High-dose Dexamethasone Suppression Test Research Articles

Efficacious Primary Pasireotide Therapy in a Case of a Large Invasive Adrenocorticotropin-secreting Pituitary Tumor

Abstract A 41-year-old woman presented with a headache, diplopia, weight gain, moon face, and central obesity. Her plasma adrenocorticotropin (ACTH) level was 25.5 pmol/L (116 pg/mL) (normal range, 1.6-13.9 pmol/L [7.2-63.3 pg/mL]), serum cortisol level was 397.3 nmol/L (14.4 µg/dL) (normal range, 195.1-540.7 nmol/L [7.1-19.6 µg/dL]), and urinary free cortisol was 413.9 nmol/day (150.3 µg/day) (normal range, <221.5 mmol/day [<80.3 µg/day]). ACTH-dependent hypercortisolism was present, with cortisol suppression using a high-dose dexamethasone suppression test. Cushing disease was diagnosed and a contrast-enhanced magnetic resonance imaging scan demonstrated a 36-mm pituitary tumor with right cavernous sinus invasion. Before surgery, 20 mg pasireotide long-acting-release was initiated, and her symptoms rapidly improved. After 1 month, obvious tumor shrinkage was observed, ACTH and cortisol levels decreased, and diplopia resolved; therefore, we continued medical therapy. After 11 months, her ACTH and cortisol levels normalized, and most of the tumor had disappeared. The clinical course in this case suggests that pasireotide may be useful for preoperative treatment and primary medical therapy, at least in some patients with Cushing disease caused by a large tumor predicted to have difficulty achieving remission by surgery.

THU030 Evaluation Of Combined CRH And HDDST Test Performance

Abstract Disclosure: H. Elenius: None. R. McGlotten: None. L.K. Nieman: None. Introduction: Determining the etiology of ACTH-dependent Cushing’s Syndrome (CS) is frequently a diagnostic challenge. Non-invasive tests to distinguish Cushing’s Disease (CD) from Ectopic ACTH Syndrome (EAS) are the CRH stimulation test and the 8 mg overnight high dose dexamethasone suppression test (HDDST). The CRH test is more accurate (sensitivity (Se) 83-93%, specificity (Sp) 85-100%) than the HDDST (Se 56-95%, Sp 67-100%), depending on the type of CRH and criteria used. We retrospectively reviewed the results of each test at our institution between 2005-2019 to evaluate the tests' performance at established cut offs, identify optimal response criteria and to see whether combining the two tests provided additional diagnostic accuracy. Methods: CD or EAS was confirmed by either surgical pathology or biochemical cure after tumor resection or imputed from IPSS results (n=7). We identified 100 patients with CD and 34 with EAS. Two EAS patients with cyclic CS each underwent tests with or without active hypercortisolism. Test criteria to identify CD were ≥50% suppression of cortisol for the HDDST and a ≥35% increase in mean ACTH at 15-30 minutes or a ≥20% increase in mean cortisol at 30-45 minutes for the ovine CRH test. Results: The HDDST had a Se of 81%, Sp of 81% and diagnostic accuracy (DA) of 81%, while the CRH test had Se 95%, Sp 75% and DA 90%. Each test improved with modified response criteria. Using a HDDST suppression criterion of ≥63% gave Se 78%, Sp 89% and DA 81%. Using CRH test response criteria of ≥39% increase in ACTH or ≥30% increase in cortisol gave Se 94%, Sp 92% and DA 93%. Performance improved further by combining the two tests, using the optimized criteria (≥63% for HDDST and ≥39% or ≥30% for the CRH test). Test results were concordant in 80%, giving a Se of 96%, Sp 97% and DA 96%. Among EAS patients, this approach only misidentified one subject with cyclic CS who was tested while hypocortisolemic. Removing this test improved combined test performance to Se 96%, Sp 100% and DA 97%. Among the 26 patients with discordant results (CD = 22, EAS = 4), the HDDST result was likelier to be correct in EAS vs CD (50% vs 14%, PPV 60%), while the CRH test was more often correct in CD vs EAS (86% vs 50%, PPV 90%). Conclusions: Based on this series that included a large proportion of EAS patients, the CRH test performed better than the HDDST, in line with earlier data. In cyclic CS, tests performed better in hypercortisolemic patients. The optimal response criteria were ≥63% cortisol suppression for HDDST and ≥39% ACTH or ≥30% cortisol increase for the CRH test. In the 81% of hypercortisolemic cases with concordant test results, these combined optimized cut offs provided the best diagnostic performance, improving it to Se 96%, Sp 100%, DA 97%. When results were discordant, the CRH test worked better to identify patients with CD. Presentation: Thursday, June 15, 2023

