Pathology: Adrenal Glands Flashcards
The healthy adrenal gland is approximately how big ?
2.5-3 cm
What are the two main subdivisions of the Adrenal Gland ?
Cortex
Medulla
What are the three layers of the Cortex ?
Zona Glomerulosa
Zona Fasciculata
Zona Reticulata
What does the Zona Glomerulosa produce ?
Mineralocorticoids (Aldosterone)
What does the Zona Fasciculata produce ?
Glucocorticoids
What does the Zona Reticulata produce ?
Sex hormones
What is Cushing Disease ?
Excess ACTH production in the anterior pituitary that will lead to increased cortisol production
Is Cushing Disease a primary or secondary endocrine dysfunction ?
Secondary
What is Cushing Syndrome ?
Anything that can lead to increased glucocorticoid levels (Cushing Syndrome is Hypercotrisolism and can be exogenous or endogenous.)
( In fact, the Syndrome includes Cushing Disease, which only involves hypercortisolism caused by pituitary hyper production of ACTH)
Who are affected more by Cushing Disease: Men or Women ?
Women
Cushing Disease is caused by adenoma of the pituitary gland leading to increased release of ACTH. Are they micro or macro adenomas ?
Microadenoma.
What is seen in the Adrenal glands of those with Cushing Disease (pituitary ACTH secreting micro adenoma) ?
Varying degrees of Nodular cortical hyperplasia.
What percent of Cushing SYNDROME patients have a ACTH secreting tumor that is NOT found within the adrenal gland ? (ectopic secretion)
10%
Where is the main site of Non-renal ACTH secreting tumor ? (ectopic secretion)
Lung (Small Cell Carcinoma of the Lung)
Other ectopic sites include: Carcinoids, medullary carcinomas of the thyroid, and islet cell tumors
Leads to bilateral cortical hyperplasia of the adrenals
Who is most likely to have an ectopic ACTH producing tumo ?
MEN ! (40-50 yo)
What is the morphological ‘change’ called in the pituitary which produces homogeneous and paler cells in the course of Cushing Syndrome ?
“Crooke Hyaline Change”
What are the two classification of ‘endogenous’ causes of Cushing syndrome ?
ACTH Dependent (Production of Corticosteroids is reliant on ACTH, typically caused by an ACTH secreting adenoma of the pituitary)
ACTH Independent (Tumor of the adrenals which produces Corticosteroids w/o need for ACTH stimulation)
Endogenous: occurs within the axis of the Hypothalamus/Pituitary/Adrenals. (anything outside of this is considered exogenous: drugs, ectopic tumors etc.)
What is the MOST COMMON cause of Cushing Syndrome ?
According to Pathoma and the Cleveland Clinic, it is Exongenous Corticosteroid Drug use. (iatrogenic)
Is Primary pigmented nodular adrenocortical disease malignant ? How can you tell
No, just looks nasty with lipofuscin rich granules
you can tell because most malignancies have a ‘desmoplastic’ look, meaning they have an outer ring that looks blue/ purple due to NEW collagen being placed down to wall off tumor
How large do adrenal glands get in Cushing Syndrome (secondary causes) ?
Usually up to 10-12 g (have been shown to get up to 30 but very unlikely)
What does the adrenal cortex often look like when examined in a patient with cushing syndrome ?
Diffusely thickened and variably nodular
How does the zona reticularis look with Cushing Syndrome ?
LIPID POOR
Cushings often shows compact eosinophilic cells surrounded by an outer zone of what kind of cells ?
vacuolated lipid rich cells
Primary adrenocortical adenomas
are more prevalent in which demographic ?
More common in women in their 30s to 50s
What color are primary adrenocortical adenomas ?
yellow
Do primary adrenocortical adenomas have a capsule ?
Yes !! Differentiate between them and carcinoma
How much Do primary adrenocortical adenomas weigh ?
Less than 30 g
primary adrenocortical adenomas resemble cells from which cortex ‘zone’ ?
Zone Fasciculata
Do adrenocortical carcinomas have a capsule ?
Nope !
How much do adrenocortical carcinomas weigh ?
200-300 g!!
Where does the weight gain seen in Cushings distribute ?
Trunk , Back (buffalo hump) and Face (moon facies)
Are patients with Cushings hypo or hypertensive ?
Hyper
Primary Hyperaldosteronism is considered Conn Syndrome when ….
It involves a primary adenoma that secretes Aldosterone
What is the Most common manifestation of Primary Hyperaldosteronism ?
HTN
What is the most common cause of Primary Hyperaldosteronism ?
Aldosterone-producing adenoma (Conn Syndrome)
On what side are Aldosterone-producing adenomas most prevalent ?
Left (still occur on the right)
Who is most at risk for getting a Aldosterone-producing adenoma ?
Women in 30-40s
What color are Aldosterone-producing adenomas ?
YELLOW
What kinds of cells compose the majority of Aldosterone-producing adenomas
lipid-laden cortical cells (LOTS OF FAT)
Typically uniform in size and shape.
What are spironolactone bodies ?
Characteristic finding in Aldosterone-producing adenomas
Eosinophilic, laminated cytoplasmic inclusions
Following treatment with spironolactone (for HTN but unknowing of underlying disease)
Resembles a psamomma body.
One cause of Primary Hyperaldosteronism is Bilateral idiopathic hyperplasia. What kind of hyperplasia is seen in this ?
Wedge shaped towards the middle.
What is the most common form of Adrenogenital Neoplasm ?
Adrenogenital CARCINOMA
Congenital adrenal hyperplasia (CAH) is a autosomal-recessive, inherited metabolic defect in which enzyme ?
