Stress Doses Of Hydrocortisone Research Articles

728: OUTCOMES AND TIMING OF STRESS-DOSE HYDROCORTISONE IN PEDIATRIC SEPTIC SHOCK

Introduction: Sepsis is a major contributor to pediatric morbidity and mortality worldwide. Pediatric sepsis is defined as systemic inflammatory response syndrome (SIRS) in the presence of suspected or confirmed infection. Pediatric septic shock is defined as sepsis with cardiovascular organ dysfunction. In vasoactive-inotropic recalcitrant septic shock, stress dose corticosteroids are often administered for presumed critical illness related corticosteroid insufficiency (CIRCI). However, there is not consistent data to support the use of stress dose hydrocortisone (HCT) in septic shock. To further investigate clinical outcomes related to timing of HCT, we hypothesized that children with vasoactive-inotropic recalcitrant septic shock who received early HCT (< 6 hours) would have lower vasoactive-inotropic scores (VIS) in the first 48 hours, a decreased length of stay (LOS) and increased ventilator-free days (VFD). Methods: A retrospective chart review was performed from November 2017 to December 2021 of subjects 0 to < 18 years, admitted to the pediatric intensive care unit (PICU) meeting the definition for septic shock, requiring vasopressors and/or inotropes and given HCT for CIRCI. We measured VIS, PICU and hospital LOS and VFD. Subjects with chronic steroid use or who received etomidate were excluded. Results: Of 227 subjects screened, 23 met criteria for analysis. Seven subjects received HCT within 6 hours of vasopressor initiation (early group), while 16 received HCT >6 hours (late group). Initial VIS average was 10.96 in the early group and 10.78 in the late group. At 48 hours, average VIS in the early group was 9.51 and 1.44 in the late group. Average PICU LOS was 15.58 for the early group and 10.82 for the late group. Average hospital LOS was 37.47 for the early group and 19.76 for the late group. VFD average was 15.32 in the early group and 16.61 in the late group. Pediatric Index of Mortality 3 (PIM-3) average in the early group was 2.02 and 1.61 in the late group. Mortality incidence was 2 in 7 in the early group, and 4 in 16 in the late group. Conclusions: Preliminary data suggests there is an increased VIS at 48 hours, increased PICU and hospital LOS, and decreased VFD with early administration of HCT. Although PIM-3 scores were higher in the early group, mortality was similar between groups.

PMON90 Pituitary Abscess, A rare cause of Hypopituitarism

Abstract Introduction Pituitary abscess is a rare condition, representing 0.2-0.6% of all pituitary lesions. The presentation can be non-specific, and imaging can mimic a pituitary adenoma, often making the diagnosis challenging. We present a case of a pituitary abscess from Staphylococcus epidermidis and Corynebacterium propinquum with resulting hypopituitarism and central diabetes insipidus (DI). Clinical case A 42-year-old man with a history of hypothyroidism secondary to thyroiditis presented to the emergency room with sudden onset headache, nausea, and emesis. There were associated symptoms of fatigue, weight loss, and sexual hypofunction for approximately six months. He did not have fever or leukocytosis. Brain MRI revealed a 2.5×1.8×1.6 cm sellar and suprasellar mass with rim enhancement and compression of the optic chiasm. Pre-operative pituitary hormonal evaluation showed central hypogonadism, growth hormone deficiency and secondary adrenal insufficiency: FSH 0.4 mIU/mL (n &amp;lt; 15mIU/mL), LH &amp;lt;0.2mIU/mL (n &amp;lt; 10 mIU/mL), AM Testosterone 8 ng/dL (n 250-1100 ng/dL), IGF-1 38 ng/ml (n 52-328 ng/mL), ACTH 5.6 pg/mL (n 7.2-63 pg/mL), AM cortisol 4.9 ug/mL (n 4-10 ug/dL). Prolactin was normal (14.7 ng/mL, n &amp;lt;15 ng/mL). TSH was elevated to 4.88 uU/mL (n 0.3-4.2 uU/mL) with a low FT4 of 0.5 ng/dL (n 0.6-1.5 ng/dL) on levothyroxine 75mcg daily. He was started on stress doses of hydrocortisone and underwent trans-sphenoidal pituitary resection. Intraoperative findings were significant for 3-5 mL of purulent debris in the sella suggestive of a pituitary abscess. He was started on Ceftriaxone, Metronidazole, and Vancomycin, with improvement in headache. Pituitary abscess cultures grew Staphylococcus epidermidis and Corynebacterium propinquum. Blood cultures were negative for any bacterial growth. Post-operative course was complicated by transient DI. The patient was discharged on Linezolid to complete six weeks of antibiotics, a physiological dose of hydrocortisone (20mg daily), and levothyroxine 88mcg daily. At outpatient Endocrine follow-up a month later, he was found to have a recurrence of DI and started on maintenance desmopressin with improvement in polyuria and polydipsia. Conclusion Pituitary abscesses are rare, life-threatening pituitary lesions. 70% of cases are primary pituitary abscesses, which develop in a previously healthy gland. Secondary pituitary abscesses arise within a pre-existing pituitary lesion and are less common. Clinical manifestations include headache, visual disturbance, and hypopituitarism. The diagnosis is challenging since classical signs of infection, such as fever and leukocytosis, are uncommon, and pre-operative radiological findings can be non-specific. The majority of cases are confirmed intra-operatively. Commonly isolated organisms are Gram-positive cocci (Staphylococcus and Streptococcus) and Gram-negative bacteria (Neisseria, Escherichia coli and Corynebacterium). This case highlights the importance of considering pituitary abscesses in the differential diagnosis of patients presenting with a sellar mass. Prompt recognition of a pituitary abscess will allow for rapid treatment with trans-sphenoidal evacuation, antibiotic therapy, and pituitary hormonal replacement when indicated. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP170 Check Point Inhibitor Associated Multi-Endocrine Dysfunction Presenting With Euglycemic Ketoacidosis

