Screening For Insufficiency Research Articles

Clinical and Analytical Comparison of Monoclonal and Polyclonal Immunoassays for Fecal Pancreatic Elastase.

Numerous immunoassays have been commercialized to determine pancreatic elastase (PE) in feces in screening for exocrine pancreatic insufficiency (EPI), but how the different assays compare to one another is controversial, especially in the context that all methods use the same cut-off values for interpreting the results obtained on the presence or absence of EPI or the degree of insufficiency if it is present. Our aim was to analytically verify a new method for determining PE, compare the results with a previous method, and verify the declared cut-off values for interpretation of the results. PE in the stool was assayed using a previous monoclonal enzyme-linked immunosorbent assay ("ScheBo ELISA") and a new polyclonal particle-enhanced turbidimetric immunoassay ("Bühlmann PETIA"). The direct method comparison of two immunoassays was performed in 40 samples. Clinical comparisons were conducted against each other for the binary determination of "abnormal/normal" elastase levels and the three-way determination of "severe/moderate/no" EPI in 56 samples. The indirect comparison method used external quality assessment (EQA) data to compare the monoclonal and polyclonal immunoassays for PE, and additionally compare the monoclonal ScheBo ELISA to a monoclonal chemiluminescence immunoassay ("DiaSorin CLIA"). Precision in the series and intra-laboratory precision for Bühlmann PETIA met the manufacturer's specifications for the concentration range of limit/lower values and the range of normal values. The Bühlmann PETIA immunoassay on different analytical platforms yielded comparable results and nearly perfect agreement in the case of three-way classification (kappa = 0.89 with 95%CI from 0.79 to 1.00. ScheBo ELISA tends to generate higher values of pancreatic elastase than the Bühlmann PETIA; agreement between the methods was moderate in the case of binary classification (kappa = 0.43; 95% CI 0.25 to 0.62), and substantial in the case of three-way classification (kappa = 0.62; 95% CI 0.50 to 0.75). EQA data analysis showed a statistically significant difference between ScheBo ELISA and Bühlmann PETIA peer groups (p = 0.031), as well as the DiaSorin CLIA and ScheBo ELISA peer groups (p = 0.010). The ScheBo ELISA and Bühlmann PETIA do not appear to be commutable in the analytical and clinical context. Our data address a discordance between different mono- and polyclonal immunoassays for pancreatic elastase and the potential of misclassification using its universal cut-off values in screening suspected patients for exocrine pancreatic insufficiency.

Screening for undiagnosed pancreatic exocrine insufficiency (PEI) in a cohort of diabetic patients using faecal elastase testing and PEI scoring system.

Type 1 and type 2 diabetes mellitus (DM) are often accompanied by mild forms of pancreatic exocrine insufficiency (PEI). The prevalence rates of PEI in diabetic patients are unclear and variable depending on the testing modality and the studies published. The clinical consequences of PEI in diabetics are also not well defined. We aimed to determine the prevalence of PEI in a diabetic cohort using the faecal elastase-1 (FE-1) assay as a screening test and to validate a patient-reported symptom-based scoring system, the (PEI-S) for diagnosing PEI within this patient population. Two hundred and three diabetic patients attending diabetic and gastroenterology outpatients of a university hospital without previously known PEI were recruited for the study. Demographic parameters, PEI score (PEI-S), and glycated hemoglobin (HBA1c) were documented in standardized data sheets, and a stool sample was obtained. A FE-1 value < 200μg/g and or a PEIS of > 0.6 was used as the screening cut-off for PEI. One hundred sixty-six patients returned faecal samples. The prevalence of PEI, as measured by low FE-1, was 12%. Smoking was associated with an increased risk of developing PEI in this diabetic population. No other independent risk factors were identified. The PEI-S system did not differentiate between people with diabetes having a normal and low FE1. 12% of this mixed, real-life cohort of type 1 and 2 DM patients had undiagnosed PEI, as defined by an FE-1 score of less than 200μg/g. While this may appear low, given the rising prevalence of type 2 DM worldwide, there is likely an unrecognized burden of PEI, which has long-term health consequences for those affected. The PEI-S, a symptom-scoring system for patients with PEI, did not perform well in this patient group.

