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Year 2 Medicine > Effects of Age and Diet on Endocrine Function > Flashcards

Effects of Age and Diet on Endocrine Function Flashcards

1
Q

Effects of age on endocrine function

  • look at … status
  • …/… levels
  • … axis i.e. menopause, ‘andropause’
  • GH-IGF system - what is this?
  • … levels
  • DHEA
  • … function
A
  • look at nutritional status
  • Insulin/glucose levels
  • Gonodal axis i.e. menopause, ‘andropause’
  • GH-IGF system - growth hormone / IGF system
  • Cortisol levels
  • DHEA - dehydroepiandrosterone
  • Thyroid function
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2
Q

Effects of diet on endocrine function

  • Starvation
  • … Nervosa
    • …/glucose levels
    • L… levels
    • … axis
    • GH-IGF system - what is this
    • C… levels
    • … function
A
  • Starvation
  • Anorexia Nervosa
    • insulin/glucose levels
    • leptin levels
    • Gonodal axis
    • GH-IGF system - Growth hormone IGF system
    • Cortisol levels
    • Thyroid function
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3
Q

Different perspectives on age, diet and endocrine function

  • Evolutionary perspective is what?
    • Hormonal function:
      • …pause exists
      • ‘andropause’
      • ‘somatopause’
      • ‘adrenopause’
  • Cultural perspective is what?
    • Anti-aging results in … google hits
  • Pharma perspective is what?
A
  • Evolutionary perspective
    • We are outliving our natural lifesan
    • Hormonal function:
      • menopause
      • ‘andropause’
      • ‘somatopause’
      • ‘adrenopause’
  • Cultural perspective is what?
    • Anti-aging results in 3,000,000 google hits
  • Pharma perspective is what?
    • enourmous market - especially compared to endocrine market for testosterone / GH
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4
Q

Is 80 the new 60?

“Just because that happens doesnt mean that it’s health or inevitable … there must be a supplement or hormone that I can take to counteract it”

who said this?

A

healthy 76 yo compaining of loss of flexibility (yoga expert)

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5
Q

‘Medicalisation’ - Aging and endocrine function

  • Increased … expectancy may not equate to increased … expectancy
  • ‘Usual ageing’ what does this mean?
    • physiological?
    • pathological?
    • optimal?
  • Hormonal influence
    • dwarfed by other influences, what are these? (4)
  • Balance of … and … of treatment
    • risks - esp … risk in elderly
    • … - GH/testo not … active
    • … involved
A
  • Increased life expectancy may not equate to increased health expectancy
  • Usual ageing
    • physiological?
    • pathological?
    • optimal?
  • Hormonal influence
    • dwarfed by other influences, what are these? (4)
      • Genetic
      • Environmental
      • Psychosocial
      • Co-morbidities
        • Balance of benefit and harm of treatment
    • risks - esp cancer risk in elderly
    • hassle - GH/testo not orally active
    • Costs involved
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6
Q

Association and Causation - Aging and endocrine function

  • Similar ‘phenotypes’ between …/… deficiency and aging
    • Increased … mass, increased … fat
    • Sarco…
    • Decreased bone … density
    • Decreased …/mood
    • Increased risk of … disease
  • BUT:
    • Phenotypes are non-… and high …
A
  • Similar ‘phenotypes’ between Hypogonadism/GH deficiency and aging
    • Increased fat mass, increased visceral fat
    • Sarcopaenia
    • Decreased bone mineral density
    • Decreased QOL/mood
    • Increased risk of CV disease
  • BUT:
  • Phenotypes are non-specific and high prevalence
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7
Q

Age: Nutritional status

  • Weight
    • increases from mid-…s
    • Plateau after age of … onwards
  • Lean body mass
    • declines by approx …-…% / decade from mid …s
  • Diet
    • trend towards (decrease or increase?) intake total energy and protein with increasing age
A
  • Weight
    • increases from mid-30s
    • Plateau after age of 50-70
  • Lean body mass
    • declines by approx 6-8% / decade from mid 30s
  • Diet
    • trend towards decreased intake total energy and protein with increasing age
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8
Q

Age: Insulin/glucose

  • As you get older what happens to levels of insulin and glucose?
    • What happens to insulin resistance?
    • What happens to peripheral glucose uptake?
  • Increased prevalence of … syndrome with increased age
A
  • As you get older what happens to levels of insulin and glucose? insulin and glucose levels increase
    • What happens to insulin resistance? - increases
    • What happens to peripheral glucose uptake? - decreases
  • Increased prevalence of metabolic syndrome with increased age
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9
Q

