Precocious Puberty ✅ Flashcards
What can precocious puberty be defined as in girls?
Evidence of breast or pubic hair development in girls before the age of 8 years
What can precocious puberty be defined as in boys?
Signs of testicular volume increase to at least 4ml, or other evidence of vitalisation, in boys occurring before the age of 9 years
What can the causes of precocious puberty be divided into?
- Gonadotrophin dependent
- Gonadotrophin independent
How can gonadotrophin dependent precocious puberty be differentiated from gonadotrophin independent?
LH and FSH are increased in gonadotrophin dependent, decreased in gonadotrophin independent
Is FSH or LH increased more in gonadotrophin dependent precocious puberty?
LH
Where does the increased LH and FSH come from in gonadotrophin dependent precocious puberty?
The pituitary
What is the result of increased FSH and LH in gonadotrophin dependent precocious puberty?
Enlargement of the gonads
What is the result of the enlargement of the gonads in gonadotrophin dependent precocious puberty?
- Increased oestrogen from the ovary
- Increased testosterone from the testis and adrenals
Is more testosterone produced by the testis or adrenals in gonadotrophin dependent precocious puberty?
Testis
What does the increased oestrogen in gonadotrophin dependent precocious puberty lead to in girls?
Breast development
What does the increased testosterone in gonadotrophin dependent precocious puberty lead to in boys?
- Pubic hair growth
- Acne
- Body odour
What are the causes of gonadotrophin dependent precocious puberty?
- Idiopathic/familial
- CNS abnormalities
- Hypothyroidism
What can cause CNS anomalies leading to gonadotrophin dependent precocious puberty?
- Congenital abnormalities
- Acquired abnormalities
- Tumours
Give an example of a congenital anomaly that can lead to gonadotrophin dependent precocious puberty
Hydrocephalus
Give 3 examples of acquired causes of CNS anomalies that can cause gonadotrophin dependent precocious puberty?
- Post-irradiation
- Infection
- Surgery
Give a tumour that can cause gonadotrophin dependent precocious puberty
Microscopic hamartomas
What happens in gonadotrophin independent precocious puberty?
A gonadal or extra-gonadal source leads to increased oestrogen or testosterone
Does the gonad shrink or enlarge in gonadotrophin independent precocious puberty?
Can be either
What happens to FSH and LH in gonadotrophin independent precocious puberty?
They are reduced
Why are FSH and LH reduced in gonadotropin independent precocious puberty?
The raised oestrogen/testosterone results in negative feedback on the pituitary, so there is reduced LH and FSH production
What are the causes of gonadotrophin independent precocious puberty?
- Adrenal disorders
- Ovarian causes
- Testicular causes
- McCune Albright syndrome
- Genetic mutation of LH receptor
- Exogenous sex steroids
Give 2 examples of adrenal disorders causing gonadotrophin independent precocious puberty
- Tumours
- Congenital adrenal hyperplasia
Give 2 examples of ovarian causes of gonadotrophin independent precocious puberty
- Cysts
- Tumours
Give an example of an ovarian tumour that can cause gonadotrophin independent precocious puberty
Granulosa cell tumours
Give an example of a testicular cause of gonadotrophin independent precocious puberty
Leydig cell tumour
What should be included in the history of a child with precocious puberty?
- Details of previous growth pattern and weight gain
- Timing of onset of features of puberty
- Presence of symptoms suggestive of intracranial pathology
- Risk factors in perinatal history
- Presence of disorders associated with sexual precocity
- Drug history
- Family history
- Extent to which early onset of puberty is impacting on child’s psychosocial wellbeing
What features of puberty should be asked about in the history for precocious puberty?
- Acne
- Body odour
- Breast, pubic hair, and genital development
- Increased vaginal secretions or periods
What risk factors in the perinatal history should be asked about in the history for precocious puberty?
- Prematurity
- Intraventricular haemorrhage
- Small for gestational age
Give 2 disorders that are associated with sexual precocity?
- McCune-Albright syndrome
- Neurofibromatosis
Give a drug that can be associated with precocious puberty
Oxymethalone
What should be asked about in the family history of precocious puberty?
Timing of maternal menarche
What should be noted on examination in a child with precocious puberty?
- Height
- Weight
- Tanner stage
- Measurement of testicular volume
- Features of other disorders, e.g. hyperthyroidism, McCune-Albright syndroome, neurofibromatosis
How should testicular volumes be measured?
