Exogenous Steroid Use Research Articles

6977 Unraveling Secondary Adrenal Insufficiency and an Invasive Pituitary Macroadenoma in a COVID-19 Positive Patient

Abstract Disclosure: F. El Sayed: None. A.A. Banka: None. Invasive pituitary macroadenomas extend into the extrasellar region and invade surrounding dural, periosteal, or mucosal tissues, often exceeding 1 centimeter and potentially compressing adjacent structures. Nonfunctioning pituitary adenomas (NFPAs), as they enlarge, can cause visual field impairment and ophthalmoplegia, with the decision for surgical intervention influenced by the degree of optic chiasm compression. NFPAs are sometimes associated with impaired endocrine function, particularly secondary adrenal insufficiency (sAI), which, warrants specific clinical attention. Management involves a combination of surgical interventions, such as transsphenoidal surgery, and medical approaches, including tailored hormone therapy or radiation therapy based on the tumor's characteristics. Clinical case: A 51-year-old female with a history of Sjogren's disease presented with a one-week duration of nausea, vomiting, diarrhea, and fatigue. Upon admission, she tested positive for COVID-19. Her vital signs indicated hypotension with a blood pressure in the 80s/40s range, a heart rate in the 90s, and she was afebrile on room air. Laboratory findings revealed significant hyponatremia (Na+ 118), K+ 4.3, HCO3- 19, and glucose 80. Workup for hyponatremia included a cortisol stimulation test, revealing secondary adrenal insufficiency with baseline cortisol of 3.5 ug/dl, 10.7ug/dl after 30 minutes, and 12.7ug/dl after 60 minutes. The patient denied exogenous steroid use, hypothyroid symptoms, polyuria, or polydipsia, and reported no headaches or visual symptoms. Endocrine evaluation showed hypogonadism despite post-menopausal status, with low estrone, estradiol, LH, and FSH levels. She was initiated on Cortef (hydrocortisone) with symptomatic improvement. Further investigation through an MRI revealed a large lobulated sellar mass measuring 3.2 x 2.8 x 3.5 cm compressing the optic chiasm and partially encasing the right internal carotid artery, leading to peripheral visual defects confirmed on perimetry. Following endoscopic endonasal pituitary macroadenoma resection, there was no evidence of interval growth on a one-year follow-up MRI scan. Discussion: The presented case highlights the importance of considering invasive pituitary macroadenomas in the differential diagnosis of patients with hyponatremia, particularly when accompanied by suggestive symptoms and an atypical cortisol response. The coexistence of COVID-19 adds a layer of complexity to the clinical scenario, necessitating a comprehensive approach to both infectious and endocrine management. Timely recognition, appropriate endocrine assessment, and targeted interventions, such as hydrocortisone replacement and surgical resection, are crucial for optimizing outcomes in patients with this intricate interplay of pituitary pathology and infectious states Presentation: 6/1/2024

An Unusual Case of Idiopathic Spinal Epidural Lipomatosis

An excess of adipose tissue buildup restricted to the lumbar and thoracic areas of the spine is the cause of spinal epidural lipomatosis. The etiology of spinal epidural lipomatosis can be broadly categorized based on five often related risk factors: obesity, endogenous steroid hormonal disease, spine surgery, exogenous steroid use and idiopathic disease. However, the actual pathophysiology of the condition remains unclear. Neurological impairments, myelopathy, radiculopathy, neurogenic claudication, loss of sensation, difficulties voiding, lower extremity weakness and infrequently cauda equina syndrome might result from the progression of spinal epidural lipomatosis. Conservative treatment focuses on reducing symptoms that result from common risk factors and is primarily patient-specific. Open surgical procedures and minimally invasive surgery have shown to be effective if more advanced means of treatment are required. Here, we report an unusual case of idiopathic spinal epidural lipomatosis. Treatment will depend on the neurological status of the patient. We opted to manage the patient conservatively and closely monitor her on follow up visits.

Hypoglycaemia in adrenal insufficiency.

