Dexamethasone Suppression Test Research Articles

Kidney Function in Patients With Adrenal Adenomas: A Single-Center Retrospective Cohort Study.

Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD); however, factors associated with CKD are unknown. We aimed to identify the factors associated with CKD and assess the effect of adrenalectomy on kidney function in patients with NFA or MACS. A single-center cohort study of patients with NFA and MACS, 1999 to 2020, was conducted. MACS was diagnosed based on post dexamethasone suppression test (DST) cortisol greater than or equal to 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin-converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and postadrenalectomy delta eGFR. Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 mL/min/1.73 m2; P < .001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, postadrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow-up. Factors associated with increased eGFR were younger age, lower preadrenalectomy eGFR, and longer follow-up period. DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Patients with both MACS and NFA demonstrate an increase in eGFR post adrenalectomy, especially younger patients with lower eGFR pre adrenalectomy.

Adrenalectomy Improves Body Weight, Glucose, and Blood Pressure Control in Patients With Mild Autonomous Cortisol Secretion: Results of an Randomized Controlled Trial by the Co-work of Adrenal Research (COAR) Study.

To assess the metabolic effects of adrenalectomy in patients with mild autonomous cortisol secretion (MACS). Despite retrospective studies showing the association of adrenalectomy for MACS with beneficial metabolic effects, there have been only 2 randomized prospective studies with some limitations to date. A prospective, multicenter study randomized 132 patients with adrenal incidentaloma without any features of Cushing syndrome but with serum cortisol >50 nmol/L after a 1 mg overnight dexamethasone suppression test into an adrenalectomy group (n = 66) or control group (n = 66). The primary outcomes were changes in body weight, glucose, and blood pressure (BP). Among the 118 participants who completed the study with a median follow-up duration of 48 months (range: 3-66), the adrenalectomy group (n = 46) exhibited a significantly higher frequency of improved weight control, glucose control, and BP control (32.6%, 45.7%, and 45.7%, respectively) compared with the control group (n = 46; 6.5%, P = 0.002; 15.2%, P = 0.002; and 23.9%, P = 0.029, respectively) after matching for age and sex. Adrenalectomy [odds ratio (OR) = 10.38, 95% CI = 2.09-51.52, P = 0.004], body mass index (OR = 1.39, 95% CI = 1.08-1.79, P = 0.010), and cortisol after a 1 mg overnight dexamethasone suppression test levels (OR = 92.21, 95% CI = 5.30-1604.07, P = 0.002) were identified as independent factors associated with improved weight control. Adrenalectomy (OR = 5.30, 95% CI = 1.63-17.25, P = 0.006) and diabetes (OR = 8.05, 95% CI = 2.34-27.65, P = 0.001) were independently associated with improved glucose control. Adrenalectomy (OR = 2.27, 95% CI = 0.87-5.94, P = 0.095) and hypertension (OR = 10.77, 95% CI = 3.65-31.81, P < 0.001) demonstrated associations with improved BP control. adrenalectomy improved weight, glucose, and BP control in patients with MACS.

Subcentimeter Corticotroph Adenoma: an Evaluation of Diagnostic Elements

Cushing’s disease (CD) is an uncommon yet serious disorder, linked to increased morbidity and mortality. Diagnosis of these patients are complex, and emphasis should be placed on early detection for better management of these patients. The objective of this case report is to evaluate the diagnostic elements in the identification of a subcentimeter adrenocorticotrophic hormone (ACTH)-dependent pituitary adenoma. We report a case of a 26-year-old man who presented with extensive superficial fungal infection of the skin, unintentional weight gain, hypertension, dyslipidaemia as well as cushingoid appearance suspicious of hypercortisolism. Raised midnight plasma cortisol and 24-hour urinary cortisol levels warranted further investigation. Overnight and 48-hour low-dose dexamethasone suppression test (LDDST) were non-suppressed. Subsequent bilateral inferior petrosal sinus sampling (BIPSS) was not only efficient in differentiating pituitary from ectopic Cushing’s syndrome (CS) but was shown to be superior to magnetic resonance imaging (MRI) in lateralisation of the pituitary adenoma.