21-Hydroxylase Deficiency
What will be absent in this disorder ?
CORTISOL and ALDOSTERONE
Is Congenital adrenal hyperplasia (CAH) a primary or secondary hypoadrenal disease ?
PRIMARY
Primary acute adrenocortical insufficiency is also known as …
Adrenal Crisis
Primary chronic adrenocortical insufficiency is also known as
Addison Disease.
Who typically gets Primary acute adrenocortical insufficiency
Patients who are maintained of corticosteroid therapy. When the drugs are withdrawn their cortiol levels plummet.
What is the disease of newborns who suffer adrenal infarction following an infection with N. meningitides that leads to sepsis, hypotension and DIC called ?
Waterhouse-Friderichsen Syndrome
What kind of disease is Waterhouse-Friderichsen Syndrome classified as ?
Primary acute adrenocortical insufficiency
What is seen on microscopy of adrenal with Waterhouse-Friderichsen Syndrome
adrenals were grossly hemorrhagic and shrunken; microscopically, little residual cortical architecture is discernible.
Fibrin deposition.
What is the primary cause of Addison disease ?
Progressive destruction of the adrenal cortex
Do not appear until at least 90% of the adrenal cortex has been compromised
What are the four major causes of cortex destruction in Addisons disease ?
Autoimmune adrenalitis
Tuberculosis
AIDS
Metastatic cancers
Autoimmune polyendocrine syndrome type 2 (APS2) which can cause Addisons, presents as ..
a combination of adrenal insufficiency and autoimmune thyroiditis or type 1 diabetes
Addison Disease due to Primary autoimmune adrenalitis presents as irregularly shrunken glands Scattered residual cortical cells in connective tissue
and infiltrate with what kind of cells in the cortex (possible medulla) ?
Lymphocytes.
What occurs to the architecture of the Adrenals with Tuberculous and fungal disease (leading to Addisons) ?
COMPLETE DESTRUCTION
What occurs to the architecture of the Adrenals with Metastatic carcinoma (leading to Addisons ) ?
obscures it
Secondary Adrenocortical Insufficiency is due to a problem in the hypothalamus or pituitary. How will this differ from primary (addisons ) ?
LOW ACTH levels (high in addisons) No hyperpigmentation (lots of hyper pigmentation in addisons)
What occurs to the overall size of the adrenals in Secondary Adrenocortical Insufficiency ?
Decrease in size ! (No stimulation) but retain their color
Secondary Adrenocortical Insufficiency causes the cortex to be reduced to a ‘ribbon size’. Which cells make up the majority of this ribbon ?
zona glomerulosa
Is the medulla affected in Secondary Adrenocortical Insufficiency ?
Nope….
What kind of neoplasm is more prominent in the adrenals of children ?
Carcinoma
What is the defect associated wit the adrenal cancer caused by Li-Fraumeni syndrome
Li-Fraumeni syndrome is caused by Germline p53 mutations.
Beckwith-Wiedemann syndrome is associated with adrenal neoplasm and is an Imprinting disorder that is characterized by what finding ?
Large tongue
how are most Adrenocortical adenomas found ?
Incidentally..
What size are most Adrenocortical adenomas ?
2.5 cm in diameter
Describe the morphological presentation of Adrenocortical neoplasms cells ?
Composed of cells similar to normal adrenal cortex
Nuclei tend to be small
Some degree of pleomorphism may be encountered
Cytoplasm ranges from eosinophilic to vacuolated.
Virulism is associated with which kind of Adrenocortical neoplasms ?
Carcinoma
What size are most Adrenocortical Carcinomas ?
Many exceed 20 cm in diameter
WEIGHT: 200-300 g. (HUGE)
What is a common site from which metastatic Adrenocortical Carcinomas migrate ?
THE LUNGS (bronchogenic)
Due to their strong tendency to invade local tissue (Adrenal vein, vena cava, and lymphatics) and spread hematogenously (lungs, bone) what is the overall survival for patients with Adrenocortical Carcinomas .
2 years.
Unusual benign lesions Composed of mature fat and hematopoietic cells seen in the Adrenal gland…
Adrenal myelolipoma
What kind of cells make up the Adrenal Medulla ?
Composed of specialized neural crest (neuroendocrine) cells (Chromaffin and Supporting cells)
What do chromaffin cells produce ?
catecholamines. (epi, nor epi)
Pheochromocytomas are composed almost entirely of what cells ?
chromaffin cells
What are the rules of 10 ?
10% of pheochromocytomas are extra-adrenal
10% of sporadic adrenal pheochromocytomas are bilateral (Majority are unilateral)
10% of adrenal pheochromocytomas are biologically malignant (most are benign)
10% of adrenal pheochromocytomas are not associated with hypertension (HEAVY HYPERTENSION IN MOST)
Although the size of Pheo’s varies, what is the average size ?
100 g (more than Adenoma but less than carcinoma)
Are Pheos’ well demarcated ?
yess
are pheos richly supplied by blood ?
yupp
What color are Pheo’s ?
Smaller pheochromocytomas–yellow-tan
Larger lesions–hemorrhagic, necrotic, and cystic
What stain will turn Pheo tissue brown ?
Potassium dichromate solution
causes oxidation of catecholamines
What shape will chromaffin cells take in Pheo ?
Polygonal to spindle-shaped
The nuclei in chromaffin cells of Pheo’s will have what kind of chromatin appearance ?
Stippled “salt and pepper” chromatin
Zellbalin effect in pheo’s
fibrous network clumping it into balls
What will lead a physician to believe a pheo is malignant ?
Based exclusively on the presence of metastases
but also….
Numbers of mitoses, confluent tumor necrosis, and spindle cell morphology
