Exogenous Glucocorticoid Use Research Articles

7627 Prevalence Of True Endocrinopathies In Patients Presenting To An Endocrine Clinic With Fatigue

Abstract Disclosure: C. Dimech: None. K. Barnett: None. F. Hasan: None. Introduction: Fatigue is a common chief complaint, resulting in approximately 7 million physician office visits per year in the US. Fatigue is a non-specific symptom which can be associated with many acute or chronic conditions. In our clinical experience fatigue is a frequent reason for referral to the endocrine clinic, and often assessment does not reveal an endocrine pathology. However, the prevalence of endocrinopathies discovered following endocrinology assessment has not been well studied. Methods: In this retrospective study, we completed chart review of electronic medical records of patients who were evaluated for a chief complaint of fatigue at outpatient endocrinology centers belonging to an integrated health network in the Pittsburgh Metro area. We included patients aged 18-40 years old from 01/01/2019- 12/31/2022. We hypothesized that there is not a significant incidence of endocrinopathies found on evaluation. Results: Extensive clinical and laboratory data were gathered for 226 patients during the study period. 39.9% of patients were self-referred. 60.1% of patients seen were through physician referrals, however 17.9% of these patients had no prior investigations completed. The majority of patients evaluated for fatigue were female (76.5% vs 23.5%). 55.3% of patients were 30-39 years of age. 27% of patients were overweight and 23% were obese with BMI 30 or greater. Nearly half of all patients had a diagnosis of anxiety or depression (51.7% and 48.2% respectively). Of those patients with anxiety, 57.3% were prescribed an SSRI or SNRI. Similarly, 58.7% of patients with depression were prescribed an SSRI/SNRI. Patients most commonly reported other non-specific symptoms such as weight gain, poor sleep and poor mood (51.3%, 38.9%, 25.2% respectively). 54.9% of female patients presenting with fatigue were concerned for thyroid dysfunction whereas 45.3% of male patients were concerned for hypogonadism. 12.3% of patients evaluated never completed the recommended testing. Vitamin D deficiency was notably prevalent in 42.4% of patients tested. One patient was found to have secondary adrenal insufficiency in the setting of chronic exogenous glucocorticoid use for back pain. Of 163 patients tested for thyroid dysfunction, no new diagnoses of thyroid abnormalities were revealed. Conclusion: In this study, laboratory testing from an endocrinology consultation was not useful in detecting newly discovered endocrinopathies as a cause of fatigue. Presentation: 6/2/2024

12434 History Of Surgical Menopause Is Associated With An Accelerated “Adrenal Aging” In Menopausal Women

Abstract Disclosure: J. Saini: None. R. Nathani: None. J. Larson: None. V. Fell: None. I. Bancos: None. Background: Surgical menopause due to bilateral salpingo-oophorectomy (BSO) at a younger age is associated with an increased risk of cardiovascular disease, cognitive decline, and increased mortality. Aging is associated with abnormalities in steroid metabolome, most notably an increased glucocorticoid to androgen ratio (“adrenal aging”). We hypothesized that in postmenopausal women of the same age, the duration of menopause is associated with adrenal aging. Objective: To determine the differences in the adrenal steroid metabolome of women with a history of BSO as compared to age-matched women following natural menopause. Methods: We conducted a single-center cross-sectional study in postmenopausal women with or without a history of BSO, between December 2020 to December 2022 Each participant collected 24-hour urine, which was analyzed for steroid profiling by liquid chromatography-tandem mass spectrometry (25 steroids). Exclusion criteria were inability to collect a 24h urine sample, exogenous glucocorticoid use, advanced malignancy, and chronic opioid use. Primary endpoints were glucocorticoid/androgen ratio, 11β-hydroxysteroid dehydrogenase type 2 activity (cortisol/cortisone, Tetrahydrocortisol (THF) + 5 α-tetrahydrocortisol (5 α-THF)/ Tetrahydrocortisone, THE) and 5 α-reductase type activity (Tetrahydrocortisol (THF)/5 α-tetrahydrocortisol (5 α-THF) and Etiocholanolone/Androsterone, Et/An). Results: A total of 245 women were enrolled: 124 women (median age of 66 years, IQR 63-72) with a history of BSO and 121 women (median age of 68 years, IQR 64-71) who underwent natural menopause (P=0.214). Median age at menopause was 44 years (IQR 41-46) in the BSO group, and 50 years (IQR 48-53) in the natural menopause group. History of hormone replacement therapy with estrogen was reported in 161 (66%) women, more frequently (92% vs 39%, P<0.001) and for a longer duration (median 12 years (IQR 6-16) vs 6 years (IQR 3-9), P<0.001) in in the BSO group, as compared to the natural menopause group. Although both groups had similar levels of urinary androgens (median 1387 vs 1686 mcg/24h, P=0.063) and total glucocorticoids (median 10877 vs 10277 mcg/24h, P=0.354), women with a history of BSO demonstrated a higher glucocorticoid/androgen ratio (median 7.9 (IQR 5.0-11.1) vs 6.7 (4.3-9.9), P=0.014), and a lower Et/An ratio (median 1.4 vs 1.6, P=0.045), but not THF/5aTHF ratio (median 1.7 vs 1.8, P=0.380) in comparison to women with natural menopause. No differences were found in other ratios. Conclusion: Women with a history of BSO demonstrated a higher glucocorticoid/androgen ratio in comparison to women undergoing natural menopause, suggestive of BSO-induced accelerated “adrenal aging”. Future studies need to examine associations between the abnormal steroid metabolome and increased cardiovascular morbidity, frailty, and mortality reported following BSO. Presentation: 6/3/2024