Prevalence and Risk Factors for Renal Insufficiency among Adults Living with HIV in Tanzania: Results from a Cross-Sectional Study in 2020-2021.

With improved survival, adults living with HIV (ALHIV) are increasingly likely to experience age-related and HIV-related comorbidities, including renal insufficiency. Other risk factors for renal insufficiency (high blood pressure (BP), obesity, diabetes, and dyslipidemia) are also growing more common among ALHIV. To determine the prevalence of renal insufficiency (defined as an eGFR < 60 mL/min/1.73 m2) and factors associated with reduced eGFR, we conducted a cross-sectional study at six HIV clinics in Dar-es-Salaam, Tanzania. We applied multivariable (MV) ordinal logistic regression models to identify factors associated with reduced eGFR and examined the interaction of age with BP levels. Among the 450 ALHIV on ART analyzed [26% males; median age 43 (IQR: 18-72) years; 89% on tenofovir-containing ART; 88% HIV viral load ≤50 copies/mL], 34 (7.5%) had renal insufficiency. Prevalence was higher among males (12%) vs. females (6%), p = 0.03; ALHIV ≥50 (21%) vs. <50 years (2.5%), p < 0.001; those with high [≥130/80 mmHg (15%)] vs. normal [<120/80 mmHg (4%)] BP, p < 0.01 and those with dyslipidemia (10%) vs. those without (4.5%), p < 0.03. After adjusting for covariates, age (in years) was the only covariate with a statistically significant association with reduced eGFR (OR = 1.09 (1.07-1.12), p < 0.001). No significant interaction between age and BP was found. Interventions to increase routine screening for renal insufficiency, especially among older ALHIV, and improve BP control are critical to reducing kidney disease-related morbidity and mortality.

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.

The utility of a baseline morning cortisol measurement, in the screening for adrenal insufficiency amongst non-critically ill hospital inpatients

BackgroundSerum cortisol levels vary according to the daily circadian cycle, with peak levels seen in the morning. There is evidence in ambulatory patients that a morning cortisol level can predict an adequate cortisol response to Synacthen (tetracosactide) stimulation. AimThe aim of this study is to determine the utility of baseline analysis of the serum cortisol levels in the morning “baseline morning cortisol”, determined using a newer immunoassay, in the screening for adrenal insufficiency amongst non-critically ill hospital inpatients. MethodsThis is a retrospective cross-sectional cohort study. Results64 adult inpatients had undergone a short Synacthen test (SST) (measurement of serum cortisol levels 30 and 60 min after administration of tetracosactide) during the study period. 17 patients returned an abnormal SST result. The measured level of cortisol in the morning correlated to both the 30 min and 60 min stimulated cortisol values (r = 0.612, p < 0.001 and r = 0.639, p < 0.001). After inspecting the receiver operating characteristic curve, a cortisol concentration of 200nmmol/L measured in the morning was selected as a threshold for predicting the SST result. Using this cut off, sensitivity for predicting a normal SST was 100 %, specificity 56 %, positive predictive value 45 % and negative predictive value 100 %. ConclusionA morning cortisol measurement, determined using a newer immunoassay, is sufficient in most cases to screen for adrenal insufficiency amongst non-critically ill hospital inpatients. Use of clinical judgement in conjunction with single morning cortisol measurement is likely to reduce the need for SST testing amongst inpatients.

SAT281 Screening For Adrenocortical Insufficiency In Patients With X-linked Adrenoleukodystrophy