Metabolic syndrome

  • ‘Constellation of closely associated … risk factors’
    • These are … (4)
  • … resistance is the underlying pathophysiological mechanism
A
  • ‘Constellation of closely associated CV risk factors’
    • These are … (4)
      • Visceral obesity
      • Dyslipidaemia
      • Hyperglycaemia
      • Hypertension
  • Insulin resistance is the underlying pathophysiological mechanism
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10
Q

This graph shows that the prevalence of … syndrome goes up by age

A

metabolic syndrome

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11
Q

What axis is shown?

A

Gonadal axis

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12
Q

Age: Menopause

  • Menopause means what?
    • Oestrogen levels:
      • Pre-menopausal: there is a …
      • Post-menopausal: levels are … meaning levels of LH and FSH are … - why?
    • ? What causes menopause
    • Average age of menopause is roughly … with a standard deviation of 2 years
    • Symptoms of menopause include … (2)
    • Symptoms median duration is … years
    • Morbidity:
      • Increased chance of osteo… increased CHD - what is this? increased sexual …
A
  • Menopause means ovarian failure
    • Oestrogen levels:
      • Pre-menopausal: there is a cycle
        • Post-menopausal: levels are very low meaning levels of LH and FSH are constantly high - why? - because of the lack of negative feedback
        • ? What causes menopause - brain and ovary are ‘pacemakers’
        • Average age of menopause is roughly 50 with a standard deviation of 2 years
        • Symptoms of menopause include hot flushes, night sweat
        • Symptoms median duration is 7 years
        • Morbidity:
          • Increased osteoporosis increased CHD (coronary heart disease)increased sexualdysfunction
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13
Q

Age: Menopause - Post-Menopausal HRT

  • Hormone replacement therapy
    • Initial observational studies showed benefits (… user bias)
    • Some subsequent RCTs showed what?
    • However, ratio depends on
      • other risk factors
      • … of woman and … of use
        • greater risk if >…yrs, >…yrs post-MP
      • … of HRT (oestrogen, progestogen, route)
A
  • Hormone replacement therapy
    • 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 use
        • greater risk if >60yrs, >10yrs post-MP
      • Type of HRT (oestrogen, progestogen, route)
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14
Q

Post-menopausal HRT

  • Benefits
    • Treatment of menopausal symptoms
    • decreased risk of … / fracture risk
      • for … of treatment only
  • Risks
    • increased risk of venous …-…
    • increased … cancer risk (esp >5yrs)
    • increased … cancer if unopposed oestrogen is used
A
  • Benefits
    • Treatment of menopausal symptoms
    • decreased osteoporosis / fracture risk
      • for duration of treatment
  • Risks
    • increased risk of venous thrombo-embolism - particularly smokers
    • increased breast cancer risk (esp >5yrs)
    • increased endometrial cancer - if use unopposed oestrogen used
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15
Q

Post-menopausal HRT - goals of treatment

  • Goals have shifted back:
    • from … (to prevent disorders associated with post-menopausal oestrogen deficiency, like osteoporosis)
    • To … of menopausal …
      • … term, … effective dose, … menopausal women
A
  • from replacement (to prevent disorders associated with post-menopausal oestrogen deficiency, like osteoporosis)
  • To treatment of menopausal symptoms
    • short term, lowest effective dose, younger menopausal women
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16
Q

Male Gonadal Axis

  • Gradual testosterone … with increased age
  • Wide range of … at all ages
  • @ 75 years, mean testosterone is …/… that @ 25years
  • … association between libido / erectile dysfunction and testosterone
  • Testosterone prescriptions increased by …% over the past decade
A
  • Gradual testosterone decrease with increased age
  • Wide range of normality at all ages
  • @ 75 years, mean testosterone is 2/3 that @ 25years
  • Poor association between libido / erectile dysfunction and testosterone
  • Testosterone prescriptions increased by 500% over the past decade
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17
Q

What does this figure illustrate?

A

The gradual decline in testosterone with age

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18
Q

What is this table showing?

