Adrenal Insufficiency Research Articles

6538 Find me if you can! A Case of a "Well Placed Solitary Insulinoma" in "The Center" of an SACST

Abstract Disclosure: R. Kennedy: None. D.A. D'Alessio: None. A.V. Vella: None. Introduction: Selective arterial calcium stimulation testing (SACST) can be utilized in patients to localize solitary insulinomas when imaging is non diagnostic. While a heterogenous stimulation pattern suggests NIPHS, or multiple insulinomas this case uniquely demonstrates such a pattern with a solitary insulinoma. Clinical Case: The patient is a 48 year old female who presented to the emergency department (ED) for bizarre behavior which resolved with a sweetened drink. Serum glucose was 62 mg/dL, she was treated with IV dextrose and was discharged from the ED. She was referred to outpatient endocrinology for further evaluation where continuous glucose monitoring confirmed predominantly fasting hypoglycemia. Adrenal insufficiency was excluded. She was admitted for a 72 hour inpatient fast where the patient achieved hypoglycemia within 24 hours, with glucose 46 mg/dL (associated with neuroglycopenic symptoms), beta hydroxybutyrate < 0.18 mmol/L, insulin 3.9 mcIU/mL, proinsulin 157pmol/L, c-peptide 1.4 ng/mL and a glucose rise greater than 25mg/dL after glucagon administration. Sulfonylurea screen and insulin antibodies were negative; IGF1 within normal limits. These labs were consistent with hyperinsulinemic hypoglycemia. An MRI pancreas however did not reveal an insulinoma. The patient therefore underwent a SACST, demonstrating a 10 fold response in the territory of the gastroduodenal artery and splenic artery, as well as a 3 fold response in the superior mesenteric artery. This heterogenous pattern in addition to the marked response in each arterial territory raised the possibility of multiple insulinomas. However as there were no tumors present on imaging, medical management was initiated with close follow up. She was trialed with months of somatostatin analogs and diazoxide with minimal improvement in the frequency and severity of her hypoglycemia. About a year after her initial diagnosis, repeat abdominal imaging (CT and MRI) revealed an 8 mm arterial hyper-enhancing lesion in the body of the pancreas concerning for neuroendocrine tumor. Repeat SACST was performed, this time showing a greater than 10 fold response in all three arterial territories. Angiography showed a tumor blush that was visible when each of the three major arteries were injected sequentially. She underwent laparoscopic pancreatic enucleation. The lesion was located on the body of the pancreas, with histology confirming an insulinoma. The patient responded promptly post operatively; her symptoms resolved without further need of medical management. Conclusion: Our case shows that the interpretation of an SACST should take into account the arterial anatomy before ascribing a non-focal response to multiple territories of insulin hypersecretion. Presentation: 6/1/2024

6812 A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait Due to Subacute Combined Degeneration of the Spinal Cord Associated with Pernicious Anemia

Abstract Disclosure: F. Mohammadrezaei: None. F. Sajid: None. C.A. Resta: None. J.G. Karam: None. A Rare Case of Polyglandular Autoimmune Syndrome Type 3B Presenting with Unsteady Gait due to Subacute Combined Degeneration of the Spinal Cord associated with Pernicious Anemia Background: The coexistence of Hashimoto's thyroiditis and pernicious anemia is well established and is recognized as Polyglandular Autoimmune Syndrome (PAS) Type 3B [1]. We describe a rare case of a patient presenting with subacute combined degeneration of the spinal cord leading to the diagnosis of PAS Type 3B. Case Presentation: A 37-year-old man with no known medical history presented to the Emergency Department after a fall in the subway station. On history, he complained of progressive bilateral lower extremity weakness of 10 months duration, necessitating assistance with ambulation, and significant weight gain, described as an increase in his pants size from 40 to 56. His physical examination was relevant for weight of 145kg, BMI of 46.5, normal motor strength and sensation of the upper extremities, decreased strength at 4 out of 5 of bilateral hip flexion and extension, and decreased vibration sensation of bilateral lower extremities. He could not fully stand or walk due to imbalance and weakness. Blood testing revealed a hemoglobin level of 11.4 gm/dl (14-18), MCV of 108.8 FL (80-94), a significantly low vitamin B12 at 89 pg/ml, and normal folate level. His TSH level was 9.26 MCIU/ML (0.39-4.08), with a free T4 of 0.74 ng/dl (0.8-1.8) and significantly elevated Thyroid Peroxidase Antibody titer at 4320 IU/ml (< 34.9). Intrinsic factor antibody and parietal cell antibody tests both came back elevated at 13.4 AU/mL (0.0-1.1) and 1.8 (<1.2), respectively. A head CT scan showed no acute pathology, but MRI spine with contrast revealed abnormal T2 hyperintensity, primarily affecting the lateral columns throughout the cervical and thoracic cord, likely indicative of subacute combined degeneration. The patient was diagnosed with autoimmune Hashimoto's thyroiditis, pernicious anemia, and subacute combined degeneration of the spinal cord due to vitamin B12 deficiency. He was treated with daily vitamin B12 1000mcg muscular injections, levothyroxine 75mcg orally daily (after ruling out adrenal insufficiency), and physical therapy. Conclusion: This case highlights the complexity of polyglandular autoimmune syndromes and the importance of recognizing atypical presentations early in the history of disease. Comprehensive evaluation and timely intervention are essential to mitigate the progression of these conditions and improve patients' quality of life. Reference: (1) Betterle C, Furmaniak J, Sabbadin C, Scaroni C, Presotto F. Type 3 autoimmune polyglandular syndrome (APS-3) or type 3 multiple autoimmune syndrome (MAS-3): an expanding galaxy. J Endocrinol Invest. 2023 Apr;46(4):643-665. Presentation: 6/1/2024

9337 Postprandial And “Fasting” Hypoglycemia In A Patient With A History Of Gastric Bypass Surgery And Carcinoid Syndrome

