Steroid Dose Research Articles

Utilizing a best practice advisory (BPA) to increase pneumocystis jirovecii pneumonia (PJP) prophylaxis prescribing for patients with cancer on high dose corticosteroids.

391 Background: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic fungal infection that can cause severe respiratory infection in immunocompromised patients. Corticosteroid use is a common risk factor for developing PJP in non-human immunodeficiency virus (HIV) patients. Corticosteroids are commonly prescribed medications for cancer patients to help with symptom control from cancer treatment (e.g. nausea, vomiting, and pain) as well as for immunotherapy related adverse events. The risk of developing PJP is significantly increased for patients on prednisone equal to or greater than 20 mg per day x 1 month or equivalent. Steroid related PJP (srPJP) is associated with a 30-50% mortality in non-HIV patients. Methods: We conducted an IRB-approved retrospective chart review of individuals diagnosed with PJP at an academic medical center and 6 partner hospitals between 2016-2022. Patients were excluded if they had a diagnosis of HIV or prior hematopoietic stem cell transplant (HSCT). We then created a best practice advisory (BPA) built into the electronic health record to notify clinicians if a patient is at risk of developing srPJP based on their outpatient corticosteroid prescription. The BPA is triggered system-wide if a clinician signs an outpatient prescription for a prednisone or equivalent steroid dose of 20 mg or more for a duration of at least 3 weeks. The BPA will suggest PJP prophylaxis and link to an order for the clinician to select. Results: There were 96 identified cases of srPJP in non HIV/HSCT patients. None of these patients received antibiotic prophylaxis. Among these cases, 32 patients died from ARDS due to PJP, a mortality of 33.3%. 45% of identified cases were related to steroids prescribed for cancer management, and 68% of these received dexamethasone as the primary steroid. The BPA launched in April 2023 system wide across UC Health. Since launching the BPA in April 2023, it has been triggered 911 times with action taken by selecting an order for PJP prophylaxis 24.5% of the time. Conclusions: Despite the efficacy of prophylaxis, many patients at risk of developing srPJP do not receive prophylaxis. Since launching the BPA, preliminary data shows that the BPA has increased the orders placed for concurrent PJP prophylaxis. Further work must be done to determine if these orders for concurrent PJP prophylaxis were signed and if the BPA can increase PJP prophylaxis prescribing for patients on high dose corticosteroids and ultimately decrease srPJP cases and deaths.

Influence of Long-term Oral Steroid Intake on Glaucoma and Ocular Hypertension

Purpose: The aim of this study was to evaluate the risk factors associated with glaucoma or ocular hypertension (OHT) in patients taking oral corticosteroids for extended periods, and to aid in managing intraocular pressure (IOP) in patients with these risk factors.Methods: A cross-sectional study was performed involving 690 patients who visited a tertiary referral hospital and had been using oral corticosteroids for more than six months. Patients' demographics, tonometry results, drug type, dosage, duration, ophthalmic history, and the use of glaucoma eye drops were analyzed to determine the risk factors associated with glaucoma or OHT.Results: In a generalized linear model analysis comparing patients' eyes diagnosed with glaucoma or ocular hypertension to those without such diagnoses, no statistical difference was observed between the two groups in terms of drug type, age, and duration of oral corticosteroid use. However, the dosage was found to be statistically significant (odds ratio 1.09, p = 0.0294).Conclusions: No difference in the incidence of glaucoma or OHT was found based on the type of oral steroid, age, or duration of use. However, a higher incidence of glaucoma and OHT was observed among patients taking higher doses of oral steroids. Therefore, it is suggested that using lower doses of oral steroids may be more beneficial for managing IOP.

Rituximab as a sole steroid-sparing agent in generalized myasthenia gravis: Long-term outcomes.

Rituximab, a B-cell depleting monoclonal antibody, represents an option for the treatment of refractory myasthenia gravis (MG). Its use is more established in muscle-specific tyrosine kinase positive (MuSK +) patients, while its role in managing acetylcholine receptor positive (AChR +), or double seronegative (DSN) patients, remains less clear. This study evaluates the long-term effectiveness and safety of rituximab in MG of various serotypes. We conducted an open-label study of MG patients receiving rituximab. Adults with generalized refractory MG, either anti-AChR + or DSN, and anti-MuSK + , refractory or not, who had follow-up > 12months were selected. Change in quantitative myasthenia gravis (QMG) score at last follow-up, compared with baseline was a primary outcome, as well as factors affecting response to treatment. Secondary outcomes included, long-term safety, the steroid-sparing effect and relapse rates post-rituximab. Thirty patients (16 anti-AChR + , 6 anti-MuSK + , 8 DSN) followed for a mean of 33.3months were included. Mean scores pre-rituximab compared to last follow-up significantly decreased (p < 0.001), from 11 ± 4.1 to 4.3 ± 3.8, and from 1.9 to 0.3 regarding QMG and relapse rate per patient/year, respectively, while in 93.1% a daily steroid dose ≤ 10mg was achieved. Antibody status was the only factor independently influencing several endpoints. Throughout the study period no crises or deaths occurred. The present study supports that rituximab is an effective and well tolerated treatment for refractory anti-AChR + and DSN MG patients, while anti-MuSK + remains the group experiencing the greater benefits.

Serum cortisol level to screen for significant hypothalamic-pituitary-adrenal axis suppression in patients receiving multiple steroid injections.

