Management Of Adrenal Insufficiency Research Articles

The diagnosis of adrenal insufficiency and its implications in primary care

Adrenal insufficiency can be clinically challenging to diagnose, due to relatively low incidence rates in the European population. It is a condition requiring active consideration to achieve diagnosis. The main pathologies discussed here are primary adrenal insufficiency (PAI) and tertiary adrenal insufficiency. PAI is also commonly termed Addison’s disease. Secondary adrenal insufficiency is not considered in detail in this article. The article will address the underlying pathophysiology, presentation and investigation of adrenal insufficiency. It will also consider iatrogenic adrenal insufficiency and management of adrenal insufficiency in the primary care setting.

Clinical Approach to Adrenal Insufficiency

Adrenal insufficiency refers to inadequate production of glucocorticoids, mineralocorticoids, or both by the adrenal glands. This may result from dysfunction or complete destruction of the adrenal cortex (primary adrenal insufficiency), inadequate adrenocorticotropic hormone production by the pituitary (secondary adrenal insufficiency), or inadequate corticotropin-releasing hormone production by the hypothalamus (tertiary adrenal insufficiency). Diagnosis of adrenal insufficiency requires a high index of suspicion because of its nonspecific signs and symptoms. It is associated with a high morbidity and low quality of life even in patients on treatment. When it presents as adrenal crisis it has a high mortality. Glucocorticoid replacement is the mainstay of management, and this may be combined with mineralocorticoids in the case of primary adrenal insufficiency. Health care personnel must be reminded of this condition, to improve rates of early diagnosis and improve outcomes in management. In this review, we also look at the management of adrenal insufficiency in special populations and the potential role of newer long-acting steroids in the management of adrenal insufficiency is briefly discussed.

Alkindi Sprinkle for Pediatric Patients With Primary Adrenocortical Insufficiency: A Narrative Review.

Adrenocortical insufficiency, also known as adrenal insufficiency (AI), is an endocrine disorder characterized by inadequate production of adrenal hormones, including glucocorticoids and mineralocorticoids (MCs). The condition can be categorized as primary, secondary, or tertiary AI, depending on the location of the defect. Classical symptoms of AI include weakness, fatigue, abdominal pain, tachycardia, hypotension, electrolyte imbalances, and hyperpigmentation. In children, the most common cause of AI is classical congenital adrenal hyperplasia, which results from a deficiency in the 21-hydroxylase enzyme. The 21-hydroxylase enzyme produces all steroids, such as cortisol and aldosterone. AI management primarily involves hormone replacement therapy, typically with oral hydrocortisone and MC supplementation. However, the administration of hydrocortisone to pediatric patients presents challenges related to the lack of available dose-appropriate formulations. Historically, crushed or split adult tablets were used for the pediatric treatment of AI, although this poses an increased risk of under- or overtreatment. Inadequate dosing in the pediatric population can adversely affect growth, development, and metabolic health. Alkindi Sprinkle is a pediatric-specific hydrocortisone oral granule preparation that manages cortisol levels to help facilitate accurate therapeutic dosing. Alkindi offers several advantages, including accurate dosing, taste masking, and ease of administration. The present investigation describes AI, the management of AI, and the treatment of pediatric AI using Alkindi Sprinkle, including clinical efficacy.

Extensive Expertise in Endocrinology: Adrenal crisis in assisted reproduction and pregnancy.

Appropriate management of adrenal insufficiency in pregnancy is challenging due to the rarity of both primary, secondary and tertiary forms of the disease as well as the lack of evidence-based recommendations to guide clinicians to glucocorticoid and sometimes also mineralocorticoid dosage adjustments. Debut of adrenal insufficiency during pregnancy requires immediate diagnosis as it can lead to adrenal crisis, intrauterine growth restriction and foetal demise. Diagnosis is difficult due to overlap of symptoms of adrenal insufficiency and its crisis with those of pregnancy. Adrenal insufficiency in stable replacement treatment needs careful monitoring during pregnancy to adapt to the physiological changes in the requirement of the adrenal hormones. This is hampered because the diagnostic threshold of most adrenocortical hormones is not applicable during pregnancy. The frequent use of assisted reproduction technology with controlled ovarian hyperstimulation in these patient groups with disease induced low fertility has created an unrecognised risk of adrenal crises due to accelerated oestrogen stimulation with increased risk of even be life-threatening complications for both the woman and foetus. The area needs consensus recommendations between gynaecologists and endocrinologists in tertiary referral centres to alleviate such increased gestational risk. Patient and partner education, use of the EU emergency card for management of adrenal crises can also contribute to better pregnancy outcomes. There is a strong need of more research on e.g. improvement of glucocorticoid replacement as well as crisis management treatment, and biomarkers for treatment optimisation in this field, which suffers from the rare nature of the diseases and poor funding.

