Steroids of Adrenal Cortex

Question 1

What are the steroids of the adrenal cortex

Answer 1

→ Glucocorticoids - cortisol
→ Mineralocorticoids - aldosterone
→ androgens

Question 2

What does aldosterone do?

Answer 2

→ Maintains blood volume by regulating Na+

Question 3

Where does the blood flow in the adrenal medulla?

Answer 3

→ Outer cortex to inner medulla

Question 4

What does steroid hormone synthesis always start with?

Answer 4

→ Cholesterol

Question 5

What does the cortex secrete?

Answer 5

→ Steroid hormones

Question 6

What does the medulla secrete?

Answer 6

→ Adrenaline

Question 7

What is the pathway in the zona glomerulosa?

Answer 7

Cholesterol
↓
Pregnenolone
↓
Progesterone
↓
Deoxycorticosterone
↓
Corticosterone
↓
Aldosterone

Question 8

What is the zona fasciculata pathway?

Answer 8

Progesterone
↓
17 OH progesterone
↓
Deoxycortisol
↓
Cortisol

Question 9

What is the zona reticularis pathway?

Answer 9

Pregnenolone
↓
17 OH pregnenolone
↓
DHEA
↓
Androstenedione

Question 10

What is the function of mineralocorticoid?

Answer 10

→ Na+ retention
→ Active Na+ reabsorption
→ Active secretion of K+

Question 11

What is the juxtaglomerular apparatus stimulated by?

Answer 11

→ Increased sympathetic activity
→ Decreased perfusion pressure
→ Decreased Na+ and Cl-

Question 12

What stimulates aldosterone secretion?

Answer 12

→ K+

aldosterone secretion is NOT significantly affected by changes in plasma Na concentration

Question 13

How does aldosterone work to retain Na+?

Answer 13

→ Increases Na+/K+/ATPase activity on the apical side

Question 14

Why does cortisol not work in the kidney?

Answer 14

→ Cortisol levels are higher
→ Cortisol can stimulate the mineralocorticoid receptor
→ cortisol in the kidney gets converted to inactive cortisone
→ by 11 beta HSD 2

Question 15

What is the syndrome of apparent mineralocorticoid excess?

Answer 15

→ Too much cortisol in the kidney

→ High BP

Question 16

What family is the glucocorticoid receptor a part of?

Answer 16

→ Nuclear receptor super family

Question 17

What are the 3 structural elements of the glucocorticoid receptor?

Answer 17

→ Ligand binding
→ DNA binding
→ N- terminal transcription co-factor binding

Question 18

What do the glucocorticoid receptors do when the ligand binds?

Answer 18

→ Receptors dimerize

→ Translocate to nucleus

Question 19

What is transactivation?

Answer 19

→ Glucocorticoid enhances transcription of the target gene

Question 20

What is transrepression?

Answer 20

→ Glucocorticoid represses the transcription of the target gene

Question 21

What are the functions of glucocorticoids?

Answer 21

→ Decreased glucose uptake
→ Increased proteolysis
→ Stimulates lipolysis
→ Gluconeogenesis
→ Maintaining glucose

Question 22

What does hypocortisolism lead to?

Answer 22

→ hypotension

→ Inappropriate vasodilation

Question 23

What are prostaglandins and leukotrienes derived from?

Answer 23

→ Lipid derived compounds

Question 24

What is the first molecule to be synthesized in the inflammation pathway?

Answer 24

→ Arachidonic acid

Question 25

What effect does cortisol have on the inflammation pathway?

Answer 25

→ Cortisol increases the expression of ANNEXIN - 1 | → Annexin 1 downregulates arachidonic acid

Question 26

What is the pathway for the production of cortisol?

Answer 26

``` → Hypothalamus makes CRH → CRH stimulates anterior pituitary → Anterior pituitary makes ACTH → ACTH stimulates the adrenal cortex → Adrenal cortex makes cortisol ```

Question 27

What is primary adrenal insufficiency?

Answer 27

→ Addisons disease

Question 28

What is secondary adrenal insufficiency?

Answer 28

→ Hypopituitarism → RAAS defect → Enzyme defect in steroid synthesis

Question 29

What are the clinical features of Addisons?

Answer 29

``` → Low adrenal steroids → high ACTH → Plasma Na+ - low → Plasma K+ - normal - high → high renin ```

Question 30

When there is very low cortisol what two hormones are high?

Answer 30

→ ADH - plasma dilution so low Na+ cortisol inhibits ADH → ACTH

Question 31

What is the ACTH receptor a part of?

Answer 31

→ Melanocortin group of receptors

Question 32

Why does Addisons cause hyperpigmentation?

Answer 32

→ Excess circulating ACTH → Binds to melanocortin receptors → Pigmentation

Question 33

What is Cushings disease due to?

Answer 33

→ Secondary | → Increased ACTH due to pituitary adenoma

Question 34

What is ACTH independent hypercortisolism?

Answer 34

→ Adrenal adenoma | → Iatrogenic

Question 35

What are clinical features of hypercortisolism?

Answer 35

``` → Hypertension → Hyperglycaemia → truncal obesity → Fatigue, Muscle weakness → Virilization → Depression ```

Question 36

What do low doses of dexamethasone usually do?

Answer 36

→ Suppress ACTH secretion via negative feedback

Question 37

What suppresses ACTH secretion in Cushings and why?

Answer 37

→ a higher dose of dexamethesone → Pituitary cells have increased → more cortisol/dexamethesone is needed for a negative feedback

Question 38

What happens if a high dose of dexamethesone does not suppress ACTH?

Answer 38

→ Ectopic source of ACTH

Question 39

What effect does cortisol have on NO synthesis in the CVS?

Answer 39

have effect on NO synthesis so too much NO and inappropriate vasodilation.

Question 40

What is the effect of glucocorticoids inhibit?

Answer 40

→inhibit the inflammatory response by inducing annexin-1 which inhibits phospholipase A2 →inhibits induction of COX

Question 41

What happens when cortisol is very low?

Answer 41

CRH is high, and ADH rises and hyponatremia

Question 42

Explain the rationale behind the low dose dexamethasone suppression test work

Answer 42

Dexamethasone: exogenous steroid. Act like cortisol Low doses will normally supress ACTH secretion via negative feedback

Question 43

How is ectopic ACTH linked with Cushing's syndrome?

Answer 43

pituitary adenoma results in increased ACTH secretion, which drives excess cortisol production from adrenal cortex Negative feedback loop is still intact, but greater mass of ACTH-secreting pituitary cells means set point is higher.