Morning serum cortisol level (mSCL) is a practical screening tool for hypothalamic-pituitary-adrenal (HPA) axis suppression and has been used to assess for duration of cortisol deficiency after epidural and peripheral glucocorticoid injections. More evidence is needed to establish the utility of mSCL in patients undergoing repeat injections with increasing cumulative glucocorticoid equivalent dose (CGED) that could place them at higher risk of HPA axis suppression. To estimate the prevalence of spine injection candidates with significant HPA axis suppression (sigAS), to understand the correlation between 12months of CGED and the presence of sigAS based on the timing of mSCL collection after the most recent glucocorticoid injection (within 6weeks or between 6weeks and 12months), and to investigate demographic and clinical factors relating to sigAS. Retrospective chart review of patients scheduled for spine injection who had an associated mSCL and documented histories of prior glucocorticoid injections. The steroid name, dose, type, and procedure location were recorded for each injection that occurred within 12months before mSCL. CGED was calculated from standard glucocorticoid equivalent conversion factors. SigAS was present in 7.8% to 22% of the analysis cohorts. There was no association found between CGED and sigAS regardless of timing of mSCL. There was a trend toward lower mSCL and sigAS with increasing CGED. There were no significant relationships found between sigAS and overall demographic or clinical factors. A 3-fold reduction in the rate of sigAS was noted 6weeks after the most recent steroid injection. Using mSCL provides a template to investigate the impact of CGED and the best timing for mSCL collection in order to define a more practical guideline to identify patients at higher risk of sigAS earlier and plan for future spine injections.

The Role of Neurotransmitters in Relation to Psychiatric Conditions Throughout the COVID-19 Epidemic

Various studies have reported the presence of psychiatric symptoms among individuals diagnosed with COVID-19, encompassing heightened stress levels, impaired cognitive function, depressive mood, anxiousness, post-traumatic stress disorder (PTSD), psychotic symptoms, and suicidal ideation. The objective of this review was to elucidate the involvement of neurotransmitters in psychiatric disorders following the COVID-19 pandemic. There are multiple variables that can influence the results of research studies examining the presence of symptoms or the initiation of psychiatric disorders in individuals diagnosed with COVID-19. Factors associated with mental health difficulties include direct involvement in the healthcare field, presence of a psychiatric disease within the family, limited social support, advanced age, solitary living arrangements, and the utilization of high dosages of steroids during the acute phase. Multiple types of neurotransmitters are involved in the modulation of stress levels inside the human body. The neurotransmitters implicated in this process include dopamine, serotonin, epinephrine and norepinephrine, acetylcholine, gamma-aminobutyric acid (GABA), and glutamate. In summary, cytokines have a pivotal role in modulating the hypothalamic-pituitary-adrenal (HPA) axis within the brain, hence potentially giving rise to psychiatric manifestations including impaired sleep, heightened stress, depressive affect, and several other psychological disturbances.

FRI093 Severe Hypertriglyceridemia Post Liver Transplant- A Multifactorial Disorder

Abstract Disclosure: A.R. Saand: None. A.R. Drinnon: None. F. Mubeen: None. J. Shakil: None. Introduction: Hypertriglyceridemia (HTG) is a known complication in solid organ transplant patients. In addition to increasing cardiovascular complications and mortality risk, these metabolic abnormalities also increase the risk of allograft atherosclerosis and vasculopathy. Although medications used in post-transplant management have a well-documented effect of worsening lipid profile, multiple factors may be contributing in the development of severe HTG. Case Description: We describe a 68-year-old male with elevated triglycerides (TG) of 3957 mg/dL on hospital admission for pneumomediastinum. He received liver transplant 2 years prior due to alcohol-related liver cirrhosis. He had normal TGs prior to the transplant. Immunosuppressant regimen included tacrolimus (TAC) and methylprednisone. Lipoprotein electrophoresis was normal. Intravenous insulin infusion was initiated with moderate improvement however, upon transition to oral medications: fenofibrate, omega-3 fatty acids, niacin and rosuvastatin, TGs continued to increase. Reinitiating insulin infusion showed no improvement. TAC was switched to cyclosporin with transient decrease in TGs. Upon discharge amylase and lipase levels remained normal despite TG elevation. When readmitted for an unrelated reason, his TGs were elevated at 2218 mg/dl. Plasmapheresis was initiated but was complicated by anaphylaxis with angioedema requiring intubation. After partial plasmapheresis, TGs significantly decreased and soon returned to normal. Post-discharge, the patient was changed back to previous TAC dosage due to cyclosporin related renal injury. His steroid dose was reduced and icosapent was added, resulting in no further recurrence of HTG. Discussion: Following liver transplant, about 15-40% recipients have increased cholesterol levels and about 40% have HTG. Although, immunosuppressant-induced dyslipidemia is seen frequently, additional risk factors have been identified. A retrospective study of 85 patients post liver transplant showed HTG developed early within the first month in about 67% patients and persisted throughout the first year. Some common factors predictive of HTG post liver transplant include pre-liver transplant hepatocellular disease and post-transplant renal dysfunction. A study in pediatric patients post liver transplant observed that changes in lipoprotein and HDL subfraction post-transplant may lead to hypertriglyceridemia. Our case suggests that HTG may be multifactorial given the persistent elevation of TGs despite the change in immunosuppressant regimen. Patient factors as well as genetic characteristics of the donor liver may be potential causes. Recognizing this variation in patient populations may be extremely important due to high risk for pancreatitis and cardiovascular events. Early identification and management may prevent complications. Presentation: Friday, June 16, 2023

FRI603 Treatment Of Severe Refractory Hypoglycemia Due To Malignant Insulinoma With A Novel Anti-insulin Receptor Antibody

