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2022 REI Written Boards > PCOS/Hirsutism/Obesity > Flashcards

PCOS/Hirsutism/Obesity Flashcards

1
Q

Contributors to obesity

A
  • Down-regulation of adiponectin (which increases insulin sensitivity)
  • Defect in leptin receptor
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2
Q

4 Adipokines that change after meal

A

Somatostatin, ghrelin, leptin, NPY

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3
Q

Somatostatin change after meal

A

Increases after meal

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4
Q

Somatostatin source cells

A

Release from gastric D-cells

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5
Q

Somatostatin regulation

A

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

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6
Q

Somatostatin function and MOA

A

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

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7
Q

Ghrelin change after meal

A

Decreases after meal

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8
Q

Ghrelin production location

A

Upper stomach

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9
Q

Ghrelin action

A

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

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10
Q

Ghrelin relation to fasting, eating, and hyperglycemia

A
  • Secreted under fasting conditions
  • Low levels after eating and with hyperglycemia
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11
Q

Leptin after meal

A

Increases after meal

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12
Q

Leptin function

A
  • Decreases appetite and food consumption
  • Increases heat production and activity
  • Stimulates CRH expression
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13
Q

NPY after meal

A

Decreases after meal

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14
Q

Adipokine levels after gastric bypass surgery

A

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

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15
Q

Mechanism of hyperandrogenemia in PCOS

A

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

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16
Q

When is development of hair follicles complete

A

22 weeks gestation (no new follicles develop afterwards)

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17
Q

Concentration of hair follicles where does not vary between sexes

A

Facial skin

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18
Q

Major factor determining hair follicle concentration

A

Race/ethnicity

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19
Q

MOA insulin and androgen synthesis

A

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

20
Q

Other receptor/mediator insulin acts on besides those in theca cells

A
  • Insulin also acts on the IGF-1 receptor at high concentrations
  • Insulin acts via inositolphosphoglycan (PI-3K) mediators – different than that of LH
21
Q

Metformin drug class

A

Biguanide oral insulin-sensitizing agent

22
Q

Metformin MOA

A
  • 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)
23
Q

Metformin clinical benefits

A
  • Decreases weight and BMI (3-5%)
  • Decreases BP and LDL
24
Q

Metformin guidelines for stopping pre-procedure for CT

A
  • Canadian guidelines: eGFR < 60, stop taking metformin at the time of contrast administration
  • European guidelines: eGFR < 45, stop metformin 48 hours before CT
25
Q

Metformin guidelines for stopping pre-procedure

A
  • Canadian guidelines: eGFR < 60, stop taking metformin at the time of contrast administration
  • European guidelines: eGFR < 45, stop metformin 48 hours before CT
26
Q

Ovarian drilling subsequent physiologic changes

A
  • Destroys theca cells -> decreased androgen and LH levels
  • Androstenedione, LH, and LH/FSH ratio all decrease; no change in dopaminergic inputs
27
Q

Obesity and hormone levels:

What’s increased? Decreased?

A

Decreased: NPY, SHBG, GH
Increased: E2, cortisol, testosterone, insulin, leptin

Obesity -> insulin level -> inhibit expression of neuropeptide Y (mediated via leptin)

28
Q

Exercise-induced hormone changes

A
  • Increased endogenous opioids (inhibit GnRH)
  • Increased cortisol (reflection of increased CRH activity which also inhibits GnRH)
  • Decreased leptin (recombinant leptin can restore menstrual function in amenorrheic women who exercise excessively) (suppresses the HPO, thyroid, and adrenal axis)
  • Decreased LH pulse frequency and amplitude
  • Decreased estradiol
29
Q

Risk of mood disorder in obese women?

A

25-50% more likely to experience mood disorder

Depression can also lead to obesity from low serotonin levels, leading to overeating

30
Q

Dx of metabolic syndrome

A
  • Need 3/5:
    1. HTN (130/85 or higher)
    2. TG level (>150 mg/dL or higher)
    3. HDL-cholesterol (<50mg/dL)
    4. Abdominal obesity (>35 inch waist circumference)
    5. Fasting glucose (100 mg/dL or higher)
31
Q

In PCOS, what regulatory systems are messed up?

