Somatostatin Receptor Scintigraphy Research Articles

Ectopic Cushing's syndrome from a corticotropin-releasing hormone-secreting medullary thyroid carcinoma: a rare pitfall of inferior petrosal sinus sampling.

This case report describes a rare presentation of ectopic Cushing's syndrome (CS) due to ectopic corticotropin-releasing hormone (CRH) production from a medullary thyroid carcinoma (MTC). The patient, a 69-year-old man, presented with symptoms of muscle weakness, facial plethora, and easy bruising. An inferior petrosal sinus sampling test (IPSS) demonstrated pituitary adrenocorticotrophic hormone (ACTH) secretion, but a whole-body somatostatin receptor scintigraphy (68Ga-DOTATOC PET/CT) revealed enhanced uptake in the right thyroid lobe which, in addition to a grossly elevated serum calcitonin level, was indicative of an MTC. A 18F-DOPA PET/CT scan supported the diagnosis, and histology confirmed the presence of MTC with perinodal growth and regional lymph node metastasis. On immunohistochemical analysis, the tumor cell stained positively for calcitonin and CRH but negatively for ACTH. Distinctly elevated plasma CRH levels were documented. The patient therefore underwent thyroidectomy and bilateral adrenalectomy. This case shows that CS caused by ectopic CRH secretion may masquerade as CS due to a false positive IPSS test. It also highlights the importance of considering rare causes of CS when diagnostic test results are ambiguous. Medullary thyroid carcinoma may secrete CRH and cause ectopic CS. Ectopic CRH secretion entails a rare pitfall of inferior petrosal sinus sampling yielding a false positive test. Plasma CRH measurements can be useful in selected cases.

A rare primary hepatic neuroendocrine tumour with laparoscopic resection: a case report

IntroductionPrimary hepatic neuroendocrine tumours (PHNETs) are a rare form of hepatic neoplasms, and it is difficult to differentiate them from common hepatic malignancies in routine imaging studies.Presentation of the caseWe describe the case of a 60-year-old Indian male patient with a tentative preoperative diagnosis of hepatocellular carcinoma (HCC). Nevertheless, the definitive post-operative diagnosis was made by Histopathological and immunohistochemical assessment, which revealed a grade II neuroendocrine tumour (NET) of moderate differentiation. Surgical resection was performed through a minimally invasive approach with a favourable postoperative course and a short hospital stay. One-month Post-operative Octreotide scan showed no extrahepatic primary origin of the tumour.DiscussionPHNET is a rare entity, and multi modalities investigations, including imaging, serology, endoscopy series, and histopathology findings, aside from long-term follow-up to rule out another primary origin, are essential for the final diagnosis of PHNET. Surgical resection stands as the mainstay of treatment of PHNETs.ConclusionThe absence of primary liver diseases should expand our possible differential diagnosis. Laparoscopic surgical resection of PHNETs carries a favourable outcome.

Potential Role of Somatostatin Receptor Scintigraphy for In Vivo Imaging of Vulnerable Atherosclerotic Plaques and Its Association with Myocardial Perfusion Imaging Finding: A Preliminary Study.

This study was conducted to detect atherosclerotic plaques with somatostatin receptor scintigraphy (SRS) using Tc-99m-octreotide that binds to somatostatin receptor-2. Of the 783 patients referred for myocardial perfusion imaging (MPI), 52 underwent additional chest single-photon emission computed tomography (SPECT) with Tc-99m-octreotide and participated in this study. In addition, 43 patients who underwent Tc-99m-octreotide scan for neuroendocrine tumor (NET) also received cardiac SPECT. Angiography was performed within 1 month after SRS for 19 patients who showed intensive uptake in SRS and had cardiac risk factors. Of 52 patients who underwent MPI and SRS, 15 showed intensive cardiac uptake in SRS. Moreover, of 43 patients who were referred for NET, 4 patients had marked cardiac uptake in SRS in the heart. Nineteen patients including 12 women and 7 men aged 28 to 84 (58±8.04) years underwent coronary angiography. SRS and angiography in the left anterior descending territory were concordant in 15/19 (79%) patients, whereas only 7/15 (46%) cases had concordant MPI and angiography results. In the right coronary artery territory, SRS and angiography were concordant in 16/19 (84%) cases, while MPI and angiography were concordant in 11/15 (73%) cases. In the left circumflex artery territory, SRS and angiography were concordant in 15/19 (79%) cases, whereas MPI and angiography were concordant in 6/15 (40%) cases. In the remaining 76 patients who did not undergo coronary angiography based on cardiovascular profile and SRS, no cardiac events occurred in a follow-up of 2-11 months (7.52±2.71). Tc-99m-octreotide uptake was more concordant with coronary plaques relative to MPI findings, suggesting a potential role for Tc-99m-octreotide in the evaluation of atherosclerosis.