Abstract Introduction Immune check point inhibitors have become breakthrough therapy for many types of cancers. They inhibit one of two immune regulatory pathways, the cytotoxic T-lymphocyte antigen 4 (CTLA-4), and 'programmed death-1' (PD-1) and (PD-L1) pathways. Removing immune regulation allows for anti-cancer immune responses. They also cause immune related endocrine dysfunction such as hypophysitis, thyroiditis, diabetes mellitus (DM) and primary adrenal insufficiency (AI). We describe a patient on Pembrolizumab (PEM) (an anti-PD-1 inhibitor) who presented with new onset DM, euglycemic diabetic ketoacidosis (DKA) with simultaneous secondary AI. Case report 54-year-old woman with stage 4 non-small cell carcinoma of the lung (NSCLC) with known brain metastasis, was under therapy with carboplastin, paclitaxel and PEM, presented with headache, blurry vision and altered mental status. She had past history of Graves’ disease s/p radioactive iodine therapy, currently on levothyroxine. For two weeks, she had decreased oral intake, and generalized weakness. Upon presentation, she was cachectic, BP 152/65, pulse 117 and confabulating. Laboratory evaluation showed: serum glucose 72 mg/dL, Na 139 mmol/L, K 3.2 mmol/L, Cl 113 mmol/L, HCO3 11 mmol/L, anion gap 15 mmol/L, beta-hydroxybutyrate 4.8 mmol/L, lactic acid 0.7 mmol/L, venous pH 7.2 and base excess -16.6 mmol/L. The delta-delta gap was 10 mmol/L, compatible with a mixed anion-gap and hyperchloremic acidosis (HCA). Antibodies to GAD-65, and Zinc transporter-8 were negative. To evaluate euglycemia despite DKA, levels were obtained for serum cortisol 1 mcg/dL, and ACTH &amp;lt;1 pg/mL confirming secondary AI. MRI neuroimaging showed several metastatic brain lesions, a small pituitary gland without stalk enhancement or thickening. Management of euglycemic ketoacidosis required high dose glucose infusion (&amp;gt;10 g/hour), stress doses of hydrocortisone (HC), and infusion of low chloride solute for HCA. Conclusion Awareness of the potential for multi-endocrine dysfunction, directed us towards the urgent institution of therapy for DKA with supplementation of stress dose HC for presumed AI, the latter as a cause of relative "hypoglycemia". Central AI was confirmed with undetectable levels of cortisol and ACTH. Although less frequent than with CTLA-4 inhibitors, PD-1 inhibitors are associated with hypophysitis even without abnormalities on pituitary MRI. The DM (associated with PD-1 inhibitors) although autoimmune is nature, is "antibody" positive approximately 50% of the time. Further therapy for both euglycemic DKA and HCA required adjustment of the conventional management for DKA. To our knowledge this is the first reported case of Euglycemic DKA and secondary AI due to PD-1 inhibitors per literature review. Reference: Walters AGB, BraatvedtG G. Endocrine adverse effects of immune check point inhibitors . Intern Med J. 2021Jul;51(7): 1016-1020. doi: 10.111/imj . 14992. PMID: 34278695. Hattersley R, Nana M,Lansdown AJ. Endocrine complications of immunopathies: a review . ClinMed(Lond).2021 Mar;21(2): e212-e222. doi: 10.7861/clinmed.2020-0827. PMID: 33762389;PMCID: PMC8002767 Presentation: No date and time listed

PSAT307 Patient with Myxedema Coma and Subsequent Iatrogenic Thyrotoxicosis - Role of COVID-19 Pandemic

Abstract Introduction Myxedema coma is a rare presentation of severe hypothyroidism. The low incidence of this life-threatening disease may be attributed to easy availability of TSH testing and thyroid hormone replacement therapy. Well documented cases of thyroiditis and thyrotoxicosis due to SARS-CoV-2 are now available in medical literature. Additionally, COVID-19 pandemic has also caused higher rates of non-compliance with medications and appointments. This has resulted in higher rates of exacerbations of most chronic illnesses, including thyroid diseases. We present a case of myxedema coma and subsequent iatrogenic hyperthyroidism during the COVID-19 pandemic. Clinical Case 57-year-old male with paroxysmal atrial fibrillation, CHF, CKD stage IV, type 2 diabetes mellitus, hypertension, and post ablative hypothyroidism was found unresponsive at home. Initial vitals were temperature 95.1F, HR 52 beats per minute, RR 14 breaths per min, BP 90/62 mmHg, and glucose 68 mg/dL. There was no evidence of goiter, and he had generalized edema. Initial labs showed hyponatremia, elevated CPK, TSH 111uIU/mL (0.27-4.2 uIU/mL) and free T4 was &amp;lt;0.1 ng/dL (0.93-1.7 ng/dL). He was intubated, needed vasopressor support, and was treated with empiric antibiotics. He was diagnosed with myxedema coma which was treated with 200 mcg IV levothyroxine, and stress dose hydrocortisone. He was extubated on day 4 of hospital admission after which oral levothyroxine 275 mcg daily was initiated, and steroids were tapered off. Patient's pharmacy confirmed that Levothyroxine was not last filled more than eight months ago. Patient was hospitalized 3 weeks later for pneumonia and Levothyroxine dose was further increased to 300 mcg due to persistently elevated TSH levels. Three months later, patient was admitted for Atrial fibrillation in rapid ventricular response with difficult to control tachycardia. His TSH was 0.01 uIU/mL and thyroxine of 1.93 ng/dL despite not taking any medication for 2 weeks. He admitted to not following up with endocrinologist due to the surge in COVID-19 cases. Dose of levothyroxine was decreased to weight-based dose of 225 mcg, and patient discharged with instructions to repeat labs in 6 weeks and follow up with a clinical provider. Conclusion This case highlights the consequences of under and over replacement of thyroid hormone. Viral illnesses including SARS-CoV-2 can precipitate myxedema coma in patients with severe hypothyroidism. A high index of suspicion is needed to treat this disease in a timely manner. Providers must make allowances for the limitations in our system to function in a pandemic. Prescribing extra medication refills and offering virtual medicine appointments may help lower hospitalizations. Also, understanding the effect of non-thyroidal illness on thyroid function tests and knowing that TSH takes six weeks to normalize after starting/ adjusting thyroid hormone dose will avoid premature adjustment in hormone doses. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Insuffisance surrénale au cours des états critiques : nouveaux concepts et place de la corticothérapie

The classical model of the vital increase in systemic glucocorticoid availability in response to sepsis- and hyperinflammation-induced critical illness is one of an activated hypothalamus-pituitary-adrenocortical axis. However, research performed in the last decade has challenged this rather simple model and has unveiled a more complex, time-dependent set of responses. ACTH-driven cortisol production is only briefly increased, rapidly followed by orchestrated peripheral adaptations that maintain increased cortisol availability for target tissues without continued need for increased cortisol production and by changes at the target tissues that guide and titrate cortisol action matched to tissue-specific needs. One can speculate that these acute changes are adaptive and beneficial for the host. Treatment with stress-doses of hydrocortisone has pharmacological effects but has also shown to negatively interfere with these adaptive changes. The new insights also suggest that prolonged critically ill patients, treated in the ICU for several weeks, may develop central adrenal insufficiency, although it remains unclear how to best diagnose and treat this condition.