Abstract Disclosure: S. Ntelis: None. M. Pennant: None. Background: Hypoglycemia is an increasingly recognized complication of bariatric surgery that can occur years after the procedure. Episodes most commonly occur 1-3 hours after meals. Fasting hypoglycemia is not typical and raises concerns for other etiologies, including adrenal insufficiency and other causes of endogenous hyperinsulinism. Clinical Case: A 51-year-old woman with a history of carcinoid tumor of unknown origin with liver metastases, treated with monthly octreotide injections, and history of Roux-en-Y gastric bypass presented with multiple episodes of symptomatic hypoglycemia up to 24 mg/dl. Symptoms included tremor and diaphoresis and improved with juice. Morning cortisol was 22.7 mcg/dL (n > 19.4 mc/dL), ruling out adrenal insufficiency. A continuous glucose monitor (CGM) was placed, and she was advised to have frequent low-carbohydrate meals mixed with healthy fats and protein. She was also advised to add cornstarch to meals, until mixed-meal testing could be performed. She was hospitalized for a seizure provoked by hypoglycemia after a heavy high-carbohydrate meal, and treatment with acarbose 25 mg three times daily was started. Mixed-meal testing was consistent with post-prandial hyper-insulinemic hypoglycemia, with elevated insulin (58 mcIU/ml, n: 2.6-24.9 mcIU/ml) and c-peptide (11.2 ng/ml, n: 1.1-4.4 ng/ml) levels during an episode of symptomatic hypoglycemia (glucose 22 mg/dL) 2.5 hours after the patient’s meal. CGM showed hypoglycemia mostly occurring after meals and some episodes of hypoglycemia early in the morning, that occurred after late-night snacks. Clinical picture and laboratory testing were suggestive of post-bariatric surgery hypoglycemia. Poor hepatic glycogen reserve, secondary to the liver metastases, was considered a contributing factor. Interestingly, although hypoglycemia was mediated by hyperinsulinemia, treatment with a somatostatin analogue provided no benefit. The frequency of hypoglycemia decreased with adherence to a low-carbohydrate diet, and episodes mostly occurred when acarbose use was delayed. Octreotide was transitioned to lantreotide. Due to persistence of early-morning low glucose values on follow-up, further work-up was pursued to rule out etiologies of fasting hypoglycemia. Glucose values remained >70 mg/dl during 72 hours of fasting. IGF-I (115 ng/ml, n: 53-287 ng/ml) and IGF-II (608 ng/ml, n: 267-616 ng/ml) levels were normal, and insulin antibodies were undetectable. Post-bariatric surgery hypoglycemia was confirmed and acarbose dose was increased to 50 mg three times daily. Conclusion: Postprandial hypoglycemia is a late complication of bariatric surgery. Early-morning hypoglycemia can also be seen after bariatric surgery in patients who have late-night meals and snacks. Presentation: 6/1/2024

7187 Non-islet Cell Tumor Hypoglycemia in a Patient With Metastatic Renal Cell Carcinoma

Abstract Disclosure: G.W. Bao: None. A.Y. Yin: None. We report a rare case of non-islet cell tumor hypoglycemia (NICTH) in a patient with metastatic renal cell carcinoma. NICTH is a paraneoplastic syndrome due to increased production of an incompletely processed form of insulin-like growth factor 2 (“big IGF-2”). It requires a high-level of suspicion for diagnosis and is challenging to manage. Our patient is a 69 year old gentleman with a history of deceased donor renal transplant in 1994 and 2008. He was diagnosed with renal cell carcinoma (RCC) metastatic to bone, lymph nodes, and lungs, which was initially treated with cabozantinib, later switched to lenvatinib and everolimus due to disease progression. On admission, he presented with anasarca and weakness. He had recurrent fasting hypoglycemia associated with confusion and lethargy. The lowest serum glucose was 28 mg/dL. He was also diagnosed with primary hypothyroidism (TSH 25.1 uIU/mL and free T4 0.31 ng/dL), suspected to be due to tyrosine kinase inhibitor therapy. Levothyroxine was initiated. Cosyntropin stimulation resulted in a post-stimulation cortisol of 7 ug/dL, although this was felt not to be reliably diagnostic of adrenal insufficiency in the setting of profound hypoalbuminemia. IGF-1 and IGF-2 were 16 ng/mL and 388 ng/mL, respectively; IGF-2: IGF-1 ratio was 24.3. He was treated with intravenous dextrose and prednisone 30mg daily with stabilization of glucoses for a few days. On hospital day 19, he acutely decompensated and passed away shortly after being transitioned to comfort-focused care. Non-diabetic hypoglycemia is relatively uncommon, and may be seen in patients with liver disease, sepsis, adrenal insufficiency, and malignancy. We report a case of NICTH in a patient with metastatic RCC, which is a particularly rare cause of hypoglycemia. NICTH is due to tumor production of “big IGF-2”, a precursor of IGF-2, which mimics the effects of insulin and causes fasting hypoglycemia. NICTH is more commonly associated with mesenchymal and epithelial tumors such as fibromas, fibrosarcomas, and hepatocellular carcinomas. NICTH due to RCC appears to be a much more rare entity, with as few as four cases reported in the literature. Laboratory findings of NICTH include low insulin, pro-insulin, C-peptide, and β-hydroxybutyrate during hypoglycemia. An IGF-2: IGF-1 ratio >10 is considered virtually diagnostic. Surgical excision is curative, although often delayed or not feasible, and patients frequently require intravenous dextrose. High-dose steroids (ie, prednisone 30-60mg daily) can be used, which promotes “big IGF-2” clearance. NICTH is likely under-recognized in patients with advanced malignancies. This diagnosis should be considered in those with refractory hypoglycemia, although management is challenging if tumor control cannot be achieved. Presentation: 6/1/2024

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

7560 Using a Single Pre-test Cortisol Level To Reduce The Need For Dynamic Testing For Adrenal Insufficiency In A Southeast Asian Population

