Neuroendocrine tumors Notes

NOTES NOTES NEUROENDOCRINE TUMORS GENERALLY, WHAT ARE THEY? PATHOLOGY & CAUSES ▪ Tumors arising from cells of neuroendocrine origin; most are functional with hormonesecreting capacity ▪ Can be sporadic; most associated with genetic syndromes SIGNS & SYMPTOMS ▪ Mass effect ▪ Depends on secreted hormone DIAGNOSIS DIAGNOSTIC IMAGING ▪ Location; tumor, lymph node, metastasis (TNM) staging 130 OSMOSIS.ORG LAB RESULTS ▪ Hormone level plasma measurement OTHER DIAGNOSTICS ▪ History, physical examination ▪ Histopathological analysis, tumor grading TREATMENT MEDICATIONS ▪ Chemotherapy; hormonal agonists, antagonists SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Radiotherapy

Chapter 20 Neuroendocrine Tumors CARCINOID SYNDROME osms.it/carcinoid-syndrome PATHOLOGY & CAUSES ▪ Signs, symptoms caused by tumor arising from neuroendocrine cells secreting serotonin ▪ ⅓ metastasize, ⅓ associated with secondary malignancy, ⅓ multiple tumors ▪ Most commonly arises from gastrointestinal (GI) tract; followed by lungs, liver, ovaries, thymus ▫ Most common small intestine malignancy ▫ Appendix most common GI tract site ▫ Liver most common site for metastasis; from ileal tumors DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Locate tumors LAB RESULTS ▪ Niacin deficiency Urinalysis ▪ ↑ 5-hydroxyindoleacetic acid SIGNS & SYMPTOMS ▪ Usually asymptomatic until liver metastasis; symptoms develop occasionally ▫ GI tract tumor → hormone secretion → enter into enterohepatic circulation → liver inactivates hormones → no symptoms ▫ Liver tumor → hormone secretion → released into circulation + liver dysfunction → symptoms ▪ Cutaneous flushing ▪ ↑ intestinal motility, diarrhea ▪ Collagen fiber thickening, fibrosis ▫ Heart valve dysfunction → tricuspid regurgitation, pulmonary stenosis (both right-sided) ▪ Bronchoconstriction, asthma, wheezing ▪ Pellagra (niacin/B3 deficiency) ▫ ↑ serotonin synthesis → ↓ tryptophan → ↓ niacin/B3 synthesis ▫ Dermatitis, diarrhea, dementia, death Figure 20.1 The gross pathology a lung carcinoid tumor. The cut surface is firm and yellowish brown. The tumor has obstructed a nearby bronchus, leading to an obstructive pneumonia. OSMOSIS.ORG 131

TREATMENT MEDICATIONS ▪ Somatostatin analogues ▪ Niacin supplementation ▪ Chemotherapy (if malignant) SURGERY ▪ Resection Figure 20.2 The histological appearance of a carcinoid tumorlet. The tumor cells form discrete nests. MULTIPLE ENDOCRINE NEOPLASIA 1 (MEN1) osms.it/multiple-endocrine-neoplasia-1 PATHOLOGY & CAUSES ▪ Autosomal dominant disorder ▫ Characterization: predisposition for endocrine tumor development ▪ Tumors may be functional/non-functional (NF); benign/malignant; may affect one/ more tissues simultaneously TYPES Parathyroid ▪ Most common Pancreas, duodenum ▪ Gastrinoma (ZES), insulinoma, glucagonoma, VIPoma Anterior pituitary adenoma ▪ Prolactinoma ▪ Other: corticotroph (ACTH) secreting, thyroid-stimulating hormone (TSH) secreting, growth hormone (GH) secreting, NF 132 OSMOSIS.ORG Carcinoid ▪ Thymic, lung, gastric enterochromaffin-like tumor (NF) Adrenal cortical tumor ▪ NF CAUSES ▪ Mutation of MEN1 gene located on chromosome 11 (11q13) ▫ Encodes protein menin (endocrine organ tumor suppressor) ▫ Menin function disruption/inactivation → clonal proliferation → somatic heterozygosity loss of remaining functional allele → endocrine neoplasia formation → primarily affects parathyroid, pituitary, pancreas (3Ps) RISK FACTORS ▪ Mutant MEN1 inheritance COMPLICATIONS