Giant left pheochromocytoma with vascular anomalies and pelvic horseshoe kidney: a case report

BackgroundPheochromocytoma is a neuroendocrine tumor, and its treatment is dependent on surgical resection. Due to the wide availability of cross-sectional imaging, pheochromocytomas are commonly seen as small tumors less than 10 cm in size and are mostly treated with minimally invasive surgery. Their concomitant presence with horseshoe kidney or other anatomical and vascular anomalies is rare. Herein, we present a surgically complex giant pheochromocytoma case who underwent an open left radical adrenalectomy.Case presentationA 41-year-old Hispanic female presented with a 12 × 8 cm left hypervascular adrenal mass, pelvic horseshoe kidney, and severely dilated large left retro-aortic renal vein which branched into a left adrenal vein, congested left ovarian vein, and left uterine plexus. She was managed with insulin and metformin for uncontrolled diabetes with an A1c level of 9% and doxazosin for persistent hypertension. Clinical diagnosis of pheochromocytoma was confirmed with elevated urine and serum metanephrine and normetanephrine. The pre-operative ACTH was within normal range with a normal dexamethasone suppression test and 24-hour urine free cortisol. The adrenalectomy of the highly aggressive adrenal mass was performed via open approach to obtain adequate surgical exposure. Due to the large size of the tumor and its significant involvement with multiple adjacent structures, coordination with multiple surgical teams and close hemodynamic monitoring by anesthesiology was required for successful patient outcomes including preservation of blood supply to the pelvic horseshoe kidney. The histopathological diagnosis was pheochromocytoma with negative surgical margins. The patient was followed at 1, 4, 12, and 24 weeks postoperatively. She had a normal postoperative eGFR and was able to discontinue antihypertensive and antidiabetic medications at four weeks. She had transient adrenal insufficiency, which resolved at five months. The horseshoe kidney was intact except for a minimal area of hypo-enhancement in the left superior renal moiety due to infarction, which was significantly improved at six months.ConclusionOur patient had a giant pheochromocytoma with anatomical variations complicating an already surgically challenging procedure. Nonetheless, with multiple provider collaboration, detailed pre-operative surgical planning, and meticulous perioperative monitoring, radical resection of the giant pheochromocytoma was safe and feasible with successful postoperative outcomes.

CATALYST: A Phase 4 Study of Hypercortisolism in Patients with Difficult-to-Control Type 2 Diabetes Despite Receiving Standard-of-Care Therapies Assessing Prevalence and Treatment with Mifepristone

The prevalence of hypercortisolism in persons with difficult-to-control type 2 diabetes (T2D) may be higher than currently appreciated, particularly in persons who require a greater number of antihyperglycemic agents and/or have more comorbidities. To better understand the prevalence and whether treatment of hypercortisolism may result in better control of diabetes and other hypercortisolism-associated comorbidities, we have designed CATALYST, a prospective phase 4 study in adults with difficult-to-control T2D (HbA1c 7.5–11.5%) despite receiving multiple antihyperglycemic agents. CATALYST is being conducted at about 30 sites in the United States. In Part 1, about 1000 persons with difficult-to-control T2D will be screened with a 1-mg dexamethasone suppression test (cutoff: serum cortisol >1.8 µg/dL; dexamethasone ≥140 ng/dL). Patients with ACTH-dependent hypercortisolism will be referred out of the study. The primary study endpoint—the prevalence of ACTH-independent hypercortisolism—will be evaluated in Part 1. Patients with ACTH-independent hypercortisolism may advance to Part 2, a prospective, 2:1 randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of treatment with the competitive glucocorticoid receptor antagonist mifepristone. Patients will be randomized (stratified by the presence/absence of adrenal adenomas on CT) and receive treatment for 24 weeks. The mifepristone dose will be 300 mg QD for 4 weeks, then increased to 600 mg QD for 20 weeks based on glycemic efficacy and tolerability (option to increase to mifepristone 900 mg). Secondary endpoints include changes in HbA1c from baseline to 24 weeks and changes in hypercortisolism-related comorbidities (e.g., blood pressure, weight, waist circumference, quality of life).