Adrenal insufficiency encompasses a group of congenital and acquired disorders that lead to inadequate steroid production by the adrenal glands, mainly glucocorticoids, mineralocorticoids and androgens. These may be associated with other hormone deficiencies. Adrenal insufficiency may be primary, affecting the adrenal gland's ability to produce cortisol directly; secondary, affecting the pituitary gland's ability to produce adrenocorticotrophic hormone (ACTH); or tertiary, affecting corticotrophin-releasing hormone (CRH) production at the level of the hypothalamus. Congenital causes of adrenal insufficiency include the subtypes of Congenital Adrenal Hyperplasia, Adrenal Hypoplasia, genetic causes of Isolated ACTH deficiency or Combined Pituitary Hormone Deficiencies, usually caused by mutations in essential transcription factors. The most commonly inherited primary cause of adrenal insufficiency is Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency; with the classical form affecting 1 in 10,000 to 15,000 cases per year. Acquired causes of adrenal insufficiency can be subtyped into autoimmune (Addison's Disease), traumatic (including haemorrhage or infarction), infective (e.g. Tuberculosis), infiltrative (e.g. neuroblastoma) and iatrogenic. Iatrogenic acquired causes include the use of prolonged exogenous steroids and post-surgical causes, such as the excision of a hypothalamic-pituitary tumour or adrenalectomy. Clinical features of adrenal insufficiency vary with age and with aetiology. They are often non-specific and may sometimes become apparent only in times of illness. Features range from those related to hypoglycaemia such as drowsiness, collapse, jitteriness, hypothermia and seizures. Features may also include signs of hypotension such as significant electrolyte imbalances and shock. Recognition of hypoglycaemia as a symptom of adrenal insufficiency is important to prevent treatable causes of sudden deaths. Cortisol has a key role in glucose homeostasis, particularly in the counter-regulatory mechanisms to prevent hypoglycaemia in times of biological stress. Affected neonates particularly appear susceptible to the compromise of these counter-regulatory mechanisms but it is recognised that affected older children and adults remain at risk of hypoglycaemia. In this review, we summarise the pathogenesis of hypoglycaemia in the context of adrenal insufficiency. We further explore the clinical features of hypoglycaemia based on different age groups and the burden of the disease, focusing on hypoglycaemic-related events in the various aetiologies of adrenal insufficiency. Finally, we sum up strategies from published literature for improved recognition and early prevention of hypoglycaemia in adrenal insufficiency, such as the use of continuous glucose monitoring or modifying glucocorticoid replacement.

ODP356 The Cortisol Conundrum: The Diagnostic Work up for Patients With Suspected Cushing's Disease and Hypercortisolaemia in Australia. Results of a Survey and Clinical Audit

Abstract Cushing's syndrome (CS) and the pituitary tumour causing hypercortisolaemia, known as Cushing's Disease (CD), is a rare and challenging diagnosis. It is complicated by nonspecific symptoms and a range of diagnostic tests, with an average diagnostic delay of 3 years. Our objective was to compare the intended diagnostic workup by clinicians and medical students (students) against Endocrine Society Clinical Practice Guidelines (Guidelines). Comparisons were also drawn between the Guidelines and the workup of patients with suspected CS, aiming to identify areas to improve diagnosis and reduce diagnostic delay. This study had two parts. The first was a mixed cohort cross-sectional study involving an anonymised online survey, which examined the clinical experience of respondents, intended diagnostic pathway for CD and recommendations for improvement. The survey was distributed to clinicians and students in Australia, at four tertiary hospital facilities and students at two tertiary centres. The second part was a retrospective clinical audit of the diagnostic workup for patients with suspected CS, performed by senior endocrinologists, associated with an Australian tertiary health facility. Survey responses were received from 102 individuals (52 doctors and 50 students). Most doctors were trained in endocrinology (77%). Most doctors had seen <10 CS or CD patients throughout their careers and training (79%). The most common initial screening tests for clinicians and students were 24-hour urinary free cortisol (80% and 82%, respectively) and low dose overnight dexamethasone suppression testing (67% and 50%, respectively). Plasma adrenocorticotropic hormone (ACTH) and Magnetic Resonance Imaging (MRI) were selected by most clinicians (80% and 74%, respectively) and most students (70% and 82%, respectively), as tests for localising confirmed hypercortisolism. Recommendations suggested by respondents were broadly categorised into: greater clarity of the diagnostic process, by means such as flow charts (50%); increasing awareness (44%); and non-endocrine physician training (31%). Audit inclusion criteria was met by 15 patients (53% female; 47% male; mean age 46.9 years). The mean time from endocrinology referral to diagnosis was 13.5 months. Hypercortisolism was confirmed in 11 patients; including 4 patients with CD and 1 patient with ectopic CS. ACTH was ordered prior to confirming hypercortisolism in 14 patients and 1 patient was tested prior to excluding exogenous steroid use. Our study demonstrated that the majority of clinicians and students when surveyed, would make diagnostic decisions in line with the Guidelines. Half of respondents suggested there was a lack of clarity in diagnostic algorithms available. Minor discrepancies were seen between Guideline recommendations and patients’ assessments amongst the cohort audited. However, ACTH was consistently sent during screening and a patient was assessed with iatrogenic Cushing's, which are not recommended. Our findings suggest improved resources for the diagnostic workup of hypercortisolism, such as comprehensive flowcharts, may be helpful for clinicians and students. Presentation: No date and time listed

Acute Unilateral Central Serous Chorioretinopathy after Immunization with Pfizer-BioNTech COVID-19 Vaccine: A Case Report and Literature Review

ABSTRACTIntroductionA 43-year-old Caucasian male presented to our ophthalmology clinic with blurry vision and metamorphopsia in his right eye, 24 hours after receiving the first dose of the Pfizer–BioNTech COVID-19 vaccine.MethodsClinical examination and imaging tests were consistent with acute unilateral central serous chorioretinopathy (CSCR) that completely resolved after 2 months without any treatment. He had no significant ophthalmic or medical history. He also lacked the classical risk factors for CSCR such as recent psychosocial stressors, Type-A personality traits, history of exogenous steroid use, connective tissue disorders and obstructive sleep apnea.ResultsThis appears to be only the second reported case of CSCR, temporally associated with a recombinant COVID-19 mRNA vaccine. We also present a summary of published reports demonstrating intraocular complications associated with the novel recombinant COVID-19 mRNA vaccines.ConclusionFindings in this report should not deter COVID-19 vaccinations given the rarity of aforementioned ocular complications and the greater benefit of protection from COVID-19 infection. Medical practitioners, however, should remain mindful of potential ocular complications, given the greater likelihood of occurrence with increasing vaccination booster rates.

