Endo - 2-2 - Challenging Case Of Htn

Front 1

Clinical pres of pheo

Back 1

HTN - episodic or contin
Spells - tremor, sweating, palpitation, HA
Postural hypotension

Front 2

Lab eval of pheo

Back 2

Best screening test is plasma metanephrine levels.

Can also do urine coll of catecholamines and their metabolites.

Or you can do serum catecholamines.

Front 3

Tx of pheo

Back 3

Alpha and beta blockade, volume repletion (high salt diet) and surgery

Front 4

Causes of familial pheochromocytoma

Back 4

All are autosomal dominant

Neurofibromatosis Type I
Von Hippel-Lindau disease
Multiple Endocrine Neoplasia Syndrome type 2
Succinate dehydrogenase Type B or D (SDHB, SDHD)

Front 5

Neurofibromatosis Type I

Back 5

Cutaneous neurofibromas with cafe au lait spots.
Pheo in only 1% of cases.
Inactivating mutations in NF1 gene (tumor suppressor)

Front 6

Von Hippel-Lindau disease

Back 6

Retinal angioma, cerebellar issues, renal cancer.
Pheo in 15%
Inactivating mutation in VHL gene.

Front 7

Mech of tumorigenesis in Von Hippel-Lindau and Succinate dehydrogenase Type B or D disease

Back 7

Increased signaling of hypoxia inducible factor-1 (HIF-1) which drives malignant transformation genes incl tumor angiogenesis.

Front 8

Succinate dehydrogenase Type B or D (SDHB or SDHD)

Back 8

Extra-adrenal pheo=paraganglioma
Pheo in 20%

Inactiv mutation in citric acid cycle (mitochondrial) enzyme which reduces mitochon SDH activity, increases succinate levels, and thus stabilizes HIF-1

Front 9

MEN2a and 2b

Back 9

Medullary thyroid cancer, pheo in 50% (varies with mutation), hyperparathyroidism, activ mutation in RET proto-oncogene.

2B has mucosal neuromas.

Front 10

MEN1

Back 10

Hyperparathyroidism, pituitary adenomas, pancreatic islet cell tumors

Inactivated mutation in MENIN tumor suppressor gene.

DOES NOT INCLUDE PHEO.

Front 11

RET proto-oncogene

Back 11

codes a nerve growth factor receptor.

Receptor is a tyrosine kinase and mutations cause autonomy of signaling.

Location of hte mutation correlates with the clinical presentation. (most often in cysteine - in pt in lecture it was in a serine that made it less obvious)

Front 12

Medullary thyroid cancer

Back 12

From parafollicular cells (C cells) of the thyroid that normally produces calcitonin.

Very high prevalance in those with MEN2.

C-cell hyperplasia is a precancerous state that is detected by a stimulation test that causes release of calcitonin in the blood.

Resistance to radiation (incl radioiodine because it is not a thyroid cell - it just happens to be in the thyroid) and chemo.

Front 13

Tx of MTC

Back 13

Proph thyroidectomy.

Front 14

MENIN AKA

Back 14

MEN1 gene.

Front 15

What do mucosal neuromas look like?

Back 15

Bumpy lips and tongue.

Pathognomic for MEN2B

Front 16

Inactivating mutation of RET proto-oncogene would cause...

Back 16

Hirschsprung's disease leading to megacolon and megaureter becasue there is no contractile function of those two (colon and bladder).

Front 17

New drug to inhibit RET tyrosine kinase activity

Back 17

ZD6476/Zactima.

Front 18

Why do you genotype possible family members?

Back 18

Fix them before they get MTC or you can relieve them that they won't get this later in life.