Abstract Disclosure: V. Ramadoss: None. L. Tan: None. A.E. Teo: None. K. Lazarus: None. K. Meeran: None. D. Deepak: None. L. Ong: None. C. Khoo: None. P. Eng: None. Introduction: The Short Synacthen Test (SST) is widely used in clinical practice to assess Adrenal Insufficiency (AI). Despite its relative ease of administration, Synacthen use is limited by its availability and its administration demands supervision by experienced staff, resulting in increased testing cost. A single measurement of serum cortisol has been shown to predict AI, but the suggested threshold varies according to the patient cohort studied, assay variation and the prevalence of the condition relative to the size of population tested. This study aims to (a) identify a threshold cortisol level to screen for AI in a South-East Asian population and (b) to determine the utility of a stimulated 60-minute cortisol level in the diagnosis of AI. Methods: This is a retrospective analysis of SSTs (250 micrograms) performed in our institution between 28th February 2022 to 28th February 2023. Serum cortisol in our institution was measured by Abbott Alinity analysers. We defined a normal response as a stimulated cortisol value of ≥ 420nmol/L at either 30-minutes, 60-minutes, or at both time points. Logistic regression analysis was performed to predict normal responses based on baseline cortisol level. Results: Median cortisol level at baseline, 30-minutes, and 60-minutes after Synacthen stimulation were 254 (IQR 191-320) nmol/L, 499 (IQR 415 -585) nmol/L, 574 (IQR 476 -662) nmol/L respectively. A total of 785 SSTs were performed, out of which 83.1% were normal and 16.9% were abnormal. Of the 785 SSTs, 55 (7.0%) would have failed if only the 30-minute cortisol was assessed without the 60-minute value, whereas 10 (1.4%) would have failed if only the 60-minute cortisol was assessed without the 30-minutes value. An early morning basal cortisol (0800am to 1200pm) cut-off of <300nmol/L identified subnormal cortisol with 95.0% sensitivity and an afternoon cortisol (1200pm to 1700) of < 312nmol/L achieved 95.2% sensitivity. A basal cortisol level of < 100nmol/L will confirm AI with 97.3% specificity. Using a basal cortisol level of ≥ 300nmol/L, 94.8% of individuals go on to pass the SST. Use of this basal cortisol value would avoid 252 (32.1%) SSTs. Conclusion: A single measurement of basal cortisol of ≥ 300nmol/L has the potential to exclude AI with 95% sensitivity on Abbott Alinity platform in our cohort of patients. Using a threshold cortisol level of 300nmol/L, at least 32% of the SSTs could be avoided. This would have improved patients experience with cost savings implications. Furthermore, a stimulated 60-minute cortisol level identifies 55 (7%) of individuals who would otherwise be misclassified as AI, thereby avoiding unnecessary long-term glucocorticoid replacement. Presentation: 6/1/2024

8536 Unusual Finding of Familial Adenomatous Polyposis in a Patient with X Linked Adrenoleukodystrophy

Abstract Disclosure: A. Deswal: None. A. Dwarakanathan: None. Introduction: X Linked Adrenal Leukodystrophy (X-ALD) is a rare hereditary genetic disorder of impaired peroxisomal metabolism due to a defective transmembrane protein, ADLP. Defective ADLP impairs transport of VLCFA-CoA esters across cytosol into peroxisomes leading to build-up of toxic VLCFA in the cells. X-ALD is caused by mutation in ABCD1 gene, located on X chromosome, which codes for ADLP. It has a broad clinical spectrum including Cerebral ALD, Adrenomyeloneuropathy and Adrenocortical insufficiency. X-ALD has a general prevalence of 1 in 17,000 newborns. Approximately 80% of males with X-ALD develop primary adrenal insufficiency in their lifetime. It can be diagnosed by measuring VLCFA levels in plasma , checking for ABCD1 gene mutation or by doing Brain MRI (depending upon phenotypical presentation ). Case presentation: We report a case of a 23 year old man who had primary adrenocortical insufficiency subtype of X-ALD. His mother was a carrier of ABCD1 gene mutation. He himself tested hemizygous for ABCD1 gene. He came to our office for a follow up visit after an episode of adrenal crisis for which he was hospitalized. He was started on replacement therapy with prednisone and fludrocortisone. Over the next couple of years, he was diagnosed with diabetes mellitus with initial HbA1C of 8.8%. GAD antibody test for type I DM came out negative. His diabetes was managed with metformin and pioglitazone( later discontinued) .By the age of 25,he was found to have polyposis of colon. He tested positive for APC gene mutation . He underwent a J pouch surgery . He also developed PICA aneurysm. Discussion: X-ALD is a hereditary progressive disease with no association between genetic and phenotypic presentations. Adrenal insufficiency type is usually the first to present. Cerebral ALD is typically diagnosed between the ages of 3-18 presenting as psychiatric illness. Myelopathy typically starts by middle age and involves the spinal cord, causing the affected individuals to develop gait disturbances , bladder and bowel dysfunction, with severe mobility dysfunction by 5th-6th decade of life. We present a unique case of a young man with adrenal insufficiency type of X-ALD who also developed gastrointestinal pathology. Per our literature review, X-ALD has not been seen associated with APC gene mutations or colon carcinomas . Pathology behind XLD revolves around ABCD1 gene mutaion causing VLCFA accumulation in plasma, fibroblasts, adrenal glands, oligodendrocytes , astrocytes etc. Whereas FAP involves APC gene mutation which affects the intestinal epithelial cells leading to their apoptosis and polyp formation. X-ALD and FAP are disorders of two different gene mutations with varied clinical presentations. But the question arises regarding finding of APC gene mutation in a patient with ABCD1 gene mutation that if it is a mere co-incidence or common mutation pathway linking these two disorders exists. Presentation: 6/2/2024

6564 A Case Of Severe Hypercalcemia In Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (<6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

