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BDS 2 Semester 1 > Endocrinology: Endocrine Changes with Aging > Flashcards

Endocrinology: Endocrine Changes with Aging Flashcards

1
Q

HPG axis and menopause

A
  • Ovarian secretion of estrogens decreases, and secretion of follicle-stimulating hormone (FSH) and luteinising hormones (LH) increases rather abruptly in about the sixth decade in women
  • Hormone changes during perimenopausal period associated with autonomic and emotional dysfunctions, e.g., hot flashes, heart palpitations, night sweats, mood swings
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2
Q

What is the HPG axis?

A

The hypothalamic-pituitary-gonadal (HPG) axis, which governs the reproductive system, is driven by the brain.

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3
Q

Where are FSH and LH secreted from?

A

Anterior pituitary, controlled by hypothalamus (through GnRH)

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4
Q

Effect of estrogen levels dropping with age and bone

A
  • Decreased production of cytokines (e.g., TNFa and ILs) by bone marrow and immune cells
  • Increased osteoclastic cell death (via ER-alpha receptors)
  • Increased secretion of osteoprotegrin (OPG), a decoy receptor for RANKL
  • Decreased FSH secretion (through -ve feedback)
  • Decreased osteoclast differentiation and function
  • Decreased bone resorption
  • Increased hepatic production of IGF-1 that stimulates osteoblast differentiation
  • Increased bone maintenance
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5
Q

Effect of estrogen decrease with age and the cardiovascular system

A
  • Vasculature
    o Rapid effects (nongenomic): increased dilation, increased nitric oxide)
    o Longer term effects (genomic): decreased atherosclerosis, decreased vascular injury, increased endothelial-cell growth
  • Blood clotting: increase coagulation factors, increased plasminogen, increased platelet adhesiveness
  • Lipids: increased HDL, decreased LDL
  • Heart: supports cardiomyocyte contractility, inhibits apoptosis
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6
Q

Benefits of hormone replacement therapy in women

A
  • Strengthens bone
  • Lowers LDL cholesterol
  • Raises HDL cholesterol
  • Reduces menopausal symptoms (e.g., hot flashes)
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7
Q

Negatives of hormone replacement therapy in women

A
  • Increases breast cancer risk
  • Increases uterine cancer risk
  • Increases blood clot risk
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8
Q

Male HPG axis and andropause

A
  • Testicular declines gradually with age, but the rate of decline varies between individuals
  • Average ~1-2% decrease in circulating testosterone each year from 20s
  • Sperm production stable from end of puberty to ~70 years, declines to ~50% by 90 years; accompanied by tubular fibrosis, shrinkage of testicular volume, and modest elevations of FSH
  • Declining testosterone levels may play a role in the osteoporosis and sarcopenia of the elderly
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9
Q

Benefits of testosterone supplementation

A
  • Improvements in bone density, muscle mass and strength
  • Decreases in central adiposity and insulin resistance
  • Improvements in libido and erectile function
  • Better scores on cognition and memory tests
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10
Q

Disadvantages of testosterone supplementation

A
  • Adverse effects on lipid profiles (increased CV disease and polycythaemia risk)
  • Worsened sleep apnoea
  • Increased risk of prostate cancer
  • Detrimental effects on CNS (with supraphysiological levels)
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11
Q

Growth hormone supplementation benefits

A
  • Increased lean body mass
  • Decreased adiposity
  • Improved muscle strength and VO2 max (in men)
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12
Q

Growth hormone supplementation adverse effects

A
  • Oedema
  • Carpal tunnel syndrome
  • Arthralgias (joint pain)
  • Increased risk of diabetes (increased glucose intolerance)
  • Hence: administration currently reversed for pts with documented GH deficiency
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13
Q

Age related changes in levels of adrenal androgens

A

Adrenocortical hormones: adrenal androgens
- Diminished production of adrenal androgens (e.g., dehydroepiandrosterone; DHEA) in both sexes is thought to contribute to loss of bone density and muscle mass seen in the elderly
- DHEA secretion decreases from 3rd decade onwards; 80-year old’s serum concentrations ~20% of 20-year-old
- Higher endogenous levels of DHEA have been associated with better health and longevity – however, placebo-controlled 2-year DHEA supplementation trials suggest no improvement in body composition, oxygen consumption, muscle strength or insulin sensitivity

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14
Q

Age related changes to cortisol levels

A

Adrenocortical hormones: cortisol
- Serum concentrations of cortisol tend to be more variable within a 24-hour period in older subjects; evening nadir is higher and earlier (possibly linked to sleep disorders)
- Mean 24-hour serum cortisol concentrations are 20-50% higher in elderly – some links with to decreased lean body mass, poorer memory, lower bone density, greater body fat
- Serum cortisol responses to stress are prolonged in older subjects

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15
Q

Age related changes to aldosterone levels

A

Adrenocortical hormones: aldosterone
- Secretion rate and serum concentrations of aldosterone fall with age; by 70 years down to 50%
- Together with mild renal failure can lead to sodium wasting, hyponatremia and hyperkalaemia

