10. Adrenal Glands

Question 1

What are chromogranins?

Answer 1

Chromogranins are proteins that complex with epinephrine and norepinephrine to decrease the osmotic burden of individual epinephrine molecules within the chromaffin granule.

Question 2

What enzyme is responsible for the breakdown of catecholamines?

Answer 2

Catecholamine-O-methyltransferase (COMT).

Question 3

Which adrenergic receptors are found on the α cells of the pancreas?

Answer 3

β2 receptors

Question 4

What is the function of 17,20-lyase?

What do we see in its deficiency?

Answer 4

Allows cholesterol to move past the cortisol pathway and into the androgen pathway.

Underdeveloped genitalia.

Question 5

How does cortisol cause striations and easier bruising?

Answer 5

Cortisol causes the breakdown of proteins – including elastin.

Question 6

Which adrenergic receptor is found on the β cells of the pancreas?

Answer 6

α receptors

Question 7

What three enzymes lead to congenital adrenal hyperplasia?

Answer 7

11β-hydroxylase

21β-hydroxylase

17α-hydroxylase

Question 8

When is cortisol naturally higher vs. lower?

Answer 8

Cortisol is naturally higher just after waking, and lowest in the late evening.

Question 9

What does the plasma renin activity to plasma aldosterone concentration ratio detect?

Answer 9

Primary hyperaldosteroneism.

If aldosterone is high without also having high renin, you know that something is producing aldosterone without being stimulated.

Question 10

Would we expect ACTH to be elevated or depressed in patients with Cushing’s syndrome?

What about with Cushing’s disease?

Answer 10

In Cushing’s syndrome, ACTH would be low.

In Cushing’s disease ACTH will be unusually high.

Question 11

Deficiency of which adrenocortical hormone synthesizing enzyme is likely to lead to high blood pressure?

Answer 11

11β-hydroxylase

17α-hydroxylase

Question 12

What are the primary functions of cortisol on the immune system, liver, muscle tissue, and adipose tissue?

Answer 12

Immune system – Inhibition of T cells and immune suppression (anti-inflammatory effect).

Liver – ↑ Gluconeogenesis.

Muscle – ↑ Protein catabolism.

Adipose tissue – ↑ Lipolysis.

Question 13

What is the negative feedback mechanism for the hypothalamus, pituitary, adrenal axis?

Answer 13

Cortisol feeds back and negatively inhibits the anterior pituitary’s production of ACTH, as well as the hypothalamus’s production of CRH.

Question 14

How is norepinephrine in the chromaffin granule converted into epinephrine?

Answer 14

Norepinephrine in the chromaffin granule diffuses out into the cytoplasm by facilitated transport, and then is converted into epinephrine by the cytosolic enzyme phenylethanolamine-N-methyl transferase (PNMT).

Epinephrine is then transported back into the granule by vesicular monoamine transporters (VMATs)

Question 15

What do we expect to see in 21β-hydroxylase deficiency?

Answer 15

Decreased function of aldosterone (no 11-deoxycorticosterone).

Salt wasting due to the above.

Decreased function of cortisol.

Virilization in females.

Increased renin activity to attempt to raise aldosterone.

Question 16

Which of the named diseases discussed in this lecture leads to hyperpigmentation?

What is the mechanism for this symptom?

Answer 16

Addison’s disease leads to hyperpigmentation.

ACTH is elevated in a futile effort to increase cortisol levels from a malfunctioning adrenal cortex.

Cushing’s disease also causes increased ACTH, and therefore hyperpigmentation.

Question 17

What adrenergic receptor is found in the liver?

Answer 17

β2

Question 18

What test can we use to detect adrenal gland insufficiency?

How does this test work?

What is the next step?

Answer 18

The cosyntropin (synthetic ACTH) stimulation test.

Give a patient cosyntropin, if their cortisol fails to increase, adrenal insufficiency is confirmed.

The next step is to test their ACTH to see if it is low or elevated. This determines 1°, 2°, or 3° adrenal insufficiency.

Question 19

If a patient is confirmed to have adrenal insufficiency, and their adrenocorticotropic hormone levels are high, what sort of adrenal insufficiency can we expect?

What about if ACTH is low?

Answer 19

Adrenal insufficiency with high ACTH indicates primary adrenal insufficiency (Addison’s disease).

Adrenal insufficiency with low ACTH indicates either 2° or 3° adrenal insufficiency.

Question 20

What is the rate limiting step of catecholamine synthesis?

What stimulatory molecules regulate the step?

Answer 20

Tyrosine -> DOPA

(catalyzed by tyrosine hydroxylase)

Stimulated by ACh and ACTH.

