Endo - Pathology (Adrenal)

Question 1

What is the etiology of Cushing syndrome? What are 3 contexts in which this may occur?

Answer 1

Increased cortisol due to a variety of causes: (1) Exogenous corticosteroids (2) Primary adrenal adenoma, hyperplasia, or carcinoma (3) ACTH-secreting pituitary adenoma (Cushing disease); Paraneoplastic ACTH secretion (e.g., small cell lung cancer, bronchial carcinoids)

Question 2

What is the #1 cause of Cushing syndrome? What effects does it have on ACTH levels and the adrenal glands?

Answer 2

Exogenous corticosteroids - #1 causes, results in low ACTH, bilateral adrenal atrophy

Question 3

As causes of Cushing syndrome, what effect do primary adrenal adenoma, hyperplasia, or carcinoma have on ACTH levels and the adrenal glands? Besides Cushing syndrome, how else can primary adrenal adenoma, hyperplasia, or carcinoma present, and what is another name for this?

Answer 3

Results in low ACTH, atrophy of uninvolved adrenal gland; Can also present as primary aldosteronism (Conn syndrome).

Question 4

As causes of Cushing syndrome, what effects do ACTH-secreting pituitary adenoma (Cushing disease) and/or paraneoplastic ACTH secretion (e.g., small cell lung cancer, bronchial carcinoids) have on ACTH levels and the adrenal glands?

Answer 4

Results in increased ACTH, Bilateral adrenal hyperplasia

Question 5

What is responsible for the majority of endogenous cases of Cushing syndrome?

Answer 5

Cushing disease (ACTH-secreting pituitary adenoma) is responsible for majority of endogenous cases of Cushing syndrome

Question 6

What are 10 signs/symptoms associated with Cushing syndrome?

Answer 6

(1) Hypertension (2) Weight gain (3) Moon facies (4) Truncal obesity (5) Buffalo hump (6) Hyperglycemia (insulin resistance) (7) Skin changes (thinning, striae) (8) Osteoporosis (9) Amenorrhea and (10) Immune suppression

Question 7

What are 3 screening tests for Cushing syndrome?

Answer 7

Screening tests include: (1) high free cortisol on 24-hr urinalysis, (2) midnight salivary cortisol, and (3) overnight low-dose dexamethasone suppression test

Question 8

What initial substance can be measured to differentiate causes of Cushing syndrome? What are the clinical suspicions and/or next steps if this measure is low versus high? For any next steps, explain them, including an interpretation of results.

Answer 8

Measure serum ACTH. If low, suspect adrenal tumor. If high, distinguish between Cushing disease and ectopic ACTH secretion with a high-dose (8 mg) dexamethosone suppression test and CRH stimulation test. Ectopic secretion will not decrease with dexamethasone because source is resistant to negative feedback; ectopic secretion will not increase with CRH because pituitary ACTH is suppressed.

Question 9

Draw a diagram depicting the steps taken in the clinical lab to distinguish the cause of Cushing syndrome.

Answer 9

See p. 317 in First Aid 2014 for visual near middle of page

Question 10

What are the 2 types of hypoaldosteronism?

Answer 10

(1) Primary (2) Secondary

Question 11

What causes primary hyperaldosteronism? What are 4 effects of this?

Answer 11

Caused by adrenal hyperplasia or an aldosterone-secreting adrenal adenoma (Conn syndrome), resulting in hypertension, hypokalemia, metabolic acidosis, and LOW plasma renin

Question 12

What are the Na+ levels in primary hyperaldosteronism, and why?

Answer 12

Normal Na+ due to aldosterone escape = no edema due to aldosterone escape mechanism.

Question 13

Is primary hyperaldosteronism bilateral or unilateral?

Answer 13

May be bilateral or unilateral

Question 14

What is the treatment for primary hyperaldosteronism?

Answer 14

Treatment: surgery to remove the tumor and/or spironolactone, a K+-sparing diuretic that acts as an aldosterone antagonist

Question 15

What is the pathophysiology of secondary hyperaldosteronism? What are 4 causes of this?

Answer 15

Renal perception of low intravascular volume results in an overactive renin-angiotensin system. Due to renal artery stenosis, CHF, cirrhosis, or nephrotic syndrome.

Question 16

With what plasma renin levels is secondary hyperaldosteronism associated?

Answer 16

Associated with HIGH plasma renin

Question 17

What is the treatment for secondary hyperaldosteronism?

Answer 17

Treatment: spironolactone

Question 18

What is Addison disease, and what causes it?