Abstract Disclosure: S. Osataphan: None. M. Vamvini: None. E.D. Rosen: Consulting Fee; Self; Novartis Pharmaceuticals. L. Pei: None. N. Erlikh: None. G. Singh: None. P. Dhorajiya: None. J. Parker: None. J.M. Dreyfuss: None. A. Rattani: Stock Owner; Self; Vertex Pharmaceuticals, Provention Bio, Bluebird Bio, Agenus, MacroGenics, Immunity Bio, Mirati Therapeutics, Actinium Pharmaceuticals, Bausch Health Companies, Compass Therapeutics, Magenta Therapeutics. M. Patti: Advisory Board Member; Self; Fractyl Laboratories. Consulting Fee; Self; AstraZeneca, Hanmi Pharmaceuticals, MBX. Grant Recipient; Self; Dexcom. Severe hypoglycemia caused by malignant insulinoma is often resistant to medical therapy targeting both tumor burden and insulin secretion. We report a patient who developed severe, treatment-resistant hypoglycemia after receiving 177lutetium-DOTATATE (Lu-177). Hypoglycemia was completely ameliorated after treatment with RZ358, a human monoclonal antibody that functions as a negative allosteric modulator of the insulin receptor, reducing insulin signaling. This 55 year old man presented with abdominal pain, fatigue, and weight loss; imaging showed a 1.8 cm pancreatic tail mass and numerous hepatic lesions. Liver biopsy demonstrated well-differentiated pancreatic neuroendocrine tumor, WHO Grade 2, and pathogenic MEN1 mutation. Following one year of octreotide therapy, both pancreatic and hepatic tumors increased in size, prompting Lu-177 therapy. Two days after the first dose, the patient became unresponsive, with capillary glucose 20 mg/dL. He developed recurrent neuroglycopenia on day 8, with venous glucose 41 mg/dL, insulin 45 µIU/mL, C-peptide 6.5 ng/mL and proinsulin 453 pmol/L, requiring intensive care unit admission for for intravenous glucose. High-dose diazoxide, everolimus, dexamethasone, glucagon, pasireotide, or enteral feeding did not produce a response. Despite multiple therapies, neuroglycopenia required frequent dextrose boluses and continuous intravenous glucose (up to 30 g/hr of 50% dextrose); up to 58% of sensor glucose was below 70 mg/dL and 19% below 54 mg/dL over 24 hours. CT imaging 1 month after Lu-177 showed significant reduction in liver metastases size. Given the severity of hypoglycemia despite tumor regression, we considered treatment with RZ358, a human monoclonal antibody that acts as a negative allosteric modulator of the insulin receptor, inducing insulin resistance. We obtained emergency use authorization from the FDA, approval from the local Institutional Review Board, and written informed consent. Following a 6 mg/kg dose of RZ358, there was transient worsening of hypoglycemia accompanied by an 8-fold increase in insulin, potentially due to reduced insulin clearance. After dose increase to 9 mg/kg weekly, glucose infusion was weaned. Metabolic stability was achieved after 6 doses, allowing a second dose of Lu-177 and eventual discharge. Diazoxide was discontinued, steroid doses were reduced, and RZ358 dosing was reduced to every 3-4 weeks. A third dose of Lu-177 was administered without complications. Despite elevated insulin (537 uIU/mL), C-peptide (10.1 ng/mL), and proinsulin (634.0 pmol/L), he remains free of level 3 hypoglycemia. No adverse effects have been observed. In summary, the anti-insulin receptor monoclonal antibody RZ358 effectively controlled hypoglycemia refractory to multiple other therapies, allowing restoration of normoglycemia and enabling additional successful cancer therapy. Presentation: Friday, June 16, 2023

THU246 What’s The Importance of GAD Antibodies In Patients With Stiff Person Syndrome

Abstract Disclosure: A. Barnett: None. G. Elshimy: None. Introduction: Stiff Person Syndrome (SPS) has a strong autoimmune component with positive serology for GAD-65 antibody as one of the diagnostic criteria. GAD is an enzyme selectively concentrated in neurons secreting the neurotransmitter gamma-aminobutyric acid (GABA) but is also present in pancreatic beta cells. Hence, insulin-dependent diabetes mellitus (LADA) can develop in patients with SPS. We present two cases that highlight the importance of this association and the difference in the time of onset to ensure appropriate screening. Case: Our first case was a 46-year-old female with systemic sclerosis and SPS that was diagnosed with steroid-induced diabetes in 2012 with HbA1c 8.7% (4.3-6.1%). Her GAD-65 antibody was significantly elevated at 1971 (less than 2nmol/L). For almost 8 years, the patient only required insulin therapy while on high dose steroids, but eventually developed persistent hyperglycemia requiring insulin therapy. Her C-peptide was 0.49 (0.78-5.19ng/mL) with plasma glucose of 201 (74-106mg/dL), consistent with beta-cell dysfunction. The second case was a 60-year-old female with a 20-year history of SPS who was diagnosed with type 2 diabetes in 2014 after receiving high doses of steroids while undergoing chemotherapy for breast cancer. She was initially well-controlled on oral medications until 2 years after her initial diabetes diagnosis where her HbA1c increased rapidly to 8.1% (4.8-5.9%). At that time, she was started on insulin therapy and antibody testing was pursued which showed positive GAD-65 antibody greater than 250 (less than 5IU/mL) consistent with LADA. She had a negative IA-2 antibody undetectable. Due to other autoimmune associations, she was also screened for thyroid disease revealing an elevated TPO-antibody with a normal TSH 4.02 that is being monitored. Discussion: SPS is associated with autoantibodies and other autoimmune disorders including but not limited to type 1 diabetes, anti-thyroglobulin antibodies and anti-parietal cell antibodies. In both cases, the diagnosis of SPS preceded the onset of diabetes then with a latent “honeymoon” phase not requiring long-term insulin therapy for years, most consistent with LADA. However, there are exacerbating factors including high-dose steroids which could be misleading and result in diagnosing these patients with type 2 diabetes initially. It should be taken into consideration that there is variability in the time of onset of beta-cell dysfunction, which varied from 2 to 8 years in our patients. Hence, the recognition of the correlation of autoimmune-mediated diabetes and the variable time course to insulin deficiency is critical for the continued monitoring in patients with SPS. Physicians should be aware of the importance of screening patients with SPS for type 1 diabetes mellitus and differentiate it from steroid-induced type 2 diabetes to avoid developing diabetic ketoacidosis in these patients. Presentation: Thursday, June 15, 2023