O-04 A diagnostic riddle of an adrenal incidentaloma

Abstract Clinical case A 78-year-old male underwent preoperative CT as transcatheter aortic valve implantation was planned. In addition to a 6 cm incidental mass in the right adrenal, it also revealed unspecific pulmonary nodules. The patient was referred to the Endocrine unit. Non-contrast adrenal CT demonstrated a heterogenous 6 cm tumor, < 10 HU. The patient had a history of psoriasis, type 2 diabetes mellitus, hypertension, chronic kidney disease, atrial fibrillation, peripheral artery disease, aortic stenosis and coronary artery disease. Clinical examination revealed no signs of Cushing's syndrome. First, normal blood metanephrine/normetanephrine concentrations confirmed that pheochromocytoma was ruled out. The possibility of a metastatic tumor mass was investigated by tumor biopsy, histopathology was compatible with an adrenocortical neoplasm, Ki67 2%. Further laboratory work-up is given in Table 1. How should the laboratory findings be interpreted? Primary aldosteronism was ruled out. Cortisol was not suppressed on 1mg DST, in contrast to perfectly normal 24h urinary free cortisol. Late night salivary cortisol (LNSC) was markedly increased, 1210 nmol/l and low ACTH concentration further suggested true hypercortisolism. Does the patient suffer from hypercortisolism? The patient had no clinical signs of Cushing syndrome, albeit cardiometabolic diseases. False positive DST and LNSC results were suspected. Indeed, the patient was using 1% hydrocortisone lip lotion. On repeat screening after discontinuation of hydrocortisone, LNSC was 3.8 nmol/l, and DST remained positive (258nmol). The patient was diagnosed with autonomous cortisol excess (MACS) (1). Should the patient undergo surgery for the right adrenal mass? MACS in combination with relevant co-morbidities and large tumor size indicated surgery (1), which the patient consented to. After surgery, cortisol concentrations remained suppressed which prompted hydrocortisone replacement therapy. Final pathology review classified the tumor as an adenoma, Weiss Score 0/9 and Ki-67 2%. Conclusion False positive cortisol screening tests are common and must be ruled out before surgery. For DST, common explanations are exogenous glucocorticoid use, drugs that accelerate dexamethasone metabolism and estrogen induced increase in CBG. The most common pitfalls for LNSC are deranged circadian rhythm and exogenous hydrocortisone. Reference (1). Fassnacht el al. European Society of Endocrinology clinical practice guidelines on the management of adrenal incidentalomas. European Journal of Endocrinology,2023; 189(1): G1–G42.Table 1

SAT328 Severe Exogenous Cushing Syndrome Caused By A Potent Steroid Concealed In Arthritis Supplement

