Signs Of Adrenal Insufficiency Research Articles

Excessive pickle consumption: beware of adrenal crisis

Adrenal insufficiency (AI) is one of the most life-threatening disorders resulting from adrenal cortex dysfunction. Symptoms and signs of AI are often nonspecific, and the diagnosis can be missed and lead to the development of AI with severe hypotension and hypovolemic shock.We report the case of a 13-year-old child admitted for cardiac arrest following severe hypovolemic shock. The patient initially presented with isolated mild abdominal pain and vomiting together with unexplained hyponatremia. He was discharged after an initial short hospitalization with rehydration but with persistent hyponatremia. After discharge, he had persistent refractory vomiting, finally leading to severe dehydration and extreme asthenia. He was admitted to pediatric intensive care after prolonged hypovolemic cardiac arrest with severe anoxic encephalopathy leading to brain death. After re-interviewing, the child's parents reported that he had experienced polydipsia, a pronounced taste for salt with excessive consumption of pickles lasting for months, and a darkened skin since their last vacation 6 months earlier. A diagnosis of autoimmune Addison's disease was made.Primary AI is a rare life-threatening disease that can lead to hypovolemic shock. The clinical symptoms and laboratory findings are nonspecific, and the diagnosis should be suspected in the presence of unexplained collapse, hypotension, vomiting, or diarrhea, especially in the case of hyponatremia.

Opioid-induced adrenal insufficiency: diagnostic and management considerations.

The dramatic rise in opioid use over the last two decades has led to a surge in their harmful health effects. Lesser known among clinicians is the impact of opioids on the endocrine system, especially with regard to cortisol. Opioids can suppress the hypothalamus-pituitary-adrenal (HPA) axis and may result in clinically significant adrenal insufficiency, especially in those treated at higher doses and for a longer time. A high clinical suspicion is necessary in this population for early diagnosis of opioid-induced adrenal insufficiency (OAI). Diagnosis of OAI is challenging, as the symptoms are often vague and overlap with those due to opioid use or the underlying pain disorder. Traditional assays to diagnose adrenal insufficiency have not been widely studied in this population, and more investigation is needed to determine how opioids might affect assay results. Once a diagnosis of adrenal insufficiency has been made, glucocorticoid replacement in the form of hydrocortisone is likely the mainstay of treatment, and effort should be made to taper down opioids where possible. Cortisol levels should be retested periodically, with the goal of stopping glucocorticoid replacement once the HPA axis has recovered. In this review, we provide context for diagnostic challenges in OAI, suggest diagnostic tools for this population based on available data, and offer recommendations for the management of this disorder. There is a paucity of literature in this field; given the widespread use of opioids in the general population, more investigation into the effects of opioids on the HPA axis is sorely needed.

FRI204 A Rare Case Of Cushing Syndrome In Pregnancy: Diagnosis And Therapeutic Challenges

Abstract Disclosure: Z. Cardona: None. E.D. Szmuilowicz: None. Introduction: Cushing’s syndrome (CS) rarely occurs during pregnancy, and diagnosis of Cushing’s syndrome in pregnancy is challenging due to physiologic changes during gestation. CS is associated with severe maternal and fetal complications. Clinical Case: A 36-year-old woman presented at 21 weeks gestational age with a known adrenal nodule admitted for evaluation of HTN, bilateral lower extremity edema, transaminitis, hyperglycemia, and acute hypoxemic respiratory failure. Reported proximal muscle weakness, facial swelling, anxiety, depression, perspiration, and headaches associated with HTN. Physical exam notable for mild supraclavicular fat deposition, chest and neck plethora, hypertrichosis, and bruising. CT abdomen pelvis revealed a 2.3-cm left adrenal nodule measuring 30 Hounsfield units. Biochemical evaluation included a plasma renin activity of 0.719 ng/mL/h [ref range: 0.167-5.380 ng/mL/h], aldosterone <1.0 ng/dL [ref range: 0.167-5.380 ng/dL], potassium 2.6 mEq/dL, free plasma metanephrines (MN) < 25 pg/mL [ref range: < or = 57 pg/mL], free normetanephrines (NMN) < 25 pg/mL [ref range: < or = 148 pg/mL, total free MN and NMN < 25 [ref range: < or = 205 pg/mL]. 24-hour urine free cortisol (UFC) was markedly elevated at 1854.1 mcg/24h [ref range: 3.1-50.0 mcg/24h], repeat 2186.2 mcg/24h, ACTH: 1.5 pg/mL [ref range: 7.2-63.6 pg/mL], confirming a diagnosis of ACTH-independent CS. Her case was complicated due to the adrenal nodule location. Patients with left adrenal nodules are at risk of developing inferior vena cava (IVC) syndrome during left adrenalectomies, especially in the third trimester, due to compression exerted by the uterus while lying on the right side during the procedure. She underwent an uncomplicated laparoscopic left adrenalectomy. Was started on hydrocortisone (HC) following surgery. There was concern for transient neonatal adrenal insufficiency at delivery. Measuring adrenal insufficiency in utero is challenging; however, estriol could serve as a surrogate marker of fetal adrenal function. Her estriol was normal, possibly indicating intact fetal adrenal activity. She had an uncomplicated vaginal delivery with no signs of adrenal insufficiency in her baby. Interestingly, she had a severely low alkaline phosphatase (ALP) which completely normalized soon after adrenalectomy. Clinical Lesson: This case depicts the challenges in managing CS in pregnancy and its repercussions regarding maternal, fetal, and delivery outcomes. Additionally, it highlights the importance of implementing a multidisciplinary approach, including obstetricians, endocrinologists, endocrine surgeons, and pediatricians, to ensure the optimization of therapeutic strategies. Presentation: Friday, June 16, 2023

