Laboratory Results Research Articles

7191 When Pain Is Misdiagnosed: A Case of Parathyroid Carcinoma Masked as Fibromyalgia

Abstract Disclosure: H. Pham: None. P.V. Kumar: None. S. Taylor: None. Parathyroid carcinoma is a rare and aggressive cause of hyperparathyroidism, typically associated with <1% of primary hyperparathyroidism cases. Incidence occurs mainly in the 5th decade of life, with less than 4% of all cases presenting in patients under age 30. Here, we highlight a case involving a 28-year-old woman with fibromyalgia who presented for worsening right shoulder pain in the setting of progressive, poorly characterized pain for the past year. Her initial physical exam was unremarkable aside from a non-tender left sided neck enlargement. However, her laboratory results were significant for corrected serum calcium of 15 mg/dL, serum phosphorus of 2.3 mg/dL, parathyroid hormone (PTH) >2500 pg/mL, and alkaline phosphatase 1604 units/L. X-ray of her right shoulder demonstrated mottled bone concerning for degenerative disease. Thyroid ultrasound revealed a complex cystic lesion posterior to the left thyroid lobe measuring 5.3 x 3.9 x 2.9 cm, worrisome for giant parathyroid adenoma. CT abdomen/pelvis showed diffuse osteosclerosis and innumerable lytic lesions, consistent with osteitis fibrosa cystica, as well as bilateral nephrolithiasis, likely medullary nephrocalcinosis. Her hypercalcemia was treated with aggressive hydration with normal saline and IV pamidronate. She underwent surgical resection of her parathyroid adenoma, which was unfortunately complicated by symptomatic hypocalcemia requiring prolonged care in the ICU. Her calcium levels did improve within a few days, and she was subsequently discharged with close outpatient follow-up. Final pathology report showed predominant thickened trabecular growth pattern with focal vascular invasion consistent with parathyroid carcinoma. Our patient’s case represents a rare presentation of parathyroid carcinoma in a young patient without any additional risk factors. Although atypical, her severe symptomatic hypercalcemia, nephrolithiasis, presence of large neck mass, and diffuse skeletal disease warranted immediate concern for malignant hyperparathyroidism instead of benign adenoma. Delayed diagnosis in our patient led to prolonged bone disease and severe complications. While hungry bone syndrome typically manifests post-parathyroidectomy in patients with end-stage renal disease, our patient experienced this complication in the setting of advanced, untreated hyperparathyroidism. We should consider hypercalcemia and hyperparathyroidism in our differential diagnosis for chronic pain, especially if pain remains uncontrolled with conservative measures. The most appropriate initial test for evaluation of hypercalcemia is a PTH level to distinguish between PTH-dependent and PTH-independent etiologies. Parathyroid carcinoma, even in young patients, should be considered when PTH is >3x upper limit of normal, serum calcium is >14, or skeletal and renal involvement is present. Presentation: 6/3/2024

8338 A Case Series Of 3 Patients With Unusual Miliary Lung Metastases In Paraganglioma: Diagnostic Workup, Treatment Challenges And Outcomes

Abstract Disclosure: K.M. Charles: None. M.A. Nazari: None. A. Jha: None. A. Derkyi: None. S. Talvacchio: None. M.J. Kuo: None. M. Patel: None. T. Prodanov: None. A.S. Alzahrani: None. A. Chen: None. J. Glod: None. J. Del Rivero: None. A.M. Gharib: None. K. Pacak: None. Background: Pheochromocytomas (PCCs) and paragangliomas (PGLs, together PPGLs) are uncommon neuroendocrine tumors originating from adrenal medulla chromaffin cells and sympathetic/parasympathetic ganglia. Metastatic disease occurs in a subset of PPGLs, ranging from 5% to 30% depending on the underlying genetic factors. Metastases are typically found in the bone, lung, lymph nodes, or liver. Historically, there have been no reported cases of PPGL with miliary pattern of pulmonary metastases. Methods: Three patients were identified with pulmonary metastases. All patients were evaluated between 2016 and 2023, and all developed extensive pulmonary metastatic disease. The evaluation process involved reviewing their medical history, laboratory results, and potential therapeutic approaches. Each patient underwent surgical intervention for the primary tumor and received systemic therapies once metastatic spread was detected. Results: We present three patients with either germline succinate dehydrogenase subunit D (SDHD) or von Hippel-Lindau (VHL) pathogenic variants who developed this rare condition. Patient 1: a 14-year-old female with right PCC and a recurrent left neck PGL carrying VHL type 2 pathogenic variant: VHL c.250G>T (p.Val84Leu) and received various chemotherapies with an unfavorable response. Patient 2: a 23-year-old female with a left jugular PGL carrying SDHD pathogenic variant: SDHD c.124_127delinsA TA (p.Glu42Ilefs*44). Patient 3: a 26-year-old female with a right PCC carrying a germline VHL type 2 pathogenic variant: VHL c.439C>G (p.Leu147Val). The latter two patients experienced disease stabilization through chemotherapy and systemic targeted radiotherapy, respectively. Discussion/Conclusion: This case series is unique as it highlights the rare occurrence of miliary spread of pulmonary metastases resulting from PCC or PGL. It also provides insight into prospective treatments options and outcomes for clinicians administering care within this population of patients. Though it is not clear at this time, this case series may represent a new subset of PPGL that have different genomic features and require a different therapeutic approach. Presentation: 6/1/2024

