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Endocrine > Normal Growth and Clinical Aspects > Flashcards

Normal Growth and Clinical Aspects Flashcards

1
Q

What is the difference between somatostatin and somatotrophin?

A

Somatotrophin - growth hormone and is released from the anterior pituitary

Somatostatin - GH inhibiting hormone - neurohormone released from the hypothalamus

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2
Q

What hormones does GH require the permissive actions of to allow growth?

A

Thyroid hormones and insulin

Children with untreated hypothyroidism or poorly controlled diabetes have stunted growth despite normal levels of GH

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3
Q

How is GH transported in the blood?

A

GH is a peptide hormone but, unusually for a peptide hormone, about 50% of GH circulates bound to carrier proteins.

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4
Q

What is the role of GH?

A

. Necessary for growth and development, but also secreted in the adult and it has other properties related to the maintenance of tissues and their energy supply.

GH is the predominant influence on the rate at which children grow

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5
Q

What determines growth during the foetal period and the first 8-10 months of life?

A

Largely controlled by nutritional intake

Babies with a very ready supply of glucose tend to be very large (mums with diabetes for example)

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6
Q

How does GH cause growth?

A

Growth-promoting effect of GH is mediated through stimulation of both cell size (hypertrophy) and cell division (hyperplasia) in its many target tissues.

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7
Q

Why is the effect on growth described as indirect?

A

It is achieved through the action of an intermediate known as IGF-1 Insulin like growth factor 1

It is also known as somatomedian as it mediates the action of GH

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8
Q

What structure does IGF-1 imitate?

A

Pro-insulin

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9
Q

Why is IGF-1 said to have hypoglycaemic qualities?

A

It binds to receptors very similar to the insulin receptor and has hypoglycaemic qualities (hence “insulin-like”) although latter action is limited to glucose uptake in muscle as liver and adipose tissue have few IGF receptors.

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10
Q

What secretes IGF-1?

A

Liver

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11
Q

How is GH released?

A

Released from the anterior pituitary

IGF-1 controls GH release from through a negative feedback loop

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12
Q

What is the role of IGF-2?

A

IGF-II also exists but it’s functional importance appears to limited to the foetus and neonate.

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13
Q

IGF1 is involved in a negative feedback loop, what hormones are affected?

A

IGF exhibits negative feedback on GH release both via inhibiting GHRH and stimulating GHIH/somatostatin

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14
Q

What other negative feedback loop exists to limit the secretion of GH?

A

Additional negative feedback loop of GH on GH release from somatotrophs in pituitary.

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15
Q

What is the effect of GH/IGF1 on bone?

A
  1. GH stimulates chondrocyte precursor cells (prechondrocytes) in the epiphyseal plates to differentiate into chondrocytes.
  2. During the differentiation, the cells begin to secrete IGF-I and to become responsive to IGF-I
  3. IGF-I then acts as an autocrine or paracrine agent to stimulate the differentiating chondrocytes to undergo cell division and produce cartilage, the foundation for bone growth.
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16
Q

When do epiphyseal plates close?

A

Epiphyseal plates close during adolescence under the influence of sex steroid hormones, then no further longitudinal growth is possible.

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17
Q

What are the actions of GH that release energy stores to support growth?

A

Increase in gluconeogenesis by the liver

Reduces the ability of insulin to stimulate glucose uptake by muscle and adipose tissue

Makes adipocytes more sensitive to lipolytic stimuli

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18
Q

Why is GH said to be diabetogenic?

A

Increases blood glucose when it is present in excess

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19
Q

What is the effect of GH on amino acids and protein synthesis?

A

Increases muscle, liver and adipose tissue amino acid uptake and protein synthesis = anabolic effect (cortisol stimulates protein catabolism).

20
Q

Look

A
21
Q

Which part of the brain controls GH secretion?

A

Controlled by hypothalamus which secretes GHRH and somatostatin (SS) (aka Growth Hormone Inhibiting Hormone (GHIH)

22
Q

How do the levels of GH compare in adults and children

A

Large quantities of GH are present in pituitaries of both adults and children

23
Q

Describe the rate of secretion of GH?

A

Rate of secretion undergoes rapid spontaneous fluctuations as well as increase or decrease in response to specific stimuli.

24
Q

What is the concentration of GH in the plasma

A

0-3ng/ml in children and adults. However one value does not give overall picture. Spikes of secretion occur so 24 hour mean [GH] is 2-4ng/ml in adults and 5-8ng/ml in children and puberty.

25
Q

What is the rate of GH secretion during delta sleep in children?

A

20 x increase in GH secretion during stages of delta sleep

Energy requirement is low so energy is diverted to growth

26
Q

GH has conenctration spikes, how does IGF1 compare?

A

Despite GH spikes, plamsa levels of IGF-1 remain relatively constant suggesting IGF-1 buffers the pulsatile variance in GH levels.

27
Q

How is IGF-1 transported in the blood?

