Dexamethasone Suppression Test Research Articles

Who and how to screen for endogenous hypercortisolism in patients with mood disorders.

A strict association exists between mood disorders and endogenous hypercortisolism, namely Cushing's syndrome (CS). Indeed, CS is characterized by a wide range of mood disorders, such as major depression, generalized anxiety, panic disorders, bipolar disorders up to psychosis, with major depression being the most frequent, with a prevalence of 50-80%, and potentially representing the clinical onset of disease. Despite this observation, the exact prevalence of hypercortisolism in patients with mood disorders is unknown and who/how to screen for endogenous hypercortisolism among patients with mood disorders is still unclear. In this context, an accurate anamnestic and clinical examination are crucial in order to identify those patients who may benefit from CS screening. In particular, the presence of specific signs and symptoms of CS, comorbidities typically associated with CS, and lack of improvement of depressive symptoms with standard treatments can further guide the decision to screen for CS. Anyhow, it is noteworthy that mood disorders represent a cause of functional activation of hypothalamic-pituitary-adrenal (HPA) axis, a condition formerly known as non-neoplastic hypercortisolism (NNH). The differential diagnosis between CS and NNH is challenging. Beyond anamnestic and clinical features, various tests, including measurement of daily urinary cortisol and late-night salivary cortisol, together with low dose-dexamethasone suppression test, are used for initial screening. However, considering their low accuracy, a definitive diagnosis may require a longitudinal follow-up along with second-line dynamic tests like combined dexamethasone-CRH test and desmopressin test. In conclusion, available data suggest the need for a comprehensive assessment and follow-up of individuals with mood disorders to detect possible underlying CS, considering the pitfalls in diagnosis and the overlap of symptoms with other conditions like NNH. Specialized centers with expertise in CS diagnosis and differential testing are recommended for accurate evaluation and management of these patients.

MÉTODOS DE DIAGNÓSTICOS DE HIPERADRENOCORTICISMO EM CÃES UMA REVISÃO NARRATIVA

The objective of this research was to investigate and evaluate the diagnostic methods used for hyperadrenocorticism in dogs by analyzing the available literature from the past 20 years. The methodology employed was a qualitative and exploratory literature review, conducted through databases such as PUBMED, MEDLINE, BVS, SCOPUS, PERIÓDICOS, BIBLIOTECA ABERTA USP, and SCIELO. Keywords such as "dogs," "canine," "hyperadrenocorticism," "endocrine," "endocrinopathy," and "Cushing" were used to identify relevant studies. The content analysis of the selected articles revealed that diagnostic methods vary according to the clinical suspicion and include detailed anamnesis, thorough clinical examination, and basic and imaging laboratory tests. The choice between suppression and stimulation hormone tests depends on the suspected origin of the condition, with the low-dose dexamethasone suppression test being highly sensitive for detecting hyperadrenocorticism, while the ACTH stimulation test is crucial for differentiating between origins. Diagnostic confirmation also involves abdominal ultrasonography to visualize the adrenal glands and identify possible masses, which is essential for guiding appropriate treatment and determining the patient’s prognosis.

Autonomous cortisol secretion promotes vascular calcification in vivo and in vitro under hyperaldosteronism.

Autonomous cortisol secretion (ACS) is not uncommon in patients with primary aldosteronism (PA). However, the cardiovascular burden of ACS due to its dysregulated cortisol secretion remains poorly understood. Thus, we examined the effects of ACS on vascular calcification in a hyperaldosteronism environment in vitro and in vivo. A total of 339 patients with PA with adrenal incidentaloma and low-dose dexamethasone suppression test data (cutoff level: cortisol > 1.8 μg/dL) from a prospectively maintained database were enrolled; abdominal aortic calcification (AAC) scores were quantitatively estimated. Human aortic smooth muscle cells (HAOSMCs) were used as in vitro model of vascular calcification. In this study, 65 of the 339 patients with PA had ACS; 274 did not. Patients with PA/ACS had a higher AAC score (1171.0 ± 2434.0 vs. 489.5 ± 1085.3, P = 0.012) than patients without ACS. ACS was independently associated with AAC score (β = 0.139, P = 0.004) in multivariate analysis, and post-suppression cortisol level was significantly correlated with the AAC score (P = 0.004). In the HAOSMC model, co-treatment with cortisol synergistically stimulated alkaline phosphatase activity and calcium deposition in a hyperaldosteronism environment. The stimulatory effect of cortisol was abolished by the mineralocorticoid receptor (MR) antagonist eplerenone, but not glucocorticoid receptor antagonist mifepristone, indicating a MR-dependent mechanism. In conclusion, the presence of ACS is associated with heavier vascular calcification in patients with PA. Aldosterone and cortisol synergistically activate HAOSMC calcification via MR signaling, via a process that can be attenuated by eplerenone.

Autonomous cortisol secretion in patients with primary aldosteronism is associated with left ventricular hypertrophy and diastolic dysfunction

Abstract Background and Aims: Autonomous cortisol secretion (ACS) constitutes a significant portion of patients diagnosed with primary aldosteronism (PA) and is potentially linked to adverse cardiovascular outcomes. This study aimed to explore the impact of ACS on cardiac remodeling and diastolic dysfunction in PA patients. Methods We prospectively enrolled 567 PA patients from March 2000 to March 2023. ACS was defined as a cortisol level >1.8 μg/dL after a 1 mg dexamethasone suppression test (DST). Clinical, biochemical, and echocardiographic data were collected at baseline and during one-year follow-up after targeted treatments including adrenalectomy and mineralocorticoid receptor antagonist administration. Results In this prospective cohort, 21.5% of PA patients had concurrent ACS. PA patients with ACS were older and had a higher prevalence of diabetes. They also exhibited significantly higher left ventricular mass index (LVMI) and worse diastolic function (E/e'). Baseline post-1 mg DST cortisol levels positively correlated with baseline LVMI and E/e' in restricted cubic spline analysis. Multivariable linear regression analysis showed that ACS presence was significantly associated with higher LVMI and worse E/e' after adjusting for significant variables. Among patients who underwent adrenalectomy, both those with and without ACS showed significant improvements in LVMI and E/e'. Patients who received mineralocorticoid receptor antagonist treatment also showed significant improvement in E/e', irrespective of ACS presence. However, significant LVMI improvement was observed only in PA patients without ACS who received mineralocorticoid receptor antagonist treatment. Conclusions The presence of ACS in PA patients was associated with worse left ventricular hypertrophy and diastolic dysfunction. Adrenalectomy and mineralocorticoid receptor antagonist treatment partially reversed cardiac remodeling in PA patients with ACS.