FRI198 Acute Pancreatitis And Diabetic Ketoacidosis As A Presentation Of Subclinical Cushing Syndrome

Abstract Disclosure: W.H. Alkhidady: None. N. Almefgaie: None. A. Ekhzaimy: None. Case Report: A 43-year-old Saudi woman, presented to the emergency department with two days history of right upper quadrant pain, radiating to the back. Associated with nausea and vomiting with no history of diarrhea, constipation, or constitutional symptoms. She has a 4-year history of hypertension on 5 mg amlodipine with no history of endocrine or malignant tumors. On Examination she was alert, severely dehydrated with temperature of 37 °C, pulse of 124 per minute, blood pressure of 147/61 mmHg. The abdomen was tender in the right upper quadrant area. A laboratory examination showed lipemic sample with high triglycerides level 11mmol/L (0.4-1.48), high amylase 763nu/l (25-115), lipase 5773 u/l (73-393), low potassium level 2.6 mmol/l (3.50-5.10) and low calcium level 1.25 mmol/l (2.10-2.55). The urine analysis showed 4+ glucosuria and ketonuria. Her venous blood gas showed pH of 7.18 and bicarbonate of 10 mmol/L, random blood glucose was 16 mmol/L and anion gap could not be calculated at that time. A diagnosis of DKA secondary to acute pancreatitis secondary to high triglycerides level was made and management was started along with plasmapheresis. A CT pancreatitis protocol was done which showing a 4.2 x 3.5 cm well-circumscribed left adrenal lesion. An MRCP showed 4.3 cm well defined collision tumor in left adrenal gland, its peripheral part is suggestive of adenoma. further work up showed negative 24-hours urine metanephrins, normal Aldosterone Renin ratio, High 24-hour urine cortisol level 644 nmol/l, low ACTH 0.6 pmol/l and morning cortisol level post 1 mg DST was not suppressed on two different occasions. Since the patient had no phenotypical presentation of Cushing’s a diagnosis of SCS was made. She underwent left robotic assisted adrenalectomy, with pathological diagnosis of adrenocortical adenoma. 2 days later, AM cortisol level reduced to 230 nmol/L. while blood pressure and serum potassium remained normal with no signs of adrenal insufficiency. Her Diabetes mellitus and Hypertriglyceridemia resolved after left adrenalectomy. Conclusion: This case report demonstrates the uncommon association of subclinical Cushing syndrome and acute pancreatitis as a first presentation therefore it highlights the significant role of endocrine evaluation of any young patient with unexplained acute metabolic presentations. Presentation: Friday, June 16, 2023

Primary antiphospholipid syndrome with adrenal insufficiency

Antiphospholipid syndrome (APS) is a thrombophilic condition leading to multiple complications. Primary APS rarely causes primary adrenal insufficiency, but it can be life-threatening. In the present report, a patient presents with symptoms and signs of adrenal insufficiency and subsequent hormone level tests and radiological findings led to a diagnosis of primary APS with adrenal insufficiency.

Novel mutations in the ABCD1 gene caused adrenomyeloneuropathy in the Chinese population.

As a rare genetic disease, adrenomyeloneuropathy (AMN) is the most common adult phenotype of X-linked adrenoleukodystrophy (X-ALD). Mutations in the ABCD1 gene have been identified to cause AMN. We applied clinical evaluation, laboratory tests, and neuroimaging on three patients with progressive spastic paraparesis. In genetic analysis, we investigated ABCD1 gene mutations by whole-exome sequencing and Sanger sequencing. Bioinformatics tools were used to predict the effects of identified ABCD1 mutations on the protein. All three patients were men with adult-onset disease, mainly characterized by progressive spastic paraparesis. Among them, two patients had peripheral neuropathy and one patient had signs of adrenal insufficiency. All three patients showed cerebral involvement on brain MRI, while two patients were found with diffuse cord atrophy on spinal MRI. High-VLCFA levels in plasma, as well as C24:0/C22:0 and C26:0/C22:0 ratios, were found in all three patients. In addition, three different ABCD1 mutations were identified in three unrelated Chinese families, including one known mutation (c.1415_1416delAG) and two novel mutations (c.217C>T and c.160_170delACGCAGGAGGC). Based on the clinical assessment, radiographic, biochemical, and genetic testing, the final diagnosis was AMN in these patients with spastic paraparesis. This study reported three patients with AMN and identified two novel mutations in the ABCD1 in the Chinese population. Our finding emphasized that X-ALD is an important cause of adult-onset spastic paraplegia. Thus, neuroimaging, VLCFA testing, and especially the detection of the ABCD1 gene have important implications for the etiological diagnosis of adult patients with spastic paraplegia.

