Adrenal Hormone Excess Research Articles

8180 Rare Variants Of Adrenocortical Carcinoma: A Retrospective Cohort Study

Abstract Disclosure: C.A. Villavicencio Torres: None. I. Bancos: None. Background: Adrenocortical carcinoma (ACC) is a rare malignancy with an estimated annual incidence of 0.7-2 cases per million per year. Scarce data are available on rare histological variants of ACC. Objective: To describe the clinical presentation and outcomes of patients diagnosed with oncocytic, sarcomatoid and myxoid ACC variants. Methods: Retrospective single center cohort study, 1992-2021 of patients with rare histological ACC variant. Results: A total of 20 patients were diagnosed with oncocytic (17, 85%), sarcomatoid (2, 10%), or myxoid (1, 5%) ACC. Median age of diagnosis was 47 years (range 17-80), and 14 (70%) were women. All patients had unilateral ACC (12, 60% left) with a median tumor size of 11 cm (range 4-29). Adrenal hormone excess was documented in 10 (50%) patients, mostly with either glucocorticoid or androgen excess. ENSAT stage I, II, III, and IV was documented in 2 (10%), 10 (50%), 6 (30%), and 2 (10%) patients, respectively. All patients were treated with adrenalectomy (laparoscopic in 5 and open in 15). In addition, patients were treated with mitotane (10, 50%), radiation (7, 35%), and chemotherapy (5,25%). Mitotane was administered for a median of 12 months (range 4-31) and was discontinued mainly due to side effects in 9 (90%) patients. Patients were followed for a median follow up of 6.5 years (range 0.4-12). In addition to 2 patients who presented with ENSAT stage IV metastatic disease, metastatic disease developed in additional 6 (30%) patients who initially presented with localized ACC (3 stage 2, 3 stage 3, 5 oncocytic, 1 sarcomatoid). Metastatic sites included lung (n=2), omentum (n=1), duodenum (n=1), liver (n=4), and bones (n=1). At the end of follow up, 11 (55%) patients remained disease free (53% oncocytic, 50% sarcomatoid, 100% myxoid), 5 (25%) patients were alive with metastatic ACC (23% oncocytic, 50% sarcomatoid), and 4 patients died of ACC (median time to death 21 months (range 10-50) post-adrenalectomy). Conclusions: Patients with oncocytic, sarcomatoid, and myxoid ACC may have a better prognosis than in reported literature. Larger multicenter studies are needed to identify patient and tumor-specific factors that guide management to assure improved outcomes in these very rare patients. Presentation: 6/2/2024

8571 Co existence of aldosterone excess in adrenal myelolipomas

Abstract Disclosure: I. Mishra: None. A. Baliarsinha: None. Co existence of aldosterone excess in adrenal myelolipomas Abstract: Adrenal myelolipomas are benign, lipomatous tumours, most of which present as adrenal incidentalomas.Co existence of cortisol excess states and aldosterone producing carcinomas is reported with adrenal myelolipomas,however isolated aldosterone excess without imaging features of adrenal malignancy is rare.We describe 3 cases presenting for evaluation of hyperaldosteronism but with imaging features consistent with myelolipomas. Case 1;58 year female presented with hypertension and spontaneous hypokalemia.On evaluation BMI was 25.3kg/m2,Gr 2 hypertensive retinopathy with systemic examination within normal limits.Biochemical evaluation revealed; Pl.Aldo(ng/dl)32.5; PRA(ng/ml/hr)0.54; ARR 60.5; SIT Pl.Aldo(ng/ml)27.8; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 16×13mm lesion baseline HU < - 20 ?adrenal myelolipoma; Mx Left adrenalectomy H/P Adrenocortical hyperplasia;post op-resolution of hypokalemia with persistence of hypertension controlled with decreased number of drugs. Case 2;38 year male presented with resistant hypertension ,cerebro vascular accident,right hemiparesis and diuretic induced hypokalemia.On evaluation BMI was 31 kg/m2,Gr 1 hypertensive retinopathy with right hemiparesis.Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.3; PRA(ng/ml/hr) 0.82; ARR 15; SIT Pl.Aldo(ng/ml)7.79; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 28×30mmlesion baseline HU < -20? adrenal myelolipoma; Mx Left adrenalectomy H/P adrenal myelolipoma;post op-resolution of hypokalemia ,recovery of weakness and normalization of hypertension without drugs. Case 3;49 year male presented with hypertension ,incidental detection of adrenal lesion on ultrasound for pain abdomen and normokalemia.On evaluation BMI was 27 kg/m2,no significant findings on general examination with systemic examination within normal limits. Biochemical evaluation revealed; Pl.Aldo(ng/dl)12.2; PRA(ng/ml/hr) 0.58; ARR 20.2; SIT Pl.Aldo(ng/ml)11; AVS- not done; IMAGING(CT) Left adrenal fat attenuating 22x 26 mm lesion baseline HU < -20? adrenal myelolipoma; Mx drug therapy for hypertension due to refusal for surgical therapy with monitoring of blood pressure. In surgically treated adrenal myelolipomas, adrenal hormone excess is reported in 5-6% of cases, with autonomous cortisol secretion being most common .Even on the background of CT findings consistent with myelolipomas, patients fulfilling the screening and confirmatory criterias of primary hyperaldosteronism must be subjected to apt therapeutic modality.The presence of aldosterone clusters with excessive aldosterone synthase activity in these lesions could be reason for occurrence of primary hyperaldosteronism in myelolipomas. Presentation: 6/3/2024