7003 Comparative Study Of The Properties And Differences Of Steroidogenesis Inhibitors In Vitro

Abstract Disclosure: Y. Taki: None. T. Kono: None. S. Kono: None. N. Hashimoto: None. H. Nagano: None. T. Tanaka: None. Objective: Osilodrostat (Osi) is utilized as an inhibitor of cortisol (F) synthesis and is a potent inhibitor of CYP11B2, in addition to CYP11B1. Therefore, we investigated the aldosterone (Ald) and cortisol concentration-dependent inhibitory effects of Osi in vitro, using tissues from 9 cases [5 Aldosterone-producing adenoma (APA) and 4 Cortisol-producing adenoma (CPA)] operated at our institution. Methods: Adrenal tumor surgery specimens were treated with collagenase and cultured on plates. After 3 days, the medium was changed and incubated with osilodrostat or metyrapone (0.0001 to 10 µM). After another 3 days, the medium was collected, and Ald/F concentrations were measured. The IC50 of both drugs for Ald/F were then compared. Results: In APA cases, Osi inhibited at significantly lower concentrations (IC50: 0.003 µM) than Met (0.782 µM; p=0.0159) for Ald; in CPA cases, Osi inhibited with similar potency to Met (IC50: 0.061 µM vs 0.466 µM, p=0.2286) for F. In all cases, Osi inhibited at significantly lower concentrations for Ald than F (IC50: 0.003 µM vs 0.028 µM, p=0.0008). Discussion: Osi is a potent inhibitor of Ald and F production, and its use for PA alone is challenging because clinical trials of Osi for PA were terminated due to concerns about adrenal insufficiency. Therefore, we suggest that Osi may be useful in PA-associated CPA patients for whom surgery is not indicated or as a preoperative drug therapy. Presentation: 6/1/2024

12529 Pre And Post-operative Evaluation And Outcomes After Adrenalectomy At A Tertiary Referral Center

Abstract Disclosure: C. Hung: None. L.M. Fishbein: None. M.R. Clay: None. M.B. Albuja-Cruz: None. C. Raeburn: None. K. Kiseljak-Vassiliades: None. M.E. Wierman: None. Introduction: The prevalence of adrenal nodules has increased over time due to increased abdominal CT imaging. Laboratory evaluation to screen for hypercortisolism, primary aldosteronism, or pheochromocytoma is recommended depending on nodule appearance and clinical risk factors. Our aim was to retrospectively determine the preoperative hormonal workup prior to adrenalectomy and to identify the postoperative comorbidities as they relate to preoperative hypercortisolism. Methods: From May 2017-March 2023, 205 adrenalectomies were performed for adrenal nodules. Preoperative and postoperative comorbidities, medications, laboratory results, imaging and pathology were assessed up to 1 year post surgery. Patients were stratified by degree of hypercortisolism, based on 1 mg dexamethasone suppression test, into cortisol 1.8-5 μg/dL (DST 1.8-5) or cortisol >5 μg/dL (DST >5). Statistical analysis included Fischer’s exact test and two-sample proportion test. Results: Of 205 adrenalectomies, 51 patients had primary aldosteronism (24.9%), 51 had pheochromocytoma (24.9%), 23 had ACC (11.2%), 15 had non-functional adrenal adenomas (7.3%), and 65 had adenomas associated with hypercortisolism (31.7%)—42 with DST 1.8-5 (20.5%), 23 with DST >5 (11.2%). Preoperatively 9 (17.6%) patients with PA underwent 1 mg DST, while 54 (83.1%) patients with hypercortisolism (DST >1.8) had aldosterone measured. Overall, 183/205 patients (89.3%) had hypertension preoperatively. Of the patients with hypercortisolism (DST>1.8), 58 (89.2%) had hypertension, without a difference in prevalence between DST 1.8-5 and DST >5 groups. For those with abnormal DST, no significant reduction in hypertension was observed within 2 months following adrenalectomy, but at 1 year postop, prevalence was reduced (89.2% preop vs 71.9% postop, p=0.03). There was no significant reduction in the prevalence of type 2 diabetes (p=0.78), prediabetes (p=0.48), hyperlipidemia (p=0.33), osteoporosis (p=0.53), or osteopenia (p=0.67) at 1 year postop in those with hypercortisolism. After adrenalectomy, 42.9% patients in the DST1.8-5 and 73.9% in the DST >5 group were discharged on glucocorticoids. Many patients were lost to long-term follow up. In those remaining, at 1 year postop, 14.3% patients in the DST1.8-5 and 50% in the DST >5 group still required steroids for adrenal insufficiency. Conclusions Not all patients with adrenal nodules are being screened for excess hormone production. Hypercortisolism is prevalent in patients undergoing adrenalectomy. Preoperative workup is essential to identify these patients before surgery as adrenal insufficiency can persist postoperatively. Adrenalectomy for hypercortisolism is associated with a reduction in hypertension at 1 year postoperatively. Presentation: 6/3/2024

7404 Evaluation Of Cortisol Reserve And Adrenal Imaging In Patients With Graves’ Disease Before And Six Months After Treatment

Abstract Disclosure: P. Sharma: None. S. Mir: None. S. Mohd Patto: None. A.H. Bhat: None. B. Dar: None. M. Bhat: None. Introduction: There is scarcity of data regarding the effect of thyrotoxicosis on cortisol metabolism and adrenal gland size. An increase in cortisol metabolism can deplete the functional reserve of adrenal cortex and lead to adrenocortical insufficiency even when there is no pre-existing Addison's disease. In developing countries patients with Graves’ disease present in advanced states of thyrotoxicosis. Besides they are also exposed to a variety of environmental stresses such as recurrent febrile illnesses, salt, and water loss due to manual labour in hot and humid climates etc., which can precipitate an adrenal crisis in the presence of compromised adrenal reserve. So present study was undertaken to assess cortisol reserve and adrenal gland size in patients with treatment naive Graves' disease. Objectives- The present study, was undertaken to assess cortisol reserve and adrenal imaging in patients with treatment naive Graves' disease. Specific information in this regard would help alert physicians dealing with clinical thyrotoxicosis in developing countries of tropics to the possibility of co-existing adrenal decompensation and adopt appropriate life saving measures promptly. Material & Methods: We examined 38 treatment-naive Graves' Disease patients at GMC, SSH, Srinagar, Kashmir, INDIA. Basal cortisol and cortisol response to ACTH were measured before and after six months of treatment, alongside adrenal CT imaging. Results: In hyperthyroid state, Graves' patients exhibited significantly lower basal cortisol compared to euthyroid and healthy controls (306 vs. 410 vs. 421 nmol/l, p < 0.05). 23.6% patients had subnormal cortisol response to ACTH(250ug). Those with T3 ≥ 400 ng/dl had lower cortisol response (560±133 nmol/l) and delta cortisol response than T3 < 400 ng/dl (724 ± 294 nmol/l, 213+/-73 vs. 428+/-265 nmol/l). After achieving euthyroid state, cortisol levels improved significantly (410±213 nmol/l vs. 306 ± 103 nmol/l, p < 0.05). Adrenal CT scans in 34 patients was done out of which 19 showed statistically significant increases in gland thickness, width, and AP diameter compared to controls (p < 0.01, p < 0.05. Repeat CT in 26 patients demonstrated resolution of hyperplasia (p < 0.05). Conclusion: Treatment-naive Graves' disease patients have compromised adrenocortical reserve and adrenal gland enlargement. Adrenal changes are reversible after achieving euthyroid state. These findings support steroid supplementation in impending thyrotoxic crisis and highlight a unique feature of reversible adrenal gland enlargement in this context. Keywords: Graves’ Disease, Adrenal hyperplasia, Cortisol reserve. Presentation: 6/3/2024