Preventing Female Virilisation: Role of Antenatal Dexamethasone

Antenatal treatment with dexamethasone in pregnancies affected by congenital adrenal hyperplasias (CAH) therefore suppresses fetal androgen production and prevents virilisation of female infants. Antenatal DXM is reported to be efficacious, preventing or ameliorating virilisation in 80–85% of cases. Materials and methods: In this study, we report a case of patient pregnant at 6 weeks; with a history of 2 children followed up for a classic form of HCS, she is admitted to our department for the administration of dexamethasone to prevent fetal virilization. Case Report: 23-year-old patient pregnant at 6 weeks, not known of having congenital adrenal hyperplasia (CAH), concept of consanguineous marriage 1 degree; she had a history of 2 children followed up for a classic form of HCS, the first died at the age of 1 and 10 months and the 2 child died on D26 of life. After having made a prenatal diagnosis where an analysis of the SRY gene on fetal circulating DNA showed the absence of this gene, which confirms the female sex of the fetus. An obstetrical ultrasound was done which objectified a pregnancy estimated at 6 weeks with suspicion of clitoral hypertrophy (At 16 weeks), in view of this observation the patient was referred to us for additional care and possible dexametasone. On questioning, the patient did not report any signs of hyperandrogenism. All evolving in a context of unquantified moderate weight loss and asthenia without signs of adrenal insufficiency. The clinical examination showed no melanoderma or slate spots, BP= 105/71mmHg, RR = 19 cycles/min. CF=81bpm? BMI = 28.68 kg/m2. Tanner: S5P5. the patient was put on 1.5 mg/d of dexamethasone divided into 3 doses.a monthly measurement of DHEAS and cortisol was requested. The Decrease of plasma concentrations of cortisol and DHEAS in the mother testifies to good fetal adrenal suppression. A low-calorie diet and monitoring of blood pressure and blood sugar to detect signs of under or overdose of corticosteroid .....

ODP047 Intramuscular ACTH stimulation test in a patient with liver disease

Abstract Introduction High dose (250 mcg) ACTH stimulation test is the gold standard dynamic testing to diagnose primary adrenal insufficiency (PAI). While the current guidelines do not elaborate on the preferable route of administration of corticotropin (intravenous or intramuscular), most published studies have been conducted on healthy people using the intravenous route. We present a patient with non-alcoholic steatohepatitis cirrhosis and hypotension who was thought to have suboptimal response with intramuscular ACTH stimulation test. Case 62-year-old male with cirrhosis, presented with dizziness, and was found to be hypotensive. Lab tests showed normal cell counts, electrolytes, renal function and lactic acid. His albumin was 2.6 g/dL. His blood pressure did not improve with intravenous fluids. Workup initiated for adrenal insufficiency showed 8 am cortisol level of 7. 0 mcg/dL, and ACTH level of 26 pg/mL. He underwent ACTH stimulation test with 250 mcg intramuscular cosyntropin, after which the 30-minute cortisol level was 13.7 mcg/dL and the 60-minute level was 15.1 mcg/dL (level immediately before the test 7.2 mcg/dL). Due to the patient not having signs of adrenal insufficiency and low albumin level due to liver disease, the cortisol response was considered adequate. Discussion Per the current Endocrine Society Clinical Practice Guidelines, the standard method of performing the ACTH stimulation test involves measuring baseline cortisol level, administration of 250 mcg of cosyntropin, and then measuring cortisol level 30 and 60 minutes post administration. Traditionally, an appropriate response is characterized by peak cortisol level above 18 mcg/dL, with lower values indicative of AI. While the responses can vary due to multitude of factors including time of testing etc., the individual response to the intravenous versus intramuscular injections is similar. However, the cut-off points between the two administration methods may differ. In a study on 64 healthy adult men who were administered 250 mcg cosyntropin intramuscularly, Longui et al. demonstrated lower cut-off values of 12.6 mcg/dL and 16.3 mcg/dL at 30 and 60 minutes respectively. In addition, with the introduction of newer monoclonal antibody and LC-MS/MS assays having greater specificity for cortisol, a study by Jarvosky et. al. recommends a new lower cut-off of 14-15 mcg/dL. Furthermore, several studies have shown higher prevalence of low total cortisol levels in cirrhosis and other liver disease leading to overdiagnosis of PAI, due to deficiency of cortisol binding globulin and albumin. In our patient, we hypothesize that the combination of all these factors could have caused a falsely low cortisol peak level without any underlying PAI. Our case highlights the need for additional studies on patients with underlying liver disease and hypoalbuminemia who undergo testing with intramuscular cosyntropin administration, and analysis with the new assays available. Presentation: No date and time listed

