GEP-NETs, MEN, Paraneoplastic syndromes

Gastroenteropancreatic Neuroendocrine Neoplasms (GEP-NETS)

neuro endocrine tumors that arise from the stomach, intestines, or pancreas

unresectable or metastatic

65% of GEP-NETs are

MEN 1 (most typical), Von Hippel-Lindau disease,

GEP-NETs are associated with which genetic disorders

glucagon

A cells of the pancreas (20%) secrete

insulin

B cells of the pancreas (70%) secrete

somatostatin

D cells of the pancreas (5%) secrete

gastrin

G cells of the pancreas secrete

Insulinoma (B cell adenomas)

What is the most common functional type of GEP-NET that is characterized by the hypersecretion of insulin that is unresponsive to hypoglycemia?

Plasma glucose under 40, Serum insulin 6+ microunit/mL, elevated C peptide, Low beta-hydroxybutyrate

Describe the laboratory findings of Insulinomas

Helical CT (sensitivity 79%), MRI w/ gadolinium (sensitivity 85%), Endoscopic U/S (95% sensitivity)

Ways to diagnose and find insulinomas

surgical resections

Treatment of choice for insulinomas

Gastrinomas

A tumor usually located in the pancreas or duodenum that excretes gastrin leading to excessive stomach acid

Zollinger-Ellison Syndrome

Gastrinomas are associated with ____________________ which is characterized by gastric acid secretion hypersecretion and aggressive, refractory peptic ulceration.

50%

What percentage of gastrinomas are malignant?

mulitple/refractory peptic ulcers, ulcers distal to duodenum, multiple peptic ulcers, relatives with MEN

Red flags for gastrinomas

Glucagonomas

Which type of GEP-NET is usually malignant with metastasis characteized by high levels of glucagon, weight loss, diarrhea, nausea, DM symptoms, and necrolyptic malignant erythema

Mass effect

Nonfunctional tumors produce symptoms based on the

somatostatin receptor scintigraphy (SRS)

What type of imaging detects NET (75% sensitivity) by measuring octreotide (somatostatin mimic) uptake?

surgical resection

Treatment for GEP-NETs?

Multiple Endocrine Neoplasia (MED)

An autosomal dominant disorder that causes predisposition to the development of tumors in at least two endocrine glands

Pituitary adenoma, Facial angiofibromas, collagenomas, parathyroid tumors, insulinomas, gastrinomas

Tumors common with MEN 1

hyperparathyroidism, medullary thyroid cancer, pheo

Tumors common with MEN 2 (2A)

Medullary thyroid cancer, pheo, marfanoid phenotype, mucosal neuromas, intestinal ganglioneuromas, skeletal abnoramilites, delayed puberty

Tumors common with MEN 3 (2B)

parathyroid, pancreatic neuroendrocrine, pituitary, adrenocortical adenoma, thyroid adenoma, renal, testicular, neuroendocrine cervical carcinoma

Tumors common with MEN 4

Hyperparathyroidism (treat with surgical resection)

What is normally the 1st sign of MEN 1 (Wermer Syndrome)

Enteropancreatic tumors (gastrinomas, insulinomas, glucagonomas, somatostatinomas)

70% of MEN 1 patients have __________________

aggressive macroadenomas (secrete prolactin, GH, ACTH, non-secretory)

29% of of MEN 1 patients present with

Prophylactic total thyroidectomy by age 6 for 2A and 6 month for 2B

What is recommended for patients MEN 2A (Sipple Syndrome) or MEN 3 with medullary thyroid cancer?

Different gene mutation

What is different about MEN 4 when compared to MEN 1

Paraneoplastic syndrome

Symptoms and physical findings due to the remote effects of a neoplasm that are NOT related to direct invasion, obstruction, mass effect, or metastasis

Hormones and cytokines secreted by the tumor OR in a immune response against the tumor

What mediated paraneoplastic syndromes?

fever (release of endogenous pyrogens)

What is a common initial presentation of paraneoplastic syndromes

Lung (Small cell), breast, ovarian, liver, leukemias, lymphomas, stomach, pancreas, neuroendocrine

Which cancers commonly cause some paraneoplastic syndromes

Small cell lung (15%), Nonsmall cell lung (1%)

Which cancers may produce SIADH

managing hyponatremia, starting chemo

SIADH from a paraneoplastic syndrome is treated by

squamous cell carcinoma, adenocarcinoma, small cell lung cancer, breast cancer, multiple myeloma, kidney

Cancers that commonly cause hypercalcemia as a paraneoplastic syndrome

PTHrP, calcitriol, osteoclast activating factors

What might tumors secrete to cause hypercalcemia as a paraneoplastic syndrome

insulinomas, hepatocellular carcinoma

What types of cancer may cause hypoglycemia as a paraneoplastic syndrome

Overproduction of IGF-2 to stimulate glucose utilization

Why can hepatocellular carcinoma cause hypoglycemia

Ectopic production of ACTH, SCLC

What may cause Cushing Syndrome as a paraneoplastic syndrome

treat underlying cancer

For a majority of paraneoplastic syndromes, what is our treatment plan?