Abstract Disclosure: J. Berquist: None. R.N. Kiani: None. M.P. Wahl: None. Background: A 41-year-old male initially presented to neurology clinic for complaints of poor balance, lower extremity weakness, and numbness. He previously had exam findings of lower extremity spasticity and hyperreflexia, distal vibratory loss, positive Romberg, and difficulty with Tandem gait. His symptoms had been progressive following an ankle sprain 8 years earlier and he was treated with physical therapy and baclofen. He is highly active otherwise and enjoys rock climbing, which was difficult to do given his symptoms. Clinical Case: Genetic screening was performed to evaluate for hereditary spastic paraparesis, which resulted positive for a mutation in the ABCD1 gene with a p.Lys336Glu mutation of uncertain significance. Interestingly, this ABDC1 variant was not detected in submitted maternal sample, hence patient’s mutation likely occurred de novo. This variant is not established in population databases (gnomAD no frequency) but has been observed in at least one individual with clinical features of adrenomyeloneuropathy. X-linked adrenoleukodystrophy causes impairment of beta oxidation that leads to accumulation of saturated very long chain fatty acids (VFLA) in multiple tissues. There are many clinical phenotypes, but they are hallmarked by neurologic signs and symptoms. Although neurologic symptoms can often develop in childhood, they can be delayed and present in adulthood, as can adrenal insufficiency (AI). However, males are overwhelmingly likely to develop adrenocortical insufficiency compared to females. Our patient presented with a BMI of 22.94, HR 50 bpm, and blood pressure 120/76; reflecting his active lifestyle. Recent electrolytes were within normal limits, AM cortisol was 13.0, and ACTH 544.0 Given the elevated ACTH and known cause of adrenal insufficiency, we proceeded with ACTH stimulation test. Peak cortisol resulted at 13.1 (at 60 minutes) and he was started on replacement glucocorticoid therapy per body-surface area. Upon further literature review, patients can also develop loss of mineralocorticoid production. Renin and aldosterone were ordered and were both within normal limits. Conclusion: Males with adrenoleukodystrophy are at a much higher risk of developing adrenal insufficiency (AI) compared to females. Additionally, AI will often develop later in life, so a low threshold for screening should be present for the endocrinologist. Mineralocorticoid deficiency can also develop, although not as commonly. Loss of adrenal function can lead to patient demise, and therefore adrenal function needs to be closely evaluated in people with leukodystrophy. Presentation: Saturday, June 17, 2023

Adrenal Hemorrhage in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome: A Case Report and Literature Review.

Antiphospholipid syndrome (APS) is an autoimmune disorder while adrenal hemorrhage could be its rare complication. Herein, we report the case of a 32-year-old unmarried woman with a history of systemic lupus erythematosus (SLE) who was hospitalized after complaints of upper abdominal pain, limb weakness, and loss of appetite for 2 weeks. Laboratory examination revealed hyponatremia, low plasma cortisol levels, increased adrenocorticotropic hormone levels, and a positive anticardiolipin antibody status. Furthermore, computed tomography (CT) revealed the presence of bilateral adrenal masses. Ultimately, based on dynamic changes in CT images, these masses were diagnosed as adrenal hemorrhage owing to APS. A computer-assisted literature search was conducted to identify cases of primary adrenal insufficiency associated with APS and/or SLE. The clinical features, laboratory examination, treatments, and outcomes of these cases were summarized. Our findings emphasize the importance of screening for adrenal insufficiency in patients with SLE or APS who present with abdominal complaints, asthenia, and hyponatremia. It is also recommended to test for APS all patients with adrenal hemorrhage.

Prevalence of pancreatic exocrine insufficiency after pancreatic surgery measured by 13C mixed triglyceride breath test: A prospective cohort study

BackgroundPatients undergoing pancreatic surgery are at risk of pancreatic exocrine insufficiency (PEI) and needing pancreatic enzyme replacement therapy (PERT). MethodsThis study included 254 patients undergoing pancreatic surgery for oncologic indications. A13C mixed triglyceride breath test was performed immediately preoperative and postoperative. This test analyzes the pancreatic remnant lipase activity measuring 13CO2 in breath samples after a test meal with 1.3-distearyl-(13C-Carboxyl)octanol-glycerol. Cumulative percent dose recovery after 6 h of less than 23% confirms PEI. In addition, PEI was compared between pathology subgroups. ResultsIn 197 patients undergoing pancreaticoduodenectomy, cPDR-6h decreased significantly from a median of 32.84% before to 15.80% after surgery (p < 0.0001). This decrease in exocrine function was significant in all pathology subgroups except in pancreatic neuroendocrine tumors. Exocrine function decreased most in pancreatic ductal adenocarcinoma (PDAC). In addition, the percentage of patients needing PERT because of PEI increased from 25.9% to 68.0% postoperative (p < 0.001). Overall, patients with an MPD diameter of more than 3 mm had a higher risk of developing postoperative PEI: 62.7% compared to 37.3% (p = 0.009), OR = 3.11.In contrast, the majority of the 57 patients undergoing a distal pancreatectomy did not experience any significant change in exocrine function. ConclusionsThe vast majority of patients undergoing pancreaticoduodenectomy for oncologic indications experience a significant drop in exocrine function, are at high risk of developing pancreatic exocrine insufficiency and consequently need to be treated with pancreatic enzyme replacement therapy. Therefore, systematic screening for pancreatic exocrine insufficiency is needed after pancreaticoduodenectomy.