SAT155 Insulin Receptor Autoantibody Syndrome (Iras): A Rare Occurrence In Lymphoproliferative Disease

Abstract Disclosure: C. Villatoro Santos: None. E.A. Oral: None. Insulin receptor antibody syndrome (IRAS) may present as fasting hypoglycemia, high serum insulin, and serum autoantibodies to insulin receptor at low titers. We present a case of a patient with multiple myeloma (MM) who developed hypoglycemia suspected to be related to insulin receptor antibodies. The patient is a 60-year-old male with history of prediabetes, MM, anemia, and thrombocytopenia treated with carfilzomib, dexamethasone 20 mg weekly, and prior radiation to the right pelvis, who presented to the hospital for increased right hip pain and cough. Patient reported 4 days of markedly decreased appetite with poor intake. He noted increased chronic right hip and low back pain. On exam, he was cachectic, had hyperpigmentation under bilateral eyes, and muscle wasting. Hypoglycemia as low as 38 mg/dL (70-180 mg/dL) was noted. MM studies on hospital day 4 showed increased kappa-M protein and kappa-free light chains with worsening anemia and thrombocytopenia, concerning for progression of his disease. He later developed recurrent hypoglycemia; endocrinology was consulted on hospital day 6. He also had hyponatremia and borderline low blood pressure. Cortisol on hospital day 7 at 9:00 am was 15.4 μg/dL (5.3-22.5 μg/dL) in the setting of normoglycemia. On hospital day 9, hematology started dexamethasone 40 mg daily for 3 days for MM relapse, which resulted in marked improvement in his mental status, appetite, and resolution of hypoglycemia. On hospital day 11, he started weekly cyclophosphamide, bortezomib, plus dexamethasone for 3 weeks. Results for hypoglycemia workup returned on hospital day 12 from samples of Day 7: glucose 53 mg/dL (70-180 mg/dL), C-peptide 0.2 ng/mL (1-5.2 ng/mL), insulin 14.6 μU/mL (1-21 μU/mL), insulin antibodies undetectable, negative serum screen for oral hypoglycemic agents. His course was complicated by sepsis with gram-negative bacteremia treated with antibiotics and stress dose hydrocortisone. He was discharged to rehab on hospital day 34 on dexamethasone 4 mg daily. Glucose, c-peptide and insulin levels could be consistent with exogenous hyperinsulinemic hypoglycemia but may also represent delayed insulin clearance due to insulin receptor antibodies and autocrine suppression of pancreatic insulin production in a patient with no access to insulin. Therefore, the most likely diagnosis was IRAS. The insulin antibody radioactive essay was negative for native IgG and IgM antibodies; testing for insulin receptor antibodies is in progress as a clinical test is unavailable. Treatment is common with high doses of steroids. IRAs can be seen in patients with lymphoproliferative disorders and would respond to steroid treatment for hospital management. Definitive treatment should be tailored with oncology guidance. There is a need for an accessible clinical test for IRAS in the US. Presentation: Saturday, June 17, 2023

Novel therapies for graft versus host disease with a focus on cell therapies.

Graft versus host disease (GVHD) can occur at any period post allogeneic hematopoietic stem cell transplantation as a common clinical complication contributing to significant morbidity and mortality. Acute GVHD develops in approximately 30-50% of patients receiving transplants from matched related donors. High doses of steroids are used as first-line treatment, but are unsuccessful in around 40% of patients, resulting in the diagnosis of steroid-refractory acute GVHD. Consensus has yet to develop for the management of steroid-refractory acute GVHD, and prognosis at six months has been estimated at around 50%. Thus, it is critical to find effective treatments that increase survival of steroid-refractory acute GVHD. This article describes the currently known characteristics, pathophysiology, and treatments for GVHD, with a special focus on recent advances in cell therapies. In particular, a novel cell therapy using decidua stromal cells (DSCs) was recently shown to have promising results for acute GVHD, with improved effectiveness over previous treatments including mesenchymal stromal cells. At the Karolinska Institute, severe acute GVHD patients treated with placenta-derived DSCs supplemented with either 5% albumin or 10% AB plasma displayed a one-year survival rate of 76% and 47% respectively. Furthermore, patients with steroid-refractory acute GVHD, displayed survival rates of 73% with albumin and 31% with AB plasma-supplemented DSCs, compared to the 20% survival rate in the mesenchymal stromal cell control group. Adverse events and deaths were found to be attributed only to complications of hematopoietic stem cell transplant and GVHD, not to the study intervention. ASC Therapeutics, Inc, in collaboration with the Karolinska Institute, will soon initiate a phase 2 multicenter, open-label study to further assess the efficacy and safety of intravenous DSC treatment in sixty patients with Grade II-IV steroid-refractory acute GVHD. This novel cell therapy represents a promising treatment to combat the poor prognosis that steroid-refractory acute GVHD patients currently face.

