Narayan RS 2- Adrenal Physiology

Question 1

What are some signals that can affect the HPA axis? What level would they affect it at?

Answer 1

Stressors like hypoglycemia, hypotension, fever and injury can cause the pituitary to release CRH

Vasopressin and pro-inflammatory signals can cause the pituitary to release ACTH

Question 2

Can ACTH cause negative feedback? How so?

Answer 2

Yes, ACTH will inhibit the release of CRH from the hypothalamus (short feedback loop)

Question 3

At what levels of the HPA axis can cortisol exert a negative feedback effect?

Answer 3

Cortisol can inhibit the hypothalamus and pituitary.

Question 4

Describe the RAAS system activation

Answer 4

Juxtaglomerular cells will secrete renin in response to low arterial pressure

Renin will convert circulating angiotensinogen to angiotensin I, which is converted by ACE to angiotensin II

Angiotensin II will stimulate the transcription of aldosterone synthase and aldosterone release.

Question 5

What is the role of 11B-HSD2 in cortisol regulation? How is this affected in Cushing’s/

Answer 5

Co-localizes with the mineralocorticoid receptor to convert cortisol to cortisone, because cortisol and aldosterone have similar affinity for the receptor.

In Cushing’s, high levels of cortisol overwhelm this receptor, leading to high blood pressure.

Question 6

What affects will glucocorticoids have on the anterior pituitary?

Answer 6

They decrease the release of FSH, LH, TSH and GH release

Question 7

What is the difference between Cushing syndrome and disease?

Answer 7

Any glucocorticoid excess is considered Cushing syndrome.

However, if it is due to a pituitary adenoma, it is considered Cushing’s Disease

Question 8

What mutation is responsible for most pituitary adenomas?

Answer 8

USP8 mutation

Question 9

What is inferior petrosal sinus sampling? How is it diagnostic in Cushing’s Disease/Syndrome?

Answer 9

The pituitary empties into the inferior petrosal sinus, which empties into the jugular.

The jugular vein is accessed via the femoral,.

If the IPS/P ACTH ratio is >2 or >3 after CRH, then it means there is an ACTH secreting microadenoma, and therefore the diagnosis of Cushing’s Disease can be made

Question 10

How can Cushing’s syndrome be treated at the pituitary level? Adrenal level?

Answer 10

At the pituitary, dopamine agonists such as cabergoline can be used to reduce ACTH synthesis

At the adrenal gland, non-specific enzymatic inhibitors such as ketoconazole and metyrapone can be used.

Question 11

What is Addison’s Disease? How is it different from secondary renal insufficiency?

Answer 11

Addison’s is primary adrenal insufficiency, when an issue with the adrenal gland causes a lack of hormones.

Secondary insufficiency is when there is an issue such as renal insufficiency, that leads to decreased renin stimulation

Question 12

How can 21a-hydroxlayse deficiency be distinguished from 11B-hydroxylase deficiency?

Answer 12

In 21a-hydroxylase deficiency, mineralocorticoids will be decreased, while in 11B-hydroxylase deficiency they are increased

Also, 17-hydroxyprogesterone will be increased in 21a-hydroxylase deficiency, while 11-deoxycortisol will be increased in 11B-hydroxylase deficiency.