Dexamethasone Suppression Test Research Articles

FRI190 Catching A Chimera: A Case Of Suspected Glucocorticoid Remediable Aldosteronism

Abstract Disclosure: A. Khan: None. B. Ramchandani: None. H.B. Aftab: None. Introduction: Familial hyperaldosteronism type 1 (FH-I), also known as glucocorticoid remediable aldosteronism (GRA) is responsible for 1% of cases of primary aldosteronism (PA). It is caused by a chimeric fusion of the CYP11B2 and CYP11B1 genes resulting in ACTH-sensitive aldosterone production. We describe a case of suspected GRA and outline the diagnosis of this rare condition. Case. A 52-year-old female with history of type 2 diabetes mellitus, obesity, sleep apnea, SVT with ablation presented with long-standing history of resistant hypertension (HTN). HTN was diagnosed in her late twenties. She was previously trialed on eight different classes of antihypertensive medications excluding mineralocorticoid antagonists or potassium-sparing diuretics but HTN remained uncontrolled. Current regimen included hydralazine, nebivolol, and furosemide. Her sister had HTN diagnosed in her forties, a nephew with HTN diagnosed in his early twenties and mother with HTN with unclear age of diagnosis. Her systolic and diastolic BP averaged 150 mmHg and 90 mmHg, respectively, on both home and clinic monitoring. Physical examination was significant for mild cushingoid appearance. Screening tests for pheochromocytoma and hypercortisolism were normal. Plasma aldosterone concentration (PAC) was noted to be at 14.4 ng/dl (<39.2) with a plasma renin activity (PRA) of <0.6 ng/mL/h (2.9 - 10.8), with aldosterone to renin ratio (ARR) of 24. Repeat testing showed PAC of 15.1 ng/dl, PRA<0.6 ng/ml/hr (ARR: 25.1) with potassium of 3.3 mmol/L (3.5 -5.1). PAC levels remained unsuppressed above 10 ng/dL following four-hour, seated, 2 L IV saline suppression test with serum potassium of 3.5 mmol/L. CT abdomen showed normal appearance of the adrenal glands. Given early age of onset of HTN and strong family history, 3-day dexamethasone test was performed using 1 mg oral dexamethasone every 12 hours following which PAC suppressed to <1 ng/dl. Patient was started on spironolactone 25 mg twice daily and at the time of writing is awaiting genetic testing to confirm the diagnosis of GRA. Discussion: GRA is a rare subtype of PA which has an increased risk of cardiovascular and cerebrovascular complications. Our case highlights the importance of screening for GRA in patients who have a personal and/or family history of early onset HTN who have screened positive for PA. Genetic testing for chimeric CYP11B1/B2 gene is the confirmatory step of diagnosis, however, a 3-day dexamethasone suppression test can be used to screen for GRA with a high sensitivity. Elevated levels of urine 18-hydroxycortisol and 18-oxocortisol are also noted but these are not widely available tests. Treatment of GRA is with medical management only; since surgical intervention is not required; proper diagnosis can also save the patient from unnecessary and invasive tests such as adrenal vein sampling. Presentation: Friday, June 16, 2023

THU623 Leuprolide Treatment Of Mild Cortisol Secretion (MACS) Due To Primary Bilateral Macronodular Hyperplasia (PBMAH) Expressing Aberrant LH Receptors

Abstract Disclosure: L. Branchaud-Croisetière: None. M. St-Jean: Speaker; Self; Recordati rare disease, GlaxoSmithKline. Stock Owner; Self; Spruce bioscience. Cushing syndrome (CS) is caused by PBMAH in <2% of cases. Treatment is mostly surgical with unilateral or bilateral adrenalectomy, but in some cases, identification of aberrant receptors can allow the use of targeted medical therapies. Only a few cases of adrenal CS associated with an aberrant LH/hCG receptors that were treated with GnRH agonist were described. In December 2020, we saw a 72-year-old woman for bilateral adrenal nodules and an ACTH independent hypercortisolism. Her past medical history includes depression, insomnia, and osteoporosis with multiples fragility fractures. She was taking citalopram, calcium, vitamin D and alendronate was added in 2021. In the follow-up she developed dyslipidemia and hypertension. There were no sign of CS on physical examination. In 2020, a non-contrast thoracic scan was done and showed a right adrenal nodule of 3x1,4 cm and a left adrenal nodule of 3 x 2 cm both with densities < 10 HU and no atrophy of the adrenal limbs. In August 2021, a FDG PET scan showed an SUV of 3,4 on the right side and 3,7 on the left side. Morning cortisol after 1 mg DST (done twice) were 122 and 133 nmol/L (N <50). Aldosterone to renin ratio and 17-OHP were normal. In September 2020, a 4 mg IV dexamethasone suppression test was done and cortisol was 189 nmol/L at 9h am on day 2. Between 2020 and 2021, ACTH (3 values) were between 1,3-1,7 pmol/L (N 0-10 pmol/L) and DHEAS (3 values) between 1-1,6 (N 0,95-11,67 mol/L). 24h UFC (7 values) varied from 280,6 to 600,6 nmol/d (N 153-789 nmol/d). LNSC (8 values) were normal <2 to 3 nmol/L (N <5) except for one value at 6 nmol/L. In February 2022, systematic research for aberrant receptors was done. The cortisol have showed an ACTH-independent increased of 242% following 100 mcg IV of LHRH. There was also a significant ACTH-independent increase after 10 IU of vasopressin (+ 66%) and 10 mg of maxeran PO (+ 98%). There was no significant increase in cortisol after stimulation with glucagon 1mg IV and the upright posture test. We couldn’t obtain cortisol measures after stimulation with cortrosyn and the mixed-meal test because of issues with samples. Treatment with Leuprolide 3,75mg IM monthly was started in April 2022 and the dose was increased to 7,5 mg in August 2022 because of partial response observed initially. There was a response with an increase in ACTH from <1,1 to 2,6 pmol/L until December 2022. Since January 2023, ACTH (3 values) have decreased between 1,8-2 pmol/L. In January 2023, the morning cortisol after 1 mg DST was 104 nmol/L and 24h UFC were 161 and 306 nmol/d and two LNSC were <2 nmol/L. However, with the recent decrease in ACTH, we suspect an escape to Leuprolide. In summary, this is a rare case of MACS due to PBMAH expressing aberrant LH receptors with initial response to Leuprolide. We are waiting for the results of genetic testing. The patient could eventually benefit from a left unilateral adrenalectomy if escape from medical treatment is confirmed. Presentation: Thursday, June 15, 2023