Abstract Disclosure: S. Maraqa: None. L. Bushnaq: None. R. Singh, PhD: None. N. Genere: None. Cushing syndrome (CS) is a rare disorder caused by excessive systemic glucocorticoids and associated with increased mortality and worsening quality of life. CS most commonly occurs from exogenous glucocorticoid use, while Cushing disease causes most of endogenous cases. Here, we present a case of a 64-year-old woman with rapidly progressive CS due to an over-the-counter (OTC) arthritis supplement with unlisted dexamethasone. A 64-year-old woman with reported CS who was evaluated in our Endocrinology center after she moved to the United States. She was previously diagnosed with pituitary CS in Mexico following a 6 months history of rapid 50-pound weight gain, profound proximal muscle weakness requiring assistive device, and unprovoked vertebral fractures; laboratory evaluation found elevated 24-hour urinary cortisol 272 mcg/24h, 1mg dexamethasone suppression test total cortisol 5.6 mcg/dl (< 1.8), and adrenocorticotropic hormone (ACTH) 16 pg/mL. Pituitary MRI was unremarkable. Past medical history included primary hypothyroidism and hypertension. Physical exam was notable for blood pressure 160/108 mmHg, heart rate 96, BMI 33 kg/m², moon face, supraclavicular fat pads, central obesity, skin bruises, and proximal muscle weakness. Unexpectedly, re-evaluation showed undetectable serum ACTH and cortisol. A thorough review of medications identified no recent exposure to glucocorticoids. However, a synthetic glucocorticoid screen showed markedly elevated serum dexamethasone concentration. Follow-up discussion revealed that she had started an arthritis supplement “Artri-King” 6 months prior to these symptoms. We collaborated with Mayo Clinic Labs to evaluate dexamethasone contents in this drug; each tablet was found to contain 0.9 mg of dexamethasone, which was unreported in the ingredient list. This supplement was stopped, and the patient was started on physiologic hydrocortisone. Two months later, AM cortisol was 5.6 mcg/dL and ACTH 23 pg/ml. Eight months later, she continues to have adrenal insufficiency but has had a substantial clinical improvement.Exogenous CS is readily diagnosed in patients taking prescribed glucocorticoids; however, diagnosis can be more challenging in cases where the presence of glucocorticoids is concealed. The US Food and Drug Administration follows more limited regulatory guidelines for dietary supplements compared to prescribed drugs. A study by Tucker.et.al. reported that 20% of dietary supplements have unapproved ingredients.1 This is especially concerning, considering that over half of the US population admits to taking dietary supplements.2 On April 2022, the FDA published a public notice for “Artri-King”, declaring the presence of unlisted dexamethasone.3 Should such agents prove to be the culprit of CS, they must be tapered off gradually or in the presence of physiologic hydrocortisone to avoid the risk of adrenal crisis. Presentation: Saturday, June 17, 2023

THU606 Cognitive Impairment In Patients With Mild Autonomous Cortisol Secretion: A Cross-sectional Study

Abstract Disclosure: J. Saini: None. R. Nathani: None. S. Singh: None. K. Thangamuthu: None. M. Suresh: None. C. Zhang: None. A.L. Ebbehøj: None. M. Thomas: None. V. Fell: None. E. Atkinson: None. S. Achenbach: None. N. Stricker: None. I. Bancos: None. Introduction: While patients with overt Cushing syndrome are reported to have impaired cognition, the impact of milder, long-standing hypercortisolism on cognition is incompletely characterized. Objective: To determine the impact of MACS on cognition as compared to age, sex, and education-matched referent subjects. Methods: We conducted a single-center cross-sectional study of adults with MACS and referent subjects. MACS was defined as serum cortisol>1.8 mcg/dL after 1 mg dexamethasone suppression test (DST) in patients with adrenal incidentalomas. Referent subjects were included if they had abdominal imaging and had no adrenal disorders. Exclusion criteria were malignancy and exogenous glucocorticoid use within 1 year. All participants underwent a cognitive evaluation using the NIH Toolbox Cognition Battery between 1/2019 to 7/2022. NIH Toolbox assesses 8 cognitive domains using 7 tests and yields 3 composite scores: fluid cognition (executive function, episodic memory, cognitive flexibility, working memory, and processing speed), crystallized cognition (language and vocabulary), and total composite cognition (composite of all). Results are given in fully corrected T scores (adjusted for age, sex, race, and education) with an average of 50 and a standard deviation (SD) of 10. A subgroup analysis was performed based on DST cortisol. The Kruskal-Wallis test was used to compare scores between groups. Results: A total of 94 patients with MACS (median age 57.2 years, IQR 47.8-66.5, 70% women) and 94 referent subjects (median age 58 years, IQR 49.1-66.4, 70% women) were included. The median post-DST cortisol in patients with MACS was 3.3 mcg/dL (IQR, 2.4-6.2). The mean (SD) total composite T-score was lower in patients with MACS vs referent subjects (51 (9.1) vs 56.3 (9.3), P<0.001). Patients with MACS demonstrated lower mean fluid composite T-score when compared to referent subjects (49.5 (10.4) vs 56.9 (9.7), P<0.001). However, mean crystallized composite T-scores were similar in patients with MACS and referent subjects (52.3 (8.1) vs 53.9 (9.6), P=0.342). A subgroup analysis of patients with post-DST cortisol <3 mcg/dL (n=40) vs patients with post-DST cortisol >3 mcg/dL (n=54) did not show any differences in the total, fluid, or crystalized composite scores. Conclusion: Patients with MACS demonstrate lower cognitive performances than a referent group suggesting MACS has a subtle impact on cognitive functioning. The pattern of cognitive impairment in patients with MACS is similar to that seen with normal cognitive aging: impaired fluid cognitions and unaffected crystallized cognition). Cognitive performance did not differ based on the degree of MACS suggesting that in the absence of overt features of hypercortisolism, the degree of MACS is less important than the presence of MACS. Presentation: Thursday, June 15, 2023