Unusual False Positive on 99mTc-Tektrotyd Scintigraphy Mimicking Bone Metastasis.

Somatostatin receptor scintigraphy is a key diagnostic tool in the initial staging and therapeutic evaluation of neuroendocrine tumors. Its specificity can be compromised by the presence of false positives. We illustrate here the case of a vertebral hemangioma detected on 99mTc-Tektrotyd scintigraphy as an incidental finding in a 34-year-old man referred for the staging of a well-differentiated neuroendocrine tumor of the ampulla of Vater (Fig.1).

Prediction of lymph node metastasis of well-differentiated rectal neuroendocrine tumours using multiple diagnostic modalities.

The preoperative prediction of lymph node metastasis of well-differentiated rectal neuroendocrine tumours is highly desirable and useful in defining surgical indication more accurately. We aimed to evaluate lymph node metastasis in rectal neuroendocrine neoplasms using multiple imaging modalities. The clinical records and radiological images of 70 patients with well-differentiated rectal neuroendocrine tumours who received treatment at the University of Tokyo Hospital between 2010 and 2022 were retrospectively analysed. The relationship between evaluation by multiple imaging modalities and pathological lymph node metastasis was analysed. The receiver operating characteristic curves showed that a maximum lymph node diameter ≥4 mm on computed tomography and ≥8 mm on magnetic resonance imaging were the optimal predictive factors for lymph node metastasis. Accumulation in the lymph nodes on somatostatin receptor scintigraphy (P = 0.058) and Delle's findings on colonoscopy (P = 0.014) were also significant predictors of pathological lymph node positivity, and combination of multiple modalities was useful. Pathologically, lymphatic (P = 0.0030)/venous (P = 0.0007) invasion were risk factors for lymph node metastasis. In addition to pathological risk factors, a combination of multiple radiological imaging modalities is useful for predicting lymph node metastasis in well-differentiated rectal neuroendocrine tumours.

Parahydrogen-induced polarization allows 2000-fold signal enhancement in biologically active derivatives of the peptide-based drug octreotide

Octreotide, a somatostatin analogue, has shown its efficacy for the diagnostics and treatment of various types of cancer, i.e., in octreotide scan, as radio-marker after labelling with a radiopharmaceutical. To avoid toxicity of radio-labeling, octreotide-based assays can be implemented into magnetic resonance techniques, such as MRI and NMR. Here we used a Parahydrogen-Induced Polarization (PHIP) approach as a cheap, fast and straightforward method. Introduction of l-propargyl tyrosine as a PHIP marker at different positions of octreotide by manual Solid-Phase Peptide Synthesis (SPPS) led to up to 2000-fold proton signal enhancement (SE). Cell binding studies confirmed that all octreotide variants retained strong binding affinity to the surface of human-derived cancer cells expressing somatostatin receptor 2. The hydrogenation reactions were successfully performed in methanol and under physiologically compatible mixtures of water with methanol or ethanol. The presented results open up new application areas of biochemical and pharmacological studies with octreotide.

Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms.