S2329 Iatrogenic Cushing’s Syndrome in Eosinophilic Esophagitis: A Rare Complication of Swallowed Topical Corticosteroids

Introduction: Topical corticosteroids (TCS) are a first-line treatment for eosinophilic esophagitis (EoE), effective at inducing and maintaining disease remission and well-tolerated with uncommon medication-related adverse events. Despite the theoretical risk of adrenal suppression (AS) with prolonged TCS use, data supporting clinically significant adrenal insufficiency in EoE are lacking and the risk of this rare complication is thought to be low. We present a case of iatrogenic Cushing’s syndrome associated with chronic TCS therapy in EoE and an opportunity for steroid-sparing treatment. Case Description/Methods: A 27-year-old woman with a 7-year history of EoE refractory to proton pump inhibitor, 6-food elimination diet, and swallowed fluticasone (FP) achieved disease remission with high-dose oral viscous budesonide (OVB) 4mg. Rapid recurrence of dysphagia, endoscopic findings, and esophageal eosinophilia occurred with lower OVB doses. After FP use for 5 years and transitioning to OVB for 18 months, she developed cushingoid features including prominent pathologic striae on the abdomen, breasts, and thighs, facial rounding, supraclavicular fullness, central obesity, and a dorsocervical hump. Given known exposure to exogenous steroids, features consistent with iatrogenic Cushing’s syndrome, and assumed hypothalamic-pituitary-adrenal axis (HPAA) suppression, the patient began a taper of OVB and steroid-sparing treatment was initiated with dupilumab 300mg weekly. After tapering OVB to 2mg daily over 2 months, assessment (ACTH, morning cortisol, 24-hour urine cortisol) was normal, consistent with HPAA recovery (Figure). Discussion: Topical steroids such as OVB are commonly used and recommended for long-term management of EoE with rare reports of adrenal insufficiency. As data supporting biochemical AS with TCS use in EoE is limited to observational studies with heterogenous testing for AI and lack of symptom assessment, the risk of clinically relevant AS is likely low. However, our case demonstrates that despite the favorable pharmacokinetics, systemic effects of TCS may be understated, particularly with high compliance and prolonged use of high daily doses. Clinicians should counsel patients on the non-negligible risk of AS when prescribing TCS for EoE, and consider assessment of the adrenal axis or use of steroid-sparing agents in those reliant on chronic TCS for disease control.Figure 1.: Endoscopic evidence of (B) active disease on FP (B) disease remission on OVB 4mg daily; (C) Cushingoid features of abdominal striae and dorsocervical hump.

Prevalence and Risk Factors for Adrenal Insufficiency in Patients with Multiple Myeloma Receiving Long-Term Chemotherapy including Corticosteroids: A Retrospective Cohort Study.

Multiple myeloma (MM) is the second most common hematologic malignancy and requires long-term and high-dose corticosteroid-based chemotherapy. The aim of this study was to investigate the prevalence and clinical predictors of corticosteroid-associated adrenal insufficiency (AI) in patients with MM receiving long-term chemotherapy. This retrospective study included patients with MM who were administered corticosteroid-based chemotherapy and underwent a rapid adrenocorticotropic hormone (ACTH) stimulation test between 2005 and 2018. AI was determined by a peak cortisol value < 18 μg/dL after ACTH stimulation. Demographic, clinical, and laboratory parameters were evaluated, and the prevalence and clinical risk factors of AI were examined. Of 282 patients with MM who received corticosteroid-based chemotherapy, 142 patients (50.4%) were classified as having AI. There were no differences in age, sex, body mass index, comorbidities, and laboratory findings, including serum sodium levels between the AI and no-AI groups. In univariate analysis, the cumulative dose of corticosteroid (odds ratio (OR) = 0.99, 95% confidence interval (CI) 0.98–0.99; P = 0.020) and megestrol acetate use (OR = 2.63, 95% CI 1.48–4.67; P = 0.001) were associated with the occurrence of AI. Cumulative duration and cumulative dose per duration of corticosteroid use were not associated with the occurrence of AI. However, in the multivariate analysis, only megestrol acetate use was associated with an increased risk of AI (OR = 2.54, 95% CI 1.41–4.60; P = 0.002). Approximately 95.8% of patients with AI had suspicious symptoms or signs of AI. Although clinical symptoms and signs are usually nonspecific, symptomatic patients with MM receiving long-term corticosteroid therapy have sufficient potential for developing AI, particularly when receiving megestrol acetate. These findings can help alert clinicians to consider adrenal suppression following corticosteroid-based chemotherapy in patients with MM.

