Adrenal Tumors Research Articles

8673 Exploring A Case Study On Navigating Complexities In Endocrine Health And Reproductive Challenges

Abstract Disclosure: S.Y. Rizvi: None. E. Villanueva: None. Introduction: Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting many reproductive-age women, characterized by irregular menstrual cycles, hirsutism, and challenges with fertility. In this case study, we delve into the medical history of a 24-year-old female presenting with PCOS-related symptoms, hirsutism, and infertility, unraveling the multifaceted aspects of her healthcare journey. Case Description: This patient's diagnostic path began when she received an initial diagnosis of PCOS in her home country due to irregular menstrual periods and clinical signs of hirsutism. Her treatment included metformin, but it was interrupted when she relocated to the United States. Upon her arrival in the U.S., her medical course took an unexpected turn as further evaluations revealed elevated salivary cortisol (++), and a 24-hour urine free cortisol recorded 94.2 mcg (normal 4-50 mcg), indicating hypercortisolism. DHEAS: 730 mcg/dl (normal 18-390 mcg/dl), 17-hydroxyprogesterone: 508 (pre-midluteal: 431), free testosterone: 13 pg/ml (normal 0.1-6.4 pg/ml), with normal CBC, TSH, prolactin, and TPO. CT scan showed large 4.8 cm left adrenal mass. These findings indicated adrenal Cushing's syndrome, leading to referral to a tertiary care hospital's endocrine surgeon. Two months post-adrenalectomy, successful removal of the adrenal mass left the patient with relative adrenal insufficiency. Hydrocortisone replacement therapy was initiated, addressing Cushing's syndrome and revealing a potential factor contributing to infertility. Postoperatively, the patient entered the first trimester unexpectedly, complicating her case. Ensuring proper hydrocortisone levels became crucial for her well-being and the fetus, prompting a collaborative approach with obstetricians and maternal-fetal medicine specialists for optimal pregnancy care. Despite ongoing PCOS effects, including hirsutism, treatment options were limited by pregnancy constraints, deferring Aldactone due to its contraindication during pregnancy. Continuous monitoring included hormonal assessments, metabolic panels, and thyroid tests, aiming to balance adrenal insufficiency, PCOS symptoms, and a healthy pregnancy. Conclusion: This case emphasizes challenges in differentiating PCOS from adrenal Cushing's due to overlapping symptoms. Despite classic symptoms, the initial PCOS misdiagnosis highlights the need for vigilance and comprehensive diagnostics. Complex cases underscore the importance of individualized management and interdisciplinary collaboration. Positive outcomes in complex endocrine disorders and pregnancy are attainable through accurate diagnoses and tailored treatments. The case underscores the critical importance of meticulous evaluation for successful outcomes in challenging medical scenarios. Presentation: 6/3/2024

9294 Clinical and Radiological Characterization And Outcomes of Lipid-Poor Adrenal Masses- A Multi-Center Retrospective Study

Abstract Disclosure: V. Balderrama-Brondani: None. R. Al-ward: None. K. Kiseljak-Vassiliades: None. L.M. Fishbein: None. D.A. Kirelik: None. O. Hamidi: None. R. Pishdad: None. H.K. Ghayee: None. M. Sukkari: None. S.S. Bedrose: None. A.H. Hamrahian: None. M.A. Habra: None. Background: Lipid-poor adrenal masses (LPAMs) with pre-contrast radiodensity >10 Hounsfield Units (HU) on computed tomography (CT) represent ∼25% of adrenal tumors. There is limited data about the natural history of LPAMs; therefore, we evaluated a large series of patients with LPAMs to describe the radiological and clinical features and outcomes of these cases. Methods: We conducted a multi-center retrospective cohort study of patients with LPAMs with a baseline diameter of 10-39 mm and derived from 6 institution members of the American-Australian-Asian Adrenal Alliance (A5). We excluded suspected or proven adrenal metastasis, pheochromocytoma, sarcoma, lymphoma, myelolipoma, infiltrative lesions, and adrenal hemorrhage, as well as patients with personal/familial history of genetic predisposition to adrenal neoplasms. The data is presented in percentage and median (range). Results: A total of 242 adrenal masses from 218 patients were evaluated, but only 225 (93%) masses met the inclusion criteria and were analyzed. The age was 58 (23-92), and 61% were women. LPAMs were incidentally discovered in 155 (71.1%) cases, 32 (14.7%) cases were diagnosed due to hormonal overproduction, and 17 (7.8%) due to pain/mass effect. Forty-six (21.1%) patients were on surveillance for a history of extra adrenal malignancy. Masses were unilateral in 89.9% (left side, 57.1%), with size 21 (10-38) mm, with a pre-contrast density of 24 (11-136) HU. Absolute washout was reported in 107 LPAMs and was >60% in 73 (68.2%) cases. The follow-up time was 44.4 (0.9-241) months. Hormonal overproduction developed during the follow-up in 23 (10.5%) cases as follows: cortisol in 15 (6.9%), aldosterone in 4 (1.8%), and sex hormones in 3 (1.4%) cases. LPAM growth rate was 0.03 (-2.18-11.59) cm/year. Seventy-one masses (31.5%) underwent diagnostic procedures (surgery/biopsy) with adrenocortical adenoma (n=37; 52.1%) and adrenocortical carcinoma (ACC) (n=25; 35.2%) being the two most common diagnoses. The tumor growth rate of pathologically confirmed adenomas was 0.03 (-0.30-10.50) cm/year, and of ACC was 1.31 (0.03-11.59) cm/year. A total of 154 (68.4%) LPAMs remained under surveillance at the end of the study, with a follow-up time of 51.8 (6-241) months and a tumor growth rate of 0.02 (-2.18-1.36) cm/year. Forty-five (20.6%) LPAMs decreased by 2 mm (1-13) during the study period. Cases that proved to be ACC had the most significant tumor growth rate over the study (p<0.001). The median time between the initial discovery of LPAM and the surgical resection of ACC cases was 34 (6-128) months. Conclusion: Our study showed that LPAMs carry significant malignant potential, and close long-term follow-up is warranted when surgical resection is not pursued. Prospective studies are critically needed to validate our findings and to establish high-risk molecular, imaging, and biochemical features associated with malignancy. Presentation: 6/2/2024

