Treatment Of Adrenal Insufficiency Research Articles

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.

AAV-delivered hepato-adrenal cooperativity in steroidogenesis: Implications for gene therapy for congenital adrenal hyperplasia

Despite the availability of life-saving corticosteroids for 70 years, treatment for adrenal insufficiency is not able to recapitulate physiological diurnal cortisol secretion and results in numerous complications. Gene therapy is an attractive possibility for monogenic adrenocortical disorders such as congenital adrenal hyperplasia, however, requires further development of gene transfer/editing technologies and knowledge of the target progenitor cell populations. Vectors based on adeno-associated virus are the leading system for direct in vivo gene delivery but have limitations in targeting replicating cell populations such as in the adrenal cortex. One strategy to overcome this technological limitation is to deliver the relevant adrenocortical gene to a currently targetable organ outside of the adrenal cortex. To explore this possibility, we developed a vector encoding human 21-hydroxylase and directed expression to the liver in a mouse model of congenital adrenal hyperplasia. This extra-adrenal expression resulted in reconstitution of the steroidogenic pathway. Aldosterone and renin levels normalised, and corticosterone levels improved sufficiently to reduce adrenal hyperplasia. This strategy could provide an alternative treatment option for monogenic adrenal disorders, particularly for mineralocorticoid defects. These findings also demonstrate, when targeting the adrenal gland, that inadvertent liver transduction should be precluded as it may confound data interpretation.

N14 The IBD nurse's role in screening for iatrogenic adrenal insufficiency in children with inflammatory bowel disease on discontinuing glucocorticoid therapy

Abstract Background With a wide range of medical treatment on offer, ensuring patient safety by monitoring and or preventing side effects is a key part of holistic care. Glucocorticoids are widely used in inflammatory bowel disease (IBD) treatment to induce remission or treat flares. Iatrogenic adrenal insufficiency (AI), due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis is an established side effect of exogenous glucocorticoids. Symptoms of AI can range from life-threatening adrenal crisis to more subtle chronic symptoms including fatigue, abdominal pain and diarrhoea. The rate of AI in this population is unknown. There is no standard guidance or recommendations to suggest routine screening of paediatric IBD (pIBD) patients. This study aimed to report our experience on set up a monitoring pathway to manage pIBD patients coming off glucocorticoid therapy(GT). Methods A database was created to capture all IBD patients under the age of 18 who had received GT for IBD between March 2022 and July 2023. At the time of starting treatment, predicted last day on GT was identified and patients were booked in for testing serum early morning cortisol (Vitros Ortho Clinical Diagnostics immunoassay) and ACTH. After tapering, patients remained on the lowest dose of GT until results review. Evaluation of the adrenal-axis response was then assessed by a protocol piloted by this study – see figure 1. The patients needing treatment for AI were seen in the Nurse led clinic for prescribing, education and training. The training included IM injection training, sick day training and safety netting. To ensure safe evidence based training, the IBD nurse had received training form the endocrine nurse before the pilot. Results Following the initial screening, 9 patients were seen in the clinic with AI ( 8 prednisolone and 1 Budesonide). Of these 9,8 (88%) were followed up by the IBD nurse and 1(11%) was followed up by a local paediatrician with an endocrine interest. Treatment with hydrocortisone was commenced and follow up 3 months blood tests organised. The school was notified of the risk of Adrenal suppression and emergency kits provided. Repeat adrenal axis testing was offered at 3 months (5 of 9) and 6 months (3 of 9). AI was noted in 3 patients and 2 patients at 3 and 6-month respectively. At the 6 month mark, patients were discharged from the clinic if they had returned to a normal adrenal axis or referred to the endocrine team for further follow up. Patients were discussed in a multi-displinary meeting at every point on the pathway and no child suffered an adrenal crisis during the study period. Conclusion AI following GT is common in this small pIBD cohort. The IBD nurse can play a critical role in providing safe care for these patients.

Adrenal insufficiency (hypocorticism) on the background of adrenalectomy for corticosteroma

Adrenal insufficiency (AI) occurs after adrenalectomy for adrenal corticosteroma due to inhibition of the hypothalamicpituitary-adrenal axis and decreased function of the contralateral adrenal gland. Treatment of postoperative AI is based on glucocorticoid replacement therapy and is generally required in all patients with adrenalectomy for Cushing’s syndrome, but dosage and duration of treatment may vary. It is important to educate patients for self-adjustment of substitution therapy dosages and prevention of AI decompensation, it is especially important in this pathology. The article presents a clinical case of a patient with acute adrenal insufficiency that developed against the background of adrenalectomy for corticosteroma of the left adrenal gland.

THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism

Abstract Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None. Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (<1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size >4 cm, internal calcifications, and HU >10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was <0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events. Presentation: Thursday, June 15, 2023

SAT301 Patient-centered Outcomes Measures To Assess Quality Of Life In Adrenal Insufficiency Treatment

Abstract Disclosure: W.J. Hover: None. K.E. Lowe: None. M.E. Lowe: None. J.G. Kallet: None. M.F. Slovick: None. S.L. Majka: None. M.T. McDermott: None. E.A. Regan: None. Individuals with adrenal insufficiency (AI) have been shown to have reduced quality of life in spite of hormone replacement. Although late-stage insufficiency and adrenal crisis may show signs including hypotension and electrolyte abnormalities, patient-reported symptoms may predict outcomes in AI and can be a key factor in understanding poor quality of life in adrenal insufficiency. The SF-36, a generic quality of life (QoL) survey has been reported in adrenal insufficiency but may lack disease-specific domains to define QoL deficits in AI. An AI disease-specific QoL survey, the AddiQoL has also been validated. We evaluated the AddiQol and SF-36 for distinguishing the health status of AI patients in terms of diagnosis, medication use and risk of crisis using a patient registry. Methods: We identified 344 individuals from the MyAI patient registry who had provided responses to both the AddiQoL and SF-36. We compared the AddiQoL overall score with three domains of the SF-36: physical function, role physical, vitality, and the physical and mental component scores (PCS and MCS). Results: Respondents were from all 50 US states with 83% female and mean (SD) age of 50 (15) years. AI diagnosis was Primary 63%, Central 32% and congenital adrenal hyperplasia 5% based on self-report and confirmation with medical records. Both the SF-36 and AddiQoL identified reduced QoL in the AI participants and were significantly correlated: PCS to AddiQoL 0.73 and MCS to AddiQoL 0.63. Role Physical, Vitality and General Health were the most reduced domains with mean values of 38.4 (43.5), 35.6 (24.5) and 40.8 (24.7) respectively. Primary AI showed significantly better QoL than Central AI by both SF-36 and AddiQol [80.3(15.1) vs 69.9 (14.2), p<0.001]. Respondents who reported an adrenal crisis within the past year had significantly lower AddiQol [72.8(15.4) vs 82.3 (15.4), p<0.001] and SF-36 scores. Respondents who were currently treated with hydrocortisone (HC) had better QoL than those on Prednisone [HC 78.1 (15.2), Prednisone 74.1 (15.9), p=0.02 adjusted for diagnosis group]. Conclusions: In a geographically broad cohort of US AI patients, we confirm significant reductions in QoL in spite of treatment. Both the SF-36 and AddiQoL were able to distinguish differences in QoL by diagnosis, risk of adrenal crisis and medication. Further work to define specific patterns of high-risk symptoms may improve early diagnosis of impending crisis. Presentation: Saturday, June 17, 2023

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

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. To investigate whether the implementation of NBS has altered the time to diagnosis of AI in children with ALD. We conducted a retrospective medical chart review of pediatric patients with ALD. All patients were seen in a leukodystrophy clinic in an academic medical center. We included all pediatric patients with ALD who were seen between May 2006 and January 2022. We identified 116 patients (94% boys). We extracted information about ALD diagnosis in all patients and AI surveillance, diagnosis, and treatment in boys with ALD. 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. 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.