Screening for adrenal insufficiency using home waking salivary cortisone is accurate and lowers NHS costs

Screening for adrenal insufficiency using home waking salivary cortisone is accurate and lowers NHS costs

Routine Screening for Central and Primary Adrenal Insufficiency during Immune-Checkpoint Inhibitor Therapy: An Endocrinology Perspective for Oncologists.

Background: Immune checkpoint inhibitor (ICI)-associated hypothalamic–pituitary–adrenal axis disruption can lead to hypocortisolism. This is a life-threatening but difficult to diagnose condition, due to its non-specific symptoms that overlap with symptoms of malignancy. Currently, there is no consensus on how to best screen asymptomatic patients on ICI therapy for hypophysitis with serum cortisol. Methods: A retrospective chart review of patients treated with ICI in a tertiary care centre was conducted to assess the rate of screening with cortisol and whether this had an impact on diagnosis of ICI-hypophysitis in the preclinical stage. Patients were identified as having hypophysitis with an adrenocorticotropin hormone (ACTH) deficiency based on chart review of patients with cortisol values ≤ 140 nmol/L (≤5 mcg/dL). We also assessed what proportion of cortisol values were drawn at the correct time for interpretation (between 6 AM and 10 AM). Results: Two hundred and sixty-five patients had 1301 cortisol levels drawn, only 40% of which were drawn correctly (between 6 and 10 AM). Twenty-two cases of hypophysitis manifesting with ACTH deficiency were identified. Eight of these patients were being screened with cortisol following treatment and were detected in the outpatient setting. The remaining 14 patients were not screened and were diagnosed when symptomatic, after an emergency room visit or hospital admission. Sixty percent of the cortisol tests were uninterpretable as they were not drawn within the appropriate time window. Conclusion: Measuring morning serum cortisol in asymptomatic patients on ICI therapy is a fast and inexpensive way to screen for hypophysitis and should become the standard of care. Random serum cortisol measurement has no clinical value. Education needs to be provided on when to correctly perform the test and how to interpret it and we provide an algorithm for this purpose. The adoption and validation of such an algorithm as part of routine practice could significantly reduce morbidity and mortality in patients, especially as ICI therapy is becoming increasingly commonplace.

Exocrine and Endocrine Insufficiency in Autoimmune Pancreatitis: A Matter of Treatment or Time?

Background: Autoimmune pancreatitis (AIP) is a specific form of chronic pancreatitis with a high relapse rate after treatment. AIP patients are burdened with an increased risk of long-term sequelae such as exocrine and endocrine insufficiency. Our objective was to investigate if pharmacological treatment affects both endocrine and exocrine pancreatic function in patients with AIP. Methods: We included 59 patients with definite AIP in the final analysis. Screening for diabetes mellitus (DM) and pancreatic exocrine insufficiency (PEI) was performed at the time of AIP diagnosis and during follow-up. Results: There were 40 (67.8%) males and 19 (32.2%) females; median age at diagnosis was 65 years. Median follow-up after the diagnosis of AIP was 62 months. PEI prevalence at diagnosis was 72.7% and was 63.5% at follow-up. The cumulative incidence of DM was 17.9%, with a prevalence of DM at diagnosis of 32.8%. No strong association was found between pharmacological treatment and occurrence of PEI and DM. Univariate analysis identified potential risk factors for PEI (other organ involvement and biliary stenting) and for DM (overweight, blue-collar profession, smoking, weight loss or obstructive jaundice as presenting symptoms, imaging showing diffuse pancreatic enlargement, smoking). In a multivariate analysis, only obstructive jaundice was identified as a risk factor for DM both at diagnosis and during follow-up. Conclusions: Our results suggest that the prevalence of endocrine and exocrine insufficiency in AIP is high at diagnosis with an additional risk of PEI and DM during follow-up despite pharmacological treatment.

Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study

IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency. MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years. ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency. ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.

Leg Venous Properties in Children With Myelomeningocele.

Introduction: The vascular properties of individuals with myelomeningocele (MMC) are an underestimated problem, as evidenced by the lack of relevant research. Therefore, this study was conducted to assess the venous properties of the leg in children with MMC. This study compared the duration of retrograde flow (RF) of the distal and proximal sites of the great saphenous vein (GSV) in children with MMC and typically developing (TD) children. Additionally, the impact of MMC clinical features, such as the anatomical level of the spinal cord defect, muscle strength of the lower limbs, and level of gross motor functional abilities on the of GSV sufficiency were assessed.Methods: Thirty ambulant children between 7 and 12 years with MMC and an age- and sex-matched sample of thirty children with typical development (TD) were included in the study. All participants underwent a complete physical examination that included gross motor assessment, manual muscle testing, and duplex ultrasound examination of the GSV reflux. The duration of retrograde flow (RT) in the GSV was evaluated at four sites: P1: proximal thigh; P2: medial thigh; P3: upper leg; and P4: lower leg. The measurements were performed in two body positions: horizontal position (HP) and vertical position (VP).Results: Children with MMC showed increased duration of RT of both the proximal and peripheral sites of GSV, as compared with the TD peers. The prevalence of GSV reflux in peripheral segments was significantly higher than in the proximal segments. The severity of MMC (expressed by higher level of the spinal cord defect), deficit of thigh and leg muscle strength, and lower functional independence negatively influenced the GSV sufficiency in patients with MMC. Gravity directly influenced GSV reflux occurrence and reflux hemodynamic parameters in MMC.Conclusion: These findings may help better understand aspects concerning the risk of developing venous insufficiency in children with MMC and determine better screening, prevention, and treatment algorithms for venous insufficiency in patients with SB.

Does Pentaerytrithyltetranitrate reduce fetal growth restriction in pregnancies complicated by uterine mal-perfusion? Study protocol of the PETN-study: a randomized controlled multicenter-trial

BackgroundAffecting approximately 10% of pregnancies, fetal growth restriction (FGR), is the most important cause of perinatal mortality and morbidity. Impaired placental function and consequent mal-perfusion of the placenta is the leading cause of FGR. Although, screening for placental insufficiency based on uterine artery Doppler measurement is well established, there is no treatment option for pregnancies threatened by FGR. The organic nitrate pentaerithrityl tetranitrate (PETN) is widely used for the treatment of cardiovascular disease and has been shown to have protective effects on human endothelial cells. In a randomized placebo controlled pilot-study our group could demonstrate a risk reduction of 39% for the development of FGR, and FGR or death, by administering PETN to patients with impaired uterine artery Doppler at mid gestation. To confirm these results a prospective randomized placebo controlled double-blinded multicentre trial was now initiated.MethodThe trial has been initiated in 14 centres in Germany. Inclusion criteria are abnormal uterine artery Doppler, defined by mean PI > 1.6, at 190 to 226 weeks of gestation in singleton pregnancies. Included patients will be monitored in 4-week intervals. Primary outcome measures are development of FGR (birth weight < 10th percentile), severe FGR (birth weight < 3rd centile) and perinatal death. Placental abruption, birth weight below the 3rd, 5th and 10th centile, development of FGR requiring delivery before 34 weeks` gestation, neonatal intensive care unit admission, and spontaneous preterm delivery < 34 weeks` and 37 weeks` gestation will be assessed as secondary endpoints. Patient enrolment was started in August 2017. Results are expected in 2020.DiscussionDuring the past decade therapeutic agents with possible perfusion optimizing potential have been evaluated in clinical trials to treat FGR. Meta-analysis and sub-analysis of trials targeting preeclampsia revealed ASS to have a potential in reducing FGR. Phosphodiesterase-type-5 inhibitors have recently been tested in a worldwide RCT for therapy of established FGR, failing to show an effect on neonatal outcome. The ongoing multicenter trial will, by confirming our previous results, finally provide a therapeutic option in cases at risk for FGR.Trial registrationDRKS00011374 registered at September 29th, 2017 and NCT03669185, registered September 13th, 2018.