THU577 Acth Dependent Cushing Syndrome Identification And Management Challenges

Abstract Disclosure: B.C. Barreto: None. S. Patrick: None. H. Oktaei: None. H.O. Steinberg: None. Endogenous Cushing Syndrome(CS) is rare with an incidence of 0.2-5.0 per million people per year. 70 to 80% of CS is ACTH dependent and subclassified into Cushing Disease, Ectopic ACTH Syndrome and Ectopic CRH Syndrome. Ectopic ACTH secretion(EAS) has a variable clinical presentation. Atypical features like refractory hypokalemia in a patient with a tumoral lesion should raise suspicion. When imaging is inconclusive, differentiating between pituitary or ectopic disease includes invasive and noninvasive methods. We report a case of EAS. Case: A 57-year-old male with history of metastatic small-cell lung-cancer on palliative chemotherapy was admitted for acute coronary syndrome. Endocrinology evaluated the patient’s uncontrolled hypertension, hyperglycemia, and hypokalemia (1.5 mmol/L). He had no suppression with low dose dexamethasone (cortisol>75mcg/dL, ACTH 926pg/mL). Examination was pertinent for an elevated BMI 36.1kg/m2, hyperpigmented anterior thorax but no other stigmata of hypercortisolism. Laboratory analysis showed baseline cortisol 146.1mcg/dL(8.7-22), ACTH 590pg/ml(6-50), 24hr Urine Free Cortisol 736mcg/24h(5-50), which were not suppressed by high dose dexamethasone suppression test(HDDST). Aldosterone and PRA were undetectable. Brain MRI showed an enlarged pituitary gland, but no focal mass. CT abdomen pelvis showed bilateral adrenal hyperplasia, multiple hepatic masses, and bone lesions. Since the patient was a poor surgical candidate, medical therapy was initiated with ketoconazole 200mg TID, aldactone 50mg BID and potassium chloride 40mEq TID. After twelve days cortisol levels decrease to 65.2 mcg/dL, potassium 3.8 mmol/L and glucose 146 mg/dL. Hospitalization was complicated by a small bowel ileus. Medications were held due to poor gastrointestinal absorption and parenteral octreotide 200mcg TID was initiated. Once the ileus resolved, ketoconazole 200mg TID, eplerenone 50mg daily, and dexamethasone 0.5mg daily was started. Despite medical care, the patient eventually expired. Discussion: The HDDST can help distinguish pituitary from an ectopic ACTH overproduction. HDDST with >50% suppression, has been described with sensitivity-specificity of 60 to 100% for pituitary ACTH source. Symptomatic treatment of CS requires rapid normalization of hypercortisolism action. Surgery is the first line approach. When surgery is not an option, medical therapy should be considered. Adrenal steroidogenesis inhibitors, such as ketoconazole, are the first line due to rapid onset of action. Agents such as glucocorticoid receptor antagonists have limited availability in the inpatient setting. Somatostatin analogs and etomidate that inhibit 11-ßhydroxylase are potential options but require close monitoring. Severe hypercortisolism in the critically ill prompts the use of noninvasive evaluation tools and alternative medical approaches. Presentation Date: Thursday, June 15, 2023

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

Abstract Disclosure: M. Fasen: None. S.E. Mayson: None. Background: Ewing sarcoma (ES) is a rare and aggressive neoplasm occurring in bone and soft tissue in children to young adults. It is part of a spectrum of neoplastic diseases known as the ES family of tumors that display varying degrees of neuroendocrine features. Ectopic Cushing’s syndrome (ECS) is also a rare but severe condition associated with unregulated ACTH or CRH secretion by neuroendocrine tumors (NETs) that can cause severe hypercortisolism. The most common tumors associated with ECS include small cell lung carcinoma, bronchial carcinoid and medullary carcinoma of the thyroid gland. Sarcomas causing ECS are extremely rare with only a handful of cases reported in the literature, mostly in children. Herein we detail what we believe to be the first reported case of ECS occurring in an adult male patient with ES. Clinical Case: A 23-year-old man with ES metastatic to pancreas, liver and bone was admitted to the hospital with acute on chronic back pain and lower extremity weakness, and subsequently diagnosed with cord compression and neutropenia from chemotherapy. New onset hypertension and refractory hypokalemia were observed prompting endocrinology consultation. Physical examination revealed facial fullness, central obesity and wide violaceous striae on his abdomen and axillae. Biochemical evaluation demonstrated blood glucose consistently over 300 mg/dL, serum potassium 2.5 mmol/L, renin 0.9 ng/ml/hr (0.2-1.6 ng/ml/hr), aldosterone renin ratio < 3.3, morning cortisol 73 ug/dL (4-22 ug/dL), and ACTH 1020 pg/mL (72-63 pg/mL). A 1 mg overnight dexamethasone suppression test yielded a serum cortisol of 90 ug/dL and 24-hour urine free cortisol was 6388 ug/d (<60 ug/d). MRI brain demonstrated a normal pituitary gland, and FDG PET-CT showed new areas of uptake in bone concerning for metastatic progression and new bilateral adrenal enlargement without nodularity. High dose dexamethasone suppression testing was deferred in the context of rapid neuropsychiatric deterioration characterized by somnolence and psychosis. The decision was made to treat immediately with spironolactone and ketoconazole, as well as insulin for hyperglycemia management. His mental status, blood pressure, serum potassium, glucose and cortisol improved following the initiation and titration of medical therapy. He was discharged home with addition of metyrapone and hospice support. Two months later the patient succumbed to his illness. Conclusion: The severity of hypercortisolism is a negative predictor of survival and prompt control should be the main therapeutic goal along with prevention of cortisol-induced complications in patients with ECS. ACTH and CRH immunostaining of the patient’s ES histopathology slides is pending. Presentation: Thursday, June 15, 2023

THU014 Post-surgical Remission After Resection Of Solitary Mediastinal Lymph Node In A Metastatic Occult Ectopic ACTH Syndrome Patient

Abstract Disclosure: I.P. de Magalhães: None. C.P. Oliveira: None. L.P. Lins: None. N.X. Andrade: None. M.S. Lima: None. S.A. Siqueira: None. J.S. Fonini: None. E.C. Assis Filho: None. A.W. Mariani: None. M.C. Machado: None. BACKGROUND: The prevalence of occult cases has been increasing in the most recent series of Ectopic ACTH syndrome (EAS) maybe due to the small size of pulmonary neuroendocrine tumors. We present an atypical and very rare case of EAS with initial presentation of a single metastatic mediastinal lymph node that evolved with remission after your resection with no defined primary tumor. CASE REPORT: A 15-year-old female patient presented a clinical feature of Cushing’s syndrome (CS) with a 1-year evolution. Hormonal evaluation confirmed ACTH-dependent CS: urinary free cortisol of 819 µg/24h (3-43), late night salivary cortisol of 409 ng/dL (<274) and ACTH of 105 pg/mL (<63.3). Noninvasive methods for differential diagnosis of ACTH-dependent CS did not clarify the etiology (conflicting results): pituitary MRI negative, suppression of 59.6% of cortisol after high dose dexamethasone suppression test, positive response of ACTH and cortisol at desmopressin test, suppression of 81% of ACTH at acute octreotide SC test, negative serum tumor markers (gastrin, calcitonin, CEA, CA125, alpha-fetoprotein, CA19.9 and bhCG), negative cervical and pelvic ultrasound, negative computed tomography of thorax and negative abdominal MRI. Bilateral and simultaneous petrosal inferior sinus sampling with desmopressin confirmed EAS due to negative central to peripheral ACTH gradient, even after normalized PRL/ACTH gradients. Finally, PET/CT with Ga68-DOTATATE revealed a single infracarinal nodule of 1.5x0.6 cm with high capture of radioligand, SUVmax of 23.2, suggestive of affected mediastinal lymph node. The patient was submitted to thoracic surgery and the infracarinal lymph node was dissected and removed. Anatomopathological and immunohistochemical analyses disclosed a lymph node metastatic of a well-differentiated grade neuroendocrine tumor ACTH positive, Ki-67 2%. After surgery, the patient exhibited CS improvement and impressive drop of hormones at 5th postsurgical day (serum cortisol <1.0 µg/dL and ACTH of 2.2 pg/mL) confirming remission of CS. CONCLUSION: To our knowledge, approximately 36 cases of EAS due to neuroendocrine tumor of unknown primary origin were reported. However, previous cases commonly exhibited no remission after only removal of metastasis. Our case presented initial remission even with no primary tumor identified (occult primary tumor non-functioning?). Follow up with clinical, hormonal and imaging methods are necessary due to recurrence risk. Presentation: Thursday, June 15, 2023

