24-hour Urinary Free Cortisol Research Articles

Fracture risk and bone health in adrenal adenomas with mild autonomous cortisol secretion/subclinical Hypercortisolism: a systematic review, meta-analysis and meta-regression.

Adrenal adenomas/incidentalomas with mild autonomous cortisol secretion (MACS)/subclinical hypercortisolism (SH) are often associated with metabolic syndrome, glucocorticoid-induced osteoporosis and fractures. In this background, the present systematic review and meta-analysis aimed to collate the available evidence and provide a summary of effect of MACS/SH on bone health in terms of fractures, osteoporosis/osteopenia, microarchitecture, and bone turnover. PubMed/MEDLINE, Embase, and Web of Science databases were systematically searched for observational studies reporting prevalence of fractures, osteoporosis/osteopenia or data on bone microarchitecture/bone turnover markers (BTMs). Following literature search, 16 observational studies were included. Pooled prevalence of any fractures (vertebral and non-vertebral), vertebral fractures and osteoporosis/osteopenia in MACS/SH were 43% [95% confidence intervals (CI): 23%, 62%], 45% (95% CI: 22%, 68%) and 50% (95% CI: 33%, 66%), respectively. On meta-regression, age, sex, 24-hour urinary free cortisol and dehydroepiandrosterone-sulfate did not predict fracture risk. The likelihood of any fractures [odds ratio (OR) 1.61; 95% CI: 1.18, 2.20; p = 0.0026], vertebral fractures (OR 2.10; 95% CI: 1.28, 3.45; p = 0.0035) and osteoporosis/osteopenia (OR 1.46; 95% CI: 1.15, 1.85; p = 0.0018) was significantly higher in adrenal adenomas and MACS/SH than non-functional adrenal adenomas. Subjects with MACS/SH had significantly lower bone mineral density (BMD) at lumbar spine [mean difference (MD) -0.07 gm/cm2; 95% CI: -0.11, -0.03; p = 0.0004) and femoral neck (MD -0.05 gm/cm2; 95% CI: -0.08, -0.02; p = 0.0045) than their non-functional counterparts. Limited data showed no significant difference in BTMs. Publication bias was observed in the pooled prevalence of any fractures, vertebral fractures and pooled MD of femoral neck BMD. To conclude, people with adrenal adenomas/incidentalomas and MACS/SH are at 1.5 to 2-fold higher likelihood of fractures and osteoporosis/osteopenia compared to non-functional adrenal adenomas and should routinely be screened for bone disease. Nevertheless, considering the modest sample size of studies and evidence of publication bias, larger and high-quality studies are required (CRD42023471045).

230. Cortisol and ACTH Response to Dex/CRH Testing and 24-Hour Urine Free Cortisol Levels in Women With and Those Without Premenstrual Dysphoric Disorder

230. Cortisol and ACTH Response to Dex/CRH Testing and 24-Hour Urine Free Cortisol Levels in Women With and Those Without Premenstrual Dysphoric Disorder

A dilute and shoot method for urinary free cortisol analysis by LC-MS/MS

24-hour urinary free cortisol (UFC) is considered as the first-line for screening and diagnosis of Cushing’s syndrome. Although 24-hour UFC assay has been extensively studied by liquid chromatography-tandem mass spectrometry (LC-MS/MS), an accurate assay coupled with a reliable sample preparation procedure and a method-specific reference interval would be very important for reasonable diagnosis. In this study, a simple dilute and shoot based assay by LC-MS/MS has been proposed for UFC determination. Namely, 50 µL of urine sample was mixed with 200 µL of a 50 % methanol/water solution containing the internal standard cortisol-13C3. The mixture was centrifuged and the supernatant was used for direct analysis by LC-MS/MS. This method was validated with wide linear range from 0.625 to 500 ng/ml with coefficients of variation (CVs) ≤ 3.64 %, excellent precision (intra-day CVs ≤ 5.70 % and inter-day CVs ≤ 5.33 %) and good recovery in the range of 93.3 %-109 %. The preservatives were further evaluated for urine storage. It was recommended that no preservatives could be used in collection of 24-hour urine for good detecting peaks. The investigation of reference interval and diagnostic performance finally confirmed the potential usage of this LC-MS/MS assay in routing clinical testing.

