PCOS/Hirsutism/Obesity

Question 1

Contributors to obesity

Answer 1

• Down-regulation of adiponectin (which increases insulin sensitivity)
• Defect in leptin receptor

Question 2

4 Adipokines that change after meal

Answer 2

Somatostatin, ghrelin, leptin, NPY

Question 3

Somatostatin change after meal

Answer 3

Increases after meal

Question 4

Somatostatin source cells

Answer 4

Release from gastric D-cells

Question 5

Somatostatin regulation

Answer 5

Regulated by ANS with catecholamines inhibiting and cholinergic mediators stimulating peptide release

Question 6

Somatostatin function and MOA

Answer 6

Inhibitory function; decreases blood flow, GI motility, gallbladder contraction and inhibition of GI hormones

Question 7

Ghrelin change after meal

Answer 7

Decreases after meal

Question 8

Ghrelin production location

Answer 8

Upper stomach

Question 9

Ghrelin action

Answer 9

Stimulates secretion of GH, increases food intake and produces weight gain

Question 10

Ghrelin relation to fasting, eating, and hyperglycemia

Answer 10

• Secreted under fasting conditions

- Low levels after eating and with hyperglycemia

Question 11

Leptin after meal

Answer 11

Increases after meal

Question 12

Leptin function

Answer 12

• Decreases appetite and food consumption
• Increases heat production and activity
• Stimulates CRH expression

Question 13

NPY after meal

Answer 13

Decreases after meal

Question 14

Adipokine levels after gastric bypass surgery

Answer 14

 Ghrelin – decreases
 Leptin – decreases (less body fat?)
 NPY – increases

Question 15

Mechanism of hyperandrogenemia in PCOS

Answer 15

o Insulin stimulation of theca via insulin receptor (inositolphosphoglycan mediates androgen production)
o Decreased hepatic SHBG production (+androgens, which also decrease hepatic SHBG production)
o Insulin potentiated action of LH – increase LH pulse frequency (~1 pulse/hour) and (lesser extent) amplitude

Question 16

When is development of hair follicles complete

Answer 16

22 weeks gestation (no new follicles develop afterwards)

Question 17

Concentration of hair follicles where does not vary between sexes

Answer 17

Facial skin

Question 18

Major factor determining hair follicle concentration

Answer 18

Race/ethnicity

Question 19

MOA insulin and androgen synthesis

Answer 19

Insulin acts directly on the theca cells via insulin (tyrosine kinase) receptors - to stimulate androgen synthesis

Question 20

Other places insulin acts besides theca cells

Answer 20

• Insulin also acts on the IGF-1 receptor at high concentrations
• Insulin acts via inositolphosphoglycan (PI-3K) mediators – different than that of LH

Question 21

Metformin drug class

Answer 21

Biguanide oral insulin-sensitizing agent

Question 22

Metformin MOA

Answer 22

• Decreases hepatic glucose production
• Decreases intestinal glucose uptake
• Increases peripheral insulin sensitivity (up to 20%)
• Inhibits lipolysis (decreases circulating free fatty acids, reduces hepatic gluconeogenesis)

Question 23

Metformin clinical benefits

Answer 23

• Decreases weight and BMI (3-5%)

* Decreases BP and LDL

Question 24

Metformin guidelines for stopping pre-procedure

Answer 24

• Canadian guidelines: eGFR < 60, stop taking metformin at the time of contrast administration
• European guidelines: eGFR < 45, stop metformin 48 hours before CT

Question 25

Metformin guidelines for stopping pre-procedure

Answer 25

• Canadian guidelines: eGFR < 60, stop taking metformin at the time of contrast administration
• European guidelines: eGFR < 45, stop metformin 48 hours before CT

Question 26

Ovarian drilling subsequent physiologic changes

Answer 26

• Destroys theca cells -> decreased androgen and LH levels

- Androstenedione, LH, and LH/FSH ratio all decrease; no change in dopaminergic inputs