk factors for adrenal crisis development.

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.

Current and future perspectives on clinical management of classic 21-hydroxylase deficiency.

Optimizing the glucocorticoid dosage has been a major concern in classic 21OHD (21-hydroxylase deficiency) treatment, as it is essential to adjust it meticulously to the needs of the individual patient. Insufficient glucocorticoid treatment will cause adrenal insufficiency, including life-threatening adrenal crisis, while excess of androgen could cause precocious pubertal growth in children, virilization in female patients, and infertility in male and female adult patients. Meanwhile, overtreatment with glucocorticoids causes iatrogenic Cushing's syndrome which could result in growth impairment, obesity, osteoporosis, and hypertension. The dilemma of 21OHD treatment is that glucocorticoid supplementation therapy at physiological dosage does not sufficiently suppress ACTH, consequently leading to adrenal androgen excess. Accordingly, the window for the appropriate glucocorticoid treatment would have to be substantially narrower than that of other types of adrenal insufficiency without androgen excess, such as adrenal hypoplasia. For the appropriate management of classic 21OHD, the physician has to be well versed in the physiology of the adrenal cortex, growth, and reproductive function. Comprehensive understanding of patients' requirements according to their life stage and sex is essential. Furthermore, female patients with 46,XX need to be cared for as differences in sex development (DSD) with careful psychological management. In this review, we aimed to comprehensively summarize the current status of classic 21OHD treatment, including the initial treatment during the neonatal period, management of adrenal insufficiency, maintenance therapy of each life stage, and the importance of clinical management as DSD for 46,XX female patients. The recently developed agents, Chronocort, and Crinecerfont, are also discussed.

An unusual cause of adrenal insufficiency with elevation of 17-hydroxyprogesterone: case report.

BACKGROUND: We present an intriguing case of primary adrenal lymphoma, with associated primary adrenal insufficiency (PAI), in a patient presenting a transitory partial 21-hydroxylase deficiency during the active phase of the adrenal disease. CASE PRESENTATION: An 85-years old woman was referred because of worsening asthenia, lumbar pain, generalized myalgia and arthralgia. During investigations a computed tomography (CT) scan evidenced two large bilateral adrenal masses, highly suspicious for primary adrenal tumor. The hormonal assessment revealed very low levels of morning plasma cortisol and 24-h urinary cortisol, elevated ACTH levels with low plasma concentration of aldosterone, pointing to the diagnosis of PAI. After diagnosis of PAI our patient started glucocorticoid and mineralcorticoid replacement therapy with clinical benefit. In order to further characterize the adrenal lesions, adrenal biopsy, was performed. The histology revealed a high grade non-Hodgkin lymphoma with an immunophenotype consistent with intermediate aspects between diffuse large B-cell and Burkitt lymphoma, with a high proliferation index (KI-67 > 90%). The patient received chemotherapy with epirubicin, vincristine, cyclophosphamide, and rituximab, associated with methylprednisolone that resulted in a complete clinical and radiological remission within one year. After 2 years from the diagnosis and a total of 6 cycles of rituximab, the patient was in good clinical condition and was taking only the replacement therapy for PAI. The patient initially presented also a slight increase of 17-hydroxyprogesterone (17-OHP) for age that normalize after resolution of lymphoproliferative disease. CONCLUSIONS: In the presence of bilateral adrenal disease and/or in the presence of signs and symptoms of PAI clinicians must exclude the presence of PAL. The evidence of elevated ACTH-stimulated 17-OHP levels also in patients with other adrenal masses, together with the detection of elevated basal 17-OHP levels in our patient make it more plausible, in our view, an effect of the lesion on the "healthy" adrenal tissue residue than a direct secretory activity by the adrenal tumor.

Diagnosis and management of adrenal insufficiency.

Adrenal insufficiency is the inadequate secretion of glucocorticoid and/or mineralocorticoid secretion from the adrenal cortex. Primary adrenal insufficiency is the result of failure of the adrenal gland and secondary adrenal insufficiency is due to a lack of stimulation via pituitary adrenocorticotropic hormone or hypothalamic corticotropin-releasing hormone. Adrenal insufficiency may cause non-specific symptoms. Early detection and testing based on clinical suspicion may prevent subsequent presentation with adrenal crisis. Once identified, a low baseline cortisol (often <100 nmol/L) alongside raised adrenocorticotropic hormone (ACTH) can be enough to diagnose primary adrenal insufficiency. However, confirmatory testing can be done using the cosyntopin (Synacthen®) stimulation test or the insulin tolerance test, which is the gold standard for secondary adrenal insufficiency. The underlying cause of adrenal insufficiency can often be identified via a strategic approach to investigation. Adrenal crisis is a life-threatening medical emergency which must be treated immediately if there is strong clinical suspicion with fluids and corticosteroids otherwise can be fatal. Patients must be educated and empowered to take control of their own medical management.