THU009 Subclinical Cushing’s Syndrome In An ACTH-secreting Pituitary Macroadenoma

Abstract Disclosure: N.G. Akabogu: None. D. Kumar: None. N. Sheung: None. A. Akofu: None. A. Uddin: None. S. Dejhansathit: None. F. Marium: None. L.G. Kurukulasuriya: None. Background: Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). Case presentation: We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed 8AM cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of 8AM cortisol and ACTH on the high dose DST. 24hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Conclusion: Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome. Presentation: Thursday, June 15, 2023

THU213 Posterior Reversible Encephalopathy Syndrome As A Rare Presentation Of ACTH-dependent Cushing Syndrome In A Pediatric Patient

Abstract Disclosure: E.E. Bell-Sambataro: None. C. Tatsi: None. P. Chittiboina: None. S.A. Bowden: None. Background: Cushing disease (CD), caused by ACTH-secreting pituitary adenoma, is the most common cause of Cushing Syndrome (CS) in children > 5 years of age. Hypertension is reported in up to 50% of pediatric cases with CS. We report a challenging pediatric case with a rare presentation of hypertensive emergency associated with CD. Clinical Case: A 6-year-old female with 3 month-history of rapid weight gain (8 kg), round face, and hypertrichosis presented to emergency department for abdominal pain from nephrolithiasis and was noted to have severe hypertension. While in ED, she developed status epilepticus and altered mental status. Brain MRI findings were consistent with posterior reversible encephalopathy syndrome (PRES). Her hypertensive encephalopathy gradually improved with aggressive anti-hypertensive and anti-epileptic therapy. Further studies confirmed hypercortisolism with markedly elevated urine free cortisol of 1288 ug/day (<18 ug/day) and lack of diurnal variation of serum cortisol (8 AM cortisol of 47.9 ug/dL, midnight cortisol of 20.3 ug/dL). ACTH level of 23 pg/mL suggested ACTH-dependent CS. Low dose (1 mg) dexamethasone suppression test (DST) failed to suppress 8 am cortisol (31.4 ug/dL). High dose DST (120 mcg/kg) suppressed serum cortisol to 67%- borderline threshold for CD, likely due to increased dexamethasone clearance by anticonvulsant. Pituitary MRI did not reveal a visible lesion. Desmopressin stimulation test showed stimulation of ACTH by 700% and cortisol by 160% suggesting pituitary source. Inferior petrosal sinus sampling showed a mildly increased gradient in central to peripheral plasma ACTH of 1.7 at baseline (>2) and post-stimulation of 2.5 (>3). ACTH gradient did not reach cutoffs for pituitary source, likely due to insufficient catheterization of petrosal sinus from anatomically small blood vessels. Given her severity, she underwent surgical pituitary exploration. Postoperative morning cortisol was <5 mcg/dL, with decreased midnight salivary cortisol level obtained 2 months after surgery. She developed post-operative central hypothyroidism but did not have diabetes insipidus. She had a 4 kg weight loss with increased height percentile 5 months after surgery and remains under close monitoring. Conclusion: PRES is a clinical-radiographic disorder characterized by seizures, encephalopathy with neuroimaging findings of reversible cortical and subcortical vasogenic edema. Hypertension induced by marked hypercortisolism precipitated by pain is likely the etiologic factor. Prompt recognition and treatment of PRES are crucial to prevent further life-threatening complications and permanent neurological damage. Early diagnosis and treatment of CD are critical to prevent associated morbidities. Pituitary exploration by expert neurosurgery team should be considered in patients with MRI-negative CD. Presentation: Thursday, June 15, 2023