Diagnosis and Management of Adrenocortical Carcinoma with co-secretion of Cortisol and Aldosterone

Adrenocortical carcinoma (ACC) accounts for 0.05-2% of all malignant tumors. Forty-five percent of ACCs with secretory function have excess glucocorticoids alone and only less than 1% secrete aldosterone. This is a case of a 44-year-old Filipino female with hypertension and a 12-year-history of an incidentaloma of the left adrenal gland, with recent-onset complaints of increasing abdominal girth, purple striae, amenorrhea, moon facies and a dorsocervical fat pad. Laboratory findings revealed low potassium levels, non-suppressed cortisol on dexamethasone test suggesting Cushing’s syndrome and elevated aldosterone-renin ratio and plasma aldosterone concentration pointing to primary hyperaldosteronism. A computed tomography scan revealed a left-sided adrenal mass measuring approximately 23 cm in largest diameter suggestive of carcinoma without metastasis or lymph node involvement. Complete resection via open adrenalectomy was performed and histopathologic assessment revealed Adrenocortical Carcinoma with Weiss score of 4. The Ki-67 proliferative index was found to be >20%. Radiotherapy was done as an adjuvant treatment. Although rare, co-secretion of cortisol and aldosterone can occur in functional tumors of adrenocortical carcinoma. Malignancy should always be considered in patients who present with a history of a unilateral adrenal mass and/ or in those with signs and symptoms of adrenal hormone excess. Thus, a proper assessment derived from a thorough medical history, physical examination and laboratory work-up is warranted in patients with an adrenal mass to ascertain the diagnosis and provide adequate management.

Enhanced chronic inflammation and increased branched chain amino acids in adrenal disorders: a cross-sectional study.

Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine. We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802). Referent subjects included participants of the PREVEND (Prevention of Renal and Vascular End-stage Disease) study (n=5241). GlycA, BCAA, ketone bodies, TMAO, and betaine were measured using nuclear magnetic resonance spectroscopy. Multivariable logistic analyses were adjusted for age, sex, BMI, smoking, hypertension, diabetes mellitus and statin therapy. In age-and sex-adjusted comparison to referent subjects, increased GlycA was noted in all patient categories, increased BCAA in NFA, MACS, CS, PA and ACC, increased TMAO in patients with other malignant adrenal masses, increased betaine in NFA and MACS, and increased ketone bodies in NFA, CS and ACC. Essentially similar findings were observed in fully adjusted analysis and after exclusion of subjects with diabetes and cardiovascular disease. Patients with functioning and non-functioning adrenal masses demonstrated increased GlycA and BCAA, biomarkers associated with adverse cardiometabolic disorders and mortality. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS and CS.

The Endocrine Phenotype Induced by Pediatric Adrenocortical Tumors Is Age- and Sex-Dependent.

Adrenocortical carcinomas are very rare malignancies in childhood associated with poor outcome in advanced disease. Most adrenocortical tumors (ACT) are functional, causing signs and symptoms of adrenal hormone excess. In most studies, endocrine manifestations were reported 4 to 6 months prior to diagnosis. We sought to extend knowledge on endocrine manifestations with regard to age and sex to facilitate early diagnosis. We retrospectively analyzed features of adrenal hormone excess in children and adolescents with ACT registered with the GPOH-MET studies between 1997 and 2022. Stage of puberty was defined as prepubertal in females < 8 years of age and males < 9 years. By December 2022, 155 patients (110 female, 45 male) with data on endocrine manifestations had been reported. Median age at ACT diagnosis was 4.2 years [0.1-17.8], median interval from first symptoms was 4.2 months [0-90.7]. In 63 girls of prepubertal age, the most frequently reported manifestations were pubarche (68.3%), clitoral hypertrophy (49.2%), and weight gain (31.7%); in 47 pubertal female patients, the most frequent manifestations were excessive pubic hair (46.8%), acne (36.2%), and hypertension (36.2%). Leading symptoms in 34 boys of prepubertal age were pubarche (55.9%), penile growth (47.1%), and acne (32.4%), while in 11 pubertal male patients, leading symptoms were weight gain (45.5%), hypertension (36.4%), excessive pubic hair (27.3%), and cushingoid appearance (27.3%). In pubertal patients, symptoms of androgen excess were mainly unrecognized as part of pubertal development, while symptoms of Cushing syndrome were more frequently apparent. The endocrine phenotype induced by pediatric ACT is age- and sex-dependent.