A

Testosterone range for 95% of healthy men

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19
Q

Age - Male Gonodal Axis

  • Clinical hypo…
    • … sexual function
    • … risk of osteoporosis
    • … muscle strength
  • Questions
    • are some features of ageing secondary … deficiency
    • Would treatment be beneficial or risky?
A
  • Clinical hypogonadism
    • decreased sexual function
    • increased risk of osteoporosis
    • decreased muscle strength
  • Questions
    • are some features of ageing secondary androgen deficiency
    • Would treatment be beneficial or risky?
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20
Q

Testosterone treatment in older men

  • Are there improvements in sexual function?
    • most erectile dysfunction in older age is …
    • drugs like sildenafil (‘…’) may work
  • Little or no evidence of benefit or insufficient data that testosterone improves… (3)
  • Potential risks
    • … (benign prostatic hypertrophy / cancer)
    • … (increased haematocrit)
    • ? … risk (MI/strokes)
A
  • There are small improvements in sexual function
    • most erectile dysfunction in older age is atherosclerotic
    • drugs like sildenafil (‘viagra’) may work
  • Little or no evidence of benefit or insufficient data
    • physical function, including energy & vitality
    • cognitive function
    • mood/QOL
  • Potential risks
    • prostate (benign prostatic hypertrophy / cancer)
    • erythropoeisis (increased haematocrit)
    • ? CVS risk (MI/strokes)
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21
Q

Testosterone treatment in older men (2)

  • Bones
    • increased bone … … if hypogonadal
    • What is the effect on fractures?
    • … work, independent of androgen status
  • Body composition
    • … lean body mass
    • … fat mass
    • no convincing functional benefits demonstrated
    • increased muscle … with supra-physiological doses
A
  • Bones
    • increased bone mineral density if hypogonadal
    • ? Effect on fractures - unknown
    • Bisphosphonates work, independent of androgen status
  • Body composition
    • increased lean body mass
    • decreased fat mass
    • no convincing functional benefits demonstrated
    • increased muscle strength with supra-physiological doses
22
Q

What are these quotes discussing treatment of?

A

Testosterone treatment in older men

23
Q

What axis is shown here?

A

GH-IGF-1-axis

24
Q

GH-IGF-1-Axis - age

  • … integrated GH with increased age, … IGF-1 with increased age
  • Wide variation in … range
A
  • decreased integrated GH with increased age, decreased IGF-1 with increased age
  • Wide variation in normal range
25
Q

GH treatment in older individuals

  • Body composition
    • Lean body mass?
    • Fat mass?
    • Overall are there benefits for this?
  • Is there a significant change in
    • bone mineral density?
    • Lipids?
A
  • Body composition
    • Lean body mass? - increases by about 2kg
    • Fat mass? - decreases by about 2kg
    • Overall are there benefits for this? - no convincing functional benefits demonstrated
  • Is there a significant change in
    • bone mineral density? - no
    • Lipids? - slight improvement in total cholesterol levels (reduced)
26
Q

Risks of GH treatment in older adults

  • What are the potential risks? (2)
    • higher IGF-1 is associated with…
    • increased risk of type …
  • What are the side-effects? (3)
A
  • Potential risks include:
    • increased risk of cancer (increased IFG-1) in observational studies is associated with increased risk non-smoking related cancer (i.e. prostate, colon, breast)
    • also increased risk of T2 DM
  • Side effects:
    • soft tissue oedema
    • arthralgias
    • carpal tunnel syndrome
27
Q

What is this quote discussing?

A

Growth hormone

28
Q

What axis is this?

A

Hypothalamic-pituitary-adrenal axis

29
Q

Effects of age on cortisol levels

  • … trough levels cortisol with increased age
    • … average levels with increased age
    • phase advance of … rhythm
      • time at trough and peak both earlier or later?
A
  • Increased trough levels cortisol with increased age
    • increased average levels with increased age
    • phase advance of diurnal rhythm
      • time at trough and peak both earlier
30
Q

Sapolsky’s glucocorticoid cascade hypothesis

  • … hippocampal glucocorticoid and mineralocorticoid receptors with increasing age
  • … sensitivity to glucocorticoid negative feedback
  • Hippocampal … vulnerable to damage
  • ‘feed forward cascade’
    • volume hippocampus … on MRI - no differences in volume of adjacent structures
  • Hippocampus roles include learning and memory
    • Therefore cortisol associated with what?
A
  • Decreased hippocampal glucocorticoid and mineralocorticoid receptors with increasing age
  • Decreased sensitivity to glucocorticoid negative feedback
  • Hippocampal neurons vulnerable to damage
  • ‘feed forward cascade’
    • volume hippocampus decreased on MRI - no differences in volume of adjacent structures
  • Hippocampus roles include learning and memory
    • Therefore cortisol associated with increased decline of cognitive function
31
Q

DHEAS is an … androgen

A

DHEAS is an adrenal androgen

32
Q

What happens to levels of DHEA with age?