Bone density in patients with nonfunctional adrenal incidentaloma

Aims: Adrenal incidentalomas (AI) are adrenal masses that are detected incidentally in imaging studies performed for different reasons in people who do not have any complaints suggestive of adrenal gland disease. The overall prevalence, approximately just over 4%, increases with age. AI is detected in approximately 10% of people over the age of 70. In this context, we thought that CT imaging, which is already used in the diagnosis and follow-up of AI, can contribute to the evaluation of muscle and bone mass without creating additional costs. Methods: In this retrospective study, 39 patients who were followed up with NFAI by the endocrinology department and 30 healthy individuals with normal adrenal imaging in the abdominal CT examination as the control group were included. Patients with chronic diseases or drug use that may affect bone and muscle mass, and individuals in the postmenopausal period were excluded in this study. Endocrine tests performed to exclude autonomous cortisol secretion, pheochromocytoma and primary hyperaldosteronism; VMA and fractionated metanephrines in 24-hour urine, cortisol values after 1 mg dexamethasone suppression test, baseline serum dehydroepiandrosterone sulfate (DHEAS) levels and plasma aldosterone (ng/dl)/renin (ng/ml/hour) ratio were measured. Autonomous cortisol production was excluded in patients with serum cortisol below 1.8 mcg/dl after 1 mg dexamethasone suppression. Results: 39 patients with NFAI and 30 healthy volunteers participated in the study. In the NFAI group, 69.2% (n= 27) were female and 30.8% (n=12) were male. In the healthy control group 63.3% (n=19) of the people were female and 37.7% (n=11) were male. There was no statistically significant difference between the two groups in terms of gender (p=061). The mean age of the NFAI group is 43 and the mean age of the control group is 49, and there was no statistically significant difference in age between the two groups (p=0.06) Conclusion: No decrease was found in BMD and paravertebral muscle mass values in the measurements made at L1-3 vertebral level with CT in NAFI patients. Further studies are needed in a larger patient population where the results are evaluated together with the femur and vertebral BMD measurements by DXA method, and muscle strength and performance are evaluated in addition to muscle mass in terms of sarcopenia.

Dexamethasone Suppression Testing in a Contemporary Cohort with Adrenal Incidentalomas in Two U.S. Integrated Healthcare Systems.

Autonomous cortisol secretion (ACS) from an adrenal adenoma can increase the risk for comorbidities and mortality. The dexamethasone suppression test (DST) is the standard method to diagnose ACS. A multi-site, retrospective cohort of adults with diagnosed adrenal tumors was used to understand patient characteristics associated with DST completion and ACS. Time to DST completion was defined using the lab value and result date; follow-up time was from the adrenal adenoma diagnosis to the time of completion or censoring. ACS was defined by a DST > 1.8 µg/dL (50 nmol/L). The Cox proportional hazards regression model assessed associations between DST completion and patient characteristics. In patients completing a DST, a logistic regression model evaluated relationships between elevated ACS and covariates. We included 24,259 adults, with a mean age of 63.1 years, 48.1% obese, and 28.7% with a Charlson comorbidity index ≥ 4. Approximately 7% (n = 1768) completed a DST with a completion rate of 2.36 (95% CI 2.35, 2.37) per 100 person-years. Fully adjusted models reported that male sex and an increased Charlson comorbidity index were associated with a lower likelihood of DST completion. Current or former smoking status and an increased Charlson comorbidity index had higher odds of a DST > 1.8 μg/dL. In conclusion, clinical policies are needed to improve DST completion and the management of adrenal adenomas.

Impact of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function.Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512).

E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.

E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism. This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47. E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission. E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such asdyslipidemia.

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, &amp;lt;221.5 mmol/day [&amp;lt;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.

Mfat-1 ameliorates cachexia after hypoxic-ischemic brain damage in mice by protecting the hypothalamus-pituitary-adrenal axis

AimsCachexia, a metabolic syndrome, affects 21 % of patients suffering from ischemic encephalopathy. However, the specific mechanism and prevention measures are still unclear. Omega-3 polyunsaturated fatty acids (n−3 PUFAs) have been proven to reduce inflammatory cytokine levels during ischemic events, but whether they have a protective effect against cachexia after hypoxic-ischemic brain damage (HIBD) remains unclear. Main methodsC57BL/6J wild-type and mfat-1 transgenic male mice were treated with and without HIBD. One day after HIBD, the epididymal white fat, gastrocnemius muscle and hypothalamus were weighed and analyzed the phenotypic changes. RNA sequencing was applied to gastrocnemius muscle to identify differential genes and pathways in HIBD groups. The effect of HPA axis on cachexia post-HIBD was examined via adrenalectomy, dexamethasone (0.1 mg/kg), and corticosterone injection (100 mg/kg). Key findingsThe results showed that the incidence of cachexia in mfat-1 mice, which produce high proportion of n−3 PUFAs, was significantly lower than that in wild-type mice post-HIBD. Cachexia-related factors, such as inflammation, muscle atrophy and lipid metabolism were significantly improved in mfat-1 HIBD. RNA sequencing revealed that catabolic and proteasome pathways were significantly downregulated. In hypothalamus, inflammatory cytokines, lipid peroxidation levels were reduced. Corticosterone, glucocorticoid receptor, and dexamethasone suppression test all showed that mfat-1 improved the dysfunction of the HPA axis post-HIBD. The present study elucidated for the first time that mfat-1 reduced HIBD-induced hyperactivation of the HPA axis in mice by reducing inflammation and oxidative stress and contributed to the reduction of metabolic imbalance in peripheral tissues. SignificanceOur study provides mechanistic information for the development of intervention strategies to prevent cachexia.

