Endocrinology of ageing

Question 1

Weight and lean body mass changes with age

Answer 1

Weight increases from mid-30s
- Stays stable 50-70

Lean body mass decreases
- 6-8%, from mid-30s

Question 2

Diet trend with age

Answer 2

Decrease in intake of total energy

Protein intake increases

Question 3

Insulin and glucose changes with age

Answer 3

Insulin and glucose increase

• Increase in insulin resistance
• Decrease in peripheral glucose uptake
• Increased prevalence of metabolic syndrome

Question 4

Metabolic syndrome

Answer 4

Closely related conditions that increase the risk of CVD..

• Visceral obesity
• Dyslipidaemia
• Hypertension
• Hyperglycaemia

Increased prevalence as age increases due to an increase in insulin resistance.
- Generally more prevalent in males

Question 5

Menopause

• Definition
• Symptoms
• Morbidities

Answer 5

Ovarian failure

• Drop in oestrogen
• Rise in FSH and LH
• Age 50 +/- 2 years

Symptoms

• Hot flushes
• Night sweats

Morbidities

• Osteoporosis
• Coronary heart disease
• Sexual dysfunction

Question 6

Post-menopausal replacement therapy

- Benefits

Answer 6

Relieves the symptoms

- Decreases risk of osteoporosis and fractures

Question 7

Post-menopausal replacement therapy

• Risks
• How to resolve it

Answer 7

Venous thrombolism

Breast cancer
- esp. used for >5 years

Endometrial cancer
- Unopposed E2 [only e2]

Resolved by only treating symptoms instead of preventing disorders

• Short term
• Low dose
• Started earlier.

Question 8

Male gonadal axis with age

Answer 8

Gradual decrease in testosterone but with a wide range of normality.

Poor association with libido/ erectile dysfunction and testosterones.

• Decreased sexual function and muscle strength
• Increase risk of osteoporosis

Question 9

Effects of testosterone treatment on bones

Answer 9

Increases bone mineral density

• But not their mechanical strength
• Fracture risk decreased by bisphosphanates.

Question 10

Effects of testosterone treatment on body composition.

Answer 10

Increases lean body mass

Decreases fat mass

Increases muscle strength only in very high doses

Question 11

Risks of testosterone treatment

Answer 11

Benign prostatic hypertrophy

Prostatic cancer

Erythropoiesis
- Increased RBC/ haemocrit

Question 12

Changes in GH-IGF-1 axis with age

Answer 12

Decrease in GH and IGF-1

Question 13

GH treatment

- Effects on body composition

Answer 13

Increases lean body mass [2kg]

Decreases fat mass [2kg]

Still not functional benefits.

No change for bone density or lipids

Question 14

Risks and side effects of GH therapy

Answer 14

Risks:
Cancers- Breast, colon, prostate
- T2 DM

Side effects:

• Soft tissue oedema
• Arthralgia
• Carpel tunnel

Question 15

Changes of cortisol levels and age.

Answer 15

Trough and average cortisol levels rise

Earlier time for trough and peak

Question 16

Mechanism behind increased cortisol levels with age?

Answer 16

Sapolsky’s glucocorticoid cascade hypothesis
- Decrease in hippocampal glucocorticoid and mineralocorticoid receptors [less negative feeback]

Affects hippocampal neurones= increase vulnerability to damage
- Decline in functions associated with hippocampus [memory, learning]

Question 17

DHEAS and age

Answer 17

Declines.
- 5-10% of peak by 70-80

Not as important and as potent as androgens from testes in men

Non-specific marker
- Associations may not be causal [etc with cancer, T2 DM, CVD]

Question 18

Thyroid function and age

• TSH
• T4, T3

Answer 18

Become slightly hypothyroid with age:

Slight TSH increase

Decreased peripheral conversion of T4 into T3.
= Decreased T3

Question 19

Potential harms of T4 therapy

Answer 19

Osteoporosis

A Fib

Atherosclerotic coronaries

Question 20

Effects of starvation

• Insulin
• Glucose
• Leptin

Answer 20

Decrease insulin
- Increased insulin sensitivity= decreased glucose.

Decreased levels of leptin
- Inhibits satiety, triggers starvation.

Question 21

Leptin and starvation

Answer 21

Levels decrease to signal starvation
- Due to low body fat

Increases food intake and decreases energy expenditure

Decreases fertility

Question 22

Starvation and androgens

Answer 22

Decreases fertility so
- Decreases FSH, LH, oestrogen, testosterone.

Amenorrhoea

Oestoporosis

Question 23

Leptin and reproduction

Answer 23

When used to treat obesity, also:

• Increases gonadotrophin secretion
• Improvement reproductive organ maturation
• Induce puberty and fertility

Question 24

Kisspeptin

Answer 24

Peptide that promotes release of GnRH from hypothalamus
- Especially at puberty

Can be inhibited or stimulated by oestrogen.

Reproduction and puberty modulated by leptin levels

• Leptin triggers stimulates
• So starvation inhibits Kisspeptin action

Question 25

Starvation and GH

Answer 25

GH increased= GH resistance
- Decrease in IGF-1

Reversed with re-feeding

Question 26

Starvation and cortisol

Answer 26

Increased levels

Many peaks

Question 27

Starvation and thyroid function

Answer 27

Becomes hypothyroid
- Lowers basal metabolic rate to conserve energy

TSH and T4 low

Decreased T4 conversion to FT3

Increased T4 conversion to RT3