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Year 2 - T2 Theme 1 > L12 - Effects of age and diet on endocrine function > Flashcards

L12 - Effects of age and diet on endocrine function Flashcards

1
Q

‘Similar phenotypes’ -hypogonadism/growth hormone deficiency

A
  • Increase in fat mass, increase in visceral fat
  • Sarcopaenia
  • Decrease in bone mineral density
  • Decrease in QOL/mood
  • Increase in risk of cardiovascular disease
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2
Q

Link between insulin/glucose levels and age

A
  • Increase in [insulin] and [glucose] with increase in age
  • Increase in insulin resistance
  • Decrease peripheral glucose uptake
  • Increase in prevalence metabolic
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3
Q

Closely associated CV risk factors - metabolic syndrome

A
  • Visceral obesity
  • Dyslipidaemia
  • Hyperglycaemia
  • Hypertension
  • Insulin resistance is the underlying pathophysiological mechanism
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4
Q

What does the hypothalamus secrete in the gonadal axis

A
  • The hypothalamus secretes GnRH
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5
Q

Effect of GnRH

A
  • GnRH travels down to the anterior pituitary gland
  • It binds to receptors on the pituitary gland
  • This causes the release of of LH and FSH
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6
Q

Effect of LH - male

A
  • LH stimulates leydig cells in the testicles to produce testosterone
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7
Q

Effect of FSH - male

A
  • FSH stimulates sertoli cells to produce androgen binding globulin (ABG) and inhibin
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8
Q

What is ABG

A
  • ABG is a protein which binds to testosterone and keeps it within the seminiferous tubules
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9
Q

Function of inhibin

A
  • Inhibin helps support spermatogenesis and inhibits production of FSH, LH and GnRH
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10
Q

What type of feedback does an increase in testosterone and inhibin levels provide

A
  • Negative feedback on the hypothalamus and pituitary
  • This results in a decreased production of LH and FSH
  • As a result, production of testosterone and inhibin is also decreased
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11
Q

Effect of LH and FSH - female

A
  • When FSH and LH bind to the ovaries, they stimulate production of oestrogen and inhibin
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12
Q

Effect of oestrogen

A

Oestrogen helps regulate the menstrual cycle and is essential in many body processes

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13
Q

Effect of increasing oestrogen and inhibin levels on the pituitary and hypothalamus

A

Increasing levels of oestrogen and inhibin cause negative feedback on the pituitary and hypothalamus.

  • This leads to decreased production of GnRH, LH and FSH.
  • This in turn results in decreased production of oestrogen and inhibin.
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14
Q

What is the graafian follicle

A
  • The follicle most sensitive to FSH
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15
Q

Effects of FSH on the ovaries

A

FSH binds to ovaries stimulating the development of ovarian follicles and secretion of inhibin and oestrogen

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16
Q

Effects of LH on the ovaries

A
  • Production of oestrogen which is required for ovulation and thickening of the endometrium
  • Conversion of the Graafian follicle into the progesterone producing corpus luteum
  • Progesterone causes the endometrium to become receptive to implantation of a fertilised ovum
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17
Q

What causes cessation of menstruation during pregnancy

A

Oestrogen, Progesterone and Inhibin all cause negative feedback on the pituitary and hypothalamus.

This results in reduction of GnRH, FSH and LH production.

In pregnancy GnRH, FSH and LH all remain inhibited, causing cessation of menstruation.

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18
Q

Oestrogen levels - Pre and post menopausal

A
  • Pre-menopausal - cycling
  • Post-menopausal - very low constant levels
  • Decrease in E2, increase in LH/FSH
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19
Q

Age at menopause

A

50 +/- 2 years

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20
Q

Menopausal symptoms

A
  • Hot flushes
  • Night sweats
  • Median duration of menopausal symptoms 7 years
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21
Q

Morbidities associated with menopause

A
  • Increase in risk of osteoporosis
  • Increase in risk of coronary heart disease
  • Increase in sexual dysfunction
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22
Q

Evaluation of post-menopausal hormone replacement therapy

A

• Initial observational studies showed benefits
○ ‘healthy user bias’
• Some subsequent RCTs showed no benefits and increased risks
• However risk : benefit ratio depends on
○ Other risk factors
○ Age of woman and duration of HRT use
□ greater risk if >60 yrs, >10 year post-MP
○ Type of HRT (oestrogen, progestogen, route)

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23
Q

Benefits of hormone replacement therapy

A
  • Rx menopausal Sx
  • Decrease in risk of osteoporosis/fracture risk
    for duration Rx
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24
Q

Risks of post-menopausal HRT

A
  • Increased risk of venous thrombo-embolism
  • Increased risk of breast Ca (small) esp > 5 years
  • Increase in endometrial Ca, if use unopposed E2
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25
Q

changes in testosterone levels with age

A
  • Gradual decrease in testosterone levels with an increase in age
26
Q

Factors associated with clinical hypogonadism

A
  • Decrease in sexual function
  • Increase in risk of osteoporosis
  • Decrease in muscle strength
27
Q

Effect of hypogonadism on bone density

A
  • Increase in bone mineral desnity
28
Q

What are biphosphonates

A
  • Biphosphonates are a class of drugs that prevent the loss of density, used to treat osteoporosis and similar diseases
  • Biphosphonates work, independent of androgen status
29
Q

What is most erectile dysfunction linked to

A
  • Most erectile dysfunction is atherosclerotic
30
Q

Effects of testosterone treatment

A
  • Increase in lean body mass
  • Decrease in fat mass
  • No convincing functional benefits demonstrated
  • Increase in muscle strength with supra-physiological doses
31
Q