Comorbidities in mild autonomous cortisol secretion and the effect of treatment: systematic review and meta-analysis.

To assess (1) comorbidities associated with and (2) treatment strategies for patients with adrenal incidentalomas and mild autonomous cortisol secretion (MACS; > 1.8 µg/dL (>50 nmol/L) cortisol level cut-off following the 1 mg dexamethasone suppression test). Systematic review and meta-analysis. Seven databases were searched up to July 14, 2022. Eligible studies were (randomized) trials, cohort studies, and cross-sectional studies assessing comorbidities potentially attributable to cortisol excess or mortality in patients with adrenal incidentaloma with or without MACS or the effects of conservative or surgical management of MACS. Random-effects meta-analysis was performed to estimate pooled proportions (with 95% CIs). In 30 cross-sectional and 16 cohort studies (n = 17 156 patients in total), patients with MACS had a higher prevalence of diabetes (relative risk [RR] 1.44 [1.23-1.69]), hypertension (RR = 1.24 [1.16-1.32]), and dyslipidemia (RR = 1.23 [1.13-1.34]). All-cause mortality (adjusted for confounders) in patients with MACS, assessed in 4 studies (n = 5921), was increased (hazard ratio [HR] = 1.54 [1.27-1.81]). Nine observational studies (n = 856) and 2 randomized trials (n = 107) suggest an improvement in glucometabolic control (RR = 7.99 [2.95-21.90]), hypertension (RR = 8.75 [3.99-19.18]), and dyslipidemia (RR = 3.24 [1.19-8.82]) following adrenalectomy. The present systematic review and meta-analysis highlight the relevance of MACS, since both cardiometabolic morbidities and mortality appeared to have increased in patients with MACS compared to patients with non-functioning incidentalomas. However, due to heterogeneous definitions, various outcomes, selective reporting, and missing data, the reported pooled estimates need to be interpreted with caution. The small number of patients in randomized trials prevents any strong conclusion on the causality between MACS and these comorbidities.

THU015 Unilateral Adrenal Hyperplasia Causing ACTH-independent Hypercortisolism

Abstract Disclosure: N. Mogar: None. M.A. McConnell : None. R. Yu: None. J.E. Weinreb: None. Background: Adrenal cortical hyperplasia is defined radiographically as a non-malignant growth or enlargement of the adrenal glands. Adrenal hyperplasia is most commonly bilateral, with unilateral adrenal hyperplasia occurring less frequently. Unilateral adrenal hyperplasia has been associated with primary hyperaldosteronism, and there are only a few case reports describing unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism. Clinical Case: A 56-year-old man with sleep apnea was incidentally found to have a 4.6 cm left adrenal nodule found on computed tomography (CT) chest imaging. Adrenal CT revealed a heterogeneous 4.6 x 3.3 x3.7 cm left adrenal mass with internal calcifications and a portion of the mass measuring 38 Houndsfield units (HU). His 8AM serum cortisol level was 19.80 mcg/dL (5-23 mcg/dL). No ACTH level was collected; however, a serum DHEA-S level was 55 mcg/dL (32-240 mcg/dL). After low dose dexamethasone suppression test (LDDS), the serum cortisol level was elevated at 2.3 mcg/dL (&amp;lt;1.8 mcg/dL). Repeat LDDS revealed a cortisol level of 2.9 mcg/dL. A 24-hour urine free cortisol level was 27.2 mcg/24h (4-50 mcg/24h). Testing for pheochromocytoma and hyperaldosteronism was negative. The patient had no historical or physical signs of Cushing’s syndrome and no signs of malignancy. Due to concerning features on adrenal CT imaging (tumor size &amp;gt;4 cm, internal calcifications, and HU &amp;gt;10), the patient underwent unilateral adrenalectomy. The patient did not receive intraoperative corticosteroids and remained normotensive post-operatively. However, his post-operative 8AM cortisol level was &amp;lt;0.2 mcg/dL (5-23 mcg/dL) on two separate occasions. He was discharged on a short course of hydrocortisone, with eventual recovery of his hypothalamic-pituitary-adrenal (HPA) axis. Pathology revealed a diagnosis of cortical adrenal hyperplasia. Conclusion: The presence of postoperative hypocortisolemia demonstrates that this patient had ACTH-independent hypercortisolism. This case report would be one of few describing the rare diagnosis of unilateral adrenal hyperplasia associated with ACTH-independent hypercortisolism and would add to the sparse literature currently available on this condition. Additionally, this case report highlights the clinical significance of mild autonomous cortisol secretion (MACS); despite only having an unsuppressed cortisol level following LDDS, this patient was found to have a suppressed HPA axis after unilateral adrenalectomy requiring corticosteroids. Early identification and treatment of MACS and treatment of adrenal insufficiency following adrenalectomy is essential to prevent adverse events. Presentation: Thursday, June 15, 2023

