SM_180b: Adrenal Medulla Flashcards
Adrenal gland is composed of ____ and ____
Adrenal gland is composed of medulla and cortex
Adrenal cortex is derived from the ____ and secretes ____ hormones
Adrenal cortex is derived from the mesoderm and secretes steroid hormones
Adrenal medulla is derived from ____ and secretes ____
Adrenal medulla is derived from ectodermal chromaffin tissue and secretes catecholamines
Describe the development of the adrenal medulla
Adrenal gland medulla
- 7 week gestation: chromaffin cells from the celiac plexus collect on the medial side of the primordial cortex and migrate inward
- 4 months gestation: chromaffin tissue occupies a central position in a gland
Describe histology of the adrenal gland
Adrenal gland
- Capsule
- Zone glomerulosa
- Zona fasciculata
- Zona reticularis
- Adrenal medulla
Adrenal medulla functions like a ____ but releases ____ into the ____
Adrenal medulla functions like a postganglionic sympathetic neuron but releases epinephrine into the blood stream
(receptors and effector cells located throughout body)
Adrenal medulla is part of the ____ system and derived from the ____
Adrenal medulla is part of the sympathetic nervous system and derived from the neuroectoderm (neural crest) cells that migrate from the vertebral column to the periaortic region
Paraganglia are ____
Paraganglia are sympathetic preganglionic nerve fibers that terminate in paravertebral and prevertebral nerve ganglia
- Chromaffin cells aggregated in close approximation to autonomic ganglia and plexuses
- (Postganglionic nerve fibers secrete norepinephrine)
- Develop at 2 months of gestation
Paraganglia contain ____ cells similar to ____ cells
Paraganglia contain neuroendocrine cells similar to adrenal medullary cells
(catecholamines present)
Describe locations of the paraganglia
Paraganglia locations
- Mediastinum
- Abdomen: along sympathetic nerve chains in paravertebral and prevertebral positions
- Around the celiac axis
- Renal medullae
- Aortic bifurcation (organ of Zuckerandl)
- Adjacent to bladder
Pheochromocytes are ____
Pheochromocytes are axonless neurons producting catecholamines
- Respond to synaptic activation by releasing preformed catecholamines: epinephrine (80%), norepinephrine (20%)
- Regulated by sympathetic cholinergic fibers acting on nicotinic receptors
____ and ____ are common chromaffin cell tumors
Pheochromocytomas and paragangliomas are common chromaffin cell tumors
(pheochromocytomas are most common)
Chromogranins are ____ that can serve as ____
Chromogranins are chromaffin cell proteins that can serve as clinical markers (Chromogranin A)
- Found in adrenal medulla or ganglia tumors (pheochromocytomas, paragangliomas)
Circulating catecholamines are metabolized in ____ and ____
Circulating catecholamines are metabolized in neuronal tissues and liver
- Metabolites are excreted in the urine: 24 h urine metanephrines (catecholamine metabolites) are very valuable diagnostic tool
Describe catecholamine metabolite synthesis
Catecholamine metabolite synthesis
- MAO degrades epinephrine and norepinephrine
- COMT converts dihydroxymandelic acid to vanillylmandelic acid
Adrenal medulla secretes ____ and ____
Adrenal medulla secretes epinephrine and norepinephrine
Alpha receptors mediate ____ in vasculature and ____ in endocrine pancreas
Alpha receptors mediate constriction (arteries and veins) in vasculature and inhibition of secretion in endocrine pancreas
Beta receptors mediate ____ in vasculature and ____ in endocrine pancreas
Beta receptors mediate dilatation (arteries) in vasculature and stimulation of secretion in endocrine pancreas
Catecholamines (epinephrine and norepinephrine) are responsible for ____, ____, and ____
Catecholamines (epinephrine and norepinephrine) are responsible for fright, flight, and flight
Tumors in the adrenal medulla are ____
Tumors in the adrenal medulla are pheochromocytomas
Tumors from extra-adrenal sympathetic and parasympathetic ganglia are ____
Tumors from extra-adrenal sympathetic and parasympathetic ganglia are paragangliomas
Patients with disease-causing germline mutations are likely to have ____
Patients with disease-causing germline mutations are likely to have pheochromocytomas or paragangliomas
Pheochromocytomas are tumors arising from ____ cells producing one or more ____
Pheochromocytomas are tumors arising from adrenomedullary chromaffin cells producing one or more catecholamines
(epinephrine, norepinephrine, and dopamine)
Adrenal masses are most commonly ____
Adrenal masses are most commonly non-functioning adenomas
Multiple endocrine neoplasia is ____ with ____ inheritance
Multiple endocrine neoplasia (MEN) is familial endocrine neoplasms with autosomal dominant inheritance
- Due to gene mutations affecting the germline
- Tumors are often bilateral or multifocal
- Hyperplasia may occur in conjunction with neoplasia
MEN 2A involves ____, ____, and ____
MEN 2A involves medullary thyroid carcinoma, pheochromocytoma, and primary hyperparathyroidism
MEN 2B involves ____, ____, ____, ____, and ____
MEN 2B involves medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, GI tract ganglioneuromatosis, and marfanoid habitus
Thin face, big lips, and nodules on the tongue are indicative of ____