THU108 Pituitary Carcinoma Diagnosed After Ten Years Of Smoldering Ectopic Nasopharyngeal Cushing’s

Abstract Disclosure: L. Carafone: None. E. Vates: None. M. Johnson: None. I. Shafiq: None. Introduction: Pituitary carcinomas are rare and typically carry a poor prognosis. Diagnosis of pituitary carcinoma is made when there is metastasis to one or more sites distant from the pituitary, including craniospinal or systemic metastases. Clinical Case: A 54-year-old man presented to the endocrine clinic in 2011 with recurrent urinary tract infections, thoracic compression fractures, uncontrolled hypertension with hypokalemia, and weight gain. Examination revealed facial plethora, supraclavicular fat pad, central obesity, multiple ecchymoses, proximal muscle weakness and muscle atrophy of the upper and lower extremities. Workup demonstrated abnormal 1 mg overnight dexamethasone suppression test (cortisol after 1 mg dexamethasone 25.7 mcg/dL, n≤1.8 mcg/dL), elevated salivary cortisol (4340 and 2950 ng/dL, n≤99 ng/dL), elevated 24 hr urinary-free cortisol (271.7 mcg/24hr, n≤60 mcg/24 hr), and elevated ACTH (240 pg/mL, n≤46 pg/mL). MRI brain showed a large, lobulated mass in the sphenoid sinus adjacent to the inferior left lateral aspect of the pituitary fossa. He underwent surgical resection of the mass and pathology was consistent with pituitary adenoma, corticotroph cell type. Following surgery, laboratory studies showed normal salivary cortisol (<50 ng/dL, n≤99 ng/dL) and 24 hr urinary-free cortisol (22.4 mcg/24hr, n≤60 mcg/24 hr). After two years of sustained remission, he experienced local recurrence for which he underwent repeat surgery with subsequent remission. One year later, this was again followed by recurrence for which he was treated with intensity-modulated radiation therapy and medical therapies including cabergoline, ketoconazole and eventually metyrapone. Six years after the second surgery, MRI showed increasing heterogeneous enhancement at the postoperative site, and he underwent a third surgery with tumor resection and the same pathology results as the initial resection. He was subsequently treated with fractionated proton therapy. He continued to require metyrapone to manage hypercortisolism despite reassuring serial MRI scans. A right neck mass was palpated in 2022 and CT demonstrated a right level 2b lymph node measuring 2.3 x 1.8 x 2.3 cm. FNA revealed neoplastic cells and he underwent right neck dissection with excision of the lymph node. Pathology was consistent with pituitary tumor, corticotroph cell type. Given metastasis of the pituitary tumor to a cervical lymph node, a diagnosis of pituitary carcinoma was made. Conclusion: The time course in pituitary carcinoma is highly variable from the initial diagnosis of the pituitary tumor to the diagnosis of metastatic disease. In this case, the diagnosis of pituitary carcinoma was made nearly one decade after the initial identification of a pituitary tumor. Metastatic disease should be considered in aggressive pituitary tumors when biochemical and radiologic findings are discordant. Presentation: Thursday, June 15, 2023

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

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

FRI110 Prevalence Of Thromboembolic Events In 51 Patients Treated For Cushing’s Disease With Pituitary Surgery At University Hospital Of Wales Over A 15-year Period

Abstract Disclosure: R. Suresh John: None. J. Witczak: None. A. Rees: None. C. Hayhurst: None. A. Lansdown: None. Background: Hypercortisolism is associated with a hypercoagulable state and both arterial and venous thromboembolic events (TE). Aim: To determine the prevalence of TE in our cohort of patients with Cushing’s Disease (CD) undergoing pituitary surgery. Methods: Patients with a clinical & biochemical diagnosis of Cushing’s Disease who had undergone pituitary surgery at University Hospital of Wales between 2007-2022 were identified from a database. Clinical, biochemical and radiological data were studied from the time of diagnosis to the period of 6 months following pituitary surgery. Results: 51 patients were identified: 15 Male, 36 Female, median age 46 (11-77)y. Total group: 5/51 (9.8%) patients had a TE. Pre-surgery: 2/51 (3.9%) had a TE (Deep vein thrombosis (DVT) = 1; Aortic thrombus = 1), both at time of diagnosis. Mean 24-h Urinary Free Cortisol (UFC) was 1126nmol in TE group vs 662nmol in non-TE group (p=0.64) and mean cortisol after overnight dexamethasone suppression test (ODST) was 251nmol/L in the TE group vs 327nmol/L in the non-TE group (p=0.64). Post-surgery: All patients received standard thrombo-prophylaxis with low-molecular weight heparin peri-operatively. 3/51 (5.9%) had TE within 6-months post-surgery (DVT=1, pulmonary embolism (PE)=1, cavernous sinus thrombosis=1), all occurred within 21 days of surgery and none had other risk factors for VTE. Mean time from diagnosis to surgery was 187 days in TE group vs 127 in non-TE group (p=0.43). At diagnosis, mean 24-h UFC was 560nmol in TE group vs 699nmol in non-TE group (p=0.82), mean cortisol after ODST was 420nmol/L in TE group vs 321nmol/L in non-TE group (p=0.46). Mean post-op cortisol was 221nmol/L in TE group vs 257nmol/L in no TE group (p=0.85). No TE events occurred between 22 days-6 months post-surgery. Conclusion: In our cohort, 9.8% patients had a TE event. 3.9% occurred pre-surgery and 5.9% in the early post-operative period, which concurs with data from other studies. There was no correlation with level of hypercortisolism and TE events in our group. Timing, dose & duration of prophylactic anticoagulation in CD patients needs careful consideration. Presentation: Friday, June 16, 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

