Growth and Puberty 2

Question 1

At what age is development of secondary sexual characteristics considered premature in the UK? What is this called when accompanied by a growth spurt?

Answer 1

Before the age of 8 in girls and 9 in boys.

When accompanied by a growth spurt this is known as precocious puberty.

Question 2

How is precocious puberty categorised?

Answer 2

According to the levels of the gonadotropins FSH and LH. Precocious puberty can be:
1) Gonadotrophin-dependent, from premature activation of the hypothalamic-pituitary-gonadal axis. This is know as central or true precocious puberty.
or it can be…
2) Gonadotropin independent, from excess sex steroids, also known as pseudo or false precocious puberty.

Question 3

What are the medical terms for breast development and pubic hair development?

Answer 3

• Thelarche (breast bud)

- Pubarche

Question 4

What is the usual (most common) cause of precocious puberty (PP) in females?

Answer 4

PP is usually idiopathic or familial and tends to follow the normal sequence of puberty.

Question 5

Organic causes of precocious puberty in females are rare. When they do occur, what are they associated with?

Answer 5

1) Dissonance
2) Rapid onset
3) Neurological signs and symptoms e.g. neurofibromatosis

Question 6

Define dissonance

Answer 6

Abnormal sequence of pubertal changes e.g. isolated pubic hair with with virilisation of the genitalia suggesting excess androgens.

Question 7

What could be the cause of excess androgens causing dissonance and virilisation in females?

Answer 7

• An androgen secreting tumour

- Congenital adrenal hyperplasia

Question 8

What investigation is useful in establishing the cause of precocious puberty in females? And what would be seen in the premature onset of normal puberty?

Answer 8

USS of the ovaries and uterus

Multicystic ovaries and an enlarging uterus

Question 9

What is the usual cause of precocious puberty in males?

Answer 9

Precocious puberty in males in uncommon and usually has an organic cause, particularly intracranial tumours.

Question 10

Describe how examination of the testis can be helpful in establishing the likely cause

Answer 10

• Bilateral enlargement of the testes suggest gonadotrophin release, usually from an intracranial lesion
• Small testes suggests an adrenal cause (e.g. a tumour or adrenal hyperplasia)
• A unilateral enlarged testis suggests a gonadal tumour

Question 11

How are tumours in the hypothalamic region best investigated?

Answer 11

Cranial MRI

Question 12

What are the principles of management of precocious puberty?

Answer 12

• Identify and treat any underlying pathology
• In gonadotrophin-dependent disease, gonadotrophin-releasing hormone analogues are used
• In gonadotrophin independent disease: Inhibitors of androgen or oestrogen production/action can be used e.g. cyproterone acetate, medroxyprogesterone acetate, testolactone and ketoconazole.

Question 13

When does premature breast development (thelarche) most often occur and how is it differentiated from precocious puberty?

Answer 13

Usually affects girls between 6 months and 2 years old.
Breast enlargement may be asymmetrical and rarely progresses beyond tanner stage 3.
It is differentiated from PP by the absence of axillary hair, pubic hair and a growth spurt.

Question 14

What is the management of premature thelarche?

Answer 14

It is non-progressive and self limiting so there is usually no need for investigations or treatment.

Question 15

What is the usual cause of premature pubarche?

Answer 15

Accentuated adrenarche (the normal maturation of androgen production by the adrenal glands)

Question 16

Which ethnicities is premature pubarche more common in?

Answer 16

Afro-caribbean and Asian children

Question 17

What investigations should be carried out in premature pubarche?

Answer 17

An USS of the ovaries and uterus in girls and a bone age should be obtained to exclude central precocious puberty.

Question 18

What other differentials (apart from central precocious puberty) should be considered in premature pubarche?

Answer 18

• Late onset congenital adrenal hyperplasia

- An adrenal tumour

Question 19

What are girls who develop premature pubarche at increased risk of later on in life?

