179/180 Adrenal Flashcards
What are the three zones of the adrenal cortex (outside to inside)?
(outside) zona glomerulosa, zona fasciculata, zona reticularis
Cells in the zona glomerulosa…
produce:
look like on histology:
Cells in the zona glomerulosa…
produce: mineralocorticoids
look like on histology: clustered, high nuclear to cytoplasm ratio, pink cytoplasm, finely vaculated
Cells in the zona fasciculata…
produce:
look like on histology:
Cells in the zona fasciculata…
produce: glucocorticoids
look like on histology: arranged in columns perpendicular to capsule
Cells in the zona reticularis…
produce:
look like on histology:
Cells in the zona reticularis…
produce: androgens
look like on histology: haphazardly arranged, appear smaller, granular and pink cytoplasm
What are adrenal cortical heterotopia and accessory adrenal glands?
normal adrenal cortical in abnormal places
What is adrenal cortical hyperplasia? What are the three patterns?
bilateral increase in adrenal cortical mass due to documented endocrine abnormality
three patterns: diffuse (congenital adrenal hyperplasia, cushing syndrome), micronodular (cushing syndrome), and macronodular (rare)
What type of neoplasm is a unilateral solitary mass that is bright yellow in color and usually > 2 cm?
adrenal cortical adenoma
What are the microscopic pathological findings of adrenal cortical adenoma?
mixed growth pattern, cells with vesicular/vacuolated clear cytoplasm, can have nuclear pleomorphism
do not typically see mitoses and necrosis
Can you determine if a tumor is functional or non-functional from morphology?
generally no, it is not possible to tell based on morphology alone
In an adult patient, > ______ grams and > _______ cm favors an adrenal cortical carcinoma.
In a pediatric patient, > ______ grams and > _______ cm favors an adrenal cortical carcinoma.
In an adult patient, > 100 grams and > 6.5 cm favors an adrenal cortical carcinoma.
In a pediatric patient, > 400 grams and > 10.5 cm favors an adrenal cortical carcinoma.
What type of adrenal neoplasm is large and bulky with a red-brown to yellow color, hemorrhage, and necrosis?
adrenal cortical carcinoma
What is the microscopic pathology of adrenal cortical carcinoma? What criteria are used to determine malignancy?
highly cellular tumors in variable patterns, increased nuclear to cytoplasmic ratio, clear to pink cytoplasm, mitotic activity and atypical mitoses present
use Weiss criteria to determine malignant potential
An example of primary acute adrenal insufficiency is ___________, which is characterized by _____________.
An example of primary acute adrenal insufficiency is Waterhouse-Friderichsen Syndrome, which is characterized by hypotension, shock, and purpura of skin following an overwhelming bacterial infection (ex. Neisseria meningitidis).
What type of adrenal insufficiency is associated with neisseria meningitidis infection?
primary (acute) insufficiency –> Waterhouse-Friderichsen Syndrome
An example of primary chronic adrenocortical insufficiency is ____________, which is characterized by ______________.
An example of primary chronic adrenocortical insufficiency is Autoimmune adrenalitis like Addison’s disease, which is characterized by autoantibodies against cortical cells.
An example of secondary adrenal insufficiency is ____________ that often arises from ______________ (3).
An example of secondary adrenal insufficiency is metastatic carcinoma that often arises from breast, lung, kidney.
What is the main cell type of the mature adrenal medulla? What do they produce? What do they look like?
pheochromocytes (aka chromaffin cells)
produces catecholamines
blue cytoplasm, large, salt and pepper chromatin, prominent nucleoli
What is a pheochromocytoma?
catecholamine secreting tumor arising from adrenal medulla composed of neoplastic pheochromocytes (chromaffin cells)
What is the difference between a paraganglioma and a pheochromocytoma?
paragangliomas are catecholamine secreting tumors that are outside of the adrenal medulla (histologically the same as pheochromocytoma)
What are the 10% rules (5) that characterize pheochromocytomas?
10% bilateral
10% paragangliomas
10% in children
10% are malignant
10% are associated with familial syndromes
What is the gross and microscopic pathology of pheochromocytomas?
gross: solitary, unilateral masses, well-circumscribed, gray/white mass, large
microscopic: nested (zellballen) growth pattern, richly vascular, blue to purple cytoplasm, “salt and pepper” nuclei, rare mitoses
What is a ganglioneuroma? What is their pathology?
benign tumor of neural crest derivation composed of mature ganglion cells and schwannian stroma
gross: solitary, unilateral mass, may be calcified, well-circumscribed, firm, tan-yellow, large
microscopic: mature schwannian stroma and interspersed ganglion cells
What is a neuroblastoma? What metabolites are detectable in urine?
malignant tumor of neural crest derived neuroblastic cells
can detect catecholamine metabolites (VMA, HVA) in urine
What is the pathology of neuroblastomas?
