Adrenal Insufficiency Research Articles

A-099 Case Study of a Patient With Heterophile Antibodies Interfering with Both Competitive and Immunometric Assays

Abstract Background Immunoassay results may be affected by the presence of interfering substances including heterophile antibodies. These heterophile antibodies can cause either an increase or decrease in the result based on assay design and antibody target. We report a case study wherein we identified several analytes whose results were either increased or decreased by heterophile antibodies in a patient. Methods 74 year male presented to Endocrinology with history of hypocalcemia and his previous lab tests were suggestive for idiopathic hypoparathyroidism, Hashimoto’s disease and Addison’s disease raising physician concern for a possible Type 1 autoimmune endocrinopathy. Cortisol was ordered (for an ACTH stimulation test for adrenal insufficiency); upon testing the post-stimulation cortisol result was higher than the analytical measurement range (AMR), and so the sample was diluted 1:2 and repeated. The repeat cortisol result after correction for the dilution factor was well within the AMR and prompted an investigation for an interfering substance. Serial dilution of analytes was performed and send-out testing for the same with another immunoassay from a different manufacturer and/or mass spectrometry method where available were done. Results The results for most analytes did not match with the reference lab results. Serial dilution showed non-parallelism in the results. For most analytes, after dilution of the sample by 1:4 or 1:8 times, the interfering substance was diluted enough to obtain a result matching the reference lab result. Conclusions Based on non-parallelism in serial dilution results, discordant results with other methods, and loss of interference after dilution it was determined that the most likely cause was a heterophile antibody. Formal testing using blocking antibodies was not done as it seemed that the reference lab used did not run our method and their assays were not affected by this particular heterophile antibody. Analysis of the assay designs and analyte results showed that competitive assays showed falsely high results, while immunometric assays showed falsely low results. The physician was contacted and the case discussed in detail and it was recommended that further testing on this individual be sent out to a reference lab using the alternate method or to use mass spectrometry based assays for further testing if needed. Today, the patient continues to have low calcium, high phosphate and an undetectable PTH suggestive of idiopathic hypoparathyroidism but his other endocrine functions are within normal limits.

Adrenocortical insufficiency after bilateral adrenal hemorrhage due to anticoagulation and chronic immunothrombocytopenia.

Adrenocortical insufficiency is defined as the clinical manifestation of chronic glucocorticoid and/or mineralocorticoid deficiency due to failure of the adrenal cortex. It may result in an adrenal crisis, which is a life-threatening disease; thus, prompt initiation of therapy with hydrocortisone is necessary. Symptoms such as hypotension, weight loss, or fatigue are not specific, which is why diagnosis is delayed in many cases. Our patient suffered from immune thrombocytopenia (ITP), an acquired thrombocytopenia caused by an autoimmune reaction against platelets and megakaryocytes. Primary ITP, in which no triggering cause can be identified, must be distinguished from secondary forms (e.g. in the context of systemic autoimmune diseases, lymphomas, or (rarely) by drugs). Patients may be asymptomatic at presentation or may present with a range of mild mucocutaneous to life-threatening bleeding. Here, we report on a 43-year-old woman who had developed adrenocortical insufficiency due to bilateral hemorrhage in the adrenal glands. Because of anticoagulation with phenprocoumon after pulmonary embolism and thrombocytopenia on the basis of ITP, the patient had an increased risk of bleeding. Due to the nonspecific and ambiguous symptoms of adrenocortical insufficiency, prompt diagnosis remains a challenge. Hypocortisolism or adrenal crisis with nonspecific symptoms, especially abdominal and gastrointestinal, is often misinterpreted. Diagnosis of adrenal insufficiency is often delayed because of the initial ambiguous presentation; physicians must be aware to avoid adrenal crisis. Especially in patients with several risk factors for bleeding, unusual bleeding manifestations, such as adrenal hemorrhage, must be considered. Immediate treatment is necessary by substituting hydrocortisone in a higher dosage, and in most cases, fludrocortisone. During the course of treatment, the amount of hydrocortisone can be reduced to a substitution dosage (15-25 mg/day divided into two to three doses/day). Fludrocortisone should be continued at a dosage of 0.05-0.1 mg/day, depending on blood pressure and sodium and potassium levels. All patients should carry a medical alert notification or a steroid emergency card. In the case of trauma, surgery, or other stressful events, hydrocortisone must be administered in higher dosages (e.g. 100 mg i.v.).