71 Adrenal Insufficiency among Children treated with Hormonal Therapy for Infantile Spasms

Abstract Primary Subject area Endocrinology and Metabolism Background Hormonal therapy is a standard treatment for children with infantile spasms. However, the high doses given and long treatment duration exposes patients to the potential risk of adrenal insufficiency (AI). There is, presently, limited data on occurrence of AI after hormonal therapy in this population. Objectives This study aims to quantify the incidence of AI among children with infantile spasms treated with high-dose corticosteroids and/or adrenocorticotropic hormone (ACTH). Design/Methods A retrospective chart review of patients less than 2 years old treated for infantile spasms was performed between January 2009 to March 2020 in one pediatric specialized hospital. Variables collected included sex, age, etiology, age at treatment initiation, type of hormonal treatment, dose and duration of treatment, concomitant medication and illness, other corticosteroid uses, hydrocortisone replacement therapy use, adrenal function testing, and signs of AI. Analysis included descriptive statistics, such as incidence and bivariate analysis. Results Thirty-one patients met the inclusion criteria and received a total of 33 separated courses of hormonal treatment. Adrenal function following each course of treatment was evaluated in all patients, either by tests or by the presence of adrenal crisis. Oral hydrocortisone replacement therapy was received by 32/33 (97%) children. AI occurred in 25/33 (76% [95% CI 58-89]) children. There was no predictive factor for adrenal insufficiency after hormonal treatment, and no drug regimen (duration or total received dose) was safe. Two patients (6%) presented to the emergency room with an acute adrenal crisis the day following the weaning off of hormonal treatment. They were the youngest children of the cohort, with an age of 1,6 and 2,7 months at the initiation of treatment. All other patients were aged 4 months and older. Conclusion This study suggests that adrenal suppression is frequent after standard hormonal therapy regimen for infantile spasms. This can lead to serious complications, such as adrenal crisis, if not supplemented. A routine laboratory assessment of adrenal function should be done after hormonal therapy for all patients. We suggest that hydrocortisone replacement therapy should be given at the end of hormonal therapy and until testing results for adrenal function are obtained, particularly for younger patients.

Postoperative adrenal insufficiency in Conn's syndrome-does it occur frequently?

Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Recently, frequent clinically significant adrenal insufficiency after adrenalectomy in subjects with PA has been reported, which may make the early postsurgical management difficult. We retrospectively searched for possible adrenal insufficiency in subjects who underwent adrenalectomy for PA and have measured cortisol in the early postoperative course. We included subjects with confirmed diagnosis of PA who underwent either posture testing (blood draw at 06:00 and 08:00) and/or adrenal venous sampling (AVS) (blood draw between 08:00 and 09:00) and have also measured cortisol after surgery (cortisol measured approximately at 07:00). Cortisol was measured by immunoassay. In this study, we identified 150 subjects (age 48.5 ± 10.3 years) with available cortisol values in the early postoperative course (median [25th percentile, 75th percentile]) 6 [5,6] days. Postoperative cortisol values (551 ± 148 nmol/l) were normal and significantly higher, compared to preoperative standing cortisol values (404 ± 150 nmol/l; (P < 0.001) and AVS cortisol values (493 ± 198 nmol/l; P = 0.009), and did not significantly differ from preoperative supine cortisol values. Postsurgical cortisol values were not different among subjects with or without abnormal dexamethasone suppression test or elevated urinary free cortisol pre-surgery, and were significantly higher in subjects with abnormal diurnal cortisol variability compared with subjects with normal diurnal variability. No patient presented with adrenocortical crisis in the later follow-up. In conclusion, postoperative cortisol values did not indicate any suspicion of possible adrenal insufficiency. To exclude possible adrenal insufficiency, it may be sufficient to measure morning cortisol in the early postoperative course.

S382 Long-Term Safety of Budesonide Oral Suspension for Eosinophilic Esophagitis: An Integrated Safety Analysis of Phase 1–3 Clinical Trial Data

