Genetic/neuroendocrine

Question 1

Bilateral CN VIII schwannomas and multiple meningiomas. AD

Answer 1

NF 2

Chrom 22

Question 2

Neurofibromas, optic nerve gliomas, Lisch nodules, café au lait spots

Answer 2

NF 1 (von Recklinghausen disease)
Chrom 17

Question 3

Cutaneous facial angiomas, leptomeningeal angiomas. V1 and V2 distributions of trigeminal nerve

Answer 3

Sturge-Weber syndrome

Tram-track calcifications

Question 4

Kidney, liver, pancreatic cysts, cortical and subependymal hamartomas, rhabdomyoma, Ash-leaf spots, subependymal astrocytoma - AD

Answer 4

Tuberous sclerosis
Renal angiomyolipomas (benign tumor w/blood vessels, smooth mm and fat) are also assoc w/TS

Question 5

Congenital telangiectasias – AD

Answer 5

Osler-Weber-Rendu syndrome (hereditary hemorrhagic telangiectasia)

Question 6

Cerebellar hemangioblastoma, congenital cysts of kidneys, liver and pancreas - AD, pheo

Answer 6

Von Hippel-Lindau

Risk for bilateral RCC

Question 7

How does prolactinoma cause amenorrhea, galactorrhea, and osteoporosis?

Answer 7

High prolactin suppresses GnRH from hypothal –> hypogonadism (low estrogen), anovulation, amenorrhea.
Sustained hyperprolactin –> low estrogen accelerates bone loss.

Question 8

Fibrous dysplasia of the bone, endocrine problems, cafe-au-lait spots

Answer 8

McCune-Albright syndrome

Activating mutation in the G protein/CAMP/adenylate cyclase signaling pathway

Question 9

Primary hyperparathyroidism (hypercalcemia/stones), pituitary tumors (periph vision loss), pancreatic tumors (includes ZE), angiofibromas and lipomas

Answer 9

MEN1

Question 10

Medullary thyroid cancer (calcitonin), pheochromocytoma, mucosal neuromas/marfanoid habitus

Answer 10

MEN2B

Question 11

Medullary thyroid cancer (calcitonin), pheochromocytoma, parathyroid hyperplasia

Answer 11

MEN2A

Question 12

What does it mean when a drug has high lipophilicity?

Answer 12

high Vd, good penetration into CNS

Preferentially processed by the liver into more polar compounds

Question 13

What is the MC secretory product of the pancreatic and duodenal endocrine lesions?

Answer 13

gastrin (can lead to peptic ulcers)

Question 14

How can a carcinoid tumor cause pellagra?

Answer 14

The tumor secretes serotonin, depleting tryptophan (precursor to serotonin and niacin)

Question 15

How does treatment of ZE syndrome with secretin cause increased serum gastrin?

Answer 15

Secretin inhibits gastrin release from stomach antrum, but stimulates gastrin secretion from a gastrinoma (pt with ZE).
Note: ZE patients typically have peptic ulcers (often beyond the duodenal bulb), abd pain/acid reflux, and diarrhea

Question 16

Patient with ZE should be queried for a family history of what disorder?

Answer 16

MEN1 (pancreatic tumor - esp gastrinomas)
Primary hyperparathyroidism
Pituitary tumors

Question 17

Differentiate localized vs metastatic carcinoid tumors

Answer 17

Localized to intestine - do not cause carcinoid synd bc secretory products are metabolized by the liver bf entering the systemic circ
Metastatic - release vasoactive substances that avoid first-pass metabolism –> flushing, diarrhea, bronchospasm

Question 18

Small cell carcinoma can secrete what?

Answer 18

ACTH
Vasopression
Note: Squamous cell lung cancer can secrete PTHrP –> hypercalcemia)

Question 19

Acoustic schwannomas are commonly located where in the brain? What other sx can develop due to the tumor?

Answer 19

Cerebellopontine angle
CN VIII - ipsilat SNHL/tinnitus and vertigo
CN VII - facial paresis
CN V - loss of facial sensation

Question 20

Associated genes?
Lynch synd
FAP
VHL
Li-Fraumeni synd
MEN1
MEN2

Answer 20

Lynch - MSH2, MLH1, MSH6, PMS2
FAP - APC
VHL - VHL
Li-Fraumeni - TP53
MEN1 - MEN1
MEN2 - RET

Question 21

What genetic study can be done to diagnose Klinefelter?

Answer 21

Chromosomal analysis of lymphocytes

47XXY

Question 22

What does unfavorable lyonization mean

Answer 22

Female patient who is a carrier of a X-linked disease gets the normal X chromosome inactivated –> displays phenotype. Hemizygous
Note: A chromosome in a diploid organism is hemizygous when only one copy is present.

Question 23

Neck mass by carotid artery bifurcation that is positive for synaptophysin, chromogranin, and neuron-specific enolase. Dx?

Answer 23

Paraganglioma - rare neuroendocrine neoplasm that may develop at various body sites (including the head, neck, thorax and abdomen)

Question 24

presence of multiple polyps in the colon together with tumors outside the colon.The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas and sebaceous cysts

Answer 24

Gardner syndrome (familial colorectal polyposis) - AD
mutation in the APC gene located in chromosome 5q21 (band q21 on chromosome 5). This is the same gene as is mutant in familial adenomatous polyposis (FAP), a more common disease that also predisposes to colon cancer.

Question 25

infant with HTN, rapid eye movement, firm nodular midline abdominal mass and inc urine concentrations of homovanillic and vanillylmandelic acids. Dx?

Answer 25

Neuroblastoma - May cross midline. Assoc with N-Myc oncogene. Neural crest origin. common tumor of the adrenal medulla in children. HVA is a breakdown product of Dopamine in urine

Note: Wilms tumor is intrarenal

Question 26

Female with excess skin on nape of neck and lymphedema of hands and feet. Chromosome analysis shows some cells with normal 46 XY and some cells with 45 X. What caused this cytogenetic abnormality?

Answer 26

Mosaic Turner’s syndrome and the mosaic trisomies result from nondisjunction during mitosis. In total monosomy/trisomies, the cause is nondisjunction during meiosis. Uniparental disomy is essentially only tested via the Prader-Willi and Angelman syndromes (chromosome 15).
Note: Excess skin = cystic hygroma