Long-term outcome of unilateral adrenalectomy for primary bilateral macronodular adrenal hyperplasia.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a form of Cushing's syndrome (CS) characterized by heterogeneous cortisol secretion and clinical comorbidities. Previously, bilateral adrenalectomy was the standard treatment for PBMAH, but this approach carried a high risk of primary adrenocortical insufficiency. In recent decades, unilateral adrenalectomy (U-Adx) has emerged as an effective alternative. However, limited research exists on its postoperative efficacy and prognostic predictors. Therefore, the present study aimed to investigate the long-term effectiveness and prognostic predictors of U-Adx in treating PBMAH. A total of 61 patients with PBMAH diagnosis who underwent U-Adx at a single center between 2004 and 2022 were retrospectively evaluated. Patients were categorized into persistent hypercortisolism and remission groups based on postoperative biochemical outcomes at the last follow-up (>12 months after U-Adx). Clinical characteristics, comorbidities, plasma adrenocorticotropic hormone (ACTH), serum cortisol, and 24-h urinary-free cortisol (24-h UFC) levels were analyzed pre- and postoperatively. We further examined whether baseline plasma ACTH, serum cortisol, 24-h UFC levels, and the inhibition of cortisol and 24-h UFC after a low-dose dexamethasone suppression test (LDDST) could predict non-remission following U-Adx. Additionally, we explored the improvements in hypertension, abnormal glucose metabolism, osteoporosis, and other complications in patients with PBMAH post-U-Adx. After U-Adx, 22 of the 45 patients (48.89%) achieved initial remission within 6 months. At the last follow-up, 25 of the 45 patients underwent all required biochemical tests and cortisol assessment tests, among which eight of 25 (32.00%) were in remission and 17 of 25 (68.00%) were experiencing persistent hypercortisolism. Moreover, five of those 25 patients exhibited recurrence after initial remission. Baseline 24-h UFC level > 2 times the upper limit of normal (2ULN) and unsuppressed 24-h UFC after LDDST may predict persistent hypercortisolism postoperatively. Lastly, long-term postoperative follow-up revealed that hypertension decreased with hypercortisolism remission, whereas osteoporosis worsened with persistent hypercortisolism. The short-term remission rate of hypercortisolism was 48.89% in patients with PBMAH treated with U-Adx, while a long-term remission rate of 32.00% was achieved after a median follow-up of 38.58 months. Furthermore, this finding suggests that baseline 24-h UFC level > 2ULN and unsuppressed 24-h UFC after LDDST predict persistent hypercortisolism in the long-term post-U-Adx. Finally, U-Adx improved cortisol circadian rhythm alterations and ACTH suppression in the patients in the remission group, thereby substantially alleviating hypertension and delaying the development of osteoporosis linked to PBMAH.

12376 Comparison Of 1 Mg Versus 2 Mg Dexamethasone Suppression In Obesity

Abstract Disclosure: H. Babu: None. A. Nawaz: None. A.J. Spiro: None. T.D. Hoang: None. M.K. Shakir: None. The overnight 1 mg dexamethasone suppression test (DST) is widely used to screen for Cushing’s Syndrome (CS), especially due to its low incidence of false negative results. Serum cortisol concentrations <1.8 µg/dL suggests adequate HPA axis suppression and usually excludes CS. Concentrations >1.8 µg/dL should be verified with a second test. However, the lack of suppression on DST has been documented previously in 1.46% to 15% of obese patients without CS. Previous studies have suggested simultaneous measurements of serum cortisol, ACTH, and dexamethasone levels after DST to ensure adequate suppression. In this retrospective analysis, we compared the plasma levels of ACTH, dexamethasone, and cortisol levels after 1 mg and 2 mg DST in healthy obese (class III) subjects. The study involved 6 subjects (2 males, 4 females, age 37.5 ± 8.79 years, BMI 43.65 ± 3.12 (kg/m2) who were referred for evaluation of abnormal weight gain. Exclusion criteria for these subjects included diabetes mellitus, pregnancy, history of CS, psychiatric disorders, chronic liver disease, chronic renal failure, malabsorption disorders and nephrotic syndrome. The exclusion of CS was done by history and physical examination showing the lack of specific clinical features of CS. Additionally, none of the subjects were taking drugs that interfered with CYP3A4 or oral contraceptives within 3 months preceding the study. None of the participants reported alcohol consumption of more than 30 g per day. Screening tests for CS involved 1 mg, 2 mg DST, LNSC and 24-hour urine cortisol levels. Results: Following 1 mg DST in 5 subjects, the mean serum cortisol levels were 1.35 ± 0.13 mcg/dL and the mean serum dexamethasone levels, and ACTH levels were 282 ± 44 ng/dL and 5.92 ± 1.56 pg/mL, respectively. However, in one subject (BMI 43.5) the post-DST cortisol level was 2.96 mcg/dL with corresponding dexamethasone level of 138 ng/dL and ACTH level of 21 pg/mL. However, following 2 mg DST in all 6 subjects the serum cortisol levels were less than 1.8 mcg/dL (1.21± 0.22 mcg/dL) with ACTH levels (3.87 ± 0.70 pg/mL) and dexamethasone levels of 482 ± 80 ng/dL. The LNSC levels were normal in 4 subjects (0.010 ± 0.005 mcg/dL), whereas in 2 subjects these were minimally elevated. 24-hour urine cortisol levels were normal in 5 subjects (29.4 ± 3.74 mcg) and in one subject this was mildly elevated (67 mcg). Long term follow-up of all subjects confirmed normal cortisol status. Previous studies have demonstrated that routine CS screening of patients affected by severe obesity is not indicated. However, other investigations have shown CS may occur in a small percentage of severe obese patients. In conclusion, 2 mg DST is a preferred test in obese patients suspected to have CS although 1 mg DST generally can be used as an initial screening test. Additionally, serum dexamethasone and ACTH measurements may still be useful in patients who are suspected to have a false-positive DST. Presentation: 6/1/2024

6426 Pregnancy-induced ACTH-independent Cushing Syndrome: A Rare Phenomenon Secondary To Aberrant Receptors On Adrenal Glands

