Fa: Endocrine - Pathology - 1

Front 1

What can cause Cushing syndrome?

Back 1

Excess cortisol due to a variety of causes:
- Exogenous steroids
- Primary adrenal adenoma, hyperplasia, or carcinoma
- ACTH-secreting pituitary adenoma

Front 2

What is the number one cause of Cushing syndrome? Characteristics?

Back 2

Exogenous corticosteroids: results in ↓ ACTH and bilateral adrenal atrophy

Front 3

What causes of Cushing syndrome result in ↓ ACTH? Effect on adrenals?

Back 3

- Exogenous steroids - bilateral adrenal atrophy
- Primary adrenal adenoma, hyperplasia, or carcinoma - atrophy of uninvolved adrenal gland

Front 4

What can primary adrenal adenoma / hyperplasia / carcinoma produce?

Back 4

- ↑ Cortisol (= Cushing Syndrome)
OR
- ↑ Aldosterone (1° Aldosteronism = Conn Syndrome)

Front 5

What is Conn Syndrome?

Back 5

1° Aldosteronism (due to primary adrenal adenoma, hyperplasia, or carcinoma)

Front 6

What causes of Cushing syndrome result in ↑ ACTH? Effect on adrenals?

Back 6

ACTH-secreting pituitary adenoma (Cushing disease)
- Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids
- Bilateral adrenal hyperplasia

Front 7

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

Back 7

Cushing Disease
- ACTH-secreting pituitary adenoma
- Paraneoplastic ACTH secretion: small cell lung cancer, bronchial carcinoids

Front 8

What are the findings associated with Cushing Syndrome?

Back 8

- Hypertension
- Weight gain
- Moon facies
- Truncal obesity
- Buffalo hump
- Hyperglycemia (insulin resistance)
- Skin changes (thinning, striae)
- Osteoporosis
- Amenorrhea
- Immune suppression

Front 9

How do you screen for Cushing Syndrome?

Back 9

** Measure serum ACTH **

You can also evaluate:
- ↑ Free cortisol on 24-hr urinalysis
- Midnight salivary cortisol
- Overnight low-dose dexamethasone suppression test (measure serum ACTH)

Front 10

What should you suspect / do if a patient you suspect of having Cushing Syndrome has a low ACTH (<5 pg/mL)?

Back 10

Suspect ACTH-independent Cushing Syndrome (primary adrenal adenoma, hyperplasia, or carcinoma)

* Order MRI to confirm adrenal tumor

Front 11

What should you suspect / do if a patient you suspect of having Cushing Syndrome has a high ACTH (>20 pg/mL)?

Back 11

Suspect ACTH-dependent Cushing Syndrome

* Order high-dose dexamethasone suppression test
* Order CRH stimulation test

Front 12

What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and adequate suppression via high-dose dexamethasone suppression test?

Back 12

Cushing Disease (ACTH-secreting pituitary adenoma)

Front 13

What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and no suppression via high-dose dexamethasone suppression test?

Back 13

Ectopic ACTH secretion (paraneoplastic syndrome: small cell lung cancer or bronchial carcinoids)

- Ectopic secretion will not decrease with dexamethasone because the source is resistant to negative feedback

Front 14

What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and after after a CRH stimulation test there was ↑ ACTH and cortisol?

Back 14

Cushing Disease (ACTH-secreting pituitary adenoma)

Front 15

What diagnosis does a patient you suspect of having Cushing Syndrome, with an elevated ACTH, and after after a CRH stimulation test there was no increase in ACTH and cortisol?

Back 15

Ectopic ACTH secretion

- Ectopic secretion will not increase with CRH because pituitary ACTH is suppressed

Front 16

What are the causes of primary hyperaldosteronism?

Back 16

- Adrenal hyperplasia
- Aldosterone secreting adrenal adenoma (Conn syndrome)

(May be unilateral or bilateral)

Front 17

What are the consequences of adrenal hyperplasia or aldosterone-secreting adrenal adenoma?

Back 17

Primary Hyperaldosteronism:
- Hypertension
- Hypokalemia
- Metabolic alkalosis
- Low plasma renin
- Normal Na+ due to aldosterone escape → no edema

Front 18

How do you treat primary hyperaldosteronism?

Back 18

Surgery to remove the tumor and/or spironolactone (K+ sparing diuretic that acts as an aldosterone antagonist)

Front 19

What are the causes of secondary hyperaldosteronism?

Back 19

- Renal artery stenosis
- Congestive Heart Failure
- Cirrhosis
- Nephrotic Syndrome

Front 20

What are the consequences of renal artery stenosis, CHF, cirrhosis, or nephrotic syndrome?

Back 20

Secondary Hyperaldosteronism
- Renal perception of low intravascular volume → over-active renin-angiotensin system
- Associated with high plasma renin

Front 21

How do you treat secondary hyperaldosteronism?