Diagnosis and management of adrenal incidentaloma: use of clinical judgment and evidence in dialog with the patient

AbstractThe prevalence of adrenal incidentaloma (AI) in imaging studies, including those of the adrenal glands, is estimated to be 1–5%. Essential factors for the proper management of AI include a correct diagnosis, adequate surgical skills, appropriate perioperative management, and sound dialogue with the patient. Aside from the possibility of overdiagnosis, patients with apparent signs or symptoms attributable to adrenal hormone excess have reasonable indications for surgery. At the same time, milder patients may be candidates for active surveillance without intervention. Even individuals with nonfunctioning AI may benefit from surgery if imaging studies depict the tumor as suggestive of malignancy. However, a differential diagnosis of AI may not be easy for surgeons with little experience in seeing such patients.Furthermore, a patient without a correct diagnosis may miss the window of opportunity for a cure or incur a greater risk of developing complications, such as adrenal insufficiency or cardiovascular events during or after surgery, due to inadequate management. The clinical practice guidelines for AI from around the world may be helpful for shared decision-making; however, Japan lacks established guidelines. In this review article, we propose practical guidelines relevant to management by summarizing the evidence for five key questions that are often asked in dialog with patients with AI.

FRI228 Primary Adrenal T-cell Lymphoma: A Case Report

Abstract Disclosure: H. Tabassum: None. S. Xu: None. A. Manavalan: None. Introduction: Primary T-cell adrenal lymphoma (PAL) is exceedingly rare. Adrenal insufficiency (AI) is common in these cases. Here we describe a patient with bilateral, large, T-cell PAL with rapid progression, without adrenal insufficiency. Clinical Case: A 62-year-old male, with coronary artery disease and recent coronary intervention, hyperlipidemia and hypertension presented to the hospital with abdominal pain, fever, night sweats and weight loss for a month. Work up revealed a 5.8 cm left adrenal mass with 14% absolute washout, measuring 34 Hounsfield Units (HU) pre-contrast, 68 HU postcontrast, and 63 HU on delayed images, and a 5.2 cm right adrenal mass with 42% absolute washout, measuring 35 HU pre-contrast, 81 HU postcontrast, and 62 HU on the delayed images with no other suspicious lesions or lymphadenopathy. The patient demonstrated no clinical symptoms or signs of adrenal hormone excess or deficiency. Levels of renin, aldosterone, serum cortisol, ACTH, 24-hour urine free cortisol, serum metanephrines, and thyroid function were normal. Additional tests to rule out adrenal cortical carcinoma (ACC) revealed normal levels of androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and estradiol. Persistent non-significant elevation of 11-deoxycortisol was observed at 51 ng/dL and 63ng/dL (Ref &amp;lt; 42 ng/dL). Adrenal biopsy was suggested but deferred due to the increased risk of hemorrhage given recent coronary revascularization and use of dual antiplatelet therapy. Follow up imaging in a few weeks revealed diffuse, retroperitoneal lymphadenopathy with unchanged adrenal masses. A lymph node biopsy confirmed a diagnosis of peripheral T-cell lymphoma. The left adrenal gland demonstrated an uptake SUV of 22.7 and the right, 19.17 on FDG PET. The patient was initiated on chemotherapy with etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin. Imaging three months later revealed a marked decrease in FDG activity SUV 6.98 g/mL on the left and SUV up to 3.32 g/mL on the right. Adrenal function remained intact on follow up. Conclusion: Peripheral T-cell lymphoma with adrenal involvement is an extremely rare and aggressive disease with rapid progression. Mostly seen in males over the age of 50, it may present with abdominal pain, B symptoms or both. While ACC is usually unilateral, lymphoma and metastatic disease may present bilaterally, however, other imaging features can be similar. AI is expected when 90% of the adrenal glands are destroyed by tumor infiltration, however, this does not always correlate with tumor size. In our patient, AI was not observed on presentation or follow up. As adrenal insufficiency can occur at any time in the disease course and may mimic symptoms of cancer or chemotherapy, the clinician should always be vigilant for its development in these cases. Presentation: Friday, June 16, 2023

Expanded indication for EUS-guided radiofrequency ablation: management of adrenal tumors

EUS-guided radiofrequency ablation (EUS-RFA) has been performed as an alternative to surgery for the treatment of pancreatic tumors. The promising results obtained using this procedure suggest that the indication for EUS-RFA could be expanded to the management of extrapancreatic tumors. Here, we evaluate the feasibility, efficacy, and safety of EUS-RFA in the treatment of left adrenal tumors. This single-center, prospective study was conducted at Asan Medical Center between January 2016 and November 2021. A total of 11 patients with left adrenal tumors were enrolled in the study. The technical success rate, treatment response, and adverse events were evaluated. EUS-RFA was performed successfully in all patients (technical success rate, 100%). The indications for the procedure were an increase in tumor size (n= 8), and adrenal tumor with adrenal hormone excess (n= 3). After a median of 2 EUS-RFA sessions (range, 1-2), 73% of patients had a complete response, and 27% had a partial response. During follow-up, 5 patients experienced self-limiting mild abdominal pain; no moderate or severe adverse events were reported. EUS-RFA showed high technical feasibility, clinical success, and an acceptable safety profile in the treatment of left adrenal tumors. In patients at high surgical risk, EUS-RFA can be considered as an alternative therapeutic modality to surgery for the treatment of left adrenal tumors.

