Paediatrics: Growth + Puberty

Question 1

What are the four phases of normal human growth?

Answer 1

1) Fetal Phase
2) Infantile Phase
3) Childhood Phase
4) Pubertal Growth Spurt Phase

Question 2

Describe the foetal phase of growth:

Answer 2

1) The fastest period of growth
2) Accounts for 30% of eventual height
3) Size at birth is determined by size of mother and placental nutrient supply, which modulates foetal growth factors (insulin, IGF-2) –> this supply depends on maternal diet
4) Size at birth is independent of father’s height and GH

Question 3

Describe the infantile phase of growth:

Answer 3

1) Birth –> 18 months old
2) Nutrition is the main cause of growth!
3) Accounts for 15% of final height
4) By the end of this phase the child is now largely determined by their genetics rather than their uterine environment
5) An inadequate rate of weight gain during this period is called ‘faltering growth’

Question 4

Describe the childhood phase of growth:

Answer 4

1) Accounts for 40% of final height, and is slow and steady but prolonged
2) Pituitary GH secretion produces IGF-1 at the epiphyses, this is the main determinant of the rate of growth
3) Profound chronic unhappiness can decrease GH secretion and accounts for psychological short stature

Question 5

Describe pubertal growth spurt phase of growth:

Answer 5

1) Sex hormones (testosterone + oestradiol) cause the back to lengthen and boost GH secretion
2) 15% of final height
3) The same sex steroids cause fusion of the epiphyseal growth plates and a cessation of growth
4) If puberty is early, the final height is reduced because of early fusion of the epiphyses.

Question 6

In each of the stages of growth, what determines the growth?

Answer 6

Fetal: Size of mother and placental nutrient supply

Infantile: Nutrition

Childhood: Pituitary GH secretion

Puberty: Sex hormones

Question 7

In what 4 ways is growth measured?

Answer 7

1) Weight
2) Height (lying height in under 2s)
3) Head circumference
4) BMI

Question 8

What are three significant abnormalities of height measurements?

Answer 8

1) Measurements below 0.4th or above the 99.6th centile if the parent isn’t abnormally tall/short
2) If markedly discrepant from weight
3) Serial measurements which cross growth centile lines after the first year of life

Question 9

What are the features of puberty in females?

Answer 9

1) Breast development (first sign)
2) Pubic hair growth and rapid height growth (almost straight after breast development)
3) Menarche

Question 10

What are the features of puberty in males?

Answer 10

1) First sign: testicular enlargement (to over 4ml volume- orchidometer)
2) Pubic hair growth (10-14 years)
3) Rapid height growth 18 months after first signs of puberty (occurs later than females but is of a greater magnitude)

Question 11

How is short stature defined?

Answer 11

A height below the 2nd centile

The further the child is below these centiles, the most likely it is there will be a pathological cause

Question 12

What is the cause of short stature in most children?

Answer 12

Short parents

Question 13

What are the causes of short stature?

Answer 13

1) Familial
2) Constitutional delay in growth and puberty (normal)
3) Small for gestational age + extreme prematurity
4) Chromosomal disorder/syndromes (Down’s, Turner, Noonan etc.)
5) Nutritional/Long-term illness (coeliac, crohn’s, CKD, CF, congenital heart disease)
6) Psychosocial deprivation
7) Endocrine (hypothyroidism, GH deficiency, steroid excess)
8) Extreme short stature (SHOX gene abnormalities)

Question 14

If puberty is abnormally early or late, how can it be assessed?

Answer 14

1) Bone age measurement from a hand and wrist x-ray to determine skeletal maturation
2) Pelvic US scan to assess uterine size and endometrial thickness

Question 15

How is short stature investigated and examined?

Answer 15

1) Plotting present + previous heights and weight on growth charts, combined with clinical features, usually allows for cause to be identified
2) Bone age (delayed in endocrine disorders)
3) FBC (anaemia, crohn’s)
4) Creatinine, U+E (CKD)
5) anti-endomysial + anti-TTG (coeliac)
6) TSH (primary hypothyroidism)
7) IGF-1 (growth hormone disorders)

Question 16

How can short stature be ‘treated’?

Answer 16

Synthetic growth hormone if deficiency

Treat underlying cause

Question 17

What are the causes of tall stature?

Answer 17

1) Familial (most common)
2) Obesity
3) Secondary endocrine (hyperthyroidism, congenital adrenal hyperplasia, precocious puberty, gigantism)
4) Syndromes (Long-legged tall stature: Marfan’s, Klinefelter’s, homocystinuria)
5) Excessive growth at birth (maternal diabetes, primary hyperinsulinism, Beckwith syndrome)

Question 18

How can tall stature be treated in prepubertal/early pubertal adolescent children?

Answer 18

Oestrogen and testosterone therapy (variable results and serious side effects)

Question 19

At what ages in males and females can the development of secondary sexual characteristics be considered abnormal?

Answer 19

Males: 9

Females: 8

Question 20

What are the different patterns of premature sexual development?

Answer 20

1) Precocious puberty (when accompanied by a growth spurt)
2) Premature breast development (thelarche)
3) Premature pubic hair development (pubarche)
4) Isolated premature menarche

Question 21

What are the two categories of precocious puberty?

Answer 21

Gonadotrophin Dependent (true PP): premature activation of the HPG axis

Gonadotrophin Independent (false PP): excess sex steroids outside the pituitary gland

Question 22

What can cause gonadotrophin dependent precocious puberty?