SAT627 Is Cyberknife Stereotactic Radiosurgery Effective For Treating Cushing’s Disease?

Abstract Disclosure: G. Wintermyer: None. E. Villanueva: None. Patients with pituitary adenoma can often present with endocrine abnormalities. Transsphenoidal surgery(TSS) is the “gold standard” treatment. In patients with recurrent or post-surgery remaining adenoma, stereotactic radiosurgery with CyberKnife (CKRS) has demonstrated to be a good adjuvant therapy. Occasionally patients develop hypopituitarism and adrenal insufficiency (AI) post CKRS. Here is a patient with ACTH-secreting pituitary adenoma with Cushing’s disease who developed remission afterCKRS:52-year-old-male with PMHx of T2DM, hypothyroidism, HTN presented to hospital complaining of fatigue, ataxia, 40-lbs weight loss over four months and mood changes. Due to ataxia, CT of the head was done which revealed an Empty Sella. During the workup, ACTH and cortisol were detected 131 pg/mL and 37.5 ug/dL respectively. After ruling out life-threatening medical conditions, he was discharged with endocrinology referral for Empty Sella syndrome (ESS) and elevated ACTH. During endocrinology evaluation, patient was sent for testosterone, LH, FSH, ACTH, AM cortisol, prolactin and DHEAS tests. Results were as follows: elevated ACTH (91 pg/mL) and Cortisol (33.5ug/dL), elevated DHEAS (401 ug/dL) and prolactin (15 NG/dL), low testosterone (72 NG/dL), within appropriately low LH and FSH. Later, PM Salivary cortisol level, Dexamethasone suppression test(DST), and urine free cortisol (UFC) level were tested. He had pituitary MRI concurrently. Salivary cortisol and UFC were high. There was no suppression of cortisol level after DST. Pituitary MRI demonstrated pituitary tumor. He was diagnosed with Cushing’s disease and was referred to neurosurgery for pituitary tumor TSS. Patient was started on Ketoconazole prior to surgery. Pathology confirmed ACTH-secreting pituitary adenoma. After surgery, Cortisol level normalized, and the patient regained his energy. Post-surgery MRI showed complete resection of adenoma. Ketoconazole was discontinued post-operatively. Two years later, during routine workup, there were elevations in 24-hour and PM salivary cortisol levels. The patient was asymptomatic. He failed his DST. Repeat pituitary MRI showed small hypo enhancement at the bottom of Sella suspicious for pituitary adenoma recurrence. The patient underwent CKRS. Cortisol level and pituitary axis activity remained normal since CKRS. No change was noted in the six-month and one-year surveillance MRI. Even though TSS is a “gold standard” treatment for pituitary adenoma, the likelihood of remaining residues or recurrence of the tumor is high. Frequent pituitary hormone checks can detect recurrence of adenoma before emerging symptoms. CKRS should be considered as a therapeutic option for recurrent adenoma. Clinicians should frequently check patients for hypopituitarism and AI post-CKRS. Clinicians should also recognize that ESS may contribute to MRI-negative Cushing’s disease. Presentation: Saturday, June 17, 2023

FRI173 Investigation Of Cut Off Values For Identifying Cortisol Excess In Adrenal Venous Blood Sampling