SAT300 Use of Overnight Metyrapone Test In Suspected Adrenal Insufficiency: A Retrospective Single Center-Study

Abstract Disclosure: J. Saini: None. R. Gregg Garcia: None. J. Herndon: None. D.Z. Erickson: None. L. Gruber: None. I. Bancos: None. Context: Overnight metyrapone test (OMT) is a dynamic test used to diagnose secondary adrenal insufficiency (SAI). However, it is uncommonly used and the data on the OMT indications and performance are scarce. We aimed to characterize the indications, performance, and safety of outpatient OMT. Methods: Single center retrospective study in adults with OMT between April 1st, 2018 -July 31st, 2022. We evaluated three post-OMT cutoffs diagnostic of SAI: 1) 11-deoxycortisol ≤7 mcg/dL (11D≤7); 2) 11-deoxycortisol ≤10 mcg/dL (11D≤10), or 3) sum of cortisol and 11-deoxycortisol ≤15 mcg/dL (sum≤15), in comparison to pre-test probability and reference standard, defined as clinician-made diagnosis of SAI. When available, OMT-based SAI diagnosis was compared to results from the cosyntropin stimulation test (CST). Results: OMT was performed in 109 patients (76, 70% women) at a median age of 48 (IQR, 37-59) years. Pre-test probability for SAI was high in 13 (12%), moderate in 46 (43%), and low in 49 (45%) patients. Indications for OMT included evaluation of symptoms without clear SAI risk factors (38, 35%), suspected SAI due to chronic opioid use (25, 23%), pituitary pathology/therapies (25, 23%), exogenous glucocorticoid use (8, 7%), other (13, 12%). Overnight metyrapone was administered at a median dose of 2500 (IQR, 2125-3000). Adverse events were reported by 9 (8%) patients and were mild (nausea, fatigue) except for 1 patient who had to be hospitalized. The final diagnosis of SAI was made in 25 (48%) patients: 92%, 52%, and 12% of patients with high, moderate, and low pre-test probability. When compared to the clinician-made SAI diagnosis, OMT-based diagnosis of SAI was made in 60% of patients using the 11D≤7 cutoff, and in 81% of patients using the other cutoffs (11D≤10 or sum≤15). In 50 patients with concomitant CST, the final diagnosis of SAI was made in 23 (46%) patients, despite the normal CST results (post-cosyntropin peak cortisol ≥18 mcg/dL) in 12/23 patients. In patients with post-cosyntropin peak cortisol ≥18 mcg/dL, OMT was abnormal in 14% of patients (using post-OMT cutoff 11D≤7), 29% of patients (based on cutoff 11D≤10), and in 30% of patients (based on sum≤15). Conclusions: Outpatient OMT is well tolerated and was mostly used in patients with low/moderate pre-test probability for SAI. In patients with normal CST, OMT may diagnose SAI in additional 30% of patients, especially if the pre-test probability is high. Post-OMT sum of 11-deoxycortisol and cortisol <15 mcg/dL performs well in diagnosing SAI while allowing confirmation of adequate cortisol suppression. Presentation: Saturday, June 17, 2023

Adrenal insufficiency.

Adrenal insufficiency (AI) is a condition characterized by an absolute or relative deficiency of adrenal cortisol production. Primary AI (PAI) is rare and is caused by direct adrenal failure. Secondary AI (SAI) is more frequent and is caused by diseases affecting the pituitary, whereas in tertiary AI (TAI), the hypothalamus is affected. The most prevalent form is TAI owing to exogenous glucocorticoid use. Symptoms of AI are non-specific, often overlooked or misdiagnosed, and are related to the lack of cortisol, adrenal androgen precursors and aldosterone (especially in PAI). Diagnosis is based on measurement of the adrenal corticosteroid hormones, their regulatory peptide hormones and stimulation tests. The goal of therapy is to establish a hormone replacement regimen that closely mimics the physiological diurnal cortisol secretion pattern, tailored to the patient's daily needs. This Primer provides insights into the epidemiology, mechanisms and management of AI during pregnancy as well as challenges of long-term management. In addition, the importance of identifying life-threatening adrenal emergencies (acute AI and adrenal crisis) is highlighted and strategies for prevention, which include patient education, glucocorticoid emergency cards and injection kits, are described.