The hypothalamus-pituitary-adrenal axis in sepsis- and hyperinflammation-induced critical illness: Gaps in current knowledge and future translational research directions.

SummaryThe classical model of the vital increase in systemic glucocorticoid availability in response to sepsis- and hyperinflammation-induced critical illness is one of an activated hypothalamus-pituitary-adrenocortical axis. However, research performed in the last decade has challenged this rather simple model and has unveiled a more complex, time-dependent set of responses. ACTH-driven cortisol production is only briefly increased, rapidly followed by orchestrated peripheral adaptations that maintain increased cortisol availability for target tissues without continued need for increased cortisol production and by changes at the target tissues that guide and titrate cortisol action matched to tissue-specific needs. One can speculate that these acute changes are adaptive and that treatment with stress-doses of hydrocortisone may negatively interfere with these adaptive changes. These insights also suggest that prolonged critically ill patients, treated in the ICU for several weeks, may develop central adrenal insufficiency, although it remains unclear how to best diagnose and treat this condition.

Diagnosis and Management of Adrenal Crisis in 46XX Congenital Adrenal Hyperplasia Infant

Highlight: The diagnosis and therapy of Congenital Adrenal Hyperplasia (CAH) children with Adrenal crisis (AC) case report. Adrenal crisis (AC) is a life-threatening emergency that contributes to the high death rate of children with adrenal insufficiency. The early detection and prompt treatment can improve the outcomes of patients with CAH and AC. Abstract: Adrenal crisis is the acute complication of the patient with congenital adrenal hyperplasia. Congenital adrenal hyperplasia (CAH) is a rare condition. Children with CAH commonly come to the emergency room due to acute complications. The condition has high mortality and thus needs early recognition. Newborn screening for CAH in Indonesia is not routinely performed and has not been suggested yet. The purpose of this case report was to report a case of adrenal crisis in a congenital adrenal hyperplasia patient focused on diagnosis and therapy. A female, 10 months old infant, was admitted to the emergency department with a chief complaint of a decrease of consciousness for 3 hours before admission and frequent vomiting since born. On physical examination, there was clitoromegaly. Laboratory showed 17-OH progesterone: 173 ng/dL (7-77 ng/dL) and karyotyping: 46 XX. Management of adrenal crisis is a stress dose of hydrocortisone and rehydration. Education is the key to optimal outcomes and normal growth and development.

Abstract #1183604: Check point inhibitor associated multi-endocrine dysfunction presenting with euglycemic ketoacidosis

Immune check point inhibitors have become breakthrough therapy for many types of cancers. They inhibit one of two immune regulatory pathways, the cytotoxic T-lymphocyte antigen 4 (CTLA-4), and ‘programmed death-1’ (PD-1) and (PD-L1) pathways. Removing immune regulation allows for anti-cancer immune responses. They also cause immune related endocrine dysfunction such as hypophysitis, thyroiditis, diabetes mellitus (DM) and primary adrenal insufficiency (AI). We describe a patient on Pembrolizumab (PEM) (an anti-PD-1 inhibitor) who presented with new onset DM, euglycemic diabetic ketoacidosis (DKA) with simultaneous secondary AI. 54-year-old woman with stage 4 non-small cell carcinoma of the lung (NSCLC) with known brain metastasis, was under therapy with carboplastin, paclitaxel and PEM, presented with headache, blurry vision and altered mental status. She had past history of Grave's disease s/p radioactive iodine therapy, currently on levothyroxine. For two weeks, she had decreased oral intake, and generalized weakness. Upon presentation, she was cachectic, BP 152/65, pulse 117 and confabulating. Laboratory evaluation showed: serum glucose 72 mg/dL, Na 139 mmol/L, K 3.2 mmol/L, Cl 113 mmol/L, HCO3 11 mmol/L, anion gap 15 mmol/L, beta-hydroxybutyrate 4.8 mmol/L, lactic acid 0.7 mmol/L, venous pH 7.2 and base excess -16.6 mmol/L. The delta-delta gap was 10 mmol/L, compatible with a mixed anion-gap and hyperchloremic acidosis (HCA). Antibodies to GAD-65, and Zinc transporter-8 were negative. To evaluate euglycemia despite DKA, levels were obtained for serum cortisol 1 mcg/dL, and ACTH < 1 pg/mL confirming secondary AI. MRI neuroimaging showed several metastatic brain lesions, a small pituitary gland without stalk enhancement or thickening. Management of euglycemic ketoacidosis required high dose glucose infusion ( >10 g/hour), stress doses of hydrocortisone (HC), and infusion of low chloride solute for HCA. Awareness of the potential multi-endocrine dysfunction, directed us towards the urgent institution of therapy for DKA with supplementation of stress dose HC for presumed AI, the latter as a cause of relative “hypoglycemia”. Central AI was confirmed with undetectable levels of cortisol and ACTH. Although less frequent than with CTLA-4 inhibitors, PD-1 inhibitors are associated with hypophysitis even without abnormalities on pituitary MRI. The DM (associated with PD-1 inhibitors) although autoimmune is nature, is “antibody” positive approximately 50% of the time. Further therapy for both euglycemic DKA and HCA required adjustment of the conventional management for DKA.