7165 A Case of Severe Myxedema Coma with Levothyroxine Allergy

Abstract Disclosure: A. Rothstein Costris: None. A. Yaseen: None. S. Levy: None. Introduction: Myxedema coma is a life threatening condition with a mortality rate of 25-60%. Untreated, it can lead to fatal physiological changes. The treatment is thyroid hormone replacement therapy, alongside supportive care for complications. Clinical Case: A 65-year-old woman, who has been dealing with untreated hypothyroidism since 2012 and reported allergies to various levothyroxine brands, presented with falls, weakness, and exacerbated leg numbness. During the examination, she exhibited periorbital edema, non-pitting edema in the lower extremities, bradycardia, and hypothermia. The blood work revealed an elevation in TSH levels at 301 uIU/L (0.45-5.33 uIU/mL). The patient was administered IV Synthroid (200 mcg), Atropine, and Hydrocortisone due to concerns about myxedema coma. After four hours, the patient experienced angioedema and hypotension, necessitating intubation. This situation was complicated by a pulseless electrical activity (PEA) arrest. Following cardiopulmonary resuscitation and the administration of epinephrine, the patient achieved return of spontaneous circulation. The allergy team assessed the patient for potential anaphylactic shock from IV Synthroid. Subsequently, the patient was initiated onIV Liothyronine and Hydrocortisone, leading to improvement in mental status over a period of a few weeks, and no adverse effects were reported. Thyroid labs improved to TSH of 53 (0.45-5.33 uIU/mL), FT3 of 3.3 (2.5-4.4 pg/mL) and total T3 of 133 (87-178 ng/dl). Upon discharge, the patient was prescribed Liothyronine, with plans to perform a Levothyroxine desensitization test in the outpatient setting. Conclusion: Myxedema coma is an endocrine emergency. Patients usually present with deteriorating mental status, hypothermia, and multiple organ system abnormalities. The diagnosis relies more on the clinical presentation and physical examination than on laboratory results. Thyroid replacement therapy serves as the cornerstone of treatment, with a preference for T4 due to its greater availability and lower likelihood of adverse events compared to Liothyronine, which may increase the risk of mortality at higher doses. Despite associated risks, incorporating low doses of Liothyronine is still considered in treatment plans, driven by concerns about reduced T4 to T3 conversion in myxedema patients. Hypersensitivity reactions to Levothyroxine are uncommon but may manifest as widespread hives, swelling, eczema-like skin rashes, elevated body temperature, and compromised liver function, with only one case reporting an anaphylactic reaction to Levothyroxine. In summary, the potential for experiencing an anaphylactic reaction to Levothyroxine exists, highlighting the need to contemplate alternative treatments, such as Liothyronine. Desensitization methods can be considered once the patient's condition is stable. Presentation: 6/2/2024

6889 Potential Impact of Parental Origin of Inheritance in Presentation of Familial Partial Lipodystrophy

Abstract Disclosure: D. Gilio: None. M.C. Foss de Freitas: Advisory Board Member; Self; PTC Therapeutics. Speaker; Self; Amryt. O. Besci: None. M. Celik Guler: None. A. Neidert: None. I. Yildirim: None. B. Akinci: Advisory Board Member; Self; Amryt. Consulting Fee; Self; Regeneron Pharmaceuticals, Alnylam Pharmaceuticals, Amryt, AstraZeneca, Boehringer Ingelheim, Lilly, MSD, Novartis Pharmaceuticals, Novo Nordisk, Sanofi-Aventis, Servier, Third Rock Ventures. E.A. Oral: Advisory Board Member; Self; Amryt, Regeneron Pharmaceuticals. Consulting Fee; Self; Regeneron Pharmaceuticals, Amryt, Third Rock Ventures. Grant Recipient; Self; Regeneron Pharmaceuticals, Amryt. Research Investigator; Self; Novo Nordisk, Fractyl, Ionis Pharmaceuticals Inc., GI Dynamics, Rhythm Pharmaceuticals. Other; Self; Amryt. Background: Familial partial lipodystrophy Type 2 (FPLD2) caused by autosomal dominant LMNA variants is characterized by partial loss of subcutaneous adipose tissue in the limbs, trunk, and gluteal region with accumulation in other parts of the body, such as the face and neck. It is usually associated with different degrees of insulin resistance and hypertriglyceridemia and body composition patterns. We wanted to know the contributing factors for the different metabolic abnormalities and body composition presentations of FPLD2. We hypothesized that parental inheritance line may be a contributory factor to the expression of the metabolic phenotype and body composition characteristics. Methods: We retrospectively collected clinical data of 77 FPLD2 cases from the Divisions of Metabolism and Endocrinology of 3 different sites: the University of Michigan, the University of São Paulo and The Turkish Lipodystrophy Study Group (TuLip). We further selected 53 published cases curated from 15 studies in the literature. For inclusion of the studies, we used web search tools including PubMed, OMIM and Google Scholar. Only patients where we could assess the genetic inheritance were included in this study. Data collected included demographic information, medical history and laboratory results. Results: 79 patients inherited the LMNA variant from the mother (Group 1; 18 males and 61 females), and 51 patients inherited it from the father (Group 2; 14 males and 37 females). The median age at lipodystrophy diagnosis was lower in Group 1 than in Group 2. Diabetes was reported in more than half of the groups; however, the prevalence rates were not significantly different. The mean age (± SEM) at first diagnosis of diabetes was 30 ± 15 years in Group 1 and 32 ± 11 years in Group 2; the microvascular complications were present in 8 patients with diabetes in Group 1 (36.3%) and in 5 patients in Group 2 (23.8%). Both groups' mean triglycerides levels were >150 mg/dL, with a trend of higher triglycerides in Group 2 than in Group 1. Episodes of acute pancreatitis were identified in 9 patients (19.5%) of Group 1 and 10 patients (31.2%) of Group 2; however, patients in Group 1 showed 1.7 episodes of pancreatitis per person while Group 2 showed 8.1 episodes per person on average. The fatty liver disease was the most common liver abnormality identified and it seemed to be more frequent in Group 2 than in Group 1. There was no difference between the two groups in relation to the body mass index (BMI) and the ratio of percent fat mass of the trunk to percent fat mass of the legs (FMR); however, the DEXA (dual x-ray absorptiometry) showed a higher total fat mass in Group 1 compared to Group 2 (22.2 versus 17.3 Kg, p=0.040) in the presence of comparable total lean mass. Conclusion: Our data suggest that there is a difference in body fat mass according to the genetic inheritance, however the metabolic impact is not completely clear and require more detailed analysis. 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