Abstract Disclosure: K. Manglani: None. S.T. Sharma: None. Pregnancy-induced hypercortisolism is a rare phenomenon with very few cases reported in the literature. The pathogenesis is thought to be secondary to the expression of aberrant LH/hCG receptors on the adrenal gland that stimulate cortisol production in pregnancy. We present a case of a 31-year-old female with no past comorbidities until her first pregnancy in 2017 when she gained around 50lbs, developed violaceous striae, acne, hirsutism, depression with suicidal ideation for which she was hospitalized twice, and underwent emergent C-section at 34 weeks’ gestation due to pre-eclampsia. She was referred to the Endocrinology clinic post-delivery, and screening for Cushing syndrome was negative at that time: 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC) and 1-mg dexamethasone (dex) suppression test (DST) were normal. She presented again in 2020 during her second pregnancy at 14 weeks gestation, with 20lb weight gain in the first trimester, acne, hirsutism, and easy bruising. Labs showed cortisol of 22.4 mcg/dL (6.2-19.4), ACTH <1.5 pg/mL, total testosterone 168 ng/dL (8-48), androstenedione 751 ng/dL (41-262), DHEAS 91.2 mcg/dL (84.8-378), 24-hour UFC 277 mcg/day (6-42), LNSC 0.671 mcg/dL, 1mg DST with post-dex cortisol 24 mcg/dL (dex level 58 ng/dL), and 8-mg DST with post-dex cortisol level of 28.2 mcg/dL (dex level 457 ng/dL). Testing was consistent with ACTH-independent Cushing syndrome. Ultrasound and MRI of the abdomen/pelvis showed normal adrenal glands with no hyperplasia or mass. Given worsening hypercortisolism and her course during a prior pregnancy, medical treatment with metyrapone was initiated. We started at a dose of 500 mg daily and gradually increased to 1500 mg with close monitoring of her blood pressure and cortisol levels. She underwent vaginal delivery at 38 weeks’ gestation, and the baby required a brief stay in the NICU for respiratory distress but was otherwise doing well. The patient developed secondary adrenal insufficiency post-delivery requiring hydrocortisone, with recovery of her HPA axis in around 10 weeks. Since then, she has been off hydrocortisone with normal UFC, ACTH, and cortisol levels. This case enables discussion regarding the underlying etiology, diagnostic difficulties, and management of this rare condition. Although the exact etiology is unknown, the postulated mechanism is aberrant LH/hCG receptor expression given the patient’s presentation during each pregnancy, normal cortisol levels between both pregnancies, and a brief period of adrenal insufficiency post-delivery. Management of hypercortisolism during pregnancy remains challenging. Metyrapone, a steroidogenesis inhibitor, can be considered for control of hypercortisolemia during pregnancy (off-label) in select cases to prevent maternal and fetal complications. Presentation: 6/1/2024

8475 Automated Insulin Delivery System with Concentrated Regular U500 Insulin in Cushing Syndrome

Abstract Disclosure: F. Erenler: None. J. Aurora: None. Background: Concentrated regular U-500 (U-500R) insulin is commonly used in patients with T2DM, who are highly insulin-resistant, requiring more than 200 units of insulin per day. Utilizing U-500R reduces the number of daily injections, decreases injection volume, and improves cost effectiveness. There has been a case report with U-500R in an automated insulin delivery (AID) system with successful results (1). To our knowledge there is no data on AID system use in Cushing patients with T2DM using U-500R. We present a case of a patient with Cushing Syndrome (CS) with poor BG control using >250 units/day of SC U-500R with improved BG control after switching to Omnipod 5 AID system. Clinical Case: A 57 y.o. male initially presented with hypogonadotropic hypogonadism and subsequently diagnosed with ACTH-dependent CS, which is complicated by obesity, uncontrolled T2DM, lower extremity wounds, and DVTs. He was diagnosed with CS with multiple abnormal 1 mg dexamethasone suppression tests (DST) (max AM cortisol 5.9 mcg/dL; RR <1.8 mcg/dL, dexamethasone level 300), elevated urine free cortisol (UFC) (max UFC/Cr 77.6 mcg/mg/L; RR: 5-64 mcg/24-hr) and elevated salivary cortisol (max cortisol 0.2 mcg/dL; RR: <0.09 mcg/dL). He had suppressed cortisol with 8 mg DST. An MRI sella showed left-sided hypoechoic 0.9 cm mass. Desmopressin (DDAVP) stimulation test and Ga-68 DOTATATE-PET scan were negative. As a result of his abnormal MRI sella and elevated cortisol, he underwent transsphenoidal surgery of the left pituitary. Pathology was non-diagnostic for a pituitary adenoma. Post-op 24-hr UFC and 1 mg DST levels remained high. DDAVP stimulation test and Ga-68 DOTATATE-PET were repeated post-op and were negative. Due to complications of CS, he was initially treated with cabergoline, but switched to osilodrostat due to intolerances. He is currently on 2 mg BID dose and 24-hr UFC has been normal since then (UFC 20 mcg/L, Cr 0.67 mg, UFC/Cr 12 mcg/mg/L). He continued to have uncontrolled hyperglycemia despite normalization of UFC. On his CGM data, he was in target range (70-180 mg/dL) 5% of the time despite using U-500R 95 units SC TID. Given his severe hyperglycemia and insulin resistance, he was switched to an AID system with U-500R and his time in target range improved over 60% after a month of use and his total daily dose of insulin decreased to less than 200 units. Conclusion: U-500R proved to be safe and effective with Omnipod 5 AID. To our knowledge, this is the first reported patient with CS using U-500R with Omnipod 5 AID. In patients without CS, the AID algorithm continuously kept BG well below the set target, especially overnight. Notably, our patient did not have this overnight hypoglycemia trend, which should be expected with his disease. We are hoping to increase the awareness of U-500R with AID systems, especially for patients with incurable CS. Reference:1.Aurora J Jr, Saraswat A. J Endocr Soc. 2023;7(Suppl 1):bvad114.873. Presentation: 6/3/2024

9360 Evaluating The More Accurate Indicator Of Kidney Function In Mild Autonomous Cortisol Secretion: EGFR Creatinine Versus EGFR Cystatin