8234 Composite Pheochromocytoma-Ganglioneuroma: Two Clinical Cases Presenting To St. Elizabeth’s Medical Center

Abstract Disclosure: M. El Najjar: None. E. Naous: None. C. Blake: None. A.T. Sweeney: None. Introduction: Pheochromocytomas (PCCS) are rare catecholamine producing tumors that originate from the chromaffin cells of the adrenal medulla. In 3-9% of cases, they may be accompanied by other tumors. Ganglioneuromas are the most encountered tumor type that occur with PCC and are termed composite PCC-GN. The entity is very rare with < 35 cases reported. Herein, we present 2 cases of composite PCC-GN. Case Presentation: Patient 1 (Pt1) & Patient 2 (Pt2): were 35- & 54-year-old obese females. Pt1 had controlled hypertension and symptoms of anxiety along with palpitations, diaphoresis and flushing. Pt2 had type 2 diabetes and complained of abdominal pain. Metabolic studies showed elevated total plasma fractionated metanephrines(MNs). MNs in Pt1 and Pt2 were: 76 and 61pg/ml respectively (normal <57 pg/ml) and normetaneprines levels were 161 and 116pg/ml respectively (normal <148 pg/ml). Abdominal computed tomography (CT) scans demonstrated right adrenal masses in both cases with Pt1 having a 2.3 x 2.3 x 2.6 cm mass (Figure1) with smooth margins measuring 36 Hounsfield units (HU) on non-contrast(NC) CT imaging with 0% washout on delayed imaging after IV contrast. Pt2 on NCCT had a 4.5 x 3.5 cm right adrenal mass measuring 73 HU and a subsequent abdominal MRI(Figure2) demonstrated the mass to have heterogenous signal intensity. Both patients were prepared with pre-operative a and b blockade and underwent laparoscopic robotic adrenalectomies without complications. Pathological analyses in both cases revealed composite PCC-GN. Pt2 underwent genetic testing which did not reveal any known mutations. Surveillance in both patients demonstrated no recurrence. Clinical lesson: The clinical presentation of PCC-GNs is indistinguishable from isolated PCCs. The definitive diagnosis is through histopathological analysis. Histologically the composite tumor is composed of two distinct patterns with PCC showing angular cells with granular, basophilic cytoplasm, arranged in nests, while GNs show ganglion cells in fibrous stroma. Immunohistochemistry show the PCCs staining for chromogranin A and synaptophysin while GNs stain for S-100 protein and neurofilament antibody. Most cases occur in patients between 40 - 60 years old. Most PCC-GNs are functional, with increased MNs. PCC-GN composite tumors may occur sporadically but have also been described as part of syndromes such as MEN2A and NF1. The definitive treatment for PCC-GN is complete surgical excision which is associated with an excellent prognosis. The probability of recurrence is low though distant metastases have rarely been reported. Therefore, lifetime surveillance is critical. Presentation: 6/3/2024

12325 Adrenocortical Carcinoma Masquerading As Pheochromocytoma In A Patient With Congenital Adrenal Hyperplasia

Abstract Disclosure: E.M. Niedzialkowska: None. A.A. Banka: None. Introduction: The development of adrenocortical carcinoma (ACC) in patients with congenital adrenal hyperplasia (CAH) is rare. The patients with CAH are at increased risk of adrenal tumors which is attributed to ACTH stimulation of adrenal gland if the disease is not appropriately treated. ACC cases mistaken for pheochromocytomas have been reported in the literature and are attributed to the variety of immunohistochemical markers expressed by the tumors. Case description:59 y.o female with salt-wasting CAH diagnosed at the age of 2 (21-hydroxylase deficiency) on hydrocortisone supplementation reported to the hospital due to episodes of sweating, tachycardia and hypertension. Work up revealed mildly elevated plasma normetanephrine 1 nmol/l (N <0.9), urine normetanephrine 1762 mcg (N<899), VMA 11.2 mcg/24hr (N 3.3-7.2). MRI of the abdomen revealed 2 left adrenal masses of 3.7 and 2.4 cm, right adrenal gland hyperplasia and low T1 and T2 enhancement. I-123 MIBG revealed increased activity and thickness of the right adrenal gland and no significant uptake on the left with nodular masses. The patient underwent left adrenalectomy with pathological report consistent with pheochromocytoma due to positive chromogranin and synaptophysin staining and moderate Ki activity. A year later follow up imaging showed an enhancing mass up to 7 cm at the suprarenal fossa invading the left kidney that was positive for nodular adrenocortical hyperplasia per pathology report. The patient continued to have elevated 17-OH- progesterone (2740 ng/l, N <51) despite compliance with her steroid therapy and suppressed ACTH. She underwent mass resection along with nephrectomy, splenectomy, partial colectomy and partial pancreatectomy. Pathology report was positive for adrenocortical carcinoma (positive chromogranin, synaptophysin, CAM 5.2, polycystic cytokeratin, Ki positive in greater than 10% of the tumor cells) with renal and regional lymph node invasion and colonic metastases. The patient was started on mitotane therapy but a year later PET scan was positive for liver and omental metastases and was subsequently started on carboplatin/etoposide followed by streptozocin/adriamycin with initial good response, however repeat PET a year afterwards showed progression of the liver lesions, metastases to omentum and metastatic lesion to calvarium and the patient expired soon afterwards. Discussion: CAH predisposes patients to adrenal tumors which is attributed to increased ACTH stimulation of the adrenal gland but ACC in this population is extremely rare. In very rare cases ACC can present clinically as pheochromocytoma with elevated catecholamine levels and positive synaptophysin and chromogranin staining which poses a clinical challenge. Both CAH and ACC can lead to increased androgen levels and ACTH levels can help to differentiate the origin of the hyperandrogenemia. Presentation: 6/2/2024

12426 Performance Of Dehydroepiandrosterone-Sulphate In Diagnosing Mild Autonomous Cortisol Secretion: A Systematic Review And Meta-Analysis