OR29-2 Comprehensive Steroid and Global Metabolome Analysis by Mass Spectrometry and Machine Learning to Understand Metabolic Risk in Benign Adrenal Tumours With Mild Autonomous Cortisol Secretion

Abstract Background Benign adrenal tumours are found in 3-10% of adults and can be non-functioning (NFAT) or associated with adrenal hormone excess. Analysing 1305 prospectively recruited patients with benign adrenal tumours, we recently demonstrated that 45% of patients had mild autonomous cortisol secretion (MACS), i.e. biochemical evidence of cortisol excess without distinct signs of Cushing syndrome (CS). We found that MACS increases the prevalence and severity of type 2 diabetes and hypertension and primarily affects women (Ann Int Med. 2022 Doi: 10.7326/M21-1737). Here we analysed the cohort's steroid metabolome and non-targeted global metabolome to reveal underlying metabolic processes. Methods We analysed 24-h urine samples from 1305 patients (649 NFAT, 591 MACS, 65 CS) using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-steroid profiling assay. In addition, we performed non-targeted serum metabolome analysis in a representative sub-cohort (104 NFAT, 140 MACS, 47 CS) employing two complementary LC-MS assays, HILIC and C18-lipidomics. The steroid and global metabolome data were analysed by two supervised machine learning approaches, generalized matrix learning vector quantization and ordinal regression, to identify the most relevant metabolic changes. Findings Urine steroid metabolome analysis revealed an increase in glucocorticoid excretion from NFAT over MACS to CS, whereas androgen excretion decreased. Increased glucocorticoid metabolites were also the major differentiators between MACS patients with and without type 2 diabetes and hypertension, respectively. Lipidome analysis by machine learning identified glycerophospholipids, lysoglycerophospholipids, triacylglycerides, ceramides, sphingolipids, and acylcarnitines as the most relevant metabolite classes exhibiting gradually progressive changes with increasing cortisol excess (NFATInterpretation: We show a gradual change in the lipidome towards lipotoxicity with increasing cortisol excess. MACS patients with type 2 diabetes and hypertension had higher glucocorticoid output than other MACS patients, suggestive of a causative contribution of cortisol excess to their increased cardiometabolic burden. Observed changes may hold promise for risk stratification in MACS, a highly relevant and previously largely overlooked metabolic risk condition. Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.

OR12-4 Metabolic Profiling in Adrenal Tumors Demonstrates Enhanced Chronic Inflammation, Branched Chain Amino Acids and Ketone Bodies, Biomarkers that Predict High Cardiometabolic Risk

Abstract Background Patients with adrenal hormone excess demonstrate an increased cardiovascular risk and mortality. We aimed to determine the impact of adrenal hormone excess on the metabolic profile that included plasma lipoproteins, total branched-chain amino acids (BCAA), ketone bodies, and GlycA (a proinflammatory glycoprotein biomarker). Method: We conducted a single-center cross-sectional study of consecutive patients with adrenal adenomas, Cushing syndrome (CS), and pheochromocytoma/paragangliomas (PPGL) between January 2015 and May 2021. Adrenal adenomas comprised nonfunctioning adenomas (NFA), adenomas with mild autonomous cortisol secretion (MACS), and primary aldosteronism (PA). Malignant and other benign tumors were excluded. Collected fasting plasma samples were measured using nuclear magnetic resonance spectroscopy for lipoproteins, BCCA, ketone bodies and GlycA. The results were compared to referent subjects from PREVEND (Prevention of Renal and Vascular End-stage Disease) study. Lipoprotein Insulin Resistance Index (LP-IR) which predicts incident diabetes was calculated based on 6 lipoprotein parameters. Results NFA (n=166, median age 60.1years, 63.3% women), MACS (n=158 (median age 61.8 years, 62. 0% women), CS (n=101, median age 43.8 years, 85.1% women), PA (n=71 (median age 55.8 years, 31. 0% women), PPGL (n=43, median age 55.5 years, 46.5% women) was diagnosed in 539 patients. Referent subjects (n=6540) were younger with a median age of 48.4, 50.2% women. When compared to referent subjects, and after age and sex-adjustment, GlycA was highest in patients with CS (OR 3.3, 95% CI 2.8-3.8), followed by PPGL (OR 2.3, 95%CI 1.8-2.9), MACS (OR 2, 95%CI 1.7-2.3), NFA (OR 1.9, 95%CI 1.7-2.2), and PA (OR 1.5, 95%CI 1.2-1.8). When compared to referent subjects, and after sex- and age adjustment, all patient groups demonstrated increase in BCAA: CS (OR 2.7 (95%CI 2.3-3.2), PPGL (OR 2.3, 95% CI 1.8-2.9), NFA (OR 2.4, 95% CI 2.1-2.7), PA (OR 2. 0, 95%CI 1.7-2.5), MACS (OR 2.2, 95% CI 1.7-2.6). Total ketone bodies were increased in patients with cortisol excess (OR of 1.4, 95%CI 1.2-1.5 in CS, and OR of 1.2, 95%CI 1-1.3 in MACS) and NFA (OR 1.2, 95%CI 1.1-1.3), but not in PA or PPGL. All patient groups except PPGL were more likely to have a higher LP-IR score. When compared to referent subjects, the highest sex- and age-adjusted LP-IR increase was in patients with CS (OR 1.9 (95%CI 1.5-2.2), followed by MACS (OR 1.4, 95% CI 1.2-1.7), PA (OR 1.4, 95%CI 1.1-1.8), and NFA (OR 1.4, 95% CI 1.2-1.7). Conclusion Patient with adrenal adenomas and PPGL demonstrate an increase in GlycA, BCAA, and ketone bodies - biomarkers associated with adverse cardiometabolic disorders and mortality. All patients except those with PPGL also demonstrated a higher LP-IR index that was reported to predict incident diabetes. Patients with NFA demonstrated an adverse metabolic profile similar to patients with MACS. Presentation: Sunday, June 12, 2022 11:45 a.m. - 12:00 p.m.