Modern possibilities and prospects in the treatment of adrenal insufficiency

Adrenal insufficiency (AI) is a life-threatening disease characterized by a decrease in the production of hormones by the adrenal cortex and requires lifelong replacement therapy with glucocorticoids (GCs) and, in some cases, mineralocorticoids (MCs). The number of individuals with primary and secondary AI in Europe is estimated at 20-50 per 100 thousand people, the increase in the number of cases of this disease in the world may be partly due to the rapid increase in the frequency of use of GC in various clinical strategies, including in oncological diseases.In AI, hormone replacement therapy is vital, but long-term use of GC may be associated with various adverse effects, especially at non-physiological concentrations of GC. This review provides a brief overview of the current therapeutic possibilities of AI hormone therapy, which contributes to the prevention of the development of adrenal crises, as well as promising opportunities for more effective imitation of the physiological profile of cortisol, aimed at preventing the development of undesirable effects of therapy. Several different forms of AI are currently available, differing in profile, duration of action, and route of administration. The most preferred currently in the treatment of AI are GCs with a short half-life, which provides a more manageable action profile and a lower risk of side effects. Promising substitution therapy options include modified-release hydrocortisone preparations, as well as new methods of drug administration using an insulin pump, which will better mimic the physiological effects of endogenous cortisol.

Steroid Use in the NICU: Treatment and Tapering

The adrenal gland cortex produces life-sustaining steroid hormones that are critical for the development and survival of the fetus and neonate. Antenatal and postnatal administration of steroids has critical therapeutic effects in preterm infants. However, prolonged postnatal steroid therapy for more than 1 to 2 weeks is associated with iatrogenic adrenal insufficiency and should prompt consideration of a steroid taper and stress dose precautions. In this review, we will describe fetal adrenal development and steroidogenesis, the effect of antenatal exogenous steroids, the therapeutic role of postnatal steroids, evaluation and treatment of adrenal insufficiency, and the role of steroid tapers after prolonged steroid treatment.

Delay in diagnosis of PD-1 Inhibitor induced Secondary adrenal Insufficiency

Introduction: Immune checkpoint inhibitors including PD-1 inhibitors, were initially approved for the treatment of metastatic melanoma but are now increasingly being used for different types of solid organ malignancies. Despite the important clinical benefits, they are associated with immune-related adverse events. The most critical endocrinopathy associated with PD -1 inhibitor is adrenal insufficiency (AI), which requires prompt diagnosis and management to avoid fatality. Case presentation: We present the case of a 78-year-old woman with colon adenocarcinoma treated with Nivolumab (PD-1 inhibitor) after her pulmonary metastases progressed on chemotherapy. She presented to the hospital with progressive generalized weakness, fatigue, headache, lightheadedness, nausea, myalgia, reduced oral intake. She had 2 prior hospitalizations on account of similar symptoms with workup negative for cancer progression or gastrointestinal obstruction. Her laboratory values showed Na 128mmol/L, K 3.4mmol/L, Cr 0.52mg/dL and blood sugar 42mg/dL. Morning cortisol was low at 2.2µg/dL and ACTH stimulation test was positive. She was diagnosed with AI secondary to Nivolumab use and was started on Hydrocortisone while Nivolumab was discontinued. Conclusion: Immune checkpoint inhibitors have a unique side effect profile of immune-related adverse events, the most critical of which is AI. However, the non-specific manifestations of AI can lead to misdiagnosis or delay in diagnosis. Therefore, it is important for physicians to have high index suspicion for AI in acutely ill patients on PD-1 inhibitors for prompt recognition, diagnosis and treatment of AI which is important to prevent life-threatening adrenal crisis.

Simultaneous Presentation of Secondary Adrenal Insufficiency and Primary Hypothyroidism due to Pembrolizumab: A Case Report.

Checkpoint inhibitors have gained increased traction in recent years as they have improved prognosis in various malignancies. Pembrolizumab, an anti-programmed cell death protein (PD-1) monoclonal antibody, has become a first-line chemotherapeutic agent for stage II non-small cell lung cancer since 2019. Although much more common with nivolumab, several immune-related adverse effects, particularly endocrinopathies, have been linked with pembrolizumab. We describe a case of a 59-year-old man with a history of unspecified lung cancer who presented with severe hyponatremia later attributed to secondary adrenal insufficiency and accompanying primary hypothyroidism secondary to pembrolizumab. Diagnosing adrenal insufficiency in patients on immune checkpoint inhibitors like pembrolizumab can be challenging due to nonspecific symptoms, making it crucial to rule out other causes of hyponatremia. Immunotherapy is known to cause thyroid immune-related adverse events, and anti-thyroid antibodies may not always be present in the diagnosis of hypothyroidism. Although there are some reported cases of pembrolizumab-induced adrenal insufficiency, the link between immunotherapy and endocrine disorders remains unclear. To our knowledge, no case reports exist that describe both primary hypothyroidism and secondary adrenal insufficiency after taking pembrolizumab, although such cases have been documented with axitinib. Timely diagnosis and treatment of adrenal insufficiency is crucial to prevent adverse effects, especially in patients with cancer receiving immunotherapy, as highlighted in this case.