MRI Features and Clinical Significance of Spinal Epidural Lipomatosis: All You Should Know.

Spinal epidural lipomatosis (SEL) is defined as the abnormal accumulation of unencapsulated adipose tissue in the spinal epidural space. SEL can be asymptomatic or can cause a wide range of symptoms, the most common of which is neurogenic claudication. Several other neurological manifestations may also occur, above all myelopathy and radicular symptoms. The spinal level most frequently involved in patients with SEL is the lumbar one, followed by the thoracic one. Imaging plays a key role in the disease assessment. MRI is considered the most effective and sensitive modality for diagnosing and staging SEL. Anyway, also CT scan can diagnose SEL. The diagnosis may be incidental (in mild-moderate disease) or may be taken into account in cases with neurological symptoms (in moderate-severe disease). There are some recognized risk factors for SEL, the most common of which are exogenous steroid use and obesity. Recent studies have found an association between SEL and obesity, hyperlipidemia and liver fat deposition. As a matter of fact, SEL can be considered the spinal hallmark of metabolic syndrome. Risk factors control represents the initial treatment strategy in patients with SEL (e.g. weight loss, steroid therapy suspension). Surgical decompression may be required when conservative treatment fails or when the patient develops acute/severe neurological symptoms.

Prevalence of adrenal insufficiency among patients with euvolemic hyponatremia.

BackgroundThe diagnosis of syndrome of inappropriate anti-diuresis requires the exclusion of secondary adrenal insufficiency (AI) among patients with euvolemic hyponatremia (EuVHNa). Studies have suggested that about 2.7–3.8% of unselected patients presenting to the emergency room with EuVHNa have undiagnosed AI and it is as high as 15% among patients admitted to specialized units for evaluation of hyponatremia.ObjectiveTo study the prevalence of AI among in-patients with EuVHNa in a general medical ward setting.MethodsThis was a prospective, single-center observational study conducted among general medical in-patients with EuVHNa, defined as patients with a serum sodium <135 mmol/L, clinical euvolemia and urine spot sodium >30 mmol/L. Additionally, patients with recent vomiting, current renal failure, diuretic use and those with uncontrolled hyperglycemia were excluded. Adrenal functions were assessed by a modified adrenocorticotropic hormone (ACTH) stimulation test called the Acton Prolongatum™ stimulation test (APST). A cut-off cortisol value of <18 mg/dL after 60 min of ACTH injection was used to diagnose AI.ResultsOne hundred forty-one patients were included and underwent an APST. APST suggested 20/141 (14.2%) had undiagnosed AI. The commonest cause of AI (9/20) was secondary AI because of the use of steroids including inhaled steroids and indigenous medicines contaminated with steroids. In 5 (3.5%) patients hypopituitarism was newly diagnosed. Despite primary AI (PAI) not commonly presenting as EuVHNa, 2/20 patients had PAI.ConclusionsAI is much commoner in our country, among in-patients with EuVHNa primarily driven by exogenous steroid use and undiagnosed hypopituitarism.

Hypothalamic-pituitary-adrenal axis suppression and intranasal corticosteroid use: A systematic review and meta-analysis.

Intranasal corticosteroids (INCS) are used in the management of sinonasal conditions. Use of exogenous steroids can be associated with hypothalamic-pituitary-adrenal axis dysfunction and adrenal insufficiency (AI). We aimed to estimate the rate of AI after INCS use in a meta-analysis, stratified by steroid type and treatment duration. Ovid Medline, Embase Classic, PubMed, Web of Science, and CINAHL databases were searched following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify studies investigating INCS use and AI. AI was defined as morning serum cortisol<550nmol/L and<80nmol/L with and without adrenocorticotropic hormone stimulation. INCS were classified as first (beclomethasone dipropionate, triamcinolone acetonide, beclomethasone, budesonide, dexamethasone) and second (ciclesonide, mometasone furoate, and fluticasone propionate) generation. Duration of treatment was classified as short (<1 month), medium (1-12 months), and long-term (>12 months) time periods. This search identified 3668 articles. A total of 39 studies (1678 patients) were included in the final analysis. The pooled percentage of AI for routinely utilized first- and second-generation INCS was 0.70% (95% confidence interval [CI], 0.29-1.12%). Stratified by type, AI was observed in 0.78% (95% CI, 0.25-1.30%) of first-generation and 0.58% (95% CI, -0.1% to 1.26%) of second-generation steroids. AI was seen in 0.48% (95% CI, -0.01% to 0.96%) of short-term, 1.13% (95% CI, 0.2-2.1%) of medium-term, and 1.67% (95% CI, 0.37-2.9%) of long-term use of INCS. Overall, the use of INCS carries a low risk for AI. Although modest, this risk may differ depending on the length of duration and type of INCS used. Informing patients of these risks is of importance for the treatment of chronic sinonasal conditions.