RF19 | PSUN33 Adrenocortical Carcinoma as a Rare Manifestation of Birt-Hogg-Dubé Syndrome

Abstract Adrenocortical carcinoma (ACC) can occur as part of hereditary cancer syndromes, particularly Lynch syndrome and Li-Fraumeni syndrome. Here we describe 5 patients (3 women) with adrenal tumors and Birt-Hogg-Dubé syndrome (BHDS). BHDS is a hereditary tumor syndrome characterized by fibrofolliculomas/trichodiscomas, renal tumors, lung cysts, and spontaneous pneumothoraces. All five patients had a confirmed germline FLCN pathogenic variant. One case was previously reported by our institution. Age of diagnosis (AD) ranged from 36 to 62 years with a mean AD of 46 years. All patients identified as Caucasian. Three patients had non-functioning adrenal tumors, while the remaining two patients did not undergo biochemical assessment preoperatively but did not have symptoms or history of adrenal hormone excess. Histologically, four patients had confirmed ACC while one had an adrenocortical tumor of uncertain malignant potential, most consistent with an oncocytoma. All patients were initially treated with mitotane. Three patients developed metastatic disease requiring additional systemic chemotherapy, immunotherapy, and/or radiation. A total of 8 confirmed ACCs in patients with BHDS have been reported to date, raising suspicions that these tumors might be a part of the BHDS tumor spectrum. When BHDS patients are screened for renal malignancies, special attention should be paid to the adrenal glands. Adrenal nodules should undergo prompt assessment as &amp;gt;50% of reported cases developed metastatic disease. Given possible association with BHDS, testing for FLCN pathogenic variants should be considered during the genetic evaluation of patients with ACC. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:54 p.m. - 12:59 p.m.

PSAT009 Cushing's Syndrome Developing 42 Years After Successful Treatment for Metastatic Adrenocortical Carcinoma

Abstract Introduction ACC is a rare malignancy with poor prognosis. ACC is associated with CS in about 10% of the cases. Herein we report a case of a patient with metastatic ACC who developed contralateral functional adrenal adenoma causing Cushing's syndrome 42 years later. Clinical Case A 72-year-old female presented for evaluation of right adrenal incidentaloma, measuring 4.4×3 cm, on CT abdomen and pelvis (CTAP), done as part of the evaluation for hip pain. In addition to the adrenal incidentaloma, a large left adnexal mass (8×7 cm) was also observed. Her past medical history was significant for left adrenal ACC diagnosed at the age of 30, The patient's initial presentation included virilization and menstrual abnormalities. Laboratory evaluation revealed hyperandrogenism and hypercortisolism. There was no evidence of metastatic disease, and the patient was managed surgically (total left adrenalectomy) with normalization of laboratory abnormalities and resolution of symptoms. Four years later, patient pulmonary metastasis were observed in a surveillance scan and the patient underwent wedge resection and chemotherapy. The patient did not have any evidence of recurrent disease thereafter. At the current presentation, there were no symptoms or signs of adrenal hormone excess. Hormonal workup revealed borderline elevation of plasma metanephrines, with normal 24 h urinary metanephrines and catecholamines. DHEA-S and testosterone levels, as well as other androgens, were normal. 1 mg dexamethasone suppression (DST) was abnormal, with cortisol of 5.5 mcg/dL 8 h after dexamethasone administration (normal &amp;lt;1.8 mcg/dL). High dose DST was repeatedly abnormal, with cortisol levels at 4.0 and 4.4 mcg/dL (normal &amp;lt;1.8 mcg/dL). AM cortisol was elevated, at 23.4 mcg/dL (normal 4-22 mcg/dL) with ACTH at 12 pg/mL (normal &amp;lt;45 pg/dL). 24 h urinary free cortisol (UFC) was repeatedly elevated at 123.2 and 83.8 mcg/d (normal &amp;lt;45.0 mcg/d). CA 125 was normal. As there are case reports of ectopic Cushing's syndrome related to ovarian malignancies, and the patient had a large adnexal mass, adrenal and ovarian vein sampling was performed. Cortisol levels were higher in the right adrenal vein compared to the periphery, and the gradient was normal for the left ovarian vein. The right ovary was not visualized, and it was not possible to catheterize the right ovarian vein. Whole body FDG scan revealed intermediate uptake by right adrenal mass and normal uptake by left adnexal mass. Based on these results, it was determined that the right adrenal was the source of excess cortisol, and the patient underwent laparoscopic right adrenalectomy. Pathology evaluation showed adrenal adenoma, without evidence of ACC. The patient was started on physiologic replacement doses of hydrocortisone and fludrocortisone. The patient has been doing very well clinically. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Critical Care Implications of Adrenal Disease States