Effect of weight loss on testosterone

A
  • Positive correlation

- Increase in weight loss showed increased testosterone levels

32
Q

Link between [GH], [IGF-I] and age

A
  • Decrease in integrated [GH] with an increase in age
  • Decrease in [IGF-I] with an increase in age
  • Wide variation in ‘normal range’
33
Q

Effects of growth hormone treatment

A
  • Increase in lean body mass - 2kg
  • Decrease in fat mass - 2kg
  • No convincing functional benefits demonstrated
  • No significant change in bone mineral density or lipid levels
34
Q

Potential risks of growth hormone treatment

A

• ↑ cancer: ↑ [IGF-I] in observational studies is associated with ↑ risk non-smoking related Ca
○ prostate, colon, breast
• ­Increase in risk of T2 DM

35
Q

Side effects of growth hormone treatment

A
  • Soft tissue oedema
  • Arthralgias
  • Carpal tunnel syndrome
36
Q

Changes in cortisol levels with age

A
  • Increase in trough levels cortisol with age
  • Increase in average levels of cortisol with age
  • Phase advance of diurnal rhythm (time at trough and peak both earlier)
37
Q

What is sapolsky’s glucocorticoid cascade hypothesis

A
  • Decrease in hippocampal glucocorticoid and mineralocorticoid receptors
  • Decrease in sensitivity to glucocorticoid negative feedback
  • Increase in glucocorticoid levels
  • ‘feed forward cascade’ - decrease in hippocampal volume on MRI - no differences in volume of adjacent structures
  • Other roles of hippocampus: learning, memory - increase in cortisol associated with decline in cognitive function
38
Q

Changes in dehydroepiandrosterone with age

A
  • Overall decline in dehydroepiandrosterone with age
39
Q

What is DHEA production under the regulation of

A
  • DHEA production is controlled by ACTH production and by the gonads under the control of GnRH
40
Q

What receptors does DHEA act on

A
  • Action via androgen and/or oestrogen receptors

- ‘Pro-hormone’

41
Q

Importance of DHEA in men

A
  • Overwhelming excess of more potent circulating androgens

- Contribution to androgenic effects in men ‘modest’ at most

42
Q

Link between [DHEAS] and age

A
  • [DHEAS] decreases with age

- By 70-80 years, [DHEAS] - 5-10% of peak

43
Q

What is an increase in [DHEAS] associated with

A
  • Improvement in quality of life, increase in bone mineral density, decrease in cognitive decline and decrease in risk of coronary heart disease
44
Q

What can [DHEA] be a marker of

A
  • [DHEA] is a non-specific marker of ill health
  • Associations may not be not casual
  • Decrease in [DHEA]: cortisol ratio found in cancer, inflammatory diseases, T2DM, CV disease
45
Q

Is there evidence to suggest that DHEA has beneficial effects

A

No evidence of beneficial effects on

  • Body composition
  • Physical performance
  • Insulin sensitivity
  • QOL
  • Multiple studies have not demonstrated any positive effect of DHEA in ageing individuals
46
Q

How do thyroid levels change with age

A
  • Slight increase in [TSH] with age
  • Decrease in peripheral T4 –> T3 conversion with age
  • Decrease in [T3] with age
  • No evidence for beneficial effect of T4 treatment
47
Q

Why might a slight increase in [TSH] with age have harmful effects

A
  • Increase in risk of osteoporosis, atrial fibrillation

- Risk in elderly with atherosclerotic coronaries

48
Q

What is leptin produced by

A
  • White adipose tissue
49
Q

What does [leptin] correlate with

A
  • [Leptin] correlates with BMI and body fat
50
Q

What does a decrease in [leptin] cause

A
  • Decrease in [leptin] causes an increase in food intake and decrease in energy expenditure
  • Decrease in [leptin] also has detrimental effects on fertility
51
Q

Effect of starvation on LH, FSH, oestrogen/testosterone levels

A
  • Decrease in LH and FSH
  • Decrease in oestrogen/testosterone
  • Decrease in fertility, amenorrhoea
  • Osteoporosis - treat with HRT/COCP
52
Q

What is hypothalamic amenorrhoea

A
  • Hypothalamic amenorrhea is a condition in which menstruation stops for several months due to a problem involving the hypothalamus
53
Q

Features of the Ob Ob mouse

A
  • Hyperphagic and obese
  • Low gonadotrophins
  • Incomplete development of reproductive organs
  • Does not reach sexual maturity
  • Infertile
54
Q

Effect of leptin treatment on the Ob Ob mouse

A
  • Reduce obesity
  • Restore Gn secretion
  • Mature gonad
  • Induce puberty
  • Restore fertility
55
Q

What is kisspeptin

A
  • A GnRH secretagogue
56
Q

What are KISS1 neurons highly responsive to

A
  • KISS1 neurons are highly responsive to oestrogen, implicated in both positive and negative feedback of sex steroids on GnRH production
57
Q

What metabolic influences on reproduction are mediated by leptin

A
  • Metabolic influences on reproduction mediated by leptin via the kisspeptin system include puberty and reproduction
58
Q

Effect of leptin on kisspeptin

A
  • Leptin has a permissive effect on kisspeptin
59
Q

Effect of starvation/AN on GH/IGF axis

A
  • ‘GH resistance’
  • Increase in GH, decrease in IGF-I
  • Seen in acute starvation and in AN
  • Down-regulation hepatic GH receptor and/or post-receptor defect
  • Reversible with re-feeding
60
Q

Effect of starvation/AN on thyroid function

A
  • TSH and T4 lower limit of normal
  • Decrease in T4 conversion to T3 (active)
  • Increase in T4 conversion to rT3 (inactive)

Consequences:

  • Lower basal metabolic rate
  • Conserve energy

Year 2 - T2 Theme 1 (20 decks)

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