SAT-380 Screening for Central Adrenal Insufficiency in Children with Prader-Willi Syndrome (PWS) with Single Collection Of ACTH and Cortisol Levels

Baseline a.m ACTH and Cortisol levels in Children with Prader-Willi-syndrome are no different from general population. Moris Angulo, MD1 & Mariano Castro-Magaña, MD1 1Dept of Peds, NYU-Winthrop Hospital, New York, NY Background Prader-Willi syndrome (PWS) is a multi-system genetic disorder resulting from the lack of expression of the paternal genes from chromosome 15q11.2-q13 due to paternal deletion, uniparental disomy (UPD) or an imprinting center defect. Many of their features are explained by hypothalamic dysfunction, therefore individuals with PWS are at high risk for pituitary hormonal deficiency. When the pituitary begins to fail, there is generally a specific sequential failure of pituitary hormones, starting with GH, continuing through LH and FSH deficiency, and culminating in loss of TSH and ACTH. Generally, ACTH is the last to be lost. A high prevalence (60%) of central adrenal insufficiency (CAI) however, has been reported in Prader-Willi syndrome (PWS) using the metyrapone test. Many children, including infants have undergone stimulation testing to confirm or rule out CAI. Several studies however, using same test and other different testing methods including insulin tolerance test (ITT), low dose/high dose ACTH stimulation, glucagon stimulation tests have reported differing results with prevalence between 0 to 7·5%. Previous study has shown that basal cortisol is closely correlated with adrenal response to stimulation. Methods: We studied 105 children with genetic diagnosis of PWS, age 2 to__years. (60 males and 45 females) after basal Cortisol and ACTH level collected at 0800 h. Sixty eight children (60 %) had deletion I and II, 24 (23%)UPD and 13 had only positive DNA Methylation testing . All participant were already on GH treatment without illness or any other stressful condition during testing. Results: All had normal morning Cortisol and ACTH level but 2 children, age 2 and 5 years with low and 4 y.o. male with increased cortisol level. These 3 children had normal ACTH level. Repeat sample after a week, revealed normal both Cortisol and ACTH level. Conclusion: suggesting that clinically significant adrenal insufficiency in PWS is rare

MON-351 Bilateral Adrenal Haemorrhage Secondary to Intra-Abdominal Sepsis: A Case Report

Introduction Adrenal failure secondary to bilateral haemorrhage is a rare presentation with a significantly high mortality rate. Sepsis, caused by a deregulated inflammatory response to infection, can result in bilateral adrenal haemorrhage particularly with predisposing factors such as major surgery and anticoagulation. Clinical Case A 58-year-old white man presented to the emergency department with a two-week history of diarrhoea and vomiting. On examination, the abdomen was tender over the right lower quadrant with guarding. An abdominal CT confirmed diverticulitis with small bowel perforation. Patient deteriorated with conservative management, and a repeat abdominal CT showed worsening colonic inflammation with new pelvic collection suggesting of intra-abdominal sepsis. The patient underwent urgent laparotomy for Hartman’s procedure. However, he did not improve post-operatively, remaining hypotensive and febrile with elevated inflammatory markers despite continuous IV antibiotics. The working diagnosis remained as intra-abdominal sepsis. He had a series of abdominal CT scans at different intervals, and on the 4th scan, a new bilateral adrenal enlargement consistent with haemorrhage/infarction was identified. However, an unreported early haemorrhagic transformation is visible on the previous scan from ten days earlier. A random Cortisol was 157nmol/L (200-650nmol/L-morning peak) which appeared low for critical illness. Serum Aldosterone was 206pml/L (61-980pmol/L) and Aldosterone/Renin ratio was 12.6 (<70). The patient was treated with intravenous hydrocortisone with excellent response and later discharged on oral hydrocortisone. He remains well with stable blood pressure. A repeat adrenal CT, five months post discharge show normal adrenal glands. He is due for an ATCH stimulation test prior to weaning of oral steroids. Conclusion This case describes a potentially life-threatening complication of bilateral adrenal haemorrhage following intra-abdominal sepsis and surgery. It highlights the importance of screening for adrenal insufficiency with close attention to adrenal anatomy on imaging, for patients who remain in shock despite treatment for sepsis.