Abstract Disclosure: L. Rahimi: None. J. Saini: None. E. Atkinson: None. S. Achenbach: None. A. Kattah: None. I. Bancos: None. Introduction: Patients with mild autonomous cortisol secretion (MACS) have higher prevalence of cardiovascular comorbidities including chronic kidney disease. However, considering that patients with MACS may have relative skeletal muscle atrophy, it is unclear whether the creatine-based assessment of kidney function is accurate in this population. Objective: To characterize the differences in assessing estimated glomerular filtration rate using cystatin (eGFRcys) versus creatinine (eGFRcre) in patients with MACS versus referent subjects. Methods: Cross-sectional single-center study, 2019-2022. MACS was defined as serum cortisol concentration >1.8 mcg/dL after the 1 mg overnight dexamethasone suppression test (DST). For each patient, eGFRcre, eGFRcys and eGFRcre/eGFRcys ratio were measured and compared between the two groups. Body composition was measured by DXA scan. The Kruskal-Wallis test was used to compare measurements between groups. Result: A total of 37 patients with MACS (median age 59 years (interquartile range, IQR 47-67), 25 (68%) women) and 45 referent subjects (median age 57 years (IQR 51-66), 30 (67%) women) were included. The distribution of BMI, total body fat mass and total body lean mass were similar between the two groups. In the MACS cohort, the median cortisol following 1-mg DST was 3.0 ug/dL (IQR, 2.2-4.0). While assessment of kidney function with eGFRcre showed no differences between patients with MACS and referent subjects (median 85.1 vs 87.0 ml/min/1.73m2, P=0.431), kidney function using eGFRcys was lower in MACS (median 78.0 vs 89.3 ml/min/1.73m2 in referents, P<0.014), resulting also in a higher eGFRcre/eGFRcys ratio (median 1.07 vs 0.97 in MACS vs referents, P=0.053). After adjusting for age, sex, and BMI, a higher 1 mg DST cortisol level in the MACS cohort was associated with a higher eGFRcre/eGFRcys ratio (Spearman correlation coefficient of 0.35, P = 0.042). Lower eGFRcys was associated with higher fat mass (Spearman correlation of -0.26, P = 0.023), and a higher eGFRcre/eGFRcys ratio showed a trend towards lower lean mass (Spearman correlation of -0.20, P = 0.081). Conclusion: Creatinine-based eGFR assessment in patients with MACS underestimates the degree of kidney dysfunction, likely due to underlying skeletal muscle atrophy. eGFRcys is a more accurate indicator of kidney function in patients with hypercortisolism. Presentation: 6/1/2024

7822 Mild Autonomous Cortisol Secretion In High Suspicious Adrenal Incidentaloma

Abstract Disclosure: N. Zavrashvili: None. N. Margvelashvili: None. K. Chanturishvili: None. Mild Autonomous Cortisol Secretion in High Suspicious Adrenal IncidentalomaIntroduction: Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. 55-year-old women with 5-year history of hypertension and hyperlipidemia. She was treated with a three-drug program: verapamil 250 mg daily, combined B-blocker, atenolol 100 mg and chlorthalidone 25 mg daily. Blood pressure control remained suboptimal. Her body mass index was 29,5 kg/m2. She had no signs or symptoms of overt Cushing syndrome.She was referred to CT coronary angiogram by her cardiologist, which revealed adrenal incidentaloma.Adrenal dedicated CT showed left-sided 3,4 cm high density node (41HU), with absolute washout <60. She was consulted by oncologist to exclude adrenal metastasis. The baseline laboratory test results excluded PA and Pheochromocytoma. The diagnosis of glucocorticoid secretory autonomy was based on positive low-dose dexamethasone suppression test (DST), low serum ACTH concentration, low-normal DHEA-S and lack of complete suppression of serum cortisol with an overnight 8-mg DST. Patient was referred to left-sided laparoscopic adrenalectomy with perioperative glucocorticoid coverage (100 mg hydrocortisone administered IV and again 8 hours later). Conclusion: Mild autonomous cortisol secretion is a term used to describe biochemical evidence of abnormal cortisol secretion in patients with adrenal incidentaloma, but without the classical external manifestations of overt CS, such as central muscle weakness, adipose tissue redistribution, and skin fragility. The management of patients with an incidentally discovered adrenal adenoma who do not have overt Cushing’s syndrome but who have MACS is more controversial as the available studies comparing outcomes of adrenalectomy vs conservative management have been generally small. It is associated with an increased risk of Type 2 diabetes mellitus, HBP, obesity, dyslipidemia, and global cardiovascular risk. Therefore, it is of great importance to correctly identify these patients. There are different tests for the screening of hypercortisolism. However, in the absence of a single test considered as the gold standard, it is necessary to combine the different tests to reach an adequate diagnostic capacity. The indication of surgery in ACS patients should be based mainly on the hormonal evaluation and the comorbidities potentially mediated by cortisol. Presentation: 6/1/2024

8356 Total Hypophysectomy in Cushing’s Disease: Results from a Terciary Center

Abstract Disclosure: M.V. Lopes: None. M.D. Severino: None. J. Rocha: None. C.R. Peixe: None. M.I. Alexandre: None. A. Gomes: None. M.J. Bugalho: None. Introduction: Transsphenoidal surgery (TSS) is the first line treatment for Cushing’s disease (CD), leading to remission in 70-80% of cases. Though selective adenomectomy is the preferred approach, total hypophysectomy may be needed. Objective: To describe 3 CD patients in which total hypophysectomy was performed. Clinical cases 1. A 58-year-old man with a history of type 2 diabetes (T2D) and obesity, was referred to the Endocrinology Clinic due to abdominal purple striae and facial plethora. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, high 24h urinary cortisol and no cortisol suppression in the overnight 1mg dexamethasone suppression test (DST). The CRH test was suggestive of CD but no adenoma was found on pituitary MRI. Inferior petrosal sinus sampling (IPSS) was compatible with CD with right-sided lateralization. Right hypophysectomy was performed but no CD remission was achieved, so the patient underwent total hypophysectomy. Corticotroph hyperplasia was identified in histology. After 9 months of follow-up, he mantains CD remission. 2.A 37-year-old woman was diagnosed with ACTH dependent hypercortisolism after referral to the Endocrinology Clinic for alopecia, amenorrhea, hypertension and hirsutism. Laboratory tests showed severe hypokalemia, high plasma ACTH and 24h urinary cortisol and the MRI showed a right-sided macroadenoma. Nonetheless, considering the clinical severity, an IPSS was performed and definitely excluded an ectopic Cushing’s syndrome (CS) thus confirming the diagnosis of CD with right-sided lateralization. The patient underwent selective TSS, however, for lack of CD remission, total hypophysectomy was performed. Histology revealed an adenocorticotrophic adenoma. Yet, a year later, she maintains persistence of CD, although less severe, and is under treatment with metyrapone. 3.A 58-year-old woman with a history of T2D and class 3 obesity, was evaluated in our Endocrinology Clinic due to obesity. Her physical examination suggested CS, so this hypothesis was investigated. Laboratory tests suggested ACTH dependent hypercortisolism, with normal serum ACTH, elevated 24h urinary cortisol and no cortisol suppression in the overnight 1mg DST. The high dose DST was suggestive of CD but the pituitary MRI didn’t show an adenoma. IPSS was compatible with CD but it was not possible to determine lateralization. So, total hypophysectomy was performed. An adenocorticotrophic adenoma was identified in histology. Postoperative CD remission was achieved and persists 3 months later. Conclusions: These 3 cases highlight the challenge of treating CD and suggest that in certain cases total hypophysectomy may be the treatment of choice to cure or at least improve CD. Although it is associated with more complications than selective TSS, our patients had no complications, only developed panhypopituitarism and diabetes insipidus. Presentation: 6/1/2024