Abstract Disclosure: J. Saini: None. B. Salama: None. S.R. Chacko: None. K. Yu: None. I. Bancos: None. Objective: Measurement of baseline dehydroepiandrosterone sulfate (DHEAS) is suggested by the guidelines in support of diagnosing mild autonomous cortisol secretion (MACS). However, evidence on the diagnostic accuracy of DHEAS in MACS is difficult to interpret due to differences in the diagnostic cutoffs, small sample size, and heterogeneous reference standards. We aimed to conduct a systematic review and meta-analysis of published literature to assess the performance of DHEAS in diagnosing MACS, as defined in the 2023 guidelines. Methods: A comprehensive search was conducted using several databases from each database’s inception to January 8th, 2024. Databases include Ovid MEDLINE (R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Databases of Systematic Reviews, and Scopus. Only original studies of at least 20 participants were included. MACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. QUADAS-2 was used to assess the risk of bias. Bivariate and random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results: The initial search yielded 285 articles, and only 7 studies met the inclusion criteria. In 7 studies (1 from North America, 3 from Asia, and 3 from Europe), a total of 574 patients with MACS and 830 referent subjects (patients with adrenal tumors without MACS) were included. The mean age was specified only in 5 studies and was similar in patients with MACS (55.5 years) and referent group (53.3 years). Patients with MACS had a higher number of women (323/472, 68.4%) as compared to the referent group (352/658, 53.4%). DHEAS cutoffs studied included: lower cutoff of age-and sex-specific ranges (3 studies), 40 mcg/dL (3 studies), 60 mcg/dL (1 study), and 67.5 mcg/dL (1 study). With increasing DHEAS cutoff, sensitivity for MACS diagnosis increased, and specificity decreased. Most studies (4 studies) used the chemiluminescent immunoassay to measure DHEAS. A meta-analysis of studies using DHEAS cut-off between 40-70 mcg/dL was performed, with a pooled sensitivity of 68% (95% CI: 51-81) and a pooled specificity of 85% (78-89). The positive likelihood ratio was 4 (95% CI: 3-6; I2=36.94, P=0.175) and the negative likelihood ratio was 0.4 (0.3-0.6; I2=49.97, P=0.092). Most studies were at a high risk of bias for selection of patients, index, or reference standard. Conclusion: Based on limited heterogeneous evidence, measurement of DHEAS provides additional value in diagnosing MACS. Further larger diagnostic accuracy studies should explore various DHEAS cutoffs and consider assay variability. Presentation: 6/3/2024

7777 The Adrenal Tumor Volumes Help Predict Surgical Indications And Postoperative Recurrence Of PMAH

Abstract Disclosure: S. Suzuki: None. K. Ishiwata: None. Y. Ruike: None. K. Igarashi: None. S. Watanabe: None. M. Sugo: None. M. Fujimoto: None. H. Koide: None. K. Yokote: None. Introduction: Primary macronodular adrenal hyperplasia (PMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing's syndrome (CS). Unilateral adrenalectomy of the largest gland has been proposed as a treatment for PMAH. However, there are cases of recurrence or persistence of hypercortisolism after unilateral adrenalectomy, and remaining tumor volumes might be associated. Objective: This study aimed to analyze whether tumor volume helps select treatment and predict postoperative recurrence. Patients and methods: We conducted a retrospective study of thirteen patients (five males and eight females, mean age 59 years) with CS due to PMAH in a single center. Eight patients with PMAH underwent unilateral adrenalectomy, but five PMAH were not. Long-term clinical and biochemical outcomes were analyzed in operated and non-operated patients (112±57 months after unilateral adrenalectomy and 144±49 months after initial diagnosis, respectively). Results: Eight PMAH patients who underwent unilateral adrenalectomy had total tumor volumes greater than 1500 mm2. After unilateral adrenalectomy, when the size of the remaining adrenal tumor was greater than 1000 mm2 (1053, 1268, and 1910, respectively), recurrence occurred along with enlargement of the residual adrenal tumor in two cases, and diabetes worsened in one case. However, when the size of the remaining adrenal tumor was less than 500 mm2 (18.2, 201, 214, 327, and 446, respectively), CS resolved. Among five PMAH patients who did not receive surgery, three PMAH patients with total tumor volume less than 1500 mm2 (856, 1038, and 1496, respectively) were biochemically controlled. However, in two PMAH patients with a total volume greater than 1500 mm2 (1610 and 1650), Cushing's signs, including buffalo hump and central obesity, appeared and worsened metabolic complications during follow-up. Conclusions: Our data suggest that adrenalectomy should be considered in PMAH with a total tumor volume greater than 1500 mm2. Unilateral adrenalectomy might have a risk of recurrence if the remaining adrenal tumor is over 1000 mm2. Further large-scale examination is required. Presentation: 6/3/2024

12326 Is Non-functional Adrenal Incidentaloma (AI) Benign Or A Long-haul Culprit?

Abstract Disclosure: J. Mehta: None. F. Rauf: None. C. Salafia: None. S. Salam: None. R.K. Trousdale: None. I. Sachmechi: None. Introduction: Patients with non-functional AI have adrenal tumors that are incidentally discovered during abdominal imaging performed for clinical indications unrelated to adrenal glands and their AM serum cortisol post overnight 1 mg dexamethasone suppression test (DST) are ≤1.8µg/dL. There has been emerging evidence that non-functional AI may pose cardiometabolic risks. Hypothesis: Patients considered to have non-functional AI have increased cardiometabolic risks as compared to patients without AI. Methodology: A cohort study via retrospective chart review utilizing electronic medical records across NYC Health and Hospitals sites. The data collection was from 1/1/2000 to 7/31/2022 and 2965 records were reviewed. Primary composite outcome assessed was the presence of at least one out of hypertension, peripheral vascular disease, coronary artery disease, transient ischemic attack or cerebral vascular accident. Target had patients considered to have non-functional AI and ≥5-year follow-up, and the three target cohorts categorized based on AM serum cortisol post 1mg overnight DST were: Target Cohort 1: 0 to 1µg/dL (lower limit inclusive and upper limit exclusive), Target Cohort 2: 1 to 1.5µg/dL, and Target Cohort 3:1.5 to 1.8µg/dL. Control had patients from general adult population with absence of adrenal incidentaloma, absence of pregnancy during the time points of chart review and presence of ≥5-year follow-up. Two by two comparisons were made between target (N=76) versus control (N=100) at baseline and ≥5-year follow-up. The target cohorts were also compared individually against control at baseline and ≥5-year follow-up. Results: Mean age for target and control at follow-up were 64.4 (±12.1) and 56.2 (±14.2) years respectively (association between age and target versus control status of p=0.001). 54% of target had primary outcome at baseline, compared to 36% of control (p=0.017). When target cohorts were compared individually against control at baseline, 70% of Target Cohort 2 had primary outcome compared to 36% of control (p=0.0003). At follow-up, 68% of Target Cohort 2 had primary outcome compared to 47% of control (p=0.028). Discussion and Conclusion: Patients considered to have non-functional AI show correlations between target status and age, and target status and primary outcome. This study’s results clearly show that patients considered to have non-functional AI are not free of their cortisol’s adverse cardiometabolic effects. Non-functional AI, along with Cushing’s and subclinical Cushing’s syndromes, may present a continuum of cortisol secretion that poses cardiometabolic risks. Current clinical guidelines may require re-evaluation such that patients considered to have non-functional AI are monitored regularly for an early diagnosis, prevention and management of cardiometabolic outcomes. Presentation: 6/3/2024

