Precocious Puberty
How long after the thelarche does menarche start?
2-2 and a half years, however, this may be up to six years
What is the value of prepubertal testosterone in boys?
<10-20ng/dl
What is the value of the prepubertal oestrogen in girls?
<5-10pg/ml
How can you classify the types of precocious puberty?
AS central, gonadotropin dependent, true OR peripheral, gonadotropin independent, precocious pseudopuberty
How does the GnRH agonist stop the precocious puberty?
It disrupts the normal stimulation of the GnRH receptors and causes insensitivity to it, thereby reducing the secretion of LH and FSH and then reduces estradiol and testosterone
What is McCune-Albright syndrome?
It is a genetic disorder that affects the bones, skin and the endocrine system. It is suspected if at least one of the following is present: Hyoerfunctioning endocrine disease, fibrous dysplasia or café-au-lait patches or macules
Compare the time frame for the peak height velocity in males to females?
It is about 2 years apart
What is premature adrenarche?
It is isolated pubic and axillary hair, and apocrine gland developing because of either increase in DHEA or hypersensitivity of the pilosebaceous hair unit. Acne, increased height, body odour, increased bone age
What are some of the GnRH agonists used to treat central precocious puberty?
Leuprolide acetate IM once per month or the depot form every 90 days OR histrelin SC implant that lasts for 12 months. Goserelin acetate. Naferelin
Which hormone changes at about three years before the clinical onset of puberty?
Luteinizing hormone, it is released at nights in a pulsatile fashion, and this increases as one gets closer to puberty. This is responsible for the enlargement and maturation of the gonads, and to secrete sex hormones
How will a male be affected if he has aromatoase deficiency and oestrogen receptor defects?
Males will be taller than usual. This proves that oestrogen and not androgens are responsible for bone maturation that leads to epiphyseal fusion and cessation of growth
Which group of persons tend to get organic central nervous system causes of central precocious puberty?
Males; girls with rapid breast development or estradiol levels >30pg/ml or those younger than 6 years
Do periods tend to be regular in girls with precocious puberty?
No
Is the hypothalamic pituitary gonadal axis active during pre-puberty?
No
True or false, the level of testosterone in the serum is low or undetectable in the early phases of central precocious puberty?
No, the levels are detectable provided an early morning sample is obtained
Can one become pregnant with precocious puberty?
Not usually, but this is because the cycles are usually anovulatory
Which hormones are responsible for the pubertal growth spurt?
Oestrogen, growth hormone and sex steroids. The oestrogen stimulates the production of growth hormone. So growth hormone is directly responsible for the spurt
Which comes first, peak height velocity or menarche?
Peak height velocity
How do the uterus and ovaries change with central precocious puberty?
Pelvic ultrasound will show progressive enlargement of the ovaries, enlargement of the fundus and then the whole uterus. This is similar to the changes in normal puberty
What are some conditions that may cause pseudoprococious puberty?
Ovarian tumors or cysts, McCune-Albright syndrome, neurofibromatosis, adrenal lesions
How can peripheral precocious puberty induce central precocious puberty?
Peripheral precocious puberty can cause activation of the hypothropic pituitary gonadal axis and this may trigger central precocious puberty
How does radiation to the brain related to central precocious puberty?
Radiation to the brain increases the risk, and this could be directly to the hypothalamus or directed elsewhere in the brain
What are the three main patterns of pubertal progression with central precocious puberty?
Rapidly progressive puberty; Slowly progressive puberty; Spontaneously regressive central precocious puberty - -this is the rarest type
What causes true precocious puberty?
Anything in the brain that increases the prevalence of excitatory inputs or by interfering with neurogenic inhibition of hypothalamic gonadothrophic releasing hormone
At what age and Tanner stage of breast development do girls reach their peak height velocity?
At breast stages II-III, usually between 11 and 12 years
Why is gonadotropin releasing hormone agonists used in the management of central precocious puberty?
Because a pulsatile releases of GnRH is needed to stimulate the pituitary cells to maintain the on-going releases of gonadotropins. The agonists work longer than the native GnRH and are more potent. The agonists after a while desensitises the cells of the pituitary gland to the effects of endogenous GnRH and so halt the progression of central precocious puberty
What is the commonest cause of precocious puberty?
CRaniopharyngiomas - these start in the pituitary gland so brain imaging is important in these patients
Compare central and peripheral precocious puberty
Central precocious puberty stems from hypothalamic pituitary gonadal activation. Peripheral precocious puberty does not causes activation of the hypothalamic pituitary gonadal axis
What are the kinds of precocious puberty?