Fertility and pregnancy in adrenal insufficiency.

Despite the availability of adrenal hormone replacement therapy, patients with adrenal insufficiency can be affected by reduced fertility and parity. Patients with well-managed adrenal insufficiency are expected to have uneventful pregnancies and favourable outcomes, but an increased risk of maternal and neonatal complications has been reported in some cases. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making a new diagnosis and management of adrenal insufficiency challenging. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid as pregnancy progresses and in some circumstances mineralocorticoid replacement (in primary adrenal insufficiency patients only), especially in the third trimester. To date, there are no prospective data guiding management of adrenal insufficiency in pregnancy. In this review, we focus on the impact of adrenal insufficiency on fertility and parity based on the aetiology of adrenal insufficiency and provide a practical approach to the management of patients with adrenal insufficiency before and during pregnancy.

Implementation of IT supported standardization of individualized hydrocortisone management for treatment of patients with adrenal insufficiency.

Hydrocortisone stress dosing guidelines for children with adrenal insufficiency (AI) recommend a wide range of acceptable stress doses. This has led to variability in dosing recommendations resulting in confusion among endocrine, non-endocrine providers and patient families. This quality improvement project sought tostandardize documentation and hydrocortisone stress dosing within our pediatric endocrine division to optimize communication regarding AI management. Plan-Do-Study-Act (PDSA) cycle one aimed to address documentation of components important in AI management including body surface area (BSA), home daily dose, home stress dose, in-patient stress dose, procedure dose and crisis dose using a smart phrase within the electronic health record (EHR). To automate the process, PDSA cycle two introduced two smart buttons within the endocrine notes. PDSA cycle three focused on standardizing hydrocortisone stress doses. Initial documentation targets were met for all AI management components except for the crisis dose. The second target was only met for the home stress dose. Implementing the smart buttons aided in reaching the second target for home daily and home stress doses. Dosestandardization targets were achieved in all categories except for the on-going crisis dose. A follow up survey after an in-service for non-endocrine providers showed increased knowledge of locating hydrocortisone stress dosing recommendations within the EHR. With the assistance of technology, this quality improvement project ultimately enhanced communication through the standardization of documentation and individualized hydrocortisone stress dosing for children with AI. Although not all secondary targets were met, there was meaningful improvement in documentation and stress dose standardization compliance.

Outcomes of a self-reported knowledge survey on the management of adrenal insufficiency within a local accident and emergency Department

Outcomes of a self-reported knowledge survey on the management of adrenal insufficiency within a local accident and emergency Department

Do We Need AI to Diagnose AI? Diagnosis and Management of Adrenal Insufficiency Following Steroid Therapy in a Patient with Inflammatory Bowel Disease.

Do We Need AI to Diagnose AI? Diagnosis and Management of Adrenal Insufficiency Following Steroid Therapy in a Patient with Inflammatory Bowel Disease.

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

BackgroundIn 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.MethodsSingle-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).ResultsAmong 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).Conclusionchildren 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.

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.

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.

Adrenal insufficiency in Patients with Rheumatoid Arthritis: Prevalence, Clinical Implications, and Management Strategies

Rheumatoid arthritis (RA) is a chronic autoimmune-inflammatory disease that affects a significant proportion of the global population. It is characterized by synovial inflammation and joint destruction, leading to disability. The treatment of RA often involves the use of glucocorticoids, which can result in adrenal insufficiency (AI) due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis. The prevalence of AI in RA patients varies but is generally higher compared to the general population. The diagnosis of AI can be challenging due to its nonspecific symptoms and overlap with RA manifestations. Delayed recognition and inadequate management of AI can lead to adrenal crises, which are life-threatening emergencies. Regular monitoring of adrenal function, glucocorticoid replacement therapy, optimization of RA treatment, and patient education are crucial in the management of AI in RA patients. Future research should focus on risk stratification, the development of novel biomarkers, the exploration of alternative treatment strategies, and the evaluation of long-term outcomes to enhance our understanding and improve the management of AI in RA patients.

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.

Diagnosis and management of adrenal insufficiency in pregnancy

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

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

BackgroundAdrenal 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. ObjectiveThis 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. DiscussionA 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. ConclusionsEmergency clinicians must be prepared to recognize, evaluate, and manage those with known or suspected adrenal insufficiency or adrenal crisis.

Adrenal insufficiency in pregnancy: Physiology, diagnosis, management and areas for future research.