6436 Adrenal Venous Congestion Clinically Mimicking Carcinoma In A Large Degenerated Adrenocortical Adenoma

Abstract Disclosure: K. Ishiwata: None. S. Suzuki: None. S. Watanabe: None. Y. Yamazaki: None. H. Sasano: None. K. Yokote: None. Introduction: A large heterogenous adrenal tumor is often malignant. Only eight reported cases of adrenal adenoma harboring hemorrhage or venous thrombosis have been reported but their details not. We encountered a case of large degenerated adrenocortical adenoma harboring adrenal venous congestion mimicking adrenocortical carcinoma. Case: Adrenal tumor was incidentally detected in a 71-year-old woman with a history of hypertension, dyslipidemia, and osteoporosis in her regular health check-up. Abdominal CT and MRI demonstrated a heterogenous mass measuring 7.6 cm with peripheral enhancement in the left adrenal gland. [1]3[1]I-adosterol scintigraphy revealed accumulation only in the left tumor margins with no accumulation in [1]8F-FDG-PET scan. Results of endocrinologic evaluation were consistent with subclinical Cushing syndrome. The large size and heterogeneous nature of the mass clinically suggested adrenocortical malignancy, and left laparoscopic adrenalectomy was subsequently performed. The resected left adrenal lesion was encapsulated and measured 6.5 x 6.3 x 5.8 cm appearing almost black and partially yellow on the cut surface. Microscopically, the nodule was composed of SF-1 positive, clear cortical cells with abundant hyaline stroma containing numerous dilated veins with CD31/34-positive endothelial cells, and no foci of necrosis or hemorrhage were detected. The tumor cells above were positive for steroidogenic enzymes including CTP17, HSD3β and CYP11B1 but negative for CYP11B2. Ki-67 labeling index was <2% in the tumor. The criteria of Weiss (0 out of 9) revealed that the tumor was cortisol-producing adrenocortical adenoma. Discussion: In this case, clusters of SF1-positive cortisol producing adrenocortical adenoma cells were present in the hyalinized stroma containing many dilated blood vessels. These findings indicated that those histological features were caused by ischemic degeneration due to intratumoral circulatory disturbance, which clinically simulated adrenocortical carcinoma. Conclusion: We have experienced a very rare case of cortisol-producing adrenocortical adenoma with adrenal venous congestion, resulting in marked enlargement of the lesion. Presentation: 6/3/2024

6365 An Atypical Case Of Large Metastatic Pheochromocytoma With Negative Catecholamine Secretion

Abstract Disclosure: D. Caesario: None. J.K. Fernandes: None. Introduction: Pheochromocytomas (PCCs) are rare tumors arising from chromaffin cells of the adrenal medulla. Diagnosis is suggested by clinical presentations and confirmed by biochemical hypersecretion of metanephrines (MN) and catecholamines (CA). We report an atypical case of large metastatic PCC with normal MN and CA. Case Report: A 61-year-old female presented with uncontrolled HTN despite taking amlodipine, losartan, and carvedilol. No other symptoms reported. She had presented 12 years prior with an 8.7 cm left adrenal mass (AdM) that was incidentally found on CT scan, but she was lost to follow-up. Repeat imaging for her current presentation revealed enlargement of left AdM to 15 cm, centrally necrotic, with absolute washout of 63%. There was extensive local regional involvement, including possible invasion of the pancreas; abutment to left kidney, left renal vein, left hepatic lobe, and stomach; encasement and possible invasion of the splenic vein; and formation of perisplenic collateral vessels. Metastatic lesions were also seen in the liver, bones, and lungs. DOTATATE PET/CT scan showed variable uptake, not a definitive pattern for PCC or neuroendocrine tumor (NET). Labs showed normal levels of plasma fractionated MN and CA, dopamine, renin, aldosterone, cortisol, ACTH, and DHEA-S. Chromogranin A (CgA) was elevated to >8000 ng/dL. Biopsy taken from one of the liver lesions was consistent with metastatic PCC. No family history of NET. Genetic testing was offered, but was deferred. Due to the large tumor burden, she was determined to be nonsurgical and started on systemic therapy with sunitinib. Doxazosin was also added, which better controlled her BP. After 9 months of sunitinib therapy, a repeat CT scan showed overall stable metastatic lesions, but the left AdM had enlarged to 16 cm. Given the slowly worsening disease, patient was switched to temozolomide. She is still actively being treated and monitored today. Discussion: The clinical features of PCC result from excessive CA secretion. HTN is the hallmark of CA release, but the amount, type, and pattern of CA secretion is extremely variable, leading to varied clinical presentations. CgA secretion is also elevated in PCC, but is generally a non-specific marker as its level is also increased in multiple NETs and non-endocrine medical conditions. About 9% of patients with PCC may have normal biochemical workup, with this being even rarer in malignant cases. In general, the amount of CA, MN, and CgA released by the tumor is also positively correlated with the tumor size. The case above is unique in that despite the large tumor burden the patient only presented with HTN and had normal MN and CA levels. Her CgA was significantly elevated, which could correlate with the tumor size, but was interestingly the only marker elevated. It appears that CgA could be a useful adjunct in the diagnosis of PCC, especially in cases where PCC appeared to be non-secretory. Presentation: 6/3/2024