SAT174 Doege-Potter Syndrome In A Patient With Solitary Fibrous Tumor Of The Lung

Abstract Disclosure: N. Mon: None. S.S. Krishnasamy: None. Doege-Potter Syndrome is a non-islet cell tumor hypoglycemia (NICTH) due to a solitary fibrous tumor (SFT) with overexpression of Insulin-like growth factor 2 (IGF2). We report a case of refractory hypoglycemia in a patient with SFT of the lung. Case presentation: A 67-year-old homeless male with hypertension, chronic smoker presented with altered mental status after his blood glucose was found 34mg/dl by EMS. His confusion improved after D50W. He could not recall the event but he reported that he missed his dinner prior to the event. He denied taking any antidiabetic medications. He was diagnosed with left lung solitary fibrous tumor without metastases a week ago after he presented to ER with dyspnea, cough and wheezing. CT chest reported a 21x15.6x18.7 cm lesion with mass effect on the left hemidiaphragm, mediastinum shift to the right and occluded left lower lobe bronchi. Core needle biopsy of the mass revealed SFT with necrosis. He was discharged with Medrol dosepak 4mg daily for presumptive treatment of COPD exacerbation and a plan for elective surgery. While in the ER his BG improved to 136mg/dl after D50W. Few hours later BG dropped to 42mg/dl and D10W infusion was started. Physical exam was unremarkable except bilateral pedal edema. Work up showed BG 42mg/dl, Insulin 3.3 (2.6-24.9 uIU/mL), C peptide 0.39 (1.1-4.4ng/mL), Proinsulin 4.7 (&amp;lt;18.8pmol/L), beta-hydroxybutyrate &amp;lt;0.05 (0.02-0.27mmol/l), 8AM cortisol 10.7 (7.0-25.0 ug/dl), albumin 3.2mg/dl, HbA1c 5.8%, IGF1 53ng/mL (34-245ng/mL), IGF2 203ng/mL (267-616ng/mL) with a IGF2:IGF1 ratio of 3.8. In our patient, the IGF2:IGF1 ratio was not &amp;gt;10 since his IGF 2 was suppressed by the recent steroid use. The rest of the clinical and biochemical features strongly suggested NICTH. His preoperative evaluation showed new onset HFrEF with volume overload. He underwent staged percutaneous coronary interventions with stents placement. He was given hydrocortisone 50mg q6H then to q8H during hospitalization and discharged home with hydrocortisone 40mg TID. He underwent radical resection of lung tumor after optimization of his cardiac condition. He was on stress dose of steroid during surgery. Since he was on high dose steroid for &amp;gt; 3months, hydrocortisone dose was tapered slowly after the surgery. Final biopsy reported solitary fibrous tumor extending to parenchymal staple line. Tumor cells are positive for CD34 and STAT6, and negative for desmin, SMA, and SOX10. He recovered uneventfully and was discharged home with prednisone 5mg daily and follow up in endocrine clinic. Conclusion: NICTH is a rare paraneoplastic syndrome characterized by low levels of insulin, C-peptide, proinsulin, and beta-hydroxybutyrate. A ratio of IGF-2/IGF-1 more than 10 confirms NICTH; however, normal ratio cannot exclude the diagnosis and factors such as low IGFBP 3 or steroid therapy for other conditions need to be considered. Surgery is the mainstay of treatment. Presentation: Saturday, June 17, 2023

FRI234 A Pregnancy With Two Special Surprises A Baby And A Nonhemorrhagic Adrenal Infarction During Pregnancy

Abstract Disclosure: S. Idriss: None. N. Barua: None. I. Jamal: None. A. Jabiev: None. Introduction: Unilateral Acute adrenal infarction (AAI) is a rare cause of acute abdomen in pregnancy, with a reported incidence of 1.3%. It usually presents with sudden, severe, and unremitting flank pain. The most common cause of AAI is adrenal vein thrombosis. We present a 26-year-old pregnant female who presents with right flank and back pain, found to have AAI without hemorrhage. Case: 26-year-old female Primigravida without significant past medical history presented to the emergency room at 33 weeks of gestation with sudden onset of RUQ flank and back pain. She was afebrile and normotensive. Physical exam was positive for right flank point tenderness. She underwent multiple investigations including an abdominal US which did not reveal an acute pathology. She was admitted and started on opioids which failed to control her pain. An abdominal MRI was obtained subsequently revealing 4.6cm right adrenal gland lesion suspicious for AAI without hemorrhage and normal left adrenal gland. The pain was poorly controlled warranting Dilaudid drip and repeat imaging/CT showed adrenal gland mass with density of 41-52 HU suspicious for lipid poor adenoma versus adrenal hematoma on CT scan. Initial AM Cortisol level was 46 ug/dl, then it trended down to 31.7. DHEAS was low at 94.2 ug/dl. Plasma metanephrines and normetanephrines were normal. Course was complicated with hypotension and worsening pain on day 10 of admission, repeat MRI showed increase in right adrenal lesion size and cystic transformation, containing some T2 hypointense septations and debris without notable intrinsic T1 hyperintensity to suggest blood products, and restricted diffusion which is a finding compatible with AAI. Repeat AM Cortisol and DHEAS were low at 12 and 61.3 respectively. Despite normal left adrenal gland, clinical picture was consistent with adrenal insufficiency and she was started on stress steroids. Thrombophilia workup was negative. She ultimately underwent c-section on day 13 of admission. She was discharged on physiologic dose of steroids with a pending repeat MRI and outpatient follow up. Discussion: Adrenal glands, especially with preexisting nodules are predisposed to micro-vascular thrombosis and infarction during procoagulable states. Pregnancy is a hypercoagulable state that predisposes patients to thrombotic events. The relative risk of thrombosis is 5-6 times higher in pregnant than non-pregnant females of the same age. Our patient had evidence of adrenal insufficiency and required steroid replacement. Anticoagulation was not started due to possible subtle hematoma on CT scan on initial imaging. Follow up imaging is planned. Conclusion: Adrenal infarction is a rare cause of abdominal pain during pregnancy, and if missed, it can result in devastating clinical consequences for the mother and the child. Adrenal insufficiency if found should be addressed to prevent circulatory collapse. Presentation: Friday, June 16, 2023

Subcutaneous immunoglobulin for patients with idiopathic inflammatory myopathies: a real-world, single-centre experience.