FRI132 Aldosterone Secretory Capacity Immediately After Surgery Predicts Biochemical Outcome 1 Year After Surgery In Primary Aldosteronism

Abstract Disclosure: Y. Ishida: None. K. Nakai: None. Y. Tsurutani: None. K. Watanabe: None. J. Saito: None. T. Nishikawa: None. Background and Objective: In primary aldosteronism (PA), the biochemical outcome of the Primary Aldosteronism Surgical Outcome (PASO) study is used to assess aldosterone hypersecretion six months to one year after surgery. However, there are few reports on whether outcomes can be predicted in the early postoperative period. This retrospective study evaluated aldosterone secretory capacity immediately after surgery using the adrenocorticotropin (ACTH) stimulation test (AST) and oral salt loading test (OST). We hypothesized that these tests would predict biochemical outcomes one year after surgery. Methods: This study assessed 282 patients with PA who underwent adrenalectomy in our hospital between 2008 and 2020 and determined biochemical PASO outcomes 1 year after surgery. Patients with serum cortisol levels ≥ 5 μg/dL after a 1 mg overnight dexamethasone suppression test (n = 9) were excluded. Patients were divided into biochemical complete success (COM) and incomplete (partial + absent) success (INC) groups. AST and OST were performed within 15 days of surgery. The relationships between various AST and OST values and outcomes were analyzed. Results: Two hundred and twenty patients and 53 patients were classified into the COM and INC groups, respectively. The INC group had significantly higher plasma aldosterone concentration (PAC) and higher PAC/cortisol ratio (A/C) at baseline, 30 min, and 60 min after ACTH loading than the COM group. The INC group showed a significantly lower level of plasma renin activity. In the OST, the INC group had a significantly higher 24-hour urine aldosterone level. Of these values, A/C at 30 minutes after ACTH loading (area under the curve (AUC) = 0.77) and 24-hour urine aldosterone (AUC = 0.78) were relatively superior predictors of the outcome, with higher AUCs than plasma renin activity (AUC = 0.63), baseline PAC (AUC = 0.71), baseline ARR (AUC = 0.72), and baseline A/C (AUC = 0.70). A/C at 30 minutes after ACTH loading had 83% sensitivity and 62% specificity when 6.03 was set as the cutoff; 24-hour urine aldosterone had 84% sensitivity and 61% specificity when 2.6 was set as the cutoff. Conclusion: AST and OST immediately after surgery are useful for predicting biochemical outcomes 1 year after surgery in patients with PA. Presentation: Friday, June 16, 2023

FRI261 A Case Of Cushing Syndrome And Hyperandrogenism Secondary To An Adrenal Cortical Oncocytoma

Abstract Disclosure: E. Hall: None. S. Gupta: None. J. Lee: None. Background: Adrenal cortical oncocytomas are rare neoplasms that are often non-functional, but there have been case reports of associated hypercortisolism, hyperandrogenism, and in even rarer cases, multiple hormonal excesses. Clinical Case: A 30 year old woman with history of hypertension, prediabetes and obesity presented with 3 years of oligomenorrhea, hirsutism, weight gain, and voice deepening. She did not take any medications and had no family history of endocrine diseases. Labs revealed hyperandrogenism: elevated total testosterone of 390 ng/dL and 435 ng/dL (nl 6-82), suppressed FSH of 0.2 mIU/mL (nl 1.7-21.5) and LH of <0.1 mIU/mL (nl 1.0-95.6), normal DHEA-S of 290 ug/dL (nl 98.8-340). Morning 17-hydroxyprogesterone was elevated to 944 ng/dL and increased to 1031 ng/dL (nl 23-431) on ACTH stimulation test, which did not meet diagnostic criteria for non-classical congenital adrenal hyperplasia. Also, genetic testing for CYP21A2 gene mutations was negative. Pelvic ultrasound was unremarkable. CT of the adrenal glands showed a 4.6 x 3.8 x 4.4 cm mildly heterogeneous left adrenal mass that measured 35 HU on non-contrast images with absolute washout of 50% and relative washout of 31%. The mass was concerning for malignancy based on HU >20, size >4cm, and 50% contrast washout (borderline). Overnight 1mg dexamethasone suppression test showed non-suppressed morning cortisol of 7.1 ug/dL (nl <1.8), with dexamethasone level of 246 ng/dL (nl 180-550) and ACTH of <5 pg/ml (nl 6-50). Twenty four hour urinary free cortisol level was slightly elevated to 52.3 mcg/24h (nl 4-50). Plasma metanephrines and aldosterone/renin ratio were normal. The patient underwent left laparoscopic adrenalectomy without complications. Pathology was consistent with adrenal cortical oncocytoma. Post-operatively, morning cortisol was <0.3 ug/dL, so she was started on hydrocortisone replacement twice daily but was tapered off within three months. Three weeks after surgery, total testosterone was <8 ng/dL. Two months after surgery, her menstrual cycles resumed. Fifteen months after surgery, she had regular menstrual cycles, 20 lb weight loss, resolution of hirsutism, hypertension and prediabetes. Conclusions: Adrenal cortical oncocytomas are rare tumors of the adrenal glands that should be considered in the differential for large adrenal tumors that appear suspicious for malignancy on imaging. They may or may not be functional, and in this case, the tumor secreted both androgens and cortisol. Although androgen-secreting tumors are frequently malignant, such as adrenocortical carcinomas, androgen-secreting oncocytomas are generally considered benign. However, there have been rare reports of malignant oncocytomas and oncocytomas of uncertain malignant potential. Presentation: Friday, June 16, 2023