6917 Multiple Red Herrings Complicating the Diagnosis of Cyclic Cushing’s Syndrome

Abstract Disclosure: A. Grover: None. R. McGlotten: None. L.K. Nieman: None. Introduction: Cyclic Cushing’s syndrome (CCS) is a rare disorder characterized by intermittent hypercortisolemia. It may be caused by pituitary tumor (Cushing disease), ectopic ACTH tumor secretion (EAS), or primary adrenal disease. We present a case of CCS with multiple red herrings complicating the diagnosis. Case: A 57-year-old Cushingoid appearing woman presented elsewhere with weight gain, brain fog, weakness, hypertension, worsening diabetes, and OSA. Screening tests showed more than three episodes of hypercortisolism with interval eucortisolism: salivary and 24-urine cortisol (UFC) ranged from 0.06-0.34 µg/dL (reference range, RR, ≤0.09 µg/dL) and 59.7-137.1 µg/24 h (RR 4-50 µg/24 h) respectively. The patient was symptomatic throughout. Differential diagnosis was CCS vs a physiologic non-neoplastic condition. As she had no clear etiology for the latter, further testing was performed. ACTH was indeterminate (23-27 pg/mL, RR <46). Pituitary MRI showed a left 7 mm lesion. Inferior petrosal sinus sampling (IPSS) with Corticotropin Releasing Hormone (CRH) administration showed peripheral baseline ACTH levels of 9.0 and 10.0 pg/mL, suggesting that she had cycled out of a hypercortisolemic phase. The left petrosal baseline values were low (9 pg/mL,16 pg/mL), suggesting poor catheterization, which was confirmed by a low prolactin-normalized ACTH ratio. The petrosal levels were lower than expected (maximum 767 pg/ml), due to suppression of normal corticotropes vs poor tumor response. However, a central:peripheral step-up was consistent with Cushing's disease (CD) or pseudo-CS. She was referred to us for re-evaluation. A low FSH, LH, low normal TSH, and UFC of 160 µg/24h supported a diagnosis of CS. ACTH was 14.6 pg/mL. Pituitary MRI showed a 1.3 cm x 0.8 cm mass extending into the left cavernous sinus. She did not suppress cortisol during a dexamethasone suppression test (DST). After CRH administration ACTH levels doubled. Based on the macroadenoma and CRH response, CD was established; IPSS was not repeated. After transsphenoidal hypophysectomy, pathology revealed ACTH positive adenoma. Post-operative adrenal insufficiency required hydrocortisone replacement. Conclusion: CCS can pose a diagnostic challenge due to unpredictable duration and frequency of hypercortisolism. Intermittently elevated cortisol levels with CS symptoms should raise suspicion for CCS. In our case, low peripheral ACTH levels further suggested this possibility. DST may give spurious results in CCS owing to spontaneous falls or rises in cortisol at the time of testing. Prolonged hypercortisolism is required in all patients to ensure suppression of normal corticotropes, which if not complete, may confound results in patients with EAS. Finally, inadequate catheterization may affect accuracy of lateralization in any patient with CS and is ideally evaluated both by venography and prolactin measurement. Presentation: 6/1/2024

8117 Late-night Salivary Cortisol in the Diagnosis of Cushing's Disease Recurrence

Abstract Disclosure: A.E. Alexandre: None. P.C. Elias: None. M. De Castro: None. L.M. Mermejo: None. D.C. Aragon: None. A.C. Moreira: None. Cushing’s Disease (CD) remission following transsphenoidal surgery (TSS) is most often defined by low morning cortisol levels and the requirement of glucocorticoid (GC) replacement therapy. However, CD recurrence is not a well studied event. There is no standard definition of remission criteria and no accurate cutoff for biochemical tests on CD recurrence. Late-night salivary cortisol (LNSC) has been shown to have higher accuracy in confirming CD recurrence than urinary free cortisol and dexamethasone suppression test (DST). However, few studies addressed LNSC performance following remission after TSS. The study aimed to establish cutoff values of LNSC with higher sensitivity (S) and specificity (E) in CD recurrence diagnosis.In a retrospective cohort study of 65 patients with remitted CD after TSS, remission was defined as improvement of sign and symptoms related to CD and a plasma cortisol <5mcg/dL in 30 days following TSS. Eleven patients progressed to permanent adrenal insufficiency and were excluded from the study. All 54 patients had at least four LNSC sampling and a minimal follow-up of 24 months after TSS. LNSC was determined by RIA. A cutoff value of 270 ng/dl for LNSC is used for the diagnosis of CD. Patients were divided in three different groups: Overt Recurrence (OR): elevated LNSC and worsening of CD`s signs and symptoms. Remission (RM): normal LNSC and no clinical signs of CD recurrence. Biochemical Recurrence (BR): at least 2 elevated biochemical parameters (LNSC or DST) but no worsening of signs and symptoms associated with CD. The mean of the 2 LNSC last values when OR was diagnosed and the mean of 2 LNSC last values of follow up for RM patients were used to estimate the accuracy of LNSC for diagnosing recurrence using a ROC curve (AUC) and its 95% confidence interval. Of the 54 patients included, 46 females; 8 males; mean age at diagnosis: 32 years, (5 – 58 yrs); mean time of follow-up: 12.8 years (4 – 31.7 yrs). Thirteen were classified as OR, 18 as RM and 23 as BR; and mean time of GC use after TSS was: 8.7; 34 and 17 yrs, respectively, significantly lower in OR compared to RM (p:0.046). A LNSC cutoff value of 272 mcg/dL had sensitivity of 85% and specificity of 95% (AUC: 0.97; 95% IC = [0.93; 1,00]) for CD recurrence diagnosis. BR patients presented LSNC fluctuation along follow-up.LNSC is a useful tool for CD recurrence screening. Setting LSNC specific assay cutoff values might be needed. LSNC cutoff values were similar for the initial CD diagnosis, as well as for CD recurrence diagnosis. Shorter time of GC replacement may be an important predictor of CD recurrence. Patients with BR should be followed more carefully as they may be at higher risk of recurrence. Multiple LNSC sampling on successive days can be easily performed and may detect subtle changes in cortisol rhythm. Presentation: 6/1/2024

