Adrenals

Question 1

….is most common cause of endogenous hypercortisolism, represents…%.it is usually a…..(size)

Answer 1

Primary hypothalamic pituitary disease (Cushing’s disease)
70
Microadenoma

Question 2

Describe demographics of Cushing’s disesae

Answer 2

More in women
20-30 yrs age

Question 3

The pituitary picture in case of exogeneous or1ry adrenal hypercortisolism is……

Answer 3

Crooke hyaline change (affecting ACTH-producing cells)

Question 4

List morphologic variants of adrenals in hypercortisolism & cause of each

Answer 4

1. Cortical atrophy in exogenous glucocorticoids
2. Diffuse hyperplasia in ACTH-dependent cases
3. Macro or micronodular hyperplasia in primary adrenal hyperplasia
4. Functional adrenocortical adenoma (yellow encapsulated tumor less than 30 grams with zona fasciculata differentiation), or carcinoma

Question 5

Causes of 2ry hyperaldosteronism

Answer 5

Dec renal perfusion (arteriolar nephrocalcinosis, renal artery stenosis)
Arterial hypovolemia & edema (congestive HF, cirrhosis, nephrotic syndrome)
Pregnancy

Question 6

List causes of primary hyperaldosteronism

Answer 6

1. Bilateral idiopathic hyperaldosteronism chch by bilateral nodular hyperplasia of the adrenal glands. Most common (60%)
2. Adrenocortical neoplasm, aldosterone-secreting adenoma or an adrenocortical carcinoma
3. Familiar hyperaldosteronism

Question 7

Describe G&M picture of aldosterone-producing adenoma

Answer 7

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

Question 8

C/P of aldosterone-producing adenoma

Answer 8

1. HTN with long-term effect of CVS
2. Hypokalemia with neuromuscular manifestations

Question 9

Mode of inheritance of CAH

Answer 9

AR

Question 10

Deficient enzyme in CAH is…..

Answer 10

21-hydroxylase

Question 11

Morphology of CAH

Answer 11

Adrenals are bilterally hyperplastic, sometimes expanding 10 to 15 times their normal weight. Hyperplasia of ACTH producing cells in ant pituitary.

Question 12

Causes of adrenal crisis

Answer 12

1. Severe hemorrhage which occurs due to severe sepsis as meningitis (Waterhouse-Friderichsen syndrome), burns, hemorrhagic diseases & during pregnancy.
2. Billateral removal of adrenal cortex
3. Individuals with chronic adrenocortical insufficiency can develop acute crisis when subjected to stress exceeding their physiological reserve.
4. Sudden withdrawal of long term corticosteroid therapy.

Question 13

C/P of adrenal crisis

Answer 13

1. Shock w/ low BP
2. High fever, pain in abdomen with NVD
3. Usually fatal

Question 14

Causes of chronic adrenal insufficiency & identify most common one

Answer 14

1. Autoimmune adrenalitis (most common)
2. Infections
3. Metaplastic neoplasms

Question 15

Autoimmune adrenalitis is associated with………….

Answer 15

Hashimoto disease, pernicious anemia & type I DM

Question 16

In 2ry hypoadrenalism adrenals are……..

Answer 16

Small & flattened

Question 17

C/P of adrenal insufficiency

Answer 17

1. Progressive weakness & easy fatigability
2. GIT disturbance (NVDA)
3. No hyperpigmentation is noted in 2ry but it is present in 1ry
4. Dec aldosterone activity in 1ry leading to hyperkalemia, hponatremia, volume depletion, hypotension.

Question 18

G&M features of adrenal cortical adenoma

Answer 18

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

Question 19

G&M features of adrenal cortical carcinoma

Answer 19

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.

Question 20

Describe spread of adrenal cortical carcinoma

Answer 20

1. Adrenal cancers tend to invade renal vein & vena cava
2. Metastases to regional & peri-aortic nodes are common
3. Distant hematogenous spread to lung & other viscera, bone spread is rare.
4. Median survival 2 yrs

Question 21

What is the “rule of 10”?

Answer 21

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

Question 22

What is the role of genetic factors in pheochromocytoma?

Answer 22

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).

Question 23

G&M picture of pheochromoctoma

Answer 23

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.

Question 24

Definitive diagnosis of malignancy in pheochromocytoma is based on……

Answer 24

Presence of metastasis

Question 25

C/P of pheochromocytoma

Answer 25

1. HTN with risk of MI, HF, renal injury, CVA
2. Manifestations related to secretion of other hormones as ACTH & somatostatin
3. Free CAs, VMA or metanephrine inc in urine

Question 26

Familial neuroblastoma MOI is…..

Answer 26

AD

Question 27

Describe morphology of neuroblastoma

Answer 27

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

Question 28

Mention factors associated with favorable diagnosis in neuroblastoma

Answer 28

Younger ptient (less than 18), morphology (schwann stroma & gangliocytic differentiation)

Question 29

Genetic abnormality of neuroblastoma is…….

Answer 29

NMYC oncogene amplification

Question 30

Mention an important diagnostic feature of neuroblastoma

Answer 30

90% produce CAs leading to high urinary levels of VMA & HVA

Question 31

Mention genetic abnormality & manifestations of MEN1

Answer 31

-Inactivation of MEN1 tumor suppressor gene
-3P: primary hyperparathyroidism, tumors of endocrine pancreas & pituitary adenoma (prolactin-secreting macroadenoma)

Question 32

Mention genetic abnormality & manifestations of MEN2

Answer 32

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.