Introduction: Budesonide oral suspension (BOS) is an immediate-release swallowed topical corticosteroid developed for eosinophilic esophagitis (EoE). We present an integrated safety analysis of all clinical trials of BOS to provide the largest set of safety data on a topical corticosteroid for EoE to date. Methods: Data were pooled from 6 trials (phase 1, SHP621-101; phase 2, MPI 101-01, MPI 101-06; phase 3, SHP621-301, SHP621-302 and SHP621-303) for all participants who received ≥1 dose of BOS (any trial) or induction placebo (MPI 101-01/MPI 101-06/SHP621-301). For the ongoing open-label study SHP621-303, data were collected until August 14, 2020 (interim data cut-off). Treatment groups were BOS 2.0 mg b.i.d., BOS any dose (including BOS 2.0 mg b.i.d.) and placebo. Adverse events (AEs), clinical laboratory testing, vital-sign monitoring and physical examinations were assessed (all trials). Dual-energy X-ray absorptiometry (DXA) (participants 11–17 years old) and adrenocorticotropic hormone (ACTH) stimulation tests (all participants) were performed in the phase 3 studies. Exposure-adjusted incidence rates were calculated for AEs and AEs of special interest (AESIs); AESIs were categorized as infections, systemic effects of corticosteroids, or gastrointestinal effects. Results: Overall, 514 unique participants were included (BOS 2.0 mg b.i.d., n=292; BOS any dose, n=448; placebo, n=168). The BOS 2.0 mg b.i.d., BOS any dose and placebo groups totaled 87.2, 116.0 and 25.0 patient-years of exposure, respectively. BOS was well tolerated; most treatment-emergent AEs (TEAEs) were mild/moderate in severity (Table 1). The most common exposure-TEAEs (≥5% participants) and AESIs were upper respiratory tract infection, nasopharyngitis and sinusitis; TEAEs, AESIs and AEs leading to study or study drug discontinuation were more common in BOS- than placebo-treated participants (Table 1). AESIs of abnormal ACTH stimulation test and decreased blood cortisol were more frequent in the BOS 2.0 mg b.i.d. and BOS any dose groups (Table 1); most were mild/moderate and without other signs of adrenal insufficiency. DXA scans demonstrated no effect on growth (n=26); the intra-age distribution of TEAEs was similar for the BOS 2.0 mg b.i.d. and BOS any dose groups for participants 11–17 and ≥18 years old (data not shown). One death occurred (unrelated to BOS 2.0 mg b.i.d.). Conclusion: BOS was well tolerated, including at the highest dose (2.0 mg b.i.d.) and for maintenance therapy. Most TEAEs were mild/moderate in severity.Table 1.: Summary Of TEAEs, Exposure-Adjusted TEAEs Per 100 Patient-Years Experienced By ≥5% Of Participants In Any Treatment Group And Exposure-Adjusted AESIs Per 100-Patient Years,* By Preferred Term†.

IS POSTOPERATIVE SUBSTITUTION WITH HYDROCORTISONE NECESSARY AFTER ADRENALECTOMY FOR PRIMARY ALDOSTERONISM?

Objective: Concomitant cortisol secretion in primary aldosteronism (PA) has repeatedly been described. Recently, clinically significant adrenal insufficiency after adrenalectomy in subjects with PA has been described. In this study, we retrospectively searched for possible adrenal insufficiency in subjects who underwent adrenalectomy for PA and have measured cortisol in the early postoperative course. Design and Methods: We included subjects with confirmed diagnosis of PA who underwent either posture testing (blood draw at approximately 06:00 and 08:00) and/or adrenal venous sampling (AVS) (blood draw between 08:00 and 09:00) and have also measured cortisol after surgery (cortisol measured approximately at 07:00). Cortisol was measured by immunoassay. Design and method: We identified 110 subjects (age 49.5 ± 10.1 years) with available cortisol values in the early postoperative course (median [25th percentile, 75th percentile]) 6 [5, 6] days. Postoperative cortisol values (529 [431, 620] nmol/L) were significantly higher compared to preoperative standing cortisol values (388 [292, 482] nmol/L; (P &lt; 0.005) and AVS cortisol values (472.5 [339, 615] nmol/L; P = 0.04), and did not significantly differ from preoperative supine cortisol values. The lowest cortisol value post-surgery was 292 nmol/L. Postsurgical cortisol values were not different among subjects with or without abnormal dexamethasone suppression test or elevated urinary free cortisol pre-surgery. Conclusion: Postoperative cortisol values did not indicate any suspicion of possible adrenal insufficiency. These values were significantly higher compared to preoperative standing or AVS cortisol values obtained approximately 1 hour later, which reflects postoperative stress on one hand and normal diurnal cortisol rhythmicity on the other hand.

Bilateral adrenal hemorrhage with signs of adrenal insufficiency in the first days of life

Bilateral adrenal hemorrhage with signs of adrenal insufficiency in the first days of life

SUN-177 A Silent Bomb: A Case of Severe Primary Adrenal Insufficiency in the Context of Adrenal Metastatic Disease