Neuroendocrine neoplasms (NENs) are a heterogeneous group of neoplasms ranging from well-differentiated, slowly growing tumors to poorly differentiated carcinomas. These tumors are generally characterized by indolent course and quite often absence of specific symptoms, thus eluding diagnosis until at an advanced stage. This underscores the importance of establishing a prompt and accurate diagnosis. The gold-standard remains histopathology. This should contain neuroendocrine-specific markers, such as chromogranin A; and also, an estimate of the proliferation by Ki-67 (or MIB-1), which is pivotal for treatment selection and prognostication. Initial work-up involves assessment of serum Chromogranin A and in selected patients gut peptide hormones. More recently, the measurement of multiple NEN-related transcripts, or the detection of circulating tumor cells enhanced our current diagnostic armamentarium and appears to supersede historical serum markers, such as Chromogranin A. Standard imaging procedures include cross-sectional imaging, either computed tomography or magnetic resonance, and are combined with somatostatin receptor scintigraphy. In particular, the advent of 111In-DTPA-octreotide and more recently PET/CT and 68Ga-DOTA-Octreotate scans revolutionized the diagnostic landscape of NENs. Likewise, FDG PET represents an invaluable asset in the management of high-grade neuroendocrine carcinomas. Lastly, endoscopy, either conventional, or more advanced modalities such as endoscopic ultrasound, capsule endoscopy and enteroscopy, are essential for the diagnosis and staging of gastroenteropancreatic neuroendocrine neoplasms and are routinely integrated in clinical practice. The complexity and variability of NENs necessitate the deep understanding of the current diagnostic strategies, which in turn assists in offering optimal patient-tailored treatment. The current review article presents the diagnostic work-up of GEP-NENs and all the recent advances in the field.

Small bowel neuroendocrine tumours - casting the net wide.

Our aim is to provide an overview of small bowel neuroendocrine tumours (NETs), clinical presentation, diagnosis algorithm and management options. We also highlight the latest evidence on management and suggest areas for future research. Dodecanetetraacetic acid (DOTATATE) scan can detect NETs with an improved sensitivity than when compared with an Octreotide scan. It is complimentary to small bowel endoscopy that provides mucosal views and allows the delineation of small lesions undetectable on imaging. Surgical resection is the best management modality even in metastatic disease. Prognosis can be improved with the administration of somatostatin analogues and Evarolimus as second-line therapies. NETs are heterogenous tumours affecting most commonly the distal small bowel as single or multiple lesions. Their secretary behaviour can lead to symptoms, most commonly diarrhoea and weight loss. Metastases to the liver are associated with carcinoid syndrome.

Prospective Multicentric Assessment of 68Ga-DOTANOC PET/CT in Grade 1-2 GEP-NET.

The aim of this multicentric study was to prospectively compare 68Ga-DOTANOC PET/CT versus somatostatin receptor scintigraphy (SRS) with SPECT/CT, combined with multiphasic CT scan and MRI in patients with grade 1 or 2 gastroenteropancreatic neuroendocrine tumors (GEP-NET). Patients with histologically proven grade 1 or 2 GEP-NET with suspicion of recurrence or progression, or with typical aspects of GEP-NET on morphological imaging, were explored with conventional imaging (CI): SRS with SPECT/CT, multiphasic CT scan and/or liver MRI followed by 68Ga-DOTANOC PET/CT. The gold standard was based on histology and imaging follow-up. The data of 105 patients (45 woman and 60 men; median age) were analyzed. 68Ga-DOTANOC PET/CT sensitivity was significantly higher than CI sensitivity in per-patient (98.9% vs. 88.6%, p = 0.016) and per-region (97.6% vs. 75.6%, p < 0.001) analyses, in the detection of the primary (97.9% vs. 78.7%; p = 0.016), peritoneal carcinomatosis (95% vs. 30%, p < 0.001), and bone metastases (100% vs. 33.3%, p = 0.041). 68Ga-DOTANOC PET/CT had an impact on the therapeutic management of 41.9% (44/105) patients compared to decisions based on CI explorations. Our data confirm the superiority of 68Ga-DOTANOC PET/CT over CI in the detection of peritoneal carcinomatosis and bone metastasis, as well as its strong therapeutic impact on the management of patients with grade 1-2 GEP-NETs.