Abstract #1178145: A Rare case of Pituitary Apoplexy associated with COVID infection presenting with Central Diabetes Insipidus

Pituitary apoplexy (PA) is rare and occurs in up to 20% of patients with a non-functioning pituitary adenoma. It can occur de novo or can be precipitated by surgery, head trauma, anticoagulant therapy, and pregnancy among others. Incidence of persistent Diabetes Insipidus (DI) is only about 2% in such patients. Limited literature exists on the association of PA and COVID infection. We present a case of PA and subsequent central DI in a patient with a pituitary adenoma and severe COVID-19 pneumonia. A 64-year-old male with a history of a non-functioning pituitary macroadenoma (2 cm) of 5 months duration, primary hypothyroidism, and acute myeloid leukemia on chemotherapy presented to the emergency department with one day of headache, fever, and cough. He was diagnosed with COVID-19 pneumonia and started on dexamethasone, broad spectrum antibiotics and supplemental oxygen. Sudden loss of peripheral vision in his left eye with a persistent headache and altered mental status led to plain computed tomography that revealed a hyperattenuating suprasellar mass compressing the optic chiasm. MRI brain showed a T2 hypointense acutely hemorrhagic suprasellar mass compressing the infundibulum and the optic chiasm indicative of PA. Labs showed thrombocytopenia with platelet count 55,000/mcL (130-400), low AM cortisol 3 mcg/dL, normal prolactin 10 ng/mL, normal thyroid function and preserved somatotrophic axis. In addition, the patient developed polyuria with a urine output of up to 8 liters in a 24-hour period, acute hypernatremia (sodium 172 mmol/L), urine specific gravity < 1.005 and serum osmolality 360 mOsm/kg (275-295 mOsm/kg). Conservative management with stress dose hydrocortisone and desmopressin was the first line of therapy. Levothyroxine was continued at home dose. After resolution of COVID-19 pneumonia and improvement in electrolyte disarray, the patient underwent pituitary decompression surgery in 3 weeks with subsequent resolution of DI post-operatively. He was discharged home on hydrocortisone (20 mg total daily dose) and levothyroxine with close endocrinology follow up. Association of COVID infection and PA has been reported in 10 patients in the literature so far. Although the exact mechanism is unknown, SARS-CoV-2 neural invasion via cerebral ACE-2 expression can lead to oxidative stress and thrombogenesis, ultimately predisposing to neural hemorrhage. Thrombocytopenia secondary to chemotherapy can be a contributing factor in our patient. DI is rare and usually resolves after decompression surgery. Further research focusing on the association and pathophysiology of COVID-19 with PA in those without precipitating factors are needed.

Adrenal gland haemorrhages following motor vehicle accident with resultant adrenal insufficiency.

SummaryAdrenal gland haemorrhage is an uncommon, yet likely under-diagnosed complication of high-impact trauma, such as motor vehicle accidents (MVA). It usually occurs with multi-trauma and is associated with additional injuries to the ribs, liver, kidney, spleen and vertebrae. Trauma cases with resultant adrenal gland injury have higher mortality rates. Primary adrenal insufficiency as a result of bilateral adrenal haemorrhage is potentially fatal. We report three cases of life-threatening adrenal insufficiency following adrenal injuries sustained in MVA’s. Case 1 was a 60-year-old-male who presented with acute haemodynamic instability on admission. Case 2 was an 88-year-old female on anticoagulation for atrial fibrillation, who developed haemodynamic instability 10 days into her admission. Case 3 was a 46-year-old male who developed hyponatraemia 2 weeks post-MVA. All were commenced on stress dose hydrocortisone replacement with improvement in clinical status. Only case 1 has had complete adrenal axis recovery, whereas the other patients remain on maintenance hydrocortisone replacement. Our cases demonstrate acute and subacute presentations of adrenal insufficiency following traumatic bilateral adrenal haemorrhages and highlight the importance of assessing adrenal morphology and function in any trauma patient with haemodynamic instability or hyponatraemia.Learning pointsAdrenal gland haemorrhage is an under-diagnosed consequence of high-impact trauma.Trauma patients with adrenal haemorrhage have a significantly increased mortality risk.Bilateral adrenal gland haemorrhage can result in life-threatening adrenal insufficiency requiring urgent glucocorticoid replacement.Biochemical assessment of the adrenocortical axis should be considered in all patients presenting with high-impact trauma following motor vehicle accidents.Given the potential for delayed presentation, any patients with new haemodynamic instability should have repeat biochemistry and/or imaging performed, even if initial adrenal imaging and investigations were normal.

Critical Illness-induced Corticosteroid Insufficiency: What It Is Not and What It Could Be.

Critical illnesses are hallmarked by increased systemic cortisol availability, a vital part of the stress response. Acute stress may trigger a life-threatening adrenal crisis when a disease of the hypothalamic–pituitary–adrenal (HPA) axis is present and not adequately treated with stress doses of hydrocortisone. Stress doses of hydrocortisone are also used to reduce high vasopressor need in patients suffering from septic shock, in the absence of adrenal insufficiency. Research performed over the last 10 years focusing on the HPA axis during critical illness has led to the insight that neither of these conditions can be labeled “critical illness–induced corticosteroid insufficiency” or CIRCI. Instead, these data suggested using the term CIRCI for a condition that may develop in prolonged critically ill patients. Indeed, when patients remain dependent on vital organ support for weeks, they are at risk of acquiring central adrenal insufficiency. The sustained increase in systemic glucocorticoid availability, mainly brought about by suppressed circulating cortisol-binding proteins and suppressed hepatic/renal cortisol metabolism, exerts negative feedback inhibition at the hypothalamus/pituitary, while high levels of other glucocorticoid receptor ligands, such as bile acids, and drugs, such as opioids, may further suppress adrenocorticotropic hormone (ACTH) secretion. The adrenal cortex, depleted from ACTH-mediated trophic signaling for weeks, may become structurally and functionally impaired, resulting in insufficient cortisol production. Such a central HPA axis suppression may be maladaptive by contributing to lingering vasopressor need and encephalopathy, hence preventing recovery. Here, we review this concept of CIRCI and we advise on how to recognize and treat this poorly understood condition.