Autoimmune Disorders Associated With Surgical Remission of Cushing's Disease : A Cohort Study.

Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. Retrospective matched cohort analysis. Academic medical center/pituitary center. Patients with CD with surgical remission and surgically treated NFPA. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). The small sample of patients with autoimmune disease limited identification of independent risk factors. Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. Recordati Rare Diseases Inc.

False-Negative Inferior Petrosal Sinus Sampling in Young-Onset Cushing Disease: What Happens Next

<b><i>Introduction:</i></b> False-negative results during inferior petrosal sinus sampling (IPSS) may complicate the diagnostic evaluation of patients with ACTH-dependent Cushing syndrome (CS). The management of these patients can be confusing for clinicians and lead to delayed management. <b><i>Methods:</i></b> We studied patients with young-onset (<21 years old) CD who underwent IPSS during their diagnostic evaluation. For all patients, diagnosis of CD was eventually confirmed based on histologic evaluation of a resected pituitary tumor or remission after transsphenoidal surgery. <b><i>Results:</i></b> We recorded a rare incidence of false-negative IPSS results in 5 out of the 142 IPSS procedures (3.5%), performed in 4 unique patients. Patients with negative IPSS did not differ in demographic (age and sex) or biochemical (diurnal ACTH/cortisol or 24-hour urinary free cortisol) data from the remaining. Additional workup was performed in three of the four patients including evaluation for ectopic sources of CS and repeat IPSS. Two of these patients also received medical treatment for suppression of cortisol production. One patient decided to proceed with pituitary exploration without additional evaluation. All patients finally underwent surgery and achieved remission. <b><i>Discussion/Conclusion:</i></b> In patients with CD, IPSS may rarely lead to false-negative results. Management of these patients usually includes screening for ectopic sources of ACTH/CRH secretion, repeating IPSS if ectopic workup is negative, and considering medical management until final diagnosis of the source of hypercortisolism is made.

CHOROIDAL AND RETINAL ABNORMALITIES IN CUSHING SYNDROME: Correlation with the Cortisol Level.

To investigate the structure and blood flow of the retina and choroid in Cushing syndrome and their relationship with cortisol levels. A consecutive series of patients with Cushing syndrome with adrenocortical carcinoma were included in this study. Cortisol levels gradually returned to normal after adrenalectomy. Optical coherence tomography and optical coherence tomography angiography were used to assess patients with Cushing syndrome before and after the surgery for retina and choroid. Correlation analysis was performed between cortisol level and fundus changes. Compared with normal cortisol levels, patients with Cushing syndrome had significantly lower central macular thickness with increased cortisol level (220.82 ± 16.59 µ m and 223.68 ± 15.78 µ m, P = 0.019). However, the central choroidal thickness was higher with increased cortisol level (255.18 ± 105.89 µ m and 205.94 ± 87.04 µ m, P < 0.001). The choriocapillaris flow area was higher with increased cortisol level (2.05 ± 0.14 mm 2 and 2.00 ± 0.13 mm 2 , P = 0.02). The change of choriocapillaris flow area was correlated with the score of Huaxi Emotional-distress Index and 24-hour urine-free cortisol (24h-UFC). The increased cortisol level was correlated with lesser central macular thickness and thicker central choroidal thickness. The decrease of choriocapillaris flow area was correlated with 24h-UFC, indicating the effect of increased cortisol level on choroidal vessels.

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.

[Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension].

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

Impact of the severity of brain injury on secondary adrenal insufficiency in traumatic brain injury patients and the influence of HPA axis dysfunction on prognosis

Objective To investigate secondary adrenal insufficiency post varying traumatic brain injuries’ and its impact on prognosis. Methods 120 traumatic brain injury patients were categorized into mild, moderate and severe groups based on Glasgow Coma Scale. Adrenal function was evaluated through testing. Results Secondary adrenal insufficiency rates were 0% (mild), 22.85% (moderate) and 44.82% (severe). Hypothalamus-pituitary-adrenal axis dysfunction rates were 14.81% (mild), 42.85% (moderate) and 63.79% (severe). Differences among groups were significant (p < .05). Patients with intact hypothalamus-pituitary-adrenal axis had shorter hospital stays and higher Glasgow Coma Scale scores. Receiver operating characteristic analysis of 24-h urinary free cortisol showed an area of 0.846, with a 17.62 μg/24h cutoff, 98.32% sensitivity and 52.37% specificity. In the low-dose adrenocorticotropic hormone test, with an 18 μg/dL cutoff, the receiver operating characteristic area was 0.546, with 46.28% sensitivity and 89.39% specificity. Conclusion As traumatic brain injury severity increases, secondary adrenal insufficiency incidence rises. The low-dose adrenocorticotropic hormone test is promising for hypothalamus-pituitary-adrenal axis evaluation. Patients with hypothalamus-pituitary-adrenal dysfunction experience prolonged hospitalization and worse prognosis.