Practical Approach to Longitudinal Neurologic Care of Adults With X-Linked Adrenoleukodystrophy and Adrenomyeloneuropathy.

Although X-linked adrenoleukodystrophy (ALD) has historically been considered a childhood disease managed by pediatric neurologists, it is one of the most common leukodystrophies diagnosed in adulthood. An increase in both male and female adults reaching diagnosis due to familial cases identified by state newborn screening panels and more widespread use of genetic testing results in a large cohort of presymptomatic or early symptomatic adults. This population is in urgent need of standardized assessments and follow-up care. Adults with ALD/adrenomyeloneuropathy (AMN) may be diagnosed in a variety of ways, including after another family member is identified via genetic testing or newborn screening, presenting for symptomatic evaluation, or following diagnosis with primary adrenal insufficiency. Significant provider, patient, and systems-based barriers prevent adult patients with ALD/AMN from receiving appropriate care, including lack of awareness of the importance of longitudinal neurologic management. Confirmation of and education about the diagnosis should be coordinated in conjunction with a genetic counselor. Routine surveillance for adrenal insufficiency and onset of cerebral ALD (CALD) in men should be performed systematically to avoid preventable morbidity and mortality. While women with ALD do not usually develop cerebral demyelination or adrenal insufficiency, they remain at risk for myeloneuropathy and are no longer considered "carriers." After diagnosis, patients should be connected to the robust support networks, foundations, and research organizations available for ALD/AMN. Core principles of neurologic symptom management parallel those for patients with other etiologies of progressive spastic paraplegia. Appropriate patient candidates for hematopoietic stem cell transplant (HSCT) and other investigational disease-modifying strategies require early identification to achieve optimal outcomes. All patients with ALD/AMN, regardless of sex, age, or symptom severity, benefit from a multidisciplinary approach to longitudinal care spearheaded by the neurologist. This review proposes key strategies for diagnostic confirmation, laboratory and imaging surveillance, approach to symptom management, and guidance for identification of appropriate candidates for HSCT and investigational treatments.

S4929 Adrenal Insufficiency in Addison's Disease - A New Potential Pathway for Developing Nonocclusive Mesenteric Ischemia

S4929 Adrenal Insufficiency in Addison's Disease - A New Potential Pathway for Developing Nonocclusive Mesenteric Ischemia

7333 Does Allgrove Syndrome Have Endocrine Manifestations Beyond Adrenal Insufficiency?

7333 Does Allgrove Syndrome Have Endocrine Manifestations Beyond Adrenal Insufficiency?

Initial treatment efficacy and safety of durvalumab plus tremelimumab combination therapy in unresectable hepatocellular carcinoma in clinical practice.

We aimed to evaluate the efficacy and safety of durvalumab plus tremelimumab (Dur + Tre) combination therapy in patients with unresectable hepatocellular carcinoma (uHCC) in clinical practice. We retrospectively evaluated 37 patients with uHCC from our institutions between April 2023 and January 2024. Patients were divided into first- and later-line groups for analysis of antitumor efficacy, adverse events (AEs), and transition rate to second-line treatment according to the Response Evaluation Criteria in Solid Tumors (RECIST). The disease control rate (DCR) for the first-line group was 80.9%, which was significantly higher than that for the later-line group (50%). The incidence of immune-related AEs (irAEs) was 24.3%, with grade 3 or higher irAEs including increased transaminase (8.1%), diarrhea (8.1%), and adrenal insufficiency (2.7%). The rates of drug withdrawal and discontinuation owing to AEs were 23.8% and 19%, respectively, in the first-line treatment and 31.2% and 12.5%, respectively, in the later-line treatment, with no significant difference. Analysis of changes in liver reserve using the albumin-bilirubin (ALBI) score showed no obvious loss of liver reserve for up to 12 weeks. The transition rate from first- to second-line therapy after progressive disease (PD) was as high as 94.7%. The efficacy and safety of Dur + Tre in clinical practice were comparable to those reported in a recent phase III trial. The first-line Dur + Tre therapy had a higher DCR than that of the later lines, and the transition rate to second-line therapy was considerably high, suggesting that Dur + Tre therapy would be more beneficial in first-line treatment.