Chapter 20 Neuroendocrine Tumors ▪ Hyperparathyroidism: ↓ bone mineral density, nephrolithiasis ▪ Pituitary adenoma: mass effects (e.g. headache, diplopia, visual field defects), Cushing disease, acromegaly ▪ Gastrinoma: peptic ulcer disease, gastrointestinal bleeding ▪ Glucagonoma: necrolytic migratory erythema (NME) ▪ Metastasis, tumor recurrence SIGNS & SYMPTOMS Clinical hormone imbalance, affected organ manifestations ▪ Hyperparathyroidism ▫ Hypercalcemia (e.g. muscle weakness, constipation) ▪ Pituitary adenoma ▫ Prolactinoma: menstrual irregularities, galactorrhea, ↓ libido, infertility ▫ ↑ GH: excessive bone, soft tissue growth; arthralgias ▫ ↑ ACTH: fat redistribution, plethoric facies, thin skin, striae ▫ ↑ TSH: hyperthyroidism (e.g. palpitations, tremulousness) ▪ Pancreatic tumors ▫ Glucose dysregulation (insulinomas, glucagonomas); watery diarrhea, hypokalemia, achlorhydria (WDHA) (VIPoma); steatorrhea (somatostatinoma), abdominal pain, gastroesophageal reflux (gastrinoma) ▪ Carcinoid tumors ▫ Dyspnea, wheezing (lung), nausea, vomiting, abdominal pain (gastrointestinal), clinical manifestations of Cushing’s syndrome (↑ ACTH from thymic tumor) Cutaneous manifestations ▪ Facial angiofibroma, lipoma, collagenoma DIAGNOSIS DIAGNOSTIC IMAGING MRI/CT scan ▪ Identifies tumor, metastasis, organ structure changes; TNM staging Upper GI endoscopy ▪ Identifies gastric, duodenal carcinoid tumors, peptic ulcers; allows biopsy Endoscopic ultrasound, somatostatin receptor scintigraphy ▪ Detects pancreatic neuroendocrine neoplasms (PanNETs) LAB RESULTS Blood studies ▪ Parathyroid tumors ▫ ↑ basal serum calcium, ↑ serum PTH, hypercalciuria ▪ Anterior pituitary adenomas ▫ ↑ prolactin, ↑ ACTH, ↑ cortisol, ↑ GH ▪ PanNETs ▫ ↑ fasting gastrin, ↑ insulin, ↑ ↓ glucose, ↑ VIP OTHER DIAGNOSTICS ▪ History, physical examination ▫ Occurrence of ≥ two primary MEN1 tumor types; identification of firstdegree relatives with similar findings ▪ MEN1 gene-mutation testing TREATMENT MEDICATIONS ▪ Hyperparathyroidism ▫ Calcimimetic agents ▪ Prolactinoma ▫ Dopamine agonists ▪ Gastromas ▫ Proton pump inhibitors (PPIs) ▪ Glucagonomas, insulinomas, somatostatinoma, VIPoma ▫ Somatostatin analogue, antihyperglycemic agents ▪ Insulinoma ▫ Diazoxide SURGERY ▪ Parathyroid tumor ▫ Parathyroidectomy, ethanol ablation OSMOSIS.ORG 133

▪ Pituitary adenoma ▫ Gamma knife stereotactic radiosurgery, transsphenoidal surgical resection ▪ Glucagonoma, somatostatinoma, gastrinoma, insulinoma, VIPoma, carcinoid ▫ Tumor resection OTHER INTERVENTIONS ▪ Correction of fluid, electrolyte, glucose, nutritional abnormalities ▪ Radiation therapy (e.g. pituitary adenoma) MULTIPLE ENDOCRINE NEOPLASIA 2 (MEN2) osms.it/multiple-endocrine-neoplasia-2 PATHOLOGY & CAUSES ▪ Autosomal dominant disorder ▫ Characterization: predisposition for medullary thyroid carcinoma (MTC), pheochromocytoma, primary parathyroid hyperplasia TYPES MEN 2A ▪ Most common type, AKA Sipple syndrome ▪ Variants ▫ Classic MEN2A with MTC, pheochromocytoma, primary hyperparathyroidism (milder than MEN1) (MEN2A with cutaneous lichen amyloidosis (CLA); MEN2A with Hirschsprung disease (HD)) ▫ Familial medullary thyroid carcinoma (FMTC) MEN 2B ▪ Variants ▫ MTC ▫ Pheochromocytoma ▫ Other features: mucosal neuromas (eyelid, lip, tongue), intestinal ganglioneuromas, marfanoid habitus, medullated corneal nerve fibers CAUSES ▪ Defect in RET proto-oncogene located on 134 OSMOSIS.ORG chromosome 10 (10q11.2) ▪ Encodes transmembrane tyrosine kinase receptor RET protein (integral to intracellular signalling that regulates cellular differentiation, proliferation) ▪ Mutation → RET activation → disulfidelinked RET dimerization → intracellular substrate phosphorylation → clinical syndromes RISK FACTORS ▪ RET mutation presence COMPLICATIONS ▪ MTC ▫ Hypercalcemia, cardiac arrhythmias, nephrolithiasis ▪ Parathyroid hyperplasia ▫ Hyperparathyroidism, nephrolithiasis, osteoporosis ▪ Pheochromocytoma ▫ Hypertension (therapy-resistant) ▪ HD ▫ Functional bowel obstruction, megacolon, enterocolitis ▪ Intestinal ganglioneuromas ▫ Bowel obstruction ▪ Metastasis

