Normal Growth and Clinical Aspects

Question 1

How is growth regulated?

Answer 1

GH from anterior pituitary
Thyroid hormones
Insulin
Sex steroids
Nutrient availability
Stress
Genetics

Question 2

Growth Hormone is what type of hormone?

Answer 2

Peptide hormone

Question 3

What controls the release of growth hormone?

Answer 3

Growth Hormone Inhibiting hormone (somatostatin)

Growth hormone Releasing Hormone

Question 4

Growth hormone is also known as what?

Answer 4

Somatotropin

Question 5

What categories does the activity of growth hormone fall into?

Answer 5

Growth and development (indirect)

Regulation of metabolism (direct)

Question 6

Growth hormone requires what before it will stimulate growth?

Answer 6

Permissive action of thyroid hormones and insulin

Question 7

What is the primary controlling factor of growth in early life?

Answer 7

Nutrition (8-10 months)

Question 8

What is the role of growth hormone in adult life?

Answer 8

Maintenance and repair of tissue

Question 9

How is the growth promoting effect of GH mediated?

Answer 9

Stimulation of cell size
Stimulation of cell division
(hypertrophy + hyperplasia)

Question 10

What is the indirect function of GH on growth?

Answer 10

Intermediate - insulin-like growth factor-1 (IGF-1)

Somatomedin C

Question 11

What is the hypoglycemic quality of IGF-1?

Answer 11

Limited glucose uptake in muscles

Question 12

IGF-1 is secreted by what?

Answer 12

Liver and other cells in response to GH release

Question 13

What is the effect of IGF-1 on GH?

Answer 13

IGF-1 levels inhibit growth hormone (negative feedback)

Question 14

What is the role of IGF-II?

Answer 14

Limited to foetus and neonate

Question 15

How are GH and IGF-1 unique?

Answer 15

Bound to carrier proteins, despite being peptide hormones

Question 16

What % of GH is bound?

Answer 16

50%

Question 17

What is the benefit of binding GH to carrier proteins?

Answer 17

Smooth outs the effects of the erratic pattern of secretion

Protects from excretion

Question 18

What is the negative feedback effect of IGF-1?

Answer 18

• Inhibits GHRH
• Stimulates GHIH (somatostatin)
• Inhibits GH release from somatotrophs in pituitary

Question 19

GH/IGF-1 effects on bone growth?

Answer 19

GH stimulates chondrocyte precursor cells in epiphiseal growth plate to differentiate into chondrocytes

Question 20

What is the effect of IGF-1 on bone growth differentiation?

Answer 20

Cells begin to secrete IGF-1, and become more responsive to it

Question 21

How does IGF-1 act as an auto/paracrine agent in bone growth?

Answer 21

Stimulating chondrocytes to undergo cell division and produce cartilage

Question 22

What are the direct effects GH on metabolism?

Answer 22

Increases gluconeogenesis by liver
Reduces insulin ability to stimulate glucose uptake by muscle and adipose
Make adipocytes more sensitive to lipolytic stimuli
Increase muscle, liver, adipose uptake of AAs and protein synthesis

Question 23

When is GH said to be diabetogenic?

Answer 23

When in excess

Question 24

What is a diabetogenic?

Answer 24

Increases blood glucose

Question 25

What does GH synergise with for its anti-insulin effect?

Answer 25

Cortisol

Question 26

What needs insulin for glucose uptake?

Answer 26

Muscle and adipose tissue

Question 27

What roles does GH share with insulin?

Answer 27

Increases aa uptake | Stimulates protein synthesis

Question 28

What role does GH NOT share with insulin?

Answer 28

GH does not increase glucose uptake

Question 29

GH has a main anabolic effect on what?

Answer 29

Everything but muscle and adipose tissue

Question 30

What are the general roles of GH?

Answer 30

Mobilise glucose Inhibits insulin action Promotes lipolysis Promotes aa uptake

Question 31

When is GH secretion highest?

Answer 31

Teenage years

Question 32

What is the nature of GH secretion?

Answer 32

Rapid and spontaneous up and down

Question 33

When is the majority of GH released?

Answer 33

First 2hrs of sleep (deep delta sleep)

Question 34

How much higher is GH secretion in children? When?

Answer 34

20x higher in children in the first 2hrs of sleep

Question 35

What other GH related hormone has sleep inducing qualities?

Answer 35

Growth Hormone Receptor Hormone

Question 36

How are GH levels evaluated?

Answer 36

Repeated measurements over 24hrs

Question 37

How does IGF-1 vary through the day? What does this tell us?