Cushing's syndrome: An in-depth review of pathophysiology, diagnosis, and manifestations

Background: Cushing's syndrome results from prolonged exposure to elevated glucocorticoids, leading to significant morbidity and mortality. Despite its historical identification over a century ago, challenges remain in diagnosing and treating this condition due to its non-specific symptoms and complex underlying mechanisms. Aim: This review aims to elucidate the pathophysiology, diagnostic approaches, and treatment options for Cushing's syndrome to enhance clinician understanding and improve patient outcomes. Methods: A comprehensive literature review was conducted, synthesizing data on the etiology, classification, and epidemiology of Cushing's syndrome. The review categorized Cushing's syndrome into ACTH-dependent and ACTH-independent forms, highlighting diagnostic challenges and therapeutic strategies, including surgical, medical, and radiation options. Results: The findings reveal that Cushing's syndrome predominantly arises from either endogenous factors (e.g., pituitary adenomas, ectopic ACTH production) or exogenous glucocorticoid use. ACTH-dependent Cushing's disease accounts for the majority of cases, particularly in women aged 25-40. The review also identifies key diagnostic tools, including biochemical tests and imaging studies, and discusses the importance of recognizing both overt and subtle clinical presentations. Conclusion: Cushing's syndrome remains a complex endocrine disorder requiring a multifaceted approach for accurate diagnosis and effective management.

MON-164 Determinants of Quality of Life in Primary and Secondary Adrenal Insufficiency from Two Large Tertiary Care Centers in the United States

Background: Patients with primary adrenal insufficiency (PAI) and secondary adrenal insufficiency (SAI) report impaired quality of life. Predictors of adverse outcomes include duration of disease, supraphysiologic glucocorticoid (GC) use, and presence of other comorbidities. There is limited evidence to suggest that quality of life is disproportionately affected in one subtype of adrenal insufficiency. Objective: To identify determinants of quality of life in patients with PAI vs SAI. Method: Survey study of patients with the diagnosis of AI between 2015 and 2019 was evaluated at two large tertiary medical centers in the United States. Collected variables included data on circumstances of AI diagnosis, symptoms, management, burden of disease, and overall well-being. Patients with AI due to exogenous glucocorticoid use were excluded. Results: Patients with PAI (n=310, 65% women) were diagnosed at a younger age (37 ± 19 vs 48 ± 16 years, p<.01) than patients with SAI (n=255, 57% women). Patients with SAI were more likely not to understand their diagnosis (13% vs 4% in PAI, p<.01), or to report a discordant diagnosis (16% vs 9% in PAI, p=.02). Patients with PAI were on a higher dose of daily GC (23.8 mg vs 18.5 mg hydrocortisone (HC) equivalent, p <.01), with higher number of patients on HC> 25 mg/day (33% vs 15%, p<.01). Patients with PAI reported a higher compliance with wearing medical alert ID (79% vs 64%, p=.01) and higher availability of injectable GC (74% vs 58%, p<.01). Patients with PAI reported a higher frequency of at least one adrenal crisis within the last 12 months that required self- injectable GC (32% vs 16%, p<.01), or prompted ER visits (56% vs 29%, p<.01) compared to those with SAI. Nevertheless, patients with PAI were more likely to report good general health (78% vs 65% in SAI, p<.01). When adjusted for current age, sex, duration of disease, supraphysiologic GC use, number of current symptoms and recent adrenal crises, patients with SAI had HR of 2.6 (CI 95% 1.5-4.3) for poor health, 1.6 (CI 95% 0.95-2.8) for physical limitations, 1.7 (CI 95% 1.1-2.7) for fatigue, and 2.7 (CI 95% 1.5-4.9) for social limitations compared to those with PAI. Conclusions: Patients with PAI receive higher daily GC and experience a higher number of adrenal crises when compared to patients with SAI. However, patients with PAI report a better general perception of health, possibly due to a more robust knowledge of their disease and higher comfort level managing AI. More effort is needed to ensure patients with AI are appropriately educated regarding their medical condition and therapy.