8248 Glucocorticoid Induced Adrenal Crisis Masked By Metastatic Lung Carcinoma

Abstract Disclosure: N. Abrahimi: None. A. Abrahimi: None. Background: Chronic glucocorticoid use of three weeks or longer can cause hypothalamic-pituitary-adrenal axis inhibition by negative feedback, causing adrenal suppression. (1) Adrenal crisis is diagnosed by an acute clinical decompensation, persistent hypotension that resolves with high dose steroid administration. (2) Adrenal crisis is precipitated by several causes such as illness, dehydration, trauma, emotional distress and sometimes due to no identifiable cause. (2) Clinical Case: 64-year-old male past medical history of lung carcinoma metastatic to mediastinum who presented to the hospital with tachycardia. On presentation, patient was tachycardic, tachypneic, and hypotensive. Labs significant for WBC 22, Na+ 129, K+ 3.2, Cr 3.4. Patient received 2.5 L bolus of NS and was given one dose of azithromycin due to concern for sepsis. After fluid resuscitation, hypotension and tachycardia resolved. Presenting symptoms included ongoing nausea, decreased appetite and malaise for several weeks. Repeat labs post fluid resuscitation showed resolution of leukocytosis, improvement of AKI, and repletion of electrolytes. CT chest abdomen pelvis showed questionable pneumonia, however, consolidations were difficult to distinguish from known malignant masses. Clinical picture was not consistent with pneumonia and so additional antibiotics were held. Several hours later, blood pressure decreased, and patient began requiring vasopressors. Cefepime was started given concern for septic shock. Nearly 48 hours after initiation of broad-spectrum antibiotics hypotension persisted and patient remained on vasopressors. Given clinical decline, etiology of shock was reconsidered. Patient reported daily prednisone use over the last several months for COPD management. Given high clinical suspicion of adrenal crisis in setting of chronic steroid use and glucocorticoid withdrawal, patient was started on hydrocortisone 100 mg every 8 hours. Shortly after initiation of stress dosed steroids, the patient was successfully weaned off vasopressors with complete resolution of hypotension. Conclusion: Presentation and symptoms of adrenal insufficiency and crisis including nausea, anorexia, fatigue, malaise, hypotension and electrolyte abnormalities are nonspecific, can go unrecognized and be masked by other disease processes, such as metastatic cancer. (1) Adrenal crisis is life threatening and must be diagnosed and treated early to prevent mortality. (2) Therefore, adrenal crisis should always be on the differential in patients who present with shock.

8365 Bilateral Adrenal Hemorrhage Unveiling Adrenal Metastases In A Patient With Retroperitoneal Sarcoma

Abstract Disclosure: R.J. Shah: None. A.C. Goldberg: None. S. Jasim: None. Introduction: Metastatic disease to the adrenal gland is the most commonly occurring malignancy of the adrenal glands. Adrenal hemorrhage (AH) however is a rare but potentially fatal manifestation of malignancy. This case report highlights the unusual presentation of retroperitoneal sarcoma, manifesting as bilateral adrenal hemorrhage in the context of underlying metastases. Case Presentation: A 53-year-old man presented with a 4-week history of fatigue, intermittent abdominal pain radiating to the back, and vomiting. CT revealed bilateral adrenal masses measuring up to 8.5cm on the left side, with Hounsfield units (HU) 27, and 5.9cm on the right, HU 27, consistent with large areas of bilateral adrenal hemorrhage later confirmed on MRI. Biochemical evaluation included ACTH-stimulated cortisol, which was borderline at 17.4mcg/dl (recommended above 18-20mcg/dl), with a significantly elevated ACTH level of 103.8pg/nl (reference range 7.0-63.0pg/ml). Plasma metanephrines, electrolytes, aldosterone, and DHEA-S were normal. Although hemodynamically stable, he was started on prednisone 5mg daily as he was at high risk for primary adrenal insufficiency (AI). He was referred to endocrine surgery and further workup with PET/CT demonstrated a new FDG-avid periaortic retroperitoneal mass, with an interval increase in the size of the adrenal masses and development of hypoattenuating lesions in the kidneys and pancreas favoring aggressive metastatic disease. He underwent biopsy of the retroperitoneal mass, and pathology was consistent with high-grade sarcoma. Oncology started treatment with dexrazoxane and doxorubicin. His adrenal masses remained unchanged in size, and the patient died related to rapid progression of disease. Discussion: Spontaneous bilateral adrenal hemorrhage is rare with a reported incidence of 0.14 to 1.8%. Although most cases have been associated with sepsis, anticoagulation, hematologic disorders and trauma, it is important to maintain a high level of suspicion for underlying adrenal tumors and metastatic disease. AH can be a diagnostic challenge because of its non-specific presentation, and imaging is vital for timely recognition. Patients with bilateral AH should be managed with corticosteroids to avert AI-related fatalities. Presentation: 6/1/2024