Chapter 20 Neuroendocrine Tumors SIGNS & SYMPTOMS ▪ MTC/FMTC ▫ Palpable neck mass, cervical lymphadenopathy, facial flushing (peptide secretion by tumor), diarrhea (gastrointestinal fluid, electrolyte secretion from excess calcitonin); clinical Cushing’s syndrome manifestations (ectopic corticotropin (ACTH) production) ▪ Parathyroid hyperplasia ▫ Fatigue, muscle weakness, altered mental status, bone pain (↓ bone density), flank pain (nephrolithiasis), nausea, vomiting, thirst, frequent urination ▪ Pheochromocytoma ▫ Hypertension, paroxysms of palpitations, tachycardia, excessive sweating, facial flushing, tremors, anxiety (↑ catecholamines) ▪ HD ▫ Vomiting, abdominal distension, constipation ▪ CLA ▫ Scaly, papular, pigmented, lesions in either interscapular region/extensor surface extremities ▪ Intestinal ganglioneuromas ▫ Abdominal pain, gaseous distension ▪ Dysmorphic facies ▫ E.g. upper-eyelid margin thickening, eversion; nodules on tongue, vermilion border of lips DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI ▪ Tumor identification, TNM staging Thyroid, neck ultrasound ▪ MTC ▫ Calcification presence LAB RESULTS ▪ MTC ▫ ↑ carcinoembryonic antigen (CEA), ↑ serum calcitonin, pentagastrin/calcium stimulation test (↑ serum calcitonin) ▪ Parathyroid hyperplasia ▫ ↑ basal serum calcium, ↑ serum PTH, hypercalciuria ▪ Pheochromocytoma ▫ ↑ plasma fractionated metanephrines, ↑ 24-hour urine metanephrine OTHER DIAGNOSTICS ▪ Medical history, family history, physical examination ▫ MEN 2A: ≥ two characteristic neoplasias in individual/close family members ▫ MEN 2B: mucosal neuromas of lips, tongue; marfanoid habitus; medullated corneal nerve fibers; gut ganglioneuromatosis; MTC ▫ FMTC ≥ four MTC cases in families without pheochromocytoma/ hyperparathyroidism ▪ Fine-needle aspiration (FNA) thyroid biopsy ▫ Histological analysis: MTC with large, pleomorphic, ↑ C cell number ▪ Rectal biopsy ▫ Absent ganglion cells (HD) ▪ Ophthalmic slit-lamp examination ▫ Detects thickened, medullated corneal nerve fibers ▪ Genetic RET mutation testing TREATMENT MEDICATIONS ▪ Tyrosine kinase inhibitors ▪ Post-surgical hormone replacement ▪ Hyperparathyroidism ▫ Bisphosphonates/calcimimetics (cinacalcet) ▪ Cutaneous lichen amyloidosis ▫ Intralesional steroids, antihistamines, ultraviolet light/laser therapy SURGERY ▪ Tumor resection (e.g. thyroidectomy, adrenalectomy, partial/cortex-sparing adrenalectomy) ▪ Lymphadenectomy OSMOSIS.ORG 135