THU098 Gonadotropin Secreting Pituitary Tumor Presenting As Primary Hypogonadism

Abstract Disclosure: J.N. Shapiro: None. T.X. Lu: None. J. Eapen: None. J.G. Karam: None. Gonadotroph adenomas are the most common subtype of nonfunctional pituitary adenomas, with 35 percent secreting enough LH or FSH to raise serum gonadotropin levels, but clinical syndromes due to hypersecretion of gonadotropins are rare. A low testosterone level with high FSH or LH can mislead to a diagnosis of concomitant primary hypogonadism rather than a secreting pituitary adenoma. We present a case of a patient with an FSH-secreting pituitary macroadenoma presenting with low testosterone levels. The patient is a 67-year-old man incidentally found to have a pituitary macroadenoma measuring 12 x 13 x 12 millimeters, impinging upon the optic chiasm on MRI of the brain obtained for headaches. Visual field tests revealed abnormalities compatible with glaucoma, but not chiasm compression. He has no symptoms of hormonal excess or deficit, although his wife reported decreased erectile function. Physical examination was unremarkable except for an atrophic left testicle. Pituitary hormone function tests (ACTH, AM cortisol, IGF-1, prolactin, thyroid function tests, and 24-hour urine free cortisol) were within normal range, except for an elevated FSH 14.8-18.1 mIU/mL and decreased testosterone in range of 185-256 ng/dL, with normal LH at 7.0 mIU/mL, for which he was referred for urology for evaluation of primary hypogonadism. The patient underwent transsphenoidal resection of the pituitary adenoma. Postoperative pathology revealed a pituitary adenoma, gonadotroph cell type, with immunohistochemical staining scattered positive FSH, and rare positive LH. Postoperative MRI showed post-surgical changes with no residual nodular enhancement. Following surgery, the patient suffered from severe clinical hypogonadism with episodes of profuse diaphoresis and extreme fatigue. Postoperative laboratory values revealed panhypopituitarism with undetectable testosterone level, and low LH and FSH levels. The patient was successfully treated with hydrocortisone, levothyroxine, and testosterone, with resolution of his symptoms. Our patient presented with a pituitary macroadenoma, low testosterone, and high FSH suggestive initially of primary hypogonadism, but found ultimately to have an FSH-secreting adenoma. He likely had underlying hypogonadism, primary or secondary, and although his adenoma secreted FSH, it was not enough to maintain testosterone level in normal range, possibly in part due to biologically inactive FSH molecules or to primary testicular failure. The extremely low testosterone levels postoperatively suggest that his testicular function was mostly stimulated by the adenoma secreted FSH and was therefore drastically lost after surgery. This case increases awareness to consider a gonadotropin-secreting tumor in the differential diagnosis of a pituitary adenoma with high FSH or LH, even when testosterone level is unexpectedly low. Presentation: Thursday, June 15, 2023

THU012 Incidental Pituitary Adenoma In A Patient With Ectopic ACTH Secreting Cushing Syndrome - A Diagnostic Conundrum