Adrenal disease in the critically ill patient can present many challenges for the intensivist. Besides primary, secondary, and tertiary adrenal insufficiency, a state known as critical care–related corticosteroid insufficiency (CIRCI) has been described. Adrenal insufficiency can pose many issues to the critically ill patient as it can decrease the patient’s ability to respond to the stress that critical illness presents to the human body. Proper recognition and diagnosis of adrenal insufficiency in the critically ill patient can be extremely important in the treatment of these patients and could be a lifesaving intervention if CIRCI is discovered. A less commonly encountered issue of adrenal disease lies in the area of adrenal hormone excess caused by a pheochromocytoma or extra-adrenal paragangliomas. These tumors can release large amounts of endogenous catecholamines that cause significant patient morbidity and mortality if not recognized early and treated appropriately. Although adrenal insufficiency and adrenal excess are less commonly encountered problems in critically ill patients, the recognition and treatment of these disease states can prevent the morbidity and mortality of critically ill patients that suffer from these disease states. This review contains 5 figures, 5 tables, and 89 references. Key words: adrenal insufficiency, hypothalamic-pituitary axis, critical illness–related corticosteroid insufficiency, pheochromocytoma, steroid replacement therapy

OR25-05 Increased Overall Mortality and Cardiovascular Morbidity in Patients with Adrenal Incidentalomas and Autonomous Cortisol Secretion: Results of the ENS@T NAPACA-Outcome Study

Objective. Several smaller studies on adrenal incidentalomas (AI) suggested an association between autonomous cortisol secretion (ACS) and mortality (Di Dalmazi Lancet Diabetes Endocrinol 2014, Debono J Clin Endocrinol Metab 2014, Patrova Endocrine 2017). However, a recent meta-analysis (9 studies, 1356 patients) could not confirm these findings (Elhassan Ann Intern Med 2019). Aim. To investigate the effects of ACS on mortality, prevalence of cardiovascular (CV) risk factors, and (CV) morbidity, in a representative cohort of AI. Design. Retrospective observational study conducted at 27 ENS@T centers from 15 countries. Methods. Inclusion criteria: AI diagnosed 1996-2015, 1 mg dexamethasone suppression test, follow-up (FU) of ≥36 months, known survival status. Exclusion criteria: clinically relevant adrenal hormone excess (i.e. Cushing’s syndrome, pheochromocytoma, primary hyperaldosteronism), known malignancy. Patient stratification: serum cortisol after dexamethasone (>5 µg/dl, ACS; 1.9-5 µg/dl, possible ACS (PACS); ≤1.8 µg/dl, non-functioning adenoma (NFA)). Definition of CV events (CVE): hospitalization due to myocardial infarction and related interventions (PTCA, surgical bypass), stroke, deep vein thrombosis, pulmonary embolism. Results. 3640 patients (57% NFA, 36% PACS, 7% ACS) were considered eligible: 64% females; median age 61 years (range 18-91); median FU 84 months (36-277) (distribution between subgroups n.s.). 352 patients died during FU. Age- and sex adjusted overall survival was significantly reduced in patients with PACS (HR 1.55; 95%CI 1.24-1.94) and ACS (1.84; 1.29-2.61). Prevalence of CV risk factors were significantly higher in PACS and ACS than in NFA (hypertension: 72, 73, 57%, p<0.0001; dyslipidemia: 42, 49, 35%, p<0.0001; diabetes: 22, 25, 17%, p<0.0001) When adjusted to relevant confounders (i.e. age, sex, CV risk factors), time to first CVE was shorter in PACS (HR 1.36; 1.07-1.73) and ACS (HR 1.62; 1.10-2.40) compared to NFA. Conclusion. PACS and ACS are associated with increased overall mortality and CV morbidity. However, to prove causality a large randomized intervention trial is required.

SAT-171 Adrenocortical Carcinoma in Thailand: A 10-Year Retrospective Review in a Single Tertiary Center