Answer 18

Chronic primary adrenal insufficiency due to adrenal atrophy or destruction by disease (e.g., autoimmune, TB, metastasis)

Question 19

Give 3 examples of diseases that can cause Addison disease.

Answer 19

autoimmune, TB, metastasis

Question 20

What 2 substances are deficient in Addison’s disease? What are 4 signs/symptoms that this causes? Where applicable, explain these signs/symptoms.

Answer 20

Deficiency of aldosterone and cortisol, causing hypotension (hyponatremic volume control), hyperkalemia, acidosis, and skin and mucosal hyperpigmentation (due to MSH, a by-product of increased ACTH production from pro-opiomelanocortin (POMC))

Question 21

What characterizes Addison disease? Which parts of the adrenal does it effect?

Answer 21

Characterized by Adrenal Atrophy and Absence of hormone production; Involves All 3 cortical divisions (spares medulla); Think: “Addision = All 3 A’s”

Question 22

How is Addison disease distinguished from secondary adrenal insufficiency?

Answer 22

Distinguish from secondary adrenal insufficiency (low pituitary ACTH production), which has no skin/mucosal hyperpigmentation and no hyperkalemia

Question 23

What is Waterhouse-Friderichsen syndrome, and what causes it? What are 3 conditions with which it is associated?

Answer 23

Acute primary adrenal insufficiency due to adrenal hemorrhage associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock

Question 24

What is the most common tumor of the adrenal medulla in children? What age does it usually affect?

Answer 24

Neuroblastoma; The most common tumor of the adrenal medulla in children, usually < 4 years old

Question 25

What is the embryologic origin of Neuroblastoma?

Answer 25

Originates from neural crest cells

Question 26

Where does Neuroblastoma occur?

Answer 26

Occurs anywhere along sympathetic chain

Question 27

What is the most common presentation of Neuroblastoma? How is it distinguished from Wilms tumor?

Answer 27

Most common presentation is abdominal distension and a firm, irregular mass that can cross the midline (vs. Wilms tumor, which is smooth and unilateral)

Question 28

What substance is high in the urine of Neuroblastoma patients? From where does this substance originate?

Answer 28

Homovanillic acid (HVA), a breakdown product of dopamine, increase in urine

Question 29

What histological marker is positive in Neuroblastoma?

Answer 29

Bombesin (+)

Question 30

Compare Neuroblastoma to Pheochromocytoma in terms of the development of hypertension.

Answer 30

Neuroblastoma less likely to develop hypertension

Question 31

Neuroblastoma is associated with the overexpression of what gene?

Answer 31

Associated with overexpression of N-myc oncogene

Question 32

What can be seen on LM of Neuroblastoma?

Answer 32

LM shows rosettes and classic small, round, blue/purple nuclei

Question 33

What is the most common tumor of the adrenal medulla in adults?

Answer 33

Pheochromocytoma

Question 34

What is the embryologic origin of pheochromocytoma?

Answer 34

Derived from chromaffin cells (arise from neural crest)

Question 35

What is the rule that characterizes pheochromocytoma?

Answer 35

Rule of 10’s: 10% malignant, 10% bilateral, 10% extra-adrenal, 10% calcify, 10% kids

Question 36

What 3 substances do most pheochromocytomas secrete, and what effect can this cause?

Answer 36

Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension

Question 37

What are 3 diseases with which pheochromocytoma is associated?

Answer 37

Associated with von Hippel-Lindau disease, MEN 2A and 2B.

Question 38

Briefly describe the occurrence of symptoms with pheochromocytoma.

Answer 38

Symptoms occur in “spells” - relapse and remit

Question 39

What is the underlying cause of symptoms with pheochromocytoma, and what are 5 examples?

Answer 39

Episodic hyperadrenergic symptoms: (1) Pressure (high BP) (2) Pain (headache) (3) Perspiration (4) Palpitations (tachycardia) (5) Pallor; Think: “5 P’s”

Question 40

What is the major urinary finding of pheochromocytoma? What is its major plasma finding?

Answer 40

Urinary VMA (a breakdown product of norepinephrine and epinephrine) and plasma catecholamines are increased

Question 41

What are the treatments for pheochromocytoma? In which order must they be given, and why?

Answer 41

Irreversible alpha-antagonists (phenoxybenzamine) and beta-blockers followed by tumor resection. Alpha-blockade must be achieved before giving beta-blockers to avoid a hypertensive crisis.