Abstract Disclosure: M.S. Nali: None. R.R. Yatavelli: None. Background: Cushing’s syndrome (CS) is a rare condition with an estimated incidence of 2-3 cases/million. Endogenous CS can be divided into ACTH -dependent (80%) and ACTH Independent (20%) with Ectopic Cushing’s syndrome (ECS) accounting for 10-20% of all cases of ACTH-dependent CS. Herein we present a case with indolent onset ACTH-dependent CS who on initial work-up showed a pituitary microadenoma raising the suspicion for Cushing disease, but the source of excess ACTH was found to be from a pulmonary neuroendocrine tumor. Clinical Case: A 44-yr-old female with history of type 1 DM, Obesity, BMI 43.60, Sleep apnea was evaluated elsewhere for suspected Cushing’s due to increased insulin requirements and progressive weight gain. Outside labs showed cortisol of 4.5 ug/dl on 1 mg DST &amp; 8 mg DST cortisol was 3 ug/dl. MRI of the pituitary showed a 3.5x 2.8x 1.8 mm microadenoma &amp; she was initially presumed to have Cushing’s disease secondary to pituitary microadenoma. The patient was seen by neurosurgery who referred to endocrine for localization of cortisol excess by IPSS. Clinically she had moon facies, hirsutism, dorsocervical fat pad, violaceous striae on abdomen. On further laboratory evaluation her ACTH: 88 (0-46) and random cortisol 14 ug/dl with normal rest of pituitary hormones. Her 24-hour urine free Cortisol was 45ug/d (3.5 - 45) and late-night salivary cortisol: 74 &amp;&amp;lt;50 (Ref. range &amp;lt;100 ng/dl) on couple of nights, respectively. Due to non-suppressed cortisol on high dose DST, a CT chest was obtained which showed a 2cms non calcified nodule in the left lower lobe of lung. Transbronchial biopsy was performed, cytopathology showed well differentiated neuroendocrine tumor, likely carcinoid and stained strongly positive for ACTH confirming ectopic ACTH producing tumor. Gallium-68 Dotatate Scan showed abnormal increased uptake in the known left lung nodule. The patient was recommended for surgical removal of neuroendocrine tumor, but she could not tolerate anesthesia and had to undergo stereotactic body radiation therapy (SBRT) for the lung lesion. Repeat ACTH levels 2 months post SBRT showed the ACTH levels were elevated and lesion was still persistent on imaging, however on discussion with rad oncology, the neuroendocrine tumors tend to take longer to show response on imaging and plan is to repeat imaging and biochemical work up in couple of months. Conclusion: The diagnosis of CS and recognizing the source of hormonal excess poses significant challenges Pituitary adenomas are incidentally discovered in up to 10% of the normal population &amp; IPSS is advised for patients with ACTH-dependent Cushing's syndrome and an adenoma smaller than 6 mm, however in patients with equivocal findings, it is important to look for other sources of ACTH prior to any invasive procedure. The source of ectopic ACTH secretion should be established after diagnosis because the excision of an ACTH-producing tumor can be curative. Presentation: Thursday, June 15, 2023

THU518 Ectopic Cushing Syndrome In A Case Of Ewing Sarcoma

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

FRI204 A Rare Case Of Cushing Syndrome In Pregnancy: Diagnosis And Therapeutic Challenges

Abstract Disclosure: Z. Cardona: None. E.D. Szmuilowicz: None. Introduction: Cushing’s syndrome (CS) rarely occurs during pregnancy, and diagnosis of Cushing’s syndrome in pregnancy is challenging due to physiologic changes during gestation. CS is associated with severe maternal and fetal complications. Clinical Case: A 36-year-old woman presented at 21 weeks gestational age with a known adrenal nodule admitted for evaluation of HTN, bilateral lower extremity edema, transaminitis, hyperglycemia, and acute hypoxemic respiratory failure. Reported proximal muscle weakness, facial swelling, anxiety, depression, perspiration, and headaches associated with HTN. Physical exam notable for mild supraclavicular fat deposition, chest and neck plethora, hypertrichosis, and bruising. CT abdomen pelvis revealed a 2.3-cm left adrenal nodule measuring 30 Hounsfield units. Biochemical evaluation included a plasma renin activity of 0.719 ng/mL/h [ref range: 0.167-5.380 ng/mL/h], aldosterone &amp;lt;1.0 ng/dL [ref range: 0.167-5.380 ng/dL], potassium 2.6 mEq/dL, free plasma metanephrines (MN) &amp;lt; 25 pg/mL [ref range: &amp;lt; or = 57 pg/mL], free normetanephrines (NMN) &amp;lt; 25 pg/mL [ref range: &amp;lt; or = 148 pg/mL, total free MN and NMN &amp;lt; 25 [ref range: &amp;lt; or = 205 pg/mL]. 24-hour urine free cortisol (UFC) was markedly elevated at 1854.1 mcg/24h [ref range: 3.1-50.0 mcg/24h], repeat 2186.2 mcg/24h, ACTH: 1.5 pg/mL [ref range: 7.2-63.6 pg/mL], confirming a diagnosis of ACTH-independent CS. Her case was complicated due to the adrenal nodule location. Patients with left adrenal nodules are at risk of developing inferior vena cava (IVC) syndrome during left adrenalectomies, especially in the third trimester, due to compression exerted by the uterus while lying on the right side during the procedure. She underwent an uncomplicated laparoscopic left adrenalectomy. Was started on hydrocortisone (HC) following surgery. There was concern for transient neonatal adrenal insufficiency at delivery. Measuring adrenal insufficiency in utero is challenging; however, estriol could serve as a surrogate marker of fetal adrenal function. Her estriol was normal, possibly indicating intact fetal adrenal activity. She had an uncomplicated vaginal delivery with no signs of adrenal insufficiency in her baby. Interestingly, she had a severely low alkaline phosphatase (ALP) which completely normalized soon after adrenalectomy. Clinical Lesson: This case depicts the challenges in managing CS in pregnancy and its repercussions regarding maternal, fetal, and delivery outcomes. Additionally, it highlights the importance of implementing a multidisciplinary approach, including obstetricians, endocrinologists, endocrine surgeons, and pediatricians, to ensure the optimization of therapeutic strategies. Presentation: Friday, June 16, 2023