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16
Q

Age related changes to growth hormone and IGF system

A
  • GH secretion and serum GH concentrations fall with age, both basally and in response to stimuli; serum IGF-1 concentration also decreases
  • Decreased GH secretion is due to a decrease in GHRH secretion, as well as a decrease in pituitary responsiveness to GHRH
  • Most GH is secreted during slow-wave sleep therefore age-associated sleep disturbances may also contribute to decreased GH secretion
  • Low physical fitness and higher adiposity may also contribute to decreased GH secretion in elderly
17
Q

Age related changes to thyroid function

A
  • Volume of the thyroid gland increases slightly with age
  • No age-related changes in serum total or free thyroxine concentrations
  • Thyroxine production and clearance both decrease modestly with age (decreased clearance may have implications for replacement therapy)
  • Thyroid dysfunction occurs more frequently in older populations (age-related illnesses)
  • Hyperthyroidism: older pts often lack characteristic symptoms of heat intolerance, sinus tachycardia, sweating, tremor – instead present with fatigue, muscle weakness, weight loss and atrial arrhythmias. Elevated thyroid hormone accelerates bone loss
  • Hypothyroidism: symptoms often considered to be signs of age-related decline – weakness, somnolence, slow reactions, sensitivity to cold, loss of memory, constipation
18
Q

Age related changes to calciotropic hormones and calcium balance

A
  • Parathyroid hormone: serum PTH concentrations are slightly higher in older subjects – likely due to phosphate retention caused by declining renal function and mild vitamin D deficiency (if vit D levels are elevated to within the normal range PTH concentrations decrease)
  • Calcium balance: calcium balance is often negative in older subjects (due to decreased dietary calcium intake and decreased calcium absorption); calcium loss further accelerated in elderly persons with hyponatremia; recommended intake over age 65 = 1200mg elemental calcium daily
19
Q

Age related changes to circadian rhythm

A
  • Early onset of sleep and awakening very early in the morning (advanced sleep-phase syndrome); likely due to lower melatonin secretion from pineal gland. Further aggravated by a low day time activity and repeated use of sleeping pills
  • In some, a non-dipper BP pattern develops (BP doesn’t fall lower than day-time level at night)
  • Shifts in the timing and magnitude of the circadian rhythms of adrenocorticotropic hormone (ACTH), thyroid stimulate hormone (TSH) and growth hormone (GH)
  • Circadian rhythm of food intake may be altered (as suggested by animal studies)
20
Q

Decreased hormone action with aging

A
  • As well as changes in the secretion of many hormones, the actions of some hormones can be reduced with age due to decreased responsiveness of target cells. Increased hormonal secretion may or may not compensate for such decreases in tissue responsiveness
  • Vasodilatory response to estrogen reduced (possibly due to methylation of the estrogen receptor gene – an epigenetic change)
  • Leydig cells become less responsiveness to gonadotropin stimulation (altered cell membrane biochemistry)
  • Serum noradrenaline concentrations higher – thought to be a compensatory increase to decreased responsiveness to noradrenaline (adrenaline concentrations either same or slightly lower suggesting it is not due to increased activity of adrenal medulla itself)
  • Vasopressin secretion is response to volume depletion is increased but there is reduced renal responsiveness to vasopressin. Also, a decrease in thirst in response to osmotic stimulation. Therefore, older subjects can become more easily dehydrated
21
Q

Chronic hyponatremia

A
  • Hyponatremia (low plasma sodium) is a common problem in the elderly, particularly in women
  • Contributory factors: hypersecretion of vasopressin with water retention; aldosterone deficiency; renal tubular dysfunction (reduced sodium reabsorption)
  • Associated with CNS impairment and accelerated calcium loss from bone
22
Q

Sarcopenia and osteoporosis

A
  • Age-related loss of muscle mass/strength (sarcopenia) and that of bone mass (osteoporosis) lead to weakness, decreased activity, loss of capacity for independent living, pathological fracturs
  • Age-related decline in endocrine functions (e.g., sex steroids, GH and IGF etc.) as well as low-grade inflammation associated with life-long exposure to toxic and harmful substances, infective agents, metabolic states (acidosis), obesity, genetic factors contribute significantly to these abnormalities
23
Q

Changes to glucose metabolism with age

A
  • Insulin resistance increases with age (reduced insulin sensitivity in older subjects persists even when the data are corrected for fat mass and fitness)
  • Thought to involve decreased glucose carrier protein GLUT 4 in muscle
  • Glucose clearance tends to be decreased
  • Some older subjects have hyperinsulinemia, others have hyperproinsulinemia and in some serum insulin responses are sluggish
  • Changes are similar to those that typically precede the development of type 2 diabetes mellitus in middle age; incidence to type 2 diabetes is higher in older than younger adults
24
Q

Changes to lipid and protein metabolism with age

A
  • Dyslipidaemia (hypertriglyceridemia, high LDL and low HDL cholesterol) and hyperuricemia (accumulation of urate crystals) are more prevalent in the elderly
  • Dyslipidaemia promotes atherosclerosis, acute myocardial infarction, and stroke
  • Incidence of gout increases in the elderly; painful deposition of urate crystals (by-product or protein metabolism) in and around the joints and can lead to chronic deformities of joints

BDS 2 Semester 1 (21 decks)

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