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

THU618 Adrenal Cell Carcinoma Presenting With Post-menopausal Bleeding And IGF-2 Induced Hypoglycaemia

Abstract Disclosure: E.M. Lonergan: None. L.J. Tan: None. E. Ali: None. C.M. Joyce: None. N. Conlon: None. A. O'Sullivan: None. D.J. O'Halloran: None. Background: Non-islet cell tumour hypoglycaemia (NICTH) as a result of IGF-2 secretion is rare with a few case reports associated with adrenal tumours. Clinical Case: We present the case of a 59-year-old female initially presenting to gynaecology services with post-menopausal bleeding due to endometrial hyperplasia. Serum testosterone, oestradiol and adrenal androgens were found to be elevated and LH and FSH suppressed. A subsequent CT adrenals demonstrated a 12.8 x 13.2 x 10.6cm left adrenal mass and she failed a 1mg overnight dexamethasone suppression test. In the interim, while undergoing evaluation, the patient presented to A+E Department with point-of-care confirmed hypoglycaemia with a capillary blood glucose of 1.6mmol/L and neuroglycopaenic symptoms. There was no history of diabetes mellitus, prolonged fasting, access to sulphonylureas or insulin. During a supervised fast, symptomatic hypoglycaemia occurred within 5 hours at 2.0mmol/L fulfilling Whipple’s triad. Results of samples taken during hypoglycaemia revealed an elevated IGF-2 : IGF-1 ratio of 60.7 (normal <10) with a low paired C-peptide, insulin and pro-insulin, consistent with a suspected IGF-2-secreting tumour. Hypoglycaemia was successfully managed with low glycaemic index foods and clinical nutrition input. Radical surgical excision was undertaken including left adrenalectomy, nephrectomy, partial pancreatectomy and splenectomy. Post-operative pathology revealed an adrenocortical carcinoma (ACC) measuring 16.4cm in maximum dimension; Ki67 12%; Weiss score 5; lymph nodes negative. Tissue has been stained for IGF-2-IR. Post-operative IGF-2 : IGF-1 ratio normalised to 3.4. The patient is under active follow up with 3-monthly surveillance CT-TAP and has declined Mitotane therapy at present. Conclusion: This is a rare case of ACC secreting multiple hormones, resulting in post-menopausal bleeding and IGF-2 mediated hypoglycaemia. Presentation: Thursday, June 15, 2023

SAT435 The Quest Of Elevated Dhea-s: Is It A Tumor Or Is It Ashwagandha?

Abstract Disclosure: S. Patel: None. O.A. Aluko: None. T. Gallagher: None. Introduction: Ashwagandha (Withania somnifera) is a popular Indian ayurvedic herb that is readily available over the counter in the United States. Ashwagandha is known to increase in testosterone and DHEA-s levels in men. We hereby report a case of a female who had elevated DHEA-s due to intake of Ashwagandha. Case Report: A 27 year old female with past medical history of vitamin D deficiency, anxiety, X linked heterozygous adrenoleukodystrophy presents to establish care with endocrinology with complaints of unintentional weight gain of about 25lbs, inability to lose weight with lifestyle modifications, dizziness, light headedness and occasional salt cravings. Medication history is significant for using ashwagandha 600mg twice daily, probiotic-10. Vitals were BP 102/70 mmHg, HR 108 beats/min, RR 18 breaths/min, SpO2 98%, BMI 31.28kg/m2. Laboratory evaluation showed AM cortisol of 21.6 ug/dL H (6.2-19.4 ug/dL), ACTH 6.2 pg/mL (7.2-63.3 pg/mL), DHEA-s >1000 ug/dL H (84.8-378 ug/dL), TSH 1.39 IU/mL (0.45-4.5 IU/mL), free t4 2.39 ng/dL H (0.82-1.77 ng/dL), IGF-1 252 ng/mL (91-308 ng/mL), 1mg dexamethasone suppression test resulted AM cortisol of 1.5 ug/dL (6.2-19.4 ug/dL). Subsequently, further work up revealed 17 hydroxyprogesterone of 158 ng/dL (luteal phase 35-290 ng/dL), total testosterone 176 ng/dL H (13-71 ng/dL), free testosterone 1.8 pg/mL (0-4.2 pg/mL), androstenedione 113 ng/dL (41-262 ng/dL), LH 2.5 mIU/mL (follicular phase 2.0-12.6 mIU/mL), FSH, 3.6 mIU/mL (follicular phase3.5-12.5 mIU/mL). Patient underwent CT abdomen and pelvis with and without contrast which showed normal adrenal glands, prominent right ovary and US Pelvis was recommended. Pelvic ultrasound showed normal ovaries. MRI pelvis with and without contrast revealed 1cm right ovarian hemorrhagic cyst. Patient was subsequently asked to stop all over the counter supplement medications and a DHEA-s level was checked about 6 weeks and was markedly reduced to 435 ug/dL. TSH and free t4 improved to 0.789 IU/mL and free t4 1.43 ng/dL respectively. Conclusion: This case highlights that over the counter, readily available supplements that are marketed for reducing stress may cause remarkable alteration of natural physiology. Ashwagandha’s use in men have been known to cause elevations in DHEA-s in men and this case highlights that Ashwagandha’s use in women can also cause elevation in DHEA-s and how a simple intervention of eliminating Ashwagandha can improve DHEA-s levels Presentation: Saturday, June 17, 2023