Answer 37

Consistent | IGF-1 buffers the pulsatile variance of GH

Question 38

What is the biggest influence on GH secretion?

Answer 38

Nutritional status

Question 39

How does nutritional control mediate GH release?

Answer 39

Modulation of GHRH/GHIH

Question 40

What are the stimuli that increase GHRH secretion?

Answer 40

1. Actual or potential decrease in cell energy supply 2. Increased amounts of AA in plasma 3. Stressful stimuli 4. Delta sleep 5. Oestrogen and androgens

Question 41

What is the effect of exercise on GH?

Answer 41

Increased Growth hormone secretion

Question 42

Increased GH in delta sleep is related to what?

Answer 42

Growth spurts in children/adolescents | Tissue repair in adults

Question 43

Which stimuli increase GHIH secretion?

Answer 43

1. Glucose 2. FFA 3. REM sleep 4. Cortisol

Question 44

What hormonal effect is seen in REM sleep deprived subjects?

Answer 44

Increased GH secretion

Question 45

Physiology of growth is affected by which factors?

Answer 45

Hormones Nutrition Genetics

Question 46

Which hormones affect growth?

Answer 46

``` GH, IGF-1 Thyroid hormones Androgens & estrogens Glucocorticoids Insulin ```

Question 47

What is the impact of sex hormones on growth?

Answer 47

Minor until puberty

Question 48

What is seen in babies deficient in GH and IGF-1?

Answer 48

Born normal size as GH influence is minor

Question 49

Which hormones may dominate intrauterine growth?

Answer 49

Insulin | IGF-II

Question 50

When are thyroid hormones most important?

Answer 50

Development of the nervous system in utero and early childhood

Question 51

What is the effect of thyroid hormones on GH/IGF-1?

Answer 51

Permissive effects

Question 52

What is the effect of thyroid hormones on bones?

Answer 52

Ossification of cartilage Teeth maturation Contours of the face Proportions of the body

Question 53

What is cretinism?

Answer 53

Hypothyroid from birth

Question 54

What is the effect of cretinism on growth?

Answer 54

Stunted growth due to TH's permissive effect on GH | Retain infantile facial features

Question 55

Why do injury and disease stunt growth?

Answer 55

Increased protein catabolism (glucocorticoid effects)

Question 56

When are the periods of rapid growth in humans?

Answer 56

Infancy | Puberty

Question 57

How does growth appear in infancy?

Answer 57

Episodic growth spurts of ~2.5cm

Question 58

How does puberty cause growth spurts?

Answer 58

Androgens + estrogens produce spikes in GH secretion that ↑IGF-1

Question 59

How do puberty hormones terminate growth?

Answer 59

Androgens and estrogens cause the epiphyses of the long bones to fuse

Question 60

What are the most common causes of hypersecretion syndromes?

Answer 60

Endocrine tumours

Question 61

What is gigantism?

Answer 61

Excess GH due to pituitary tumour BEFORE epiphyseal plates of long bones grow Typically very tall

Question 62

What is acromegaly?

Answer 62

Excess GH due to pituitary tumour after epiphyseal plates of long bones grow Typically have enlarged hands and feet

Question 63

What is the classic sign of acromegaly?

Answer 63

Adult foot growth

Question 64

How are endocrine tumours treated?

Answer 64

Surgery | Somatostatin analogues

Question 65

Dwarfism may be caused by what?

Answer 65

1. GHRH deficiency 2. GH secreting cell abnormality 3. End organ unresponsive to GH 4. Genetic mutations 5. Precocious puberty 6. Hypothyroid tumours

Question 66

If dwarfism is hypothalamic in origin, how is it treated?

Answer 66

GHRH deficient - normal response to administered GHRH

Question 67

If dwarfism is pituitary in origin, how is it treated?

Answer 67

GH secreting cells abnormal - less GH produced in response to GHRH

Question 68

What is Laron Dwarfism?

Answer 68

High [GH]plasma, defective receptors prevent IGF-1 release

Question 69

Why do Laron Dwarves have high [GH]?

Answer 69

Inability to release IGF-1 stops inhibition of GH

Question 70

Why do pygmy peoples have dwarfism?

Answer 70

Mutation impairing cells ability to make IGF-1 in response to GH

Question 71

How does precocious puberty cause dwarfism?

Answer 71

Excess GnRH release stimulates puberty by promoting sex hormone release. These children have stunted growth because long bones fuse early

Question 72

Why does hypothyroid cause dwarfism in children?

Answer 72

Loss of permissive effect of TH on GH

Question 73

How do hypothyroid children differ from children deficient in GH?

Answer 73

Hypothyroid - retain infantile proportions | GH - proportionally normal