5048 A Rare Cause of Hyperandrogenism in Postmenopausal Women: Ovarian Stromal Hyperplasia

Abstract Disclosure: S. Mark: None. M.H. Shanik: None. I.J. Romao: None. Ovarian stromal hyperplasia (OSH) is a rare cause of hyperandrogenism. It is a non-neoplastic proliferation of ovarian stromal cells that leads to the overproduction of testosterone. This case report highlights that OSH should be considered in patients who present with hyperandrogenism.A 49-year-old postmenopausal woman with a past medical history of polycystic ovary syndrome, type 2 diabetes and obesity complained of unwanted hair growth. On the physical exam her BMI was 51. She had an obese body habitus, hirsutism of her chin, chest and back and acanthosis nigricans on her neck. Blood work showed a total testosterone of 203 (2-45 ng/dL) and free testosterone 29 (0.1-6.pg/dL). FSH, LH, DHEAS, estradiol, SHBG and 17 hydroxyprogesterone (17 OHP) were in the normal range. She completed a 1 mg dexamethasone suppression test that was normal. She took spironolactone for hirsutism with minimal relief. Pelvic ultrasound was limited due to body habitus. CT of the abdomen and pelvis showed no adrenal or ovarian masses. The patient had a family history of pancreatic, ovarian, and breast cancer. Given her symptoms and her family history, the patient underwent genetic testing that was negative. She underwent bilateral salpingo-oophorectomy. Pathology revealed bilateral ovarian stromal hyperplasia. After surgery, her total testosterone normalized to 18 ng/dL and free testosterone was 1.6ng/dL with improvement in hair distribution. The patient continued to struggle with her weight and diabetes management.OSH is a non-malignant proliferation of ovarian stromal cells which leads to overproduction of testosterone. It occurs more in postmenopausal women and rarely in women of reproductive age. There is approximately 1 case of OSH in every 1000 cases of hirsutism. Clinical features include obesity, insulin resistance, acanthosis nigricans, acne, and hirsutism. Testosterone levels are usually greater than 150 ng/dL. Differential diagnosis includes PCOS, Cushing’s disease, adrenal or ovarian tumor and non-classic adrenal hyperplasia. Transvaginal ultrasound can be used to assess the ovaries for tumors or increase in size. If negative a pelvic MRI or CT can be done for further assessment. The gold standard for diagnosis would be histological evaluation following bilateral oophorectomy which is curative. Pathology usually shows stromal hyperplasia that is nodular or diffuse. Alternative treatment options include GNRH agonist therapy in patients who are not surgical candidates. Complications of this condition include insulin resistance, acanthosis nigricans and diabetes mellitus. After treatment hyperandrogenism skin changes improve. It is important that clinicians consider OSH as a cause of hyperandrogenism to ensure timely diagnosis and treatment. Presentation: 6/2/2024

7019 Persistently Elevated Estradiol Levels in a Transgender Male; An Unexpected Pregnancy

Abstract Disclosure: M. Kanin: None. S. Grock: None. N. Agrawal: None. Background: Testosterone is the backbone of gender-affirming hormone therapy (GAHT) for transmasculine and non-binary individuals assigned female at birth (AFAB). While testosterone can affect fertility, it should not be used as contraception and is contraindicated in pregnancy. It is important to counsel patients on fertility preservation, pregnancy, and contraceptive options prior to testosterone initiation. However, the Endocrine Society Guidelines and World Professional Association for Transgender Health Standards of Care provide minimal guidance on reproductive health and contraceptive options. Case Description: An 18-year-old individual AFAB on GAHT with testosterone was referred to endocrinology for elevated estradiol levels. On presentation, the patient denied vaginal bleeding or breast tenderness. The date of last menstrual period was reported as two years prior. There was no significant past medical or surgical history. Medications included subcutaneous testosterone cypionate 20 mg weekly. Physical exam was notable for elevated BMI 42.6kg/m², mild facial hair and central adiposity. Hormone analysis revealed testosterone of 172 ng/dL (adult male: 200-1000) and estradiol 27,322 pg/mL (mid-cycle Female: 80-400). Estradiol by mass spectrometry obtained due to concern for immunoassay interference resulted at > 10,000 pg/mL. FSH <0.1 mIU/mL, LH<0.1 mIU/mL, DHEA-S 2,460 ng/mL (adult female: 400-3600), androstenedione 1.85 ng/mL (0.260 - 2.140), prolactin 328 ng/mL (3 -23.1). CT abdomen and pelvis and pituitary MRI were ordered to assess for ovarian, adrenal and/or pituitary tumor. Later that day additional laboratory tests revealed alpha fetoprotein 126 ng/mL (0 -6.7), progesterone 100.2 ng/mL (luteal phase: 3.0-25.0), beta-hCG 32,571 mIU/ml, inhibin B<10, inhibin A 500.1pg/ml (luteal phase: 40-80) and CA-125 19 U/mL (0 - 35). Given the elevated beta-hcg the patient was asked if they were having sex in a way that could result in pregnancy to which they answered affirmatively. CT and MRI were cancelled, and abdominal ultrasound was obtained which revealed a single living intrauterine pregnancy with estimated gestational age 35 weeks 2 days. Testosterone was stopped and they subsequently delivered a healthy baby girl. Conclusion: Gender diverse patients on testosterone can experience unplanned pregnancy. As testosterone is contraindicated in pregnancy, counseling on reproductive health and contraception is needed. A pregnancy test should be considered prior to initiating hormones for appropriate individuals. It is important to be aware that Individuals AFAB may not desire estrogen containing birth control and placement of intrauterine devices can be dysphoric. Further investigation into how contraceptive options may affect outcomes for individuals on GAHT is needed to minimize barriers to care and to enable patients to make well informed decisions. Presentation: 6/2/2024

7465 Impact Of Geography And Insurance On Healthcare Utilization Preferences Of Individuals With Congenital Adrenal Hyperplasia In The United States

Abstract Disclosure: P.N. Surampudi: Research Investigator; Self; Spruce Biosciences. A.H. Hamrahian: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. R. Charlton: Employee; Self; Spruce Biosciences. P. Ramtin: Employee; Self; Spruce Biosciences. M.E. Geffner: Consulting Fee; Self; Spruce Biosciences, Ferring Pharmaceuticals, Adrenas, Neurocrine Biosciences, Novo Nordisk, Eton, Pfizer, Inc., Nutritional Growth Solutions, Nutritional Growth Solutions. Research Investigator; Self; Novo Nordisk. Background: Relative to the general population, patients with classic congenital adrenal hyperplasia (CAH) have increased risks for morbidity and mortality which require specialized management across life stages[1]. Endocrine care, particularly as part of multi-disciplinary teams, can help mitigate risks of developing adrenal crises as well as the impact of glucocorticoid under- or overexposure, including adrenal insufficiency; cardiometabolic risk associated with insulin resistance and excess weight gain; fertility issues associated with irregular menses and gonadal adrenal rest tumors; diminished quality of life; increased mental health issues, including anxiety, depression, and sleep disturbance; and increased fracture risk associated with decreased bone mineral density. Study Objectives and Design: We hypothesized that the utilization of endocrine and multi-disciplinary care by patients with CAH in the United States (U.S.) could be adversely affected by non-therapeutic factors related to geographic location and access to health care. In this cross-sectional study, we utilized the Definitive Healthcare database (Nov. 2020-Nov. 2022) to gain insight into these factors in adults with CAH. Study Findings: Analysis of healthcare provider utilization revealed that only ∼30% of U.S. adults with CAH received care from endocrinologists. The rest utilized primary-care providers (PCPs: IM, FP, NP, PA, and Ob-Gyn) to obtain care. A review of insurance coverage of U.S. adults with CAH suggests that ∼70% had access to commercial insurance and over 50% resided in states with the largest populations (California, Texas, New York, Florida, Ohio, Michigan, and Illinois), both factors which should ordinarily increase accessibility of subspecialty endocrine and multi-disciplinary care. Conclusions: In our study, only 30% of U.S. CAH adults received care from an endocrinologist. Limited utilization of specialty care does not appear to be due to either diverse geographical distribution or access to healthcare. The gap in expert care may adversely affect the management of CAH and contribute to associated comorbidities. Increased partnership between PCPs and endocrinologists, and increased awareness and education regarding specialty care among patients with CAH are needed to improve health outcomes and thereby reduce the risk of morbidity and mortality in adults with CAH.