7246 Cardiac Paraganglioma: A Rare Entity

Abstract Disclosure: L. Javed: None. L. Jonea: None. Cardiac paragangliomas are an exceptionally uncommon subset of neuroendocrine neoplasms. We present a case of a patient presenting with this condition. 70-year-old woman with pertinent past medical history of chronic veinous insufficiency complicated by recurrent abscesses of her right leg since venaseal procedure. The patient had positive IgG lambda on immunofixation that raised concerns for MGUS. Therefore, a F-18 FDG PET-CT scan was performed for further evaluation. PET-CT revealed a hypermetabolic mass in the upper inner right thigh and the right atrium (SUV 17.6) raising concern for septic thrombi. She was admitted in the hospital for initiation of antibiotic therapy. Transesophageal echocardiogram (TEE) revealed a 4.5 cm x 4.0 cm mass in the right atrioventricular (AV) groove region, extending over the root of the main pulmonary artery. Following discharge, despite completing six weeks of IV antibiotic therapy a CT scan on a subsequent clinic visit revealed the same mass as seen on TEE. CT imaging raised suspicion of neuroendocrine tumor. This led to referral to the endocrinology department. Laboratory results showed elevated normetanephrine and dopamine levels increasing likelihood of paraganglioma. Lab Results: 24 hr urine normetaneprhine :7197(N ≤ 376 mcg), 24 hr urinary dopamine :879 (N ≤400 mcg), 24 urinary metanephrine: 84 (N ≤96 mcg) & 24 hr urinary epinephrine <3 (N ≤20 mcg). Her home systolic blood pressure readings varied between 120’s & 170’s. She was initiated on Prazosin 1 mg daily in addition to the existing antihypertensive medications of nebivilol, amlodipine & furosemide. Few months later, this patient successfully underwent cardiac mass resection. Histologic findings of the resected mass were consistent with paraganglioma. Post-surgery, anti-hypertensive medications were discontinued, and blood pressure normalized to systolic readings in the 90s to 120s and diastolic readings in the 60s to 80s. Repeat biochemical tests indicated a normalization of normetanephrine & dopamine levels, validating the success of the resection. This case features an extremely rare entity cardiac paraganglioma that had an atypical clinical manifestation of being asymptomatic. Timely diagnosis and appropriate management are crucial for patient outcomes. Surgical intervention, although fundamental, bears significant risks, necessitating meticulous preoperative management to mitigate potential complications. The medical approach focuses on averting perioperative complications such as hypertensive crisis, cardiac arrhythmias and myocardial infarction. This is achieved by administering alpha and beta adrenoceptor blockers for a minimum of two weeks before the scheduled surgery. Regular follow up is also essential due to the unpredictable malignant potential of these tumors. Presentation: 6/3/2024

7039 Isolated Gonadotropin Deficiency Transmitted From Mother to Daughter Conceived Through Assisted Reproduction Due Newly Identified, Autosomal Dominant Mutation Within the SOX10 Gene

Abstract Disclosure: S. Bakjaji: None. R.P. Hoffman: None. Title: Isolated gonadotropin deficiency transmitted from mother to daughter conceived through assisted reproduction due newly identified, autosomal dominant mutation within the SOX10 gene. Objectives: We report a case of genetic isolated gonadotropin deficiency occurring in a mother and in her daughter conceived through assisted reproductive technology using mother’s ovum. Methods Case report Results: The daughter was initially seen at 12 years 0 months for evaluation of short stature and concerns she had not grown in the last year. She was otherwise in good health and reported normal sense of smell. At the time of assessment, her height was 132.6 cm (0.61 percentile; Z=-2.5). The mother had been diagnosed with Kallmann’s syndrome and achieved pregnancy through ovarian stimulation. Her height was 152.4 cm, while the father's height was 177.8 cm. Two male siblings were born at the same time and were in normal health. Physical examination of the daughter was unremarkable. She had Tanner stage 1 pubic hair and Tanner stage 1 breasts. The growth chart displayed a notable deceleration in growth Laboratory results showed normal free T4 of (0.9 ng/dL) with slightly elevated TSH (8.348 uIU/mL), positive thyroid antibodies, normal IGFI at 164 ng/mL (normal range for Tanner I: 54 - 301) and IGFBP-3 at 5.8 ug/mL (2.4 - 8.4 ug/mL). The karyotype was 46 XX. Her peak growth hormone using glucagon-arginine stimulation was 12.8 ng/ml. When no pubertal development was seen over the next 6 months, GnRH stimulation testing revealed baseline LH of 0.04 mIU/ml and a peak of 1.78 and baseline FSH of 0.41 mIU/ml with a peak of 2.83. Bone age was 8 years 4 months.Over the next year her growth velocity was 4.8 cm/year and she remained prepubertal. Genetic testing done identified a new heterozygous sequence variant (c.226G>A) in the SOX10 gene which would lead to replacement of valine by isoleucine at position 76 and was thought to be damaging in silico. This variant was subsequently found to be shared with her mother but not her father. Conclusions: Most Kallmann’s syndrome or genetic isolated gonadotropin deficiency cases are due to autosomal dominant but spontaneous new mutations since infertility is usually present in those with the syndrome. This case emphasizes the importance of genetic counselling regarding inheritance risk when assisted reproduction technology using maternal ovum is used. Presentation: 6/2/2024

6942 Should there be a consensus statement about managing Inguinal Hernia In females? A Case of Delayed Diagnosis in Complete Androgen Insensitivity Syndrome (CAIS)