▪ HD ▫ Resect affected colon segment NEUROBLASTOMA osms.it/neuroblastoma PATHOLOGY & CAUSES ▪ Neural crest cell tumor arising in adrenal gland/spinal cord ▪ Fetal development → oncogene, tumor suppressor gene mutation → adequate cellular differentiation failure → tumor formation ▪ Most common infant cancer; most occur in age < five; better prognosis ▪ Releases chemokines (esp. CXCL12) → stimulates cell growth, migration → metastasis ▪ Half metastasize to bone ▪ Abdominal mass Bone metastasis ▪ Pain, pathologic fractures ▪ Skull base fractures → battle, “racoon eyes” sign ▪ Myelosuppression → anemia, thrombocytopenia, leukopenia → fatigue, easy bruising, frequent infections TYPES ▪ Three types: differentiation level Undifferentiated ▪ Neural crest cells, AKA small blue round cells; contains nerve fibers, AKA neuropil Poorly differentiated ▪ Partially displays characteristics of differentiated, undifferentiated Differentiated ▪ Surrounded by myelin, AKA Schwannian stroma; better prognosis SIGNS & SYMPTOMS ▪ Related to chemokine release; unspecific ▪ Fever; weight loss; sweating; fatigue Mass effect ▪ Horner syndrome → ptosis, miosis, anhidrosis ▪ Spinal cord compression syndromes → limb weakness, incontinence 136 OSMOSIS.ORG Figure 20.3 The histological appearance of a neuroblastoma demonstrating Homer-Wright rosettes. DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Renal mass/mass adjacent to spinal nerve roots; confirm diagnosis LAB RESULTS ▪ Catecholamine breakdown products: VMA, HMA Complete blood count (CBC)

Chapter 20 Neuroendocrine Tumors SURGERY ▪ Anemia, leukopenia TREATMENT MEDICATIONS ▪ Localized ▫ Resection ▪ Metastatic ▫ Resection, bone marrow transplant ▪ Metastatic ▫ Chemotherapy PANCREATIC NEUROENDOCRINE NEOPLASMS osms.it/pancreatic-ne-neoplasms PATHOLOGY & CAUSES ▪ AKA PanNETs ▫ Functional tumors arising from pancreatic neuroendocrine cells ▪ Unregulated hormone secretion → effect on target organs → hormone-related clinical syndrome TYPES Insulinoma ▪ Rare functional tumor ▫ Arises from insulin producing pancreatic beta cells ▪ Most common functioning PanNET ▪ Usually benign, indolent, small (< 2cm/0.8in), solitary lesions; rarely malignant ▪ ↑ insulin secretion → hyperinsulinemia → ↓ hepatic gluconeogenesis → hyperinsulinemic hypoglycemia VIPoma ▪ Rare functional tumor ▫ Arises from pancreatic D-1 cells that produce vasoactive intestinal polypeptide (VIP) ▫ AKA Verner–Morrison syndrome/ pancreatic cholera syndrome ▪ Malignancy: 50% ▪ ↑ VIP secretion ▫ Cellular adenylate cyclase, cAMP production by intestinal epithelial cells → secretion of fluid, sodium, chloride into intestinal lumen → high-volume secretory diarrhea Glucagonoma ▪ Rare functional tumor ▫ Arises from pancreatic glucagonproducing alpha cells ▪ Usually malignant ▪ Excessive glucagon ▫ ↑ liver’s catabolic action → ↑ amino acid oxidation, gluconeogenesis from amino acid substrates → glucagonoma syndrome (amino acid deficiency, ↑ blood glucose, glucose intolerance) ▫ Co-secretion of gastrin, VIP, serotonin, calcitonin → diarrhea Somatostatinoma ▪ Very rare somatostatin-secreting tumor ▫ Arises from pancreatic D-cells ▪ Commonly located within head of pancreas; may also arise from ampulla, periampullary region of duodenum; rarely in jejunum, liver, colon, rectum ▪ Usually malignant ▫ ↑ somatostatin → digestive organ inhibition → clinical syndrome RISK FACTORS Insulinoma OSMOSIS.ORG 137