SUN-418 An Uncommon Case of Anti-PD1 Agent Induced Secondary Adrenal Insufficiency

Introduction - Nivolumab is a monoclonal anti-programmed cell death receptor 1(PD1) antibody approved for the treatment of unresectable or metastatic melanoma and is known to be associated with a wide spectrum of endocrinologic derangements. The objective of this report is to describe a case of symptomatic hyponatremia secondary to hypophysitis induced by nivolumab immunotherapy. Case Report - A 63-year-old male with Stage 4 malignant melanoma presented for the administration of cycle 6 maintenance therapy nivolumab. He was noted to be awake but disoriented to time and place, and family members reported worsening confusion for the previous three days. His labs revealed low serum sodium (120mEq/L; 135-145 mEq/L), and he was admitted for further management. His medical history includes immune-mediated hypothyroidism secondary to nivolumab and is on levothyroxine supplementation. His initial workup showed hypotonic, euvolemic hyponatremia. Given his known adrenal metastasis, primary adrenal insufficiency (PAI) was in the differential. A morning serum cortisol level was low (3.3μg/dL; 7-28 μg/dL), and a low dose ACTH stimulation test was abnormal concerning for PAI. Curiously, his ACTH level was inappropriately low (7 pg/mL; 20-52 pg/mL) for PAI, suggestive of secondary adrenal insufficiency. MRI-brain showed mild diffuse interval enlargement in size, as well as homogeneous contrast enhancement of pituitary gland. The patient was started on hydrocortisone treatment, and the hyponatremia resolved. Diagnosis of hyponatremia secondary to hypophysitis from nivolumab therapy was established. Screening for other pituitary hormone deficiency resulted in normal FSH, LH, TSH, prolactin, IGF-1 levels. Also, serum renin, aldosterone, free and total testosterone levels were unremarkable. With clinical improvement, the patient was discharged home on maintenance dose hydrocortisone.Discussion - This report highlights a rare case of nivolumab-induced secondary adrenal insufficiency where early recognition and management plays a crucial role. Nivolumab acts by restoring natural T-Cell mediated immune response and incites concomitant T cell activation against normal tissues. This leads to immune-related adverse events mainly affecting multiple endocrine glands in an insidious manner. At present, anti-PD1 agents are widely used in clinical practice. Hypotension, hyponatremia or persistent hypoglycemia in patients receiving these agents warrant screening for adrenal insufficiency in order to prevent deleterious clinical consequences.

Resolution of Intractable Leg Ulcers Associated with Antiphospholipid Syndrome (APS) with Prophylactic Dose of Aspirin (ASA) and Enoxaparin: A Case Report