Back 21

Spironolactone (K+ sparing diuretic that acts as an aldosterone antagonist)

Front 22

What form of hyperaldosteronism is associated with a high plasma renin?

Back 22

Secondary Hyperaldosteronism

- In primary, there is negative feedback to decrease renin
- In secondary, the high renin is what is causing the high aldosterone

Front 23

What are the causes of primary adrenal insufficiency?

Back 23

Addison Disease - CHRONIC process
- Atrophy of adrenals
- Destruction by disease: auto-immune, TB, metastasis

Waterhouse-Friderichsen Syndrome - ACUTE process
- Adrenal hemorrhage associated with Neisseria meningitidis, septicemia, DIC, and endotoxic shock

Front 24

What are the implications of Addison Disease?

Back 24

- Deficiency of aldosterone and cortisol
- Hypotension (hyponatremic volume contraction)
- Hyperkalemia
- Acidosis
- Skin and mucosal hyperpigmentation

Front 25

What causes the skin hyperpigmentation in Addison Disease?

Back 25

MSH (melanocyte stimulating hormone): by-product of ↑ ACTH production from pro-opiomelanocortin (POMC)

Front 26

How is Addison Disease characterized?

Back 26

- Adrenal Atrophy
- Absence of hormone production, involving all three cortical divisions (but spares medulla)

Front 27

How do you distinguish primary adrenal insufficiency from secondary?

Back 27

Secondary adrenal insufficiency would have:
- ↓ Pituitary ACTH production
- No skin/mucosal hyperpigmentation
- No hyperkalemia

Front 28

What are the electrolyte and acid/base balance changes in primary adrenal insufficiency?

Back 28

- Hyponatremia
- Hyperkalemia
- Acidosis

Front 29

What is the name of the syndrome causing ACUTE 1° adrenal insufficiency? Cause?

Back 29

Waterhouse-Friderichsen Syndrome
- Adrenal hemorrhage associated with Neisseria meningitidis septicemia, DIC, and endotoxic shock

Front 30

What is the most common tumor of the adrenal medulla in children? When specifically?

Back 30

Neuroblastoma
- Usually <4 years old

Front 31

What is the origin of a neuroblastoma?

Back 31

Neural crest cells

Front 32

Where can a neuroblastoma appear?

Back 32

Occurs anywhere along the sympathetic chain

Front 33

What is the most common presentation of Neuroblastoma?

Back 33

- Abdominal distension
- Firm, irregular mass that can CROSS THE MIDLINE
- Usually in children < 4 years old
- Less likely to develop hypertension

Front 34

When you have a firm, irregular mass that crosses the midline of a young child, what diagnosis should you think of?

Back 34

Neuroblastoma

Front 35

When you have a smooth mass that does not cross the midline of a young child, what diagnosis should you think of?

Back 35

Wilms tumor (nephroblastoma)
- Most common renal malignancy of early childhood (ages 2-4)

Front 36

What lab studies are associated with a Neuroblastoma?

Back 36

- Homovanillic acid (HVA), a breakdown product of dopamine, is increased in urine
- Bombesin (+)
- LM: rosettes (arrow) and classic small, round, blue/purple nuclei

Front 37

What genetic change is associated with Neuroblastoma?

Back 37

Over-expression of the N-myc oncogene

Front 38

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

Back 38

Pheochromocytoma

Front 39

What is a pheochromocytoma derived from?

Back 39

Chromaffin cells (arise from neural crest)

Front 40

What rule can you use to remember characteristics of a pheochromocytoma?

Back 40

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

Front 41

What does a pheochromocytoma do?

Back 41

Most tumors secrete epinephrine, norepinephrine, and dopamine → episodic hypertension

Front 42

What genetic change is pheochromocytoma associated with?

Back 42

- Von Hippel-Lindau disease
- MEN 2A
- MEN 2B

Front 43

What symptoms are typical of pheochromocytoma?

Back 43

Symptoms occur in "spells" - relapse and remit:

Episodic hyperadrenergic symptoms (5 P's):
- Pressure (↑ BP)
- Pain (headache)
- Perspiration
- Palpitations (tachycardia)
- Pallor

Front 44

What are the lab findings associated with a pheochromocytoma?

Back 44

- ↑ Urinary VMA (breakdown product of NE and Epi)
- ↑ Plasma catecholamines (NE, Epi, etc)

Front 45

How do you treat pheochromocytoma?

Back 45

1. Irreversible α-antagonist (phenoxybenzamine)
2. β-blockers
3. Tumor resection

** α-blockade must be achieved before giving β-blockers to avoid a hypertensive crisis **

Front 46

For what diagnosis must you treat the patient first with α-antagonists before β-blockers? Why?

Back 46

For treatment of Pheochromocytoma:

This is necessary to avoid a hypertensive crisis