6903 The Treatment May Be Worse Than The Disease: The Real-World Clinical Burden Of Disease And Treatment In Congenital Adrenal Hyperplasia

Abstract Disclosure: W. Huang: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. R. Charlton: Employee; Self; Spruce Biosciences. S. Sile: Employee; Self; Spruce Biosciences. C. Dieyi: Employee; Self; STATinMED. S. Adams: Employee; Self; STATinMED. J. Maynard: Employee; Self; STATinMED. C.N. Barnes: Employee; Self; Spruce Biosciences. A.H. Hamrahian: Consulting Fee; Self; Spruce Biosciences. Research Investigator; Self; Spruce Biosciences. Background and Aims: Classic congenital adrenal hyperplasia (CAH) is a group of autosomal recessive conditions that affects the production of adrenal hormones, leading to deficiencies in cortisol and aldosterone, and excess in adrenal androgens. Current treatment includes mineralocorticoids and oral glucocorticoids (GCs) for physiologic cortisol replacement and hypothalamic-pituitary-adrenal (HPA) axis suppression to control androgen levels. The health impacts of hyperandrogenemia include accelerated skeletal maturation leading to adult short stature, precocious puberty, acne, hirsutism, male pattern baldness, adrenal rest tumors, and infertility. There are also serious adverse events due to the long-term use of supraphysiologic doses of GCs. The aim of this study was to explore the risks associated with CAH diagnosis and treatment. Methods: This cross-sectional study used medical administrative claims data within 2014-2021 from RWD Insights®, an all-payer claims database in the US. Adult patients were required to have a diagnosis of CAH (ICD-9/10-CM: 255.9, E25.0, E25.9) and continuous use of oral GCs (defined as a proportion of days covered of 75% or more in any given calendar year). Patients were further required to receive an average daily GC dose of ≥10mg/day hydrocortisone equivalent and be free of pituitary disorders. Non-CAH controls were also selected if they did not have a CAH diagnosis or any GC use. Demographic characteristics and comorbidity rates were compared between patients with and without CAH during the study period. For comorbidity rate comparisons, rate ratios (RR) and 95% confidence intervals (CI) were computed. Results: A total of 1,532,141 (CAH: 2,033; Non-CAH: 1,530,108) were eligible for the study. A lower proportion of the CAH cohort was elderly (i.e., 65+ years; 11% vs. 26%), and there were more females (67% vs. 57%), as compared to the non-CAH cohort. After propensity score matching (PSM) on demographic characteristics, there were 2,019 and 8,076 patients in the CAH and non-CAH cohort, respectively, and patient characteristics were balanced. There were higher rates of comorbidities in the CAH cohort. Some notable differences, RR (95%CI), include GC related comorbidities such as osteoporosis/necrosis, 3.48 (3.36, 3.60) and fractures, 2.14 (1.90, 2.39); metabolic disorders, 2.20 (2.08, 2.33), obesity, 1.35 (1.26-1.44), type 2 diabetes, 1.27 (1.18,1.36), and cardiovascular disorders, 1.24 (1.16, 1.33); and CAH related comorbidities, hirsutism, 11.70 (11.34, 12.06) and testicular hypofunction, 5.48 (5.24, 5.71). Conclusions: This study suggests the association of several comorbidities with CAH, highlighting the burden of both the disease and treatment. Novel, non-steroidal treatments that improve hormonal balance in CAH could ameliorate the systemic risks associated with hyperandrogenemia and chronic overexposure to GCs. Presentation: 6/1/2024

8661 A case of post-menopausal female with virilization due to Sertoli-Leydig cell ovarian tumor recurring in contralateral ovary 8 years later

Abstract Disclosure: M.S. Maharaul: None. J.L. Miller: None. Introduction: Sertoli-Leydig cell tumors (SLCTs) are rare androgen-secreting tumors of the ovaries, accounting for less than 0.5% of all ovarian tumors. Their incidence peaks in the second to third decade of life. New onset of severe hyperandrogenism with virilization in postmenopausal women is exceedingly rare, and the three most frequent causes are ovarian tumors, ovarian hyperthecosis and adrenal androgen producing tumors. We report one such case of ovarian androgen producing tumor which was further complicated by recurrence in the contralateral ovary. Case: A 66-year-old woman presented for evaluation of hyperandrogenism. Physical examination revealed evidence of virilization and clitoromegaly. Laboratory workup was remarkable for total serum testosterone level of 367 ng/dL with normal dehydroepiandrosterone sulfate and cortisol levels. A computerized scan of abdomen did not show any adrenal masses. Transvaginal ultrasound revealed uterine myomas but did not show any ovarian pathology. She underwent selective vein catheterization of her adrenal glands as well as ovaries and was noted to have right ovary secreting 3,982 ng/dL of testosterone whereas all other samples had total testosterone levels < 200 ng/dL. She underwent right salpingo-oophorectomy. Histopathologic examination revealed a 2.2 cm well differentiated Sertoli-Leydig cell tumor confined to the ovary; the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 18 ng/dL. 8 years later, she returns with recurrent symptoms of hyperandrogenism. Repeat workup revealed a total testosterone level of 662 ng/dL. A computerized scan of abdomen and transvaginal ultrasound revealed an unremarkable uterus and left ovary. Magnetic resonance imaging of the pelvis was done that showed a 1.2 cm enhancing mass in the left ovary. She then underwent left salpingo-oophorectomy and supracervical hysterectomy. Histopathologic examination revealed a 1.5 cm Sertoli-Leydig-cell tumor of the left ovary, the fallopian tube was negative for tumor. Six weeks later, her serum total testosterone level was 24 ng/dL and she felt significant improvement in her symptoms. Conclusion: We present an interesting case of virilization in a post-menopausal female due to Sertoli-Leydig cell tumor that resolved after unilateral oophorectomy but recurred 8 years later in the contralateral ovary with resolution after completion oophorectomy. Presentation: 6/2/2024