Significant risk of COVID-19 and related-hospitalization among patients with adrenal insufficiency: A large multinational survey.

To determine self-reported incidence and potential risk factors for COVID-19 in patients with adrenal insufficiency (AI). A 27-item AI survey was developed for AI and COVID-19 status, vetted by specialists and patients, and distributed via social media, websites, and advocacy groups. Participation was voluntary and anonymous. Data were collected from September 20th, 2020 until December 31st, 2020. Respondents (n=1291) with self-reported glucocorticoid treatment for AI, completed the survey, with 456 who reported having symptoms and were screened for COVID-19 during 2020; 40 tested positive (+ve), representing an 8.8% incidence. Of the COVID-19+ve, 31 were female (78%), with mean age of 39.9 years. COVID-19 among AI patients occurred most commonly in those aged 40-59 years (n=17; 42.5%); mean time since AI diagnosis was 13.5 years (range 0.2-42.0 years). Pulmonary disease, congenital adrenal hyperplasia, and higher maintenance doses of glucocorticoids were significantly associated with +ve COVID-19 (p=0.04, p=0.01, and p=0.001, respectively. In respondents the cumulative incidence of COVID-19+ve during 2020 was 3.1%; greater than the 1.03% worldwide-incidence reported by WHO, by December 31st, 2020. There was a 3-fold (95% CI 2.16-3.98) greater relative risk (RR) of COVID-19 infection and a 23.8- fold (95% CI 20.7-31.2) RR of hospitalization in patients with AI, compared with the global population. A markedly raised RR of COVID-19 and hospitalization in respondents reporting chronic AI was detected. We found that a diagnosis of congenital adrenal hyperplasia, age>40 years, male gender, pulmonary disease, and higher maintenance doses of glucocorticoids were associated with greatest risk.

Treatment of adrenal insufficiency in the netherlands from a patient perspective in the recent past. Lessions learned for europe

Treatment of adrenal insufficiency in the netherlands from a patient perspective in the recent past. Lessions learned for europe

Neonatal bilateral adrenal hemorrhage and adrenal insufficiency accompanied by Subgaleal hematoma: a case report with brief review of literature

BackgroundNeonatal adrenal hemorrhage (NAH) is an almost infrequent phenomenon (0.2–0.55%). Mechanical compression and alterations of venous pressure during delivery are considered the most probable explanations. Approximately 10% of the cases might have bilateral involvement. Clinical symptoms include abdominal mass, poor feeding, vomiting, prolonged jaundice, and anemia. Subgaleal hemorrhage (SGH) is one of the most clinically remarkable and potentially hazardous postnatal cranial injuries.Case presentationAn early-term Iranian male neonate who was born through spontaneous vaginal delivery and experienced shoulder dystocia was diagnosed with bilateral NAH leading to adrenal insufficiency requiring glucocorticoid and mineralocorticoid supplementation. The SGH and jaundice were other postnatal complications. Serial monthly abdominal and brain ultrasound revealed complete regression of lesions after 70 days. However, after 16 months, the neonate has been still treated with hydrocortisone and fludrocortisone for the adrenal insufficiency diagnosis. He has a lower limit weight for age; however, developmental milestones have been appropriate for age.Discussion and conclusionAdrenal hemorrhage and SGH should be examined and looked for, particularly with proven evidence of difficult delivery and asphyxia in at-risk newborns. Clinical and ultrasound follow-up is mandatory for the assessment of hemorrhage resolution and conservative management. The early detection and treatment of adrenal insufficiency by laboratory examination is strongly recommended in bilateral cases. Furthermore, the early recognition of postnatal SGH to prevent clinical and neurological outcomes seems essential.