6853 A Curious Case of MACS

Abstract Disclosure: M. Dillon: None. A. Syeda: None. V. Kantorovich: None. Introduction: Mild autonomous cortisol secretion (MACS) is characterized by biochemical evidence of mild hypercortisolemia inducing metabolic comorbidities without any obvious phenotypic stigmata of Cushing’s syndrome (CS). This case highlights the challenges faced in the diagnosis and management of MACS. Case: A 76-year-old female with past medical history of class II obesity (BMI 31.83 kg/m2), type 2 diabetes mellitus, hypertension, hyperlipidemia, osteoporosis and chronic kidney disease stage IIIb was diagnosed with MACS after an overnight 1 mg dexamethasone suppression test (DST) showed unsuppressed 8 AM cortisol of 2.4 mcg/dL (<1.8 mcg/dL). Dexamethasone level was appropriate at 355 ng/dL (180-550 ng/dL), ACTH was <5 pg/mL (6-50 pg/mL) and DHEA-S was normal. Late night salivary cortisol (LNSC) levels were elevated to 0.12 mcg/dL (< 0.09 mcg/dL). The 24-hour urine cortisol level was normal. Baseline 8 AM cortisol level was 17 mcg/dL and ACTH was 19 pg/mL. Abdominal CT scan showed a 1 cm left adrenal nodule of 25 HU density and a normal right adrenal with no atrophy. Phaeochromocytoma and primary hyperaldosteronism work up was negative. She started on Mifepristone 300 mg daily and titrated up to 600 mg daily. She presented to our institution one month later with 1 week of nausea, vomiting and muscle weakness. Laboratory studies revealed acute kidney injury with creatinine of 6.69 mg/dL (baseline Cr 1.5 mg/dL) and rhabdomyolysis with creatinine kinase level of 12,819 U/L (24-173 U/L) and urine myoglobin level of 888 ng/mL (0-13 ng/mL). It was evident that her catastrophic presentation was from development of adrenal insufficiency in the setting of Mifepristone glucocorticoid receptor blockade. The drug was discontinued immediately. She was treated with intravenous hydration and intermittent diuretics. Over 10 days, her clinical status gradually improved and creatinine decreased to baseline levels. Discussion: MACS is a challenging diagnosis as cortisol levels are affected by several variables including obesity, drugs, and poorly controlled diabetes. Hence, a meticulous evaluation is mandated before confirming the diagnosis. Our patient’s baseline cortisol and ACTH levels were normal, and her DST and LNSC levels were mildly elevated. Unilateral cortisol producing adenoma causes contralateral gland atrophy due to suppressed ACTH. This was not evident in our patient, thus making the diagnosis questionable. Adrenalectomy is the treatment of choice in MACS with adrenal adenoma. Off label medical management with Mifepristone, a glucocorticoid receptor antagonist, is being pursued in select cases and was trialed due to our patient's age and surgical risk. Mifepristone is approved for the treatment of hyperglycemia due to CS. The data supporting its use in MACS is sparse. Therefore, it is important to be aware of associated risks of Mifepristone when advising patients. Presentation: 6/3/2024

9388 Unusual Case Of Ectopic Adrenocorticotropic Hormone Syndrome Secondary To Non-small Cell Lung Cancer

Abstract Disclosure: A. TakallooBakhtiari: None. G.L. Nunlee-Bland: None. V. Ganta: None. A. Zenebe: None. H. Abdalla: None. A. Elobeid: None. W.A. Odonkor: None. Introduction: Ectopic adrenocorticotropic hormone syndrome (EAS) is a rare condition due to adrenocorticotropic hormone (ACTH) release from non-pituitary tumors. It increases the mortality of affected patients thus finding and removal of the ACTH-producing source allows for curing or reduction of symptoms and serum cortisol levels. The most common cause of EAS is lung cancer. Cushing syndrome (CS) due to EAS is an uncommon paraneoplastic phenomenon in non-small cell lung cancer. Clinical case: The patient is an 80-year-old man with a past medical history of hypertension, dementia, stroke, schizophrenia, and recently diagnosed lung adenocarcinoma. He presented with a few weeks history of dysuria and generalized fatigue. There was no family history for any endocrine disorders. He has a 40 pack-year history of tobacco use. He denied alcohol or illicit drug use. Upon initial evaluation, VS: BP 155/95 mmHg, HR 82 beats/min, Ht 77 inches, Wt 125 lb with a BMI 14.7 Kg/m2. He had no typical symptoms of CS. A physical exam showed a cachectic man with no other remarkable findings. Laboratory tests on admission showed severe hypokalemia of 1.8 mEq/L (3.5-5 mEq/L) with hypochloremic metabolic alkalosis. (bicarbonate 45 mEq/L (22-28 mEq/L) and chloride 79 mEq/L (96-106 mEq/L)). Patient was normoglycemic with HbA1c of 5.0%. Random morning cortisol was 55 μg/dL (13-24 μg/dL). Supine renin and aldosterone levels were 0.45 ng/ml/h (0.25-5.8 ng/ml/h) and 1.0 ng/dL (3-16 ng/dL), respectively, excluding hyperaldosteronism. Beside urinary tract infection, other biochemical workup revealed elevated 24-h urinary free cortisol level 5233 mcg/24h (4.0-50.0 mcg/24h) with creatinine 0.7 g/24h (0.5-2.15 g/24h). Failure to suppress cortisol with low dose dexamethasone suppression test (LDDST) was evident: morning cortisol >60.0 g/dL , with concurrent serum dexamethasone 299 ng/dL (180-550 ng/dL). Plasma ACTH level was elevated 327 pg/ml (6-50 pg/ml), favoring ACTH-dependent CS. A magnetic resonance imaging (MRI) of the sella and computed tomography (CT) of the abdomen did not show pituitary or adrenal masses. Therefore, a diagnosis of ectopic CS due to lung cancer was established. Pathology of the lung mass showed tumor cells were negative for synaptophysin, chromogranin, and CD52. The immunohistochemically findings support primary adenocarcinoma of the lung. Patient refused surgical or medical treatment and was discharged to a hospice facility. Conclusion: The clinical presentation of EAS ranges from the abrupt onset of the signs and symptoms of severe hypercortisolism, including hypertension, hypokalaemia, metabolic alkalosis as in our patient to the gradual and slow onset of the classical signs and symptoms of CS. Though EAS with adenocarcinoma of the lung is rare, it is important to consider it within the differential diagnosis of any adenocarcinoma of the lung presenting with the relevant symptoms. Presentation: 6/3/2024