SUN-188 Intra-Articular Triamcinolone Injections - a “Slipped” Cause of Cushing’s Syndrome

Background:Triamcinolone injections are used to treat various orthopedic and rheumatologic conditions; their effects on the hypothalamic pituitary adrenal axis have not been well characterized.Clinical Case:A 14 yo female was referred to our clinic for evaluation of low TSH (0.16 µIU/mL) and possible hyperthyroidism. There was no goiter and she appeared euthyroid and had normal free T4 (1.01 ng/dl) but she had typical features of Cushing syndrome (CS), including round facies, thinning of hair, fatigue, truncal adiposity, violaceous striae, facial hirsutism and oligomenorrhea. She was previously healthy and participated in many sports. She did not report any history of exogenous glucocorticoid use but the fasting ACTH (4 pg/ml) and cortisol (0.1 µg/dl) levels were suppressed. Subsequent chart review revealed that she received intra-articular Triamcinolone (TA) to treat “slipping rib” syndrome. This included 3 injections of Kenalog 40 mg/mL, the last in July 2019. Her cumulative TA dose was 440 mg, the equivalent of prednisone 550 mg. Triamcinolone acetonide 1.4 mcg/dL (normal 0-0.1, analyzed by LC-MS/MS) was detected in the urine over 3 months after her last injection.Conclusion:- Levels of ACTH and cortisol can be suppressed for several months after intra-articular corticosteroid injections, placing the patient at subsequent risk for adrenal crisis- In some cases, high doses of Triamcinolone administered by intra-articular injection can cause clinical Cushing syndrome

SUN-193 A Case of Cushing’s Syndrome Caused by Epidural Corticoidsteroid Injection

Introduction: Cushing’s syndrome (CS) is a collection of signs and symptoms caused by hypercortisolism that results from endogenous or exogenous glucocorticoid excess. It is associated with increased morbidity and mortality from musculoskeletal, metabolic, thrombotic, infectious and cardiovascular complications. The most common cause of CS today is the use of corticosteroid medications. It′s reported that more than 10 million American receive pharmacological doses of glucocorticoids each year. Case reports have shown that CS can be caused by non-systemic use of corticosteroids. Clinical case: A 53-year-old patient with past medical history of osteoarthritis who presented to outpatient endocrinology office for new onset facial swelling of 2 months. His PCP had attributed it to adverse effect of recent neck glucocorticoid injections and treated him with prednisone for 7 days without any relief. Subsequently, he was referred to Endocrinology due to concern about Cushing′s syndrome. The patient reported associated easy bruising and decreased libido. On further questioning, patient mentioned he had been receiving several epidural steroid injections in the neck, shoulders and back in the past. Per record review, from June to November 2018, he had received multiple triamcinolone and dexamethasone injections as follows: 10mg dexamethasone in each C4-5, C5-6 and C6-7 facet joints; 5mg triamcinolone injections in the right C4-5, C6-C7, left C4-5, C6 and C7, and 40mg of triamcinolone in C7-T1. The patient also reported he had multiple injections in 2019, but these records were not available. Physical exam showed hypertension, facial plethora, and scattered bilateral arm ecchymosis. Laboratory study showed hyperglycemia. Given suspicion for CS, further workup, including morning serum cortisol, ACTH, and 24-hour urine cortisol were ordered, which were 0.5 ug/dl (6.2-19.4 ug/dl), 4.3 pg/ml (7.2-63.3 pg/ml) and <2 ug/24 hours (5-64 ug/24 hours) respectively, suggesting iatrogenic CS secondary to corticoid steroid injection. Also, given that the patient reported lightheadedness, and decreased libido, cosyntropin stimulation test and free testosterone, FSH and LH were ordered to rule out adrenal insufficiency and hypogonadism respectively. Hypogonadism was ruled out, however, cosyntropin stimulation test showed peak cortisol of 12 and 16 mcg/dL at 30 and 60 minutes (>18 mcg/dL), suggesting adrenal insufficiency, due to suppression of endogenous cortisol production from exogenous glucocorticoid use. Patient was started on hydrocortisone and all glucocoirticoid injections were stopped. Conclusions: Many different non-systemic corticosteroid administrations can cause iatrogenic Cushing’s Syndrome, and therefore, physicians should be thoughtful when prescribing steroids regardless of administration form.

SAT-383 Prevalence of Opioid Induced Adrenal Insufficiency in Patients Taking Chronic Opioids