Glucocorticoid treatment and adrenal suppression in children: current view and open issues.

Glucocorticoids (GCs) are commonly used for several acute and chronic pediatric diseases. However, chronic treatment may result in hypothalamic-pituitary-adrenal axis (HPA) dysfunction. Glucocorticoid-induced adrenal insufficiency (GI-AI) is indeed the most frequent cause of adrenal insufficiency (AI) in children, possibly resulting in a life-threatening event such as adrenal crisis (AC). It is generally underestimated, especially when using non-systemic glucocorticoid formulations. This review aims at summarizing current evidence on the effects of long-term GC treatment on the HPA axis, management of GC tapering and assessment of the HPA recovery. We conducted a narrative review of the relevant literature focusing on pathogenic mechanisms, predictive factors, diagnosis and treatment of GI-AI. All types of GCs, whatever the route of administration, may have suppressive effects on the HPA axis, especially when compounds with higher potency and long half-life are used. Moreover, chronic GC administration is the most common cause of Cushing syndrome in children. In order to overcome the risk of GI-AI, slow withdrawal of GCs is necessary. When approaching the replacement dose, it is recommended to switch to shorter half-life formulations such as hydrocortisone. Assessment of HPA axis recovery with basal and stimulated cortisol levels may help detecting children at risk of AC that may require hydrocortisone supplementation. The management of GI-AI in children is challenging and many areas of uncertainty remain. Improving the knowledge on long-term GC effects on HPA in children, the management of steroid discontinuation and emergency dosing may help preventing GI-AI symptoms and acute hospital admission for AC.

6571 Tracking Emotional Well-being And Hormonal Interactions In Adrenal Insufficiency Through Ecological Momentary Assessment

6571 Tracking Emotional Well-being And Hormonal Interactions In Adrenal Insufficiency Through Ecological Momentary Assessment

Screening for Addison's disease through baseline cortisol levels in type 1 diabetic patients with recurrent hypoglycemia

Screening for Addison's disease through baseline cortisol levels in type 1 diabetic patients with recurrent hypoglycemia

Investigating the Clinical Appropriateness of Short Synacthen Testing and Utility of Pretest Cortisol to Predict Short Synacthen Testing Outcomes: A Tertiary Center Experience in Southeast Asia

ObjectiveNo studies have investigated the predictors of an adequate cortisol response to the short synacthen test (SST) and the appropriateness of patient selection for SST in the Southeast Asian population. The aim of our study is to investigate the predictors and indications of SSTs and concondance of SSTs conducted with outcomes. MethodsThis is a retrospective study investigating all SSTs performed over a year in a tertiary center. Clinical data of patients with SSTs between February 2022 and February 2023 were extracted. We determined the appropriateness of SST testing. Binary logistic regression was used to assess the parameters that predict adequate cortisol response on SST. The proportion of individuals with biochemical “pass” or “fail” on SST was compared with the Χ2 test. Baseline cortisol levels that predicted SST pass were determined using area under receiving operating characteristics curves. ResultsOf the 781 SSTs, 83.9% of SSTs showed an adequate cortisol response. Postural hypotension (26.9%) and exogenous glucocorticoid administration (14.2%) were common indications for SST. In our cohort, 50.2% of the SSTs were inappropriately indicated. Pretest serum cortisol and albumin predict biochemical pass on SST. A pretest cortisol level of 300 nmol/L predicted SST response with 93% sensitivity and a cortisol level of <100 nmol/L confirmed adrenal insufficiency (AI) with 97.3% specificity. Using these cortisol thresholds could avoid 302 (38.5%) of SSTs. ConclusionOur analysis showed that clinical features of AI do not reliably predict SST outcomes. We advocate careful assessment of the pretest probability of AI in patients referred for SST. A pretest cortisol level can reduce the number of SSTs, with cost savings implications.