Background: Adrenocortical carcinoma (ACC) is a rare and fatal endocrine malignancy. This retrospective review aims to investigate treatment outcomes and clinical characteristics of 18 patients diagnosed with ACC at King Chulalongkorn Memorial Hospital from 2009 to 2018. Methods: We reviewed medical records regarding the presenting symptoms, hormonal investigations, imaging results, staging, modalities of treatment and outcomes. Results: Of the 18 patients, 14 patients were female (77%). The median age at diagnosis was 47.5 years [interquartile range (IQR) 39.5-58.2]. Mass effects and/or hormonal hypersecretion were the most common presentation, documented in 7 (38%) and 6 (33%) patients respectively. Autonomous adrenal hormone excess was found in 10 patients (56%). Cushing’s syndrome and elevated dehydroepiandrosterone sulphate (DHEAS) were documented in 9 (50%) and 7 patients (41%) respectively. Mineralocorticoid excess was found in 1 patient (6%). At initial staging, 9 patients (50%) were in advance or metastatic stage. Surgery was performed in 17 patients (94%) and 13 patients (76%) were in remission. However, recurrence was observed in 6 patients (33%), with the median disease-free interval of 13.5 months (IQR 12.0-25.0 months). In patients with stage 2 disease, open surgery resulted in longer disease-free interval despite larger tumor size, compared with laparoscopic surgery. Final outcomes revealed that 8 patients (44%) had remission, 2 patients (11%) had persistent disease and 6 patients (33%) died. Combination therapy (adrenalectomy, radiation, medications and local control such as metastatectomy, radiofrequency ablation and transarterial chemoembolization) was documented in 11 patients (61%). All patients with remission received complete tumor resection and presented at early stages of cancer, with the majority of them having non-functioning tumors. The median follow-up time was 34 months (IQR 9-73). Conclusions: ACC is a rare and fatal disease with high mortality rates. Diagnosis is time-sensitive and requires multimodality approach.

SAT-170 Clinical Course of Adrenal Myelolipoma: A Long-Term Longitudinal Follow-Up Study

Myelolipoma is the second most common adrenal tumor. Yet, systematic approach to these tumors remains poorly defined. Thus, we aimed to describe natural history of myelolipoma and to identify predictors of tumor growth and need for surgery. We conducted a retrospective longitudinal follow-up study of consecutive patients with myelolipoma. A total of 321 myelolipomas (median size, 2.3 cm [range, 0.5-18.0]) were diagnosed in 305 patients at median age of 63 years (25-87). Most myelolipomas were discovered incidentally (86.6%), whereas others were discovered on imaging done for cancer staging (8.8%) or during workup of mass effect symptoms (4.6%). Median duration of follow-up was 54 months (range, 0.03-267). Compared with myelolipomas <6 cm, tumors ≥6 cm were more likely to be right-sided (59% vs 41%, P=0.02), bilateral (21% vs 3%, P <.0001), cause mass effects symptoms (32% vs 0%, P<.0001), have radiographic hemorrhagic changes (14% vs 1%, P<.0001), and undergo adrenalectomy (52% vs 5%, P<.0001). There was no difference in sex or age at diagnosis between the groups. Hemorrhagic changes were noted in 9 (3.0%) patients with median tumor size of 7.0 cm (range, 1.8-18.0). Concomitant adrenal hormone excess was diagnosed in 12/126 (9.5%) patients. Primary aldosteronism was noted in 9 patients: due to concomitant ipsilateral (n=3) or contralateral adrenocortical adenoma (n=3), or bilateral idiopathic adrenal hyperplasia (n=3). Autonomous cortisol excess was noted in 3 patients: due to concomitant contralateral (n=2) or ipsilateral adrenocortical adenoma (n=1). Of 162 patients with ≥6 months of imaging follow-up, tumor size change ranged from -10 to 115 mm (median, 0 mm) and tumor growth rate ranged from -5.6 to 140 mm/year (median, 0 mm/year). Tumor growth ≥1.0 cm (n=26, 16.0%) was associated with larger initial tumor size (3.6 vs 2.3 cm, P=0.02) and hemorrhagic changes on imaging (12% vs 2%, P=0.007), compared with <1 cm size change. Myelolipomas with ≥1.0 cm growth were more likely to undergo adrenalectomy (35% vs 8%, P<.0001). Among 37 (12%) patients that underwent adrenalectomy for myelolipoma, surgical indications included: large tumor size/tumor growth (32%), diagnostic surgery (27%), mass effect symptoms (14%), concomitant ipsilateral tumor leading to hormonal excess (11%), acute hemorrhage (8%), and concomitant resection during non-adrenal surgery (8%). In conclusion, most myelolipomas are discovered incidentally, whereas myelolipomas ≥6 are more likely to cause mass effect symptoms, have radiographic hemorrhagic changes, and more commonly undergo resection. Hormonal excess is rare and is usually attributed to concomitant adrenocortical adenoma or hyperplasia. Tumor growth ≥1.0 cm is associated with larger myelolipoma and presence of hemorrhagic changes. Surgical resection should be considered in symptomatic patients with large tumors, evidence of hemorrhage, or tumor growth.