Abstract Disclosure: S. Echetebu: None. Introduction: Androgen Insensitivity Syndrome is usually due to a missense mutation that encodes part of the androgen receptor. More than 50% of females with CAIS present with inguinal hernias (4:1 female to male ratio). Previous CAIS studies have estimated the incidence of CAIS to be 0.8% to 2.4% in girls with inguinal hernias. 90% of the girls with CAIS will undergo inguinal hernia repair during childhood. The prevalence of germ cell tumors is estimated as 0.8% therefore, post-pubertal gonadectomy is now the recommended therapy for individuals with CAIS. Clinical Case: We present a case of a 15-year-old patient with primary amenorrhea who underwent bilateral inguinal hernia repair at the age of 5 weeks and was raised as a female. Initial ultrasound imaging at the age of 14 years revealed an absent uterus and complex hemorrhagic cysts of the ovaries. Further laboratory results revealed 46 XY chromosomal analysis, confirming her diagnosis of CAIS. Her laboratory values are: FSH 6.0 mIU/ml (1.0 to 18.6), Prolactin 15.6 ng/mL (<25), 17OHProgesterone 49 ng/dl (<265), Estradiol 30 pg/ml (<47), LH 17 mIU/ml (0.4 -11.7), Anti Mullerian Hormone 368 ng/ml (<13), Testosterone 629 ng/dl (<55 ). Upon our review of her past medical records from a different hospital, the operation note reports that her gonads resembled testes. Gonads were relocated in the abdomen without follow-up or consultation with an endocrinologist. Upon receiving her new diagnosis, the patient experienced significant emotional distress. As a result, both the patient and her family received psychological counseling and were referred to a genetic counselor to assess any potential risks for her younger sister. There is currently no consensus on the management of females with inguinal hernias in the available literature. It is widely accepted to perform gonadectomy. Currently, researchers at NIH are conducting an observational study on the benefits of additional delays in gonadectomy. Although most surgeons are familiar with this condition, it would be beneficial for families and patients to have an early diagnosis and provide appropriate education regarding future sexual encounters and fertility concerns. Conclusion: We propose to initiate a consensus statement for pediatricians, surgeons, and endocrinologists to perform systematic genetic testing in females with inguinal hernia. Such testing may include either a buccal mucosal smear, karyotype, or skin biopsy in all females with inguinal hernias. If the family chooses to delay orchiectomy, it is recommended that during hernioplasty, the testes should be repositioned in a location that allows for easy monitoring using annual imaging. By adopting this methodology, we can increase awareness about the effects of diagnosis and foster discussions among healthcare professionals regarding suitable management options. Presentation: 6/3/2024

12293 Dynamic Clinical Evolution: Why Patients Require Long-Term Follow-up Over Time

Abstract Disclosure: A. Attre: None. A. Syeda: None. A. Khan: None. B. Esayag-Tendler: None. Dynamic Clinical Evolution: Why Patients Require Long-Term Follow-up Over Time Introduction Primary Hyperaldosteronism (PHA) is an increasingly recognized cause of secondary hypertension amenable to specific therapy. We describe a case of PHA with change in management trajectory over time. Case A 48-year-old woman was diagnosed with PHA in 2009 based on an aldosterone level of 42.7 ng/dL, plasma renin activity of <0.1 ng/mL/hr, and a low potassium of 3.4 mmol/L. At that time, simultaneous adrenal venous sampling (AVS) had revealed a bilateral etiology of aldosterone excess. Original imaging with CT scan had shown fullness on both adrenal glands, and she was treated with 50mg daily spironolactone. Follow-up with CT scan in 2018 revealed similar imaging phenotype. When she established care with us in 2020, the abdomen MRI revealed a 2.5 cm x 1.9 cm right adrenal nodule. In addition, the blood pressure readings were noted to be high despite increasing doses of spironolactone to 150mg. Her laboratory results revealed aldosterone 151 ng/dL [< 31 ng/dL], cortisol 0.8 µg/dL, plasma renin activity 0.8 ng/mL/hr [0.2 ng/mL/hr - 1.6 ng/mL/hr], ACTH 12.5 pg/mL [7.2 pg/mL - 63.3 pg/mL], normal plasma metanephrine and a normal thyroid panel. A decision was made to repeat AVS in 2023 following Dr. Doppman’s protocol. The patient’s spironolactone was held before AVS and the plasma renin activity before the procedure was 0.4-0.8 ng/mL/hr. Results: Repeat AVS in 2023 showed mean pre-ACTH right to left lateralization index (LI) of 29.9 and mean post-ACTH LI of 9.7 (cutoff >4). This is concordant with the right adrenal nodule noted on imaging. The selectivity index confirmed adequate adrenal venous sampling data. Analysis of our findings confirmed right adrenal excess and left adrenal suppression compared to the IVC results. This patient underwent a laparoscopic right adrenalectomy in 2023. This patient's aldosterone levels were measured two days postoperatively and were found to be 4.2 ng/dL, showing immediate improvement. Six months postoperatively, our patient’s home and clinic blood pressures are in 120s/60s mmHg range without any medications. The aldosterone remains less than 6 ng/dL and the plasma renin activity is no longer low. Her potassium remains around 4.9 mmol/L. Discussion Based on current literature, surgical treatment is preferred when there is a confirmed unilateral cause of PHA. Adrenalectomy is recommended in patients with confirmed unilateral hyperaldosteronism especially when they do not achieve clinical and biochemical goals (renin plasma activity >1 ng/mL/hr, resolution of hypokalemia and optimal BP control) despite the use of MRA at appropriate doses. Suppressed renin is known to be associated with increased cardiovascular morbidity. This case serves as an important example of the need to follow patients long-term because PHA is a dynamic clinical entity that affects quality of life. Presentation: 6/3/2024