A

Declining levels with age

33
Q

DHEA - regulation of action

  • regulation of action of DHEA - unclear
    • ?stimulated same as cortisol, by …
    • ?Action via androgen and/or oestrogen receptors
      • ‘…-hormone’
      • Potential for adverse effects of treatment (… , … tissue) - not demonstrated
A
  • regulation of action of DHEA - unclear
    • ?ACTH - same as cortisol
    • ?Action via androgen and/or oestrogen receptors
      • ‘pro-hormone’
      • Potential for adverse effects of treatment (prostate, breast) - not demonstrated
34
Q

DHEA - importance in men?

  • Overwhelming excess of more potent circulating …
  • Contribution to androgenic effects in men ‘…’ at most
A
  • Overwhelming excess of more potent circulating androgens
  • Contribution to androgenic effects in men ‘modest’ at most
35
Q

DHEAS - age

  • Levels … with age
    • by 70-80, DHEAS is …% of peak
    • Observational studies have suggested increased DHEAS is associated with increased … (2) and decreased … (2)
    • Decreased DHEA is a non-specific marker of … health
      • associations may not be …
      • decreased DHEA / DHEA:cortisol ratio found in … (4 conditions/diseases)
A
  • Levels decrease with age
    • by 70-80, DHEAS is 5-10% of peak
    • Observational studies have suggested increased DHEAS is associated with increased QOL and bone mineral density (2) and decreased cognitive decline and coronary heart disease(2)
    • Decreased DHEA is a non-specific marker of ill health
      • associations may not be causal
      • decreased DHEA / DHEA:cortisol ratio found in cancer, inflammatory disease, T2DM, CV disease
36
Q

DHEA - USA

  • Is it regulated?
  • Is it a drug or supplement?
  • Is it readily available?
  • Is it well regulated?
A
  • Is it regulated - Yes - FDA
  • Is it a drug or supplement - Food Supplement
  • Is it readily available? - yes
  • Is it well regulated? - no - composition varies - may contain 0-15% of amount stated on packet
37
Q

DHEA - overview

  • Is there evidence of beneficial effects on:
    • body composition?
    • physical performance?
    • insulin sensitivity?
    • QOL?
  • Are there any adverse effects demonstrated?
  • Have studies demonstrated any positive effect of DHEA in aging individuals ?
  • evidence for use?
A
  • Is there evidence of beneficial effects on:
    • body composition? - no
    • physical performance? - no
    • insulin sensitivity? - no
    • QOL? - no
  • Are there any adverse effects demonstrated? - no
  • Multiple studies have not demonstrated any positive effect of DHEA in aging individuals
  • No evidence for use
38
Q

What axis is shown?

A

Thyroid axis

39
Q

Age: Thyroid function

  • Slight … TSH with age
  • T4 levels?
  • … peripheral T4 -> T3 conversion with age
  • … T3 with age
  • evidence for beneficial effect of T4 treatment ?
    • may do …
      • What are 3 risks?
A
  • Slight increase TSH with age
  • T4 levels? - stay more or less same
  • Decreased peripheral T4 -> T3 conversion with age
  • Decreased T3 with age
  • No evidence for beneficial effect of T4 treatment
    • may do harm
      • risk of osteoporosis, atrial fibrillation
      • risk in elderly with atherosclerotic coronaries
40
Q

Starvation/AN - insulin, glucose and leptin

  • What happens to Insulin and glucose levels and insulin sensitivity?
  • Leptin is produced by …
    • leptin correlates with …
    • reports … information to the hypothalamus
      • ‘… signal’ signals energy availability
      • … leptin = increase food intake, decrease energy expenditure
      • decrease leptin = decreased …
        • permissive factor for initiation of …
A
  • What happens to Insulin and glucose levels and insulin sensitivity? - glucose and insulin levels decrease, insulin sensitivity increases
  • Leptin is produced by white adipose tissue
    • leptin correlates with BMI and body fat
    • reports nutritional information to the hypothalamus
      • ‘starvation signal’ signals energy availability
      • decreased leptin = increase food intake, decrease energy expenditure
      • decrease leptin = decreased fertility
        • permissive factor for initiation of puberty
41
Q