FRI128 Hiding In Plain Sight: Late Diagnosis Of Primary Hyperaldosteronism In Patient With Atypical Presentation

Abstract Disclosure: R.A. Zielinski: None. A. Syeda: None. B. Esayag-Tendler: None. Background: Primary hyperaldosteronism (PHA) can go undiagnosed in patients with primary hypertension without hypokalemia and increased plasma aldosterone concentration (PAC). Case: The patient is a 72-year-old male with a history of hypertension (HTN) diagnosed at age 55 who presented to the endocrinology clinic for further evaluation. He was asymptomatic. His antihypertensive regimen included atenolol 25 mg daily and amlodipine-benazepril 10-40 mg daily. Blood pressure (BP) was well-controlled with a goal BP under 130/80 mm Hg. Physical exam was without AV nicking in a limited retina exam, no abdominal tenderness, and no peripheral edema. Family history is notable for HTN in his father and HTN complicated by stroke in a sister and a brother, all diagnosed at an older age. Labs done 5 years prior showed potassium (K) of 4.3 mmol/L [3.6 - 5.1 mmol/L], PAC of 3.2 ng/dl [upright 4.0 - 31.0 ng/dl], and plasma renin activity (PRA) of 0.1 ng/ml/hr [upright 0.5-4.0 ng/ml/hr]. More recent labs showed K of 3.8 mmol/L, PAC of 21.5 ng/dl and PRA of 0.3 ng/ml/hr. Repeat labs 6 months later showed K of 3.4 mmol/L, PAC of 15 ng/dL and PRA of 0.2 ng/mL/hr. A 3-day dexamethasone suppression test was performed to exclude familial hyperaldosteronism or glucocorticoid remediable aldosteronism. Following the test, K was 3.6 mmol/L, PAC was 11.3 ng/dl, and cortisol was undetectable. CT abdomen showed bilateral nodular thickening of the adrenal glands without a distinct adenoma. Adrenal venous sampling was done before and after ACTH stimulation. Prior to ACTH stimulation, the mean ratio of the dominant adrenal aldosterone concentration corrected with cortisol from left to right was 1.32. Following ACTH stimulation, the ratio was 2.79. A ratio greater than 4 is consistent with a good outcome after adrenalectomy. Hence, it was decided to pursue medical management. The cause of our patient’s primary hyperaldosteronism is likely due to bilateral idiopathic hyperplasia. He was started on eplerenone 25 mg twice daily and salt restriction with a goal of increasing the PRA above 1 ng/ml/hr. Discussion and Conclusion: It was initially thought that PHA represents 1% of all patients with primary HTN. However, more recent studies indicate that the prevalence is significantly higher. Additionally, the PAC in patients with PHA can fluctuate and patients can present with normokalemia, making the diagnosis more difficult to establish. It is an important diagnosis to establish and treat appropriately because there is a higher risk of cardiovascular morbidity and mortality in patients with PHA compared to patients with primary HTN. Presentation: Friday, June 16, 2023

FRI250 Dual Aldosterone And Cortisol Secreting Adrenal Cortical Carcinoma: Pre- And Perioperative Evaluation And Management

Abstract Disclosure: R. Rosenberg: None. M.R. Clay: None. C. Raeburn: None. M.E. Wierman: None. Representing 0.3% of all adrenal tumors, adrenal cortical carcinoma (ACC) is a rare and understudied disease. It is estimated that 60% of patients with ACC present with hormone excess syndromes, while the remainder present incidentally or with compressive symptoms from tumor invasion. ACC presentation with a combination of hormonal excess syndromes from different adrenal zones is rare and only described previously in four case reports. We present a case of dual-secreting ACC with hyperaldosteronism and cortisol excess. The previously healthy patient was noted to have new onset hypertension and hypokalemia during a primary care visit. On hormonal evaluation, he was found to have evidence of hyperaldosteronism and ACTH-independent cortisol excess (aldosterone 28.2ng/dL, plasma renin activity 0.1ng/mL/hr, and overnight 1mg dexamethasone suppression test cortisol of 13ug/dL). Imaging revealed a 2.7 x 3.1 x 3.5cm left adrenal mass suggestive of an adenoma. He underwent laparoscopic adrenalectomy and required glucocorticoid replacement for adrenal insufficiency post-operatively. Pathologic review of the gross specimen showed a sizable neoplasm measuring 6.5 x 3.0 x 2.5 cm, much larger than on CT imaging. Microscopic review showed stage T2N0M0 ACC with modified Weiss score of 6 and 68 mitoses per 50 hpf, indicative of aggressive disease. The patient’s hypokalemia resolved post-operatively, and glucocorticoids were tapered within a month. The mechanism of dual aldosterone/cortisol secretion is hypothesized to be due to overlap between genes coding for 11β-hydroxylase and aldosterone synthase, resulting in a chimeric gene with increased secretion of both enzymes, and, therefore, both hormones. Though dual secretion is rare, this case report stresses the importance of screening for cortisol excess, and hyperaldosteronism in the correct clinical setting, in patients with adrenal masses detected on imaging. A complete biochemical hormone evaluation should be performed regardless of the discovery of other hormone secreting syndromes, ideally preoperatively with a multidisciplinary team including endocrinology. The medical team should continue to bear in mind that the existence of one hypersecretory syndrome does not rule out the presence of a second or third, and hormonal excess syndromes may affect patient outcomes peri- and postoperatively. Presentation: Friday, June 16, 2023

