Adrenal Pathophysiology

Question 1

What is Cushing’s syndrome?

Answer 1

It’s an umbrella term for the syndrome produced by having too much cortisol. Has lots of etiologies.

Question 2

Important: What’s the most common etiology of Cushing’s syndrome?

Answer 2

Iatrogenic - from excessive corticosteroid use.

Question 3

What’s the most common non-iatrogenic cause of Cushing’s syndrome?

Answer 3

Cushing’s disease, i.e. pituitary (corticotroph) adenoma.

Question 4

4 metabolic derangements caused by excess glucocorticoids?

Answer 4

1) Increased gluconeogenesis –> hyperglycemia.
2) Increased lipogenesis.
3) Insulin resistance.
4) Increased skeletal muscle catabolism.

Question 5

There’s no pathognomic sign of Cushing’s syndrome, but what’s the most common feature?

Answer 5

Obesity.

Question 6

What are 3 main areas of fat deposition in Cushing’s syndrome?

Answer 6

"Centripetal" fat deposition
1) Dewlap (double chin)
2) Supraclavicular fat pads
3) Buffalo hump.
(accompanied by muscle atrophy)

Question 7

What’s the term used to describe how people’s face looks in Cushing’s syndrome?

Answer 7

“Moon faced” - cheeks sort of form a circle with neck fat.

Question 8

Immune, hematopoietic, opthalmic, and musculoskeletal effects of glucocorticoid excess?

Answer 8

Immune: immune supression.
Hematopoetic: Increased clotting factors
Eyes: Cataract formation
Musculoskeletal: muscle-wasting, osteoporosis, fat-redistribution

Question 9

CV effects of too much cortisol? (3 things)

Answer 9

1) Cardiomyopathy
2) Hypertension
3) Thromboembolic events

Question 10

Effects of excess cortisol on skin?

Answer 10

Thin skin -> stretch marks where you can see red capillaries of dermis through skin.
Easy bruising.
Acne.
Hirsutism.
Hyperpigmentation (if ACTH is high).

Question 11

Psychiatric effects of high cortisol?

Answer 11

Can cause a lot of things. Most commonly causes insomnia. Can cause mania, psychosis, depression, etc.

Question 12

In what disease will you see bilateral adrenal hyperplasia?

Answer 12

Cushing’s disease - pituitary (corticotroph) adenoma producing ACTH -> drives adrenal cortical hyperplasia.

Question 13

How can you get signs of hyperaldosteronism from too much cortisol?

Answer 13

Conversion to cortisone can be overwhelmed -> hypertension and hypokalemia.

Question 14

Do you usually see “marked virilization” in women with Cushing’s disease?

Answer 14

No. Menses can be irregular, increased testosterone.

But marked virilization is more suggestive of a malignant adrenal carcinoma.

Question 15

What’s the first thing to rule out when trying to figure out the cause of Cushing’s syndrome?

Answer 15

Exogenous cortisol, prescribed or otherwise.

Question 16

3 tests done in Cushing’s syndrome workup? What does each test?

Answer 16

1) Late night salivary cortisol - tests for loss of diurnal regulation.
2) Dexamethasone suppression test - tests for independence from ACTH.
3) 24 hr urine collection for cortisol - texts for excess.

Question 17

When would a late night salivary cortisol test yield confusing results?

Answer 17

When the patient has a circadian rhythm disorder and/or works night shifts.

Question 18

What will happen in a normal dexamethasone suppression test?

Answer 18

Both ACTH and cortisol levels will decrease.

- Exogenous dex will suppress pituitary (prevent ACTH secretion– prevent adrenal production of cortisol)

Question 19

Patient has suspected Cushing’s. High urine cortisol and high cortisol are found after dexamethasone suppression test. ACTH is measured at 55 pg/ml (normal 9-57 pg/ml). What’s the cause of the Cushing’s syndrome?

Answer 19

Cushing’s disese - pituitary adenoma. The ACTH is aberrantly normal - should be suppressed if the cortisol is high.

Question 20

If cortisol is being produced by an adrenal tumor, what will ACTH levels be like?

Answer 20

They’ll be low.

Question 21

Main treatment for most causes of Cushing’s syndrome?

Answer 21

Surgery

Question 22

Does Cushing’s syndrome resolve immediately when the cause is removed?

Answer 22

No. Signs can last a long time (up to 12mo) - and psych symptoms can persist.
(Also, one should taper the patient with exogenous glucocorticoids down from the high levels they’ll be used to.)

Question 23

Primary vs. secondary adrenal failure? What are ACTH levels like in each?

Answer 23

Primary: adrenal itself fails - ACTH will be high.
Secondary: loss of ACTH - ACTH will be low.