Клиническое наблюдение тяжелого течения болезни Иценко — Кушинга

Cushing's disease is a severe neuroendocrine disorder caused by excessive release of adrenocorticotropic hormone by pituitary tumor. The rate is 39.1 per 1 million and the incidence is 1.2–2.4 per 1 million. Typical symptoms include rapid weight gain associated with muscle weakness, hypertension, diabetes, and osteoporosis. The key diagnostic tool is brain MRI after laboratory confirmation of a diagnosis of hypercortisolemia. The key treatment is transsphenoidal adenomectomy, which provides remission in 65–90% of patients. This paper describes the severe course of Cushing's disease in a male patient, which has long remained undiagnosed. Diagnostic search steps, differential diagnostic difficulties, and follow-up results (including inferior petrosal sinus sampling) are discussed. A multidisciplinary approach and teamwork ensure timely diagnosis, prevent complications of Cushing's disease, and improve prognosis and quality of life. KEYWORDS: Cushing's disease, case report, hypercortisolism, hypercortisolemia, ACTH, somatostatin receptor scintigraphy, transsphenoidal adenomectomy FOR CITATION: Gorbunova N.P., Prokhorova G.V., Zubkova A.S., Korotkikh S.M., Volynkina A.P., Reshetnyak Ya.Ya. Case report of a severe course of Cushing's disease. Russian Medical Inquiry. 2023;7(9):606–610 (in Russ.). DOI: 10.32364/2587-6821-2023-7-9-8.

PS-BPR01-9: A CASE OF CYCLIC CUSHING'S SYNDROME DIAGNOSED WITH HYPERTENSION AND LEG EDEMA

Background: Cushing's syndrome (CS) is associated with hypertension in approximately 80% of cases, which contributes to the increased mortality risk. Few cases of intermittent hypertension due to cyclic CS(CCS) have been reported. Case presentation: A 66-year-old woman with no specific medical history was referred to our hospital for evaluation of hypertension and leg edema. The Cardiovascular examination showed no abnormality in her cardiac function. Laboratory findings revealed hypokalemia, hyperglycemia, and metabolic alkalosis. She was tentatively initiated on calcium channel blocker (CCB) and insulin therapy. The endocrine examination revealed elevated ACTH and cortisol without circadian variation, which responded to neither the 8 mg dexamethasone suppression test nor CRH stimulation, leading to the diagnosis of ACTH-dependent CS. CT, FDG/PET CT, and Octreotide scan showed no obvious lesion other than bilateral adrenal enlargement. Enhanced MRI showed a normal pituitary gland with neither adenoma nor pituitary stalk deviation/tilt. Since the etiology of CS was not confirmed, metyrapone administration was initiated as symptomatic treatment. Her serum ACTH and cortisol fell rapidly after the initiation of metyrapone, and her blood pressure (BP) and blood glucose levels improved accordingly, even without the use of CCB and insulin. Since both ACTH and cortisol became normalized after discharge, metyrapone was tapered off after 4 months. Furthermore, CT showed normalization of the adrenal enlargement. For the next two months, her ACTH and cortisol remained within the normal limits, and her BP, serum potassium and blood glucose were well controlled. However, she visited our hospital because of re-elevated BP thereafter and was found to have re-elevated ACTH and cortisol with bilateral adrenal enlargement as well as re-decreased serum potassium. Since her BP and serum potassium levels were not controlled well even after she resumed taking metyrapone, the dose of metyrapone was increased, spironolactone was added, and CCB was resumed. Another two months later, her ACTH and cortisol normalized without metyrapone again, and her BP was well-controlled accordingly. This cyclical course of ACTH/cortisol elevation strongly suggested CCS. Conclusion: CCS is a clinical syndrome that exhibits a periodic or irregular increasing pattern in cortisol, which is a rare type of CS. Confirmation of CCS diagnosis is only possible during periods of relapse. In the present case, elevated BP was an indicator of hormonal fluctuations that could be appropriately treated. We report here a case of CCS that was diagnosed because of a good correlation between BP and hormone levels.

AB014. Effective somatostatin analogs in a case of advanced thymoma with no uptake in the octreotide scan

Background: Management of advanced malignant thymoma is very challenging due to the lack of evidence from randomized trials. Despite advanced and non-curable status, most patients achieve long survival and they usually receive several treatment lines along their disease. There is no standard second line, and toxicity of chemotherapy (CT) should be considered for these long survivors. Treatment with somatostatin analogs showed efficacy in patients with refractory recurrent and/or metastatic thymomas.