8482 Genetic Aetiology Of Primary Adrenal Insufficiency In Sudan

8482 Genetic Aetiology Of Primary Adrenal Insufficiency In Sudan

8695 What Comes Fast, Goes Fast: Acute Megestrol Acetate Induced Adrenal Insufficiency

8695 What Comes Fast, Goes Fast: Acute Megestrol Acetate Induced Adrenal Insufficiency

8555 Hourly Assessment Of Symptoms In 16 Adrenal Insufficiency Patients Correlates With AddiQoL

8555 Hourly Assessment Of Symptoms In 16 Adrenal Insufficiency Patients Correlates With AddiQoL

7705 Paliperidone Induced Central Adrenal Insufficiency: A Case Report

7705 Paliperidone Induced Central Adrenal Insufficiency: A Case Report

6665 A Case of Exogenous Cushing Syndrome and Acute Adrenal Insufficiency from Usage and Subsequent Withdrawal of Unregulated Glucocorticoid Supplement Ardosons

6665 A Case of Exogenous Cushing Syndrome and Acute Adrenal Insufficiency from Usage and Subsequent Withdrawal of Unregulated Glucocorticoid Supplement Ardosons

NEONATAL ADRENAL HEMORRHAGE

Introduction: Adrenal hemorrhage is a rare condition in the neonatal period. The significant size of the adrenal gland and its particular hypervascularization are predisposing factors for bleeding, especially in cases of trauma or vascular thrombosis (of the renal vessels or the inferior vena cava). The aim of this study is to analyze the medical records to perform a descriptive study of neonates hospitalized in the Neonatology and Neonatal Resuscitation Department of CHU Hassan II in Fez. Method:The cross-sectional study included all cases of neonates diagnosed with adrenal hemorrhage based on renal ultrasounds performed at the Neonatology and Neonatal Resuscitation Department of CHU Hassan II in Fez, between January 2016 and December 2023. Result: Sixteen cases of adrenal hemorrhage were identified. The incidence of adrenal hemorrhage during the study period within the department was 2 per 1,000 hospitalizations. Both sexes are equally affected, with a male predominance of 62.5%. The two main reasons for hospitalization in our series were perinatal asphyxia and jaundice. Uterine expression was reported in 87.5% of cases. The most common clinical signs, in order of frequency, are: jaundice (56.25%), abdominal mass (50%), skin and mucous membrane pallor (31.25%), fever (31.25%), respiratory distress (31.25%), and fractures in 6.25% of cases. Severe hyperbilirubinemia was found in 3 patients, accounting for 18.75%. Anemia was found in 6 patients, or 37.5%. Adrenal insufficiency was observed in 3 cases, or 18.75%. Abdominal ultrasound was performed on all patients, revealing right adrenal hemorrhage in 8 cases, left in 5 cases, and bilateral in 3 cases. The outcome was favorable in 81.25% of cases, while 18.75% of patients died. Conclusion: Adrenal hematoma is a rare condition in the neonatal period but can be severe, which justifies systematically searching for it in the presence of risk factors. Abdominal ultrasound is the key diagnostic test. The condition typically resolves spontaneously after several weeks.

Pathophysiology of Hyponatremia in Preterm Infants with Relative Adrenal Insufficiency after the Early Neonatal Period.

Preterm infants often develop relative adrenal insufficiency (RAI) not only within the early neonatal period but also beyond this period. RAI is commonly accompanied by hyponatremia, but the pathogenesis of hyponatremia with RAI has not been clarified. This study aimed to investigate the pathophysiology of hyponatremia in infants with RAI. This is a single-centered retrospective cohort study. Preterm infants born at <30 weeks of gestation or birth weight <1,000 g were enrolled. They were divided into the RAI group and the non-RAI group. The data of serum and urine examination, the amount of sodium intake, and fractional excretion of sodium (FENa) were compared between the two groups. In the RAI group, data before and after the administration of hydrocortisone were also compared. Sixteen infants in the RAI group and 35 infants in the non-RAI group were included in the analysis. In the RAI group, hyponatremia was common and preceded other clinical symptoms, such as oliguria and decreased blood pressure, therefore, hyponatremia with RAI was not likely to be caused by dilution due to oliguria. There was no difference in the FENa between the two groups (adjusted for postconceptional age at examination), therefore, it is not likely that hyponatremia with RAI was mainly caused by excessive renal sodium loss. Since sodium intake was rather higher in the RAI group than in the non-RAI group, it is unlikely that insufficient sodium supplementation was the cause of RAI. Hyponatremia with RAI was considered to be likely caused by vascular hyperpermeability. Hyponatremia is a common symptom among preterm infants with RAI and its pathogenesis can be vascular hyperpermeability. · The pathogenesis of hyponatremia with RAI can be vascular hyperpermeability.. · Hyponatremia is common among preterm infants with RAI.. · Hyponatremia with RAI preceded other clinical symptoms..

