MEN 1 Flashcards
How do MEN 1 occur?
Tumors result from Two-Hit Loss of Function at the MEN 1 Gene.
Meaning the other chromosome cannot suppress the tumor genes
How are Multiple Endocrine Neoplasia Type 1 acquired?
Familial 90%
Sporadic 10%
Which tumor suppressor protein is needed to prevent MEN 1
Menin
What is the most common MEN 1 tumor?
Parathyroid Hyperplasia 90%
multiple tumors*
What are the 3 most common types of MEN 1 tumors
Three P’s
Parathyroid Hyperplasia 90% (Hyperparathyroidism)
Pancreatic tumor
Pituitary tumors
What are examples of Non-Hormonal Tumors
Facial angiofibroma (85%) Truncal collagenoma (70%) Lipoma (30%) Leiomyoma (10%) Meningioma (5%?) Ependymoma (1%)
What are first signs see in patients with Parathyroid Hyperplasia?
Hypercalcemia
What are examples of Pacreatic Endocrine tumors?
Gastrinomas Insulinomas Glucagonamos VIPomas Somatostatinomas
What is the treatment of Parathyroid hyperplasia?
Parathyroidectomy
What are some examples of Non-classical tumors in MEN 1
Dermal tumors
Angiofibromas
Collagenomas
Lipomas
How MEN 2 occur?
Autosomal dominant mutation of RET proto-oncogene (just need one hit)
Once activated you now have this receptor forever that causes proliferation of cells
What kind of tumors occur with MEN Type 2A?
What is a definitive treatment
Medullary thyroid CA
Pheochromocytoma
Hyperparathyroidism
Total Thyroidectomy by 5-6 years old
What kind of tumors occur with MEN Type 2B
Medullary thyroid CA
Pheochromocytoma
Multiple neuromas
Marfanoid habitus
What are Pheochromocytomas?
Where do they mostly occur
tumors that secrete excess catecholamines (Epi or Epi/NE)
How do Hyperparathyroid-Jaw Tumor Syndromes occur?
associated with germline inactivating mutation of the
CDC73/HRPT2 tumor suppressor gene
Results in loss of parafibromin tumorsuppressor protein function
Where do Hyperparathyroid-Jaw tumor Syndrome occur?
Parathryoid, jaw, kidney, uterus
What is another name for Hyperparathyroidism-Jaw Tumor Syndrome?
Cemento-Ossifying Fibroma of the Maxilla
What are findings that are common in HPT-JT syndrome?
Adenomas
Frequent cystic tumors
How do Von Hippel-Lindau syndromes occur?
Autosomal Dominant disorder of VHL tumor-suppressor gene
What are characteristics of Von Hippel Lindau syndrome?
Up to 50% of patients will have bilateral pheochomocytomas
NE producing tumors
How do Neurofibromatosis type 1 occur
Inherited mutation of NF1-tumor suppressor gene
What are clinical manifistations of Neurofibromatosis type 1?
Pheochromocytoma (2-5%) (EPI & NE producing tumors)
Neurofibromas (2 or more)
Optic glioma Lisch nodules (iris hamartomas, 2 or more)
*Cafe-au-lait macules (6 or more)
What are Succinate Dehydrogenase related Pheochromocytomas
- PHEOs in younger age
- PHEOs often exrtra-adrenal and metastatic
- PHEOs may secrete only dopamine
What is the different between SDHB and SDHD Pheochromocytomas
SDHB:
- > 95% extra-adrenal, often secrete NE and DA
- Malignant at initial diagnosis
- Fx 10%
SDHD
- Most of them present as head and neck PGLs
- Most do not secrete catecholamines and are 99% benign
How do Carcinoid syndromes come about?
Due to tumor secretion of serotonin and other vasoactive peptides (histamine, prostaglandins
What are clinical symptoms from Carcinoid syndrome?
Flushing
Diarrhea
Wheezing
Right sided valvular heart diseas
What are test can be used to diagnose Carcinoid syndrome
Urinary excretion of 5-HIAA (serotonin metabolite)
What do Gastrinomas cause a rise in?
Gastrin –> hormone that stimulates gastric acid secretions
What are signs and symptoms of Gastrinomas
Zollinger-Ellison syndrome
Abdominal pain
Peptic ulcers
Gastroesophageal reflux
Diarrhea
What test can be used to detect Gastrinomas
Very high gastrin and low stomach pH
Secretin Test:
Normal response= Gastrin decreases
Response in gastrinoma=Gastrin rises
Where do Insulinomas occur
Neuroendocrine tumor of the pancreas derived from beta cells
What is the most common symptom from Insulinomas
Hypoglycemia
High insulin in the face of low blood glucose
What is Whipples triad and what does this indicate
Used to diagnose Insulinomas
- Fasting hypoglycemia
- Neuroglycopenia symptoms (confusion, h/a, blurred vision, seizures, amnesia, coma)
- Improves after glucose replacement
Elevated labs seen in Insulinomas
Insulin,
c-peptide,
proinsulin levels are not suppressed with hypoglycemia
How are Insulinomas diagnosed?
72 hour fast
NPO except non-caloric beverages and essential medications
End test when patient has plasma glucose < 50 mg/dl with neuroglycopenic symptoms or 72 hours elapse
How can insulinomas be detected with imaging
- Triphasic CT Abdomen
2. Endoscopic ultrasound (wire with light)
If you can’t locate an insulinomas what other imaging tool can you use to detect the tumor
Calcium Stimulated arteriogram
injection of calcium stimulates release of insulin so you can detect where insulin is secreted the highest in the pancreas
Treatment for Insulinomas?
Surgical removal
What medical agents can be used to treat insulinomas?
Frequent snacking to avoid prolonged fasting
Diazoxide- acts directly on beta cells to suppress insulin secretion
Ocreatide- somatostatin analog, use if hypglycemia refractory to diazoxide
What is characteristic of VIPoma (Vasoactive Intestinal Peptide tumor)?
WHDA syndrome
Watery diarrhea
Hypokalemia
Achlorhydria (hypochlorhydria)
How are VIPoms tested?
VIP levels
What is a clinical manifistation of a Glucagonoma
Migratory necrolytic erthema
Hyperglyemia
What test can be used to diagnose Glucagona
Test glucagon levels
What is being secreted in Somatostatinomas?
How can this be tested for?
Somatostatin
Somatostatin levels
If biochemical tests are positive for Somatostatins what must you do next?
Pursue imaging: CT scan or MR or PET Octreoscan
What syndromes can occur from Somatostatinomas
Diabetes
Gallbladder disease
Diarrhea
Which cells can MEN 1 tumors disperse through?
Gastrin cells (located in duodenal submucosa maybe?)