FRI165 BIUXX

Abstract Disclosure: A. Haider: None. M. Sadiq: None. J. Shakesprere: None. G.K. Sidhu: None. Background: Syndrome of inappropriate anti-diuretic hormone (ADH) secretion (SIADH) is characterized by inappropriate ADH secretion causing hyponatremia due to free water retention. Plasma volume expansion leads to renin inhibition by the renal juxtaglomerular complex, resulting in decreased aldosterone secretion with inappropriate natriuresis. However, when autonomous renin-independent aldosterone production is present, natriuresis can be suppressed, causing normal sodium levels despite inappropriately high ADH. Case: 58-year-old male with history of resistant hypertension & bipolar disorder on Oxcarbazepine presented with dizziness, lightheadedness, and severe hypokalemia (2.7 mmol/L, n 3.5-5.0 mmol/L). CT Adrenals revealed an incidental 1.2 cm left-sided adrenal adenoma [HU 6, 40% washout]. Serum aldosterone and plasma renin activity (PRA) were obtained in the supine position via LC/MS/MS assay; concurrent serum K+ was 3.4 mmol/L. Spironolactone was started and titrated to 50 mg BID for blood pressure control due to high suspicion of hyperaldosteronism. The patient was continued on Oxcarbazepine 900 mg BID. A 3 mg Dexamethasone suppression test showed suppressed morning cortisol (1.0 μg/dL, n <1.8 μg/dL). Urine catecholamines and metanephrines were obtained and normal. 3-4 days after starting Spironolactone, the patient developed severe subacute hyponatremia (119 mmol/L, n 135-145 mmol/L) from an admission level of 137 mmol/L. No active renal or GI losses, diuretic use, or untreated hypothyroidism were documented. Serum osmolality was low (262 mOsm/kg, n 275-295 mOsm/kg) with urine osmolality of 357 mOsm/kg (n 50-1200 mOsm/kg) and urine sodium of 92 mEq/L (n >20 mEq/L). Serum aldosterone and PRA levels returned with normal aldosterone (7 ng/dL, n 2-9 ng/dL) but suppressed PRA (0.07 ng/mL/hr, n 0.7-3.3 ng/mL/hr) and elevated aldosterone-renin ratio (100 ng/dL per ng/mL/hr, n ≤ 30 ng/dL per ng/mL/hr). As renin was very low despite mild hypokalemia and active Losartan use at the time of testing, these findings were suggestive of primary aldosteronism. In-hospital 24-hour urine aldosterone collection showed urine aldosterone of 29.3 mcg/24 h (n 5-19 mcg/24 h) with urine sodium of 93 mmol/ 24 h (n 40-220 mmol/24 h). Oxcarbazepine was subsequently tapered off; Spironolactone was intermittently held until complete discontinuation. Fluid restriction and oral salt repletion were started and the patient’s sodium ultimately normalized. Outpatient saline suppression testing and adrenal vein sampling were scheduled. Conclusion: Oxcarbazepine was likely causing high ADH release but co-occurring untreated hyperaldosteronism inhibited natriuresis. Use of Spironolactone unmasked natriuresis by blocking aldosterone activity on the intercalated cells of the renal nephron. Stopping Oxcarbazepine ultimately resulted in hyponatremia resolution. Presentation Date: Friday, June 16, 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

SAT341 Even Mild Cortisol Excess Is Unsafe: Use of Mifepristone In Mild Autonomous Cortisol Secretion

Abstract Disclosure: A. Figueroa Cruz: None. M. Torres Torres: None. A.M. Santiago Carrion: None. Y. Ortiz Torres: None. A. Aponte Velez: None. I.A. Rivera Nazario: None. M.M. Mangual Garcia: None. Cortisol is released from the adrenal glands and works through the glucocorticoid receptor to mediate stress, metabolism, immune and inflammatory processes. Is known as our stress hormone and have manifestations in almost every system as its receptor is present in nearly every tissue. Therefore, even mild cortisol overproduction can lead to serious complications. Mild autonomous cortisol secretion (MACS) is prevalent in nearly half of adults with benign adrenal tumors and can increase the risk of hypertension and type 2 diabetes. It may go undiagnosed if not evaluated properly. There is controversial data on how we should treat this entity. Herein we present a case of MACS denoting the importance of its detection and management. 55yo female comes for evaluation after been found with bilateral adrenal masses in an MRI perform for back pain. Patient with PMHx of diabetes, hypertension, dyslipidemia, and osteopenia refers worsening hyperglycemia and blood pressure. She was previously well controlled with less medications and has needed frequent changes in therapy without achieving treatment goals. Physical exam was negative for discriminatory findings of Cushing’s syndrome. However, she recently noted increase in weight after starting sulfonylurea and insulin for blood glucose control. A CT scan confirmed the presence of adrenal masses measuring 2.5x2.9cm on the left and 2.0x2.4cm on the right with HU 10 and washout 82%. MACS was confirmed with a post Dexamethasone Suppression Test cortisol level of 10.8 ug/dL. Normal cortisol levels were found on Late Nigh Salivary Test done twice. In view of these findings, we can argue about how mild cortisol hypersecretion can be when patient A1c is 10.7% despite multiple therapies for blood glucose and uncontrolled blood pressure despite 3 medications in maximal doses. Considering surgery in this setting is controversial due to bilateral masses with minimal size difference. Since hypercortisolism needed to be addressed it was decided to start medical therapy with the glucocorticoid antagonist Mifepristone, although its use for MACS is considered off label. After mifepristone therapy A1c decreased to 8.0%, prandial insulin was discontinued, and basal insulin decreased. Current regimen for hypertension includes spironolactone to avoid hypokalemia related to mineralocorticoid stimulation of cortisol with mifepristone therapy. Patient symptoms and quality of life has improved significantly. Benign adrenal incidentalomas can cause MACS in up to 35% of cases. Untreated hypercortisolism can lead to complications, and increased mortality risk even when is “mild”. We just need the right amount of cortisol, and minimal excess need to be identified, for which high level of suspicion is needed and more education on this entity and its available treatment options is essential. Presentation: Saturday, June 17, 2023