Spinal Epidural Lipomatosis: A Comprehensive Review.

This is a comprehensive review regarding the epidemiology, diagnosis, and management of spinal epidural lipomatosis (SEL). SEL is a relatively rare condition that has gained scientific relevance over the past few decades. Recent findings include expanding treatment strategies to include minimally invasive surgical techniques. SEL is caused by an excess of adipose tissue accumulation localized to the thoracic and lumbar regions of the spine. While the exact pathogenesis is not fully elucidated, the etiology of SEL can be broadly classified based on five commonly associated risk factors; exogenous steroid use, obesity, endogenous steroid hormonal disease, spine surgery, and idiopathic disease. Progression of SEL may lead to neurological deficits, myelopathy, radiculopathy, neurogenic claudication, loss of sensation, difficulty voiding, lower extremity weakness, and rarely cauda equina syndrome. Conservative management is largely patient-specific and aimed at mitigating symptoms that arise from shared risk factors. If more advanced treatment measures are necessary, minimally invasive surgery and open surgical techniques, have proven successful.

Twelve patients with mental illness who complained of postprandial symptoms in addition to fatigue showed central adrenal insufficiency

BackgroundAdrenal insufficiency (AI) may cause psychiatric symptoms. We evaluated the correlation between the hypothalamic-pituitary-adrenal axis (HPA) function in patients with mental illness who complained of postprandial symptoms in addition to fatigue. MethodsWe recruited 16 patients with mental illness who complained of postprandial symptoms in addition to fatigue for the evaluation of the HPA axis function using a rapid adrenocorticotropin (ACTH) test with Cortrosyn®, (250 μg), a corticotropin-releasing hormone (CRH) test, and an insulin tolerance test (ITT). The ITT results were adopted if the nadir blood glucose level was <2.2 mm/L. Patients with showed a peak cortisol level of <496.6 nmol/L (18 μg/dL) in the ITT were diagnosed with AI and the results were compared with the results of the rapid ACTH and CRH tests. The patients’ clinical characteristics were evaluated. ResultsTwelve of 16 patients met the criteria for the adoption of the ITT. A peak cortisol level of <496.6 nmol/L was detected by the rapid ACTH test in three patients, by the CRH test in ten patients, and by the ITT in all twelve patients. Six of the above 12 patients used exogenous steroids due to the comorbidities such as bronchial asthma. ConclusionsTwelve of the patients who complained of postprandial symptoms in addition to fatigue met the diagnostic criteria for AI. AI is often latent and more frequent in patients with mental illness. It is therefore necessary to inquire about exogenous steroid use for comorbidities when managing such patients.

Pituitary Macroadenoma Masked by Iatrogenic Adrenal Insufficiency: A Diagnostic Blind Spot

Background: Exogenous steroid use is the most common cause of central adrenal insufficiency. Depending on the duration and strength used, it may take months to years for the hypothalamic-pituitary-adrenal (HPA) axis to recover after the steroid is stopped. We report a case of iatrogenic hypoadrenalism with persistent suppression of the HPA axis for 13 years, discovered later to be due to a second pathology. Case: A 48 year old lady presented in 2005 with weight gain of 20 kg over 1 year and florid Cushingoid features. 9AM cortisol was undetectable (<12 nmol/L). History taking revealed use of oral dexamethasone at various dosages over the past 9 years for her knee pains. A diagnosis of iatrogenic adrenal insufficiency was made. She was started on hydrocortisone replacement, and was advised to stop the over-the-counter steroids. By 2011 her short Synacthen test (SST) showed much improved functioning of the HPA axis (cortisol 182 (0 min) -> 329 (30 min) -> 408 nmol/L (60 min) [N peak>500 nmol/L]), and she was back to her usual body weight. However, subsequent monitoring revealed declining trend of 9AM cortisol from 135 nmol/L (2013) -> 99 nmol/L (2014) -> 57 nmol/L (2015) -> 64 nmol/L (2016) -> 18 nmol/L (2017) [N 166–507 nmol/L]. Hydrocortisone compliance and abstinence from exogenous steroids was confirmed with the patient. The ongoing hypofunction of the HPA axis was continually attributed by multiple physicians to her history of prolonged use of dexamethasone. In 2018, at the age of 60, the lady presented with new onset headaches, blurred vision, and bitemporal hemianopia for 3 months. MRI showed a 1.8x1.8x3.5 cm (WxAPxH) pituitary mass with suprasellar extension compressing the optic chiasm. Blood tests revealed panhypopituitarism: SST cortisol 17 -> 59 -> 49 nmol/L, ACTH 2.7 pmol/L [N <10.1 pmol/L]; fT4 9.5 pmol/L [N 12–22 pmol/L], TSH 0.97 mIU/L [N 0.27–4.2 mIU/L]; LH <0.1 IU/L, FSH 0.52 IU/L (menopause at age of 48); IGF-1 27 µg/L [N 41–279 µg/L]; prolactin 17 mIU/L [N 102–496 mIU/L]. After partial excision of the mass her vision improved, but remained dependent on hydrocortisone and thyroxine supplements. The lesion was pathologically proven to be a pituitary macroadenoma. Discussion: This case presents the uncommon course of a patient who had almost recovered from iatrogenic hypoadrenalism, only to lapse back into worsened central adrenal insufficiency, as part of panhypopituitarism related to an undiagnosed pituitary mass. In retrospect, the unusually protracted state of hypocortisolemia and the atypical waxing and waning HPA axis should have alerted one to consider alternative etiologies at work. As LH-FSH and GH deficiencies commonly develop before ACTH and TSH deficiencies in most pituitary macroadenomas, a lower threshold for testing the other anterior pituitary hormones followed by imaging of the pituitary could have picked up the tumor earlier in this patient.