8192 A Two-Cycle Clinical Audit Testing Inpatient Management Of Hypophosphatemia In A UK District Hospital

Abstract Disclosure: J. Porto: None. E. Ssemmondo: None. N. Obike: None. A. Abobaker: None. R. March: None. N. Tun: None. T. Pawlak: None. Objective: A clinical audit was conducted to assess if there was any improvement in management of hypophosphatemia among patients admitted to the medical wards using the local Trust protocol, following structured edcational sessions to the junior doctors covering medical wards. Design and methodology: The 2 cycles of the audit were conducted between March 2020 and September 2021 in Scarborough district Hospital. The clinical notes of 52 patients (20 in the first cycle and 32 in the re-audit) with hypophosphatemia were reviewed. These were identified using the electronic laboratory results of patients within the study period. The aspects of the trust protocol for management of hypophosphatemia that were audited; documentation of symptoms associated with low phosphate levels, cardiac monitoring in severe hypophosphatemia, identification of the likely cause of hypophosphatemia, the presence or absence of associated acute kidney injury (AKI) and initiation of phosphate replacement. The results of the first audit were presented at the local hospital clinical governance meeting (August 2020). Following this, 2 teaching sessions and 2-case based discussion on hypophosphatemia were organised for all the doctors in the department of medicine. The re-audit was subsequently conducted after the fourth teaching session. The proportions of each audited item were compared between the first audit and the re-audit using Fisher exact probability test. Results:25% of patients in the first audit had severe hypophosphatemia compared to 28% in the re-audit. In patients with severe hypophosphataemia, only 33.3% had cardiac monitoring during the re-audit cycle compared to 60% in the first cycle, and the difference was not statistically significant (p=0.58). There was significant improvement in the documentation of symptoms of hypophosphataemia amongst inpatients during the re-audit cycle compared with the initial cycle; 62.5% vs only 10% (P 0.002). Most patients had an underlying cause of the hypophosphatemia identified (80% and 62.5%-first and second cycle respectively). AKI was associated with hypophosphataemia in 15% & 34.4% (P 0.2) in the first and second cycles respectively. Despite low phosphate levels, 25% and 28.1% at the initial audit and the second cycle respectively did not receive any form of phosphate replacement. Conclusion: The two-cycle clinical audit showed that the teaching sessions on management of hypophosphatemia increased the awareness of the importance to document whether the patients were symptomatic or asymptomatic following the drop in their phosphate levels, which can help to identify patients at risk of developing complications, such as cardiac arrythmias. However, these sessions were not sufficient to improve overall management of patients with low phosphate levels. Presentation: 6/1/2024

Internal Quality Controls in the Medical Laboratory: A Narrative Review of the Basic Principles of an Appropriate Quality Control Plan

To ensure the quality of their analyses, medical laboratories carry out internal quality control (IQC) on a daily basis. IQC involves control samples with known target values for all parameters used by a laboratory in clinical practice. The use of IQC enables the laboratory to monitor the accuracy and precision of laboratory results. The use of appropriate IQC strategies has been accepted in medical laboratories for decades, and IQC has been included in international recommendations and guidelines. The term “IQC strategy” (also termed a quality control plan) refers to the types of IQC materials to be measured, the frequency of IQC events, the number of concentration levels in each IQC event, and the IQC rules to be used. A scientifically sound IQC strategy must follow two principles, namely, (1) statistical follow-up on the IQC results generated in the laboratory by means of Levey–Jennings control charts and Westgard rules (i.e., quality control by means of statistical procedures) and (2) the determination of limits on the basis of medical considerations and the definition of analytical goals (quality control on the basis of medical relevance). In this narrative review, we describe the fundamental principles of an adequate IQC strategy for laboratorians and nonlaboratorians.

7452 A Diagnostically Challenging Case of Hyperandrogenism in Postmenopausal Woman

Abstract Disclosure: M.S. Hossain: None. S. Hossain: None. B. Gautam: None. H. liao: None. S.C. Kumar: None. D.S. Rosenthal: None. Background: The diagnosis of new-onset severe hyperandrogenism in postmenopausal women is rarely encountered, posing a unique challenge for clinicians. Ovarian hyperthecosis and androgen-secreting tumors are the usual suspects in post menopause. In our case ovarian hyperthecosis is the primary consideration but elevated 17-OH Progesterone (17-OHP) introduces the potential co-existence of Non classical congenial adrenal hyperplasia (NCCAH) or rare instances of Sertoli-Leydig Cell Tumor (SLCT). Case Presentation: A 70 years old female, with no past medical history, referred to the Endocrinology clinic for significantly elevated testosterone level. She reported excessive hair growth in various areas of her body since 2022, which required shaving almost every day. She also reported male pattern hair loss and weight loss of 15 lbs over the last three months. She denied headache, vision changes, deepening of voice, history of fertility problems and use of exogenous testosterone. Her vital sign were normal. On examination, she had clitoromegaly, terminal hair growth on her upper lip and chin, breast atrophy, male pattern baldness, but no cushingoid or acromegaly features. Blood tests showed significantly elevated total testosterone: 1422 ng/dl (2-45); free testosterone: 147.9 pg/ml (0.2-3.7) and Estradiol: 64 pg/ml (Postmenopausal <31) with low LH: 7.6 mIU/ml (Postmenopausal 10.0-54.7) and FSH: 22.2 mIU/mL (Postmenopausal 23-116). Her serum ACTH, DHEA Sulfate, 11-deoxycortisol, 17 OH pregnenolone, TSH, Free T4, prolactin, IGF-1 were normal while her 17-OHP: 396 ng/dl (<45 ng/dl) was significantly elevated. An ACTH stimulation test showed 17-OHP level of 734 ng/dl at 30 minutes and 901 ng/dl at 1 hour. Pelvic ultrasonography: right ovary of 2.3 x 1.6 x 1.9 cm and the left ovary of 3.1 x 1.8 x 3.0 cm. MRI showed normal adrenal glands but a prominent left ovary. Patient was referred to the Obstetrics department to undergo bilateral oophorectomy for the definitive diagnosis and treatment. Discussion: The current ACTH stimulation test for non-classical congenital adrenal hyperplasia is validated for premenopausal women but lacks standardization in post-menopausal state. In our case, distinguishing the source of elevated 17-OHP between adrenal (NCCAH) and ovarian (SLCT) was difficult. Unexpected asymmetry in ovarian size observed in our case further complicates the scenario, contrasting with the typical symmetrical enlargement seen in ovarian hyperthecosis. Pending surgical pathology will further guide the management. This case highlights the complexity of diagnosing hyperandrogenism in postmenopausal women, emphasizing the significance of thoroughly exploring differential diagnoses and meticulously analyzing laboratory results. Presentation: 6/2/2024