Using a Prayer orchidometer
What features on examination may be suggestive of neurofibromatosis?
- Cafe-au-lait patches
- Axillary freckling
What examination should be performed to look for signs of raised ICP?
- Fundoscopy
- Visual field examinations
What investigations might be considered in precocious puberty?
- XR of left wrist
- Pelvic ultrasound
- Basal blood sample
- LHRH stimualtion test
- MRI of hypothalamopituitary axis
Why might a XR of the left wrist be done in precocious puberty?
To calculate bone age
Why might bone age be useful in precocious puberty?
Is a guide to the extent of physiological advance
What information may be obtained from a pelvic USS in precocious puberty?
- Size of uterus
- Extent of endometrial response
- Size of ovaries
- Presence of ovarian follicles
What hormones may be measured in basal blood samples in precocious puberty?
- Testosterone
- Oestrogen
- LH and FSH
- Adrenal androgens
What adrenal androgens may be measured in precocious puberty?
- DHEAS
- Androstenodione
- 17-OH progesterone
What is measured in a basal blood sample for precocious puberty in boys?
Testosterone
What is measured in a basal blood sample for precocious puberty in girls?
Oestradiol
What is the purpose of a basal blood sample for testosterone/oestradiol in precocious puberty?
Confirm biochemical evidence of puberty
Why can measurement of LH and FSH be helpful in precocious puberty?
Can distinguish between gonadotrophin-dependent and independent causes
Why might adrenal androgens be measured in precocious puberty?
To exclude a defect in adrenal hormone biosynthesis
What other investigation might be useful in excluding a defect in adrenal hormone biosynthesis?
A urinary steroid metabolite profile
When is a LHRH stimulation test indicated in precocious puberty?
If basal gonadotrophins are low and sex steroids are high
What does low basal gonadotrophins and high sex steroids indicate?
Gonadotrophin-independent precocious puberty
Why is a LHRH stimulation test indicated when there is suspected gonadotrophin-independent precocious puberty?
To confirm the lack of gonadotrophin response in this scenario
When is a MRI of the hypothalamopituitary axis required in precocious puberty>
In gonadotrophin-dependent precocious puberty (especially in boys)
Why is an MRI of the hypothalamo-pituitary axis required in gonadotrophin-dependent precocious puberty?
To exclude intracranial tumour
What is true central precocious puberty defined as?
Early onset puberty which has been stimulated by activation of the hypothalamo-pituitary axis
Is true central precocious puberty more common in boys or girls?
Girls
What is the most common cause of true central precocious puberty in girls?
Usually unknown
What is the most common cause of true central precocious puberty in boys?
Consequence of intracranial pathology
What intracranial pathologies can cause true central precocious puberty in boys?
- Tumours in the region of the hypothalamus
- Following previous cerebral trauma that occurred in the perinatal period
What tumours can occur in the region of the hypothalamus?
- Gliomas
- Astrocytomas
- Benign hamartomas
Give a cause of cerebral trauma occurring in the perinatal period that can lead to true central precocious puberty
Periventricular haemorrhage
What does a diagnosis of true central precocious puberty require?
- Measurement of serum oestradiol concentrations
- Usually a LHRH stimulation test
Why is a LHRH stimulation test usually required to diagnose true central precocious puberty?
To demonstrate activation of gonadotrophin
What other investigations may be done in true central precocious puberty?
- Left wrist x-ray
- Pelvic ultrasound in girls
- MRI
What will the left wrist x-ray show in true central precocious puberty?
Advanced bone development
What may a pelvic USS show in true central precocious puberty in girls?
- Ovarian enlargement with follicles
- Uterine enlargement
Why is an MRI done in true central precocious puberty?
To exclude intracranial haemorrhage
What does treatment of true central precocious puberty require?
GnRH analogue therapy
How does GnRH analogue therapy work in true central precocious puberty?
It suppresses gonadotrophin and oestradiol secretion
What is the purpose of treating true central precocious puberty?
- Prevent psychosocial effects of advancing puberty
- Maximise potential adult height
How do GnRH analogues work?
They bind to GnRH receptors
What effect do GnRH analogues have when they bind to GnRH receptors?
Initially stimulate them, but thereafter achieve downregulation
What side effect may be produced by down-regulation of GnRH receptors by GnRH analogues?