A Predictive Risk Score to Diagnose Adrenal Insufficiency in Outpatients: A 7 Year Retrospective Cohort Study

Background: The diagnosis of adrenal insufficiency (AI) requires dynamic tests which may not be available in some institutions. This study aimed to develop a predictive risk score to help diagnose AI in outpatients with indeterminate serum cortisol levels. Methods: Five hundred and seven patients with intermediate serum cortisol levels (3–17.9 µg/dL) who had undergone ACTH (adrenocorticotropin) stimulation tests were included in the study. A predictive risk score was created using significant predictive factors identified by multivariable analysis using Poisson regression clustered by ACTH dose. Results: The seven predictive factors used in the development of a predictive model with their assigned scores are as follows: chronic kidney disease (9.0), Cushingoid appearance in exogenous steroid use (12.0), nausea and/or vomiting (6.0), fatigue (2.0), basal cortisol <9 µg/dL (12.5), cholesterol <150 mg/dL (2.5) and sodium <135 mEq/L (1.0). Predictive risk scores range from 0–50.0. A high risk level (scores of 19.5–50.0) indicates a higher possibility of having AI (positive likelihood ratio (LR+) = 11.75), while a low risk level (scores of <19.0) indicates a lower chance of having AI (LR+ = 0.09). The predictive performance of the scoring system was 0.82 based on the area under the curve. Conclusions: This predictive risk score can help to determine the probability of AI and can be used as a guide to determine which patients need treatment for AI and which require dynamic tests to confirm AI.

Endogenous Hypercortisolism in recurrent Central Serous Chorioretinopathy

Background: Central Serous Chorioretinopathy (CSCR) is an important cause of nonsurgical retinopathy leading to moderate to severe visual loss. Almost 50% cases undergo recurrence, and one of the recognizable risk factors is endogenous hypercortisolism.&#x0D; Aims and Objective: Our study intended to its presence in recurrent CSCR patients compared to non-chorioretinal disorder.&#x0D; Materials and Methods: Eighteen-month cross-sectional comparative study done on recurrent CSCR patients and matched refractive error patients comprised the comparison group. Use of exogenous steroids and diagnosed conditions of hypercortisolism were excluded. Sample size for both the groups was 34 in each. After taking history and performing ocular examination, blood samples for serum cortisol estimation collected in the morning and in the evening in patients of both the groups. Results analyzed using standard statistical methods.&#x0D; Results: All patients of recurrent CSCR were males. The mean serum levels of cortisol were higher than laboratory reference range during both times of the day in recurrent CSCR patients, and these levels were significantly higher than those in the comparison groups.&#x0D; Conclusion: Recurrent CSCR patients have higher level of endogenous cortisol compared to the non-chorioretinal patients, and its early recognition and management would certainly benefit the patients.

Evaluating tertiary adrenal insufficiency in rheumatology patients on long-term systemic glucocorticoid treatment.