8191 Navigating The Maze Of Adrenal Insufficiency, A Complex Case Of Late Presentation

Abstract Disclosure: K.N. Pereira: None. V. Sundaram: None. V. Mehta: None. K. Desai: None. B. Agrawal: None. Adrenal insufficiency, a rare but potentially life-threatening endocrine disorder, arises from the inadequate production or ineffective response to adrenal hormones, particularly cortisol and aldosterone. It poses diagnostic challenges, especially in individuals with intricate medical histories and manifests as either primary (Addison's disease) or secondary. The subtlety of initial symptoms often leads to a delayed diagnosis, emphasizing the importance of a high index of suspicion among healthcare providers. Timely recognition and intervention are crucial to prevent adrenal crises, which includes severe hypotension, electrolyte imbalances and life-threatening complications. This case report delves into the presentation, diagnosis, and management of primary adrenal insufficiency in a 51-year-old female with a myriad of co-morbidities who presented with persistent low blood pressure, syncope episodes and dizziness both at rest and with exertion, despite being on midodrine with systolic blood pressure readings ranging from 60s to 80s mmHg. She was also noted to be bradycardic and laboratory results showed hyponatremia, hyperkalemia, hypoglycemia and anemia. She was given prompt fluid resuscitation, stress dose steroids and fludrocortisone, leading to a remarkable improvement in blood pressure and overall clinical status. Subsequent testing showed low serum cortisol level and elevated ACTH level, confirming the diagnosis of primary adrenal insufficiency. Continued steroids resulted in significant symptomatic improvement and with no further episodes of hypotension or syncope on ensuing follow ups. This case serves as a poignant illustration for the need for a heightened clinical suspicion, as the symptoms of adrenal insufficiency can often masquerade within the intricate tapestry of comorbidities. When the utilization of midodrine, aimed at managing orthostatic hypotension, did not abate symptoms, it prompted a thorough investigation into the possibility of underlying adrenal dysfunction. This case also highlights the collaborative, multidisciplinary approach in the management of adrenal insufficiency, with endocrinology playing a pivotal role. Presentation: 6/1/2024

6768 A Rare Presentation of Primary Adrenal Insufficiency with Hypertension & Hypokalemia

Abstract Disclosure: A.M. San Hernandez: None. R. Alshantti: None. G. Espinoza Mercado: None. J.L. San Hernandez: None. Introduction: Adrenal Insufficiency is caused by the failure of the adrenal cortex to produce glucocorticoids +/- mineralocorticoids. This can be due to a defect in the adrenal cortex, or in the hypothalamic pituitary axis. The clinical manifestations are usually non-specific, ranging from mild vague symptoms to life threatening crisis. Therefore, diagnosis requires a high level of suspicion by providers. Unusual presentations of primary adrenal insufficiency (PAI) with hypertension and hypokalemia have been rarely described in the literature. We present a rare case of PAI with hypertension and hypokalemia. Case Presentation: A 68 years old female with a medical history of rheumatoid arthritis, hypothyroidism on Levothyroxine, chronic transaminitis, and bicytopenia presented to the hospital with a 6 weeks history of generalized weakness, loss of appetite, weight loss, and dizziness. Patient denied any diuretic or steroid use within the last 2 years. On arrival, she was afebrile, hypertensive (168/84mmHg), with normal oxygenation and pulse. Physical examination was unremarkable with normal volume status. Initial laboratory results showed low sodium 116 mEq/L, low serum osmolality 247 MEQ/kg, normal potassium 3.6 mEq/L, Creatinine 0.3 mg/dL & BUN 9 mg/dL. She was initially started on IVF normal saline. Further workup revealed normal TSH & FT4 levels. Urine study showed urine osmolality (477 MOSM/KG), & urine sodium (127 mEq/L). Given these findings, SIADH was suspected and fluid restriction was started. Sodium level continued to be low with minimal improvement to 120 mEq/L, potassium levels also dropped (3.3-3.2 mEq/L), requiring daily replacement. BP remained elevated ranging from 150s to 160s systolic and 80s to 90s diastolic. Hypertension was controlled with her home medication Amlodipine. Although atypical presentation with hypertension & hypokalemia, the diagnosis of adrenal insufficiency was considered. Laboratory evaluation showed low morning cortisol 5.2 ug/dL, with album level 3.5 g/dL. Cosyntropin stimulation test showed 1.3 ug/dL (at baseline), 9.9 (30 min post administration), and 14.4 (1 hour post administration); results confirming PAI. ACTH, Renin, Aldosterone, & DHEAS levels were normal. CT adrenal was normal. Patient was started on hydrocortisone; some of her symptoms & Na level improved. Further investigation of the etiology of PAI and possible hyperaldosteronism is pending outpatient follow up. Conclusion: Adrenal insufficiency is a life threatening condition with serious consequences if diagnosis is missed. It manifests by a wide spectrum of symptoms and signs, some can be masked by the presence of other comorbid conditions leading to atypical presentations. Our case highlights the importance of maintaining a high level of suspicion of adrenal insufficiency in patients with atypical presentation, including those with hypertension & hypokalemia. Presentation: 6/3/2024