Background: Adrenals glands are the most commonly involved endocrine organ in cancer metastasis due to its abundant lymphatic communication and blood supply. Up to 4% of non-small-cell lung cancers and 71% of lymphomas have bilateral adrenal metastasis. Early detection with hormone replacement can be life-saving.Clinical Case:A 58 year old male was admitted for hyperkalemia (potassium 6.4 mmol/L, range: 3.5-5.1) with prolonged PR interval on EKG, hyponatremia (sodium 131 mmol/L, range: 136-145), hypoglycemia (glucose 48mg/dl), and renal function impairment (creatinine level elevation of 1.38 mg/dl from a baseline of 0.94 mg/dl). He had been diagnosed with Stage IVb non-small-cell lung cancer about 20 months prior, and had a known history of chemotherapy, adrenal metastasis and left adrenal gland radiation (20 G in 5 daily fractions) about 10 months ago. For the past 10 months, the patient had reported no weight loss, nausea, vomiting, or other symptoms or signs of adrenal insufficiency, apart from intermittent fatigue, which he had attributed to his lung cancer diagnosis. On review, a previous PET/CT scan showed intense FDG uptake in the bilaterally enlarged adrenal glands, measuring 3.3 x 2.8 cm on the left, and 3.1 x 1.8 cm on the right. His ACTH level was found to be elevated to 1,023 pg/ml (range: 6-63) with borderline low free cortisol level 0.06 mcg/dl (range 0.04-0.35). Aldosterone level was found to be 3.4 ng/dl (range: 4-31), with a renin level of 36.2 ng/ml/hr (range: 0.5-4). Primary adrenal insufficiency was diagnosed, and the patient was started on hormone replacement therapy, which was titrated as outpatient. Now he is continued on a regimen of hydrocortisone 15 mg and 5 mg, at 8 am and 3 pm respectively, and fludrocortisone 0.1 mg daily. In two months, his ATCH level fell from 1,023 to 89 pg/ml with normalization of kidney functions, sodium level (now 137 mmol/L) and potassium level (now 4.8 mmol/L). He gained 4 kg, and has been feeling more energetic and functional on his follow up visits.Conclusion: Patients with adrenal metastatic cancer may have atypical symptoms and signs despite having severe primary adrenal insufficiency. High risk patients should be monitored, even in the absence of symptoms, for the development of adrenal insufficiency.Reference:1. Yamamoto, T. (2018). LATENT ADRENAL INSUFFICIENCY: CONCEPT, CLUES TO DETECTION, AND DIAGNOSIS. Endocrine Practice, 24(8), pp.746-755.2. Angelousi A, Alexandraki KI, Kyriakopoulos G, et al. Neoplastic metastases to the endocrine glands. Endocr Relat Cancer. 2019.

SAT-059 Congenital Craniopharyngioma: A Rare and Challenging Disease

Introduction: Congenital central nervous system tumors are seldomly seen, with just few reported cases of neonatal craniopharyngioma (NCP). Albeit being a benign tumor arising from epithelial vestiges along the adenohypophysis migration, NCP may have an aggressive behavior due to its location.Case Report: We report a two-month-old female infant referred to the Pediatric ward due to recurrent sepsis episodes, uncontrollable crying, large fontanelle and signs of adrenal insufficiency. Laboratory evaluation showed low serum cortisol 0.11 μg/dL(REF: 6.2-19.4 μg/dL), ACTH 6.66 pg/mL(REF: 7.2-63.3pg/mL) and Na 133 mEq/L(REF: 136-145mEq/L), normal Free T4 1.01 ng/dL(REF: 0.93-1.7 ng/dL) and a slightly elevated prolactin 59.43 ng/mL(REF: 4.79-23.3ng/mL). A transfontanelar ultrasound demonstrated a cystic and calcified sellar/suprasellar tumor. Encephalus Magnetic Resonance Imaging described a 36x42x33 mm multicystic sellar/suprasellar mass extending to the middle line and occupying all sellar space, leading to a deformed and compressed third ventricle, and displacing the mesencephalus, the cerebral pedunculus and the optic chiasm. Imaging evaluation suggested a craniopharyngioma. She started hydrocortisone therapy due to hypercortisolism and was submitted to transsphenoidal surgery, but just a partial resection of the tumor was possible. She needed levothyroxine and desmopressin replacement after surgery. On the 10th post-operative day she died due to infectious complications. The histological analysis of the tumor diagnosed an adamantinomatous-type grade I craniopharyngioma.Comments: Central nervous system tumors developing in the first 60 days of life are considered congenital. Besides being a rare condition, NCP are challenging and life-threatening. Although for some groups the complete resection of the tumor is considered the gold standard approach to those patients, sometimes it cannot be performed due to limitations intrinsic to the tumor biology and due to the patient’s age, worsening the prognosis of the infant. Multihormonal deficits and shortened survival of this patient were consequences of the tumor characteristics, delayed diagnosis of craniopharyngioma and the poor results during and after the surgical intervention.