Idiopathic inflammatory myopathies (IIMs) are heterogeneous diseases characterized by skeletal muscle inflammation associated with cutaneous, pulmonary and/or other visceral organ involvement. IVIG has been recommended as an adjunct therapy for IIM patients refractory to conventional therapy. However, IVIG has high resource needs and increased risk of adverse reactions. Subcutaneous immunoglobulin (SCIG) therapy has been used as an alternative to IVIG in primary immunodeficiencies and neuroinflammatory disorders. We assessed the satisfaction, patient preference and effectiveness in IIM patients who transitioned from IVIG to SCIG. We retrospectively reviewed consecutive 20 patients with IIM who were transitioned from IVIG to SCIG therapy for >12 months. Patient preference between IVIG and SCIG was surveyed using a questionnaire previously used in studies of neuroinflammatory conditions. In addition, disease flares, changes in immunosuppression, cumulative prednisone doses and global disease activity were evaluated using the Myositis Intention to Treat Index (MITAX) 12 months pre- and post-SCIG initiation. Most patients (78.9%) preferred SCIG over IVIG and preferred home-based therapies to hospital-based therapies. There was no significant difference in global disease activity (MITAX 3.31 vs 3.02) or in cumulative steroid doses 12 months pre- or post-SCIG initiation. Three patients experienced disease flares, five escalated in immunosuppression, while four patients deescalated in immunosuppressive medications. SCIG is preferred by most patients over IVIG without a substantial increased disease activity or need for additional CS. Future cost-effectiveness studies may provide an additional rationale for utilizing SCIG over IVIG for maintenance therapy for IIM.

SAT086 Early-onset HNF1B-MODY With Persistent Insulin Requirement In A 2-year-old Female

Abstract Disclosure: F. Ighalo: None. S.R. Kelly: None. M. Tosur: None. M.E. Craven: None. Introduction: Diabetes related to HNF1B pathogenic variants or deletions (maturity-onset diabetes of the young 5 [MODY 5]) typically presents in adolescence or early adulthood, with a median age of 20 years. Bustamante et al. previously described two patients with 17q12 deletion encompassing HNF1B presenting with diabetes and pre-diabetes before the age of 3, who were managed with dietary intervention alone without insulin requirement. This case describes a 2-year-old diagnosed with HNF1B-MODY after developing hyperglycemia in the setting of an acute illness, who continued to require insulin therapy following recovery. Clinical Case: A 2-year-old female with a history of recurrent viral infections and failure to thrive was admitted to the intensive care unit in hypovolemic shock due to hemolytic uremic syndrome due to Shiga toxin. On hospital day 7, while on supraphysiologic steroid doses, she developed hyperglycemia with glucoses above 600 mg/dL. She required an insulin drip to maintain blood glucoses between 100 and 200 mg/dL. Her four-month hospital stay was complicated by cardiogenic shock requiring extracorporeal mechanical oxygenation, renal failure requiring hemodialysis, respiratory failure resulting in a tracheostomy, and dysphagia resulting in a gastrostomy tube. During this time, she continued to require insulin despite being weaned off steroids and transitioning from total parenteral nutrition to gastrostomy tube feeds. Her hemoglobin A1c one month post-diagnosis was 4.9%, and continued to rise to 6.6% and 7.6% at 3 and 4 months post-diagnosis, respectively. Testing for islet autoantibodies was negative. A chromosomal microarray analysis revealed a micro-deletion in chromosome 17q12 that included the HNF1B gene. MRI showed a near total absent pancreas, and multiple small cysts scattered throughout both kidneys. She also had fecal elastase levels in the insufficient range (135 mcg/g, normal &amp;gt;200 mcg/g). Six weeks after the start of insulin drip, she was transitioned from an insulin drip to subcutaneous insulin injections, and eventually placed on an insulin pump prior to discharge. With continued clinical improvement, her insulin doses decreased, but she was not able to come off insulin completely. She had gradual decline in her insulin requirements from 1.0 units/kg/day down to 0.1 units/kg/day at time of discharge. Her current insulin requirement at 6 months post-diagnosis is 0.2 units/kg/day. Conclusion: This case represents the rare development of diabetes before adolescence in HNF1B-MODY, and one of the most severe presentations seen in a prepubertal child requiring persistent insulin therapy at 6 months post-diagnosis. Potential contribution of complicated hospital course on persistent insulin requirement in the setting of 17q12 micro-deletion cannot be excluded. Presentation: Saturday, June 17, 2023

FRI269 Two Cases Of Familial Polyglandular Autoimmune Syndrome Type II Presenting With Adrenal Insufficiency Precipitated By SARS-CoV-2 Infection