FRI228 Primary Adrenal T-cell Lymphoma: A Case Report

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

SAT360 Ovarian Vein Sampling in a Pre-menopausal Woman with Hyperandrogenism: Characterization of Hormonal Profiles

Abstract Disclosure: T.Y. Hu: None. M.E. Babey: None. I. Niu: None. S.M. Nanavati: None. E.J. Murphy: None. Background: Serum estradiol levels have been studied in pre-menopausal and post-menopausal women. There is limited literature on ovarian vein estradiol concentrations. Most data are from sampling done in the setting of hyperandrogenism and primarily in post-menopausal women. This case illustrates hormone concentrations in a pre-menopausal woman who underwent ovarian vein sampling in the workup of hyperandrogenism. Clinical Case: A 33-year G1P1 woman with hypertension and prediabetes presented with three years of menstrual irregularity and infertility after IUD removal. She reported rapid weight gain and hirsutism over one year. Exam was consistent with hyperandrogenism with virilization (modified Ferriman-Gallwey score of 30). Labs showed elevated total testosterone ranging from 144-208 ng/dL (ref 2-45 ng/dL), free testosterone 32.7-35 pg/mL (ref 1.3-9.2 pg/mL), and androstenedione 2.053 ng/ml (ref 0.26-2.14 ng/ml). Cortisol post 1 mg dexamethasone suppression test, 24-hour urine free cortisol, and DHEA-S were normal. Morning unstimulated 17-hydroxyprogesterone was 80.41 ng/dL (ref follicular phase 15-70 ng/dL, luteal phase 35-290 ng/dL). Given normal DHEA-S, an adrenal etiology such as adrenocortical carcinoma was less likely. CT showed no adrenal or ovarian masses. Transvaginal ultrasound revealed numerous bilateral peripheral follicles without adnexal masses or evidence of hyperthecosis and appearance suggestive of PCOS. While the testosterone elevation could be consistent with PCOS, the clinical picture was more concerning for an androgen-secreting tumor. Given the concern for ovarian etiology and patient’s desire for fertility, ovarian vein sampling was performed by a radiologist experienced with adrenal vein sampling to localize a suspected tumor. The right ovarian vein is generally harder to sample than the left. Results were consistent with androgen hypersecretion on the right (right: total testosterone 5,817 ng/dL, androstenedione &amp;gt;40 ng/mL, DHEA-S 20.084 ng/mL; left: total testosterone 189 ng/dL, androstenedione 1.798 ng/mL, DHEA-S 1.893 ng/mL). Estradiol levels were notably elevated on the right at 1945 pg/mL compared to 70 pg/mL on the left. The patient underwent right oophorectomy with pathology showing nodular stromal hyperthecosis and a large corpus luteum cyst. Hyperandrogenism resolved post-operatively with total testosterone 14 ng/dL. Conclusion: We report hormonal profiles from ovarian vein sampling in a pre-menopausal woman with unilateral stromal hyperthecosis. There is limited literature on ovarian vein in this entity and no prior data on estradiol levels. We hypothesize estradiol levels were elevated due to aromatase activity in the right ovary. Testing from the presumably unaffected left ovarian vein helps to characterize ovarian vein estradiol levels in a pre-menopausal woman with suspected hyperandrogenic anovulation. Presentation Date: Saturday, June 17, 2023