LBSUN345 Diagnostic Dilemma In A Case of Vipoma

Abstract Introduction Vasoactive intestinal polypeptide secreting tumors (VIPoma) are rare neuroendocrine tumors that have nonspecific features of watery diarrhea, hypokalemia and achlorhydria. With an incidence of 1 in a million per year, it is diagnosed based on serum VIP levels (>75pg/ml) followed by imaging studies to localize the tumor and look for metastases. We present a challenging case of VIPoma that was successfully managed with surgical exploration despite classic yet nonspecific clinical features and poor evidence on imaging. Case Discussion A 78-year-old Caucasian woman presented with persistent secretory diarrhea for 2 months. Past medical history was significant for intractable peptic ulcer disease and Billroth II reconstruction. Laboratory investigations showed severe hypokalemia (2.1 mmol/l), serum bicarbonate 13 and chloride 117. Blood glucose and calcium levels were within normal range. Stool studies confirmed secretory diarrhea with stool osmotic gap of 10 mOsm/kg but no growth. Serum gastrin, parathyroid hormone, chromogranin and urine 24-hour 5-hydroxy indoleacetic acid (5-HIAA) levels were within normal limits. Plasma VIP levels were elevated at 79 pg/mL. Computed tomography of the abdomen and pelvis did not show any evidence of pancreatic tumor or biliary ductal dilatation. Endoscopic ultrasound could not fully evaluate the head of pancreas but showed unremarkable liver, pancreatic body and tail. Capsule endoscopy was unremarkable as well. An octreotide scan, however, demonstrated increased activity near the head of the pancreas and abdominal aorta. As clinical picture and octreotide scan findings were consistent with VIPoma, operative exploration for possible pancreaticoduodenectomy was pursued. No evidence of palpable or occult metastatic disease was found; but intraoperative color doppler ultrasound localized two lesions less than 1 cm in size at the level of the uncinate process and ampulla. An open pancreaticoduodenectomy was performed and the existing Billroth II anatomy was modified to accommodate pancreatojejunostomy, gastrojejunostomy and choledochojejunstomy. A jejunostomy tube was placed for enteral access. At 2-month post-operative follow-up, the patient had significant improvement of his diarrhea. Radiographic resolution was noted on repeat octreotide scan 4 months following resection. Conclusion VIPomas are usually diagnosed by elevated VIP levels and imaging studies are used to localize the tumor for further treatment. However, this case highlights that in secretory diarrhea with elevated VIP level and no alternate diagnosis, despite negative imaging studies further exploration with octreotide scan is warranted. Surgical exploration may show the site of lesion and appropriate surgical intervention may lead to resolution of VIPoma. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PSAT222 Muscle Weakness, Bone Pain, and Stress Fractures: When a Fracture is NOT JUST a Fracture: A Case Report

Abstract Case A previously healthy 46-year-old male presented to orthopedic clinic with bilateral hip pain, and progressive weakness without history of trauma requiring cane for ambulation. X-ray and MRI evaluation revealed stress fractures of left subtrochanteric femur and right basicervical femoral neck, both requiring surgery. In hospital blood work revealed elevated total alkaline phosphatase 167 units/L, mild hypocalcemia 8.5 mg/dL, and low 25-hydroxy Vitamin D 18 ng/mL. The patient was started on calcium/vitamin D supplements upon discharge. Initial endocrinology outpatient work-up revealed low phosphorus level of 2.1 mg/dl and low 1, 25 OH vitamin D of 5.9 pg/ml (19.9–79.3). Bone mineral density revealed normal spine bone density, and 1/3 radius osteopenia (T score -1.1). Physical exam revealed profound proximal weakness with inability to rise independently from sitting position. Follow-up of low phosphorous level demonstrated an elevated FGF-23 level of 186 RU/mL (normal < 180) and elevated fractional excretion of phosphorus 16% (expect < 5% with hypophosphatemia), indicating inappropriate renal phosphate wasting. The patient was started on Calcitriol and phosphorus. Before above evaluation was completed the patient had an ED visit with complaint of small mass just below left knee associated with mild pain and warmth. Ultrasound and MRI showed a complex cyst which was aspirated and showed cystic appearing mass suggestive of hematoma. This was treated with antibiotic course. Due to suspicion of tumor-induced osteomalacia, octreotide scan (Indium-111 pentetreotide) performed showed focal increased activity in the medial left knee. MRI showed a 26 mm cystic lesion within the subcutaneous tissue along the inferomedial aspect of the left knee, which correlated with the site of radiotracer uptake on the octreotide scan. The patient underwent left knee soft tissue tumor resection, and pathology demonstrated phosphaturic mesenchymal tumor. Follow-up several weeks postoperatively showed normalization of phosphorus and FGF-23 level. The patient's mobility and weakness improved significantly within a few months. Discussion Tumor-induced osteomalacia is a rare paraneoplastic condition characterized by chronic hypophosphatemia secondary to excessive tumoral FGF 23 production. Typical presenting symptoms are profound muscle weakness, bone pain, and fractures. Diagnosis is often delayed for several years, as phosphorus levels are not included in a routine metabolic panel. Considering high morbidity of this condition including significant mobility limitation requiring use of assistive devices, healthcare provider vigilance is paramount as this condition is potentially curable if the offending tumor is detectable and amenable to surgical resection. This case illustrates the importance of consideration of an underlying metabolic bone disease in patients with unexplained atraumatic fractures and hypophosphatemia. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