Future Directions for Adrenal Insufficiency: Cellular Transplantation and Genetic Therapies.

Primary adrenal insufficiency (PAI) occurs in 1 in 5 to 7000 adults. Leading etiologies are autoimmune adrenalitis in adults and congenital adrenal hyperplasia (CAH) in children. Oral replacement of cortisol is lifesaving, but poor quality of life, repeated adrenal crises, and dosing uncertainty related to lack of a validated biomarker for glucocorticoid sufficiency persists. Adrenocortical cell therapy and gene therapy may obviate many of the shortcomings of adrenal hormone replacement. Physiological cortisol secretion regulated by pituitary adrenocorticotropin could be achieved through allogeneic adrenocortical cell transplantation, production of adrenal-like steroidogenic cells from either stem cells or lineage conversion of differentiated cells, or for CAH, gene therapy to replace or repair a defective gene. The adrenal cortex is a high-turnover organ and thus failure to incorporate progenitor cells within a transplant will ultimately result in graft exhaustion. Identification of adrenocortical progenitor cells is equally important in gene therapy, for which new genetic material must be specifically integrated into the genome of progenitors to ensure a durable effect. Delivery of gene-editing machinery and a donor template, allowing targeted correction of the 21-hydroxylase gene, has the potential to achieve this. This review describes advances in adrenal cell transplants and gene therapy that may allow physiological cortisol production for children and adults with PAI.

[Acute adrenal insufficiency: an entity that should not be missed]. / Insuffisance surrénalienne aiguë†: une entité à ne pas manquer.

Acute adrenal insufficiency is a rare pathology which can be life threatening if not diagnosed and treated adequately. Clinical presentation is aspecific. Etiologies are classified as central or adrenal origins. Diagnosis of adrenal insufficiency is based on dosage of morning cortisol combined with a Synacthen test. When acute adrenal insufficiency is suspected, 100 mg of hydrocortisone should be administered as soon as possible, even before biological confirmation. This article, illustrated by a clinical case, will review the clinical presentation, diagnostic approach, and treatment of adrenal insufficiency.

L'insuffisance surrénalienne (IS) aiguë est une pathologie qui engage le pronostic vital si elle n'est pas diagnostiquée et traitée rapidement. Sa présentation clinique est aspécifique. Les étiologies sont classées en origines surrénaliennes ou centrales. Le diagnostic d'IS repose sur le dosage du cortisol matinal ainsi que sur un test au Synacthen. Lors d'une suspicion d'IS aiguë, le traitement par hydrocortisone 100 mg IV doit être administré dans les meilleurs délais sans attendre la confirmation biologique. Cet article, illustré par un cas clinique, a pour but de rappeler la présentation clinique, la démarche diagnostique et la prise en charge médicamenteuse de l'IS.

Professional practices in the management of adrenal insufficiency in two tertiary referral hospitals (Tunis, Tunisia).

BACKGROUND: Adrenal insufficiency (AI) is a rare and life-threatening disease. Glucocorticoid replacement therapy and patient education are crucial. Few is known about physician practice in this topic. AIMS: To describe physician practice in the management of AI and to identify the associated factors. METHODS: the physicians, all grades and specialties, from two university hospitals in Tunis, were invited to respond to a paper-based 16- multiple choice item-questionnaire about the management of AI and the prevention of acute AI. Each question was scored 1 if correct or 0 if incorrect. The global score was calculated by adding the score of the first 15 questions. RESULTS: 200 physicians responded to the questionnaire, sex ratio: 0.47, mean age: 29.0 ± 5.8 years (24 - 60). The overall rate of correct answers was 59.6%. The rate of correct responses was good for the type of replacement therapy (92%), the lifelong duration of treatment (88%), the symptoms of overtreatment (73.5%), the type of diet indicated (77%), and the necessity of special measures during the peri operative period (100%). However, the rate of correct responses was low for the half-life of hydrocortisone (12.5%), biological signs suggesting acute AI (17.5%), situations during which an increase in the dose of glucocorticoid is required (26.5%) and the risks of intermittent fasting (2%). Endocrinology specialty and overall medical specialties were independently associated with a better global score. CONCLUSION: physician practice in the management of AI need to be improved.