334P - Incidence and characteristic of adrenal insufficiency due to immune checkpoint inhibitors therapy

BackgroundImmune checkpoint inhibitors (ICI) have been approved for non-small lung cancer (NSCLC). Adrenal insufficiency (AI) is a distinctive adverse event related to ICI. This can be either primary adrenal gland destruction or interference with corticotrophin (ACTH) secretion by the pituitary gland (secondary). As AI is relatively rare and symptoms and signs of AI are non-specific, the diagnosis of AI is often difficult. To clear the incidence and characteristics of AI related with ICI. We conducted a retrospective single center study. MethodsWe reviewed the medical records of patients with NSCLC who received pembrolizumab, nivolumab, atezolizumab or duravalmab at JCHO Kyushu Hospital between Feb 2017 and Jun 2019. ResultsA total of 114 patients with NSCLC received ICI. Eight patients (7.0%) were diagnosed with AI. Median age was 67 (range: 54 to 79). Six were male. Six out of eight patients were secondary AI, one patient was primary AI, and one patient was unknown. The median onset of AI from the first dose of ICI was 203 days (range: 38 to 763). The patients presented with fatigue, fever, nausea, diarrhea and/or dizziness. One patient was diagnosed because of repeating COPD/asthma attack. Hypocholesterolemia, hyponatremia, eosinophilia, hypoglycemia, and hyperkalemia were found 4, 2, 3, 1 and 1 out of 8 patients respectively. One patient didn’t exhibit any above symptom. All of the patients had rapid resolution of symptoms after hydrocortisone replacement. ConclusionsICI-associated AI developed in 7.0% of patients requiring hydrocortisone replacement therapy. Symptoms and laboratory abnormalities at the time of onset varied. It is thought that patients using ICI therapy will further increase in the future, and patients who develop ICI-related AI will also increase. Clinicians should deepen their understanding of the nature of AI and provide appropriate information to patients so that AI can be quickly diagnosed and treated. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Adrenal function following acute discontinuation of glucocorticoids in children with acute lymphocytic leukemia: A prospective study

Background: Children with acute lymphocytic leukemia (ALL) are enrolled in advanced treatment protocols involving high doses of glucocorticoids (GCs). Current protocols do not advocate tapering of GCs doses postinduction phase. Prolonged administration of supra-physiologic doses of GCs can induce transient suppression of the hypothalamic pituitary adrenal axis (HPA). Timely recognition of adrenal insufficiency is important in order to ensure that children at risk receive the necessary treatment and follow-up including stress coverage during illness and surgical procedures.Methods: 21 newly diagnosed patients with ALL aged 3–10 years old were prospectively enrolled in the study over a 2-year period. All enrolled patients received high doses of GCs as part of a chemotherapy treatment protocol. The HPA axis was assessed prior to the induction phase of chemotherapy and 1–2 weeks after un-tapered discontinuation of GCs.Results: All children had normal HPA axis at baseline. Postinduction 1 mcg ACTH stimulation test result was normal (cortisol > 500 nmol/L) in 75% of children and partially responsive in 25% (cortisol 300–500 nmol/L). None of the participants demonstrated clinically significant adrenal insufficiency following abrupt cessation of GCs.Conclusion: All children in our cohort had either normal or subnormal cortisol response during a low dose ACTH stimulation test 1 to 2 weeks following abrupt discontinuation of GCs, suggesting that any inhibition of the HPA axis is of short duration. We suggest that future studies investigate the timing of adrenal function recovery following GC discontinuation as well as whether tapering of the GC should be recommended.

Isolated hypoaldosteronism as first sign of X-linked adrenal hypoplasia congenita caused by a novel mutation in NR0B1/DAX-1 gene: a case report

BackgroundX-linked Adrenal Hypoplasia Congenita (AHC) is a rare cause of primary adrenal insufficiency due to mutations in the NR0B1 gene, causing a loss of function of the nuclear receptor protein DAX-1. Adrenal insufficiency usually appears in the first 2 months of life, but can sometimes emerge during childhood. Hypogonadotropic Hypogonadism is often associated later in life and patients may develop azoospermia. We describe an unusual onset of AHC started with isolated hypoaldosteronism as first and only sign of the disease.Case presentationA 18-days-old newborn presented with failure to thrive and feeding difficulties. Blood tests showed severe hyponatremia, hyperkalemia and hypochloremia. Renin was found over the measurable range and aldosterone was low whereas cortisol level was normal with a slightly increased ACTH. In the suspicion of Primary Hypoaldosteronism, correction of plasmatic electrolytes and replacement therapy with Fludrocortisone were promptly started. The subsequent evidence of low plasmatic and urinary cortisol and increased ACTH required the start of Hydrocortisone replacement therapy and it defined a clinical picture of adrenal insufficiency. Genetic analysis demonstrated a novel mutation in the DAX-1 gene leading to the diagnosis of AHC.ConclusionsAHC onset may involve the aldosterone production itself, miming an isolated defect of aldosterone synthesis. NR0B1/DAX-1 mutations should be considered in male infants presenting with isolated hypoaldosteronism as first sign of adrenal insufficiency.