THU517 Aggressive Cushing’s: A Rare Case Of Pancreatic ACTHoma In A Young Female

Abstract Disclosure: O.C. Reyes: None. A. Sison: None. M. Villa: None. D. Dimayuga: None. Introduction: Adrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is a rare type of pancreatic neuroendocrine tumor that causes ectopic adrenocorticotropic hormone syndrome. Cushingoid manifestations and metabolic abnormalities can occur rapidly. High index of suspicion is required for early diagnosis. Case: A 31-year-old Filipino female presented with facial and ankle swelling that occurred 6 weeks before the visit. She also had acne, easy bruising, amenorrhea and frequent mood swings. There was reported weight gain of 3 kg a month prior. She had no history of hypertension and diabetes, and had no unusual family history. At the time of admission, vital signs were blood pressure of 130/80mmHg, pulse of 92/min, respiratory rate 20/min and body temperature of 37.2C. Her body mass index was 28kg/m2. She had muscle atrophy of the upper and lower extremities, facial flushing, posterior cervical fat pad, abdominal violaceous striae, and skin pigmentation. Her external genitalia was normal, Tanner Stage 5 consistent with adult pattern. Neurologic exam was unremarkable. She was examined for Cushing’s syndrome. On initial tests, glucose was 406 mg/dl, HbA1C 10.7%, thyroid stimulating hormone 0.122 (NV: 0.55-4.78), Free T3 0.77 (NV: 2.3-4.2), Free T4 0.58 (NV: 0.89-1.76). Creatinine was 0.86 mg/dL, sodium was 140 mEq/L, potassium was 2.1 mEq/L showing hypokalemia. There was leukocytosis on her blood count, white blood cells 15,310/mm3 (neutrophils 94%, lymphocytes 3%). In the low-dose dexamethasone suppression test (DST), the serum cortisol concentration was 991.03nmol/L. Her adrenocorticotrophic hormone (ACTH) level was elevated at 577pg/mL. After high-dose DST, the serum cortisol concentration was > 1750 nmol/L. No tumor was observed on pituitary magnetic resonance imaging. On abdominal computed tomography (CT), a large, lobulated, heterogeneously-enhancing mass arising from the pancreatic body and tail measuring 7.5cm x 10cm x 10.9cm was seen. The mass had infiltrated the gastric fundus, and encased the splenic artery. Multiple non-calcified subcentimeter pulmonary nodules were observed on chest CT. CT-guided biopsy of the pancreatic mass was done. On microscopic examination, numerous atypical cells arranged with small clusters and sheets and scattered singly were found in the tumor. The cells had small to enlarged, hyperchromatic, ovoid to round nuclei and scant to ample delicate cytoplasm. On immunohistochemical staining, the tumor cells were stained positive for synaptophysin and chromogranin A, which are both neuroendocrine markers, as well as ACTH. However, the patient died prior to any definitive management. Conclusion: ACTHoma is a very rare disease that causes hypercortisolemia. Reporting of similar cases will provide insight into its clinical features, immunohistochemical characteristics, diagnosis, therapy, and prognosis. Presentation: Thursday, June 15, 2023

THU011 Cushing’s Disease Diagnosis Challenge With Standard Pituitary MRI: A Clinical Case Report

Abstract Disclosure: E. Kasiri: None. N. Shah: None. Introduction: Cushing’s disease (CD); the most common cause of endogenous Cushing’s syndrome (CS) is mainly caused by an adrenocorticotropin (ACTH)-secreting pituitary adenomas. Although MRI remains the preferred imaging to detect these adenomas, still about 50% of microadenomas may be missed using standard 1.5-Tesla MRI and on the other hand higher resolution MRI with 3T magnets is not widely used. Here we present a case of Cushing’s disease with equivocal 1.5T MRI which made a next step of management rather challenging. Case presentation: A 57-year-old female with history of hypertension, type 2 diabetes mellitus and obesity (BMI: 34.41 kg/m2) presented to our endocrinology clinic to establish care. Her main complaint was difficulty losing weight. She denied taking any steroids or oral contraceptive pill. Vitals showed BP: 124/85 mm Hg, HR: 100 bpm and T: 98.3 °F. Physical exam was significant for moon facies, buffalo hump and abdominal obesity. She was screened for Cushing syndrome with 1mg overnight low dose dexamethasone test which resulted in abnormal cortisol response with a level of 2.1mcg/dl (<1.8 mcg/dl). A 24hr urine free cortisol: 7.3 mcg/dl (<45 mcg/dl) and two late night salivary cortisol measurements resulted in 0.388 and 0.229 mcg/dl (> 3 times upper limit of normal). Other labs showed elevated baseline ACTH :67.4 pg/ ml (7.2 - 63.3 pg/mL), cortisol :19.4 mcg/dl (4.5-23 mcg/dl) and normal DHEAS:1864.1ng/ml (650-3400 ng/mL). We decided to distinguish ectopic vs pituitary source of hypercortisolism by an 8 mg (high dose) dexamethasone suppression test which showed suppressed ACTH <1.5 pg/ml, Cortisol :2.6 mcg/dl (>50% suppression from baseline) suggesting pituitary origin. The standard pituitary 1.5T MRI with and without contrast as next step resulted in questionable microadenoma in the right aspect of pituitary gland and was equivocal. Within the multidisciplinary team decision was made to perform 3T pituitary MRI rather than invasive inferior petrosal sinus sampling (IPSS) which confirmed the pituitary microadenoma of 8.1 mm size with no mass effect and patient is scheduled for transsphenoidal pituitary surgery without needing further testing. Discussion: 3T MRI, with higher magnetic field than 1.5T allows to improve image quality and help with tumor detection in Cushing’s disease. It reportedly has higher sensitivity (80%) and specificity (∼100%) compared to 1.5T MRI which has overall sensitivity and specificity of 71% and 87% respectively. However, it is not the first to order by the clinicians when evaluating the ACTH secreting pituitary adenoma. In the case of equivocal 1.5 T MRI usually the next step is IPSS which is invasive. With availability of Corticotropin Releasing Hormone in the USA being difficult, limited studies of using DDAVP and limitations in finding tertiary centers to perform IPSS, a 3T MRI would be more feasible as a next step to identify a pituitary adenoma. Presentation: Thursday, June 15, 2023

C7 (Clinical Case) ACTH-dependent Cushing’s in an 8-Year-Old: A Diagnostic Challenge