Diagnosis and Management of Adrenal Insufficiency and Adrenal Crisis in the Emergency Department.

BACKGROUND: Adrenal insufficiency can result in significant patient morbidity and mortality, but due to the range of symptoms and variable clinical course and etiologies, it can be a challenging condition to diagnose and manage. OBJECTIVE: This narrative review will discuss the evaluation of an adult patient at risk for a new diagnosis of adrenal insufficiency and the management of a patient with known or suspected adrenal insufficiency. DISCUSSION: A new presentation of adrenal insufficiency can range from nonspecific, minor symptoms including fatigue, to a life-threatening adrenal crisis with hemodynamic instability. Due to the variety of signs and symptoms, the diagnosis is often missed. Those with known adrenal insufficiency are at risk for adrenal crisis, which may occur due to a variety of triggers. Initial evaluation includes assessment for the underlying etiology or concomitant condition, laboratory analysis, and imaging, when clinically indicated. Although not necessary for evaluation in the emergency department setting, the diagnosis is confirmed by specific testing such as the cosyntropin stimulation test. The mainstay of treatment in adrenal crisis is hydrocortisone, intravenous fluid, glucose repletion, and treatment of the underlying acute trigger. CONCLUSIONS: Emergency clinicians must be prepared to recognize, evaluate, and manage those with known or suspected adrenal insufficiency or adrenal crisis.

Lived experience of people with adrenocortical carcinoma and associated adrenal insufficiency.

INTRODUCTION: Adrenocortical carcinoma (ACC) is a rare cancer with an annual incidence of 0.7-2 cases per million population and 5-year survival of 31.2%. Adrenal insufficiency (AI) is a common and life shortening complication of ACC, and little is understood about how it impacts on patients' experience. OBJECTIVE: To understand patients' lived experience of the condition, its treatment, care process, impact of AI on ACC wellbeing, self-care needs and support. METHODS: Systematic review of MEDLINE, EMBASES, CINAHL, PsycINFO and Open Grey for studies published until February 2021. All research designs were included. The findings underwent a thematic analysis and narrative synthesis. Studies quality was assessed using mixed method assessment tools. RESULTS: A total of 2837 citations were identified; 15 titles with cohort, cross-sectional, case series and case report study designs met the inclusion criteria involving 479 participants with adrenal insufficiency secondary to adrenocortical carcinoma (AI/ACC). Quantitative research identified impacts of disease and treatment on survivorship, the burden of living with AI/ACC, toxicity of therapies, supporting self-care and AI management. These impact factors included adjuvant therapies involved and their toxicities, caregivers/family supports, healthcare and structure support in place, specialist skill and knowledge provided by healthcare professional on ACC management. No qualitative patient experiences evidence was identified. CONCLUSION: ACC appears to have high impact on patients' wellbeing including the challenges with self-care and managing AI. Evidence is needed to understand patient experience from a qualitative perspective.

Central adrenal insufficiency: who, when, and how? From the evidence to the controversies - an exploratory review.

Central adrenal insufficiency (CAI) is a life-threatening disorder. This occurs when ACTH production is insufficient, leading to low cortisol levels. Since corticosteroids are crucial to many metabolic responses under organic stress and inflammatory conditions, CAI recognition and prompt treatment are vital. However, the diagnosis of CAI is challenging. This is not only because its clinical presentation is usually oligosymptomatic, but also because the CAI laboratory investigation presents many pitfalls. Thus, the clarification of when to use each test could be helpful in many contexts. The CAI challenge is also involved in treatment: Several formulations of synthetic steroids exist, followed by the lack of a biomarker for glucocorticoid replacement. This review aims to access all available literature to synthesize important topics about who should investigate CAI, when it should be suspected, and how CAI must be treated.

Adrenal insufficiency.

Adrenal insufficiency (AI), first described by Thomas Addison in 1855, is characterised by inadequate hormonal production by the adrenal gland, which could either be primary, due to destruction of the adrenal cortex, or secondary/tertiary, due to lack of adrenocorticotropic hormone or its stimulation by corticotropin-releasing hormone. This was an invariably fatal condition in Addison's days with most patients dying within a few years of diagnosis. However, discovery of cortisone in the 1940s not only improved the life expectancy of these patients but also had a dramatic effect on their overall quality of life. The diagnosis, easily confirmed by demonstrating inappropriately low cortisol secretion, is often delayed by months, and many patients present with acute adrenal crisis. Sudden withdrawal from chronic glucocorticoid therapy is the most common cause of AI. Currently, there remains a wide variation in the management of this condition across Europe. As primary AI is a relatively rare condition, most medical specialists will only manage a handful of these patients in their career. Despite many advances in recent years, there is currently no curative option, and modern cortisol replacement regimens fail to adequately mimic physiological cortisol rhythm. A number of new approaches including allograft of adrenocortical tissue and stem cell therapy are being tried but remain largely experimental.