Temporary episode of vaginal blood loss
What causes a temporary episode of vaginal blood loss with downregulation of GnRH receptors?
Faling oestradiol levels
How long should GnRH treatment be continued for?
Until the child and family are comfortable to allow puberty to progress, or until the child has achieved the normal age-range for the stage of puberty that has been achieved
What happens to FSH and LH in gonadotrophin independent precocious puberty?
They are reduced
What causes androgen-mediated precocious puberty?
Excess androgen secretion
What does excess androgen secretion lead to?
Virilization, including pubic and axillary hair development
What can excess androgen secretion lead to in severe cases?
- Genital maturation in boys
- Cliteromegaly in girls
What is the most common form of androgen-mediated precocious puberty?
Exaggerated adrenarche
What is exaggerated adrenarche associated with?
The physiological activation of the adrenal gland from the age of 6 years
What does the physiological activation of the adrenal gland from the age of 6 years produce?
Relatively weak androgens such as DHEAS (dehydroepiandrosterone) and androstrenedione
How does the activation of the adrenal gland at age 6 usually clinically manifest?
Usually unnoticed
How does exaggerated adrenarche present?
- Production of small amounts of pubic or axillary hair
- Sometimes increased skin secretions and body odour
How is exaggerated adrenarche managed?
- No specific therapy required
- Reassurance
What is exaggerated adrenarche associated?
- Reduced brith weight
- PCOS
What is it important to distinguish exaggerated adrenarche from?
Congenital adrenal hyperplasia (CAH)
How is exaggerated adrenarche distinguished from CAH?
- Measurement of 17OH-progesterone
- Urinary steroid metabolite profile
In what form of CAH will there be abnormalities in 18OH-progesterone levels?
21-hydroxylase deficient variant
In what form of CAH will there be abnormalities in urinary steroid metabolite profiles?
Virilising forms
What form of CAH is more common?
21-hydroxylase deficient variant
What are virilising forms of CAH usually associated with?
Significant virilisation including cliteromegaly and evidence of growth spurt with marked advance in bone age
What tumours can produce androgen-mediated precocious puberty?
Virilising tumours of the ovarian or adrenal glands
What is required to treat virilising tumours producing precocious puberty?
Surgery
Give 2 causes of gonadotrophin-independent precocious puberty caused by genetic mutations
- Testotoxicosis
- McCune-Albright syndrome
What causes testotoxicosis?
Autosomal dominant activating mutations of the LH receptor
What gender is affected by testotoxicosis?
Males
What causes precocious puberty in McCune-Albright syndrome?
Activating mutations of a gene involved in G-protein coupled signalling
What gender can be affected by McCune-Albright syndrome?
Both
Will GnRH therapy work in gonadotrophin independent precocious puberty?
No
Why will GnRH therapy not work in gonadotrophin-independent precocious puberty?
Because the defect lies distal to the action of GnRH
What does therapy for gonadotrophin-independent precocious puberty use in girls?
Anti-oestrogens
What does therapy for gonadotrophin-independent precocious puberty use in girls?
- Androgen synthesis blockers
- Aromatase inhibitors
- Androgen receptor blockers
Give 2 androgen synthesis blockers
- Cyproterone
- Ketoconazole
Give an aromatase inhibitor
Testolactone
Give 4 androgen receptor blockers
- Spironolactone
- Ketoconazole
- Cyproterone
- Flutamide
Is premature thelarche common?
Relatively
What is premature thelarche?
Isolated breast development in young girls 6-12 months in the absence of any wider evidence of puberty or rising oestradiol concentration
What happens on LHRH stimulation testing in premature thelarche?
There is a FSH response
What is the mechanism of breast development in premature thelarche?
Unclear
What treatment is required for premature thelarche?
None - condition benign and self-limiting, no therapy required
What is thelarche variant?
A similar phenomenon to premature thelarche that occurs at 5-8 years
What might thelarche variant be associated with?
- Slight increase in height velocity
- Brief period of vaginal blood loss
What is premature menarche?
Cyclical vaginal bleeding occurring in the absence of wider signs of puberty
At what age does premature thelarche occur?
5-8 years
What is the mechanism of premature menarche?
Unknown
What are the differential diagnoses for premature menarche?
- Vulvovaginitis
- Vaginal trauma
- Foreign bodies
- Tumours
- Sexual abuse