Thin face, big lips, and nodules on the tongue are indicative of MEN 2B
MEN 2 involves activation of ____
MEN 2 involves activation of RET proto-oncogene
- RET: cell surface tyrosine kinase receptor
- RET germline poitn mutations are found in the majority of MEN 2A and 2B patients
- Mutations are few and clustered
- Genotype-phenotype correlation
RET is a ____
RET is a cell surface tyrosine kinase receptor
Von Hippel Lindau Disease involves ____, ____, ____, and ____
Von Hippel Lindau Disease involves retinal angiomas, CNS hemangioblastomas, renal cysts / carcinomas, pancreatic cysts, pheochromocytomas
- VZHL gene on chromosome 3 (3 exons, 284 codons)
Pheochromocytoma in Von Hippel Lindau disease involves ___ mutations in the ___ gene
Pheochromocytoma in Von Hippel Lindau disease involves missense mutations in the VHL tumor suppressor gene
- Chromosome 3p25-26
- Encodes a protein regulating hypoxia-induced protein
- Specific mutations associated with particular patterns of tumor formation
Neurofibromatosis-1 is an ____ disorder characterized by ____, ____, ____, and ____
Neurofibromatosis-1 is an autosomal dominant disorder characterized by neurofibromas, cafe au lait spots, axillary and inguinal freckling, and iris hamartomas (Lish nodules)
Some people with NF-1 develop ____
Some people with NF-1 develop catecholamine-secreting tumors
- Solitary benign adrenal pheochromocytoma
- Bilateral adrenal pheochromocytoma
- Peri-adrenal abdominal paraganglioma
Paragangliomas are characterized as ____ or ____ depending on the type of paraganglia of origin
Paragangliomas are characterized as sympathetic or parasympathetic depending on the type of paraganglia of origin
- Sympathetic: arise from chromaffin cells of paraganglia along sympathetic chains in the chest, abdomen, or pelvis
- Parasympathetic: arise from glomera along parasympathetic nerves in the head / neck / upper mediastinum
Parasympathetic paragangliomas are usually ____ and produce ____
Parasympathetic paragangliomas are usually non-functional and produce no or low levels of catecholamines
Paragangliomas usually present as ____
Paragangliomas usually present as slow-growing painless cellular masses
- Many patients are asymptomatic
- Tumor space occupation may cause pain, hearing disturbances, hoarseness, and dysphagia
Familial paragangliomas are ____ disorders with location most commonly in the ____
Familial paragangliomas are autosomal dominant disorders with location most commonly in the abdomen
(second most common location in head / neck)
Familial paragangliomas result from genetic mutations in the ____ genes
Familial paragangliomas result from genetic mutations in the SDH succinate dehydrogenase subunit genes
(SDHB, SDHC, SDHD)
Succinate dehydrogenase is a component of the ____ that ____
Succinate dehydrogenase is a component of the mitochondrial ETC complex II that catalyzes oxidation of succinate to fumarate in the Krebs cycle
Subunits SDHA and SDHB constitute the ____ of succinate dehydrogenase, while subunits SDHC and SDHD ____
Subunits SDHA and SDHB constitute the catalytic core of succinate dehydrogenase, while subunits SDHC and SDHD anchor the complex to the matrix face of the mitochondrial inner membrane
Defects in SDHA cause ___
Defects in SDHA cause neurodegenerative disorders
Mutations in SDHB, SDHC, and SDHD predispose to ____
Mutations in SDHB, SDHC, and SDHD predispose to familial paraganglioma syndromes (PGLI 1, 2, 3, 4)
SDHB mutation carriers develop paraganglioma ___
SDHB mutation carriers develop paraganglioma early
- More likely to develop malignant paragangliomas and additional neoplasms (e.g. renal cell carcinoma)
Patients with sporadic pheochromocytomas / paragangliomas present at a ___ age
Patients with sporadic pheochromocytomas / paragangliomas present at a later age
Headache, palpitations, diaphoresis, HTN, and abdominal pain indicate ____
Headache, palpitations, diaphoresis, HTN, and abdominal pain indicate pheochromocytomas / paragangliomas
____, ____, ____, and ____ increase catecholamine levels
Pheochromocytomas, caffeine, marijuana, and nicotine increase catecholamine levels
Paragangliomas are commonly associated with ____
Paragangliomas are commonly associated with syndromes
(such as due to SDHB mutations)
These are ____
These are pheochromocytomas
Pheochromocytomas is treated with ___ after ___
Pheochromocytomas is treated with surgical resection after preparation with alpha and beta blockade to control HTN and expand volume
____ and ____ blockade is utilized to control BP and prevent intraoperative hypertensive crisis in patients with pheochromocytoma
Combined alpha and blockade is utilized to control BP and prevent intraoperative hypertensive crisis in patients with pheochromocytoma
____ is given first in pharmacological preparation of pheochromocytoma
Phenoxybenzamine (alpha adrenergic blockade) is given first in pharmacological preparation of pheochromocytoma
- NEVER start beta adrenergic blockers before alpha blockers b/c can further elevate BP
High Na+ diet is used in preparation of pheochromocytoma for surgery by ____ and ____
High Na+ diet is used in preparation of pheochromocytoma for surgery by counteracting catecholamine induced volume contraction and orthostasis associated with alpha blockade
(> 5 g Na/day)