Background: Lower extremity ulcers are one of the most common skin manifestation in patients (pts) with APS, observed in 20-30% of pts. These skin ulcers typically respond poorly to conventional treatment. Although incompletely understood, the pathogenesis of the skin ulcers (and most of the clinical manifestations of APS) appears to be the result of vascular endothelial damage at the microcirculation level, leading to intracapillary thrombosis and focal inflammation. Systemic treatments with immunomodulatory agents such as glucocorticoids, intravenous immunoglobulin (IVIG) and immunosuppressants have been reported to improve outcomes, but typically carry substantial side-effects, and may not be available outside specialized referralcenters. The use of anticoagulation, with or without immunosuppression, in pts with APS and skin ulcers has been reported with variable results. Our group and others have documented an excellent safety profile with the combination of ASA 81 mg orally and enoxaparin 40 mg subcutaneously given to pregnant patients with APS and recurrent pregnancy loss. Patient with APS appear to share similar microcirculatory changes in the organs involved.Methods: Case report.Results: A 72 year-old gentleman was diagnosed with APS in 2000, when he was evaluated for recurrent deep venous thrombosis in the lower extremities, and was found to have a positive lupus anticouagulant serum test. He received anticoagulation with warfarin, with a target International Normalized Ratio (INR) of 2.5-3.5. In 2011, the patient was evaluated for full-thickness ulceration of the bilateral medial distal legs. He had been treated years earlier with venous ablation, and screening for lower extremity arterial insufficiency showed adequate peripheral circulation. The ulcers were treated with moist antimicrobial wound dressings, serial wound debridement, ongoing compression therapy, and a course of skin substitute therapy. After over one year of treatment the ulcers healed. Over the next several years the patient experienced several episodes of re-ulceration of the lower extremity ulcers despite continued use of compression stockings. He was treated in the same fashion, and each episode of re-ulceration required months of therapy to achieve healing. In mid-2017 he developed another episode of re-ulceration. Similar treatment was again initiated, with little improvement over the first several months of therapy. Physical findings and the recalcitrant nature of the ulcers suggested a direct casual relation with his underlying APS. Since our pt was not a candidate for any form of immunosuppression, he was started on daily subcutaneous enoxaparin 1 mg/kg and daily oral ASA 81 mg. A complete healing of the skin ulcers was noted three months after initiation of the above therapy. He continues on this treatment without any side-effects.Conclusion: A multidisciplinary approach allows for a more detailed evaluation of these challenging cases and helps to improve clinical outcomes. DisclosuresNo relevant conflicts of interest to declare.

Adrenoleukodystrophy: Guidance for Adrenal Surveillance in Males Identified by Newborn Screen.

Adrenoleukodystrophy (ALD) is a peroxisomal disorder associated with neurologic decompensation and adrenal insufficiency. Newborn screening for ALD has recently been implemented in five states with plans to expand to all 50 states in the United States. Adrenal insufficiency ultimately develops in most males with ALD, but the earliest age of onset is not well established. These clinical recommendations are intended to address screening for adrenal insufficiency in boys identified to have ALD by newborn screen. Seven members of the Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee, with clinical experience treating children with ALD and adrenal insufficiency, and a pediatric endocrinologist and laboratory director were selected to be on the working committee. The authors comprised the working group and performed systematic reviews of the published literature regarding adrenal insufficiency and ALD. The recommendations were reviewed and approved by the larger Pediatric Endocrine Society Drug and Therapeutics/Rare Diseases Committee and then by the Pediatric Endocrine Society Board of Directors. There is limited literature evidence regarding monitoring of evolving adrenal insufficiency in male infants and children with ALD. The recommendations suggest initiating assessment of adrenal function at diagnosis with ALD and regular monitoring to identify boys with adrenal insufficiency in a timely manner and prevent life-threatening adrenal crisis. These recommendations are intended to serve as an initial guide, with the understanding that additional experience will inform future guidelines.

Screening for convergence insufficiency in school‐age children

BackgroundConvergence insufficiency (CI) is a common binocular vision disorder which often causes symptoms when doing near work. However, the best screening test for CI is unknown. The purpose of this study was to evaluate the ability of common tests of binocular and accommodative function to identify children with CI in a school screening setting.MethodsChildren aged nine to 14 were invited to participate. Positive fusional vergences, near point of convergence (NPC), accommodative amplitude, accommodative facility, Modified Thorington, and the Convergence Insufficiency Symptom Survey were evaluated.ResultsOf the 282 children tested, approximately 20-per cent had 2–3 signs of CI. One half of 2–3 signs of CI and 66-per cent of three signs of CI subjects were symptomatic. Approximately 61-per cent of subjects with symptomatic 2–3 signs of CI had an accompanying low accommodative amplitude. The largest area under the receiver operating characteristic curve was obtained using NPC break measurements. NPC break ≥ 6-cm for CI and NPC break ≥ 7-cm for symptomatic CI were the cut points that maximised the sum of sensitivity and specificity.ConclusionNPC break performed best in identifying children with CI.