Abstract Introduction/Background Cushing’s syndrome (CS) is rare, with 2-5 cases per million annually, and only 10% of these occurring in children. Cushing’s disease (CD) (excessive adrenocorticotropic hormone [ACTH] secretion by a pituitary source leading to hypercortisolism) is the most common organic etiology of CS in children (75-90%). Ectopic ACTH syndrome (EAS), in contrast, accounts for less than 1%. Case Description An 8-year-old male presented with extensive vertebral compression fractures, rapid weight gain, and headaches. He was found to have hypertensive urgency (blood pressure 170/110 mmHg, > 99.9 percentile) and Cushingoid features. Investigations revealed hypokalemia (2.0 mmol/L), elevated serum cortisol (1654 nmol/L, ref 85-620) and elevated 24-hour urine cortisol (27244 nmol/day, ref < 25). An elevated ACTH (35pmol/L, ref 1.6-13.9) confirmed ACTH-dependent CS. Although non-invasive dynamic testing (high dose dexamethasone suppression and desmopressin stimulation tests) suggested an ectopic source, inferior petrosal sinus sampling (IPSS) suggested a pituitary source. Unfortunately, anatomical (3T MRI Sella) and functional imaging (18 F-DOPA and Gallium-68 dotatate PET/CT scans) have not identified a causative lesion to date. On 18 F-DOPA PET/CT imaging, a 1cm focus of avidity was found in the small bowel, concerning for neuroendocrine tumour. However, excisional biopsy identified the mass as a Meckel’s diverticulum with cortisol and ACTH persistently elevated post-operatively. As such, he has been started on ketoconazole to control the hypercortisolemia and reduce morbidity. This has been mainly effective, with 24-hour urine cortisol reduced to 70 nmol/day. He will undergo serial imaging and continue medical therapy as long as tolerated. Exploratory pituitary surgery may be considered if medical therapy proves ineffective or overly burdensome over time. Discussion We present a diagnostically challenging case of ACTH-dependent Cushing’s syndrome, suspected Cushing’s disease. Non-invasive dynamic tests have limited sensitivity and specificity when used in isolation. As a result, source localization in ACTH-dependent Cushing’s can be challenging. Ultimately, IPSS was suggestive of a pituitary source. However, a causative lesion has not been identified despite multiple modalities of anatomic and functional imaging. Medical therapy can be a useful temporizing measure while pursuing further workup, but can have problematic side effects and requires frequent laboratory monitoring. This patient’s story highlights the difficulty in diagnosis and in choosing a management strategy for a patient without an identified source of excess ACTH, as all options carry risk of morbidity. Conclusion CS is rare in paediatrics but should be considered in a patient with suggestive exam findings and refractory hypertension. Diagnostic workup should proceed in sequential order to confirm hypercortisolemia, distinguish between central vs peripheral origin, and localize the responsible lesion. In cases with inconclusive investigations, IPSS remains necessary for localization.

Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors

Background18Fluorine-Fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities. Although the usefulness of 18F-FDG PET has been reported in several endocrine diseases, studies on pituitary disease are extremely limited. To evaluate whether dexamethasone (DEX) suppression can improve 18F-FDG PET for the localization of adrenocorticotropic hormone-secreting adenomas in the pituitary gland in Cushing’s disease (CD).MethodsWe included 22 patients with CD who underwent PET imaging before and after DEX administration. We compared the success rates of PET before and after DEX suppression, magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus sampling (BIPSS). We determined the final locations of adenomas based on intraoperative multiple-staged resection and tumor tissue identification using frozen sections. Standardized uptake value (SUV) were analyzed to confirm the change of intensity of adenomas on PET.ResultsTwenty-two patients were included (age at diagnosis: 37 [13–56] years), and most were women (90.91%). Pituitary adenomas compared to normal pituitaries showed increased maximum SUV after DEX suppression but without statistical significance (1.13 versus. 1.21, z=-0.765, P = 0.444). After DEX suppression, the mean and maximum SUV of adenomas showed a positive correlation with nadir cortisol levels in high-dose DEX suppression test (Rho = 0.554, P = 0.007 and Rho = 0.503, P = 0.017, respectively). In reference sites, mean SUV of cerebellum was significantly decreased (7.65 vs. 6.40, P = 0.006*), but those of the thalamus and gray matter was increased after DEX suppression (thalamus, 8.70 vs. 11.20, P = 0.010*; gray matter, 6.25 vs. 7.95, P = 0.010*).ConclusionDEX suppression did not improve 18F-FDG PET/CT localization in patients with CD.

Ovine CRH Stimulation and 8 mg Dexamethasone Suppression Tests in 323 Patients With ACTH-Dependent Cushing's Syndrome.

Determining the etiology of adrenocorticotropin (ACTH)-dependent Cushing's syndrome (CS) is often difficult. The gold standard test, inferior petrosal sinus sampling (IPSS), is expensive and not widely available. Evaluate the performance of the corticotropin-releasing hormone stimulation test (CRH-ST) and the 8 mg high-dose dexamethasone suppression test (HDDST) in distinguishing Cushing's disease (CD) from ectopic ACTH syndrome (EAS). Retrospective review in a tertiary referral center. A total of 323 patients with CD or EAS (n = 78) confirmed by pathology or biochemical cure (n = 15) in 96% underwent CRH-ST and HDDST performed between 1986 and 2019. We calculated test sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value, and diagnostic accuracy (DA) for the diagnosis of CD, and determined optimal response criteria for each test, alone and in combination. The CRH-ST performed better than the HDDST (DA 91%, 95% CI 87-94% vs 75%, 95% CI 69-79%). Optimal response criteria were a ≥40% increase of ACTH and/or cortisol during the CRH test and a ≥69% suppression of cortisol during the HDDST. A ≥40% cortisol increase during the CRH test was the most specific measure, PPV 99%. Seventy-four percent of subjects had concordant positive CRH test and HDDST results, yielding Se 93%, Sp 98%, DA 95%, and PPV 99%, with a pretest likelihood of 85%. A proposed algorithm diagnosed 64% of patients with CD with near perfect accuracy (99%), obviating the need for IPSS. CRH is a valuable tool to correctly diagnose the etiology of ACTH-dependent CS. Its current worldwide unavailability impedes optimal management of these patients.

Abstract #1413755: Subclinical Cushing’s Syndrome in an ACTH-secreting Pituitary Macroadenoma

