Pheo and MEN syndromes

Question 1

clinical manifestations of pheochromocytoma

Answer 1

1. hypertension, episodic or continuous
2. spells: tremors, sweating, palpiations, headaches
3. postural hypertension

Question 2

lab eval for pheo

Answer 2

best = plasma metanephrine

second best = 24 hour urine catecholamines; serum catecholamines

Question 3

four causes of familial pheochromocytoma. form of inheritance?

Answer 3

all are AD

1. neurofibromatosis type I
2. von Hippel-Landau disease
3. MEN type 2
4. Succinate dehydrogenase type B or D

Question 4

Neurofibromatosis type 1

Answer 4

cutaneous neurofibromas, cafe au last spots
1% pheo
INACTIVATING mutation of tumor suppressor NF

Question 5

von Hippel Lindau disease

Answer 5

retinal angioma, cerebellar hemangioblastoma, renal cancer
pheo in 15% of cases
INACTIVATING mutation in VHL –> increased HIF-1 –> angiogenesis

Question 6

MEN 2

Answer 6

ACTIVATING mutations in RET proto-oncogene
MEN2a:
- MTC, pheo in 50%, hyperPTH
MEN2b:
- MTC, pheo in 50%, hyperPTH, mucosal neuroma

Question 7

MEN1

Answer 7

INACTIVATING mutation in menin tumor suppressor

- hyperPTH, pituitary adenoma, pancreatic islet cell tumor)

Question 8

precursor state to MTC

Answer 8

thyroid c-cell hyperplasia

Question 9

tx for MEN2 in kindreds

Answer 9

prophylactic thyroidectomy of all children w/ RET mutation

Question 10

what conditions increase nuclear HIF-1?

Answer 10

VHL and SDH

Question 11

succinate dehydrogenase type B or D

Answer 11

can cause extra-adrenal pho
pheo in 20% of mutations
may be malignant
inactivating mutation of citric acid cycle enzyme –> increased succinate –> stabilized HIF-1 –> malignancy

Question 12

Hirschsprung’s disease

Answer 12

inactivating mutation of RET photo-oncogene –> neural plexus in gut fails to develop –> lack of gut motility –> megacolon, megaureter

Question 13

ZD5476 Zactima

Answer 13

orally active inhibitor of RET tyrosine kinase –> blocks MTC in MEN2