Immune checkpoint inhibitor induced hypophysitis: a specific disease of corticotrophs?

The aim of this study was to define functional and anatomical pituitary disease at the time of presentation following immune checkpoint inhibitor (ICI) therapy and to describe any changes in pituitary function over time. We conducted a retrospective observational audit of patients on ICI therapy at our centre between January 2013 and September 2023. We reviewed all patients on ICI therapy under the care of the oncology department at University Hospital Plymouth, a 1000-bedded hospital serving a population of 500,000 people. From this group, we identified all individuals referred to the endocrinology department with a suspected diagnosis of adrenal insufficiency. Patients were established on adrenal steroid replacement and subsequently underwent formal pituitary testing. People were included if they had pituitary disease, as evidenced by low ACTH, other pituitary dysfunction and/or abnormalities on pituitary imaging. Nine hundred and fifty-four patients received ICI therapy during the study period, and 37 (a prevalence of 3.9%) developed hypothalamic-pituitary-adrenal axis dysfunction. Their mean age was 65 years, and 70% were male. About 86.5% of the total patients affected were treated for metastatic malignancies. Ten of the 37 patients died during follow-up as a direct consequence or complication of their primary cancer diagnosis. The median interval for the onset of symptoms was 4 months. Following repeated testing, there was no recovery in cortisol or ACTH levels for any individual. Other permanent anterior pituitary hormone defects were unusual. Hypophysitis associated with immunotherapy appears to specifically target the corticotrophs, with no evidence of recovery over time. There was a specific abnormality seen in MRI scans of 7 of 27 patients who had scans, which appeared to be a particular feature of immune-mediated hypophysitis. These were confined to the anterior aspect of the pituitary gland, appearing as striations, and were not visible on any of the scans performed more than 3 months after the likely onset of the disease. These data show that immune-related hypophysitis is a common complication of immune checkpoint inhibitor therapy. This may result in an imaging abnormality within the areas of the pituitary that are richest in corticotrophs. The endocrine consequence of this is a permanent defect in ACTH and, therefore, cortisol production.

Whitaker syndrome: A case report of autoimmune polyendocrine syndrome type 1 with dilated cardiomyopathy.

This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS-1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow-up are crucial in managing these atypical presentations to optimize patient outcomes. APS-1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS-1 are infrequently reported in the literature. We present a case of a 28-year-old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x-ray showed left-sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS-1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS-1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients.

QUALITY OF LIFE IN CHILDREN AND ADOLESCENTS WITH CONGENITAL ADRENAL HYPERPLASIA

BACKGROUND: Congenital Adrenal Hyperplasia (CAH) is a hereditary endocrine condition, defined by insufficiency of enzymes that cause abnormalities in adrenal steroidogenesis, resulting in adrenal insufficiency and hyperandrogenism. In adults, Congenital Adrenal Hyperplasia has been linked to a lower quality of life (QoL). However, research in children has yielded inconsistent results. Therefore, this study was conducted to investigate the impact of CAH on the quality of life of children and adolescents. OBJECTIVE: To assess the Quality of Life of children and adolescents with Congenital Adrenal Hyperplasia (CAH). METHODS: It was a descriptive cross-sectional study with six months duration. We enrolled all children and adolescents in the range of 8 to 18 years of age who have been diagnosed with CAH. The World Health Organization Quality of Life-BREF (QOL-BREF) instrument was used for data collection. Four health domains including physical, psychological, social, and environmental areas were assessed, with higher transformed scores indicating better QOL. Data was entered on SPSS Version 23. RESULTS: Our study population comprised of 30 children and adolescents with a mean age of 12.75 ±3.23 years. Mean transformed scores of physical, psychological, social, and environmental health domains were 31.37±12.15, 45.13±12.50, 34.8±20.49 and 37.6± 12.06 respectively. CONCLUSION: The quality-of-life score in our population was relatively low in the physical and social domains of health as compared to psychological and environmental health domains. Larger community-based studies are required to further elaborate the causes and remedies of poor quality of life in children and adolescents.