Development and assessment of a low-health-literacy, pictographic adrenal insufficiency action plan.

OBJECTIVES: Adrenal insufficiency (AI) is an overall rare disorder characterized by the chronic need for pharmacotherapy to prevent threat to life. The Pediatric Endocrine Society has recommended the use of clinical action tools to improve patient education and help guide acute management of AI. We aimed to develop and assess an easy-to-use, patient-friendly, evidence-based, personalized pictogram-based adrenal insufficiency action plan (AIAP) to aid in the management of AI in children. METHODS: Patients/caregivers (P/Cs) responded to surveys which measured the concepts of transparency, translucency, and recall in order to assess the pictograms. Readability was assessed using six formulas to generate a composite readability score. Quality was graded by P/Cs using the Consumer Information Rating Form (CIRF) (>80% rating considered acceptable). Understandability and actionability was assessed by medical librarians using the Patient Education Materials Assessment Tool-Printable (PEMAT-P) (>80% rating was acceptable). Suitability was evaluated by clinicians using the Suitability Assessment of Materials (SAM) instrument (>70% rating considered superior). RESULTS: All pictograms met criteria for inclusion in the AIAP. Composite readability score=5.4 was consistent with a fifth-grade level. P/Cs (n=120) judged the AIAP to be of high quality with CIRF rating=85.2%. Three medical librarians rated the AIAP to have 100% understandability and 100% actionability. Thirty-three clinicians completing the SAM generated a suitability rating of 90.0%. CONCLUSIONS: The AIAP visually highlights individualized care plan components to facilitate optimized preventative and acute AI care. Further investigation will determine if AIAP improves clinical outcomes for patients with AI.

Adrenal Insufficiency and Its Implications on Dental Treatment.

Adrenal insufficiency is a rare disease affecting the function of the adrenal glands leading to hormone deficiency. Medical management of these patients often consists of a scheduled regimen of hormone replacement therapies along with patient education on the management of medical emergencies, such as adrenal crisis. The primary goal of the clinician in the dental management of these patients is the minimization of stressful stimuli while being adept and equipped to manage spontaneous occurrences of adrenal crisis. Understanding the pharmacological effects and interactions of these patients' medications is also important in managing their treatment. This article outlines the underlying pathology and clinical manifestation of adrenal insufficiency and underscores specific recommendations for the medical and dental management of such patients to avoid adrenal crisis both inside and outside the clinical setting. The dentist, as one of the primary care providers for these patients, should be able to identify the physical and orofacial signs and symptoms associated with this disorder so that the patient may be diagnosed and treated as best as possible.

The epidemiology of primary and secondary adrenal malignancies and associated adrenal insufficiency in hospitalised patients: an analysis of hospital admission data, NSW, Australia.

BACKGROUND: Adrenal insufficiency (AI) causes considerable morbidity but may remain undiagnosed in patients with adrenal malignancy (AM). The epidemiology of AI and adrenal crises (AC) in AM is uncertain. METHODS: This was a retrospective study examining hospital admission data from 2006 to 2017. All admissions to all hospitals in NSW, Australia over this period with a principal or comorbid diagnosis of an adrenal malignancy were selected. Data were examined for trends in admissions for AM and associated AI/AC using population data from the corresponding years. RESULTS: There were 15,376 hospital admissions with a diagnosis of AM in NSW over the study period, corresponding to 1281 admissions/year. The AM admission rate increased significantly over the study period from 129.9/million to 215.7/million (p < 0.01). An AI diagnosis was recorded in 182 (1.2%) admissions, corresponding to an average of 2.1/million/year. This rate increased significantly over the years of the study from 1.2/million in 2006 to 3.4/million in 2017 (p < 0.01). An AC was identified in 24 (13.2%) admissions with an AI diagnosis. Four patients (16.7%) with an AC died during the hospitalisation. CONCLUSION: Admission with a diagnosis of AM has increased over recent years and has been accompanied by an increase in AI diagnoses. While AI is diagnosed in a small proportion of patients with AM, ACs do occur in affected patients.