7286 Higher Order Associations Linking Tryptophan, Kynurenine, And Tyrosine As Serum Markers Of Glucocorticoid Downstream Action In Adipose Tissue

Abstract Disclosure: K. Bennett: None. T. Garner: None. D. Chantzichristos: Speaker; Self; Sanofi, Takeda. P. Jansson: None. A. Stevens: None. G. Johannsson: Consulting Fee; Self; Novo Nordisk, Shire, AstraZeneca. Speaker; Self; Novo Nordisk, Pfizer, Inc.. Introduction: Treatment of Adrenal Insufficiency (AI) by glucocorticoid (GC) replacement therapy is mainly guided by clinical judgement, as there is no biomarker of GC action to individualise its dosage. Hypergraphs are networks modelling higher order associations (HOAs), which are interactions between more than two ‘omic elements. The aim of this study was to use hypergraphs to identify serum markers that reflect the action of GCs in adipose tissue (AT). Methods: In a randomised, cross-over trial, 10 patients with primary AI received saline i.v. (GC withdrawal), or circadian infusion of hydrocortisone (GC exposure), with > 2 weeks apart. After 26 hours (8AM), AT biopsy and PBMCs were collected for transcriptomic analysis, and abdominal subcutaneous microdialysis and PBMCs were collected for metabolomic profiling using LC/MS. Hypergraph models were generated to integrate serum and AT transcriptomics and metabolomics, identifying clusters of putatively causally linked metabolites which could represent serum markers of downstream GC action in AT. Hypergraph structure was assessed in AT and serum using entropy to infer associations within pre-defined metabolic pathways. Differences in entropy between the interventions was measured using Bayes Factor. Univariate ROC curve analysis was used to calculate AUCs for the serum markers. Results: In AT dialysate, 22 metabolites were identified as significantly different between GC exposure and withdrawal states. These included metabolites found in lipolysis and proteolysis pathways, such as acyl carnitines, lysophosphatidylcholines, fatty acids, and peptide derivatives. Nine metabolites were significantly different between the interventions in the serum. DEGs in AT (n=2048) were found to be enriched in metabolic pathways. Hypergraphs were used to refine clusters in the serum based on their HOAs with AT differentially expressed genes and metabolites. Tryptophan, Kynurenine, and Tyrosine clustered together, demonstrating a relationship between their expression in serum, and the metabolomic and transcriptomic profile of AT. These HOAs were shared with cortisol in the exposure intervention, but not in GC withdrawal, suggesting GC dependent regulation. All 3 metabolites had AUC-ROCs > 0.8, with Kynurenine performing the best at 0.86. Tissue specific differences were seen in the entropy of metabolic pathways between GC exposure and withdrawal, with similar changes seen in lipid and proteolysis pathways, but no difference seen in serum in carbohydrate and amino acid biosynthesis. Conclusions: During near physiological exposure, we identified changes to hypergraph structure and metabolite concentrations in lipid, protein, and carbohydrate pathways in AT and serum, compared to GC withdrawal. Hypergraph integration of multi-omic data identified tryptophan, kynurenine, and tyrosine as potential serum markers reflecting GC action in AT. Presentation: 6/3/2024

7988 A Case of Spontaneous Pituitary Hemorrhage in Late Pregnancy

Abstract Disclosure: D. Poudyal: None. G.L. Prince: None. Background: Pituitary apoplexy (PA), caused by hemorrhage into the pituitary gland, is rare. The prevalence in pregnancy is also quite rare, with PA complicating 1 in 10,000 pregnancies. PA usually occurs in patients with pre-existing pituitary adenomas. Spontaneous pituitary hemorrhage (PH) causing PA in the absence of a known adenoma or other precipitating factors is less frequently described. Presenting symptoms of PA are non-specific and can pose diagnostic challenges, yet PA must be managed urgently and decisively due to the risk of life-threatening hormonal deficiencies that can ensue. Physiologic changes in pregnancy pose additional challenges in evaluating and managing patients with possible PA. Here we present a case of spontaneous PH during the third trimester of pregnancy in the absence of pre-existing pituitary pathology or known precipitants. Case presentation: A 31-year-old female, G2P1, with an uncomplicated first pregnancy, presented with acute-onset headache and vision loss at 36 weeks gestation. Her symptoms resolved spontaneously in 45 minutes. MRI brain without contrast showed hemorrhage within the left aspect of the pituitary gland, a mildly displaced infundibulum, but no mass effect on the optic chiasm. MRI brain obtained 1 year prior for headache was unremarkable. Lab work showed an 8AM cortisol of 19 ug/dL (Ref range 3.7 - 19.4 ug/dL), and a total T4 of 11.3 ug/dL (Ref 4.9 - 11.7 ug/dL). Ultimately, interpretation of her cortisol testing was limited by: elevated cortisol-binding globulin in the high-estrogen state of pregnancy, elevated cortisol production by an intact hypothalamic-pituitary-adrenal (HPA) axis during the latter portion of pregnancy, and the lack of validated cutoff values for 8AM serum cortisol levels during pregnancy. In light of these factors and the risk of undiagnosed adrenal insufficiency (AI), she was treated empirically with oral hydrocortisone. Subsequently, she had an uneventful vaginal delivery, supported by stress dosing of her steroids. Postpartum, she had a normal 8AM cortisol level of 14 ug/dL, and she was noted to quickly begin breastfeeding without incident. Conclusion: PA remains a critical diagnosis that cannot be missed in patients presenting with concerning symptoms and signs, in order to identify and treat life-threatening hormonal deficiencies. Pregnancy poses unique challenges in diagnosing hormonal deficiencies such as AI due to normal physiologic changes affecting the HPA axis as well as other pituitary axes. Therefore, the benefit of empiric hydrocortisone treatment likely outweighs any associated treatment risk in cases with consistent symptomatology and radiographic findings. Presentation: 6/2/2024