ODP624 A case of Cushing disease demonstrated rapid deterioration of clinical findings and marked hypercortisolemia

Abstract Introduction In cases of ACTH-dependent Cushing syndrome, the differentiation between Cushing disease and the ectopic ACTH syndrome (EAS) can sometimes be challenging. Herein we report on a case of Cushing disease who showed clinical features resembled EAS caused by malignant neoplasms and required a detour for the diagnosis. Clinical case A 49-year-old Japanese woman presented a rapid exacerbation of muscle weakness of her limbs, leg edema and moon face from two months ago. She did not have any past medical history, hypertension, diabetes mellitus, or osteoporosis. Her serum K was 2.6 mEq/L, ACTH level was 151 pg/mL, serum cortisol level was 36.6 μg/dL, and urinary free cortisol (UFC) level was 4250 μg/day. Serum cortisol after 1 mg dexamethasone suppression test (DST) showed 41.9 μg/dL and that after 8 mg DST was 14.1 μg/dL. A pituitary MRI demonstrated a poor enhancement area with a clear margin of 10 mm in diameter in her dorsal side of the pituitary gland. She was diagnosed with ACTH-dependent Cushing syndrome and metyrapone was initiated. Soon she developed severe cough with infiltrative shadows on her lungs two days later. Her respiratory condition deteriorated rapidly, and she was urgently transferred to our hospital and intubated one week later. She had complicated pneumocystis carinii, nocardia pneumonia, and severe respiratory failure based on immunodeficiency due to hypercortisolemia. She was treated with systemic management in the intensive care unit, infection treatment and dose adjustment of metyrapone. Her condition improved and she was extubated on the 8th day. Although she had the pituitary tumor, EAS caused by a malignant neoplasm was suspected because of a combination of rapid clinical deterioration, marked hypercortisolemia and hypokalemia. However gastrointestinal tract survey, 18F-PET/CT and somatostatin receptor scintigraphy did not show any significant lesions. Finally, selective inferior petrosal sinus sampling (IPSS) demonstrated over secretion of ACTH from the pituitary gland. ACTH decreased to an undetectable level and hydrocortisone was supplemented after transsphenoidal surgery. No recurrence was observed in 1 year of follow-up. Pathological findings showed a densely granulated type of ACTH-producing adenoma without Crooke's change. KI-67 index were 4.7%, which was higher than that in general ACTH producing pituitary adenomas. Conclusion We experienced Cushing disease with the rare clinical course. This case suggests that although a step-by-step approach is often adopted to make a differential diagnosis of patients with ACTH-dependent Cushing's syndrome, ultimately IPSS is required. Because her KI-67 index showed 3 or higher despite the gentle tumor behavior, careful follow-up is required. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

LBODP066 A Conservative Approach To The Management Of Glucagon Receptor (GCCR) Mutation (Mahvash Syndrome)