Question 24

What is it called when you don’t have enough cortisol?

Answer 24

Addison’s disease.

Question 25

In primary adrenal failure, is it just the zona fasiculata (cortisol) that’s affected?

Answer 25

No, often the production of all cortical hormones is lost - can cause hypoaldosteronism (hyponatremia, hyperkalemia, hypotension)

Question 26

6 clinical characteristics of primary adrenal failure?

Answer 26

Hyperpigmentation (due to high ACTH -> MSH).
Weight loss.
Muscle and joint pains.
Fatigue.
Nausea, abdominal pain.
Hypoglycemia.
(some of these are the opposite of Cushing’s syndrome)

Question 27

Most common etiology of primary adrenal insufficiency? What was most common in Addison’s day? Other important common?

Answer 27

Today most common: Auto-immune.
In Addison’s day: TB.
Other causes: infections, metastatic cancer (lung and breast), hemorrhage/infarct, trauma, various drugs.

Question 28

What do you do right away if you patient is hypotensive and you expect Addison’s?

Answer 28

Give dexamethasone right away, test cortisol levels later. (won’t interfere with assay… somehow)

Question 29

4 etiologies of adrenal crises?

Answer 29

1) New primary adrenal failure.
2) Under treatment of existing adrenal insufficiency.
3) Acute withdrawal of high dose glucocorticoids.
4) Pituitary apoplexy.

Question 30

What’s pituitary apoplexy?

Answer 30

Pituitary adenoma gets too large -> hemorrhage and infarct -> sudden loss of pituitary function.

Question 31

Short term treatment of Addisonian crisis?

Answer 31

Saline (they’ll be dehydrated)
Dexamethasone
Monitor electrolytes and BP.

Question 32

What “syndromes” are associated with auto-immune Addison’s?

Answer 32

Polyglandular syndromes - stuff like T1D, thyroiditis… don’t worry about the details.

Question 33

5 signs of hyperaldosteronism? Why does each one happen?

Answer 33

1) Hypertension - water retention (following Na+).
2) Hypokalemia - aldosterone increases K+ excretion.
3) Mild hypernatremia - aldosterone increases Na+ resorption.
4) Metabolic alkylosis - adolesterone increases H+ excretion.
5) Muscle weakness - (electrolyte/pH imbalance?)

Question 34

2 etiologies of hyperaldosteronism?

Answer 34

1) Benign aldosterone-producing adenoma.

2) Bilateral adrenal hyperplasia.

Question 35

If blood pressure is high, what should renin levels be like? Test for this.

Answer 35

Renin should be low - and thus so should be aldosterone.

Can measure aldosterone:renin ratio after salt load.

Question 36

Treatment for hyperaldosteronism caused by bilateral adrenal hyperplasia?

Answer 36

Mineralocorticocoid receptor antagonist.

Question 37

Are adrenal adenomas secreting androgens common? Presentation in men vs. women?

Answer 37

No, they’re not common.
Women - verilization.
Men - more subtle: impaired libido, fertility, etc. etc.

Question 38

What do you call a catecholamine-secreting tumor?

Answer 38

Pheochromocytoma

Question 39

Classic presentation of a pheo?

Answer 39

Spells of hypertension (headaches), feelings of doom, etc. due to epinephrine being dumped into system.

Question 40

3 endocrine causes of hypertension?

Answer 40

1) Cushing’s syndrome
2) Hyperaldosteronism
3) Pheochromocytoma

Question 41

Is biopsy-ing a suspected pheo helpful?

Answer 41

No!!! That can cause a massive release of catecholamines that could kill the patient.
Surgical removal requires alpha blocking and beta blocking the patient first.

Question 42

What are the 3 “Derangements” of the HPA Axis seen in Cushing’s? (IE. What is the pathogenesis)

Answer 42

1) Loss of diurnal variation of cortisol secretion (normal= highest upon waking, lowest at bed time)
- Cortisol peaks are LONGER and HIGHER
2) Autonomy from “central” ACTH–> Loss of response to feedback inhibition
3) Excess cortisol secretion

Question 43

If you suspect Cushing’s–> get abnormal DST–> and get low ACTH- what is the cause? What is ATCH is normal or high?

Answer 43

If ACTH is low–> consider adrenal source

If ACTH is normal/high–> consider pituitary/ectopic source

Question 44

How do you DX adrenal insufficiency?

Answer 44

1) Early AM cortisol levels/ ACTH concentration
2) Cosyntropin stimulation test
- Inject synthetic ACTH–> measure cortisol response at intervals
- If cortisol still low–> DX of adrenal failure