Patients with rheumatic diseases are often treated with prolonged, high-dose systemic glucocorticoids which can cause hypothalamic-pituitary-adrenal (HPA) axis suppression and development of tertiary adrenal insufficiency. Adrenal insufficiency carries the risk of serious, potentially life-threatening adrenal crisis. Our study evaluated the prevalence, characteristics and recovery of patients with underlying rheumatology conditions who had received prolonged glucocorticoid treatment. Retrospective, cross-sectional study. We evaluated 238 patients seen in outpatient rheumatology clinic, managed in accordance with current nationally and internationally accepted clinical guidelines. Data collected included patient demographics, historical steroid data, 09.00h cortisol/short synacthen test (SST) results and follow-up data on those with repeat assessments. Overall, 65% of our cohort had a 09.00h cortisol <350nmol/L. On SST, 43% of patients demonstrated evidence of possible tertiary adrenal insufficiency. Prednisolone equivalent dose at time of SST was significantly higher in the group who failed SST vs. those who passed; mean of 5.57mg vs. 3.59mg (p=.005). 09.00h cortisol result correlated with 30-min cortisol on SST (R2 =.20, p=.002). 0-min cortisol on SST correlated more strongly with 30-min cortisol than 09.00h cortisol (R2 =.59, p-value<.001). Patients with 0-min cortisol >350nmol/L, all passed their SST. Patients who remained on prednisolone were more likely to recover (71%) vs. those switched to hydrocortisone (27%), P=.02. Peak steroid dose was predictive of recovery; significantly lower in those who recovered (mean of 22.3mg vs. 33.8mg, P=.03). Steroid duration was not found to be a predictor of recovery [recovery (64.2months) vs. non-recovery (55.6months), P=.58]. There was no correlation found to outcome on SST with age, sex, peak steroid dose, steroid duration, underlying rheumatological condition, additional exogenous steroid use or serum sodium. Forty three percent of our patients demonstrated sub-optimal adrenal function on SST. Steroid dose at the time of SST was the only significant predictive risk factor for tertiary adrenal insufficiency. 09.00h cortisol demonstrated good correlation with outcome on SST and could represent a valid screening test to reduce need for SST if 09.00h >350nmol/L. Further prospective data are required to further characterize risk factors, predictive features of recovery and establish optimal management strategy of steroids (prednisolone vs hydrocortisone) to encourage adrenal recovery.

Systemic evaluation of patients with central serous chorioretinopathy: A case-control study.

To investigate the systemic associations of central serous chorioretinopathy (CSCR) with help of clinical and biochemical investigations. Case-control study. Eighty seven CSCR patients (case) and 82 Asian-Indian patients with primary non-traumatic rhegmatogenous retinal detachment (control) were recruited between July 2017 and December 2018 at a tertiary eye-care center in North India. The patients underwent ophthalmological examination and systemic evaluation based on history and biochemical investigations. Logistic regression was performed to identify the associations of CSCR. The age was similar between cases and controls (36.9 ± 7.8 years vs 35.7 ± 10.8 years, p = 0.38). On univariate analysis, the significant factors with higher odds of CSCR were alcohol use (odds ratio, OR: 3.4; 95% confidence interval: 1.36-8.53), sleep disturbance (OR: 5.44; 1.76-16.8), gastroesophageal reflux (OR: 9.34; 1.15-75.50), psychological disorder (OR: 5.78; 1.24-26.97), tuberculosis history (OR: 8.2; 1.0-67.10), serum albumin: globulin ratio (AGR) > 2 (OR: 10.43; 2.33-46.57), and serum hemoglobin (per unit increase; OR: 1.35; 1.14-1.61). Although the mean blood pressure was significantly higher in cases, the distribution among various hypertension categories was not significantly different. Exogenous steroid use and morning 8 am serum cortisol levels were not significantly different between the groups. On multivariable analysis, alcohol use (OR: 4.72; 1.33-16.76), sleep disturbances (OR: 5.04; 1.36-18.70), dysthyroid state (OR: 3.02; 1.04-8.74), serum AGR > 2 (OR: 14.28; 2.33-87.28), and serum hemoglobin (per unit increase; OR: 1.43; 1.13-1.81) were significant independent associations. Other than the previously described associations of CSCR like alcohol use and sleep disturbances, this study reports possible association with deranged serum protein and thyroid hormone profile. Further large-scale prospective studies need to validate these results.

OR25-04 Over 14% of Inpatients with Euvolemic Hyponatremia Have Undiagnosed Adrenal Insufficiency

Background- The commonest cause of euvolemic hyponatremia (EvHNa) is the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The diagnosis of SIADH requires the exclusion of secondary adrenal insufficiency (AI) and untreated hypothyroidism. Studies have suggested about 4% of unselected patients presenting to the emergency room with EvHNa have undiagnosed SAI.1 Among patients admitted to specialized endocrine units this prevalence maybe as high as 20%.2Objective- To study the prevalence of undiagnosed AI among inpatients with EvHNa admitted to general medical wards. Methods- This was a prospective, single centre observational study conducted among inpatients with EvHNa. EvHNa was defined as patients with a serum sodium (Na) <135 mEq/L, with no clinical evidence of dehydration or fluid excess, and a urine spot Na >30mmol/L. In addition patients with recent vomiting, renal failure, recent diuretic use, uncontrolled hyperglycemia and patients with history of use of oral or parenteral steroids in the last 6 months were excluded. Adrenal functions were assessed by a modified porcine ACTH stimulation test which has been described recently by Nair et al. A cut off cortisol value of <18mg/dl after 60 minutes of ACTH injection was used to diagnose AI.3Results- One hundred and forty one (141) patients were included after informed consent and all underwent a modified ACTH stimulation test. They had a mean age of 58 years and 52.3% (n=74) were males. Modified ACTH stimulation testing suggested 20/141 (14.2%) had undiagnosed AI. The mean age among those with AI was 55.2 years. In only 25% (5/20) AI was suspected based on clinical presentation by the treating physician. Despite excluding patients with documented steroid use, the commonest cause of AI (9/20) was secondary AI due to exogenous steroid use including high potency inhaled steroids (5/9) and the use of undocumented steroids or steroid containing medicaments by alternative practitioners (4/9). Hypopituitarism was diagnosed as the cause of AI in 5 patients, which included unsuspected Sheehan’s syndrome in post menopausal women (3/5), non functioning pituitary adenoma (1/5) and lymphocytic hypophysitis (1/5). Despite primary AI not commonly presenting as EvHNa, 3/20 patients had primary AI and in the remaining 3 patients the aetiology of AI remained unclear. Conclusions- Undiagnosed AI is much more common in our country among inpatients presenting with EvHNa to medical units. This increase is primarily driven by inhaled and undocumented exogenous steroid use and undiagnosed Sheehan’s syndrome. An assessment of the hypothalamic-pituitary-adrenal axis is mandatory before making a diagnosis of SIADH. References -(1) Diederich et al. Eur J Endocrinol 2003; 148: 609-617. (2) Cuesta et al. Clin Endocrinol (Oxf) 2016; 85: 836-844. (3) Nair A et al. Eur J Endocrinol. 2019 Oct 1. pii: EJE-19-0558.R2.

