SM152 Adrenal Medulla Pathophysiology

Question 1

Enzyme difference between adrenal medulla and paraganglia?

Answer 1

Presence of PNMT, which converts norepinephrine to epinephrine

Question 2

What nervous system is the adrenal medulla part of?

Answer 2

ANS: sympathetic/adrenergic systems

Question 3

Zones of the adrenal cortex and hormones elaborated?

Answer 3

Zona glomerulosa (mineralocorticoids - aldosterone)
Zona fasciculta (glucocorticoids - cortisol)
Zona reticularis (androgens - DHEA)

Question 4

Paraganglia: locations, nerve type, termination point, hormone secreted

Answer 4

Mediastinum, abdomen, aortic bifurcation, bladder, renal medulla

Pre-ganglionic nerves

Terminate in para-vertebral and pre-vertebral nerve ganglia

Secrete norepinephrine (do NOT secrete epinephrine)

Question 5

Catecholamine synthesis

Answer 5

Tyr –(tyrosine hydroxylase)–> DOPA –> DA –> norepi –(PNMT)–> epi

Question 6

Pheochromocytoma: cell type, hormone produced

Answer 6

Chromaffin cells, catecholamines

Question 7

Genetic syndromes associated with pheochromocytoma

Answer 7

MEN2 (A and B), von Hippel Lindau disease, NF type I

Question 8

Genetic syndromes associated with paragangliomas

Answer 8

Succinate dehydrogenase (SDH): SDHB, SDHC, and SDHD

Question 9

Most common adrenal masses

Answer 9

Non-functioning adenoma > subclinical Cushing’s syndrome > pheo

Question 10

Pheochromytoma rule of 10’s

Answer 10

10% bilateral, 10% children, 10% familial, 10% malignant, 10% extra-adrenal, 10% or calcified

Question 11

How to differentiate pheochromocytomas and paragangliomas?

Answer 11

Pheos produce epinephrine and extra-adrenal tumors don’t, so metanephrine or epinephrine levels

Question 12

von Hippel Lindau disease: gene/chromosome, mutation type needed to get pheochromocytomas, clinical signs

Answer 12

vHL gene is a tumor suppresor on chromosome 3
Need the missense mutation
Retinal angiomas, CNS hemangioblastomas, renal carcinomas, pancreatic cysts, pheochromcytomas

Question 13

Succinate dehydrogenase (SDH): gene function, associated tumor type

Answer 13

Component of the ETC, catalyzes oxidation of succinate to fumarate in the Krebs cycle

Paragangliomas (SDHB, SDHC, SDHD)

Question 14

Imprinting of SDHD mutations

Answer 14

No disease when inherited from mother, high penetrance of disease when inherited from father

Question 15

SDHB mutation associations, malignancy risk, age of disease development

Answer 15

Families with abdominal, pelvic, and thoracic paragangliomas

Very high risk of malignancy

Develop disease early (avg. 34)

Question 16

PGL1, PGL3, PGL4

Answer 16

Diseases resulting from germline mutation in SDH

PGL1: SDHD
PGL3: SDHC
PGL4: SDHB (think PGL4 if you see mostly norepi)

Question 17

Clinical presentation of pheochromocytoma

Answer 17

Headache, palpitations, diaphoresis, HTN, abdominal pain

Question 18

Biochemical testing for medulla excess

Answer 18

24-hour urine for catecholamines and metanephrine/normetanephrine, plasma metanephrine/normetanephrine

Question 19

Treatment for pheochromocytoma/paraganglioma, pharmacologic considerations (what do you need to give and why?)

Answer 19

Surgical resection

Alpha-blockers initially (phenoxybenzamine) to prevent hypertensive crisis, then beta-blockers

Question 20

What would happen if you started beta-blockers before alpha-blockers in a pheo resection patient?

Answer 20

Hypertensive crisis from stimulation of alpha receptors

Question 21

Episodic hyperadrenergic symptoms in pheochromocytoma

Answer 21

5 P’s: pressure (HTN), pain (headache), perspiration, palpitations, pallor

Question 22

Neurofibromatosis type I (NF I): inheritance pattern, clinical signs

Answer 22

Autosomal dominant

Neurofibromas, cafe au laid spots, axillary and inguinal freckling, iris hamartomas (Lisch nodules)