Starvation/AN - oestrogen/testosterone

  • …. LH and FSH
  • … oestrogen and testosterone
  • … fertility, amenorrhoea
    • termed ‘hypothalamic amenorrhoea’
    • makes evolutionary sense in times of …
    • osteo… - treatment HRT / COCP
A
  • Decreased LH and FSH
  • Decreased oestrogen and testosterone
  • Decreased fertility, amenorrhoea
    • ‘hypothalamic amenorrhoea’
    • makes evolutionary sense in times of famine
    • osteoporosis - treatment HRT / COCP
42
Q

Links between metabolism and reproduction

  • Ob Ob mouse
    • hyperphagic and obese
  • Also had:
    • low …trophins
    • incomplete development of … organs
    • does not reach … maturity
    • fertile?
  • … - treatment
    • reduced obesity
  • Also:
    • restored … secretion
    • … gonad
    • induced …
    • restored …
A
  • Ob Ob mouse
    • hyperphagic and obese
  • Also:
    • low gonadotrophins
    • incomplete development of reproductive organs
    • does not reach sexual maturity
    • infertile
  • Leptin - treatment
    • reduced obesity
  • Also:
    • restored GN secretion
    • mature gonad
    • induced puberty
    • restored fertility
43
Q

Central mediator: kisspeptin

  • A … secretagogue - at the apex of the reproductive axis in the hypothalamus
  • KISS1 neurons highly responsive to …, implicated in both + and - central feedback of sex steroids on GnRH production
  • Metabolic influences on reproduction:
    • mediated by …: permissive effect
    • via the kisspeptin system
    • puberty and reproduction
A
  • A GnRH secretagogue - at the apex of the reproductive axis in the hypothalamus
  • KISS1 neurons highly responsive to oestrogen, implicated in both + and - central feedback of sex steroids on GnRH production
  • Metabolic influences on reproduction:
    • mediated by leptin: permissive effect
    • via the kisspeptin system
    • puberty and reproduction
44
Q

What does this show the permissive effect of?

A

Permissive effect of leptin on kisspeptin

45
Q

Starvation/AN: GH/IGF axis

  • GH …
    • … GH, … IGF-1
  • Seen in acute … and in AN
  • ? down-regulation hepatic GH receptor and / or post-receptor defect
  • Reversible with …
A
  • GH resistance
    • high GH, low IGF-1
  • Seen in acute starvation and in AN
  • ? down-regulation hepatic GH receptor and / or post-receptor defect
  • Reversible with re-feeding
46
Q

Starvation/AN: cortisol

  • Left (Individual data) = fed state
  • Right (Individual data) = fasting state
  • What happens to cortisol in fasting state?
A
  • In fasting state - starvation - stress response - increased cortisol pulses - loss of diurnal trough - get increased pulsatility of cortisol
47
Q

Starvation/AN: Thyroid function

  • TSH and T4 … limit of normal
  • … T4 conversion to T3 - (active)
  • … T4 conversion to rT3 (inactive)
  • Consequences?
A
  • TSH and T4 lower limit of normal
  • Less T4 conversion to T3 - (active)
  • More T4 conversion to rT3 (inactive)
  • Consequences?
    • lower basal metabolic rate
    • conserve energy
48
Q

Do you treat issues with thyroid function during starvation/ anorexia nervosa with thyroxine?

A
  • no - treat starvation / AN
  • body is trying to conserve energy
49
Q

With increasing age: decrease or increase

  • E2/T levels …
  • DHEA levels …
  • FSH (women) levels …
  • GH/IGF-1 levels …
  • Cortisol levels …
  • T3 levels …
  • Insulin/glucose levels …
A
  • E2/T - decrease
  • DHEA - decrease
  • FSH (women) - increase
  • GH/IGF-1 - decrease
  • Cortisol - increase
  • T3 - decrease
  • Insulin/glucose - decrease
50
Q

During starvation/AN: high or low

  • E2/T levels …
  • Leptin levels …
  • FSH/LH levels …
  • GH levels …
  • IGF-1 levels …
  • Cortisol levels …
  • T3 - active levels .. inactive levels..
A
  • E2/T - low
  • Leptin - low
  • FSH/LH - low
  • GH - high
  • IGF-1- low
  • Cortisol - high
  • T3 - low active, high inactive

Year 2 Medicine (162 decks)

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