MON-169 Diagnostic Utility of Free Cortisol in Dexamethasone Suppression Test. A Prospective Study in Healthy Subjects

OBJECTIVE: Low dose dexamethasone suppression testing (DST) is standard of care in patients with adrenal incidentalomas or suspected endogenous hypercortisolism. False positive total serum cortisol (TC) results occur due to poor absorption, rapid metabolism or estrogen use. Free serum cortisol (FC) measurement is an alternative, but optimal cut-offs are unknown. We aimed to establish the optimal serum dexamethasone concentrations (DEXA) to interpret TC and FC results and identify reasons for discrepancies between TC and FC values in healthy male and female (with and without oral contraceptive therapy, OCT) subjects. METHODS: Single center prospective study of healthy subjects >17 years old undergoing assessment with DST between 2016 and 2019. Measurement of FC and DEXA was performed by tandem mass spectrometry and TC by immune-enzymatic assay at 8 AM following overnight administration of 1 mg dexamethasone at 11pm. Subjects were excluded if they had a known adrenal adenoma, any form of endogenous cortisol excess, or exogenous steroid use. RESULTS: DST was performed in 165 healthy volunteers, median age of 29.5 (18-74) years; 53 men (32%) and 112 (67%) women, median BMI 25 (18-42) kg/m2, 47 (42%) of which were taking OCT (median daily ethinyl-estradiol dose of 30 (20-35) mcg). The median DEXA was 0.34 (0.09-1.12) mcg/dl, median TC was 0.8 (0.25-15.7) mcg/dl and median FC was 24 (4-714) ng/ml. TC and FC measurements were highly correlated (r2=0.89, p<0.0001). The median FC/TC was 3% (0.3-6.7), lowest in women on OCT (median 2.5% vs 3.3% in women not on OCT and men, p<0.0001). TC>1.8 mcg/dl was demonstrated in 18 (11%) healthy subjects (men: 3/53, 5.7% vs women not on OCT: 3/65, 4.6% and women on OCT: 12/47, 25.5%, p=0.0007). Excluding women on OCT, the proportion of subjects with TC>1.8 was higher when DEXA was <0.2mcg/dl (4/15, 27%) vs when DEXA was >0.2mcg/dl (2/101, 2%),(p<0.0001). After excluding 24 (14%) healthy subjects with DEXA <0.2 mcg/dl, in the remaining 142 subjects (51 (35%) men, 54 (38%) women not on OCT and 39 (27%) women on OCT), median TC was 0.75 (0.25-4.6) mcg/dl and median FC was 23 (4-103) ng/ml). Significant differences were noted in both TC and FC following DST within subgroups: men vs women not on OCT vs women on OCT, TC: 0.6 vs 0.7 vs 1.3 mcg/dl, (p<0.0001) and FC: median 20 vs 22 vs 31 ng/ml, (p<0.0001). All men and all women not on OCT demonstrated post-DST FC <50 ng/ml (97.5% cutoff of 47 and 37), while women on OCT demonstrated post-DST FC <50 in 80% and FC<75 in 95%. CONCLUSION: Post-DST TC>1.8 mcg/dl was demonstrated in 11% of all healthy subjects, of which 1 in 4 were women on OCT and 1 in 4 had DEXA<0.2 mcg/dl. Simultaneous measurement of serum DEXA during DST may be valuable when false positive results are suspected. Despite a lower FC/TC ratio in women on OCT, post-DST FC cutoffs were higher in women on OCT. Measurement of FC after DST may be helpful in some but not all women on OCT.