FRI205 Splenic Infarct: A Rare Presentation Of Cushing Syndrome

Abstract Disclosure: G. Virella: None. Splenic Infarct: A Rare Presentation of Cushing Syndrome Geover, Virella M.D. 1,2, Carlos Santiago Botero Suarez, M.D.1,2, Alfredo Palomino Abella, M.D. 1,2, Mustafa Kinaan, M.D. 1,2 1) University of Central Florida HCA Healthcare GME, Greater Orlando, Florida2) Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida Disclaimer: This research was supported (in whole or in part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.Introduction Cushing’s syndrome (CS) is associated with a hypercoagulable state leading to increased incidence of thromboembolic events. The mechanism behind this phenomenon is due to an imbalance between activity of pro- and anticoagulant pathways. We report a case of newly diagnosed CS in a patient presenting with acute splenic and inferior vena cava (IVC) infarcts. Case Description A 59-year-old woman with no significant medical history presents with acute left upper quadrant pain. She denied other symptoms. Physical examination was remarkable for tachycardia, left upper quadrant tenderness, and centripetal adiposity with BMI of 19. Labs showed marked leukocytosis (WBC 26 x 109/L) and thrombocytopenia (platelet 96,000 cells/uL). She was also found to be diabetic (HgA1C 12.5%). Abdominal CT imaging showed a wedge-shaped 4.3 x 3.1 x 2.3 cm splenic infarction, peri-splenic abscess, and thrombosis of the left renal and gonadal veins extending into the IVC. Additionally, there was a left adrenal incidentaloma measuring 4.5 x 3.8 x 2.9 cm. MRI of the left adrenal gland was consistent with an adenoma. The right adrenal gland was unremarkable. Screening for pheochromocytoma and hyperaldosteronism was normal. A morning serum cortisol was 33.4 mcg/dL, and ACTH level of < 1.5 pg/mL. An overnight 1-mg dexamethasone suppression test revealed post-dexamethasone cortisol of 4.58 mcg/dL. These findings were consistent with Cushing syndrome secondary to adrenal cause. The patient was initially treated with heparin infusion and underwent a successful thrombectomy of the IVC and gonadal vein. She later underwent a successful laparoscopic left adrenalectomy and splenectomy. Pathology reports confirmed an adrenocortical adenoma. A random post-surgical cortisol was 22.8. The patient had an uneventful postoperative course and was discharged home with outpatient endocrine follow-up planned to evaluate for hypercortisolism resolution and management of diabetes. Conclusion Cushing Syndrome patients have been shown to have an almost 18-fold higher rate of venous thromboembolism (VTE). This is an often-overlooked complication of hypercortisolism. The pathogenesis is not fully understood but is believed to be related to shortening of activated partial thromboplastin time (aPTT), increased clot lysis time, and glucocorticoid-induced increase in procoagulant factors such as fibrinogen, von Willebrand factor, and factor VIII. Our case will closely demonstrate the link between hypercortisolism and hypercoagulability. Presentation: Friday, June 16, 2023

FRI171 Can 11-Dehydrodexamethasone Improve The Salivary Dexamethasone Suppression Test?

Abstract Disclosure: D. Marshall: None. B.G. Issa: None. B.G. Keevil: None. Background: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended as a first-line test for the investigation of Cushing Syndrome. Measurement of dexamethasone alongside cortisol in a 9am serum sample has been credited with improving diagnostic sensitivity of the test. Previous studies have also looked at the utility of salivary dexamethasone and have observed poor correlation with serum dexamethasone. Herein we introduce the concept of measuring 11-dehydrodexamethasone: a dexamethasone metabolite produced in the salivary duct through metabolism with 11β-hydroxysteroid dehydrogenase type 2 (11Β-HSD2). Methods: Paired 9am serum and saliva samples (n=44) were collected post ONDST. The saliva samples were analysed utilising a novel in-house LC-MS/MS assay which measured cortisol, cortisone, dexamethasone and 11-dehydrodexamethasone. Serum cortisol and dexamethasone had previously been analysed separately by LC-MS/MS. Results were compared and correlations were assessed using Pearson regression. Results: Serum and salivary dexamethasone exhibited poor correlation (R-squared = 0.16), supporting what has been observed previously. Salivary dexamethasone and 11-dehydrodexamethasone also showed poor correlation (R-squared = 0.19). Serum dexamethasone and salivary 11-dehydrodexamethasone yielded a positive correlation with an R-squared of 0.65. However, at higher concentrations the correlation appeared non-linear. Conclusion: Correlation of serum dexamethasone with 11-dehydrodexamethasone is a novel finding, which to the author’s knowledge, has not been previously established/investigated. It is hypothesized that the non-linear correlation might be due to saturation kinetics of the enzyme 11Β-HSD2 in the salivary duct, a similar relationship was observed when comparison of salivary cortisol and cortisone was assessed. The development of this LC-MS/MS assay for salivary measurement of 11-dehydrodexamethasone opens the possibility for a fully remote DST, whereby patients could administer the drug and take a 9am saliva sample. Further sample comparisons are required to develop a 11-dehydrodexamethasone cut-off which equates to a serum dexamethasone concentration of 3.3 nmol/L. Presentation: Friday, June 16, 2023

THU010 A Case Of Cushing's Disease Due To T-pit Positive, ACTH Negative Aggressive Corticotroph Pituitary Adenoma