Abstract Disclosure: K. Watanabe: None. K. Nakai: None. Y. Tsurutani: None. R. Hirose: None. J. Saito: None. T. Nishikawa: None. Objective: Primary aldosteronism (PA) is sometimes accompanied by subclinical Cushing’s syndrome (SCS). However, there is no defined cutoff value for excess cortisol (Cort) in adrenal venous blood sampling (AVS). Meanwhile, some reports have shown AVS usefulness in overt Cushing’s syndrome. This study analyzed AVS parameters to determine the cutoff value of excess Cort in AVS. Methods: The Cort-producing adenoma (CPA) group included patients with adrenal tumors who had a Cort level of ≥ 5 mg/dL after a 1 mg dexamethasone suppression test (DST) and underwent segmental AVS (sAVS) at our hospital from 2009-2020 (n = 75). Patients who underwent AVS on only one side had an adrenocorticotropic hormone (ACTH) level of &amp;gt; 10 pg/mL after 1 mg DST, a midnight Cort level of &amp;lt; 5.0 mg/dL, bilateral cortisol-producing tumors, and/or adrenal cancer, were excluded (n = 26). The control group with normal Cort secretion included patients with Cort level of &amp;lt; 1.8 mg/dL after 1 mg DST who underwent sAVS and whose resected adrenal tumor was negative or weakly positive in 11β-hydroxylase cytochrome P450 staining (n = 45). We compared the various sAVS values between the CPA and control groups. Results: Forty-nine patients in the CPA and 45 in the control groups were analyzed. Compared with the control, the CPA group had a significantly higher maximum Cort level in the tributary veins flowing from the tumor (1220 [860.1-1584.4] vs. 928 [695.5-1350.0], p = 0.016). Meanwhile, Cort levels in the central vein on the tumor side were not significantly different between the two groups (895 [614.7-1312.7] vs. 820 [590.5-1065.0], p = 0.202). The CPA group had a significantly lower minimum Cort level in all tributary veins (117 [73.1-241.5] vs 559 [386.0-794.0], p &amp;lt; 0.001), and Cort level in the central vein on the non-tumor side (176 [93.9-394.0] vs 766 [499.5-1090.0], p &amp;lt; 0.001). The ratio of each value showed that the maximum Cort level in tributary veins flowing from the tumor/minimum Cort level in all tributary veins (9.59 [3.75-21.23] vs 1.65 [1.45-2.06], p &amp;lt; 0.001) and Cort level in the central vein on the tumor side/Cort level in the central vein on the non-tumor side (4.44 [1.95-11.35] vs 1.04 [0.73-1.34], p &amp;lt; 0.001) were significantly higher in the CPA group. The former had the largest area under the curve for the receiver operating characteristic curve in various indices (AUC = 0.948, 81.6% sensitivity and 97.8% specificity when 3.28 was set as the cut-off value). Conclusion: Novel cutoff values were proposed to identify excess cortisol in AVS. Presentation: Friday, June 16, 2023

SAT598 7mg-dexamethasone Suppression Test For The Differential Diagnosis Of Cushing’s Syndrome

Abstract Disclosure: D. Cuevas Ramos: None. G. Garza García: None. W. Hernández Núñez: None. F.J. Gómez Pérez: None. Introduction: Establishing the cause of Cushing’s syndrome remains challenging. Bilateral Inferior Petrosal Sinus Sampling (BIPSS) is the gold standard for distinguishing between Cushing's disease (ACHT-secreting pituitary adenoma) and an ectopic source of ACTH. However, BIPSS is an invasive test and is not widely available. Therefore, we sought to explore the diagnostic efficacy of the 7 mg dexamethasone suppression test (7mg-dexa) for establishing the diagnosis of Cushing's disease (CD). Methods: We reviewed 1375 cases with pituitary adenomas. From them, 191 cases had confirmed diagnosis of CD from 1999 to 2022. Of these, 25 patients underwent 7 mg dexamethasone suppression test together with BIPSS during their diagnosis workup. A diagnosis of CD was established in 21 patients, confirmed after neurosurgery, with a pathology report of ACTH+ secreting pituitary adenoma, and a biochemical resolution of CS. The additional 4 cases showed an adrenal source of CS. Suppression of 50% or more in the afternoon (of day 1 after 7 mg-dexa IV infusion by 7h starting at 7:00 hrs at 1 mg/hr) was considered consistent with CD. A central-to-peripheral plasma ACTH gradient of ≥2 before and after desmopressin stimulation was also considered consistent with CD during the BIPSS. We calculated kappa index to evaluate concordance between diagnostic test. Also, sensitivity (S), specificity (E), positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were calculated. Results: The mean age was 43±12.1 years, with a BMI of 30±5.6 kg/m2, 86% females. For the basal ACTH values during BIPSS, the S=76%, E=75%, PPV=94%, NPV=37%, LR+=3, LR-=0.3. For the post-stimulation BIPSS, the S=95%, E=75%, PPV=95%, NPV=75%, LR+=3, LR-=0.06. Using the 7mg-dexa, a S=91%, E=75%, PPV=95%, NPV=60%, LR+=3.6, LR-=0.12. Kappa between test was 0.6 before stimulation, and 0.7 after desmopressin stimulation showing acceptable concordance. Conclusion: The 7 mg-dexa showed similar and acceptable diagnostic performance in comparison with basal or stimulated BIPSS. Since 7mg-dexa inhibition test is less invasive and less expensive, further clinical research to evaluate its utility in CD diagnostic approach is in order. Presentation: Saturday, June 17, 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