FRI248 A Case of Cyclic Cushing’s Disease With No Peripheral ACTH Response But A Marked Inferior Petrosal Sinus ACTH Response After Desmopressin Administration

Abstract Disclosure: M. Guay-Gagnon: None. R. Cheng: None. N. Younes: None. A. La Fontaine: None. S. Larose: None. É. Thérasse: None. C. Beauregard: None. A. Lacroix: None. Background: Desmopressin is commonly used for the diagnosis of Cushing’s disease (CD) especially when CRH is unavailable. We report a case of CD with no peripheral ACTH response but with an unexpectedly marked ACTH and prolactin (PRL) response in inferior petrosal sinus sampling (IPSS) performed with desmopressin. Following failure of pituitary surgery, cabergoline was introduced, which rapidly induced central adrenal insufficiency (AI). Case Report: A 32-y.o. man was referred to our center for Cushing’s syndrome (CS). Over the last years he had developed diabetes, hypertension, hypokalemia, osteoporosis, obesity, and an overt Cushingoid appearance. Morning cortisol was variable with values up to 8065 nmol/L (292 μg/dL) with elevated ACTH of 63 pmol/L (285 pg/mL). The 1 mg dexamethasone suppression test (DST), 24-hour urinary free cortisol (up to 422 x ULN) and bedtime salivary cortisol (up to 74 x ULN) were elevated. The 4 mg IV DST showed partial cortisol suppression, but a very elevated value of 3750 nmol/L (136 μg/dL) the following morning. Desmopressin (10 mcg IV) stimulation test showed no response: ACTH went from 3.8 pmol/L (17.3 pg/mL) to 3.9 pmol/L, and cortisol, from 688 nmol/L (25 μg/dL) to 622 nmol/L. Pituitary MRI, thoracic CT and DOTATATE PET/CT identified no lesion; abdominal CT showed bilateral adrenal hyperplasia. IPSS with desmopressin stimulation identified a pituitary origin with central/peripheral (C/P) ACTH ratios that rose from 7.1 to 34.2 on the left. PRL increased by 83% in left IPSS after desmopressin, while peripheral ACTH and PRL remained stable. During pituitary exploration, the surgeon suspected a tumor on the left, but pathology showed normal pituitary tissue. Hypercortisolism persisted with partial DI requiring oral desmopressin, and cabergoline 0.5 mg twice weekly was initiated. Two weeks later, he was admitted with nausea, vomiting, lethargy, hypotension, hyponatremia, hyperkalemia and a negative septic evaluation. Morning cortisol was 233 nmol/L (8.4 μg/dL), abnormally low in this context. His condition resolved with IV hydrocortisone and fluid resuscitation. ACTH was not measured initially but was 2 x ULN a few weeks later and 4 mg IV DST showed an early cortisol and ACTH rebound. In view of recurrent hypercortisolism, the patient underwent bilateral adrenalectomy resulting in rapid clinical remission. Under hydrocortisone replacement, his most recent ACTH was 21 pmol/L. Conclusions: This is the first report of a petrosal sinus ACTH response to desmopressin without any peripheral response, suggesting a central source of ACTH. Thus, the use of desmopressin during IPSS should still be attempted in patients with no prior peripheral response. It is unclear whether the acute AI episode was due to a combination of nadir of cyclic CD or partial apoplexy and response to cabergoline of a residual corticotroph tumor with desmopressin induced prolactin co-secretion. Presentation: Friday, June 16, 2023