Clinical and biochemical factors to predict biochemical adrenal insufficiency in hospitalized patients with indeterminate cortisol levels: a retrospective study

BackgroundAdrenal insufficiency (AI) in hospitalized patients is a fatal condition if left undiagnosed. Most patients may require an adrenocorticotropic hormone (ACTH) stimulation test to facilitate AI diagnosis. We aim to identify simple biochemical and clinical factors and derive a predictive model to help identify hospitalized patients with biochemical AI who have indeterminate 0800 h serum cortisol levels.MethodsA seven-year retrospective study was performed in a tertiary care medical center. We identified 128 inpatients who had undergone low-dose or high-dose ACTH stimulation tests. The association between biochemical AI and other factors was evaluated using a logistic regression model clustering by ACTH dose. Stepwise regression analysis was used to demonstrate the predictive model. Diagnostic performance was evaluated using ROC analysis.ResultsOf the 128 patients, 28.1% had biochemical AI. The factors associated with biochemical AI were serum random cortisol < 10 μg/dL (OR = 8.69, p < 0.001), cholesterol < 150 mg/dL (OR = 2.64, p = 0.003), sodium < 140 mmol/L (OR = 1.73, p = 0.004)). Among clinical factors, cirrhosis (OR = 9.05, p < 0.001), Cushingoid appearance in those with exogenous steroid use (OR = 8.56, p < 0.001), and chronic kidney disease (OR = 2.21, p < 0.001) were significantly linked to biochemical AI. The AUC-ROC of the final model incorporating all factors was 83%.ConclusionsThese easy-to-perform biochemical tests and easy-to-assess clinical factors could help predict biochemical AI in hospitalized patients with high accuracy. The physician should therefore have a high index of suspicion to perform dynamic tests for AI diagnosis in those who meet the proposed model criteria.

Spinal Epidural Lipomatosis: A Rare Complication From Hormonal Therapy for Infantile Spasms

BackgroundSpinal epidural lipomatosis (SEL) represents pathologic overgrowth of extradural adipose tissue in the spinal canal that can result in spinal cord compression. SEL has been associated with excess corticosteroids, whether from exogenous steroid use or from excess endogenous steroids. Spinal epidural lipomatosis is rarely reported in children and has not been reported in association with hormonal therapy for infantile spasms. MethodsWe performed a detailed retrospective chart and literature review. ResultsWe describe two children with symptomatic SEL associated with the use of high-dose hormone treatment for infantile spasms.

SAT-220 Oral Contraceptives and Their Effect on the Evaluation of Cushing's Syndrome: A Case Report

Background In the evaluation of Cushing’s syndrome (CS), oral contraceptives may lead to false-positive results by raising the serum levels of cortisol-binding globulin (CBG). Clinical Case An 18-year old Chinese lady presented with weight gain, irregular menses and hirsutism. History was unremarkable for hypothyroidism, hyperprolactinemia, eating disorders, and exogenous steroid use. On examination, she was overweight (body mass index (BMI) 26.9 kg/m2) with rounded facies, hirsutism and dorsal cervical fat pad. Initial biochemical tests showed high cortisol and ACTH levels: ACTH 66.6 pmol/L (RI 0-10.2 pmol/L) and random cortisol 958 nmol/L (RI: 240-618 nmol/L). She was referred to our department for evaluation of possible Cushing’s syndrome. Further history revealed that the patient was on a combined estrogen-progestin oral contraceptive pill (OCP). Confirmatory tests after cessation of the OCP for 6 weeks revealed normal 24-hr urinary cortisol levels (231 and 255 nmol/day, RI: 59-413 nmol/day) and a normal 1 mg dexamethasone suppression test (44 nmol/L after administration of 1 mg dexamethasone overnight, RI <50nmol/L). A progesterone challenge test induced withdrawal bleeding, consistent with an estrogen-sufficient anovulatory state such as that seen in Polycystic Ovarian Syndrome. Regular menstrual cycles returned after deliberate weight loss to a BMI of 26.0 kg/m2). Discussion and Conclusion OCPs increase total cortisol concentrations by increasing circulating CBG without affecting the unbound fraction (1). Women on OCPs may hence display elevated serum total cortisol concentrations without increased cortisol activity. These elevations are dependent on estrogen dose, and usually not seen with progestogen-only or low-dose estrogen (0.05 mg mestranol or less) preparations (2). Other drugs interfering with cortisol clearance, such as CYP3A4 inhibitors and inducers, may also influence test results (3). Current guidelines suggest that estrogen-containing drugs should be discontinued for at least 6 weeks so as to prevent false-positive results, which can potentially lead to unnecessary procedures or surgery. A thorough drug history is therefore crucial in the evaluation of CS. References (1) Qureshi AC, Bahri A, Breen LA, et al. The influence of the route of oestrogen administration on serum levels of cortisol-binding globulin and total cortisol. Clin Endocrinol (Oxf). 2007; 66: 632-5 (2) C. W. Burke. The effect of oral contraceptives on cortisol metabolism. J Clin Pathol Suppl (Assoc Clin Pathol). 1969; 3: 11-18. (3) M. Vastbinder, M. Kuindersma et al. The influence of oral contraceptives on overnight 1 mg dexamethasone suppression test. Neth J Med. 2016 May;74(4): 158-61.