Subclinical Cushing’s syndrome (SCS) is characterized by subtle cortisol hypersecretion, which does not result in the typical signs and symptoms of Cushing’s syndrome (CS). While many of the signs and symptoms of CS are common in the general population, there are some that are discriminatory and specific for CS: supraclavicular fat pads, proximal muscle weakness, facial plethora, and violaceous striae. SCS manifests mostly as obesity, type 2 diabetes, and hypertension. Diagnosing SCS is challenging; however, the best screening test to uncover the subtle hypercortisolism is the dexamethasone suppression test (DST). We report a case of SCS in a 62 years old Caucasian postmenopausal patient with a medical history of total thyroidectomy for Graves’ disease, post-surgical hypothyroidism, 7.4cm right pheochromocytoma status post partial right adrenalectomy, incidentally discovered pituitary macroadenoma (during imaging to look for subarachnoid hemorrhage), untreated type 2 diabetes mellitus (A1c 6.6% and stable for 1 year before treatment), hypertension, atrial fibrillation, cerebrovascular accident, and worsening migraines. Patient’s physical exam was mostly unremarkable; she had central obesity and bilateral lower extremity swelling. Pituitary work-up showed evidence of secondary hypogonadism and secondary hypothyroidism with elevated adrenocorticotropic hormone (ACTH) of 130 (AM range: 7.2-63) and cortisol of 12.6, at 11:52AM. Further work-up for hypercortisolism revealed non-suppressed cortisol (5.83mcg/dL) on the low dose DST and 49% suppression of cortisol and ACTH on the high dose DST. 24-hour urinary cortisol was normal. Patient did not perform the midnight salivary cortisol. Patient subsequently underwent trans-sphenoidal resection of the pituitary macroadenoma. Pathology analysis of the pituitary mass showed weak to moderate immunoreactivity for ACTH. Our patient had abnormal DST but normal 24hour urine cortisol. We may have missed her SCS if we screened her only with a 24hour urine cortisol. This confirms the fact that dexamethasone suppression test should be the first test in the evaluation of subclinical Cushing’s syndrome.

Cushing's syndrome due to atypical carcinoid of the mediastinum

Ectopic Cushing's syndrome, caused by a neuroendocrine tumor (NET), is a rare finding. NETs of the mediastinum are extremely rare. NETs arising from the anterior mediastinum are generally aggressive. They are widely characterized at clinical presentations, and may be asymptomatic or present with atypical symptoms. Prognosis is often poor due to their local recurrence and distant metastasis despite a multimodal approach. A 33-year-old male patient was admitted to our department with a femoral soft tissue abscess, diabetes, and hypokalemia. He had no typical features of Cushing's syndrome. However, with a few simple tests, that is, a basal hormone profile, and low-dose and high-dose dexamethasone suppression tests, we diagnosed this complicated condition of ectopic adrenocorticotrophic hormone (ACTH) secretion. Thoracic computed tomography revealed an anterior mediastinal mass of 35×22 mm. A surgical excision of the tumor was proposed, and intra-operative pathology consultation returned positive for the suspected NET. Immunohistochemically, the tumor cells were positive for CK, CD56, Chromogranin, Synaptophysin, S100, and CD117. No thymic tissue was found. The Ki-67 was 4%. A diagnosis of primary NETs of the mediastinum, intermediate grade (G2), of atypical carcinoids according to WHO 2015 was established. This patient survived with no sequelae, no distant metastasis, no recurrence, and without adjuvant radiotherapy or chemotherapy 2 years after surgery thanks to earlier diagnosis and prompt surgical intervention. Mediastinum ectopic ACTH-secreting tumors are a rare type of cancer. According to recent research, these tumors frequently display more aggressive behavior and are linked to endocrinopathies. It is noted that patient might have a better outcome and a longer survival time due to earlier detection and complete resection of malignancies.

Comparison of the preoperative diagnostic accuracy of BIPSS versus MRI for Cushing disease: a single-centre experience

BackgroundCushing disease (CD) arises due to a pituitary corticotroph adenoma, which is the most common cause of Cushing syndrome (CS). Bilateral inferior petrosal sinus sampling (BIPSS) is a safe method for differentiating CD from ectopic adrenocorticotropic hormone (ACTH)-dependent CS. Enhanced high-resolution magnetic resonance imaging (MRI) can localize tiny pituitary lesions. The aim of this study was to compare the preoperative diagnostic accuracy of BIPSS versus MRI for CD in CS patients. We performed a retrospective study of patients who underwent BIPSS and MRI between 2017 and 2021. Low- and high-dose dexamethasone suppression tests were performed. Blood samples were collected simultaneously from the right and left catheter and femoral vein before and after desmopressin stimulation. MRI images were obtained, and endoscopic endonasal transsphenoidal surgery (EETS) was performed in confirmed CD patients. Dominant sides of ACTH secretion during BIPSS and MRI were compared with surgical findings.ResultsTwenty-nine patients underwent BIPSS and MRI. CD was diagnosed in 28 patients, 27 of whom received EETS. Localizations of microadenomas by MRI and BIPSS agreed with the EETS findings in 96% and 93% of the cases, respectively. BIPSS and EETS were successfully performed on all patients.ConclusionBIPSS was the most accurate method (gold standard) for establishing a preoperative diagnosis of pituitary-dependent CD and was more sensitive than MRI in diagnosing microadenoma. High-resolution MRI with enhancement had an advantage over BIPSS in microadenoma lateralization diagnostics. The combined use of MRI and BIPSS could improve the preoperative diagnosis accuracy in ACTH-dependent CS patients.

Dynamic Testing for Differential Diagnosis of ACTH-Dependent Cushing Syndrome: A Systematic Review and Meta-analysis.

Diagnostic accuracy of testing currently used for the differential diagnosis of Cushing disease (CD) vs ectopic adrenocorticotropic hormone secretion (EAS) is difficult to interpret. The present study aimed to identify and evaluate the diagnostic accuracy of the corticotropin-releasing hormone (CRH) test, the desmopressin test, and the high-dose dexamethasone suppression test (HDDST) when used to establish a CD or EAS diagnosis. This study is a systematic review of the literature and meta-analysis. MEDLINE, OVID, and Web of Science databases were searched for articles published between 1990 and 2021. Articles included described at least 1 test(s) (CRH, desmopressin, or HDDST) and the diagnostic reference standard(s) (histopathology, petrosal sinus sampling, surgical remission, imaging, and long-term follow-up) used to establish a CD or EAS diagnosis. Sixty-two studies were included: 43 reported the use of the HDDST; 32, the CRH test; and the 21, the desmopressin test. The CRH test was found to have the highest sensitivity in detecting CD (ACTH 86.9%, 95% CI 82.1-90.6, cortisol 86.2%, 95% CI 78.3-91.5) and the highest specificity in detecting EAS (ACTH 93.9%, 95% CI 87-98.3, cortisol 89.4%, 95% CI 82.8-93.7). This resulted in a high diagnostic odds ratio (58, 95% CI 43.25-77.47), large area under the curve, and a receiver operating characteristic of 0.934. The diagnostic accuracy of the HDDST and desmopressin test was lower than that of the CRH test. The meta-analysis indicates that a patient with a positive ACTH response after a CRH test is highly likely to have CD. Further studies analyzing role of dynamic testing in addition to imaging are needed.

