LC 3.4 Ageing and the Endocrine System Flashcards
By what possible mechanisms can ageing affect the endocrine system?
Reduced synthesis or turnover of hormones
Defective binding
Impaired post-receptor activation
Increased prevalence of endocrine autoimmune disease
Increased prevalence of adenomas or malignancies
Menopause/andropause
What causes decreased vitality in the elderly?
endocrine disease
metabolism and nutritional factors
What generally happens to circulating hormone levels with age and why?
Remains the same
Atrophy and fibrosis of endocrine glands causes decreased secretion
However, there is decreased breakdown and clearance due to decreased kidney and liver sizes
What changes occur in target tissues with age?
Less responsiveness to hormones
What changes occur in the HPT (hypothalamic pituitary thyroid) axis with age?
A progressive loss of sensitivity to feedback control
Blunted TSH response to TRH
Which key hormones are affected by ageing?
T3 triiodothyronine (active version)
PTH (increases)
Free testosterone
Insulin
Vasopressin
Noradrenaline
GH
DHEA dihydroepiandosterone
Which form of thyroid hormone is measured in blood tests?
T4
Which neurones are found in the hypothalamus which are involved in the HPA axis for sexual reproduction?
GnRH neurones - secrete GnRh
KNDy neurones - negative feedback control
Why does the sexual HPA axis shut down if you are too skinny?
Adipose tissue produces leptin which up-regulates the axis through KNDy neurones.
What effect does stress have on the sexual HPA axis?
Inhibits hypothalamus neurones, to inhibit the axis
What causes most changes to the HPT axis?
What changes are brought about by this?
Illness
Effects of medications:
NSAIDs
Radiocontrast agents
Iodine-containing compounds
What does GnRH stimulate the secretion of?
LH and FSH
What effects does illness have on the HPT axis?
decreased T3
if severe, decreases T4
Blunted response of TSH to TRH
The reduction in production in thyroid hormone due to ingestion of iodine containing compounds (such as radiocontrast agents)?
Wolff-Chaikoff effect
In healthy elderly, what are the changes in T3, T4 and TSH production and ranges
T3 production decreases 30%, range same
T4 production decreases 25%, range same
TSH production and range increases
What is the diagnosis for hypothyroisim?
Low free T4 and high TSH
What are the symptoms of hypothyroidism?
Fatigue and sluggishness Dry skin Slow pulse Croaking speech Frank dementia
What causes primary hypothyroidism? (lightbulb is broken, not turned off [secondary])
Autoimmune thyroiditis
Thyroidectomy
Radiation
Lithium
Impaired intake of L-T4 medication
Why does lithium cause primary hypothyroidism?
It inhibits T4 and T3 release from the gland
What is HYPERthyroidism induced by iodine such as those found in radiocontrast agents called?
Jod-Basedow phenomenon
Doesn’t occur people with normal thyroid glands
What can cause impaired intake of L-T4 medication?
Iron supplements
Bile acid sequestrants
What causes secondary hypothyroidism?
Posterior pituitary surgery
Why is TSH level useless for diagnosis and monitoring of secondary hypothyroidism?
Because there is low TSH level
What is overt hypothyroidism?
Increased T4
decreased TSH
What is subclinical hyperthyroidism and which gender is it more common in?
High-normal T3 & T4
Low TSH
What are the causes of hyperthyroidism?
Toxic multinodular goiter
Grave’s disease
What does the hypothalamus release with relation to the Growth Hormone and IGF-1 axis?
GHRH
Somatostatin (GHInhibitingH)
What does GH do? (i.e. act on, etc.)
Stimulates hepatic and local production of IGF-1
GH and IGF-1 work synergistically
What does GH cause?
Linear growth in childhood
Metabolic changes:
Fat breakdown
Early insulin resistance
What is the effect of age on GH production? What are the mechanisms for this?
GH production declines by 14% with every decade of ageing
CAUSED BY: • Reduced pituitary function • Increased hypothalamus somatostatin • Decreased GHRH activity • Menopause and andropause (because E2 stimulates GH)
What does the change in GH with age lead to?
- Increased body fat
- Decreased muscle mass
- Decreased bone mass
- Fat redistributed from subcutaneous to central visceral sites
- Decreased IGF-1
What does the change in IGF-1 (due to the change in GH)with age lead to?
• Increased apoptosis (because IGF-1 decreases apoptosis)
How can the effects of GH change with age be reversed?
Give GH to elderly
Exercise (increases GH levels in elderly)
How does calorie restriction retard physiological ageing?
Food restriction reduces pituitary hormone secretion
GH accelerates ageing and shortens life
Describe the importance of a correct GH balance
GH accelerates ageing if too high, but causes negative morphological changes if too low.
A balance is needed for optimal life expectancy
What is the age effect on sex steroids and corticosteroids? What can exacerbate these changes?
Adrenal androgens decline
Aldosterone declines
Cortisol during evenings and at night increase with age (morning is normal)
Exacerbated by dementia
What causes the increase in cortisol with age?
Impaired HPA steroid feedback
What can increased cortisol with age cause and why?
Type 2 diabetes mellitus and CVD due to anti-insulin effects (catabolic)
Damage to cell regeneration machinery due to:
• increased free radicals
• increased arachidonic acid
• increased intracellular calcium