THU013 A Rare Case of Ectopic Cushing’s Syndrome Caused By Metastatic Parotid Gland Carcinoma

Abstract Disclosure: E. Punni: None. I. Goyal: None. Introduction: Ectopic Cushing’s Syndrome (ECS) is a rare condition that accounts for only a small percentage of all Cushing’s syndrome cases. Although rare, the typical tumors associated with ECS are small cell lung carcinomas, bronchial carcinoids, pancreatic neuroendocrine tumors, medullary thyroid carcinomas, thymic carcinoids and pheochromocytomas. Metastatic acinic cell carcinoma (ACC) of the parotid gland has very rarely been associated with ectopic Cushing’s syndrome. Case Presentation: A 67-year-old Caucasian male with a known diagnosis of high grade metastatic ACC of the parotid gland presented to the hospital with progressively worsening proximal muscle weakness and bilateral lower extremity edema of 6 weeks duration. A month prior to presentation, he developed persistent hypokalemia requiring potassium supplementation and was diagnosed with new onset type 2 diabetes mellitus. Laboratory results on admission were remarkable for low potassium at 2.5 mEq/L (N: 3.5-5.3 meq/L), a random cortisol level of 107 mcg/dL (N: 6 - 30 mcg/dL), and an ACTH level of 485 pg/mL (N: 7.2 - 63.3 pg/mL). Subsequently, a 24-hour urine cortisol was &amp;gt; 1600 ug/24 hours (N 5-64 ug/24 hours). A 1 mg dexamethasone suppression test failed to suppress an 8 a.m. cortisol with level of 110.8 mcg/dl (N &amp;lt; 1.8 mcg/dl). Following, an 8 mg dexamethasone suppression test also failed to suppress 8 a.m. cortisol with a value of 100.8 mcg/dl. A MRI of the pituitary with and without contrast showed mild diffuse enlargement of the pituitary gland concerning for pituitary hyperplasia. At the time, ECS was highly suspected given the rapid course of patient’s presentation, known metastatic malignancy, and failed 8 mg dexamethasone suppression test. An inferior petrosal sinus sampling (IPSS) could not be performed given the patient’s guarded condition. Instead, a PET/CT Ga-68 DOTA-TATE scan obtained showed widespread DOTA-TATE avid malignancy concerning for neuroendocrine type tumor. Patient was a poor surgical candidate, therefore bilateral adrenalectomy could not be performed for the rapid treatment of ECS. Patient was started on a steroidogenesis inhibitor ketoconazole. However, he elected to undergo hospice care and passed away shortly after. Conclusion: This case is particularly interesting given that metastatic ACC of the parotid gland causing ECS is rare with only a few cases reported in the literature. This case highlights the importance of maintaining a high degree of suspicion for diagnosing ECS especially when patients present with rapid onset of signs and symptoms of Cushing’s syndrome and a known underlying malignancy. Recognizing less common causes of ECS may prompt early diagnosis and intervention. Presentation: Thursday, June 15, 2023