7019 Persistently Elevated Estradiol Levels in a Transgender Male; An Unexpected Pregnancy

Abstract Disclosure: M. Kanin: None. S. Grock: None. N. Agrawal: None. Background: Testosterone is the backbone of gender-affirming hormone therapy (GAHT) for transmasculine and non-binary individuals assigned female at birth (AFAB). While testosterone can affect fertility, it should not be used as contraception and is contraindicated in pregnancy. It is important to counsel patients on fertility preservation, pregnancy, and contraceptive options prior to testosterone initiation. However, the Endocrine Society Guidelines and World Professional Association for Transgender Health Standards of Care provide minimal guidance on reproductive health and contraceptive options. Case Description: An 18-year-old individual AFAB on GAHT with testosterone was referred to endocrinology for elevated estradiol levels. On presentation, the patient denied vaginal bleeding or breast tenderness. The date of last menstrual period was reported as two years prior. There was no significant past medical or surgical history. Medications included subcutaneous testosterone cypionate 20 mg weekly. Physical exam was notable for elevated BMI 42.6kg/m², mild facial hair and central adiposity. Hormone analysis revealed testosterone of 172 ng/dL (adult male: 200-1000) and estradiol 27,322 pg/mL (mid-cycle Female: 80-400). Estradiol by mass spectrometry obtained due to concern for immunoassay interference resulted at > 10,000 pg/mL. FSH <0.1 mIU/mL, LH<0.1 mIU/mL, DHEA-S 2,460 ng/mL (adult female: 400-3600), androstenedione 1.85 ng/mL (0.260 - 2.140), prolactin 328 ng/mL (3 -23.1). CT abdomen and pelvis and pituitary MRI were ordered to assess for ovarian, adrenal and/or pituitary tumor. Later that day additional laboratory tests revealed alpha fetoprotein 126 ng/mL (0 -6.7), progesterone 100.2 ng/mL (luteal phase: 3.0-25.0), beta-hCG 32,571 mIU/ml, inhibin B<10, inhibin A 500.1pg/ml (luteal phase: 40-80) and CA-125 19 U/mL (0 - 35). Given the elevated beta-hcg the patient was asked if they were having sex in a way that could result in pregnancy to which they answered affirmatively. CT and MRI were cancelled, and abdominal ultrasound was obtained which revealed a single living intrauterine pregnancy with estimated gestational age 35 weeks 2 days. Testosterone was stopped and they subsequently delivered a healthy baby girl. Conclusion: Gender diverse patients on testosterone can experience unplanned pregnancy. As testosterone is contraindicated in pregnancy, counseling on reproductive health and contraception is needed. A pregnancy test should be considered prior to initiating hormones for appropriate individuals. It is important to be aware that Individuals AFAB may not desire estrogen containing birth control and placement of intrauterine devices can be dysphoric. Further investigation into how contraceptive options may affect outcomes for individuals on GAHT is needed to minimize barriers to care and to enable patients to make well informed decisions. Presentation: 6/2/2024

7696 Ovarian Steroid Cell Tumor Presenting As Non-classical Adrenal Hyperplasia

Abstract Disclosure: V. Reddy: None. A. Gowda: None. V. Vattipally: None. D. Kunduru: None. Ovarian Steroid Cell Tumor Presenting as Non-classical Adrenal Hyperplasia IntroductionSteroid cell tumors(SCT) of the ovary make up less than 0.1% of all ovarian tumors. The three subtypes are stromal luteoma, Leydig cell tumor, and steroid cell tumor-not otherwise specified (NOS) which is the commonest subtype. Androgen excess is seen in 75% tumors and presents with virilization. Tumors are usually benign but maybe malignant in 25-43% cases. Factors predicting malignancy include size >7 cm, mitotic activity, necrosis, hemorrhage, and nuclear atypia. Case ReportA 29 y/o Caucasian female presented with secondary amenorrhea and hirsutism. History includes DM2,hypothyroidism,depression and morbid obesity. She reported early pubarche by age 8,menarche at age 13 and developed hirsutism and irregular menstrual cycles from age 15. No workup due to poor follow up until she saw PCP at age 21.She was diagnosed with PCOS and started on Metformin. Eventually referred to endocrinology at age 27, since amenorrhea and hirsutism persisted. On exam she had significant male pattern hair loss and hirsutism over face and body.She reported three first trimester miscarriages.Labs showed testosterone 370 ng/dl, 17 OHP 808 ng/dl, DHEAS 47 ng/dl, Estradiol 117 pg/ml, FSH 2.2 mIU/ml, LH 2.5 mIU/ml, androstenedione 319 ng/dl.Transvaginal US was unremarkable. She was diagnosed with non classical adrenal hyperplasia (NCAH) and started on treatment with prednisone 5 mg daily, drospirenone and spironolactone 100 mg daily.3 months later, labs showed 50% lowering of testosterone to 199 ng/dl and 17 OHP to 407 ng/dl.There was continued biochemical and clinical improvement at the next visit with 17 OHP 73 ng/dl and testosterone 55 ng/dl. Labs done 21 months after initial presentation, showed sudden dramatic rise in 17 OHP to 1148 ng/dl and testosterone to 639 ng/dl. Normal AFP, HCG, CEA, CA125, CA19-9, Inhibin A. CT showed 10.4 cm solid right ovarian mass and underwent right salpingo-oophorectomy. Pathology showed steroid cell tumor, NOS. Labs 1 month postoperatively showed complete normalization of testosterone to <3 ng/dl, 17 OHP to 11 ng/dl and DHEAS 0.66 ng/dl. Steroid therapy was tapered and discontinued. DiscussionWe present the case of a patient with ovarian SCT presenting as NCAH.SCTs are very rare accounting for only 0.1% of all ovarian tumors. Since they commonly secrete androgens, they present similarly to CAH or PCOS and may rarely even co-exist with CAH. Differentiating between NCAH and SCT is difficult especially when there is initial response to steroid therapy and imaging is unremarkable as with our patient. It is important to consider SCT in patients with hyperandrogenism even in the setting of elevated 17 OHP levels. Care should be taken to follow up both clinical and metabolic metrics closely and investigate if any change is noticed. Early diagnosis can prevent irreversible symptoms of hyperandrogenism. Presentation: 6/1/2024