Clinical Utilization of Stress Dose Hydrocortisone in Adult Patients With Septic Shock: A Retrospective Observational Study at a Large Academic Medical Center

Background: The use of stress dose corticosteroids, specifically, hydrocortisone, in septic shock is heterogeneous, and current clinical trials yield conflicting results. Regardless, they are still recommended by guidelines for vasopressor-dependent septic shock. Objectives: This study sought to characterize current practice of hydrocortisone use in patients with septic shock and secondarily to compare clinical outcomes of those who received hydrocortisone to those who did not. Methods: This single center, retrospective cohort study evaluated patients with septic shock admitted to a tertiary care center between 2012 and 2017. Patients receiving hydrocortisone for at least two doses were compared to those without. Results: 3411 septic shock patients were included; 1593 (47%) received hydrocortisone and 1818 (53%) did not. Patients who received hydrocortisone had higher lactate (4.0 vs 3.4 mmol/L; P < .01) and Acute Physiology and Chronic Health Evaluation (APACHE) III scores (104.1 vs 91.0; P < .01). Vasopressor duration was 1.7 days longer in the hydrocortisone group (P < .01), and the hydrocortisone group had higher hospital mortality (52% vs 38%; P < .01). A propensity score–matched population was conducted in patients with APACHE scores >100: vasopressor duration was longer in those who received hydrocortisone (3.9 vs 2.0 days; P < .01), and hospital mortality was higher (59.3% vs 53.1%; P = .036); however, after multivariable adjustment, no association between receipt of hydrocortisone and hospital mortality was detected (OR 1.2 [95% CI .9–1.6]). Conclusions: Patients who received hydrocortisone were more severely ill than those that did not, making retrospective evaluation of this question challenging. These results highlight the wide variability and heterogeneity in hydrocortisone use in clinical practice.

Successful Treatment with ALVR105 for Disseminated Adenovirus Infection in an Infant after Allogeneic Hematopoietic Cell Transplantation: A Case Report

Background: Adenovirus (AdV) disease is one of the most difficult-to-manage complications in infants and children who have received allogeneic hematopoietic cell transplantation (HCT). Cidofovir has been used off-label as preemptive anti-adenoviral therapy. It is the current standard of care treatment, but data supporting its therapeutic value are lacking, and its use is limited by severe renal toxicity.Case: A 10-month-old male with infantile osteopetrosis underwent a single-unit umbilical cord blood transplant (TNC = 21.78 × 10 7/kg, CD34 = 10.5 × 10 5/kg) after myeloablative conditioning (busulfan, cyclophosphamide, and anti-thymocyte globulin). Cyclosporine and mycophenolate mofetil (MMF) were used for graft versus host disease (GVHD) prophylaxis. A positive test for adenovirus from a respiratory viral panel pre-transplant delayed conditioning for six weeks until the patient had two negative tests, one week apart. His post-transplant course was complicated by severe veno-occlusive disease starting on day +3, with secondary respiratory and renal failure. The patient was started on continuous renal replacement therapy along with intravenous defibrotide and high-dose steroids. Neutrophil engraftment did not occur until day +38. Post-engraftment, the patient developed a skin rash diagnosed as GVHD by biopsy, which was treated with corticosteroids at 2 mg/kg/day. As part of viral infection surveillance, the patient received a weekly blood PCR test for adenovirus; on day +25 it was noted he had reactivated adenovirus. He had been demonstrating overall clinical improvement, including declining hepatic transaminases and bilirubin, and reduced respiratory support requirements until day +39, when he developed fever with an increased need for respiratory support and rising transaminases. The respiratory viral panel showed that the patient was positive for adenovirus. Further workup also showed adenovirus PCR positive in stool and increase in quantitative adenoviremia, all consistent with disseminated adenoviral infection. The use of cidofovir was contraindicated in this patient due to renal toxicity.ALVR105 (Viralym-M), an allogeneic, off-the-shelf, multivirus-specific T-cell therapy (VST) that can target AdV, BKV, CMV, EBV, HHV-6, and JCV, was provided by AlloVir on a compassionate-use basis. A cell line that was HLA matched to the patient at 2 out of 8 HLA-A, HLA-B, HLA-DR, and HLA-DQ alleles was identified. After emergency IND approval, institutional review board approval, and family consent, one ALVR105 dose of 0.7 × 10 7 cells was infused on day +48. The dosage was calculated based on the patient's age, weight (8.5 kg), body surface area (0.35 m 2), and the dosing regimen used in a previous phase 2 trial. The patient developed fever and low blood pressure around 30 hours post-infusion, requiring an increase in his existing inotropic support and stress dose hydrocortisone. This was likely associated with underlying post-transplant complications, but a possible association with ALVR105 infusion could not be ruled out.The patient's viral load decreased substantially in the following weeks (Table 1). Concurrently, his liver enzymes, pulmonary secretions, and respiratory support requirements all improved. His respiratory secretions became negative for adenovirus PCR at day +28 post-infusion of ALVR105.At the time of writing, the patient was day +100 post-transplant (day +56 post-infusion of ALVR105), and his veno-occlusive disease had improved. Supplemental oxygen was no longer required, but volume-assured pressure was still in use, likely due to hepatosplenomegaly. The patient had detectable adenovirus viremia but below the threshold of quantitative measurement (<190 copies/ ml). The patient remains well-engrafted with evidence of persistent ALVR105 (Viralym-M) as illustrated in Table-2, but the % of Allovir cells are below our lab's 5% validation threshold. The patient's GVHD has resolved. MMF dosing was stopped on day + 31 from transplant, and the patient is receiving only cyclosporine and physiologic doses of hydrocortisone.Conclusion: In this infant with post allogeneic HCT disseminated adenovirus infection, ALVR105 appeared to be safe and was temporally associated with marked clinical improvement, suggesting VSTs may be of value in very young patients with adenovirus infection. This represents the first use of ALVR105 in an infant (< 1-year-old) patient. [Display omitted] DisclosuresMoon: Allovir: Current Employment, Current equity holder in publicly-traded company. OffLabel Disclosure:Virus specific cell therapy, used against adenovirus infection in post-transplant setting.

