Endocrinology of aging

Question 1

Which condition increases with age and what is the underlying pathophysiological mechanism?

Answer 1

Metabolic syndrome: visceral obesity, dyslipidaemia, hyperglycaemia, hypertension.
Insulin resistance.

Question 2

How does menopause affect hormone levels and what are the symptoms?

Answer 2

Constant low oestrogen levels, increased FSH and LH.

Hot flushes, night sweats.

Question 3

Which morbidities are associated with menopause?

Answer 3

increased CHD, osteoporosis and sexual dysfunction

Question 4

What are the risks and benefits of post-menopausal HRT?

Answer 4

risk:benefit ratio depends on risk factors - greater risk if >60 yrs and >10 year duration of use post-menopause, type of HRT (oestrogen, progestogen, route).
prescribed for menopausal symptoms, reduces risk of osteoporosis / fractures.
venous thrombo-embolism, increased risk of breast and endometrial cancer.

Question 5

How does increasing age affect testosterone levels in men?

Answer 5

Gradual reduction in [testosterone].

Poor association between libido / erectile dysfunction and [testosterone].

Question 6

What are the negative effects of hypogonadism?

Answer 6

decreased sexual function
increased osteoporosis
decreased muscle strength

Question 7

What are the risks and benefits of testosterone treatment?

Answer 7

Increase in bone mineral density if hypogonadal, bisphosphonates work independent of androgen status.
increased lean body mass, decreased fat mass, no convincing functional benefits,
increased muscle strength.
Benign prostatic hypertrophy / prostatic cancer,
erythropoeisis (increase in haematocrit).

Question 8

How does age affect GH and IGF-I?

Answer 8

decreased [GH] and [IGF-I] with increasing age

Question 9

What are the positive effects of GH treatment?

Answer 9

increase in lean body mass, decrease in fat mass, no convincing functional benefits.
no significant change in bone mineral density and lipids.

Question 10

What are the potential risks and side effect of GH treatment?

Answer 10

increased [IGF-I] is associated with increase in risk in non-smoking related cancer.
increased risk of T2 DM.
Side-effects: soft tissue oedema, arthralgias, carpal tunnel syndrome.

Question 11

How does age effect cortisol levels?

Answer 11

increase in cortisol levels with increasing age, less of a trough, peaks earlier.

Question 12

what are the circulating androgens?

Answer 12

androstenedione, DHEAS, testosterone, dihydrotestosterone.

Question 13

How does age effect DHEAS and what is it associated with?

Answer 13

decrease in [DHEAS] with increasing age.
increase in [DHEAS] is associated with: increased quality of life and bone mineral density, reduced cognitive decline and coronary heart disease.

Question 14

How beneficial is DHEA treatment?

Answer 14

no evidence of beneficial effects. no adverse effects.

Question 15

How does age affect thyroid function and how beneficial is T4 treatment?

Answer 15

Slight increase in [TSH]
T4 is the same
decreased peripheral conversion of T4 to T3
decrease in [T3]
no evidence for beneficial effect of T4 treatment. may do harm

Question 16

How does starvation/anorexia nervosa effect insulin, glucose and insulin sensitivity?

Answer 16

decrease in insulin and glucose.

increase in insulin sensitivity.

Question 17

What is the function of leptin and how is it affected by starvation / AN?

Answer 17

produced by white adipose tissue and correlates with BMI and body fat. reports nutritional information to hypothalamus.
decreased [leptin] leads to increased food intake, decreased energy expenditure and decreased fertility.
permissive factor for initiation of puberty.

Question 18

How does starvation / AN affect oestrogen and testosterone and what are the risks?

Answer 18

decrease in LH, FSH, oestrogen / testosterone, fertility. ‘hypothalamic amenorrhoea’
osteoporosis - prescribe HRT / COCP.

Question 19

Outline the kisspeptin system and what effect does leptin have on kisspeptin?

Answer 19

GnRH secretagogue.
KISS1 neurons highly responsive to oestrogen, implicated in both + and – central feedback of sex steroids on GnRH production.
Metabolic influences on reproduction and puberty mediated by leptin via the kisspeptin system.
Leptin has a permissive effect on kisspeptin.

Question 20

What effect does starvation/AN have on the GH/IGF axis?

Answer 20

GH resistance. increase in GH, decrease in IGF-I.

Reversible with re-feeding.

Question 21

What are the effects of starvation/AN on thyroid function and what are the consequences?

Answer 21

TSH and T4 lower limit of normal.
decreased T4 conversion to T3 leads to reduced active T3.
increased T4 conversion to rT3 leads to increased inactive rT3.
Lower basal metabolic rate, conserve energy.

Question 22

What are the effects of old age on insulin and glucose?

Answer 22

Increased [insulin] and [glucose] with increase in age:
increased insulin resistance, reduced peripheral glucose uptake.
Higher prevalence of metabolic syndrome.

Question 23

Outline the gonadal axis in men

Answer 23

hypothalamus secretes GnRH
anterior pituitary releases LH and FSH.
LH stimulates Leydig cells in testicles to produce testosterone.
FSH stimulates Sertoli cells to produce androgen binding globulin (ABG) and inhibin.
high levels of testosterone and inhibin cause negative feedback on pituitary and hypothalamus resulting in decreased production of LH and FSH and consequently decreased production of testosterone and inhibin.

Question 24

Outline the gonadal axis in women

Answer 24

hypothalamus secretes GnRH
anterior pituitary gland releases LH and FSH.
LH and FSH bind to ovaries and stimulate production of oestrogen and inhibin.
high levels of oestrogen and inhibin cause negative feedback on pituitary and hypothalamus resulting in decreased production of GnRH, LH and FSH; consequently, decreased production of oestrogen and inhibin.

Question 25

Outline the GH - IGF-I axis

Answer 25

hypothalamus secretes GHRH
anterior pituitary secretes GH
liver then secretes IGF-I which acts via negative feedback to pituitary to decrease production of GH.