8354 OVARIAN HYPERTHECOSIS: AN UNCOMMON CAUSE OF HYPERANDROGENISM IN A POSTMENOPAUSAL WOMAN

Abstract Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None. Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV <6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool. Presentation: 6/2/2024

8354 Ovarian Hyperthecosis: an Uncommon Cause of Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None. Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV <6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool. Presentation: 6/2/2024

7036 Luteinizing Hormone/Human Chorionic Gonadotropin Receptor And Cyclooxygenase-2 Expression In Adrenocortical Carcinoma

Abstract Disclosure: R. Sheskier: None. A. Kirschenbaum: None. I. Zappi: None. S. Yao: None. A.C. Levine: None. Adrenocortical carcinoma (ACC) is a rare malignancy that has a poor prognosis. The current mainstays of therapy are surgical resection of primary and oligometastases, and systemic therapy with mitotane with or without combination of etoposide, doxorubicin, and cisplatin for more advanced disease. New therapeutic targets are needed to increase options for medical management of mitotane-resistant disease. Expression and function of the luteinizing hormone/human chorionic gonadotropin receptor (LH/hCG-R) have been demonstrated in non-gonadal tissues and malignancies (1). In the adrenal gland, LH/hCG-R expression has been noted in some secretory benign adenomas but its expression in ACC is underexplored (1, 2). Cyclooxygenase-2 (COX-2) is expressed in a variety of cancers, but has not been previously evaluated in ACC (3). We examined the immunohistochemical expression of LH/hCG-R and COX-2 in 15 tissue samples from 7 patients with ACC of varying ENSAT stages with 5 samples from primary ACC tumors and 10 metastatic samples from varying sites. LH/hCG-R was expressed in 13/15 ACC tissue samples (6/7 patients; 4/5 primary ACC; 9/10 metastases). COX-2 expression was demonstrated in 12/15 ACC tissue samples (6/7 patients; 4/5 primary ACC; 8/10 metastases with one metastasis post-mitotane negative for COX-2). Specimens from one patient were also examined for LH/hCG-R and COX-2 expression prior to and following treatment with mitotane. Compared to the primary ACC tumor pre-treatment with mitotane, the post-mitotane ACC metastasis showed an increase in LH/hCG-R expression and a decrease in COX-2 expression. In comparison, a liver ACC metastasis from a separate patient with mitotane-resistant disease demonstrated persistent LH/hCG-R and COX-2 expression. Our findings suggest that LH/hCG-R and COX-2 are expressed in the majority of ACC primary and metastatic lesions. Our results further imply that LH/hCG-R expression persists in mitotane-resistant disease and COX-2 expression initially decreases with mitotane therapy, but is re-expressed in mitotane-resistant disease. Both LH/hCG-R and COX-2 may therefore serve as potential therapeutic targets in the management of advanced ACC. (1) Carlson HE. Human adrenal cortex hyperfunction due to LH/hCG. Mol Cell Endocrinol. 2007 Apr 15;269(1-2):46-50. (2) Doroszko DM, Chrusciel M, Stelmaszewska J, Slezak T, Anisimowicz S, Plöckinger U, Quinkler M, Bonomi M, Wolczynski S, Huhtaniemi I, Toppari J, Rahman NA. GnRH antagonist treatment of malignant adrenocortical tumors. Endocr Relat Cancer. 2019 Jan 1;26(1):103-117. (3) Hu Z, Yang Y, Zhao Y, Huang Y. The prognostic value of cyclooxygenase-2 expression in patients with esophageal cancer: evidence from a meta-analysis. Onco Targets Ther. 2017 Jun 9;10:2893-2901. Presentation: 6/1/2024

6963 A Rare Case Presentation of Untreated Congenital Adrenal Hyperplasia with Bilateral Giant Myelolipoma

Abstract Disclosure: F. Omran: None. S. Bromley: None. M. Ilahi: None. M. Zena: None. W. Al-Refaie: None. J. Delto: None. A. Singh,: None. Background: Adrenal myelolipoma is a rare benign neoplasm predominantly composed of mature adipose tissue and intermixed myeloid tissue, often associated with conditions like Congenital Adrenal Hyperplasia. The etiology of this neoplasm is not definitively known although there are numerous hypotheses, including research suggesting that excess ACTH could be responsible for the pathogenesis. Clinical Case: A 40-year-old female with a history of congenital adrenal hyperplasia noncompliant with treatment. She presented with cholelithiasis (s/p laparoscopic cholecystectomy), abdominal imaging revealed incidental finding of a large right retroperitoneal mass. She was noted to have generalized excessive hirsutism in male distribution, small breasts, enlarged clitoris, male body habitus, and amenorrhea after stopping steroids years prior. Laboratory workup showed the following hormonal abnormalities: elevated ACTH (1080 pg/ml), elevated testosterone (243 ng/dl) and free testosterone (31.3 pg/ml), elevated androstenedione (23.431 ng/ml), and low LH (<0.02 miu/ml), low FSH (<0.02 miu/ml). CT abdomen showed right lobulated retroperitoneal mass of 4x14.3x20cm with internal fat and soft tissue components, left lobulated retroperitoneal mass of 13.7x4.7x7.5cm with soft tissue and fat components. CT guided-biopsy showed pathology consistent with adrenal myelolipoma: fatty areas with interspersed hematopoietic tissue components, peripheral rim of normal adrenal cortical tissue. Given the large size of the mass and compressive effects on surrounding organs, patient underwent exploratory laparotomy with resection of right retroperitoneal mass, nephrectomy, and adrenalectomy. Discharged on hydrocortisone and fludrocortisone, instructed to follow up by endocrinologist, always wear medical alert bracelet, and provided with hydrocortisone emergency kit. Conclusion: This case serves as a classic presentation of a rare disease state. Adrenal myelolipomas, a rare benign adrenal neoplasm, have been found in several disorders associated with chronic ACTH hypersecretion including congenital adrenal hyperplasia. Most CAH patients with myelolipomas have untreated or poorly treated CAH. Adrenal myelolipomas that are asymptomatic and <5cm in size are usually monitored if one is certain there is no occult malignancy. If these tumors are symptomatic or >7cm, patients should undergo surgical excision. These patients should be followed by endocrinology. Importantly, further guidelines should be further developed for management. Presentation: 6/3/2024