Bod: Endocrinology: Adrenal Disorders

Front 1

What is the peritoneal association of the adrenal glands?

Back 1

Retroperitoneal.

Front 2

What are the four functional components of the adrenal gland? What does each component produce?

Back 2

From outside (cortex) to in (medulla):
1. Zona glomerulosa --> Mineralocorticoids (aldosterone)
2. Zona fasiculata --> Glucocorticoids (cortisol)
3. Zona reticularis --> Sex steroids (precursors to testosterone and DHEA-S)
4. Medulla --> Catecholamines (epinephrine, norepinephrine & dopamine)

Front 3

Embryologically, what does the cortex of the adrenal gland develop from?

Back 3

From the mesoderm and the urogenital ridge.

Front 4

Embryologically, what does the medulla of the adrenal gland develop from?

Back 4

From the endoderm and the neural crest.

Front 5

What is Conn's syndrome?

Back 5

Primary aldosteronism

Front 6

What is the pathway that leads to synthesis and release of cortisol?

Back 6

Hypothalamus releases CRH --> Pituitary releases ACTH --> Zona fasiculata releases cortisol.

Front 7

Overproduction of cortisol = what disease?

Back 7

Cushing's syndrome.

Front 8

Underproduction of cortisol = what disease?

Back 8

Adrenal insufficiency, CAH (congenital adrenal hyperplasia)

Front 9

What chemical regulates the release of sex steriods from the zona reticularis?

Back 9

ACTH

Front 10

What stimulates the release of catecholamines from the adrenal medulla?

Back 10

SNS stimulation.

Front 11

What are three different types of Conn's disease? (three different etiologies)

Back 11

1. Aldo producing adrenal adenoma.
2. Bilateral adrenal hyperplasia.
3. Rare: cortical carcinoma, familial hyperaldosteronism.

Front 12

What are the signs and symptoms of Conn's disease? (3 are classic)

Back 12

Conn's = primary hyperaldosteronism

Classic: HTN, hypokalemia, metabolic alkalosis.

- HTN can be mild to severe
- May have hypokalemia sx (muscle weakness, cramping)
- Nonspecific sx: HA, fatigue
- Mild hypernatremia

Front 13

What are 3 screening tests for Conn's disease?

Back 13

1. Plasma aldo/plasma renin will be high ( > 30) because excessive aldo suppresses renin release.

2. Absolute plasma aldo will be high ( > 20 ng/dL)

3. 24 hour urine will have high K ( >30 mEq/day) or high aldo (> 15 mcg/day)

Front 14

What is a "confirmatory" test for primary aldosteronism?

Back 14

Saline suppression test: give 2 L saline over 4 hours and observe whether aldo is downregulated. Aldo > 10 ng/dL is a positive test.

Front 15

What is a way that you can tell the difference between an adenoma causing Conn's or bilateral hyperplasia?

Back 15

CT or MRI of adrenals. If these are inconclusive, then you can try sampling of aldo in the adrenal veins.

Front 16

What is the treatment for an adenoma? What do you treat with pre-op?

Back 16

Surgical unilateral adrenalectomy.

Treat hypokalemia and HTN preop with spironolactone.

Front 17

How do you treat bilateral adrenal hyperplasia?

Back 17

Medically, with:

1. Spironolactone (aldactone) - an aldo antagonist. 200-400 mg PO daily in divided doses. AE: antiadrenergic limits use (men: gynecomastia, ED; women: abnormal menstrual effects)

2. Eplerenone (Inspra) - aldo antagonist with less antiadrenergic effects. Dose 50 mg once daily and titrate up.

3. Amiloride - K sparing diuretic. Dose 5-10 mg po daily, titrate up to 20 mg daily

4. Triamterene - K sparing diuretic. Dose 50-300 mg daily in 1-2 divided doses.

Front 18

Hyperpigmentation is seen in what adrenal disorder? Why?

Back 18

In ACTH-dependent Cushing's syndrome. ACTH is synthesized from POMC. POMC --> ACTH, MSH, beta-lipotropin. MSH simulates melanocytes.

Front 19

Where does cortisol bind?
Where does aldosterone bind?

Back 19

Corisol binds in the nucleus.
Aldo binds to the mineraldocortical receptor.

Note that at high concentrations cortisol can also bind to the mineralocorticoreceptor.

Front 20

Cushing's syndrome signs and symptoms.

Back 20

From increased cortisol:
- Truncal obesity, thin extremities, moon facies, buffalo hump.
- Thinning of skin
- Hyperglycemia
- HTN
- Proximal muscle weakness

From increased androgen:
- Women: amenorrhea, hirsutism, acne
-

Front 21

What are two etiologies of ACTH-dependent Cushing's syndrome?

Back 21

1. ACTH producing pituitary adenoma.

2. Ectopic ACTH production. (rapid sx onset, SCLC paraneoplasm)

Patients with ACTH-dependent etiologies will have hyperpigmentation as MSH is secreted with ACTH.

Front 22

What are four etiologies of ACTH-independent Cushing's syndrome?

Back 22

1. Cortisol-producing adrenal adenoma.

2. Adrenal carcinoma (rare)

3. Adrenal nodular hyperplasia (rare)

4. Iatrogenic, exogenous glucocorticoid administration (very common)

Front 23

What test can you do to confirm the diagnosis of Cushing's syndrome?

Back 23

1. 24 hour urine check for cortisol. Better than a plasma cortisol level because cortisol release is pulsatile.

2. Overnight dexamethasone suppression test. 1 mg at 11:00 pm, measure plasma cortisol in morning. A high level ( > 5 ug/dL) is a positive test.