▪ Multifocal insulinomas associated with MEN 1 VIPoma, glucagonoma ▪ Associated with MEN 1 Somatostatinoma ▪ Associated with MEN1, neurofibromatosis type 1 (NF1) COMPLICATIONS Insulinoma ▪ Hypoglycemia, seizures, rarely metastasis Vipoma ▪ Dehydration, electrolyte imbalances, metastasis Glucagonoma ▪ NME, weight loss (secondary to hyponutrition) ▪ Diabetes, chronic diarrhea, venous thrombosis (deep vein thrombosis, pulmonary embolism) ▪ Neuropsychiatric complications (e.g. depression, psychosis, agitation, paranoid delusions) ▪ Metastasis Somatostatinoma ▪ Cholelithiasis, diabetes mellitus, metastasis SIGNS & SYMPTOMS Insulinoma ▪ Whipple’s triad: hypoglycemia, hypoglycemia signs, intravenous (IV) glucose → symptom resolution ▫ Neuroglycopenic manifestations: visual disturbances, weakness, confusion ▫ Sympathetic/adrenergic manifestations: diaphoresis, tremors, palpitations, hunger VIPoma ▪ WDHA; stools tea-colored, odorless ▪ ↑ potassium secretion into large bowel → hypokalemia ▪ ↓ gastric acid secretion → hypochlorhydria ▪ ↑ glycogenolysis → hyperglycemia ▪ ↑ bone resorption → hypocalcemia 138 OSMOSIS.ORG ▪ ↑ vasodilation → flushing Glucagonoma ▪ Hyperglycemia, weight loss ▪ NME ▫ Erythematous, sometimes painful rash with papules/plaques on face, perineum, extremities; hair loss, nail dystrophy ▫ If mucous membranes affected: glossitis, angular cheilitis, stomatitis, blepharitis Somatostatinoma ▪ Classic syndrome ▫ ↓ cholecystokinin → colelithiasis ▫ ↓ pancreatic enzyme, ↓ intestinal lipid absorption → steatorrhea ▫ ↓ gastrin → hypochlorhydria ▫ ↓ insulin → diabetes mellitus ▪ Abdominal pain ▪ Weight loss MNEMONIC: 6 Ds Glucagonoma symptoms Dermatitis Diabetes Diarrhea Deep Venous Thrombosis Decreased Weight Depression DIAGNOSIS DIAGNOSTIC IMAGING Endoscopic ultrasound ▪ Insulinoma, VIPoma, glucagonoma, somatostatinoma ▫ Detects small tumors, establishes local disease extent, allows for needle biopsy CT scan/MRI ▪ Insulinoma, VIPoma, glucagonoma, somatostatinoma ▫ Tumor localization, TNM staging CT scan ▪ VIPoma ▫ Homogeneous, well-circumscribed

Chapter 20 Neuroendocrine Tumors lesions; may have cystic regions ▪ Glucagonoma ▫ May appear solid/contain central lowattenuation areas ▪ Somatostatinoma ▫ Isodense; may be cystic MRI ▪ VIPoma, glucagonoma, somatostatinoma ▫ Low signal intensity on T1-weighted images, high signal intensity on T2weighted images hyperchromasia, mitotic activity TREATMENT MEDICATIONS Insulinoma ▪ Diazoxide: inhibits insulin release, enhances glycogenolysis VIPoma ▪ Somatostatin analogue GLP-1 scintigraphy ▪ Insulinoma ▫ Identifies insulinoma via radiolabeled GLP-1 receptor imaging Glucagonoma, somatostatinoma ▪ Somatostatin analogue ▪ Anti-hyperglycemic agents Somatostatin receptor scintigraphy ▪ VIPoma, glucagonoma, somatostatinoma ▫ Detects metastases via radiolabeled form of somatostatin analog octreotide (Indium-111 [111-In]) pentetreotide SURGERY Functional PET imaging with 68-Ga DOTATATE ▪ Glucagonoma, somatostatinoma ▫ Detects small tumors LAB RESULTS Insulinoma ▪ Overnight fasting plasma levels/72 hour fast test (inpatient) ▫ ↓↓ glucose, ↑ insulin, ↑ proinsulin, ↑ C-peptide VIPoma ▪ Hormonal assay: ↑ plasma VIP ▪ ↓ stool osmotic gap (<50mOsm/kg) Glucagonoma ▪ Hormonal assay: ↑ plasma glucagon ▪ ↑ glucose Insulinoma, VIPoma, glucagonoma, somatostatinoma ▪ Resection ▪ Ultrasound-guided fine needle ethanol ablation (insulinoma only) OTHER INTERVENTIONS Insulinoma ▪ Oral carbohydrate administration; IV glucose VIPoma ▪ Manage complications: fluid, electrolyte replacement ▪ Treat metastatic disease (e.g. chemotherapy, radiation) Glucagonoma, somatostatinoma ▪ Correct nutritional deficiencies ▪ Treat metastatic disease (e.g. chemotherapy, radiation) Somatostatinoma ▪ Hormonal assay: ↑ somatostatin ▪ ↑ glucose OTHER DIAGNOSTICS ▪ Histopathological analysis, grading ▫ Determines degree of pleomorphism, OSMOSIS.ORG 139