8238 Thyroidectomy for Thyroid Storm Complicated by Drug-Induced Hepatotoxicity and Thyrotoxic Cardiopulmonary Disease

Abstract Disclosure: T.A. John: None. A.C. Suarez: None. J. Genkil: None. S. Patil: None. C. Anastasopoulou: None. Case Presentation: A 59-year-old female with hypertension and type 2 diabetes presented with palpitations, and several months of hyperthyroid symptoms, lower extremity swelling, and dyspnea on exertion. On presentation, patient was diaphoretic, tachycardic, volume overloaded and had symmetric swelling of the thyroid gland. Lab results revealed FT4 3.28 ng/dL, total T3 384.59 ng/dL, TSH < 0.01 µIU/mland elevated TSI. Electrocardiogram showed sinus tachycardia. Chest radiography showed pulmonary edema. Echocardiography showed a reduced ejection fraction of 35%, dilation of right ventricle, severe mitral and tricuspid regurgitation, and severely elevated pulmonary artery systolic pressure (55-60 mm Hg). Thyroid ultrasound revealed enlarged, heterogeneous thyroid gland with normal vascularity. The diagnosis of thyroid storm due to Graves' disease was made with a score of 50 on the Burch-Wartofsky Point Scale. Patient was started on propylthiouracil (PTU), metoprolol tartrate and furosemide. Corticosteroid therapy was not utilized due to the risk of worsening heart failure from sodium retention. After two days of PTU, patient developed drug induced liver injury (DILI). Patient was then transitioned to methimazole which was also discontinued thereafter due to progression of DILI. She was started on potassium iodide to suppress thyroid hormone production, and N-Acetyl cysteine (NAC) for DILI. Due to persistent thyrotoxicosis, the patient underwent a total thyroidectomy on hospital day 13 and was started on levothyroxine for post-surgical hypothyroidism. Liver function returned to normal on day 16. A surveillance echocardiogram obtained 3 months later showed recovered biventricular function (ejection fraction 55-60%), mild mitral and tricuspid regurgitation and normal pulmonary pressures. Educational value: Thyroid storm is an uncommon, life-threatening emergency. Thioamides remain the cornerstone of treatment, but rarely, they can result in adverse events such as hepatotoxicity. When thioamides are contraindicated, other agents (e.g., iodine, lithium, potassium perchlorate, cholestyramine, glucocorticoids) can be utilized; however, refractory cases might require total thyroidectomy as definitive treatments. Our patient had marked recovery of cardiac function and resolution of pulmonary hypertension and DILI after timely surgical intervention. Multidisciplinary care is pivotal for the successful management of thyroid storm. Presentation: 6/3/2024

7295 Giant Pituitary Adenoma with Rapid Symptomatic Progression and Postoperative Mortality

Abstract Disclosure: R.D. Kennedy: None. M. Nicholson: None. Introduction: Giant pituitary adenomas, defined as pituitary adenomas measuring greater than 4 cm, present a therapeutic challenge because of their size, clinical features, and increased potential for complications following surgical intervention. Early detection and intervention to prevent growth and progression is paramount. We present a case of a patient with a giant 6.3 cm pituitary adenoma who had significant neurologic compromise, requiring surgical intervention, with resultant postoperative complications and death. Case:Patient is a 41 year old male with known history of pituitary adenoma who presented on 11/1/2023, from outside hospital, to the Neuroendocrine clinic with complaints of excessive truncal obesity, impotence, fatigue, and apathy. Vital signs were within normal limits. Physical exam revealed clouding of consciousness, grossly intact cranial nerve function, truncal obesity, and diminished power, tone, and bulk of the extremities. Formal visual field testing revealed bitemporal hemianopsia. A head CT scan revealed a 6.3 cm sellar mass with expansion of the sella, invasion of soft tissue into the sphenoid sinus, and extension of soft tissue cranially to the level of the third ventricle eccentric to the left. There was no evidence of apoplexy. Lab results revealed Prolactin of 924 ng/mL. The patient had been taking Bromocriptine, 2.5 mg daily, for at least three weeks. Less than three weeks after his initial evaluation, he returned to the hospital with complaint of acute ataxia. Pituitary MRI revealed 6.3 cm sellar mass with evidence of acute and subacute blood products, stretching of the optic chiasm from mass effect, extension into the bilateral cavernous sinuses, superior left MCA displacement, posterior left PCA displacement, 5 mm midline shift, uncal herniation and descending transtentorial herniation. The patient underwent endoscopic transsphenoidal resection with subsequent craniotomy for debulking. Postoperatively, he developed new right sided hemiplegia with aphasia with subsequent MRI finding of watershed infarct at the left MCA/PCA lateral posterior border zone territories with increasing mass effect over a 30 day hospital stay. He developed progressive global edema with worsening uncal and tonsillar herniations. Brain death was pronounced on 11/30/23. Discussion:This case highlights the importance of early intervention in patients with giant pituitary adenomas. Our patient had been experiencing right sided weakness for at least one year prior to his admission to our facility. In this case, earlier treatment with a dopamine agonist may have decreased the size of the adenoma or prevented rapid growth. This may have precluded the need for surgical intervention on an adenoma of this size, which carries increased risk for postoperative complications. Presentation: 6/2/2024

7247 Adrenal Insufficiency In Advanced Cirrhosis: A ‘Shocky’ Clinical Dilemma

Abstract Disclosure: L. Aboishava: None. A. Pareek: None. A. Mertens: None. A. Erokhin: None. Background: In patients with advanced cirrhosis, profound hypoproteinemia can complicate the laboratory assessment of the hypothalamic-pituitary-adrenal axis, but a clinical phenotype of persistent hypotension and suboptimal cortisol response to ACTH stimulation raises the question of whether adrenal insufficiency could also be a contributing factor. Clinical Case: A 65-year-old man with a history of cirrhosis complicated by esophageal varices, ascites, encephalopathy and hepatorenal syndrome was admitted to the ICU with worsening fatigue, profound hypotension, and respiratory arrest. He was started on pressors, antibiotics and was also intubated for a short time. A broad workup was negative for cardiac or infectious causes of shock and showed decreased total protein and albumin (1.6 g/dl (3.5-5.2), with normal serum sodium and potassium. The patient had no previous history of adrenal disease or corticosteroid use. Workup for adrenal insufficiency was initiated and showed decreased morning blood serum cortisol (10.6 ug/dl (2.5-19.5)) and ACTH (<5.0 pg/ml (7.2-63)), as well as suboptimal cortisol response on ACTH stimulation testing (12.5 ug/dl initially, 16.7 ug/dl after stimulation). Head CT on admission was negative for intracranial pathology, and lab results showed normal TSH and mildly increased prolactin of 36.2 ng/ml (4.0-15.0). Pt was started on IV hydrocortisone 50 mg TID. Glucocorticoid therapy didn’t improve his state significantly but was continued with a gradual tapering down of the dose. After intense treatment in the ICU the patient’s state was stabilized. Unfortunately, an endoscopy performed for worsening anemia and blood in stools showed gastric cancer. The patient was transferred to comfort care after a discussion of goals of treatment and died within the next 24 hours. Conclusion: The nature of decreased cortisol levels in patients with cirrhosis is most likely multifactorial, due to impaired hepatic synthetic function, dysregulation of hormone-binding protein balance, abnormal ACTH secretion, and other factors. Impaired corticosteroid-binding globulin synthesis might affect the ratio of globulin-bound and free hormone fractions and alter the accuracy of cortisol assays. Whether adrenal insufficiency is truly one of the complications of advanced cirrhosis contributing to persistent hypotension, or a mere laboratory finding is difficult to answer. It is also yet to be determined whether patients with advanced cirrhosis might benefit from screening and treatment of adrenal insufficiency in circumstances of persistent hypotension, and studies are needed to decide on optimal diagnostic tests to recognize the disease and develop treatment algorithms. Presentation: 6/3/2024