HYPOTHYROIDISM GONE AWRY: A CASE OF MYXEDEMA COMA

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Myxedema coma (MC) is a severe form of hypothyroidism and considered a medical emergency. It is characterized by decreased mentation, bradycardia, depressed respiratory status, hypotension, and general slowing of bodily systems. This a rare condition usually induced by stressors such as infection or malignancy. Here we present a patient undergoing treatment for metastatic carcinoma with incidental diagnosis of this aggressive endocrinological emergency. CASE PRESENTATION: 45-year-old Chinese gentleman with a 2-year history of metastatic esophageal cancer who presented unresponsive. He was undergoing palliative treatment, residing in a nursing home. On admission he required intubation and was found to have mets to his brain which can induce seizures, and was thought to be the cause of his unresponsiveness. He was hypotensive, hyponatremic, minimally responsive, with a lower respiratory rate on arrival. These features fit hypothyroidism. He was started on Dexamethasone for possible vasogenic edema from the brain mets. Lab work discovered TSH to be 162.4 with a FT4 of 0.27. Labs also discovered evidence of adrenal insufficiency with AM cortisol being low despite two days of high dose steroids. He received IV levothyroxine and Stress dose Hydrocortisone. DISCUSSION: : Our patient may have had many precipitating factors of his MC. He had a history of undergoing chemo-radiation before transitioning to palliative care in light of his aggressive cancer. He was receiving PEG tube feeds for over a year which may have impaired metabolism of his levothyroxine. He also continued to lose weight due to his malignancy, without proper readjustment in his weight-based medications. His chronic malnourished state may have contributed to refractory hypothyroidism precipitating MC. CONCLUSIONS: The mortality rates for myxedema coma can range between 30-50% based on different studies. In patients who are terminal, such as our patient with metastatic carcinoma, it is still prudent to keep in mind a simple chronic underlying condition such as hypothyroidism should not go unchecked. Fatal consequences may ensue if thyroid levels are not routinely checked in such individuals. REFERENCE #1: Acharya, R., Cheng, C., Bourgeois, M., Masoud, J., & McCray, E. (2020, September 16). Myxedema Coma: A forgotten medical emergency with a PRECIPITOUS ONSET. Retrieved February 10, 2021, from https://www.cureus.com/articles/41411-myxedema-coma-a-forgotten-medical-emergency-with-a-precipitous-onset REFERENCE #2: Aksoy, N., & Odabasi, G. (n.d.). 23 - case REPORT: Myxedema coma as a complication of cancer treatments. Retrieved February 10, 2021, from https://www.morressier.com/article/23--case-report-myxedema-coma-complication-cancer-treatments/5cdbe0a6618793e647b11e09 REFERENCE #3: Gummalla, S., Manjunath, M., & Phillips, B. (2020, October 22). Myxedema Coma: A life-threatening condition in patients USING PEMBROLIZUMAB. Retrieved February 10, 2021, from https://www.hindawi.com/journals/crie/2020/8855943/ DISCLOSURES: No relevant relationships by Padmini Giri, source=Web Response No relevant relationships by Victoria Gonzalez, source=Web Response No relevant relationships by Zain Kulairi, source=Web Response No relevant relationships by Sourabh Sourabh, source=Web Response No relevant relationships by DANYAL TAHERI ABKOUH, source=Web Response

Cardiac Arrest in a Child with Non-classic Lipoid Congenital Adrenal Hyperplasia Associated with a New STAR Gene Mutation

Abstract Introduction: Steroidogenic acute regulatory (STAR) protein regulates steroid hormone synthesis by transporting cholesterol into mitochondria. STAR gene mutations lead to lipoid congenital adrenal hyperplasia (LCAH), the rare but most severe form of congenital adrenal hyperplasia in children. We present an unusual case with an episode of cardiac arrest in a young girl during an acute febrile illness and later she was diagnosed with adrenal insufficiency secondary to a non-classic LCAH. Case: 2-year 11-month-old previously healthy white female was brought to an urgent care clinic due to severe lethargy and a seizure-like activity during a fever illness. She was found to have an undetectable blood glucose level and went into cardiac arrest shortly after arrival. CPR was performed for approximately 11 minutes. She then developed sever respiratory distress and was intubated. She was transferred to the PICU with IV sodium bicarbonate given en route. On admission, her body weight was 13.26 kg (36.80th percentile), height 90 cm (17.56th percentile), and BMI 16.17 (62.88th percentile). Her physical exam revealed normal external female genitalia and normal skin pigmentation. Lab evaluation revealed normal sodium and potassium but elevated anion gap, hyperuricemia, elevated creatinine kinase, abnormal liver function tests and abnormal coagulation profile. Brain MRI revealed findings consistent with hypoxic-ischemic encephalopathy. Renal function improved within 24 hours and hepatic function returned to normal after 20 days. Due to her severe hypoglycemic event, a high-dose ACTH stimulation test was performed. The results were consistent with adrenal insufficiency: baseline cortisol level, 7.3 μg/dL; 30 minutes cortisol, 7.8 μg/dL; 60 minutes cortisol, 9 μg/dL (normal response, ≥18 mcg/mL at 30 or 60 minutes). The baseline ACTH level was significantly elevated, 1688 pg/mL (0–46) as well as the renin activity, 24.3 ng/hour (1.7–11.2). Genetic testing revealed a 46 XX karyotype. STAR gene analysis identified compound heterozygosity; a novel deletion (c.811delC, p.Leu271Cysfs*50) and a previously reported missense mutation (c.661G&amp;gt;A, p.Gly221Ser). The girl is now 11 years old and exhibits normal growth, normal cognitive development, and she has developed early signs of puberty (Tanner stage 2 for breast). She takes daily hydrocortisone, fludrocortisone and stress dose hydrocortisone as needed. Conclusion: In non-classic LACH, the onset is generally late or not acute. Initial clinical features are variable and nonspecific. For this reason, non-classic LCAH may be overlooked. Adrenal crisis is a life-threatening complication, and it is important that clinicians are aware of the clinical features of non-classic LCAH and consider it in the differential diagnoses. Genetic testing for STAR should be considered in individuals with non-autoimmune primary adrenocortical insufficiency.