SAT-LB37 Frailty in Patients With Mild Autonomous Cortisol Secretion Is Higher Than Patients With Nonfunctioning Adrenal Tumors

Background: Mild autonomous cortisol secretion (MACS) affects up to 50% of patients with adrenal adenomas. Frailty is a syndrome characterized by diminished strength and endurance and serves as a marker of declining health and dependency. We hypothesized that patients with MACS are more frail when compared to patients with nonfunctioning adrenal tumors (NFAT). Methods: This is a retrospective study of adult patients with adrenal adenoma evaluated at a tertiary center from 2004 to 2018. MACS and NFAT were defined as cortisol after 1 mg overnight dexamethasone suppression (DST) between 1.8-5 mcg/dl and <1.8 mcg/dl, respectively. Frailty index (FI, range 0-1) was calculated using a 47 variables -deficit model (20 comorbidities, 14 activities of daily living, and 13 symptoms). Patients were excluded if treated with exogenous glucocorticoids, if diagnosed with overt adrenal hormone excess, another adrenal disorder, or if missing variables of interest. Results: MACS was diagnosed in 168 patients (67% women) at a median age 65 (30-91) years and NFAT in 275 patients (61% women) at a median age of 59 (21-84) years. Patients with MACS demonstrated higher prevalence of hypertension (73% vs 62%), cardiac arrhythmias (50% vs 40%), and chronic kidney disease (25% vs 17%), but lower prevalence of asthma (5% vs 14%), when compared to patients with NFAT, p<0.05 for all. Patients with MACS reported more symptoms of weakness (21% vs 11%), falls (7% vs 2%), and sleep difficulty (26% vs 15%) as compared to patients with NFAT, p<0.05 for all. Age, sex and BMI-adjusted FI was higher in patients with MACS vs patients with NFAT (0.17 vs 0.15, p=0.009). Using cut-off FI of 0.2, 42% of patients with MACS were frail, versus 30% of patients with NFAT (p=0.01). Conclusion: Higher frailty in patients with MACS supports a more aggressive management, such as adrenalectomy over conservative follow up. Future prospective studies are needed to characterize frailty in greater detail in patients with MACS, as well as to examine frailty reversal by adrenalectomy.

Endocrine causes of hypertension in pregnancy.

Hypertension is a common and morbid complication of pregnancy. While endocrine causes of secondary hypertension are not rare, women with these conditions do not often conceive, and even less commonly are these disorders diagnosed during pregnancy. This review will consider conditions of adrenal hormone excess that cause secondary hypertension: primary aldosteronism (PA), Cushing syndrome (CS), and pheochromocytoma/paraganglioma. We emphasize that pregnancy itself elicits changes in the regulation of aldosterone and cortisol production and standard endocrine testing algorithms. Furthermore, conventional imaging modalities and pharmacotherapies are often contraindicated in pregnancy, which complicates diagnosis and management. Nevertheless, surgical management in the second trimester is the preferred treatment strategy for most of these rare cases when feasible. This article will discuss the approach to patients with endocrine causes of hypertension during pregnancy with emphasis on those aspects that deviate from the assessment and treatment of non-pregnant patients.

Evaluation of bone health in patients with adrenal tumors.

Adrenal tumors occur in 5% of population with higher prevalence in elderly. Patients with adrenal tumors present with overt hormonal excess in up to 15% of cases, and mild autonomous cortisol secretion in 30-40% of cases. Overt Cushing syndrome, mild autonomous cortisol secretion, pheochromocytoma, and primary aldosteronism have been associated with higher cardiovascular morbidity and mortality. Increasing experimental and clinical evidence also suggests that adrenal hormone excess is detrimental to bone health. This review aims to discuss the effect of cortisol, aldosterone, and catecholamine excess on bone metabolism, secondary osteoporosis, and fragility fractures. Several studies have reported that patients with hormonally active adrenal tumors demonstrate increased prevalence of fragility fractures incongruous to bone density scan findings. The utility of dual absorptiometry X-ray (DXA) in diagnosing secondary osteoporosis is unclear in patients with cortisol, aldosterone, and catecholamine excess. Trabecular bone score and bone turn over markers could serve as potential diagnostic tools in assessment of severity of bone disease in patients with hormonally active adrenal tumors. Adrenalectomy is the mainstay of therapy in patients with overt hormone production. Appropriate case detection strategies to identify patients at risk of fragility fractures are needed in patients not treated with adrenalectomy, such as bilateral primary aldosteronism and mild autonomous cortisol secretion.

The Evaluation of Incidentally Discovered Adrenal Masses

The objective of this Disease State Clinical Review is to provide clinicians with a practical approach to the evaluation of incidentally discovered adrenal masses. A case-based clinical approach to the evaluation of adrenal masses is presented. Recommendations were developed using available prospective and randomized studies, cohort studies, cross-sectional studies, anecdotal observations, and expert opinions. Incidentally discovered adrenal masses are common. The approach to the patient with an adrenal mass should involve assessment of malignant potential via imaging characteristics and adrenal hormone excess via clinical and biochemical features. The roles of biopsy, surgical or medical therapy, and longitudinal surveillance are also important to consider and are influenced by case-specific factors. Inappropriate or inadequate evaluations may put patients at increased risk for developing preventable adverse cardiometabolic outcomes or cancer. Incidentally discovered adrenal masses require a multimodal assessment that involves interpretation of multiple imaging characteristics, dynamic and static hormonal measurements, and a nuanced approach to considering interventional diagnostics, treatments, and longitudinal surveillance. Herein, we review these evaluations and provide a practical approach for clinicians. ACTH = adrenocorticotropic hormone; CS = Cushing syndrome; CT = computed tomography; DHEAS = dehydroepiandrosterone sulfate; HU = Hounsfield units; MRI = magnetic resonance imaging; UFC = urinary free cortisol.