Fa: Endocrine - Embryology, Anatomy, & Physiology -3

Front 1

What is the first step in production of adrenal steroids?

Back 1

Conversion of Cholesterol → Pregnenolone via Cholesterol Desmolase

Front 2

How do you produce Aldosterone?

Back 2

1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → Progesterone (3β-hydroxysteroid dehydrogenase)
3. Progesterone → 11-deoxycorticosterone (21-hydroxylase)
4. 11-deoxycorticosterone → Corticosterone (11β-hydroxylase)
5. Corticosterone → Aldosterone (Aldosterone Synthase)

Front 3

What are the molecules on the way from Cholesterol to Aldosterone?

Back 3

1. Cholesterol
2. Pregnenolone
3. Progesterone
4. 11-deoxycorticosterone
5. Corticosterone
6. Aldosterone

Front 4

What are the enzymes on the way from Cholesterol to Aldosterone?

Back 4

1. Cholesterol Desmolase
2. 3β-hydroxysteroid dehydrogenase
3. 21-hydroxylase
4. 11β-hydroxylase
5. Aldosterone Synthase

Front 5

How do you produce Cortisol?

Back 5

1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → 17-hydroxypregnenolone (17α-hydroxylase)
3. 17-hydroxypregnenolone → 17-hydroxyprogesterone (3β-hydroxysteroid dehydrogenase)
4. 17-hydroxyprogesterone → 11-deoxycortisol (21-hydroxylase)
5. 11-deoxycortisol → Cortisol (11β-hydroxylase)

Steps 2 and 3 can be switched around, but need both enzymes

Front 6

What are the molecules on the way from Cholesterol to Cortisol?

Back 6

1. Cholesterol
2. Pregnenolone
3. 17-hydroxypregnenolone
4. 17-hydroxyprogesterone
5. 11-deoxycortisol
6. Cortisol

OR

3. Progesterone (depending on order of enzymes)

Front 7

What are the enzymes on the way from Cholesterol to Aldosterone?

Back 7

1. Cholesterol desmolase
2. 17α-hydroxylase
3. 3β-hydroxysteroid dehydrogenase
4. 21-hydroxylase
5. 11β-hydroxylase

(Enzymes 2 and 3 can be done in either order)

Front 8

How do you produce Estradiol?

Back 8

1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → 17-hydroxypregnenolone (17α-hydroxylase)
3. 17-hydroxypregnenolone → Dehydroepiandrosterone (DHEA)
4. DHEA → Androstenedione
5. Androstenedione → Estrone (Aromatase)
6. Estrone → Estradiol

OR

5. Androstenedione → Testosterone
6. Testosterone → Estradiol (Aromatase)

Front 9

What are the actions of Aromatase?

Back 9

- Androstenedione → Estrone
- Testosterone → Estradiol

Front 10

What are the actions of 5α-Reductase?

Back 10

Testosterone → Dihydrotestosterone (DHT)

Front 11

Which enzyme deficiency would cause:
- Mineralocorticoids: ↑
- Cortisol: ↓
- Sex Hormones: ↓

Back 11

17α-Hydroxylase (A)

Glucocorticoid and Androgen/Estrogen precursors cannot be produced, which shuttles more Pregnenolone / Progesterone substrate through the Aldosterone pathway

Front 12

Which enzyme deficiency would cause:
- Mineralocorticoids: ↓
- Cortisol: ↓
- Sex Hormones: ↑

Back 12

21-Hydroxylase (B)

Progesterone and 17-Hydroxyprogesterone cannot continue towards formation of Aldosterone and Cortisol, so they get shuttled to the sex hormone pathway

Front 13

Which enzyme deficiency would cause:
- Mineralocorticoids: ↓ / ↑
- Cortisol: ↓
- Sex Hormones: ↑

Back 13

11β-Hydroxylase (C)

- ↓ Aldosterone
- ↑ 11-deoxycorticosterone (results in ↑ BP)
- Cortisol can't be made
- Sex hormones increased due to extra substrate

Front 14

What is similar about 17α-hydroxylase, 21-hydroxylase, and 11β-hydroxylase deficiencies?

Back 14

All congenital adrenal enzyme deficiencies → enlargement of both adrenal glands due to ↑ ACTH stimulation (due to ↓ cortisol)

Front 15

What labs are associated with 17α-hydroxylase deficiency?

Back 15

- ↑ Mineralocorticoids
- ↓ Cortisol
- ↓ Sex hormones (↓ DHT)

- Hypertension
- Hypokalemia

Front 16

How does a patient with 17α-hydroxylase deficiency present?