FRI180 Prevalence Of Vertebral Fractures In Patients With Adrenal Adenomas

Abstract Disclosure: H. Han: None. H. Lam: None. S.D. Rao: None. S. Athimulam: None. Background: Approximately 5% of adults undergoing cross-sectional imaging are reported to have an adrenal adenoma. Although most adenomas are considered non-functioning (NFAT), up to 48% can present with mild autonomous cortisol secretion (MACS). Published studies have reported an increased prevalence of vertebral fractures (VFx) in MACS. However, findings are limited by sample size, selection bias and lack of diversity in patient population. Objective: To determine the prevalence of vertebral fractures and associated risk factors in patients with adrenal adenomas Design: Retrospective cross-sectional study of patients with adrenal adenomas over a 10-year period (Jan 2012 - Dec 2021). Setting: Academic primary and tertiary care setting Main outcomes measured: 1) MACS was diagnosed based on cortisol level ≥ 1.8cmg/dL after overnight 1mg dexamethasone suppression testing (DST) and NFAT if cortisol &amp;lt; 1.8mcg/dL. Patients who did not undergo 1mg DST were categorized as unknown cortisol status (UCS).2) Bone mineral density (BMD), T- and Z-scores of the lumbar spine (LS). 3)Vertebral morphometry, as assessed by Genant scale, to identify asymptomatic vertebral fractures. Results: Preliminary results included 198 patients with adrenal adenomas [(135 women (67%) with a median age of 67y, 106 Black (54%), 83 White (42%) and 9 other races (4%)]. 74 patients (37%) were diagnosed with NFAT, 42 (21%) with MACS, and 82 (41%) with UCS. Prevalence of vertebral fractures by vertebral morphometry assessment was 6%. (n=12, 5 Black, 7 White). In those with VFx (8 UCS, 2 MACS, 2 NFAT), Black patients had lower BMD (Mean BMD ± SD in Black vs Caucasians: 0.85 ± 018 vs 1.02 ± 0.24 g/cm2, p=0.26). Overall, there was no significant difference in mean LS BMD ± SD (0.97 ± 0.23 vs 1.03 ± 0.20 g/cm2, p=0.41) and mean T-score LS ± SD (-1.11 ± 2.28 vs -0.60 ± 1.71, p=0.49), in patients with and without vertebral fractures, respectively. Conclusions: Patients with adrenal adenoma are at risk of vertebral fractures despite normal or osteopenic BMD. Black patients with adrenal adenomas and vertebral fractures have lower BMD compared to White patients. 41% (n=82, 61% AA, 30% Caucasians, 2% Other) of patients were classified as unknown cortisol status indicating further need to educate health care professionals on evaluation of adrenal adenomas to improve health care outcomes and disparities in management. Presentation: Friday, June 16, 2023

SAT588 Cushing’s Syndrome Due To Ectopic ACTH Secretion From Ovarian Teratomas

Abstract Disclosure: Y. Kang: None. M.S. Gildenberg: None. B.J. Quade: None. R.A. Blair: None. Background: Approximately 9-18% of Cushing’s syndrome (CS) cases are secondary to ectopic ACTH secretion, most commonly from sources in the lung or mediastinum. However, ACTH-producing tumors are rarely found in distant organs, occasionally making the localization and management challenging. Clinical Case: A 32-year-old woman with class 3 obesity, hidradenitis suppurativa, anxiety, and depression experienced atraumatic pelvic and sacral fractures. DXA scan result showed Z-scores of -3.1 in the lumbar spine, -2.6 in the femur neck, and -0.5 in the total hip. She reported a steady weight-gain of 250 lbs over 7 years despite lifestyle modifications and liraglutide. On examination, she had a round face with plethora, acne, violaceous abdominal striae, and dorsocervical fat pad. Laboratory findings revealed elevated midnight salivary cortisol levels of 453 and 424 ng/dL (n: &amp;lt;100 ng/dL), elevated 24-hour urine cortisol levels of 254 and 741 (n: 3.5-45 mcg), and an abnormal 1 mg dexamethasone suppression test (DST) result at 15.1 ug/dL. AM plasma ACTH and cortisol levels were 190 pg/mL and 18.5 ug/dL, suggesting ACTH-dependent hypercortisolism. The plasma cortisol level after an 8 mg DST was unsuppressed at 13.1 ug/dL with a dexamethasone level of 3,380 ng/dL (n: &amp;gt;800 ng/dL). Abdominal CT and MRI scans showed large bilateral adnexal masses measuring up to 13.7 cm on the left and 9.3 cm on the right, with heterogeneous solid and cystic components, consistent with mature cystic ovarian teratomas. DOTATE-PET scan did not show any areas of increased uptake. The patient underwent a laparoscopic right cystectomy and left oophorectomy, with immediate drop in cortisol (1.6 ug/dL) and signs of adrenal insufficiency post-operatively, requiring hydrocortisone replacement. After holding hydrocortisone for 24 hours prior to laboratory assessment one week post-operatively, her ACTH and cortisol were undetectable, reflecting successful source removal. Pathology report showed neuroendocrine tumor with pituitary differentiation with positive ACTH immunohistochemical staining and Ki-67 proliferative index of 22.6% on the left adnexal mass, and a mature cystic teratoma on the right. Conclusion: Although rare, pituitary differentiation of ovarian teratomas should be considered as a possible source of ectopic ACTH secretion in CS patients without obvious sources identified in commonly involved organs. Presentation: Saturday, June 17, 2023