PMON98 High-dose dexamethasone suppression test in ACTH-dependent Cushing's syndrome: Lessons learned on the lack of cortisol suppression

Abstract Background The overnight 8-mg high-dose dexamethasone suppression test (HDDST) has been used to discern Cushing's disease from ectopic ACTH production. However, because of its reported low diagnostic accuracy, its use is limited to the assessment of ACTH-dependent Cushing's disease when combined with a corticotropin releasing hormone (CRH) or a desmopressin stimulation test. We evaluated a patient with Cushing's disease in whom the HDDST failed to identify the pituitary source. We point to limitations in test interpretation and highlight the need of future studies to enhance understanding of the clinical utility of this non-invasive test. Clinical Case A 42-year-old male presented with lower extremity cellulitis and hypertensive emergency. He reported increased abdominal girth, easy bruising, severe back pain and proximal muscle weakness and noted headache and blurred vision. Exam was pertinent for obesity (body mass index 31.5 kg/m2), moon facies, dorso-cervical hump and prominent abdominal striae. Lumbar and thoracic compression fractures were noted on imaging. The elevated 24-hour urinary free cortisol level (198 ug/dL; reference: 10-100 ug/24hr) and lack of suppression on the overnight 1-mg dexamethasone suppression test (morning cortisol 23.7 ug/dL) confirmed Cushing's syndrome; a high ACTH level of 92 pg/dL defined it as ACTH-dependent. The 8-mg HDDST resulted in only a 9.7% reduction of his baseline morning cortisol. The patient was not on any medications that enhanced dexamethasone clearance. Serum dexamethasone levels were measured to aid in test interpretation and, although a level was provided, reference values for the single overnight 8-mg dose of dexamethasone were lacking. A CRH stimulation test was performed and resulted in a 60% increase in ACTH levels from baseline, supporting the diagnosis of Cushing's disease. Additionally, a pituitary MRI revealed a suprasellar 2.5×1.5×1.3 cm mass. Due to ambiguity posed by the HDDST result, despite tumor size, neurosurgery requested inferior petrosal sinus sampling (IPSS). Prior to this procedure, the patient underwent an overnight 16-mg HDDST. While limited information remains on the diagnostic performance of this test, we observed that the baseline morning cortisol decreased by 53.9%. IPSS confirmed the diagnosis of Cushing's disease and pathology identified a corticotroph adenoma. Conclusion The diagnosis of Cushing's disease is complex and recommendations continue to evolve. Th role of the HDDST in combination with another dynamic test remains clinically relevant. It is important that when considering a HDDST, clinicians review medication history to exclude agents that may interfere with dexamethasone metabolism. Our case highlights the need of studies that determine an appropriate reference range for dexamethasone plasma levels after a single 8-mg overnight dose and that evaluate the diagnostic performance of the HDDST in this context. It also brings attention to the need of further elucidating the diagnostic utility of a higher dexamethasone dose in the evaluation of ACTH-dependent Cushing's syndrome. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

ODP309 Ectopic Cushing's Syndrome: Importance of Methodical Approach to Hide and Seek

Abstract Cushing's syndrome (CS) is associated with high morbidity and fivefold excess mortality. Ectopic ACTH syndrome accounts for 20% of CS cases. It is crucial to identify and localize the source of extrapituitary ACTH secretion because surgical resection of the primary, often malignant, tumor has a high probability of cure with complete remission in 80% of cases. A 72-year-old female was admitted to a community hospital for lateral chest pain after a fall. She endorsed progressive weight gain, new HTN, emotional lability and worsening cognition over the prior 6 months. ACTH and cortisol levels were elevated. MRI brain failed to identify a pituitary lesion. CT chest showed multiple rib fractures and anterior mediastinal mass which was biopsied. While awaiting pathology results, IPS sampling attempted but aborted due to pulmonary edema necessitating ICU care. She was transferred to our institution for planned TSR of suspected pituitary adenoma. Examination showed Cushingoid features. Labs showed hypokalemia, high cortisol and high ACTH. MRI pituitary showed normal sella. MRI spine showed multilevel vertebral compression fractures. CT chest showed interval growth of mediastinal mass. A 1 mg dexamethasone suppression test failed to suppress ACTH and cortisol, confirming ACTH dependent hypercortisolism. A high dose 8 mg dexamethasone test failed to suppress ACTH and cortisol, a 10 mcg DDAVP stimulation test showed a flat response, with ACTH and cortisol levels remaining comparable before and after DDAVP injection. Dynamic testing therefore consistent with ectopic ACTH dependent hypercortisolism. Gallium-68 DOTA-TATE PET Scan demonstrated uptake in mediastinal mass suggestive of somatostatin receptor positive neuroendocrine tumor. Biopsy specimens processed at our institution showed cells positive for epithelial markers Cytokeratin and PAX8. Sample showed neuroendocrine differentiation with positive staining for Chromogranin A, synaptophysin and CD 117. Findings consistent with neuroendocrine thymic neoplasm. The patient was started on oral ketoconazole to control hypercortisolism. Surgical resection of tumor was planned with intent to cure CS. Ultimately, due to proximal myopathy and multiple vertebral fractures her performance status was too poor for safe tumor resection. Unfortunately, she died of complications related to CS while attempting preoperative rehabilitation. This case illustrates the importance of a timely, systematic evaluation for ACTH source in ACTH dependent hypercortisolism. Delay in CS diagnosis and localizing correct ACTH source led to missing the window of fitness for curative surgery. If ACTH is elevated, the most common source is pituitary neoplasia, however ectopic ACTH production must be ruled out. Dynamic testing including high dose dexamethasone suppression test, CRH and DDAVP stimulation tests should be used for preliminary localization of ACTH production. IPS sampling is invasive with greater potential for complications, as in the case of our patient. Therefore, it is only indicated if there are conflicting results from different dynamic tests and imaging studies. Presentation: No date and time listed