Abstract Disclosure: J. Sassic: None. N. Hosein: None. G. Jackson: None. Introduction: Polyglandular autoimmune syndrome (PGA) type II is characterized primarily by autoimmune adrenal disease and thyroid disease. Additionally, about 50% of patients will experience autoimmune diabetes mellitus. The incidence of PGA type II is around 1:20,000 but shows strong familial clustering, and predominantly affects women in a 3:1 ratio. Here we report a case of two patients, a woman and her son, who were diagnosed 6 months apart with type II PGA who presented with adrenal insufficiency acutely affected by SARS-CoV-2 infection. Clinical Case: Patient 1 is a 59 year-old female with history significant for previously-diagnosed autoimmune thyroiditis who presented with complaint of generalized fatigue and weight loss for months following a SARS-CoV-2 infection, who was found to have severe hyponatremia with serum sodium of 106 mmol/L (137-145 mmol/L) and was admitted to the intensive care unit. There, she received cosyntropin testing which revealed severe adrenal insufficiency, with post-cosyntropin cortisol level at 1.2 mcg/dL (&amp;gt;14 mcg/dL). Anti-21-hydroxylase antibodies were positive. Her A1c was found to be 5.8% (&amp;lt;5.7%), indicating prediabetes in a patient with BMI of 18.5 kg/m2. Glutamic acid decarboxylase antibodies were tested and were also positive. Patient’s sodium was repleted and she was tapered from stress-dose to physiologic steroid dosing and was discharged on hydrocortisone and fludrocortisone. About 6 months later, Patient 2, a 25-year-old male and the son of Patient 1 presented to the emergency department with complaint of a week of nausea and vomiting, and three months of generalized fatigue. He was found to be SARS-CoV-2 positive and was also hyponatremic with serum sodium of 122 mmol/L. He also received cosyntropin testing which was revealed undetectably low cortisol levels both pre- and post-cosyntropin administration. Anti-21-hydroxylase antibodies and anti-thyroid peroxidase antibodies were positive, the latter at 243.3 IU/mL (&amp;lt;5.61 IU/mL). Patient responded well to stress-dose steroids and normal saline to normalize his sodium levels. Due to his mother’s positive antibodies, glutamic acid decarboxylase, anti-islet, and anti-insulin antibodies were also tested, which were negative. Patient was discharged on physiologic hydrocortisone and fludrocortisone. Conclusion: Polyglandular autoimmune syndrome is a relatively uncommon disease but with strong polygenic inheritance. This case was an interesting presentation where SARS-CoV-2 infection likely precipitated the symptoms and acute effects of adrenal insufficiency. Additionally, knowledge of the patient’s family history resulted in rapid diagnosis and management of the patient’s underlying pathophysiology. Presentation: Friday, June 16, 2023

Anti-Ma2 Antibody-Mediated Paraneoplastic Cerebellar Degeneration and Myeloneuropathy Secondary to Lymphoma.

A 61-year-old woman with a history of untreated low-grade B-cell lymphoma presented with blurry vision, unsteadiness, and worsening pain on touching skin of the upper trunk was enrolled. Blurry vision was attributed to oscillopsia from downbeat nystagmus, which later evolved into macrosaccadic oscillations. MRI brain and spine showed mild, longitudinally extensive T2 hyperintensity in the central gray matter of the spinal cord extending from the medulla to T11 level. Serum paraneoplastic panel was negative; however, she had very high titers of anti-Ma2 antibodies in cerebrospinal fluid. The diagnosis of paraneoplastic neurological syndrome was made. Empiric treatment with high dose of intravenous steroids followed by intravenous immunoglobulin infusions did not improve her symptoms. An extensive search for an underlying tumor commenced and was initially unrevealing. However, two-month follow-up positron emission tomography scan showed increased uptake in a right pulmonary nodule, which when biopsied confirmed diagnosis of extranodal marginal zone lymphoma. The final diagnosis was anti-Ma2 antibody-mediated paraneoplastic cerebellar degeneration and myeloneuropathy secondary to lymphoma.

Multimodal imaging in radiation retinopathy following orbital metastasis

Background: Radiation retinopathy is a major cause of vision loss in patients receiving radiotherapy to the head and orbit. Diabetic retinopathy is included in the differential diagnosis owing to similar clinical features, including microaneurysms, cotton-wool spots, hard exudates, and macular edema. The only significant pathological difference is that radiation retinopathy spares pericytes, unlike diabetic retinopathy. Multimodal imaging helps diagnose and predict the prognosis of radiation retinopathy, which is presented in this case report.&#x0D; Case Presentation: A 55-year-old woman diagnosed with stage-4 metastatic breast carcinoma presented with gradual diminution of vision in the left eye (OS) over 5 months. Vision in the right eye was lost because of orbital radiotherapy for orbital metastasis. The patient underwent multiple sessions of chemotherapy and radiotherapy. Examination of the left eye revealed a best-corrected distance visual acuity (BCDVA) of 20/30. Fundus examination of the OS revealed multiple cotton-wool spots and retinal hemorrhages. Fundus fluorescein angiography (FFA) showed diffuse macular leakage with capillary nonperfusion. Multicolor imaging (MCI) with Spectralis™ revealed black dots in the blue and green reflectance images, corresponding to capillary dilatation on FFA. Darker dots were more evident in the infrared images. BCDVA improved to 20/20 in OS after tapering the dose of oral steroids for 2 months, with improvements in hemorrhages and cotton-wool spots. Focal laser photocoagulation was recommended for the treatment of persistent macular edema. The patient declined further treatment, was lost to follow-up, and passed away 6 months later.&#x0D; Conclusions: This case highlights the importance of multimodal imaging for the identification and classification of radiation retinopathy. MCI using SpectralisTM has been described for the first time in radiation retinopathy and can be used to complement existing imaging modalities. Future studies involving more patients and a longer follow-up duration may provide better results for the applicability of these imaging modalities in the clinical setting.

Prevalence of Helicobacter pylori infection in adult immune thrombocytopenia patients

Background: Helicobacter pylori is a Gram-negative, microaerophilic bacteria colonizing more than half of the world’s human stomachs. It is the causal agent of active chronic gastritis and the most common cause of peptic ulceration, including gastric and duodenal ulcers. Aims and Objectives: This study aims to the prevalence of H. pylori infection in adult immune thrombocytopenia (ITP) patients. Materials and Methods: An interventional and prospective study was conducted over 6 months with over 50 ITP patients, including those admitted to the general medicine ward and those in regular follow-up in medicine outpatient department. In addition, in all primary ITP patients, a stool antigen test for H. pylori Ag and baseline complete blood count, including platelet count, were done. In addition, all patients’ platelet count was monitored twice weekly for 6 months. Results: Of the 50 patients, 40 are female and 10 are male. The bleeding manifestation was present in 34 patients (68%) and absent in 16 (32%). Among 34 patients, purpura was more frequent (35.3%), followed by gum bleeding 17.6%. Fourteen people tested positive for the H. pylori antigen. Thirty-six patients were found to be H. pylori antigen negative. H. pylori positive frequency was 28%. Patients who receive both steroids and an H. pylori regimen are 9 (18%). Patients who received the H. pylori regimen were only 5 (10%). Patients only receiving steroid doses are 27 (54%). Conclusion: We conclude that 28% of our study patients are infected with H. pylori, and eradicating this organism significantly improves the platelet count. However, a more extended follow-up period is needed to detect the true prevalence of H. pylori infection and the duration of remission.