Central/true and peripheral/pseudo
What are some conditions that cause true precocious puberty?
Cerebral palsy, hydrocephalus, head trauma, chronic inflammatory diseases, tumours like pinealoma, gliomas, craniopharyngiomas
What are some causes of peripheral precocious puberty in boys?
Congenital adrenal hyperplasia, adrenal tumours, Leydig cell tumours. Chorionic gonadotropin producing tumours, exogenous androgens, familial male precocious puberty
In adrenarche, which hormone is increased?
Dehydroepiandrosterone (DHEA) and its sulphate, DHEAS. This is at about age 6-8 years, even before LH surges
What is DHEA?
Dehydroepiandrosterone, an androgen
What investigations would you need to do for precocious puberty?
Determine the growth velocity; determine bone age; orchidometer volume. Get the level of LH, FSH, DHEA, testosterone and oestradiol. Pelvic U/S for ovarian volume. LHRH stimulation test (not done routinely anymore). You do a brain scan depending on the cause
What is a hamartoma?
Disorganised tissue growth where it belongs-----------------
What is the cause of central precocious puberty?
Early activation of the hypothalamic pituitary gonadal axis
What age do you consider prepubertal?
Early childhood to about 8-9 years
Which sex gets central precocious puberty more?
Females
Which sex is more at risk for precocious puberty from low dose radiation?
Females
Who gets central precociouspuberty more?
Females
Which sex gets true precocious puberty more?
Females, they tend to have relatively high levels of gonadotrophin
Which sex tends to get idiopathic precocious puberty more?
Girls - they tend to have relatively high levels of gonatrophin. Boys tend to have a cause
How do you manage the child with central precocious puberty due to irradiation to the brain?
GnRH agonists are effective. You must look for other hormone problems like growth hormone deficiency and hypothyroidism and treat them so that adult height prognosis will improve
How do you manage the child with central precocious puberty due to an organic CNS lesion?
GnRH agonists regardless of the cause
What other conditions are usually seen with precocious puberty due to brain irradiation?
Growth hormone deficiency, spinal irradiation, hypothyroidism and other hormone imbalances
What are the first signs of puberty in males?
Growth of the testes and thinning of the scrotum. This is followed by pigmentation of the scrotum and growth of the penis, then pubarche
Which dose of radiation is enough to affect boys as it relates to precocious puberty?
High doses. High doses affect both sexes
What is the likely cause of a rapidly progressive central precocious puberty in a very young child?
Hypothalamic hamartoma
What is the most common brain lesion causing central precocious puberty?
Hypothalamic hamartomas
How does the pituitary gland change with central precocious puberty?
The gland enlarges physiologically like in normal puberty. MRI best demonstrates this
What happens to the menses when you treat central precocious puberty?
The menses stop
How does the hypothyroidism in a child with precocious puberty present?
The presentation is unusual. There is retardation od growth and osseous maturation. Normally, the child with hypothyroidism has delayed puberty
How do the serum levels of the sex hormones change with treatment of central precocious puberty?
The serum sex hormones decrease to prepubertal levels
How does the penis change when treating central precocious puberty?
The size of the testicle is decreased, there is pubic hair regression and a decrease in the frequency of the erections
How does the concentration of luteinizing hormone change during puberty?
The surge of release is increased, and release now happens in the daytime. Girls get a distinct increase in LH during every cycle of menstruation
What is usually the first sign of puberty in females?
Thelarche. This is followed by pubic hair formation (pubarche)
When do you discontinue the treatment of central precocious puberty?
Therapy is discontinued at the time when it is physiologically supposed to occur. However time has to be adjusted for when to actually stop the drugs, example puberty will begin ~18 months after stopping IM therapy
How do the lesions causing organic CNS central precocious puberty present if they show presentations other than precocious puberty?
There are neuroendocrine signs and symptoms up to 1-2 years before the tumour can be detected radiologically. Hypothalamic signs include diabetes insipidus, adipsia, hyperthermia, unnatural crying or laughing, obesity or cachexia. Visual signs may be present. All this is dependent on the kind of lesion
How does treatment of central precocious puberty affect the growth?
There is a decrease in the growth rate. In girls, breast development may regress if they are at Tanner stage II-III
When treating central precocious puberty, what happens to the size of the ovaries and the uterus?
There is a size decrease
How does syndrome of precocious puberty and hypothyroidism present in girls?