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

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

8800 A Case of Hypopituitarism Due to Sheehan Syndrome

Abstract Disclosure: N. Akabogu: None. S. Dejhansathit: None. F. Marium: None. B. Stanley: None. E.M. Bazuaye: None. L.S. Krusniak: None. L.G. Kurukulasuriya: None. U.Z. Khan: None. Background: Sheehan syndrome, which is also known as postpartum pituitary infarction, refers to the necrosis of the anterior pituitary gland due to postpartum hypovolemia, hemorrhage, shock, resulting in various degrees of hypopituitarism. The pituitary gland enlarges during pregnancy due to estrogen stimulation and becomes hyper-vascular, making it prone to infarction with postpartum hemorrhage. The initial symptoms include hyponatremia, weakness, weight loss, but the most prominent specific symptoms are inability to nurse and postpartum amenorrhea. Depending on the severity of hypopituitarism, symptoms may develop within the first few days to weeks after delivery or may take months to years to develop. Case presentation: 35year-old Caucasian female with a medical history of gestational diabetes, hyperlipidemia, and hypertension, who presented to the hospital with flu-like symptoms, leg pain, abdominal pain, and proximal muscle weakness. The evaluating hospitalist observed that patient appeared sluggish and spoke with a deep coarse voice, which concerned him for hypothyroidism. Thyroid function test revealed undetectable free T4 with inappropriately normal TSH of 1.38 – consistent with secondary hypothyroidism. Additional history from patient uncovered 9 months history of constant fatigue, weight gain, dry skin, hair loss, cold intolerance, and intermittent ankle swelling. There is no history of brain irradiation or head trauma. She has 4 biological children, and her last childbirth 3years ago was complicated by severe bleeding from her incision site, requiring transfusion of 6 units of blood. She has been amenorrheic since and is neither on birth control nor had hysterectomy. Physical exam showed mildly enlarged tongue, diffuse pallor, dry scaly skin on upper arms, scanty eyebrows, and slowed speech. Further work-up for pituitary insufficiency showed secondary adrenal insufficiency, secondary hypogonadism, low prolactin, and growth hormone deficiency. There was no evidence of AVP deficiency. Other lab and clinical findings were hypoglycemia, hyperlipidemia, elevated CK, elevated Cr, pericardial effusion, and diastolic hypertension. Pituitary MRI showed markedly attenuated and flattened pituitary gland with no focal mass. Patient was given stress dose hydrocortisone and thyroid hormone replacement, initially IV then oral. Following hydrocortisone and thyroid hormone replacement, her diastolic BP, hypoglycemia, CK, and Cr improved. Further management plans include initiating estrogen (plus progesterone) for bone health. Conclusion: Although Sheehan syndrome is rare in developed countries, it does occur. This case emphasizes the importance of detailed history taking, to discover the root of patients’ presentation. Even though TSH is the screening test for thyroid disease, when pituitary etiology is suspected, it is important to also check a free T4. Presentation: 6/1/2024

8186 Hypoglycemia as an Unusual Presentation of Panhypopituitarism

Abstract Disclosure: P. Chalasani: None. M. Asfaw: None. M. Mansour: None. M. Hammoud: None. T. Altaweel: None. H. Ilyas: None. L. Lawrence: None. Introduction: Hypopituitarism refers to the diminished or complete absence of anterior pituitary function, which may arise from acquired or congenital factors. The symptoms depend on the patient’s age and the hormones affected. We report a case where hypoglycemia led to a new diagnosis of panhypopituitarism in an adult patient. Clinical Case:A 53-year-old female with a past medical history of hypertension was brought to the emergency department after syncope. Patient experienced diaphoresis and loss of consciousness associated with urinary incontinence. She did not have confusion, tongue biting, or muscular weakness after the episode. On presentation, the patient was hypoglycemic with blood glucose of 39 mg/dl and received IV dextrose. No focal neurologic deficits were noted on physical examination. She was mildly hypotensive with blood pressure 98/66 mmHg, and received hydrocortisone 100 mg IV once, and started on IV dextrose infusion. Hypoglycemia workup revealed elevated insulin 16.6 uIU/mL and C-peptide 4.8 ng/mL (1.1-4.4) levels for a blood glucose level of 132 mg/dl, with normal beta-hydroxybutyrate of 0.14 mmol/L (0.02-0.27). Sulfonylurea screen was negative. CT abdomen revealed no pancreatic lesions or abnormalities. Hyperinsulinemia was attributed to insulin resistance in this patient with a BMI of 34 kg/m2. CT head revealed a heterogeneous low-density expansile mass in the sella/suprasellar region measuring approximately 2.5 x 2.3 x 2 cm. MRI brain confirmed a heterogeneous sellar mass with suprasellar extension measuring 3.4 x 2.3 x 2.1 cm abuting the optic chiasm without displacement. Biochemical workup revealed panhypopituitarism with secondary adrenal insufficiency ACTH < 1.5 pg/mL (7.2-63.3) and cortisol 3.63 ug/dL (3.70-19.40); secondary hypothyroidism TSH 0.84 mIU/mL (0.27-4.20) and FT4 < 0.50 ng/dL (0.70-14.8); growth hormone deficiency with low IGF-1 23 ng/mL (65-216); secondary hypogonadism FSH < 1 mIU/mL (46-177), LH < 1 mIU/mL (7.7-59) and estrone < 6 pg/mL (0-125); with normal prolactin 14.1 ng/mL (4.8-23.3). Patient revealed she had been amenorrheic since 23 years old and conceived one child prior. Patient was transitioned to oral hydrocortisone 20 mg AM and 10 mg PM, and started on levothyroxine 50 mcg PO daily. No neurosurgical intervention was recommended. Subsequently, patient requested a second opinion and was transferred to a tertiary center. Conclusion: The link between hypoglycemia and hypopituitarism, may be attributed to hypocortisolism and growth hormone / IGF-1 deficiency. Intriguingly, this patient's initial clinical presentation centered around hypoglycemia, and further evaluation led to the identification of a sellar mass and new diagnosis of panhypopituitarism. This case demonstrates the need to include hypopituitarism in the differential when evaluating hypoglycemic patients. Presentation: 6/2/2024