Re-Irradiation for Diffuse Intrinsic Pontine Glioma with 3 Gy per Fraction

Radiotherapy (RT) improves survival in pediatric diffuse intrinsic pontine glioma (DIPG). After recurrence, re-irradiation (re-RT) offers palliation of symptoms and extends life in patients after exhaustion of investigational options and clinical decline. Practice patterns vary in dose and fractionation for re-RT, with majority of reported cases treated with conventional fractionation. Given radiobiologic rationale for hypofractionation in glioblastoma, we hypothesized that treatment with 3 Gy per fraction is safe and effective for re-RT to the brainstem for DIPG. We identified patients at our institution, ages 1-25, treated with re-RT to the brainstem for DIPG from 2012-2022. Patient demographics, treatment details, and clinical outcomes were reviewed from the medical record. Analysis was completed in R 4.2.2 using Kaplan-Meier method with log-rank test for survival estimates and Fisher's exact test for categorical variables. A total of 22 patients received re-RT for DIPG. All patients had received 54-59.4 Gy with conventional fractionation at the time of diagnosis. Re-RT dose was initially 20-24 Gy in 2-Gy fractions (n = 6) and continued at 30-36 Gy in 3-Gy fractions (n = 14). Two patients did not complete re-RT due to continued clinical decline from disease progression after 1-2 fractions. Of the 20 that completed re-RT, 11 were female, median age was 5 years (3-14), median interval since initial RT was 8 months (3-20), 12 (60%) received concurrent bevacizumab, and OS from diagnosis was 18 months. Median OS from start of re-RT for patients treated with 3 Gy per fraction was 8.2 months and 13 (93%) clinically improved to taper pre-treatment steroid dose down (n = 9) or off (n = 4) within 2 months after re-RT. For those treated with 2 Gy per fraction, median OS from re-RT was 7.5 months and 3 (75%) improved to taper steroids down (n = 2) or off (n = 1). Overall, 2 patients were not on steroids, 2 were maintained at same steroid dose, and 0 required increase from pre-treatment steroid dose within 6 weeks after re-RT. There was no significant difference in OS from re-RT (p = 0.2) or steroid taper (p = 0.4) between fractionation groups. No patients developed radionecrosis of normal brain tissue. Patients receiving re-RT achieved extended survival comparable to published outcomes and majority experienced clinical improvement to allow steroid taper. While radionecrosis is a reported risk in prior published series, our experience demonstrates the safety and effectiveness of using 3 Gy per fraction to 30-36 Gy for meaningful palliation in this population.

Total Lymphoid Irradiation in the Treatment of Heart Transplant Rejection: Single Institution Long-Term Results

Acute cardiac allograft rejection is a major cause of morbidity and mortality post-transplant. Total lymphoid irradiation (TLI) has been shown to cause long-lasting alterations in lymphocyte sub-sets, and thereby induces a state of partial response that is useful to prevent organ transplant rejection. In our previous report, treatment with TLI resulted in decreased episodes of acute rejection and steroid dosage requirements for up to 9.1 years post cardiac transplantation. In this study, we report an update on the short- and long-term effects of TLI in the treatment of cardiac transplant rejection. We performed a retrospective analysis of patients with intractable cardiac allograft transplantation evaluated in the department of radiation oncology at our institution over 23 years (1998-2021). Cardiac allograft rejection was defined as multiple or persistent episodes of rejection despite aggressive immunosuppressive therapy. The prescribed dose was 8 Gy in 10 fractions to be delivered over 5 weeks. All episodes of pathologic acute cardiac rejection, duration of immunosuppression, and episodes of acute infection requiring treatment before and after TLI were documented. Overall survival (OS) was analyzed using Kaplan-Meier method. The median time to first cardiac allograft rejection and the median time to first acute rejection was monitored. Of the 29 patients included, 21 (72.4%) had ISHLT grade 1R, 5 (17.2%), grade 2R, and 2(6.9%) grade 3R rejection. Rejection grade was unknown for 1 patient. The mean number of acute rejections after transplant was 14.4 episodes per patient (range 1-44) with median time to first rejection of 0.63 months. The median radiation dose was 8 Gy (range 7.2-8 Gy) delivered over a mean of 31 days. Treatment was stopped early in 2 (6.5%) patients (after 7.2 Gy and 7.9 Gy) for severe bone marrow suppression and drop in CD4 counts, respectively. The number of rejections dropped from 14.2 to 3.97 per patient over a median time of 29.0 months vs 28.1 months pre and post TLI (p = 0.01). The frequency of ISHLT acute grade 3R rejections decreased from 0.58 to 0.06 episodes per patient pre and post TLI (p = 0.02). Immunosuppressant requirements decreased from 2.83 before TLI to 2.69 after TLI (p = 0.71). Infection rates per patient were 0.71 pre TLI and remained at 0.63 post TLI. Treatment was well tolerated with 4 (13.8%) grade 2 or higher radiation toxicity. Median follow up was 76.3 months. Median and 3-year OS were 53.4 months and 60.9%, respectively. TLI is a safe and effective treatment for control of intractable cardiac rejection. The episodes of acute rejection and immunosuppressant requirements are decreased, but with long-term follow up, these patients continue to experience rejection. However, TLI lowers the frequency of ISHLT moderate to severe rejection episodes for up to 6.4 years. There was no increased risk of severe infections and there were only minimal short- and long-term grade 2 or higher radiation toxicities.