Adrenals Flashcards
….is most common cause of endogenous hypercortisolism, represents…%.it is usually a…..(size)
Primary hypothalamic pituitary disease (Cushing’s disease)
70
Microadenoma
Describe demographics of Cushing’s disesae
More in women
20-30 yrs age
The pituitary picture in case of exogeneous or1ry adrenal hypercortisolism is……
Crooke hyaline change (affecting ACTH-producing cells)
List morphologic variants of adrenals in hypercortisolism & cause of each
- Cortical atrophy in exogenous glucocorticoids
- Diffuse hyperplasia in ACTH-dependent cases
- Macro or micronodular hyperplasia in primary adrenal hyperplasia
- Functional adrenocortical adenoma (yellow encapsulated tumor less than 30 grams with zona fasciculata differentiation), or carcinoma
Causes of 2ry hyperaldosteronism
Dec renal perfusion (arteriolar nephrocalcinosis, renal artery stenosis)
Arterial hypovolemia & edema (congestive HF, cirrhosis, nephrotic syndrome)
Pregnancy
List causes of primary hyperaldosteronism
- Bilateral idiopathic hyperaldosteronism chch by bilateral nodular hyperplasia of the adrenal glands. Most common (60%)
- Adrenocortical neoplasm, aldosterone-secreting adenoma or an adrenocortical carcinoma
- Familiar hyperaldosteronism
Describe G&M picture of aldosterone-producing adenoma
G: almost always solitary, small, well-circumscribed, bright yellow cut section, they do not usually suppress ACTH secretion; therefore adjacent cortex & C/L gland are not atrophic.
M: neoplastic cells are vacuolated bec of the presence of intra-cytoplasmic lipid & chch contain eosinophilic, laminated cytoplasmic inclusions, known as spironolactone bodies. Bilateral idiopathic hyperplasia is marked by diffuse or focal hyperplasia of cells resembling those of normal zona glomerulosa
C/P of aldosterone-producing adenoma
- HTN with long-term effect of CVS
- Hypokalemia with neuromuscular manifestations
Mode of inheritance of CAH
AR
Deficient enzyme in CAH is…..
21-hydroxylase
Morphology of CAH
Adrenals are bilterally hyperplastic, sometimes expanding 10 to 15 times their normal weight. Hyperplasia of ACTH producing cells in ant pituitary.
Causes of adrenal crisis
- Severe hemorrhage which occurs due to severe sepsis as meningitis (Waterhouse-Friderichsen syndrome), burns, hemorrhagic diseases & during pregnancy.
- Billateral removal of adrenal cortex
- Individuals with chronic adrenocortical insufficiency can develop acute crisis when subjected to stress exceeding their physiological reserve.
- Sudden withdrawal of long term corticosteroid therapy.
C/P of adrenal crisis
- Shock w/ low BP
- High fever, pain in abdomen with NVD
- Usually fatal
Causes of chronic adrenal insufficiency & identify most common one
- Autoimmune adrenalitis (most common)
- Infections
- Metaplastic neoplasms
Autoimmune adrenalitis is associated with………….
Hashimoto disease, pernicious anemia & type I DM
In 2ry hypoadrenalism adrenals are……..
Small & flattened
C/P of adrenal insufficiency
- Progressive weakness & easy fatigability
- GIT disturbance (NVDA)
- No hyperpigmentation is noted in 2ry but it is present in 1ry
- Dec aldosterone activity in 1ry leading to hyperkalemia, hponatremia, volume depletion, hypotension.
G&M features of adrenal cortical adenoma
G: small, 1-2 cm, yellow to yellow brown cut surface
M:
1. Composed of cells similar to adrenal cortex
2. Nuclei tend to be small, although some degree of pleomorphism may be encountered (endocrine atypia)
3. Cytoplasm of neoplastic cells ranges from eosinophilic to vacuolated, depending on lipid content, mitotic activity is usually inconspicuous
G&M features of adrenal cortical carcinoma
G: large, invasive with variegated cut surface and areas of hemorrhage, necrosis & cystic degeneration
M: may be well-differentiated resembling cortical adenoma or undifferentiated with bizzare cells & high mitotic activity difficult to distinguish from metastasis.
Describe spread of adrenal cortical carcinoma
- Adrenal cancers tend to invade renal vein & vena cava
- Metastases to regional & peri-aortic nodes are common
- Distant hematogenous spread to lung & other viscera, bone spread is rare.
- Median survival 2 yrs
What is the “rule of 10”?
In Pheochromocytoma:
10% are extra-adrenal occurring organ of Zuckerkandl & carotid body where they are called paraganglioma
10% are bilateral
10% are malignant, frank malignancy is more common in extra-adrenal sites
One “traditional” 10% rule has since been modified pertains to familial cases
What is the role of genetic factors in pheochromocytoma?
25% of individuals with pheochromocytoma & paraganglioma harbour germline mutations in one of 6 genes
RET (MEN1), NF-1, VHL, genes encoding succinate dehydrogenase subunits (SDHB, SDHC, SDHD).
G&M picture of pheochromoctoma
G: ranges from small, yellow-tan circumscribed to large hemorrhagic cystic weighing several Kgs
M: -There are polygonal cells & spindle shaped cells arranged in small nests or Zenballen separated by vascular network. Cytoplasm is finely granular, nuclei are pleomorphic.
Definitive diagnosis of malignancy in pheochromocytoma is based on……
Presence of metastasis
C/P of pheochromocytoma
- HTN with risk of MI, HF, renal injury, CVA
- Manifestations related to secretion of other hormones as ACTH & somatostatin
- Free CAs, VMA or metanephrine inc in urine
Familial neuroblastoma MOI is…..
AD
Describe morphology of neuroblastoma
G: large, fleshy, greyish white mass infiltrating surrounding tissues with areas of hemorrhage, necrosis & calcification
M:
1. Classic neuroblastomas are composed of small, primitive-appearing cells with dark nuclei, scant cytoplasm & poorly defined cell borders growing in solid sheets or rosettes (Homer-Wright), mitotic activity, nuclear breakdown (karyorrhexis) & pleomorphism may be prominent
2. Some neoplasms show maturation either spontaneous or therapy induced. Larger cells have more abundant cytoplasm, vesicular nucleus & prominent nucleolus may be admixed with primitive neuroblasts (ganglioneuroblastoma)
3. Maturation of neuroblasts into ganglion cells is accompanied with appearance of Schwann cells
Mention factors associated with favorable diagnosis in neuroblastoma
Younger ptient (less than 18), morphology (schwann stroma & gangliocytic differentiation)
Genetic abnormality of neuroblastoma is…….
NMYC oncogene amplification
Mention an important diagnostic feature of neuroblastoma
90% produce CAs leading to high urinary levels of VMA & HVA
Mention genetic abnormality & manifestations of MEN1
-Inactivation of MEN1 tumor suppressor gene
-3P: primary hyperparathyroidism, tumors of endocrine pancreas & pituitary adenoma (prolactin-secreting macroadenoma)
Mention genetic abnormality & manifestations of MEN2
RET proto-oncogene activating mutations
2A: meduallary carcinoma of thyroid, primary hyperparathyroidism & pheochromocytoma
2B: in thyroid & medulla similar to 2A BUT NO 1ry hyperparathyroidism & presence if ganglioneuromas of mucosal site & marfanoid habitus.