ODP302 Cushing's Disease: A Challenging Diagnosis in Patients with Underlying Co-Morbidities

Abstract Introduction Cushing's disease (CD) is a rare endocrine disorder with significant morbidity and mortality. This case is a complicated ACTH (adrenocorticotropic hormone)-dependent hypercortisolism with a negative pituitary MRI inthe setting of underlying liver cirrhosis and chronic kidney disease. Hypercortisolism work up was challenging due to liver and kidney disease. Case Presentation A 42-year-old woman with a history of liver cirrhosis(MELDscore: 19) and stage 3b chronic kidney disease (CKD) presented with nausea, vomiting and abdominal pain. She reported proximal muscle weakness. On examination, she had central adiposity with large purple abdominal striae and proximal muscle wasting. Medical history was pertinent for uncontrolled hypertension and type 2 diabetes mellitus. Due to concern for Cushing's syndrome, an overnight 1 mg dexamethasone suppression test (DST) was performed. She had an inappropriately elevated morning cortisol of 10.1 mcg/dL (n < 1.8 mcg/dL), but suboptimal dexamethasone level of 104 ng/dL (140-295 ng/dL), suggesting incomplete absorption secondary to emesis. A repeat DST was not performed given concerns for reduced dexamethasone clearance with her underlying renal and liver disease. Her 24-hour urine free cortisol (UFC) was elevated at 55 ug/24 hr (6-42 ug/24 hr). A repeat 24-hour UFC was again elevated at 265 ug/24 hr (6-42 ug/24 hr). Three late night salivary cortisol levels were also elevated at 0.231 ug/dL, 0.429 ug/dL and 0.19 ug/dL (n <0. 01-0. 09 ug/dL). Diagnosis of Cushing's syndrome was confirmed. ACTH level obtained was detectable at 70.1 pg/mL (7.2-63.3 pg/mL), suggestive of ACTH-dependent Cushing's syndrome. Pituitary MRI without contrast was obtained due to CKD. MRI reported no pituitary abnormalities. High dose DST was not performed due to concerns for aforementioned reduced dexamethasone clearance and due to lack of availability of CRH (corticotropin-releasing hormone), CRH stimulation testing was not done. She underwent inferior petrosal sinus sampling (IPSS) which showed central to peripheral ACTH ratio of 2.11 at baseline and ratios of 3.53, 3.45 and 3.32 at 5 minutes, 10 minutes and 15 minutes respectively after vasopressin stimulation, solidifying the diagnosis of Cushing's disease. Patient is now scheduled for an exploration of the sella via endoscopic endonasal approach. Conclusion This case highlights the limitations of biochemical tests and imaging modalities in the workup of hypercortisolism, notably in patients with underlying liver and kidney disease. The ordering physician should be mindful of the caveats associated with each biochemical testing. ACTH-dependent Cushing's syndrome can be difficult to diagnose properly in the setting of a negative pituitary MRI. IPSS, although an expensive and invasive test, has the best diagnostic accuracy. This case further demonstrates the importance of performing an IPSS to diagnose CD and distinguish from an ectopic source when imaging is non-diagnostic. Presentation: No date and time listed

ODP618 The profile of patients with ACTH-secreting pituitary adenomas and subclinical pituitary apoplexy

Abstract Background Subclinical hemorrhage or necrosis of pituitary adenomas (PAs), often defined as subclinical pituitary apoplexy (SPA), presents in up to 20% of all PAs and is more common in large prolactinomas. SPA in corticotropinomas in patients with Cushing disease (CD) is not common and the clinical and biochemical characteristics of patients with CD and SPA are not known. Subjects and methods: Pediatric patients with confirmed CD diagnosed between 2005-2021 with available MRI images before any surgical intervention were included in the study (n= 171). SPA diagnosis was based on MRI findings. Although MRI sequences and machines were not same for all patients and varied over time, the results were based on possible signs of hemorrhage on the available images, but smaller areas of bleeding or necrosis may have been missed. Statistical analyses were performed with Wilcoxon signed-rank test, chi-square or Fisher's exact test, and Cox proportional hazard as appropriate. Results are shown as median [Q1, Q3], count (percentage) and odds ratio (OR) (95% confidence intervals, 95%CI). Results Out of 171 patients, 12 patients (7%) were found to have imaging characteristics of possible hemorrhage or intratumor infarct. Patients with and without SPA were similar in age (median age: 12.5 years [10.6, 15.6] in SPA group vs 13.1 years [10.6, 15.4] in non-SPA group, p= 0.95) and gender distribution (n of female= 5 (41.7%) in SPA group vs 89 (56%) in non-SPA group, p= 0.51). Patients with SPA had shorter duration of disease as noted by changes in their growth chart parameters (median duration: 1. 0 year [1. 0, 2. 0] in SPA group vs 2.5 years [1.5, 3. 0] in non-SPA group, p= 0. 014). Morning and midnight cortisol and 24hour urinary cortisol levels were similar in both groups, but patients with SPA had higher levels of morning ACTH (60.8 pg/mL [43.5, 80.3]) compared to patients without SPA (39.8 pg/mL [28.5, 53.4], p=0. 017). Change of cortisol and ACTH levels during CRH stimulation test were similar between the two groups, but patients with SPA had lower suppression of cortisol after overnight high dose (8mg or weight-based equivalent) dexamethasone suppression test (58. 0% [-85.4, -49.7]) compared to patients without SPA (85.8 [-90.5, -76.8], p= 0. 035). Specifically, patients with SPA had lower chance of passing the threshold of 69% that it suggestive of pituitary source of hypercortisolemia compared to patients without SPA (OR: 0.18, 95%CI: 0. 03-0.95). The odds of remission after surgery and the risk of recurrence after initial remission did not differ based on the presence of SPA. Conclusion Patients with CD and sings of hemorrhage or necrosis in their tumor may present with different characteristics on their biochemical evaluation which should be considered during their diagnostic workup, especially in the setting of a discordant dexamethasone suppression test. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.