Answer 22

1) Pituitary adenoma
2) Idiopathic/familial
3) Other CNS abnormalities (hydrocephalus, acquired)
4) Hypothyroidism

Question 23

What can cause gonadotrophin independent precocious puberty?

Answer 23

1) Adrenal disorders (tumours, congenital adrenal hyperplasia)
2) Ovarian tumour (granulosa cell)
3) Testicular tumour (Leydig cell)
4) Exogenous sex steroids

Question 24

Why is gonadotrophin dependent precocious puberty more common in girls than boys?

Answer 24

The ovaries are sensitive to gonadotrophin secretion from the pituitary. The testes are relatively insensitive.

Question 25

What is useful in the examination of males with precocious puberty and why?

Answer 25

Testicular examination

Bilateral enlargement suggests gonadotrophin dependent (intracranial tumour)

Prepubertal testes suggests gonadotrophin independent (adrenal tumour, CAH)

Unilaterally enlarged testis suggests gonadal tumour

Question 26

How is precocious puberty managed?

Answer 26

1) Detect and treat underlying pathology
2) Reduce rate of skeletal maturation
3) Address psychological/behavioural problems caused by early progression through puberty
4) Gonadotrophin dependent treatment: GnRH analogues
5) Gonadotrophin independent disease: inhibit androgen or oestrogen production/action

Question 27

How is delayed puberty defined?

Answer 27

Absence of pubertal development by 14 years in females, and 15 in males

Question 28

Why is delayed puberty more common in males?

Answer 28

Due to the relative insensitivity of the testes to gonadotrophin secretion

Question 29

What are the causes of delayed puberty?

Answer 29

1) Constitutional delay in growth and puberty (most common)
2) Low gonadotrophin secretion (hypogonadotrophic hypogonadism): systemic disease (CF, asthma, Crohn’s), hypothalamo-pituitary disorders, acquired hypothyroidism)
3) High gonadotrophin secretion (hypergonadotrophic hypogonadism): chromosomal abnormalities (Klinefelter, Turner syndromes), acquired gonadal damage

Question 30

What three things will a child with delayed puberty have?

Answer 30

1) Delayed sexual changes
2) Bone age shows moderate delay
3) Legs long in comparison to back

Question 31

What does assessment of boys with delayed puberty involve?

Answer 31

Common in boys so usually constitutional delay

1) Pubertal staging (esp. testicular volume)
2) Identification of long-term systemic disorders

Question 32

What does assessment of girls with delayed puberty involve?

Answer 32

Rare in girls so seek cause

1) Karyotyping (Turner’s)
2) Thyroid and sex steroid hormones measured
3) Consider eating disorder and pituitary pathology
4) Treat with oestradiol for several months to induce puberty

Question 33

How is delayed puberty managed?

Answer 33

1) Assure that puberty will occur (treatment usually not required)
2) Low-dose IM testosterone accelerates growth and induces secondary sexual characteristics)

Question 34

What is congenital adrenal hyperplasia?

Answer 34

An autosomal recessive disorder of adrenal steroid biosynthesis

Question 35

What is the epidemiology of congenital adrenal hyperplasia?

Answer 35

1 in 5000 live births

More common in consanguineous marriages

Question 36

What is the pathology of congenital adrenal hyperplasia?

Answer 36

90% have a deficiency of the enzyme 21 hydroxylase, which is needed for cortisol biosynthesis

80% are unable to produce aldosterone, leading to salt loss

In the foetus, the resulting cortisol deficiency stimulates the pituitary to produce ACTH, which drives overproduction of adrenal androgens

Question 37

How does congenital adrenal hyperplasia present?

Answer 37

Females: virilisation of external genitalia- clitoral hypertrophy and variable fusion of the labia

Males:

1) Enlarged penis + pigmented scrotum (rarely identified)
2) 80%: salt-losing adrenal crisis (vomiting, weight loss, floppiness, circulatory collapse)
3) 20%: non-salt losers (tall stature)

Both male and female non-salt losers: muscular build, adult body odour, pubic hair, acne –> precocious puberty

Question 38

How is congenital adrenal hyperplasia diagnosed?

Answer 38

Markedly raised levels of precursor 17a-hydroxyprogesterone in the blood

Question 39

Congenital adrenal hyperplasia: what are the biochemical abnormalities of salt losers?

Answer 39

1) Low plasma sodium
2) High plasma potassium
3) Metabolic acidosis
4) Hypoglycaemia

Question 40

Congenital adrenal hyperplasia: how are affected females managed?

Answer 40

Corrective surgery to external genitalia in first year

Definitive surgical reconstruction delayed until late puberty

Question 41

How is a salt-losing crisis managed in congenital adrenal hyperplasia?

Answer 41

IV saline, dextrose, and hydrocortisone

Question 42

What is the long term management of congenital adrenal hyperplasia?

Answer 42

1) Lifelong glucocorticoids (suppress ACTH –> normal growth)
2) Mineralocorticoids (fludrocortisone)/sodium chloride if there is salt loss
3) Monitor growth, skeletal maturity, plasma androgens, and 17a-hydroxyprogesterone
4) Additional hormone replacement to cover illness and surgery

Question 43

Can congenital adrenal hyperplasia be diagnosed and treated prenatally?

Answer 43

Yes, if previous affected child

Give dexamethasone around time of conception, and continue if female (reduces foetal ACTH drive and hence virilisation)