gross: large, firm, gray/white, hemorrhage and necrosis, cystic changes
microscopic: small cells with hyperchromatic nuclei, very little cytoplasm, high mitotic rate, abundant nuclear debris, “small round blue tumor, neuropil in stroma, homer-wright pseudo-rosettes
What is this?
pheochromocytoma
- grossly pink, red, or gray*
- microscopically form nests (zellballen)*
What is this?
neuroblastoma
homer-wright pseudo-rosettes, little blue cells
What is the relationship between the adrenal medulla and the autonomic nervous system?
parts of the adrenal medulla (derived from neuroectoderm) produce epinephrine that is released into the blood stream
What are paraganglia?
sympathetic pre-ganglionic nerve fibers that terminate in paravertebral and prevertebral nerve ganglia
When do paraganglia arise in the embryo? What are their major cellular components?
start forming after 2 months of gestation
contain chromaffin cells (neuroendocrine)
What are chromaffin bodies?
chromaffin masses arising along the course of the aorta made up of chromaffin cells and connective tissues
What chromaffin marker is used to assess for adrenal medulla or ganglia tumors?
chromogranins
Catecholamine synthesis starts with _________ that becomes oxidized to ___________ via ___________.
Catecholamine synthesis starts with tyrosine that becomes oxidized to L-DOPA via tyrosine hydroxylase.
How does norepinephrine become epinephrine?
an enzyme PNMT methylates it (with an S-adenosyl methionine cofactor that donates a methyl group)
What are the systemic effects of epinephrine and norepinephrine?
epinephrine: increased systemic BP, increased HR, decreased gut motility, circulation diverted to limb muscles, bronchodilation, mydriasis, hyperglycemia
norepinephrine: increased systolic and diastolic BP, decreased HR, hyperglycemia
What are the two major types of adrenal medulla tumors?
in the adrenal medulla proper –> pheochromocytoma
in the extra adrenal sympathetic ganglia –> paragangliomas
What are the major symptoms of MEN 2A?
medullary thyroid carcinoma (most common)
primary hyperparathyroidism
pheochromocytoma
What are the major symptoms of MEN 2B?
medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas, GI tract ganglioneuromatosis, marfanoid habitus
What is the genetic basis of MEN 2?
activation of the RET proto-oncogene (a cell surface tyrosine kinase receptor)
What types of tumors are associated with von hippel lindau disease?
retinal angiomas, CNS hemangioblastomas, renal cysts, renal cell carcinomas, pancreatic cysts, pheochromocytomas
Where is the von hippel lindau gene located? What kind of gene is it?
chromosome 3
tumor suppressor gene that encodes a protein regulating hypoxia-induced proteins
What features are associated with neurofibromatosis type 1?
neurofibromas, cafe au lait spots, axillary/inguinal freckling, iris hamartomas, rarely pheochromocytomas
Where are most paragangliomas located?
abdomen
What genetic syndromes are associated with paragangliomas?
mutations in succinate dehydrogenase gene (SDHB, C, and D)
What are the symptoms of pheochromocytomas?
headaches, palpitations, diaphoresis, hypertension, abdominal pain, insulin resistance
could also be asymptomatic
What are tests available for pheochromocytomas?
24-hour urine collection for fractionated catecholamines
24-hour urine collection for fractionated metanephrines
plasma free metanephrines (negative predicatve value)
What is the treatment for pheochromocytomas?
surgical resection (usually laproscopic)
pre-surgical prep with alpha and beta blockade to prevent hypertensive crisis
What are the necessary pre-op steps for pheochromocytoma management?
alpha (given first) and beta blockade to control blood pressure and prevent intraoperative hypertension
also start a high sodium diet
Why does it matter if beta or alpha blockers are given first in patients with pheochromocytoma before surgery?
beta blockers lead to blockade of vasodilatory peripheral beta-adrenergic receptors (which further increases blood pressure)
alpha-adrenergic receptor stimulation must be given first to normalize blood pressure and expand blood volume
A 21 yo woman presents with renal masses, adrenal masses, and brain hemangioblastomas. What is her most likely diagnosis?
a) pheochromocytoma
b) MEN 2B
c) paraganglioma
d) Von-Hippel Lindau
e) neurofibromatosis 1
d) Von-Hippel Lindau
the combination of renal masses, adrenal masses, and hemangiomas is consistent with VHL
A 55 yo man has an extra adrenal pheochromocytoma. What is the most likely abnormal hormone level in this patient?
a) Epinephrine
b) DOPA
c) Norepinephrine
d) Calcitonin
e) Parathyroid hormone
c) Norepinephrine
paragangliomas usually secrete norepinephrine; the enzyme phenylethanolamine N-methyltransferase (PNMT) is present only in the adrenal medulla, not the paraganglia
A 15 yo boy presents with MEN2B. What of the findings below are not consistent with MEN2B?
a) hyperparathyroidism
b) marfanoid habitus
c) medullary thyroid cancer
d) mucosal neuromas
e) digestive problems
a) hyperparathyroidism
hyperparathyroidism is consistent with MEN2B