PHEOCHROMOCYTOMA osms.it/pheochromocytoma PATHOLOGY & CAUSES ▪ Pheo = dark; chromo = colored; cyto = cell; oma = tumor ▪ Arises from chromaffin cells in adrenal medulla; secretes catecholamines ▪ Rule of 10s: 10% bilateral; 10% in children; 10% metastasize; 10% calcify; 10% extraadrenal ▪ Most common adult adrenal medulla tumor ▪ Most common in older biologically-male individuals; may be part of inherited syndrome (25%) ▫ MEN 2A, MEN 2B → RET protooncogene mutation ▫ Von-Hippel-Lindau (VHL) → VHL gene mutation ▫ Neurofibromatosis type 1 (NF1) → NF1 mutation → impaired neurofibromin function Figure 20.4 The gross pathological appearance of an adrenal pheochromocytoma. The tumor has been bissected revealing a hemorrhagic and necrotic cut surface. SIGNS & SYMPTOMS ▪ Catecholamine excess-related → ↑ epinephrine, norepinephrine, dopamine ▪ Sweating, anxiety, palpitations, tachycardia, transient, episodic hypertension, headaches ▪ May be associated with polycythemia MNEMONIC: Ps Pheochromocytoma symptoms Perspiration Palpitation Pallor ↑ Blood Pressure (BP) Pain (headache) 140 OSMOSIS.ORG Figure 20.5 The histological appearance of an adrenal pheochromocytoma. The tumor cells are arranged in nests and display prominent nucleoli and occasional nuclear inclusions.

Chapter 20 Neuroendocrine Tumors DIAGNOSIS DIAGNOSTIC IMAGING CT scan/MRI ▪ Suprarenal mass; confirm diagnosis LAB RESULTS Screening ▪ Urinary, serum catecholamine breakdown products → homovanilic acid (HMA), vanilmandellic acid (VMA) CBC ▪ Polycythemia Figure 20.6 An abdominal CT scan in the coronal plane demonstrating a large adrenal pheochromocytoma on the left hand side. TREATMENT SURGERY ▪ Removal (requires pre-operatory preparation) ▫ Block alpha effects with phenoxybenzamine → give beta blocker ZOLLINGER–ELLISON SYNDROME (ZES) osms.it/zollinger-ellison_syndrome PATHOLOGY & CAUSES ▪ AKA gastrinoma syndrome ▪ Functional gastrin-secreting tumor ▫ Most commonly arises from “gastrinoma triangle” (head of pancreas, curve of duodenum, cystic, common bile duct) ▪ Usually malignant ▪ ↑ gastrin secretion ▫ ↑ gastric acid output from parietal cells, enterochromaffin-like (ECL) → malabsorption, mucosal lining erosion (stomach, duodenum) ▫ Inhibition of sodium, water absorption by small intestines → loose stools ▪ May co-occur with other PanNET syndromes RISK FACTORS ▪ 20–30% of cases associated with MEN1 ▪ More common in biologically-male individuals COMPLICATIONS ▪ Diarrhea, steatorrhea, peptic (potential for bleeding, perforation), esophageal strictures, pancreatitis (with duct obstruction) ▪ Most gastrinomas malignant OSMOSIS.ORG 141

TREATMENT SIGNS & SYMPTOMS ▪ Abdominal pain; gastroesophageal reflux; nausea, vomiting; dysphagia; weight loss; loose stools; gastrointestinal (GI) bleeding DIAGNOSIS DIAGNOSTIC IMAGING Upper endoscopy ▪ Enlarged gastric rugal folds, esophagitis, ulcer presence Endoscopic ultrasound ▪ Gastrinomas appear as hypoechoic, homogeneous masses Somatostatin receptor scintigraphy ▪ Somatostatin analog (111 indiumDTPA-D-Phe1 octreotide) administered, somatostatin analog binds to somatostatin Type II receptors on gastrinomas ▪ Visualize gastrinoma(s), metastatic lesions LAB RESULTS ▪ Basal (fasting) gastrin levels: ↑ serum gastrin Secretin stimulation test ▪ Secretin administered IV ▪ If ZES tumor present ▫ ↑ serum gastrin > basal levels ▪ If other cause of hypergastrinemia ▫ Gastrin inhibition OTHER DIAGNOSTICS ▪ MEN1 screening 142 OSMOSIS.ORG MEDICATIONS ▪ Chemotherapy ▫ Metastatic disease SURGERY ▪ Resection OTHER INTERVENTIONS ▪ Proton pump inhibitors ▫ ↓ gastric acid ▪ Somatostatin analog ▫ ↓ gastrin levels; may slow tumor growth