Adrenal insufficiency requires prompt diagnosis in pregnancy, as untreated, it can lead to serious consequences such as adrenal crisis, intrauterine growth restriction and even foetal demise. Similarities between symptoms of adrenal insufficiency and those of normal pregnancy can complicate diagnosis. Previously diagnosed adrenal insufficiency needs monitoring and, often, adjustment of adrenal hormone replacement. Many physiological changes occur to the hypothalamic-pituitary-adrenal (HPA) axis during pregnancy, often making diagnosis and management of adrenal insufficiency challenging. Pregnancy is a state of sustained physiologic hypercortisolaemia; there are multiple contributing factors including high plasma concentrations of placental derived corticotropin-releasing hormone (CRH), adrenocorticotropin (ACTH) and increased adrenal responsiveness to ACTH. Despite increased circulating concentrations of CRH-binding protein (CRH-BP) and the major cortisol binding protein, corticosteroid binding globulin (CBG), free concentrations of both hormones are increased progressively in pregnancy. In addition, pregnancy leads to activation of the renin-angiotensin-aldosterone system. Most adrenocortical hormone diagnostic thresholds are not applicable or validated in pregnancy. The management of adrenal insufficiency also needs to reflect the physiologic changes of pregnancy, often requiring increased doses of glucocorticoid and at times mineralocorticoid replacement, especially in the last trimester. In this review, we describe pregnancy induced changes in adrenal function, the diagnosis and management of adrenal insufficiency in pregnancy and areas requiring further research.

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

IntroductionAdrenocortical 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.ObjectiveTo understand patients' lived experience of the condition, its treatment, care process, impact of AI on ACC wellbeing, self‐care needs and support.MethodsSystematic 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.ResultsA 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.ConclusionACC 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.

Quality of Life and its Determinants in Patients With Adrenal Insufficiency: A Survey Study at 3 Centers in the United States.

Current evidence on determinants of quality of life (QoL) in patients with adrenal insufficiency (AI) is limited. This work aimed to identify the determinants of QoL in different subtypes of AI. This multicenter cross-sectional survey study was conducted using a patient-centered questionnaire, the Short Form-36. Of 529 participants, 223 (42.2%) had primary AI, 190 (35.9%) had secondary AI, and 116 (21.9%) had glucocorticoid-induced AI. Median age was 58 years (interquartile range: 43-68 years) and 342 (64.8%) were women. In multivariable analyses, patients were more likely to report worse physical scores if they were women (odds ratio [OR]: 3.3; 95% CI, 1.8-6.0), had secondary AI or glucocorticoid-induced AI (OR: 2.5; 95% CI, 1.4-4.3), had shorter duration of AI (OR: 2.0; 95% CI, 1.1-3.6), were treated with more than 25 mg hydrocortisone equivalent daily (OR: 2.3; 95% CI, 1.2-4.6), had more comorbidities related to glucocorticoid excess (OR: 2.3; 95% CI, 1.3-4.0), reported a higher financial burden from AI (OR: 2.1; 95% CI, 1.3-3.6), and reported difficulties with AI management (OR: 2.5; 95% CI, 1.2-5.2). Women (OR: 2.1; 95% CI, 1.08-4.0), shorter duration of AI (OR: 2.4; 95% CI, 1.4-4.3), higher financial burden (OR: 2.3; 95% CI, 1.3-4.0), difficulties with AI management (OR: 2.6; 95% CI, 1.4-4.9), and lack of family support (OR: 9.1; 95% CI, 2.3-33.3) were associated with worse mental component scores. In patients with AI, QoL could be improved by addressing certain determinants, such as avoiding GC overreplacement, providing in-depth education on self-management, offering more comprehensive insurance coverage, and ensuring better family support.

Monitoring for and Management of Endocrine Dysfunction in Adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is a peroxisomal disorder affecting the nervous system, adrenal cortical function, and testicular function. Newborn screening for ALD has the potential to identify patients at high risk for life-threatening adrenal crisis and cerebral ALD. The current understanding of the natural history of endocrine dysfunction is limited. Surveillance guidelines for males with ALD were developed to address the unpredictable nature of evolving adrenal insufficiency. Early recognition and management of adrenal insufficiency can prevent adrenal crisis. While testicular dysfunction in ALD is described, the natural history and complications of low testosterone, as well as the management, are not well described.

Adrenal gland diseases: Addison's Disease

Addison's disease typically results from the autoimmune destruction of the adrenal cortex and requires lifelong replacement with glucocorticoids and mineralocorticoids. Main symptoms are non-specific and, therefore, often overlooked or misleading. Patients are frequently not diagnosed until experiencing a life-threatening adrenal crisis. This article highlights the essential clinical characteristics, diagnostic aspects and principles of management of adrenal insufficiency.