Hyponatremia as the Initial Presentation of Evolving Pituitary Apoplexy

Pituitary apoplexy (PA) is a known, often under-recognized medical emergency and is characterized by ischemic or hemorrhagic necrosis of the pituitary gland. It is a rare clinical syndrome that occurs in 2-12% of pituitary tumors. Hyponatremia can occur secondary to hypocortisolism (12-40%) or, rarely, to the syndrome inappropriate antidiuretic hormone (ADH) secretion.We present the case of a 69-year-old man who presented with altered mental status on post-operative day 3 from total knee replacement surgery. Initial testing revealed hyponatremia of 124 mmol/L, low serum osmolality of 266 mOsm/kg, and high urine osmolality of 664 mOsm/kg with urine sodium of 179 mmol/L. Head computerized tomography revealed a sellar mass of 1.8 x 2.4 cm. Initial testing revealed low prolactin (0.7 ng/mL), normal TSH (0.458 mcIU/mL) with borderline low free T4 of 0.72 ng/dL. Morning cortisol was 12.7 mcg/dL with ACTH of 8.5 pg/mL. Cosyntropin stimulation test was done revealing baseline cortisol of 5.8 mcg/dL (at midnight), increasing to 25.8 mcg/dL after 30 minutes and to 30.9 mcg/dL 60 minutes after cosyntropin administration. His sodium and mental status initially improved with fluid restriction and salt tablets, for the assumed syndrome of inappropriate ADH secretion. The patient remained hemodynamically stable. On the fourth day, however, his mental status deteriorated. Magnetic resonance imaging revealed expansion of sella with hyperintense mass 2.2 x 2.0 x 2.8 cm with compression of the optic chiasm. He was given stress dose hydrocortisone and levothyroxine and underwent emergency transsphenoidal resection. Biopsy revealed acute hemorrhage within infarcted adenoma. Postoperatively, both the patient’s sodium and mental status improved significantly and he was discharged to home on hydrocortisone and levothyroxine.The main clinical concern in the management of PA remains under-diagnosis at presentation. Prognosis is dependent on management during the acute phase. PA can present as hyponatremia even in the absence of overt hypocortisolism, presumably due to inappropriate ADH secretion. Therefore, PA should be considered as one of the differential diagnoses in hemodynamically stable patients with altered mental status and hyponatremia.

Skin Deep: A Rare Case of Thyrotoxic Periodic Paralysis in an African American Patient

Background: Thyrotoxic Periodic Paralysis (PP) is a rare form of hypokalemic PP that occurs in association with hyperthyroidism, especially Grave’s disease. This disease is frequently seen in males and is particularly prevalent among Asians with an incidence rate of 2%. In non-Asian populations, the incidence among those with hyperthyroidism is even lower at 0.1 - 0.2% and therefore significantly rare in African populations. Inability to recognize this emergency in the non-Asian population can therefore result in potentially fatal outcomes. Case Presentation: A 27 year old African American male with a history of Grave’s disease presented to the emergency department (ED) with the inability to move his muscles. Patient was initially diagnosed with Grave’s disease in 2017 when he was found to have suppressed TSH with elevated TSI and started on methimazole 40mg daily. The patient ran out of methimazole about 2 weeks prior to presentation and woke up on the day of admission with extreme muscle weakness. At the outside hospital, he was found to have potassium of 1.5mEq/L,TSH of < 0.1uL/ml and Free T4 of 3.4 ng/dL. He was given 1000 mg Propylthiouracil, stress dose hydrocortisone, propranolol and potassium replacement and then transferred to our ED for Endocrine evaluation. On assessment, he complained of nausea, vomiting, full body muscle weakness, tingling in his extremities and irritability. He denied any recent illnesses. On physical exam, Temperature 97.4 F, Respiration 18, Pulse 84, BP 157/72, O2 saturation 99%. His thyroid gland was enlarged however non-tender and without bruit. He had normal respiratory and cardiac exam. He was lying flat in bed and unable to raise his limbs against gravity and also unable to hold up his limbs when raised. He lacked his patellar and ankle jerk reflexes bilaterally. He was otherwise alert and oriented x 3. On labs, TSH was 0.004 uL/ml, Total T3 was 294 ng/dL, Free T4 of 3.01 ng/dL, Potassium was 2.1 mEq/L. His potassium was cautiously replaced and improved to 4.7 mEq/L later in the day, at which time, the patient was able move and sit up in bed. He was restarted on Methimazole 40mg daily for his thyroid disease and arranged for outpatient follow up. Discussion: Thyrotoxic PP is seen in a male-to-female ratio ranging from 17:1 to 70:1 and occurs at an average age of 20-40 years. Thyrotoxic PP is especially rare in the non-Asian population at an incidence rate of 0.1 - 0.2%. Nevertheless, in setting of ever-growing diversity due to immigration and inter-race relationships, it is difficult to predict one’s genetics based on the color of their skin. It is possible that our African American patient may have an Asian ancestor unbeknownst to him. Therefore, we must keep a broad differential regardless of one’s race so as to not miss timely diagnosis of medical emergencies which can result in reduced muscle strength, flaccid paralysis, respiratory failure, cardiac arrhythmias and eventual death.

Polyuria in a Patient With a Pituitary Mass

Background: Hypocortisolism can develop in patients with a pituitary mass because of hypopituitarism and is appropriately managed with steroid replacement. However, these patients often have co-existing endocrine derangements that can become clinically evident after administration of steroids. Clinical Case: A sixty-year-old Caucasian female with known non-small cell lung cancer on chemoimmunotherapy was admitted for management of an enlarging suprasellar mass. Her symptoms included nausea, vomiting and multiple syncopal episodes over the preceding three weeks. At the time of admission, physical examination was unremarkable. She was noted to be hypotensive with systolic blood pressure in the high 70s and was treated with intravenous fluids. Laboratory evaluation showed low random cortisol (0.99 ug/dL, n: 0.4-22.6 ug/dL), undetectable ACTH (<5 pg/mL, n: 7.2-63 pg/mL), low free thyroxine (1.01 ug/dL, n: 0.93-1.7 ug/dL), low free T3 (1.6 pg/mL, n: 2-4.4 pg/mL) and low TSH (0.023 ug/dL, n: 0.27-4.2 ug/dL), consistent with central hypothyroidism and secondary adrenal insufficiency. Importantly, she was normonatremic and normokalemic at admission. She was started on stress dose hydrocortisone (100 mg IV q8h) for presumed adrenal crisis. Following institution of steroid replacement therapy, the patient rapidly became polyuric while simultaneously developing hypernatremia. Her daily urine output peaked at 4400 mL corresponding temporally to a maximum serum sodium of 160 mmol/L. A single dose of 0.5 mg of desmopressin resulted in immediate lowering of daily urine output to 750 mL and appropriate improvement in urine osmolality from 147 mOsm/kg to 565 mOsm/kg, confirming a diagnosis of central diabetes insipidus (cDI). Conclusion: Hypocortisolism is known to impair free water excretion by stimulating arginine vasopressin (AVP) secretion through renal sodium loss and consequent volume depletion as well as direct feedback stimulation of corticotrophin releasing hormone (CRH) and AVP within the hypothalamus. Conversely steroid replacement leads to loss of feedback stimulation, unmasking cDI. This unique convergence of cDI with hypocortisolism is most often encountered in patients with hypopituitarism. Hence patients with secondary adrenal insufficiency should be carefully monitored for cDI after initiation of steroid replacement therapy.