There is breast enlargement and menstruation. Ultrasound may show polycystic ovaries. There is no pubic hair development
Central precocious puberty is isosexual, what does this mean?
There is development of phenotypically appropriate secondary sexual characteristics. They develop appropriately for their sex
What changes may you see in the brain of a child with syndrome of precocious puberty and hypothyroidism?
There is enlargement of the sella which is typical of chronic primary hypothyroidism
How does rapidly progressive precocious puberty do to the height of the child?
There is rapid physical and osseous maturation so that there is a loss of height potential ----------ad others
What are some other conditions of the CNS that may cause central precocious puberty?
They are usually involving the hypothalamus - scarring, ivasion or pressure. Postencephalitic scars, tuberculous meningitis, tuberous sclerosis, severe head trauma, hydrocephalus (isolated or due to meningomyelocele). Neoplasms like astrocytomas, ependymomas, optic tract tumours
How does syndrome of precocious puberty and hypothyroidism present in boys?
They have testicular enlargement with modest or no penile enlargement. There is no public hair development
What is the cause of idiopathic true precocious puberty?
This is as a result of premature triggering of the normal pubertal mechanism. Puberty is completely normal
What is premature thelarche?
This is isolated non-progressive breast development. It is normal and is as a result of a subtle overfunction of the hypothalamic pituitary ovarian axis. FSH is mildly elevated and LH is normal
Define precocious puberty
This is the onset of secondary sexual characteristics before the age of 10 in boys and 8 in girls
Define precocious puberty
This is the onset of secondary sexual characteristics before the age of 10 in boys and before 8 in gilrs
At what age and Tanner stage of genitals do boys reach their peak height velocity?
This is well after puberty at stages IV-V at around 13-14
What is premature menarche?
This is where girls menstruate at an unusually early age without the other signs of puberty. These are usually short lived and rare so you must look for other causes of per vaginum bleeding
Which group of children tend to get optic tract tumours?
Those with neurofibromatosis type I
Which patterns of central precocious puberty do you want to treat?
Those with rapidly progressive precocious puberty
How does true precocious puberty and pseudo precocious puberty differ?
True is as a result of stimulation of the hypothalamic pituitary gonadal axis, while pseudo is independent of the axis
What are some causes of peripheral precocious puberty in girls?
Tumours of the ovaries, ovarian cysts, feminising adrenal tumours, McCune Albright syndrome, sources of exogenous oestrogen
True or false, all children at risk for get organic central nervous system causes of central precocious puberty should undergo an MRI of the brain and pituitary gland?
Yes
True or false, boys may continue to grow beyond 18 years?
Yes
True or false, females tend to get idiopathic central precocious puberty?
Yes
True or false, neurofibromatosis may give central and or peripheral precocious puberty?
Yes
True or false, puberty occurs in the same direction regardless of the age of onset?
Yes
True or false, the level of estradiol in the serum is low or undetectable in the early phases of central precocious puberty?
Yes
True or false, the risk of developing precocious puberty from radiation increases the younger the child is?
Yes
True or false, LH is usually undetectable in prepubertal children but detectable in children with central precocious puberty?
Yes with the use of highly sensitive tests
True or false, there is a relation between the level of adipose tissue and the onset of puberty in girls?
Yes, more adipose tissue leads to earlier puberty. Compare this to the leaner more athletic girls
True or false, the sex hormones have growth promoting effects?
Yes, this is why a growth hormone deficiency may be masked in some cases of central precocious puberty
True or false, peripheral precocious puberty can be isosexual as well as heterosexual?
Yes. Heterosexual is also called contralateral
True or false, the lesions that cause organic CNS central precocious puberty tend to remain static or grow slowly?
Yes. They usually produce no other signs but precocious puberty
What are some of the conditions that a mixed type of precocious puberty occur in?
You may get a central and peripheral precocious puberty in congenital adrenal hyperplasia, McCune-Albright syndrome and familial male limited precocious puberty
What is the average age of menarche?
~12.75 years
What are the hormone levels like in a child with syndrome of precocious puberty and hypothyroidism?
TSH is markedly elevated; prolactin and eostradiol are mildly elevated
How does a hypothalamic hamartoma work to cause central precocious puberty?
The cells produce transforming growth factor alpha that has the potential to activate GnRH pulse generator
What is telarche?
The development of the breast buds in females
Why may the child with central precocious puberty be shorter than their normal counterpart?
The epiphyses mature and close earlier. Without treatment, they become short adults