A

GH and IGF-I are peptide hormones, but like steroid and thyroid hormones, they are transported in the blood associated with binding protein. About 50% of GH is in the bound form.

28
Q

What is the effect of having 50% bound to protein?

A

This helps to provide a “reservoir” of GH in the blood which helps to smooth out the effects of the erratic pattern of secretion.

29
Q

What is the hypothalamic / pituitary regulation of GH/IGF-1?

A
  1. Fluctuations in GHRH and coincident surges in GH occur spontaneously as well as in response to specific stimuli.
  2. SS secretion tends to be tonic (slow and responsive to need)
  3. There is negative feedback control via long and short loops by GH and IGF-I (see earlier).
  4. There are many inputs which influence hypothalamic control.
30
Q

What are the stimuli that increase GHRH?

A

Actual or potenital decrease in energy supply to cells

GH needed for the maintenance of tissues and their energy supply - fasting, exercise, during cold weather

Increased amounts of amino acids in the plasma

GH promotes amino acid transport and protein synthesis by the muscle and the liver

Stressful stimuli (infection, psychological stress)

Delta sleep (growth spurts children and adolescents and tissue repair in adults

Oestrogen and androgens

31
Q

What are the stimuli that increase GHIH release?

A
  1. Glucose
  2. FFA
  3. REM sleep (Subjects deprived of REM sleep have ­ GH secretion)
  4. Cortisol (although inhibitory effect on growth may be more to do with ­increase protein catabolism than stimulating GHIH release)
32
Q

What three factors affec the physiology of growth?

A

Hormones

Nutrition

Genetics

33
Q

When sex hormones have an influence in growth?

A

Sex hormones influence is minor until puberty when they dominate the growth spurt.

34
Q

What is the role of GH in foetal life?

A

GH influence is also minor during foetal life. Babies born deficient in GH and IGF-1 are of normal size. Insulin and IGF-II may dominate intrauteriene growth.

35
Q

What are thyroid hormones particulary important for the growth of?

A

Thyroid hormones are essential for normal growth, particularly important for development of the nervous system in utero and early childhood.

36
Q

What is the influence of thyroid hormones on GH?

A

Effects are permissive to GH/IGF-I.

GH requires permissive action of thyroid hormones and insulin before it will stimulate growth

37
Q

What are the effects of thyroid hormones?

A

Involved in the ossification of cartilage and teeth maturation as well as the contours of the face and the proportions of the body.

Cretinism is a condition where children are hypothyroid from birth. They have retarded growth because of the loss of TH’s permissive action on GH. They retain infantile facial features = hypothyroid dwarf. GH levels are normal

38
Q

What are the influences of nutrition on growth?

A

Nutrition: Adequate diet in terms of protein content and essential vitamins and minerals is just as important as enough calories. Important in utero and during development.

Injury and disease stunt growth because there is an increase in­protein catabolism (glucocorticoid effects).

39
Q

When are the 2 periods of rapid growth?

A

Infancy and puberty

40
Q

Describe the growth during infancy

A

Amazing growth spurts 2.5cm in a few days and then nothing i.e. episodic, mechanism not known.

41
Q

What is the role of sex hormones in the rapid growth during puberty?

A

Androgens and oestrogens produce spikes in GH secretion, therefore there is an increase in IGF-1 and resultant increase in growth (bone elongation, increased height and body mass)

These same hormones also cause the epiphyses of the long bones to fuse

42
Q

What causes gigantism?

A

XS GH due to a pituitary tumour before epiphyseal plates of long bones close and so there is excessive growth, may be more than 7ft tall (210cm), called pituitary giants.

43
Q

What causes acromegaly?

A

: XS GH due to a pituitary tumour after epiphyseal plates have sealed. Long bones cannot increase so there is no longitudinal growth and no increase in height. However, can still grow in other directions and the characteristic features are enlarged hands and feet

In adults feet should NOT get bigger = classic sign of ACROMEGALY

Surgery to remove tumour or somatostatin analogues to treat.

44
Q

What are the features of acromegaly?

A
45
Q

What are the mechanisms of dwarfism?

A
  1. A deficiency of GHRH
  2. GH secreting cells may be abnormal.
  3. End organ is unresponsive to GH (Laron Dwarfism). Individuals may have ­ [GH] in plasma. Defective GH receptor prevents IGF-1 release and peripheral tissues cannot respond to growth signal. Loss of IGF-1 negative feedback loop - GH production has no brakes
  4. Genetic mutations. Pygmies have a genetic mutation that impairs the ability of cells to produce IGF-I in response to GH.

Pygmies - Pygmies (e.g. the Mbuti and Twa peoples) are typically nomadic hunter-gatherers with an average male height not above 150 cm (4 ft 11 in.). Equitorial africa and parts of SE asia.

  1. Precocious puberty - long bones fuse early
  2. Hypothyroid children retain infantile features with stunted growth due to loss of permissive effect of TH on GH. Limits bone growth and promotes fat storage. Also severely impacts on neurological development.
46
Q
A

Endocrine (25 decks)

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