Abstract Background Mahvash Syndrome a rare autosomal recessive cause of pancreatic neuroendocrine tumors (pNET) results from inactivation of GCCR. Clinically it presents with hyperglucagonemia without glucagonoma syndrome. Since described in 2008 all surviving adult cases have been managed surgically. We describe 2 related cases managed medically. Case 1 In 2015 a 52 year old female with history of an enlarged pancreas (Aunt of Case 2) presented with incidentally identified hypovascular pancreatic masses while being assessed for back pain. An EBUS-guided FNA of the pancreas demonstrated a pNET with elevated serum glucagon of 100,991 pmol/ml, and Chromogranin A of 183 ng/ml but normal C-peptide, insulin, glucose, and HbA1C. CT chest abdomen pelvis, and octreotide scan had no evidence of metastasis. Due to vague abdominal discomfort, persistently high glucagon levels and pruritis without rash she was started on somatostatin analog therapy. Given her high glucagon without glucagonoma syndrome she was referred to genetics for GCCR sequencing which was notable for homozygous c.187G>A p. Asp63Asn variant (subsequently reclassified as pathogenic). Her case was also reviewed at the multidisciplinary tumor board given her dominant but stable conglomerate 3.2×1.7cm pancreatic lesion (individually measuring 1.6 and 1.4cm). Continued SSA for 7 years showed a slow change in size of the pNET with the dominant lesion at the pancreatic head (1.8cm from 1.6cm in 2015), with no evidence of metastatic spread or clinical changes. Case 2 a 46 year old man with IBD and Psoriatic Arthritis, presented in 2010 with choledocholithiasis. Imaging identified a bulky pancreas with a 1.2 cm nodule consistent with a neuroendocrine tumor. His investigations included 5HIAA, Gastrin, Prolactin, Chromogranin A, Insulin, Fasting Glucose, and HgbA1C all of which were normal. In 2015 following identification of an Aunt (Case 1) with a GCCR Variant of Uncertain Significance his glucagon level was found to be above the limit of detection for the assay. Given his preferences and lack of symptoms, he was monitored clinically without surgery or medications. His Glucagon levels have remained stably elevated at 12940 pg/ml, and the initial pNET has slowly progressed to 1.3cm with an additional 1.1cm and 0.5cm pNETs identified over a 7 year interval. Conclusion These cases describe 2 patients with homozygous c.187G>A GCCR variants, resulting in Mahvash Syndrome. In contrast to previously published cases of the syndrome, and specifically the case report with the same variant, they have been managed non-surgically with regular imaging, and in Case 1 with SSA therapy. While there has been slow growth of the underlying pNET, there has been no clinical changes or evidence of metastatic disease, providing insight into the natural history of Mahvash Syndrome caused by c.187G>A variant, and possibly supporting a less aggressive clinical approach. Presentation: No date and time listed

PMON40 A Rare Etiology of Chronic Diarrhea: Zollinger-Ellison Syndrome

Abstract Introduction Zollinger-Ellison Syndrome (ZES) is a rare etiology of chronic diarrhea caused by a gastrin-secreting neuroendocrine tumor. Early suspicion can prevent multiple readmissions for recurrent diarrhea thus improving clinical outcomes through prompt diagnosis and treatment, as the following case highlights. Case presentation A 74-year-old African-American female with hypertension and chronic atrial fibrillation presented to the ED complaining of watery, non-bloody diarrhea for the past 3 weeks. She reports her symptoms worsened after completing a course of amoxicillin for pharyngitis one week prior. On further questioning, she reported intermittent diarrhea for over 20 years lasting approximately two days per episode. She denied recent travel, sick contacts, pet reptiles, and recent ingestion of undercooked meat. On arrival, she was afebrile and hemodynamically stable. She was admitted for an acute kidney injury with an elevated creatinine of 3.23 mg/dL (N: 0.6-1.1 mg/dL) due to dehydration. Her renal function improved with fluids, but she developed bloody diarrhea for which gastroenterology was consulted. Stool studies were negative for Shiga-toxin, C. difficile, lactoferrin, and parasites. Computed Tomography of the abdomen showed enteritis with fluid noted throughout the colon consistent with colitis. Unprepped colonoscopy revealed blood throughout the length of the colon, suggestive of an upper gastrointestinal bleed. Esophagogastroduodenoscopy (EGD) revealed multiple bleeding duodenal ulcers controlled with hemostasis. Her symptoms improved and she was discharged home on oral pantoprazole, and told to follow up outpatient. Two weeks later, she denied any new episodes of diarrhea, and a random serum gastrin level was elevated at 413 pg/mL (N: <180 pg/mL). Repeat gastrin level off pantoprazole for 7 days was also elevated at 678 pg/mL, and a serum Chromogranin A level was elevated at 629 pg/mL (N: <390 pg/mL). Repeat EGD found her Gastric pH to be 1 with multiple non-bleeding duodenal ulcers. Somatostatin receptor scintigraphy revealed a high intensity signal consistent with a duodenal gastrinoma causing ZES. She elected for surgical resection, and was discharged home on high dose pantoprazole. Three months later, she stated that her diarrhea had completely resolved. Conclusion This case confirms ZES as a rare cause of chronic diarrhea in the setting of multiple duodenal ulcers refractory to proton pump inhibitors. Diagnosis can be made with a fasting serum gastrin level >1000 pg/mL or >400 pg/mL with a gastric pH <1. A Secretin Stimulation Testing can also be used. Treatment starts with high dose proton pump inhibitors, octreotide for hormonal regulation, and surgical resection if necessary. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Multimodality imaging differentiation of pancreatic neuroendocrine tumors and solid pseudopapillary tumors with a nomogram model: A large single-center study.