Testosterone Use and Adrenal Hemorrhage

Background: Testosterone supplementation has been associated with a variety of side effects, such as polycythemia, and can potentially increase the risk of cardiovascular disease. Testosterone use has also been associated with increased thrombotic events, especially in patients with underlying hypercoagulable state. Clinical Case: A 57-year-old man presented with abdominal pain and distention. He had history of previous intramuscular (IM) and oral testosterone use for ten years. For 8 weeks prior to initial presentation, he reported using weekly IM 500mg Testosterone injections. Computed Tomography (CT) of the abdomen and pelvis revealed multiple thrombi of the portal, splenic, superior mesenteric and inferior mesenteric veins. He was started on Warfarin and discharged home. A few weeks later, he presented with similar symptoms with labs now showing an International Normalized Ratio (INR) of 10.2. Repeat CT was significant for presence of bilateral adrenal hemorrhage, measuring 2.9cm on the right and 2.4cm on the left, which were not seen on previous imaging done one week prior. During the hospital course, he was found to be hypotensive with low platelet count so Intravenous Immunoglobulin therapy was initiated for suspected catastrophic antiphospholipid syndrome (CAPS). Morning cortisol was 5.82 ug/dL (6.2–29.0) so this critically-ill patient was started on stress dose hydrocortisone, which was subsequently tapered to physiological dose after clinical improvement. Cosyntropin stimulation test was performed after withholding the prior dose of hydrocortisone. The baseline cortisol was 0.88 ug/dL (6.20–29.00ug/dL), after administration of 250mcg of Cosyntropin 30- and 60-minute cortisol levels were 1.5 ug/dL (4.3–22.4ug/dL) and 1.6 ug/dL (4.3–22.4ug/dL) respectively. Baseline ACTH of 121.0 pg/mL (7.2–63.3pg/mL), consistent with primary adrenal insufficiency. Dehydroepiandrosterone Sulfate (DHEA-S) level was 15.7 ug/dL (80.0–560.0ug/dL). Hypercoagulability workup was significant for the presence of lupus anticoagulant and antibodies positive for heparin induced thrombocytopenia, so patient was diagnosed with Antiphospholipid syndrome. Conclusion: This is a case of hypercoagulability in a patient with history of anabolic steroid misuse who developed extensive intraabdominal venous thrombosis, adrenal hemorrhage, and primary adrenal insufficiency. Adrenal vein thrombosis and hemorrhage can be life threatening sequalae of testosterone misuse and should be considered in the differential for patients with history of testosterone misuse and adrenal insufficiency.

Adrenal Cushing’s in Pregnancy, Managed with Metyrapone to Optimize for Adrenalectomy at 27 Weeks Gestation

Background: Cushing’s syndrome in pregnancy is associated with increased fetal and maternal morbidity and mortality. Prompt diagnosis and management during pregnancy is critical to improving these outcomes. Clinical Case: Patient is a 28-year-old female who presented to our hospital at 25 weeks of pregnancy with severe striae, high blood pressure, mildly elevated blood sugars and hypokalemia. Striae began in the 6th week of her pregnancy but progressed in the 2nd trimester to encompass multiple sections of skin. Blood pressure on presentation was 146/100 mmHg (on labetalol) and fasting glucose 113 mg/dL (goal <95 mg/dL in pregnancy). Labs were consistent with ACTH-independent Cushing’s Syndrome: AM serum cortisol of 42.3 mcg/dL (n < 22.6 mcg/dL), PM serum cortisol of 46 mcg/dL (n < 11.9 mcg/dL), ACTH of <1 pg/mL (normal 7–63 pg/mL), 24-hour urinary free cortisol of 1388 mcg/day (n <45 mcg/day), and salivary midnight cortisol of 2.2 mcg/dL (n <0.3 mcg/dL). An abdominal MRI scan without contrast showed a 3.2 cm fat-containing right adrenal lesion consistent with an adenoma. The fetus was large for gestational age at 98th percentile. Patient was started on metyrapone 250 mg twice daily, which was titrated up to 250 mg three times daily. Her blood pressure and glucose levels, treated with labetalol and insulin respectively, improved on metyrapone. Surgery, Maternal Fetal Medicine, Endocrine, Anesthesia, and Neonatal physicians reviewed her case at an interdisciplinary meeting. She received metyrapone for 1 week pre-operatively. AM serum cortisol improved to 21.4 mcg/dL and 24-hour urinary free cortisol improved to 139 mcg/day. She underwent laparoscopic right adrenalectomy at 27 weeks of pregnancy. Betamethasone was given 2 days prior to ensure fetal lung maturity in case of preterm labor. Stress dose hydrocortisone 100 mg was given intra-operatively. Fetal heart monitoring was normal throughout the surgery and post-operatively. After surgery, metyrapone was stopped and hydrocortisone was tapered to 20 mg and 10 mg. Five weeks after her adrenalectomy, striae decreased in size and glucoses normalized. Remarkably, fetal size is now appropriate for gestational age in the 62th percentile at 34 weeks. However, blood pressure remains elevated and is being treated with labetalol. She is planned for induction of labor at 37 weeks due to her elevated blood pressures and will be given stress dose steroids intraoperatively. Conclusion: Medical management of adrenal Cushing’s in pregnancy with metyrapone followed by adrenalectomy required a multidisciplinary team approach. Patient underwent successful adrenalectomy without complications of severe hypercortisolism, including infection, thromboembolism, pre-eclampsia, preterm labor and pregnancy loss. After surgery, there was normalization of maternal blood sugars as well as fetal size, and persistent, but improved, elevated blood pressure.