THU310 A Presentation Of Diabetic Ketoacidosis In Gestational Diabetes

Abstract Disclosure: C. Yim: None. S.L. Liu: None. T. Spaic: None. Diabetic ketoacidosis (DKA) is a diabetic emergency characterized by wide anion gap acidosis, presence of ketones (in serum and/or urine) and, frequently, uncontrolled hyperglycemia. In pregnancy, DKA more commonly occurs in women with pre-existing diabetes, usually type 1 diabetes, and is exceptionally rare in women with gestational diabetes mellitus (GDM). We report a case of a 37-year-old woman in her second pregnancy who presented to hospital with DKA at 29+3 weeks gestation shortly after diagnosis of GDM 4 days earlier. In her first pregnancy, she was diagnosed with GDM at 28 weeks, required treatment with metformin at 35 weeks, which she stopped postpartum. She conceived her second pregnancy 3 months postpartum so was not screened for diabetes postpartum. In her second pregnancy, there was no evidence of diabetes on early antenatal labwork at 7 weeks: Hemoglobin A1c (HbA1c) 5.6%, random glucose 3.6 mmol/L. Early GDM screening at 21+1 weeks with 75 gram oral glucose tolerance test (OGTT) was normal: fasting glucose 4.4 mmol/L 1-hour glucose 9.0 mmol/L, 2-hour glucose 6.5 mmol/L. She presented to hospital at 29+3 weeks gestation with a 2-day history of polyuria, polydipsia, dizziness, and decreased oral intake without nausea or vomiting. Four days prior to presentation, she was diagnosed with GDM on a 75g OGTT (fasting glucose 6.2 mmol/L, 1-hour glucose 15.1 mmol/L, 2-hour glucose 11.9mmol/L). Admission labwork showed serum glucose 34.8 mmol/L, anion gap 18, pH 7.29, bicarbonate 17 and beta-hydroxybutyrate 2.97. She was treated with IV fluids and insulin and initiated on multiple daily injections of insulin. Other than pregnancy, no clear precipitating factor was found. HbA1C was 6.4%, serum insulin and C-peptide levels were inappropriately low at 22 pmol/L and 296 pmol/L respectively. Her anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Lipase was mildly elevated at 226U/L but improved to 144U/L with treatment. Abdominal ultrasound did not demonstrate any findings suggestive of acute pancreatitis. Her 24-hour urinary free cortisol was 366 nmol and 442 nmol, both within normal trimester-specific range. Her salivary cortisol was in the normal range (10.5nmol and 10.9nmol). Following discharge, she remained significantly insulin resistant with suboptimal glycemic control (total daily insulin requirements ∼3.5 units/kg/day, HbA1C 7.9% at 35+6 weeks). Due to increased insulin resistance in pregnancy, DKA can progress more rapidly compared to nonpregnancy. Given increased rates of perinatal morbidity and mortality associated with DKA, treatment and monitoring should be promptly initiated. A high index of suspicion is especially important given that DKA is a rare presentation in GDM. Other precipitating factors of newly decompensated diabetes should also be ruled out. Presentation: Thursday, June 15, 2023