Question 21

Why might we see low levels of serum cortisol in a patient who is taking oral prednisone?

Answer 21

Because exogenous glucocorticoids have the same negative feedback effect as cortisol.

Question 22

What adrenergic receptors are found in adipose tissue?

Answer 22

β2, β3

Question 23

Which receptor respond better to epinephrine then norepinephrine?

Answer 23

β2 receptors.

Question 24

If a high dose dexamethasone suppression test fails to decrease cortisol levels, what should your differential be limited to?

Answer 24

Cushing’s syndrome (1° Cushing’s).

Ectopic ACTH secreting tumor.

Question 25

What are the symptoms of cortisol excess?

(It’s a lot, just do your best.)

Answer 25

↑ Hepatic glycogen deposition.

↑ Peripheral insulin resistance – especially in adipose tissue.

↑ Gluconeogenesis.

↑ Free fatty acid production.

Adipose tissue distribution toward the abdomen and face.

↑ Salt and water retention.

↓ Bone formation – osteoporosis.

Protein catabolism and collagen breakdown of the skin, muscle, and connective tissue.

T cell inhibition and immunosuppression – anti-inflammatory actions.

↓ Linear growth.

Question 26

If a low-dose of dexamethasone does not suppress cortisol levels, but a high dose of dexamethasone does – what might you suspect in your differential?

Answer 26

Adrenocorticotropic hormone releasing tumor – Cushing’s disease (2° Cushing’s).

Question 27

Which adrenergic receptors found in the G.I. and urinary tracts?

Answer 27

β2

Question 28

Where is DOPA converted into dopamine?

What enzyme catalyzes this step?

Answer 28

In the cytoplasm.

Catalyzed by aromatic amino acid decarboxylase (AADC).

Question 29

What is the function of 11β-hydroxylase?

What will we see if this enzyme is deficient?

Answer 29

Allows the conversion of 11-deoxycorticosterone into aldosterone, as well as the final step of the conversion of cholesterol into cortisol.

Low aldosterone, high unregulated 11-deoxycorticosterone (net symptoms of high mineralcorticoids).

Low cortisol.

Increased presentation of androgens, leading to ambiguous genitalia in females.

Question 30

The increase of what hormone should we associate with hyperpigmentation?

Answer 30

ACTH – the breakdown of which leads to α-melanocyte stimulating hormone.

Question 31

How might you diagnose neck topic ACTH secreting tumor vs. Cushing’s disease?

Answer 31

In Cushing’s disease the pituitary tumor is derived from the same tissue of the anterior pituitary – and will respond to dexamethasone suppression at high doses.

An ectopic ACTH tumor will not have the ability to respond to negative feedback from cortisol or dexamethasone.

Question 32

What adrenergic receptor is found both on the arterioles and cells of skeletal muscle?

Answer 32

β2

Question 33

What is a pheochromocytoma?

Answer 33

A tumor of the adrenal medulla that secretes catecholamines.

Question 34

Where is dopamine converted into norepinephrine?

What enzyme catalyzes the step?

Answer 34

Within the chromaffin granule.

Dopamine’s conversion into norepinephrine is catalyzed by dopamine β-hydroxylase.

Question 35

What affect what elimination of ACTH have on aldosterone secretion?

Answer 35

Slight decrease, but essentially nothing, because aldosterone is primarily regulated by the RAAS system.

Question 36

How do adrenocorticotropic hormone and cortisol influence the production of catecholamines?

Answer 36

ACTH stimulates synthesis of DOPA from tyrosine.

Cortisol stimulates the enzyme PNMT which converts norepinephrine into epinephrine.

Question 37

What is Conn’s syndrome?

Answer 37

Hyperaldosteronism due to an adenoma in the adrenal cortex.

Question 38

What are the signs and symptoms of Cushing’s syndrome?

(It’s a lot – do your best)

Answer 38

Truncal obesity.
Moon face.
Buffalo hump.
Easy bruising.
Purple striae.
Hypertension.
Edema.
Weakness.
Osteoporosis.
Hirsutism.
Acne.
Virilization.
Diabetes.
Immunosuppression.
Cognitive effects.

Question 39

Why would we use a dexamethasone suppression test?

Answer 39

Dexamethasone suppression tests help us diagnose Cushing’s at low doses, and help us differentiate between primary and secondary Cushing’s (Cushing’s syndrome vs. Cushing’s disease) at high doses.

Question 40

Which reaction is common for every pathway of adrenocortical hormone synthesis (towards aldosterone, cortisol, and androgens)?

Answer 40

Cholesterol -> pregnenolone.

(Catalyzed by cholesterol desmolase.)