AACE2021-A-1022: Management of Adrenal Insufficiency: Survey of Physicians’ from the Middle East and North Africa

Treatment of adrenal insufficiency (AI) requires correct lifelong use of glucocorticoids with early dose adjustments to cover the increased demand in stress to avoid life-threatening emergencies. We aimed to determine physicians' knowledge on the pathophysiological and clinical aspects of AI in the two regions of North Africa and the Middle East. An electronic questionnaire on physiology, pharmacology, and clinical management of AI of 96 participants. Half of the participants were attending physicians, and 44,.2% practiced adult endocrinology. Knowledge of physiology and pharmacology of GC hormones (e.g., normal, daily cortisol production and half-life of hydrocortisone (HC) was variable. Physicians' patterns in prescribing and monitoring the adequacy of glucocorticoid (GC) replacement therapy revealed that the majority (81.3%) identified HC preparations for use in GC replacement therapy, followed by prednisone/prednisolone (46.9%), longer-acting prednisolone formulations (13.5%), and Dexamethasone (13.5%). The most frequently reported sign for GC under-replacement was “nausea” (84.4%), followed by “weight loss” (81.3%), “headaches” (44.8%) and “sleep disturbances” (36.5%). The most frequently reported for GC over-replacement was “high blood pressure” (91.6%), followed closely by “weight gain” (90.5%) and “increased blood glucose” (86.3%). A few, 6.3% and 3.2% of respondents considered “weight loss” and “low blood pressure” as symptoms of GC over-replacement, respectively. The situations most frequently identified as necessary for adjustments of GC dosages were "acute severe disease" (92.7%) and "fever more than 38°C" (79.2%) during acute severe disease, dose increase 2-5-fold by 77.1% of respondents. Strangely, some respondents reported dose reduction or even omission. The majority (80.9%) identified the need for emergency, standby medications for patients with AI. Additionally, 94.7% reported the need to issue an emergency card, and 80.9% reported the need for relative and friends' education regarding AI. When traveling, packing adequate GC preparations would be recommended by 90.5%, emergency card (89.5%), and emergency medications (70.5%). In the investigated settings, physicians’ knowledge of physiology and pharmacology of glucocorticoids, medical replacement strategies in AI, and prevention of adrenal crisis may be insufficient. There is a need for more education and training on AI in both medical and endocrine forums.

Management of adrenal insufficiency: A survey of perceptions and practices of physicians from the Middle East and North Africa

Introduction: Treatment of adrenal insufficiency (AI) requires correct lifelong use of glucocorticoids (GCs) with early dose adjustments to cover the increased demand in stress to avoid life-threatening emergencies. Objectives: We determine the current specific knowledge of physicians in a convenience sample on the pathophysiological and clinical aspects of AI in the two regions of North Africa and the Middle East. Materials and Methods: Participants (n = 96) were invited to complete an electronic questionnaire with various possible answers on the subject of multiple-choice questions covering physiology, pharmacology, and clinical management and define respondents' professional profiles. Results: The present study suggests that in the investigated settings, physicians' knowledge of physiology and pharmacology GCs, medical replacement strategies in AI, and prevention of adrenal crisis may be insufficient. Great knowledge gaps were demonstrated. Conclusions: There is a need for continuous structured education and training on AI in both general medical and endocrine forums.

The Efficacy, Safety, and Side Effects of Intrapericardial Triamcinolone Treatment in Children with Post-surgical Pericardial Effusion: A Case Series

Intrapericardial triamcinolone can be used to treat chronic pericardial effusion (PE) in adults; however, pediatric data are lacking. In this case series we aim to evaluate the efficacy, safety, and side effects of intrapericardial triamcinolone in children with PE. The incidence and treatment of post-surgical PE from 2009 to 2019 were determined using the institutional surgical database and electronic patient records. Furthermore, a retrospective analysis of efficacy, safety, and side effects of intrapericardial triamcinolone treatment for chronic post-surgical PE was performed. The incidence of postoperative PE requiring treatment was highest after atrial septal defect (ASD) closure when compared to other types of cardiac surgery (9.7% vs 4.3%). Intrapericardial treatment with triamcinolone resolved pericardial effusion in 3 out of 4 patients. All patients developed significant systemic side effects. Surgical ASD closure is associated with an increased risk of development of PE requiring treatment. Intrapericardial triamcinolone is an effective treatment for chronic postoperative PE in children, but is always associated with significant systemic side effects. Close monitoring and treatment of adrenal insufficiency are mandatory in these cases.