BACKGROUND: Chronic opioid use may lead to adrenal insufficiency due to central suppression of the hypothalamic-pituitary-adrenal axis. Opioid induced adrenal insufficiency (OIAI) is likely under-recognized and its prevalence is unclear. OBJECTIVE: To determine the prevalence of OIAI in patients taking opioids for chronic pain and to identify predictors of OIAI. METHODS: A prospective study of patients admitted to the Pain Rehabilitation Center (PRC) at an academic medical center completed between 2016 and 2018. Inclusion criteria were: 1) age ≥18 years, 2) intermittent or continuous opioid use of at least 90 days, 3) am cortisol measurement on admission. Exclusion criteria were: 1) known pituitary or adrenal dysfunction, 2) exogenous glucocorticoid use within 3 months. Each patient’s opioid daily dose was converted into a morphine mg equivalent (MME). All patients had a functional 5-minute walk test and measurements of quality of life on admission to the PRC. Diagnosis of OIAI was based on the endocrine evaluation. RESULTS: One hundred sixty-two patients (median age of 53.5 years (range 21-84), 67% women, 95 % Caucasian) met inclusion criteria. Patients used opioids daily (141, 87%) or as needed (21, 13.0%) at a median MME of 30 mg (3-840), median duration of 60 months (3-360). In addition to morning cortisol (CORT), 112 (69.1%) patients had measurements of corticotropin (ACTH) and 106 (65.4%) - dehydroepiandrosterone sulfate (DHEAS). CORT was directly correlated with both DHEAS (p=0.04) and ACTH (p<0.0001). Overall, low concentrations of CORT (<7mcg/dl), ACTH (<10pg/mL) and DHEAS (<25mcg/dL) were observed in 17%, 14% and 21% of patients, respectively. Patients with either low CORT or ACTH had a lower performance on the 5-minute walk test (1080 feet (range 175-1899) vs 1261 feet (361-2008), p=0.04). No significant differences were found on measures of quality of life. OIAI was confirmed through endocrine evaluation in 8 (5%) patients (7 women, median age 53 years (48-76)). At the time of admission, patients with OIAI had median CORT of 5 mcg/dl (1-9.9), ACTH of 11.5pg/mL (5-15), and DHEAS of 17mcg/dL (15-22). MME of patients with OIAI was higher than patients without OIAI (median 110 (20-392) vs. 30 (1-840), p=0.01). No patient taking opioid at <MME of 20 mg/day developed OIAI (sensitivity of 100% for MME>20 mg), however specificity of MME cutoff >20 mg to predict OIAI development was only 34%. After opioid discontinuation, 3/8 patients recovered adrenal function when reassessed at 14 months (5-14). CONCLUSION: The prevalence of OIAI based on the endocrine evaluation was 5%, with MME being the only predictor for OIAI development. Patients on MMED of 20 mg and above should be monitored for OIAI. Abnormalities in the hypothalamic-pituitary-adrenal axis were frequent, affecting 14-21% of patients taking opioids, possibly contributing to patients’ symptoms, physical performance and well-being.

Cushing's Syndrome: Where and How to Find It.

The diagnosis of Cushing's syndrome is challenging to endocrinologists as patients often present with an insidious history, together with subtle external clinical features. Moreover, complications of endogenous hypercortisolism, such as visceral obesity, diabetes, hypertension and osteoporosis, are conditions commonly found in the population, and discerning whether these are truly a consequence of hypercortisolism is not straightforward. To avoid misdiagnosis, a careful investigative approach is essential. The investigation of Cushing's syndrome is a three-step process. Firstly, after exclusion of exogenous glucocorticoid use, the decision to initiate investigations should be based on whether there is a clinical index of suspicion of the disease. Specific signs of endogenous hypercortisolism raise the a priori probability of a truly positive test. Secondly, if the probability of hypercortisolism is high, one should carry out specific tests as indicated by Endocrine Society guidelines. Populations with non-distinguishing features of Cushing's syndrome should not be screened routinely as biochemical tests have a high false-positive rate if used indiscriminately. Thirdly, once hypercortisolism is confirmed, one should move to establish the cause. This usually entails distinguishing between adrenal or pituitary-related causes and the remoter possibility of the ectopic adrenocorticotropic hormone syndrome. It is crucial that the presence of Cushing's syndrome is established before any attempt at differential diagnosis.

Cushing's syndrome: update on signs, symptoms and biochemical screening

Endogenous pathologic hypercortisolism, or Cushing's syndrome, is associated with poor quality of life, morbidity, and increased mortality. Early diagnosis may mitigate against this natural history of the disorder. The clinical presentation of Cushing's syndrome varies, in part related to the extent and duration of cortisol excess. When hypercortisolism is severe, its signs and symptoms are unmistakable. However, most of the signs and symptoms of Cushing's syndrome are common in the general population (e.g., hypertension and weight gain) and not all are present in every patient. In addition to classical features of glucocorticoid excess, such as proximal muscle weakness and wide purple striae, patients may present with the associated comorbidities that are caused by hypercortisolism. These include cardiovascular disease, thromboembolic disease, psychiatric and cognitive deficits, and infections. As a result, internists and generalists must consider Cushing's syndrome as a cause, and endocrinologists should search for and treat these comorbidities. Recommended tests to screen for Cushing's syndrome include 1 mg dexamethasone suppression, urine free cortisol, and late night salivary cortisol. These may be slightly elevated in patients with physiologic hypercortisolism, which should be excluded, along with exogenous glucocorticoid use. Each screening test has caveats and the choice of tests should be individualized based on each patient's characteristics and lifestyle. The objective of this review is to update the readership on the clinical and biochemical features of Cushing's syndrome that are useful when evaluating patients for this diagnosis.