A
  1. Gonadotropin secretion
  2. Insulin secretion & action
  3. Weight & energy regulation
  4. Androgen biosynthesis & action
32
Q

IGF-1: Where is it made? and in response to what?

What are low levels associated w/?

A

Made in liver in response to GH

Low levels associated w/ DM

33
Q

Insulin transduction pathways up & down-regulated in PCOS

A
  • Phosphatidyl-inositol 3-kinase (PI-3K) pathway (down-regulated in PCOS)
    • Metabolic effects via Akt (signal transduction molecule)
      1. Akt activation moves glucose transporter 4 (GLUT4) from intracellular compartments to the plasma membrane – thus increasing glucose uptake
    • Mitogen-activated protein kinase (MAPK) pathway (up-regulated in PCOS)
      1. Proliferative actions
34
Q

Most common mechanism of insulin resistance?

A

Obesity

35
Q

Causes of hyperandrogenism in PCOS (2)

A
  1. Insulin acts on insulin receptors within ovarian theca and stromal cells
    1. Hyperinsulinemia → increased GnRH pulse frequency → LH over FSH dominance → increased ovarian androgen production → decreased follicular maturation
    2. Decreases SHBG production from the liver
36
Q

Cutoffs for 75g 2hr OGTT (insulin & glucose)

A
  1. Interpretation of insulin response (2h)
    1. Normal <100 U/mL
    2. Insulin resistance likely 100-150 U/mL
    3. Resistance 151-300 U/mL
    4. Severe resistance >300 U/mL

Interpretation of glucose response

  1. Fasting: <110 mg/dL normal, 110-125 mg/dL borderline, >125 mg/dL dx of DM
  2. 2h: <140 mg/dL normal, 140-200 mg/dL impaired glucose tolerance, >200 dx of DM
37
Q

Effects of metformin on cholesterol levels

A
  • Decreases total serum cholesterol
  • Decreases LDL
  • No change in HDL cholesterol
  • No change in triglycerides
38
Q

How is insulin receptor DEactivated?

A
  • Tyrosine dephosphorylation via tyrosine phosphatase**
  • Degradation by cathepsin D
  • Acidification of the internalized insulin receptors (within endosomes)
  • Sequestering of activated insulin receptor from signal transduction elements

In insulin resistance, more serine phosphorylation instead of tyrosine phosphorylation (see other card)

39
Q

Spironolactone effect on DHT? SHBG?

A

blocks DHT binding to skin androgen receptors

Increases SHBG concentration

40
Q

Best test for insulin resistance…but no longer used

A

Euglycemic clamp technique

Insulin-induced glucose uptake is measured while blood glucose concentration is maintained at a steady concentration (via exogenous dextrose infusion) to avoid the confounding effects of counter-regulatory hormones such as epinephrine and glucagon.

Ratio of fasting glucose: insulin (ratio <4.5 = insulin resistance)

varies w/ ethnicity, takes time & IV sticks

41
Q

Effect of OCPs on patients with PCOS

A

Mechanism of action

  1. Increases SHBG (decreases free androgens)
  2. Decreases LH (decreases androgen production by theca cells)
  3. Inhibits 5α-reductase and androgen receptor binding
42
Q

most elevated serum androgen with hirsutism?

A

Free testosterone

43
Q

1st test in PCOS-appearing pt? when would you want to check 17-OHP?

A
  1. Total testosterone

Early onset hirsutism (pre- or perimenarcheal)

Family history of CAH

High-risk ethnic group (Hispanic, Mediterranean, Slavic, Ashkenazi Jewish)

44
Q
  • Which of the following does NOT inhibit an androgen receptor?
  • Finasteride
  • Spironolactone
  • Flutamide
  • Danazol
A

Danazol - Binds androgen receptors (displaces testosterone, increases free testosterone levels)

45
Q

MOA of spironolactone

A

Selective aldosterone blocker (competes with aldosterone for receptor sites in distal renal tubules)

Blocks DHT binding to skin androgen recpetors

46
Q

What enzyme does a pilosebaceous unit (i.e., hair follicle, sebaceous gland, and arrector pili muscle) display?

A

substantial aromatase activity - significant source of estrogen synthesis, both in men and women

2022 REI Written Boards (21 decks)

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