BackgroundPancreatic neuroendocrine tumors (pNETs) and solid pseudopapillary tumors (SPTs) are two of the most common pancreatic neoplasms with different treatment procedures. However, the broad heterogeneity of pNETs and SPTs in clinical manifestations and radiological features often confuse the presurgical discrimination in clinical practice, and the clinical and molecular differentiation of the two tumors remains elusive to date. We presume that a large and comprehensive study into the multimodality features of pNETs and SPTs is necessary for precise clinical management.MethodsWe collected and analyzed the clinicopathological information and multimodality features of nonfunctional pNET and SPT patients, for a total of 631 cases from 2006 to 2021. Univariate analysis of imaging features, including contrast-enhanced computed tomography (CT), magnetic resonance imaging, endoscopic ultrasound (EUS) and nuclear medicine imaging, and clinical characteristics was performed, and CT features and clinical information were integrated to establish a nomogram model.ResultsWe recruited 354 nonfunctional pNET and 277 SPT patients in our cohort. Regarding demographic information, pNET patients had a lower female percentage (55.4% vs. 72.9%), smaller tumor size (2.8 vs. 4.8 cm), and older age (53.4 vs. 35.3 years). In CT imaging and EUS, pNETs tended to appear as solid and homogenous lesions with strong enhancement intensity. Multifocal lesions, duct dilation, and lymph node (LN) enlargement were more likely to be observed in pNETs, while calcification was more common in SPT lesions. On positron emission tomography (PET)/CT, pNETs exhibited significant sensitivity to somatostatin receptor scintigraphy (SRS), with positive rates of 81.4% and 95% on 99mTc-HYNIC-TOC and 68Ga-DOTATATE PET/CT, respectively, while SPTs were all negative on SRS. Multivariate analysis identifies tumor size, age, enhancement intensity, calcification, and LN enlargement as statistically significant variables.ConclusionsCompared to SPT patients, pNET patients exhibit an older age and smaller tumor size. CT manifestations of strong intensity, LN enlargement, and no calcification could indicate a higher possibility of pNET. Meanwhile, the similarity in the immunohistochemical profile indicates that the two tumors could potentially develop from the same origin.

ЛУЧЕВАЯ И РАДИОНУКЛИДНАЯ ВИЗУАЛИЗАЦИЯ В ДИАГНОСТИКЕ АКТГ-ПРОДУЦИРУЮЩИХ НЕЙРОЭНДОКРИННЫХ ОПУХОЛЕЙ

Ectopic ACTH syndrome caused by excessive production of adrenocorticotropic hormone (ACTH) by a neuroendocrine tumor (NET) is an extremely rare disease, the main manifestation of which is pronounced hypercortisolism. In order to avoid the development of life-threatening complications and disability of the patient, timely topical diagnosis and rapid decision-making on further management tactics are necessary. The problem of the diagnosis of NET and differential diagnosis with other formations remains relevant and one of the little-studied. Despite the existing wide arsenal of methods of conventional diagnostics, functional and receptor imaging, the source of the disease remains unidentified in about 20% of patients. This article discusses the modern possibilities of NET visualization using conventional and radionuclide imaging methods, demonstrates the diagnostic capabilities of somatostatin-receptor scintigraphy and single-photon emission computed tomography combined with computed tomography (SPECT/CT) and combined positron emission and computed tomography (PET/CT) in the visualization of NET producing ACTH, and analyzes existing radiopharmaceuticals.

Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report

BackgroundEctopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases.Case presentationWe present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient’s death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-β-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation.ConclusionsWe experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.