Back 16

↑ Mineralocorticoids, ↓ Cortisol, and ↓ Sex hormones causes:

- XY: pseudo-hermaphroditism (ambiguous genitalia, undescended testes)

- XX: lack secondary sexual development

- Both: hypertension, hypokalemia

Front 17

What labs are associated with 21-hydroxylase deficiency?

Back 17

- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones (↑ 17-hydroxy-progesterone)

- Hypotension
- Hyperkalemia
- ↑ Renin activity

Front 18

How does a patient with 21-hydroxylase deficiency present?

Back 18

↓ Mineralocorticoids, ↓ Cortisol, and ↑ Sex Hormones causes:

- Presents in infancy with salt-wasting or in childhood with precocious puberty

- XX: virilization

- Hypotension, hyperkalemia, ↑ Renin activity

Front 19

What labs are associated with 11β-hydroxylase deficiency?

Back 19

- ↓ Aldosterone
- ↑ 11-deoxycorticosterone (results in ↑ BP)
- Hypertension
- Low renin

- ↓ Cortisol

- ↑ Sex hormones

Front 20

How does a patient with 11β-hydroxylase deficiency present?

Back 20

↓ Aldosterone, ↑ 11-deoxycorticosterone, ↓ Cortisol, and ↑ Sex hormones causes:

- XX: virilization

- Hypertension

Front 21

What diagnosis should you consider in an XY patient who presents with pseudo-hermaphroditism (ambiguous genitalia, undescended testes)? Other findings?

Back 21

17α-hydroxylase deficiency
- Hypertension
- Hypokalemia
- ↓ Sex hormones (↓ DHT)
- ↓ Cortisol
- ↑ Aldosterone

Front 22

What diagnosis should you consider in an XX patient lacking secondary sexual development? Other findings?

Back 22

17α-hydroxylase deficiency
- Hypertension
- Hypokalemia
- ↓ Sex hormones (↓ DHT)
- ↓ Cortisol
- ↑ Aldosterone

Front 23

What diagnosis should you consider in an infant presenting with salt wasting? Other findings?

Back 23

21-Hydroxylase deficiency
- Hypotension
- Hyperkalemia
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones

Front 24

What diagnosis should you consider in an child with precocious puberty? Other findings?

Back 24

21-Hydroxylase deficiency
- Hypotension
- Hyperkalemia
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones

Front 25

What diagnosis should you consider in an XX patient with virilization? Other findings?

Back 25

21-Hydroxylase deficiency
- Hypotension
- Hyperkalemia
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones

OR

11β-Hydroxylase deficiency
- Hypertension (d/t ↑ 11-deoxycorticosterone)
- ↓ Aldosterone
- ↓ Cortisol

Front 26

What is the source of Cortisol? What does it bind in the blood?

Back 26

- Adrenal Zona Fasciculata
- Binds to corticosteroid-binding globulin

Front 27

What are the effects of Cortisol?

Back 27

Cortisol is a BIG FIB:
- ↑ BP
- ↑ Insulin resistance
- ↑ Gluconeogenesis, lipolysis, and proteolysis

- ↓ Fibroblast activity
- ↓ Inflammatory and immune responses
- ↓ Bone formation

Front 28

How does cortisol affect BP?

Back 28

↑ BP: upregulates α1-receptors on arterioles → ↑ sensitivity to NE and Epi

Front 29

How does cortisol affect insulin?

Back 29

↑ Insulin resistance → diabetogenic

Front 30

How does cortisol affect stored forms of energy?

Back 30

- ↑ Gluconeogenesis
- ↑ Lipolysis
- ↑ Proteolysis

Front 31

How does cortisol affect fibroblasts? Effect?

Back 31

↓ Fibroblast activity → causes striae

Front 32

How does cortisol affect inflammation / immune responses?

Back 32

↓ Inflammatory and Immune responses:
- Inhibits production of leukotrienes and prostaglandins
- Inhibits leukocyte adhesion → neutrophilia
- Blocks histamine release from mast cells
- Reduces eosinophils
- Blocks IL-2 production

Front 33

How does cortisol affect bones?

Back 33

↓ Bone formation due to ↓ Osteoblast activity

Front 34

What infections can be reactivated after administration of exogenous corticosteroids? How?

Back 34

Reactivation of TB and Candidiasis
- Due to blocked IL-2 production

Front 35

How is Cortisol regulated?

Back 35

- CRH (hypothalamus) stimulates ACTH release (pituitary), causing cortisol production in adrenal zona fasciculata
- Excess cortisol ↓ CRH, ACTH, and cortisol secretion

Front 36

What is the effect of chronic stress on cortisol?

Back 36

Chronic stress induces prolonged secretion of Cortisol