Characteristics of preoperative steroid profiles and glucose metabolism in patients with primary aldosteronism developing adrenal insufficiency after adrenalectomy

Treatment of choice in patients with unilateral aldosterone producing adenoma (APA) is adrenalectomy. Following surgery, most patients retain normal adrenal function, while some develop adrenal insufficiency (AI). To facilitate early detection and treatment of AI, we aimed to identify variables measured pre-operatively that are associated with post-operative AI. Variables obtained from 66 patients before and after surgery included anthropometrical data, clinical chemistry, endocrine work-up. LC–MS/MS steroid hormone profiles from tests before surgery (ACTH-stimulation, saline infusion, dexamethasone suppression) were obtained. Based on 78 variables, machine-learning methods were used in model fitting for classification and regression to predict ACTH-stimulated cortisol after surgery. Among the 78 variables, insulin concentration during pre-operative oral glucose tolerance test (OGTT) correlated positively, and dexamethasone suppressed glucocorticoids correlated negatively with ACTH-stimulated cortisol after surgery. Inclusion of LC–MS/MS measurements allowed construction of better models associated with the occurrence of AI in the training data, but did not allow reliable prediction in cross-validation. Our results suggest that glucocorticoid co-secretion (low insulin during pre-operative OGTT and insufficient suppression of glucocorticoids following dexamethasone) are correlated with the development of post-operative AI. Addition of steroid profiles improved the accuracy of prediction, but cross validation revealed lack of reliability in the prediction of AI.

Long-term corticosteroid use, adrenal insufficiency and the need for steroid-sparing treatment in adult severe asthma.

Secondary adrenal insufficiency (AI) occurs as the result of any process that disrupts normal hypothalamic and/or anterior pituitary function and causes a decrease in the secretion of steroid hormones from the adrenal cortex. The most common cause of secondary AI is exogenous corticosteroid therapy administered at supraphysiologic dosages for ≥ 1 month. AI caused by oral corticosteroids (OCS) is not well‐recognized or commonly diagnosed but is often associated with reduced well‐being and can be life‐threatening in the event of an adrenal crisis. Corticosteroid use is common in respiratory diseases, and asthma is a representative condition that illustrates the potential challenges and opportunities related to corticosteroid‐sparing therapies. For individuals with severe asthma (approximately 5%–10% of all cases), reduction or elimination of maintenance OCS without loss of control can now be accomplished with biologic therapies targeting inflammatory mediators. However, the optimal strategy to ensure early identification and treatment of AI and safe OCS withdrawal in routine clinical practice remains to be defined. Many studies with biologics have involved short evaluation periods and small sample sizes; in addition, cautious approaches to OCS tapering in studies with a placebo arm, coupled with inconsistent monitoring for AI, have contributed to the lack of clarity. If the goal is to greatly reduce and, where possible, eliminate long‐term OCS use in severe asthma through the increasing adoption of biologic treatments, there is an urgent need for clinical trials that address both the speed of OCS withdrawal and how to monitor for AI.

A Predictive Risk Score to Diagnose Adrenal Insufficiency in Outpatients: A 7 Year Retrospective Cohort Study

Background: The diagnosis of adrenal insufficiency (AI) requires dynamic tests which may not be available in some institutions. This study aimed to develop a predictive risk score to help diagnose AI in outpatients with indeterminate serum cortisol levels. Methods: Five hundred and seven patients with intermediate serum cortisol levels (3–17.9 µg/dL) who had undergone ACTH (adrenocorticotropin) stimulation tests were included in the study. A predictive risk score was created using significant predictive factors identified by multivariable analysis using Poisson regression clustered by ACTH dose. Results: The seven predictive factors used in the development of a predictive model with their assigned scores are as follows: chronic kidney disease (9.0), Cushingoid appearance in exogenous steroid use (12.0), nausea and/or vomiting (6.0), fatigue (2.0), basal cortisol <9 µg/dL (12.5), cholesterol <150 mg/dL (2.5) and sodium <135 mEq/L (1.0). Predictive risk scores range from 0–50.0. A high risk level (scores of 19.5–50.0) indicates a higher possibility of having AI (positive likelihood ratio (LR+) = 11.75), while a low risk level (scores of <19.0) indicates a lower chance of having AI (LR+ = 0.09). The predictive performance of the scoring system was 0.82 based on the area under the curve. Conclusions: This predictive risk score can help to determine the probability of AI and can be used as a guide to determine which patients need treatment for AI and which require dynamic tests to confirm AI.