6424 From Hyperparathyroidism To Neurologic Crisis: A Tale Of Brown Tumor And Spinal Cord Compression

Abstract Disclosure: A. Kormanis: None. M. Anderson: None. M. McKnight: None. H. Darapu: None. Background/Objective: In this case, we present a rare and severe consequence of secondary hyperparathyroidism, a Brown tumor leading to spinal cord compression, in a young adult with end-stage renal disease. Case Report: A 26-year-old male with a medical history of polycystic kidney disease and IgA Nephropathy complicated by ESRD, history of brown cell tumors (s/p surgery) was admitted for hospitalization due to hypocalcemia after presenting to the Emergency Department with right lower extremity weakness. Examination revealed right hip flexor weakness and right foot clonus. Lab results showed serum calcium of 10.4 mg/dL . MRI displayed a 2.5cm X 3.7 cm soft tissue mass with circumferential encroachment of the epidural space leading to severe spinal canal stenosis of T4-T5 at the site of prior Brown tumor resection. Ultimately, the patient underwent subtotal parathyroidectomy with left cervical thymectomy, leading to an intra-operative PTH drop from >3500 to 247 pg/mL. Discussion: In the context of treating vertebral brown tumors, the consensus suggests that parathyroidectomy plays a crucial role in achieving both clinical and radiographical amelioration of the tumor. However, in cases like ours where paresis is present, surgical decompression of the tumor becomes imperative. Conclusion: The development of Brown tumors is a severe and rare long-term complication for hyperparathyroidism, and the location of a Brown tumor in the thoracic spine causing symptomatic cord compression is even more rare. Presentation: 6/2/2024

7467 Supplement Use Among Transgender Patients: Case Reports and Literature Review

Abstract Disclosure: H. Cunningham: None. Q. Jones: None. C. Kelley: None. The barriers to initiating gender affirming medical treatment are innumerable and increasing in the wake of wide-sweeping anti-trans legislation, leading many transgender individuals to utilize more accessible means of transitioning. We provide examples of patient-initiated supplement use at a gender medicine clinic in the Southeast. We describe a 60-year-old transgender woman who was unable to establish care due to lack of affirming providers in her region and insurance approval delays. She began taking Pueraria mirifica, along with saw palmetto and fenugreek, for feminization. Subsequently, her breast size increased from an A to B cup, and she noticed fat redistribution to her hips. When finally seen one year later, labs demonstrated suppressed luteinizing and follicle stimulating hormones and increased sex hormone binding globulin, with an associated decrease in estradiol and testosterone levels. Cessation of supplements resulted in lab normalization. Our second case describes masculinizing effects, including voice deepening, experienced by a transgender man using a supplement that contained "orchic extract.” Supplements used for gender affirmation can also have more adverse effects, including polycythemia in the setting of trenbolone, an illicit steroidogenic performance enhancing supplement used for masculinization by some patients assigned female at birth. Patients without access to gender affirming hormones through a medical provider, or who do not feel comfortable accessing health care, may be more likely to use supplements purchased online without a prescription. Considering this, we must create more safe spaces for gender affirming care and ask all transgender patients about supplement use. Providers should consider supplement use as a possible explanation for unexpected lab results. The literature on supplement use for gender-affirming effects is sparse; this presentation provides a summary of and contributes to the current literature on this topic. Presentation: 6/2/2024

Incidentally detected pancreatic duct dilatation on ultrasound and role of MRI.

The clinical significance of incidentally detected pancreatic duct (PD) dilatation at ultrasound (US) without a visualized underlying cause is unclear. We aimed to assess the role of subsequent MRI (including MRCP) and to identify US imaging and laboratory findings predictive of underlying pancreaticobiliary malignancy at the time of initial US. Patients with incidentally detected PD dilatation at ultrasound from 2011 to 2019 that had an ensuing MRI were included. Based on MRI results patients were divided into three groups: malignant pancreaticobiliary causes, benign causes and idiopathic PD dilatation. Subsequently the diagnostic ability of MRI was assessed. Initial ultrasound findings and laboratory results were compared between groups to identify predictors of underlying pancreaticobiliary pathology. A p-value < .05 was considered statistically significant. In 37/59 (63%) patients PD dilatation was confirmed on MRI. MRI demonstrated malignant 7/59 (12%) and benign 10/59 (17%) causes of PD dilatation detected at initial ultrasound. Sensitivity, specificity, negative predictive value, positive predictive value and accuracy of MRI to ascertain the cause of PD dilatation was 89%, 100%, 95%, 100% and 97% respectively. Patients with a larger magnitude of PD dilatation, concomitant CBD dilatation and elevated lipase values were more likely to have underlying pancreaticobiliary malignancy (p < 0.05). No patient with initial negative MRI had pancreaticobiliary malignancy on subsequent work-up. Incidentally detected PD dilatation on ultrasound is an important finding and should prompt referral to MRI. MRI is an accurate, noninvasive method for identifying the underlying cause of PD dilatation in these patients and in excluding pancreaticobiliary malignancy.