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

SAT339 Osteopenia In The Setting of Mild Autonomous Cortisol Secretion

Abstract Disclosure: J.J. Mao: None. K.C. McCowen: None. C. Choe: None. Jimmy J. Mao, MD (1); Karen C. McCowen (1); Charles H. Choe (1)(1) Division of Endocrinology, Diabetes, and Metabolism, University of California San Diego, La Jolla, CA. Background: Over 80% of adrenal incidentalomas are benign adrenal cortical adenomas, of which 30-50% are found to have mild autonomous cortisol secretion (MACS). Bone fragility is a known complication of MACS. Clinical Case: A 57-year-old postmenopausal female with no prior history of fracture, venous thromboembolism, and atherosclerotic cardiovascular disease, was referred for incidental bilateral adrenal nodules. Body mass index was normal at 21 kg/m2, and no clinical stigmata of Cushing syndrome were noted on physical exam. Unenhanced computed tomography scan revealed a 4.6 cm right adrenal nodule and a 3.3 cm left adrenal nodule; both nodules measured less than -18 Hounsfield Units. Biochemical work-up for pheochromocytoma, primary aldosteronism, and non-classical congenital adrenal hyperplasia was negative. Evaluation for hypercortisolism revealed a morning cortisol of 20.3 mcg/dL (ref. 4-22 mcg/dL) with concurrent adrenocorticotropic hormone of &amp;lt;5 pg/mL (ref. 6-50 pg/mL), 24-hour urine free cortisol of 16.9 mcg (ref. 4-50 mcg), and midnight salivary cortisol of 0.07 mcg/dL (ref. &amp;lt;0.09 mcg/dL). A 1 mg dexamethasone suppression test measured on two separate occasions was elevated at 6.3 mcg/dL and 7.9 mcg/dL (ref. &amp;lt;1.8 mcg/dL). A subsequent 8 mg dexamethasone suppression test was also elevated at 6.1 mcg/dL (ref. &amp;lt;1.8 mcg/dL). The diagnosis of MACS was made. A bone mineral density (BMD) scan revealed T-scores at the right femoral neck, left femoral neck, and lumbar spine at -1.6, -1.3, and -0.8, respectively. Ten-year probability of major osteoporotic fracture and hip fracture were 8.3% and 1.0%, respectively. To reduce the risk for future fractures, the decision was made to proceed with adrenal vein sampling (AVS) in preparation for potential adrenalectomy. Conclusion: MACS is the most frequent hormonal abnormality in adrenal incidentalomas, with an estimated prevalence of 0.8-2 cases per 1000 persons. A previous prospective study found that surgical cure of unilateral MACS may lead to a substantial risk reduction (up to 15-fold) of future incident asymptomatic vertebral fractures. Additionally, the highest risk for clinical fracture in those with adrenal adenomas (either nonfunctional or with cortisol hypersecretion) appears to occur at 7-10 years after initial diagnosis. BMD does not perfectly correlate with fracture risk, so unilateral adrenalectomy (if lateralization is observed on AVS) and/or pharmacotherapy should be strongly considered in patients with an expected longevity of &amp;gt;10 years even with mild osteopenia and low fracture risk assessment tool scores. Presentation: Saturday, June 17, 2023

THU505 Severe Acute Hypercortisolism From Stable Pre-existing Lung Nodule

Abstract Disclosure: N. Raza: None. S. Wagle: None. R.N. Kiani: None. K. Kaput: None. A 63-year-old male with uncontrolled hypertension and Rheumatoid arthritis was admitted for acute psychosis, progressive asthenia, and severe refractory hypokalemia. He was afebrile on admission and blood pressure was 151/99 mmHg. Physical examination lacked typical Cushingoid appearance of moon facies, central obesity, or purple striae. Labs showed a potassium of 1.8 (ref: 3.3-5 mmol/L), HbA1c 6.0% (ref&amp;lt;=5.6 %), 24-hour urinary free cortisol of 9438 (ref&amp;lt;=60.0 ug/d) and random ACTH level of 229 (ref:7.7-63.3pg/ml). The presentation was felt to be consistent with ectopic ACTH dependent Cushing's syndrome. He was treated with ketoconazole 400 mg BID, Deep veinous thrombosis prophylaxis and trimethoprim-sulfamethoxazole daily for PJP prophylaxis. CT chest/abdomen/pelvis was performed and showed a 1.9 cm right middle lobe pulmonary nodule. Past records were reviewed and showed a stable lung nodule from 2020 (2.5 years earlier). Elective lung biopsy was discussed, and the patient was discharged home with plan for outpatient biopsy. Prior to his biopsy, he was readmitted with worsening agitation, hypertension, and extremity edema. After extensive discussion with CT surgery, a decision was made to perform robotic-assisted thoracoscopic resection of the right middle lobe with mediastinal lymph node dissection. Post-surgery his BP improved, agitation resolved, and cortisol level declined to 3.4 (ref: 6.0 - 18.4 ug/dL). Final pathology showed a well differentiated neuroendocrine tumor, low grade. Lymphovascular invasion was present, and one lymph node was positive for tumor. ACTH immunostaining was performed and was also positive. Ectopic ACTH dependent Cushing syndrome represents a rare condition, contributing to 5-20% of Cushing’s cases. Lung carcinoid tumor is one of the major causes of ectopic ACTH syndrome and typically resolves with surgery. Unusual in our case is the stability of the lung lesion prior to his acute decompensation and lymph node positivity. To date, we have not identified a reason for the indolent nature of his tumor. He is currently on a hydrocortisone taper and is actively undergoing treatment planning with our multidisciplinary peer review process. Essential to his management is the coordination of multiple providers, which includes complex medical decision making and treatment decisions. In the future, lung carcinoid should be considered in the differential for persons with difficult to control hypertension and a stable pulmonary nodule Presentation: Thursday, June 15, 2023