Central hypoadrenalism.

Central hypoadrenalism is a frequent complication of pituitary and hypothalamic pathology and is associated with increased morbidity and mortality. Optimal exogenous glucocorticoid use is dependent on the use of appropriate diagnostic tests and careful assessment of the clinical response to glucocorticoid replacement therapy. A PubMed search for the terms central hypoadrenalism, ACTH deficiency, glucocorticoid suppression, and glucocorticoid replacement was conducted; the papers identified and the references listed were used to build a reference list. The published literature was assessed to present a summary of the available evidence with regard to etiology, diagnosis, and treatment of central hypoadrenalism. A functional hypothalamic pituitary adrenal axis is essential for normal health and life expectancy; its complexity presents challenges to the clinician in the identification of patients and in the maintenance of such patients in a glucocorticoid-sufficient state. The most common cause of central hypoadrenalism remains exogenous glucocorticoid use. Further research in this field should be directed toward disease prevention by minimizing glucocorticoid exposure and toward the identification of a biomarker for glucocorticoid sufficiency that will aid clinicians in optimizing treatment.

Interdisciplinary problems: Cushing’s syndrome

The article is an overview of the key provisions of the Guidelines for the diagnosis of Cushing’s syndrome, developed by the Society for Endocrinology United States (2008). After excluding exogenous glucocorticoid use, this guide recommends testing for Cushing’s syndrome in patients with multiple and progressive features compatible with the syndrome, and patients with adrenal incidentaloma. It is recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test).

The Diagnosis of Cushing's Syndrome: An Endocrine Society Clinical Practice Guideline

The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushing's syndrome. The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer. The Task Force received no corporate funding or remuneration. Consensus was guided by systematic reviews of evidence and discussions. The guidelines were reviewed and approved sequentially by The Endocrine Society's CGS and Clinical Affairs Core Committee, members responding to a web posting, and The Endocrine Society Council. At each stage the Task Force incorporated needed changes in response to written comments. After excluding exogenous glucocorticoid use, we recommend testing for Cushing's syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma. We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test). We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasone-CRH test. Patients with concordant abnormal results should undergo testing for the cause of Cushing's syndrome. Patients with concordant normal results should not undergo further evaluation. We recommend additional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.

Impact of exogenous glucocorticoid use on salivary cortisol measurements among adults with asthma and rhinitis

The diurnal rhythm of cortisol secretion in chronic disease can reflect the interactions between exogenous and endogenous factors. Exogenous glucocorticoid use may impact salivary cortisol measurements, but this has not been well-studied in ambulatory settings. In this report salivary cortisol levels were used to evaluate aspects of the diurnal rhythm of cortisol secretion within an ambulatory population of patients with asthma and allergic rhinitis. 183 persons with asthma with or without concomitant rhinitis and 34 persons with rhinitis alone were asked to collect at home, two saliva samples, 30 min after awakening and 12h later. The salivary cortisol levels were quantified by enzyme immunoassay. The recent use of glucocorticoids in the study group was determined by interview and direct examination of medications. We report that the median salivary cortisol levels 30 min post-awakening significantly differed by exogenous steroid status: no glucocorticoid use (n = 91), 10.1 nmol/l; nasal gluco-corticoid use alone (n = 25), 11.4 nmol/l; inhaled glucocorticoids (with or without concomitant nasal glucocorticoids; n = 76), 9.0 nmol/l; systemic glucocorticoids (n = 17), 4.0 nmol/l; (P = 0.02). 12-h post-awakening salivary cortisol values among the groups were similar (P = 0.85). The median 30-min post-awakening cortisol differed significantly by type and amount of inhaled steroid used: non-fluticasone users (n = 21), 11.5 nmol/l; lower dose fluticasone (<800 microg per day, n = 35); 9.2 nmol/l; and higher dose fluticasone (> or =800 microg, n=20), 5 nmol/l; (P=0.01). We conclude that in an ambulatory setting, exogenous glucocorticoid use can decrease the 30 min post-awakening but not the 12-h post-awakening salivary cortisol levels, an effect that should be taken into account in assessing the effects of other potential determinants on cortisol secretion.