7469 A Case of Severe Transient Hypercortisolism In a Patient With Bacterial Meningitis

Abstract Disclosure: R. Harxhi: None. D.V. Mihailescu: None. Background: Increased cortisol levels are known to occur in states of significant stress caused by acute illness. This may be attributed to stress leading to a rise in the corticotrophin releasing hormone thereby increasing adrenocorticotrophic hormone levels. This may consequently result in severe transient hypercortisolism and bilateral adrenal structural changes.Clinical case:A 55-year-old female with a past medical history of HTN and pre-diabetes presented to the hospital with a headache and altered mental status starting the day prior to admission. On arrival, she was found to be hypertensive, confused and was diagnosed with acute bacterial meningitis caused by streptococcus pneumoniae. Initial labs were notable for a potassium level of 2.5 mEq/L (normal 3.5-5 mEq/L). Work-up of persistent hypokalemia revealed a cortisol of 54.83 ug/dL (normal 6.7-22.6 ug/dL), ACTH 166 pg/mL (normal 9-50 pg/mL), aldosterone < 1 ng/dL (normal 3-16 ng/dL), and renin 0.57 (normal 0.25-5.82). CT of the abdomen showed bilateral periadrenal fat stranding, larger on the left with no adrenal nodules. On physical exam, patient did not exhibit any cushingoid features. Significantly elevated AM cortisol levels persisted despite treatment with high dose dexamethasone as part of the meningitis regimen (20 mg) resulting in unsuppressed AM cortisol of 9.22 ug/dL. An MRI of the brain showed a partially empty sella rendering a pituitary adenoma unlikely. Patient’s clinical status improved rapidly, and hypokalemia resolved. A low dose dexamethasone suppression test performed 9 days post admission produced an appropriately suppressed cortisol (1.0 ug/dL) and ACTH (14 pg/mL) levels, thus confirming a functional response to acute illness. Conclusion: This is a rare case of severe transient hypercortisolism with periadrenal congestion (“fat stranding”) resulting in hypokalemia (likely due inappropriate activation of mineralocorticoid receptors) in the setting of acute illness. There have been a very limited number of similar cases reported in literature, particularly with respect to CNS infections. It is important to recognize the response to acute stress could produce significant elevation of cortisol levels leading to the activation of mineralocorticoid receptors, therefore mimicking primary hyperaldosteronism. Presentation: 6/1/2024

8411 Ectopic ACTH-dependent Cyclical Cushing’s Syndrome- the Art of Hide-and-seek

Abstract Disclosure: H. Mon: None. A. Kapoor: None. S. Qureshi: None. M. Martineau: None. K. Meeran: None. Case report: A 72-years-old lady was admitted with hypokalaemia, hyperglycaemia with metabolic alkalosis with background hypertension, type2 diabetes, osteoporosis and right-sided breast cancer treated with chemotherapy and radiotherapy 3years ago. She was previously seen in Endocrinology Clinic for similar episode and deemed not having Cushing’s or Conn’s syndrome on workup. During this admission, although there was no obvious Cushingoid appearance, there was refractory hypokalaemia. On further exploration, there were previous admissions with similar episodes in UK and in her home country, within the same year, a few months apart. Therefore, endocrinology workup was conducted for suspected cyclical Cushing’s syndrome. It demonstrated raised 24-hour urinary free cortisol of 5643 nmol/24hour (reference range 0-164 nmol/24hours), unsuppressed low dose dexamethasone suppression test with cortisol level of 800 nmol/L and increased ACTH level of 429 ng/L. MRI (pituitary) showed no pituitary lesion with probable empty sella and CSF filled. However, CT (thorax) showed enlarging lesion (previously from 1cm to 1.6cm) in the left lower lobe, concerning lung metastasis or primary lung malignancy. PET scan showed left lower lobe nodule having low-grade activity with likelihood of indolent malignancy and appearances of physiologic adrenal hyperplasia. Management: Given persistently high cortisol levels during admission with ongoing hyperglycaemia and refractory hypokalaemia, metyrapone was started and titrated accordingly. Her clinical condition including potassium and cortisol levels effectively responded to metyrapone. Gallium scan was booked for detail localization with ongoing lung MDT (multidisciplinary team meeting) and neuroendocrine tumour MDT.However, after starting metyrapone, she had type 1 respiratory failure, not responding to initial antibiotics. After excluding other possible respiratory aetiologies, empirical treatment for Pneumocystosis pneumonia (PCP) was initiated, after which blood test for Beta-D-glucan was found out to be significantly raised, supporting the presumptive diagnosis. Conclusion: Our case highlighted the following interesting points 1. diagnostic challenges, due to the fluctuating nature of cyclical Cushing’s syndrome, presenting with recurrent hypokalaemia. 2. the interesting nature of likely ACTH-dependent cyclical Cushing’s syndrome, progressing into florid Cushing’s syndrome, with efficacy to metyrapone 3. rare and compelling combination of 3 conditions of Cyclical Cushing’s syndrome, being ectopic ACTH-dependent and complicated by Pneumocystosis pneumonia (PCP). Presentation: 6/1/2024

7109 "My Stomach hurts": A Rare Case of Adrenal Cortical Carcinoma

Abstract Disclosure: R.C. Attah: None. I. Sirisena: None. Pheochromocytoma/Paragangliomas are rare neurogenic tumors that arise from chromaffin cells present in the adrenal medulla or extra-adrenal paraganglia, these cells produce catecholamines. Typically, these tumors are discovered as incidentalomas. They can be hereditary as seen in genetic syndromes like multiple endocrine neoplasia type 2A or 2B, neurofibromatosis type 1 or Von Hippel Lindau syndrome but can occur sporadically. Patients typically present with hormonal hypersecretion signs or symptoms like abdominal pain, episodic headaches, sweating, hypertension and tachycardia, but some patients are asymptomatic. Patient is a 37-year-old female with past medical history of hypertension, type 2 diabetes mellitus and fatty liver who presented to the ED with abdominal pain for a few weeks. On arrival, her vitals were BP 205/124, HR 102, RR 14 and SpO2 100% on room air. CT abdomen was obtained which showed a 7.6 x 4.7 x 5.7 cm mass replacing left adrenal gland with small left retroperitoneal hemorrhage worrisome for adrenal cortical carcinoma, metastatic disease or pheochromocytoma. Hormonal workup revealed elevated 24-hr urine cortisol 124.2mcg (ref 4.0-50.0mcg/24h), normal aldosterone/renin ratio 10.63ng/dL (ref <30ng/dl), failed low dose dexamethasone suppression test with post-dex AM cortisol 7.20ug/dL (ref <1.8ug/dL), slightly elevated serum total catecholamine 1256pg/mL (242-1125 pg/mL), norepinephrine 1155pg/mL (ref 217-1109 pg/mL), total metanephrine and normetanephrine 341pg/mL (reg <205 pg/mL), normetanephrine 244.1 (ref <210.1pg/mL), elevated 24-hr urine normetanephrine 700ug/L (ref 131-612ug/L), metanephrine 136ug/L (ref 36-209ug/L) and DHEA-s level 285ug/dl (ref 23-266ug/dL). Due to elevation in cortisol, adrenal cortical carcinoma was suspected as these tumors are frequently associated with cortisol secretion. However, pheochromocytoma with co-secretion of ACTH could not be excluded. She was started on doxazosin for alpha blockade and eventually started on beta blockade with Metoprolol. She underwent a left adrenalectomy and was started on steroid taper post-op due to concern of cortisol co-secretion. Surgical pathology was positive for Left adrenal malignant pheochromocytoma and ganglioneuroma. Genetic panel was negative with no mutation identified in the 54 gene Hereditary paraganglioma-pheochromocytoma panel. This patient had a large adrenal tumor (>4cm mass) but mildly elevated catecholamines which could have led to misdiagnosis as her catecholamine levels were less than 2-3x ULN which is unusual for pheochromocytomas. Roughly 25% of people with pheochromocytoma are undiagnosed throughout their lifespan. This condition can be life-threatening, hence early diagnosis and intervention can be lifesaving. Prognosis of malignant pheochromocytoma is dependent on tumor size, presence of SDHB gene mutation or visceral metastases. Presentation: 6/1/2024