Abstract Disclosure: C. Gopinath: None. P. Pagadala: None. C. Choudhary: None. D.R. Tilden: None. Introduction: The 2017 WHO classification of Pituitary Adenomas utilizes pituitary transcription factors for its classification system. It can be helpful in identifying cell lineages in adenomas without expression of pituitary hormones. We describe a case of recurrent Cushing’s disease due to an ACTH negative, elevated Ki-67, TPIT positive aggressive corticotroph adenoma. Case report: A 54-year-old male presented with c/o diplopia, fatigue, decreased sexual drive. MRI brain showed a 2.4 x 1.4 x 1.6 cm sellar mass with suprasellar extension, displacement of the optic chiasm, extension into the left cavernous sinus. Hormonal work up showed evidence of central hypothyroidism (free T4- 04 ng/dl(0.6-1.6 NG/dl), TSH- 0.08 MCU/ml(0.35-5.00 MCU/ML) low testosterone (76 ng/dL(270-1070 NG/DL)),random cortisol of 20.1mcg/dL( 5.0-20.0 MCG/DL), ACTH- 136 pg/ml(7-63 pg/ml). Patient underwent transsphenoidal surgery (TSS). Pathology showed a pituitary adenoma of 1.5 cm with conspicuous mitoses and elevated Ki67 proliferation index (range- 15-35%). Immunohistochemistry was positive for prolactin; synaptophysin and negative for ACTH, GH, FSH, LH, TSH. Transcription factors for T-pit, Pit-1 and SF-1 were not assessed. Diagnosis of non-functioning adenoma was made. Repeat MRI showed residual tumor and due to elevated Ki-67, radiation therapy was recommended which was received at an outside hospital. 2.5 years later he was readmitted with profound hypokalemia, metabolic alkalosis and altered mental status. He appeared Cushingoid with facial plethora, moon facies, dorsocervical fat pad and violaceous striae on the abdomen. Dexamethasone suppression testing revealed elevated cortisol of 26.7 mcg/dl, AM cortisol -44.7mcg/dl (6.7-22.6mcg/dl),ACTH-280 pg/mL(7-63 pg/mL),24 hour urine free cortisol was elevated 2065 mcg/24 hour(3.5-45 mcg/24 hr). Given initial negative ACTH staining on the macroadenoma, there was concern for ectopic ACTH given acute presentation and absence of growth on the MRI compared to post radiation scans. IPSS was pursued which showed central ACTH source. Given stable size of residual tissue post radiation and location on MRI neurosurgery recommended against repeat surgery at this time. Patient was started on medical treatment for hypercortisolism with ketoconazole but had elevated liver enzymes limiting dose increase. Clinically patient continued to decline. Given significantly elevated cortisol with high risk of infectious and thrombotic events, poor short term outcomes decision was made for b/l adrenalectomy which he underwent successfully. Immunostains were ordered on the original adenoma resected and showed strong positivity for TPIT. Conclusion: Immunohistochemistry is an important step to aid classification of pituitary adenoma. Management of aggressive corticotroph adenoma with high ki-67 index can be a therapeutic challenge. Presentation: Thursday, June 15, 2023

THU603 Bone Fragility In Mild Autonomous Cortisol Secretion: A Cross-Sectional Cohort Study

Abstract Disclosure: C.D. Zhang: None. S. Singh: None. J. Saini: None. M. Suresh: None. K. Thangamuthu: None. R. Nathani: None. A.L. Ebbehøj: None. V. Fell: None. S.J. Achenbach: None. E.J. Atkinson: None. S. Khosla: None. I. Bancos: None. Background: Patients with mild autonomous cortisol secretion (MACS) have higher rates of fractures compared to patients with non-functioning adrenal nodules, but bone mass is typically only modestly reduced. We hypothesized that chronic exposure to mild levels of cortisol excess may lead to a deterioration in bone quality. Objective: To characterize the effect of MACS on bone metabolism and bone microarchitecture, as measured by high-resolution peripheral quantitative computed tomography (HR-pQCT). Methods: In this cross-sectional single-center study, patients with MACS were matched by age, sex, and gonadal status to referent subjects without adrenal nodules. MACS was defined as serum cortisol concentration >1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (1-mg DST), in the absence of a classic Cushingoid phenotype. Those with other known secondary causes of osteoporosis and/or on pharmacologic treatment for low bone mass were excluded. All study participants underwent a bone health interview, blood draw for bone turnover markers, dual-energy x-ray absorptiometry (DXA) scan with trabecular bone score (TBS), and HR-pQCT of the non-dominant radius and tibia. Participants with a recent fracture within 12 months were excluded from the analysis of bone turnover markers. The Kruskal-Wallis test was used to compare measurements between groups. Results: A total of 82 patients with MACS and 82 referent subjects were prospectively enrolled between 1/2019 and 7/2022. The median age of study participants at the time of enrolment was 57 years (interquartile range [IQR], 47-65), and 57 (70%) were women. In the MACS cohort, the median cortisol following 1-mg DST was 3.2 mcg/dL (IQR, 2.3-6.5) with median ACTH of 8.7 pg/mL (IQR, 6.0-14.0) and median DHEA-S of 42.0 mcg/dL (IQR 23.0-68.0). While no differences in bone mineral density (BMD) were observed at any site (lumbar spine, total hip, femoral neck, or distal radius) between the two groups, patients with MACS had decreased TBS (1.374 vs 1.467, P <0.001) and lower osteocalcin concentrations (16.9 vs. 19.7 ng/mL, P = 0.005) than referent subjects without adrenal nodules. On HR-pQCT at the tibia, patients with MACS had significantly reduced trabecular volumetric BMD (151.6 vs 167.4 mg hydroxyapatite/cm3, P = 0.002), trabecular bone volume/tissue volume ratio (0.219 vs 0.237, P = 0.011), and number of trabeculae (1.428 vs 1.506 1/mm, P = 0.045), while trabecular separation (0.707 vs 0.656, P = 0.023) was increased compared to referent subjects. Conclusions: Patients with MACS have altered bone metabolism and microstructural deterioration that is not evident on routine DXA BMD testing. These changes may mediate their increased fracture risk and could serve as biomarkers of cortisol-induced changes in the bone. Presentation: Thursday, June 15, 2023