3. Two day low dose dexamethasone suppression test: 0.5 mg po every 6 hrs for 48 hours, measure 24 hour urine cortisol on day 2. A positive test is a high (> 80% from baseline) urine free cortisol.

Front 24

How do you determine if Cushing's is ACTH dependent or independent?

Back 24

Measure serum ACTH and cortisol on 2 at least 2 days.

High cortisol and high ACTH = ACTH-dependent

High cortisol and low ACTH = ACTH-independent

Front 25

What test do you use to determine the source of ACTH in ACTH dependent Cushing's?

Back 25

Two day high dose dexamethasone suppression test: 2.0 mg po every 6 hours for 48 hours, measure 24 hour urine cortisol on day 2. A positive test is a high (> 80% of normal) urine free cortisol.

This test works because an ACTH-producing tumor of the pituitary will be suppressed at high dex levels. An ectopic ACTH secreting tumor will not be suppressed by high levels and will continue to sec ACTH.

Front 26

What is the idea treatment for Cushing's disease?

Back 26

Removal of the tissue causing the primary problem.

Front 27

What are some (3) medications that can help Cushing's patients if the offending tissue is not resectable?

Back 27

1. Ketoconazole: inhibits p450 enzymes. AE: transaminitis, gynecomastia, GI upset, edema

2. Metyrapone: inhibits 11β-hydroxylase. AE: nausea, vomiting, rash, acne.

3. Mitotane: inhibits 11β-hydroxylase, cholesterol side-chain cleavage, toxic to adrenal cortical cells. AE: GI sx, dizziness, gynecomastia, hyperlipidemia, rash, transaminitis, hypoaldosteronism.

Front 28

What are the cortisol, aldo, and ACTH levels in primary adrenal insufficiency? Side effects?

Back 28

cortisol down, aldo down --> ACTH up --> hyperpigmentation.

Front 29

What is the list of the causes of primary AI?

Back 29

Autoimmune adrenalitis (Addison's)
Infections (TB, histoplasmosis)
Metastatic cancer (lung, breast, colon)
Amyloidosis
Bilateral adrenalectomy
Acute hemorrhagic destruction (Waterhouse-Friederichsen)
Drugs (ketoconazole, rifampin, phenytoin)
CAH

Front 30

What are the levels of cortisol, aldo, and ACTH in secondary AI?

Back 30

The problem is with a low amount of ACTH, so cortisol is low, but aldo levels are normal (since it is not under the control of ACTH)

Front 31

What is the list of causes of secondary AI?

Back 31

Pituitary mass
Iatrogenic causes (chronic high dose glucocorticoid therapy)

Front 32

What are some classic signs and lab values of primary AI (only)?

Back 32

Hyperpigmentation
Salt craving (because aldo is low)
Hyponatremia
Hyperkalemia

Front 33

What are some signs and symptoms associated with adrenal crisis?

Back 33

Hypotension
Shock
Confusion
Hypothermia
Hypoglycemia

Front 34

How do you test for/diagnose adrenal insufficiency?

Back 34

ACTH stimulation test

Front 35

Treatment for adrenal insufficiency?

Back 35

Glucocorticoid replacement:
Hydrocortisone (Cortef)

Mineralocorticoid replacement:
Fludricortisone (Florinef)

Front 36

What is the most commonly deficient enzyme in CAH?

Back 36

21 hydroxylase

Front 37

What causes the hyperplasia in CAH?

Back 37

CAH is essentially adrenal insufficiency, so cortisol is down, therefore ACTH is up. This increased ACTH leads to hyperplasia.

Front 38

What are some of the effects of CAH?

Back 38

21 hydroxylase is deficient, so cortisol is low, thus the creation of androgens is not downregulated.

In women this manifests as hirsutism, etc.

Front 39

What is the treatment for CAH?

Back 39

Give glucocorticoids in levels high enough to shut off ACTH and thus decrease androgen production.

Front 40

Pheochromocytomas are tumors of what types of cells?

Back 40

The neurochromaffin cells of the adrenal medulla.

Rarely, some arise from sympathetic ganglia, usually in the abdomen (paraganglioma).

Front 41

What is the 10% rule for pheochromocytomas? (5)

Back 41

10% extra adrenal
10% familial
10% bilateral
10% malignant
10% occur in childhood

Front 42

What is the classic symptom triad of pheochromocytomas?

Back 42

1. Headaches
2. Sweating
3. Palpitations

Also HTN paroxysms.

Front 43

Diagnois of pheochromocytoma?

Back 43

24 hour urine collection for catecholamines (usually 2x normal in pheo), and catecholamine metabolites (metanephrines, VMA, usually 3x normal in pheo)

Front 44

What do you do to localize a pheochromocytoma?

Back 44

MRI useful because of the good vascularization of the pheo

Front 45

What do you give preop to patient going to have removal of a pheo?

Back 45

Give an α blockade with phenoxybenzamine (Dibenzyline)

Give saline preop to prevent hypotension after surgery.

Front 46

It is a bad idea to treat pheo patients with what types of drug?

Back 46

β blockers. If you block β stimulation, then you will have unapposed α stimulation and vasoconstriction. If need to treat HTN, use IV α blocker phentolamine (Vasomax) or IV nitroprusside (Nitropress)

Front 47

What is a neuroblastoma?

Back 47

A neuroendocrine tumor that can arise from any neural crest element of the SNS.

Presents on average at 21 months of age

Vague symptoms

Front 48

What are two important questions to ask about adrenal incidentaloma?

Back 48

1. Is the mass benign or malignant?
2. Is the mass producing hormone?

90% are benign, non-functioning masses.

Front 49

What size of adrenal incidentaloma would get a physician worried?

Back 49

Anything from 4-6 cm