8412 Resolution of Central Hypothyroidism shortly after Transsphenoidal Surgery For Cushing’s Disease

Abstract Disclosure: L. Esper: None. A. Ibrahim: None. N. El Asmar: None. Background: Cushing's disease is a rare endocrine disorder characterized by excessive cortisol production, resulting in various metabolic disturbances. Hypercortisolism is known to cause central hypothyroidism. The mechanism is complex and involves hypercortisolism mediated decreased TRH and TSH secretion in addition to inhibition of peripheral deiodination. This case details the successful management and recovery of a patient with Cushing's disease and reversal of central hypothyroidism after pituitary surgery.Case:A 43-year-old man was evaluated for central hypogonadism, 20 pound weight gain with central weight distribution, and the development of purple abdominal striae for the past year. He had a normal thyroid exam and appeared euthyroid. He was alsodiagnosed with hypertension and prediabetes in the past yearrequiring medical therapy.A low dose dexamethasone suppression test (DST) resulted in AM cortisol of 12.9 mcg/dl. Two adequate 24hr Urinary cortisol measurements showed elevated cortisol excretion at 458 and 378mcg/24. Lab evaluation revealed elevated cortisol levels along with elevated adrenocorticotropic hormone (ACTH) levels(ACTH of 172 pg/ml with a cortisol level of 23.9 mcg/dl). A high dose DST demonstrated suppression of cortisol to 3.4 mcg/dl. MRI pituitary was performed which showed a clearright sided 7mm pituitary adenoma.Thyroid function tests performed were consistent with central hypothyroidism, with low levels of free thyroxine (FT4) at 0.67ng/dl along with an inappropriately low normal thyroidstimulating hormone (TSH) at 0.596 uIU/ml. Total T4 was low at 4 ug/dl in addition to a low total T3 of 66 ng/dl. Remaining labs revealed central hypogonadism along with slightly elevated prolactin of 16 ng/ml. He was not started on thyroid hormone.He then underwent transsphenoidal surgery for tumor removal. He developed post-operative adrenal insufficiency (cortisol 2.12 mcg/dl) 16 hours post-op after which he was started on hydrocortisone replacement, indicating remission. 12 hours post-op, his TSH was 0.656 uIU/ml with a free t4 of 0.79 ng/dl, both in the normal range. 36 hours post-op, TSH was 0.524 uIU/ml and free t4 was 1.15 ng/dl. Histopathological examination confirmed the diagnosis of an ACTH-secreting pituitary adenoma.At 4 weeks post-op, thyroid labs showed normal FT4 (1.07ng/dl) and TSH (2.06uIU/ml). Conclusion: Hypercortisolism causes a global inhibition of the thyroid axis, with decreased levels of TSH, T4, and T3 (1). Previous studies suggest the monitoring of thyroid function at 6 and 12 months after surgical cure of hypercortisolism. Our case suggests that the resolution of hypothyroidism occurs shortly after surgery for Cushing’s disease and the need for earlier monitoring. Presentation: 6/3/2024

8479 A Challenging Case of Hypercortisolism in an Adult Patient With McCune Albright Syndrome

Abstract Disclosure: P. Kesavan Chary: None. S. Jasim: None. Background: McCune Albright Syndrome (MAS) is a rare genetic disorder that occurs due to a spontaneous post-zygotic missense mutation in the GNAS gene resulting in activating gain of function mutations in G-proteins. MAS classically presents as a triad of café-au-lait skin pigmentation, fibrous dysplasia of bone, and precocious puberty. However, continuous autonomous stimulation of endocrine glands can also result in various other endocrinopathies. We present a rare case of hypercortisolism due to bilateral multinodular adrenal hyperplasia (BMAH) in an adult patient with MAS. Case Report: A 38 year old female had MAS, clinically manifested by precocious puberty, renal phosphate wasting with rickets and osteomalacia, fibrous dysplasia of bone with history of multiple fractures, growth hormone excess, and multinodular thyroid status-post total thyroidectomy. A surveillance CT abdomen showed bilateral (right 3.8 x 1.3 cm and left 1.0 x 0.9 cm) adrenal adenomas with low intrinsic attenuation and washout. On diagnosis, the patient had an AM cortisol of 32.5 ug/dL (6.2-19.4 ug/dL) after a low-dose dexamethasone suppression test (DST), and an AM cortisol of 27.3 ug/dL after a high-dose DST. Late night salivary cortisol was 0.518 ug/dL (<0.010-0.090 ug/dL), 24-hour urine cortisol was 78 ug/24hrs (6-42 ug/24hrs), and ACTH was <1.5 pg/mL (7.2-63.3 pg/mL). The patient was initially asymptomatic and monitored for a few months, but subsequently developed easy bruising, recurrent skin infections, and irritability. The patient declined surgical intervention and was initiated on Osilodrostat. Shortly after medication initiation, she was hospitalized for perforated diverticulitis, hypokalemia, and hypomagnesemia. During hospitalization, AM Cortisol was 49 mcg/dL (4.8-19.5 mcg/dL) and 24-hour urine cortisol was 1023 mcg/24hrs (normal range 3.5-45 mcg/24hrs; the patient’s level prior to admission was 170-190 mcg/24hrs). Osilodrostat was held and the patient was initiated on Etomidate infusion. Once plasma cortisol levels normalized, she resumed Osilodrostat prior to discharge. The patient subsequently tried multiple medical therapy options before undergoing a bilateral adrenalectomy as a definitive treatment choice. Conclusion: The gain of function mutations in MAS result in autonomous endocrine gland function that can manifest clinically as various endocrinopathies. While the most common endocrinopathies in MAS are precocious puberty, hyperthyroidism, and pituitary dysfunction, active surveillance is critical to monitor for less common presentations such as hypercortisolism. This is the first report of adrenal Cushing’s in an adult patient with MAS. Presentation: 6/3/2024