170. Adrenal Medulla Pathophysiology Flashcards
Enzyme that creates EPI from NE
Only found in the adrenal medulla
PNMT
Start a ___ to counteract catecholamine-induced volume contraction and orthostasis associated w/ alpha blockade
High sodium diet
Autosomal dominant disorder w/:
- neurofibromas
- Cafe au lait spots
- axillary and inguinal freckling
- iris hamartomas (lish nodules)
2% of patients develop pheochromocytomas
NF1
Proteins that can serve as clinical markers of adrenal medulla or ganglia tumors
Contained within the chromaffin cells within the paraganglia
Chromogranins
Includes:
- Medullary thyroid carcinoma
- Pheochromocytoma
- Mucosal neuromas
- GI tract ganglioneurosis
- marfanoid habitus
- Peculiar facial features: thin face, big lips, nodules on tongue
MEN2B
Arise from the glomera along parasympathetic nerves in the head, neck, and upper mediastinum
Clinically non-functional and produce low levels or no catecholamines
Parasympathetic paragangliomas
Tumors arising in the adrenal medulla
Pheochromocytoma
Surgical resection
Patients need to be prepared with alpha and beta blockade
Treatment of pheochromocytoma
Result of the activation of RET proto-oncogene
- cell surface tyrosine kinase receptor RET germ-line point mutations are found in the majority
MEN2
Presentation is mostly age-dependent
Gene is located on chromosome 3
- tumor suppressor gene
Pheochromocytoma associated w/ missense mutation
Von Hippel Landau Disease
Clinical presentation:
- HA (71%)
- Palpitations (65%)
- Diaphoresis (65%)
- HTN
- Abdominal pain
- Asymptomatic (10%)
- insulin resistance state
Pheochromocytoma
Should never be started first because blockade of vasodilatory peripheral beta-adrenergic receptors with unopposed alpha-adrenergic receptor stimulation can lead to further elevation in BP
Beta-blockade
Familial paragangliomas are associated to genetic mutations in ___
Component of the ETC complex II
Catalyzes the oxidation of succinate to fumarate
Succinate DH
Given first in preoperative medical therapy for pheo resection
Given 7-10 days preoperatively to normalize BP and expand the contracted blood volume
Alpha-adenergic blockade (phenoxybenzamine)
Autosomal dominant gene mutations affecting the germ-line
- syndrome of familial endocrine neoplasms
Two types: A and B
MEN 2
Consist of chromaffin cells that collect in close approximation to autonomic ganglia and plexuses
Found in the mediastinum, abdomen, around celiac axis, renal medullae, aortic bifurcation and adjacent to bladder
Paraganglia
Can be sporadic and familial (AD disorders)
Locations:
- head and neck (5%)
- thorax
- Abdomen (50%)
- pelvis
- bladder
Paragangliomas
Secretes calcitonin Most common component of MEN2 w/ a 90% penetrance
Medullary thyroid carcinoma
Most common of the MEN2 syndromes
Includes:
- Medullary thyroid carcinoma is the most common with over 90% penetrance
- Primary hyperparathyroidism
- Pheochromocytoma (50%)
MEN2A
Associated with families with abdominal, pelvic, and thoracic catecholamine-secreting familial paraganglioma and have the greatest risk of malignancy
Carriers develop disease early (~34yo)
More likely to develop malignant paragangliomas and additional neoplasms (renal cell carcinoma)
SDHB mutation
Syndrome that includes multiple tumors:
- retinal angiomas
- CNS hemangioblastomas
- Renal cysts, renal cell carcinomas
- pancreatic cysts
- pheochromoctyomas (25%)
Von Hippel Landau Disease
Catecholamine-producing tumor of chromaffin cells
Usually intra-abdominal <0.2% of hypertension
Occasionally bilateral (10%)
Associated w/ inherited diseases:
- MEN2A
- MEN2B
- Von Hippel-Lindau
- NF1
Pheochromocytoma
Target of preoperative medical therapy before pheo removal
Control hypertension and expand volume
Causes the following:
- Increase in systolic and diastolic BP
- decrease of HR
- hyperglycemia
NE
Causes the following:
- increase in systemic BP
- increase in HR
- decrease of gut motility
- diversion of circulation to limb muscle
- bronchodilation
- mydriasis
- hyperglycemia
EPI
Tumors arising from the extra-adrenal sympathetic ganglia
Paragangliomas
Measures metanephrine and normetanephrine in a 24 hr collection for ___
Fractionated metanephrines
Variants include:
- Familial MTC (FMTC)
- w/ cutaneous lichen amyloidosis (CLA)
- w/ Hirshsprung’s disease
MEN2A
Arise from chromaffin cells of paraganglia along sympathetic chains in the chest, abdomen, or pelvis
Sympathetic paragangliomas
Sympathetic pre-ganglionic nerve fiber that terminates in para-vertebral and pre-vertebral nerve ganglia
Postganglionic nerve fibers secrete NE
Paraganglia
Measures EPI and NE in a 24hr collection for __
Fractionated catecholamines
Has both an embryologic and functional link with the autonomic nervous system
- part of the autonomic/sympathetic nervous system
Functions much like the postganglionic sympathetic neurons but epinephrine is released into the blood stream, rather than the synaptic junction
Adrenal medulla
Has a negative predictive value 100%
Plasma free metanephrines