8301 A Rare Case of IgG4-Related Hypophysitis

Abstract Disclosure: P. Kesavan Chary: None. J.M. Silverstein: None. Background: IgG4-related disease (IgG4-RD) is an immune-mediated condition that presents as systemic inflammation and fibrosis of tissues, often affecting multiple organs. Isolated IgG4-related Hypophysitis is rare and characterized by lymphoplasmacytic infiltration of the pituitary gland by IgG4-positive plasma cells. A combination of clinical, serologic, radiologic, and histopathologic findings is used for diagnosis of IgG4-RD and approximately two-thirds of all patients have elevated serum IgG4 levels. We report a case of isolated IgG4-related Hypophysitis in a middle-aged woman serologically negative for IgG4-related disease. Case Report: A 52 year old female with history of steroid dependent severe persistent asthma, allergic rhinitis, and chronic sinusitis presented with one month of headache, polyuria, and polydipsia. MRI Brain demonstrated an enlarged, rounded pituitary gland 16 x 11 x 9 mm, with homogeneous enhancement, extension into the suprasellar cistern, and mild thickening of the infundibulum suspected to represent a pituitary adenoma. Lab evaluation revealed mild hyperprolactinemia (prolactin 83.2, normal 4.8-23.3 ng/mL) and secondary adrenal insufficiency based on an abnormal high-dose cosyntropin stimulation test in the setting of a low adrenocorticotrophic hormone (ACTH) level (<2.0 pg/mL). Remaining pituitary hormone levels were normal. Inpatient work-up for polyuria and polydipsia showed a low urine specific gravity of 1.003. An overnight water deprivation test was performed. Baseline urine osmolality (UOsm) was 95 mOsm/kg and serum sodium was 144 mmol/L; after 3 hours of water deprivation, serum Osm increased to 301 mOsm/kg (275-300 mOsm/kg) and UOsm only to 215 mOsm/kg, while her sodium increased to 145 mmol/L. Results were felt to be consistent with AVP deficiency (Central Diabetes Insipidus) and the patient was started on desmopressin. Because of the presence of AVP deficiency, further work-up was done to evaluate for an infiltrative process or malignancy. ANA, RPR, ESR, CRP, CBC, ACE level, T-SPOT, and IgG subclasses were unremarkable. Further imaging studies yielded a negative nuclear bone scan and PET/CT scan. For diagnostic purposes, the patient underwent biopsy via an endoscopic endonasal transsphenoidal approach. Pathology showed the presence of >10 IgG4+ plasma cells in a single high-power field, consistent with a diagnosis of IgG4-related Hypophysitis. Conclusion: Isolated IgG4-related Hypophysitis is the least common clinical presentation of IgG4-RD, which is itself a rare and relatively newly recognized condition. IgG4-related Hypophysitis should be suspected in patients presenting with AVP deficiency and pituitary stalk enlargement with an otherwise negative work up. Presentation: 6/2/2024

8528 An Unusual Case Of Adrenal Hemorrhage As An Initial Manifestation Of Castleman Disease In A 29 yo Male With Unsuspected Late-Onset Congenital Adrenal Hyperplasia

Abstract Disclosure: L.M. Martel: None. F. Mercier: None. S. Parisien-La Salle: None. A. Lacroix: None. A. Liberman: None. N. Bettache: None. H. Olney: None. I. Bourdeau: None. Background: Castleman disease is a lymphoproliferative disorder with no clear etiology. We report the case of a 29 yo man presenting with an adrenal hemorrhage as initial manifestation of Castleman disease and unsuspected late-onset congenital adrenal hyperplasia. Clinical case: A 29-year-old male with no significant past medical history except for unilateral orchiectomy at 1 year-old for a possible testicular mass was referred to our adrenal clinic for a 6,2x7,5 cm left adrenal mass showing at CT scan necrosis and an hemorrhagic component (HU52). The patient presented initially with acute left abdominal pain. The adrenal mass showed at peripheral high uptake at PET-FDG (SUVmax 5,3) with no central uptake. His physical exam was unremarkable except for obesity. The hormonal work-up for the adrenal mass revealed normal metanephrines, and normal 1mg-dexamethasone suppression test with morning cortisol of 18 nmol/L (N<50). Further hormonal investigations based on the high adrenal mass uptake and possible adrenocortical carcinoma included: 17-OH Progesterone: 7.7 nmol/L (N:1.1-7.0), Androstenedione: 14.1 nmol/L (N: 1.5-9.0), Testosterone: 11.3 nmol/L (N: 9.0-28.3) and DHEAS: 3.6 umol/L (2.3-18.7). The ACTH levels were increased at 21.2 pmol/L (N:2-11) with morning cortisol of 220 nmol/L. During the consultation, the patient reported a pleuritic chest pain and underwent an urgent CT pulmonary angiography showing a pulmonary embolism with lung infarction in addition to mediastinal lymphadenopathy (biopsy negative) and a mass in his thymus. He underwent thymectomy and the pathology report described Castleman disease (hyaline vascular type). Taking into account the increased level of 17-OH progesterone, we performed an ACTH stimulation test (250 mcg) that showed an increase of cortisol levels from 333nmol/L to 874nmol/L at 60 minutes and of 17OH Progesterone levels from 5.2nmol/L to 44.2nmo/L excluding adrenal insufficiency, but confirming the diagnosis of late-onset congenital adrenal hyperplasia. Genetic analyses: After written consent, the patient underwent genetic analysis of the CYP21A2 gene by direct sequencing and MLPA. The analyses revealed a heterozygous pathogenic variant in the CYP21A2 gene (c.293-13A/C>G). No other genetic variant was identified in the gene. Follow-up: Subsequent adrenal MRIs showed decreasing size of the left adrenal mass; 3 cm at 3 months, 2 cm at 6 months and no residual mass was seen at 9 months supporting the diagnosis of adrenal hemorrhage. Conclusion: To our knowledge, we report a first case of Castleman disease presenting with adrenal hemorrhage as initial symptom with the association of late-onset congenital adrenal hyperplasia. The possible link between these diseases remains to be explored. Presentation: 6/3/2024