Answer 19

Polycystic ovarian syndrome (PCOS)

Question 20

Define delayed puberty

Answer 20

The absence of pubertal development by 14 years of age in females and 15 years of age in males

Question 21

Which sex is delayed puberty more common in and what is the main cause?

Answer 21

Males; due to a constitutional delay in growth and puberty

Question 22

What assessment should be carried out in delayed puberty in males and females?

Answer 22

In boys: assessment includes pubertal staging, especially testicular volume; and identification of chronic systemic disorders.
In girls: thyroid and sex hormones should be measured; karyotype should be performed to identify Turner syndrome.

Question 23

What treatment can be given to males with delayed puberty?

Answer 23

Oral oxandrolone (a weak androgenic anabolic steroid) will induce catch up growth.
In older boys, low dose IM testosterone will accelerate growth and will induce development of secondary sexual characteristics.

Question 24

How can you treat females with delayed puberty?

Answer 24

Oestradiol

Question 25

Name four hypothalamo-pituitary disorders that can cause low gonadotrophin secretion and hence delayed puberty

Answer 25

1) Panhypopituitarism 2) Isolated gonadotrophin or GH deficiency 3) Intracranial tumours including craniopharyngioma 4) Kallman syndrome

Question 26

What is Kallmann syndrome?

Answer 26

A genetic condition in which the patient has LHRH deficiency and an inability to smell (anosmia).

Question 27

Name two causes of hypogonadotropic hypogonadism (and thus delayed puberty) that are not related to the HP axis.

Answer 27

1) Acquired hypothyroidism 2) Systemic disease e.g. CF, severe asthma, Crohn's disease, organ failure, anorexia nervosa, starvation, excess physical training.

Question 28

Delayed puberty can still occur when there is high gonadotrophin secretion (hypergonadotrophic hypogonadism). Think of 3 situations where this is the case.

Answer 28

1) Chromosomal abnormalities such as Klinefelter's syndrome (47 XXY) and Turner syndrome (45 XO) 2) Steroid hormone enzyme deficiencies 3) Acquired gonadal damage e.g. post surgery, chemotherapy, radiotherapy, trauma, testicular torsion and autoimmune disorders

Question 29

What four scenarios may cause a disorder of sexual differentiation?

Answer 29

1) Excessive androgens - producing virilisation in the female 2) Inadequate androgen action - producing under virilisation in the male 3) Gonadotrophin insufficiency 4) Ovotesticular disorder of sexual development (DSD) -caused by both XX and Y containing cells being present in the fetus leading toa complex external phenotype (this is rare).

Question 30

What is the commonest cause of excessive androgen production in the fetus?

Answer 30

Congenital adrenal hyperplasia

Question 31

What three things can cause inadequate androgen action?

Answer 31

1) An inability to respond to androgens e.g. androgen insensitivity syndrome (which is a receptor problem). 2) Inability to convert testosterone to dihydrotestosterone e.g. 5alpha-reductase deficiency 3) Abnormalities of the synthesis of androgens from cholesterol

Question 32

Name two conditions which can result in gonadotrophin insufficiency

Answer 32

1) Prader-willi syndrome | 2) Congenital hypopituitarism

Question 33

What diagnostic test can be used to confirm the presence of congenital adrenal hyperplasia?

Answer 33

Markedly raised levels of 17-alpha-hydroxyprogesterone in the blood.

Question 34

Over 90% of people with congenital adrenal hyperplasia have a deficiency of the enzyme needed to produce cortisol. What is the name of this enzyme?

Answer 34

21-hydroxlase

Question 35

How does overproduction of androgens occur in congenitala adrenal hyperplasia?

Answer 35

The cortisol deficiency stimulates the pituitary gland to produce ACTH which drives the overproduction of adrenal androgens.

Question 36

80% of of patients with congeintal adrenal hyperplasia are also deficient in aldosterone. What can this result in?

Answer 36

A salt-losing adrenal crisis. It occur at 1-3 weeks of age and presents with vomiting, weight loss, floppiness and circulatory collapse