Precocious puberty

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A 7 year old girl comes to visit you in clinic because her mum has noticed she has started developing breasts. She asks you – is this normal?

Is this child too young to have breast development?

Precocious puberty is defined as 2.5-3 standard deviations from the mean onset of puberty, usually below the age of 8 for girls and below the age of 9 for boys. However, this varies between ethnic populations. For example, those of African descent tend to experience puberty before those of Caucasian descent.

Normally, pubertal milestones vary greatly between males and females.

Girls begin puberty at approximately 10.5 years of age, starting with thelarche (formation of breast buds, Tanner breast stage 2), followed 6-12 months later by the onset of pubarche (formation of pubic hair, axiliary hair and acne). The arrival of these secondary sex characteristics usually corresponds with a rapid increase in growth velocity, which accelerates and peaks between 11 to 12 years of age. Conveniently, this growth spurt declines as menarche begins. The median duration between thelarche and menarche is 2.75 years.

For boys, puberty begins at approximately 11.5 years of age with the thinning of the scrotum and the enlargement of both testicles (longest diameters exceeding 2.5cm). More obvious genitalia changes follow this, as the penis begins to enlarge and the scrotum becomes pigmented. When pubarche occurs, it heralds a prolonged growth spurt for both height and physical musculature. Peak growth velocity is usually experienced around 14-15 years of age. Since puberty is generally slower and has a later onset in boys than in girls, precocious puberty in boys is more alarming and is often due to organic causes.

So, it is a bit early. How do I know what the cause is?

Precocious puberty is due to an early activation of the hypothalamic-pituitary-gonadal axis and is classified according to processes within the axis or processes bypassing the axis.

Gonadotropin-dependent precocious puberty (GDPP) is where factors within the axis prematurely trigger the onset of puberty. 80% of GDPP in girls are idiopathic and are of no need for concern. However, GDPP can be caused by various CNS abnormalities, such as an acquired defect (abscess, post-meningitis, chemotherapy, radiation), a congenital defect (arachnoid cyst, hydrocephalus, primary severe hypothyroidism), or a CNS tumour (astrocytoma, craniopharyngioma, hamartoma). Exogenous steroids and sexual abuse can trigger GDPP. These must be ruled out.

The only clinical difference between normal puberty and GDPP is its early onset. Development is sequential and well timed, and sexual characteristics are appropriate to the patient’s gender (isosexual). Serum gonadotropin and sex steroid levels are at pubertal levels, with LH responding when challenged with GnRH. Thyroid function tests and an MRI of the brain are used to rule out any central pathologies. Assessment of bone age is used to infer the progression of puberty, as well as to aid in estimations of anticipated adult height. Further evaluations are warranted if the bone age is >20% older than chronological age.

Gonadotropin-independent precocious puberty (GIPP) occurs when excessive secretion of oestrogen or androgens bypass the hypothalamus and cause an inappropriate activation of puberty. Development may not follow typical progression and may be appropriate to the patient’s gender (isosexual) or inappropriate (contrasexual). Serum gonadotropins are suppressed and LH does not respond to GnRH challenges.

Exogenous sources include ovarian cysts, Leydig cell tumours hCG-secreting germ cell, testotoxicosis, McCune-Albright syndrome, untreated congenital adrenal hyperplasia, virilzing adrenal tumours, adrenal cancers and exogenous sex steroid use. Investigations are used as indicated, including serum testosterone, estradiol, LH, FSH, cortisol, DHEA, DHEAS, 17-hydroxyprogesterone, CT scan, MRI, ultrasound and genetic testing.

Incomplete precocious puberty can also occur, defined as isolated premature thelarche in girls and isolated premature adrenarche in boys. These are variants of normal puberty but should be monitored in case they progress to precocious puberty.

When is intervention appropriate, and if so what's the best management?

Intervention focuses on preserving the child’s adult height and alleviating psychosocial stresses, while preventing progression of secondary sex characteristics in the short term. Benefit from treatment should be estimated according to their age, rate of maturation and predicted height (based on height, height velocity and bone age), as not all children need treatment. These variables should be monitored regularly, with pubertal growth and development monitored every 3-6 months, and bone age radiographs every 6-12 month.

Slow clinical progression indicates conservative treatment, whereas young age and rapid clinical progression indicates rapid intervention.

For GDPP, using GnRH agonist therapy to suppress the HPG axis is usually safe and effective. The effectiveness of this suppression should be monitored and adjusted accordingly, until the patient’s age no longer indicates suppression therapy. Patients with any associated CNS abnormalities should be referred and monitored appropriately.

Treatment for GIPP does not involve GnRH agonists, but is instead centred around treating any underlying pathology. Management for inadequately controlled CAH should be optimized. Surgery for tumors of the testes, ovaries and adrenals should be considered. Exogenous drugs should be identified and discontinued. Patients with McCune-Albrjght syndrome or testotoxicosis require pharmacotherapy to inhibit gonadal steroid synthesis, such as ketoconazole, cyproterone, aromatase inhibitors or anti-androgens.

Bottom line

  • Precocious puberty is more acceptable in girls than in boys.
  • 90% of central precocious puberty in girls is constitutional.
  • GnRH dependent precocious puberty has a normal pubertal progression. Growth is linear, bone age is advanced and serum sex hormones are at pubertal levels.
  • GnRH independent precocious puberty doesn’t follow the normal pattern of puberty, with abnormal pubertal progression and either isosexual or contrasexual development.
  • Anthropometric measurements, physical examination, pubertal staging, and radiographic bone age are key clinical indicators.
  • Investigations include (according to indication) bone age assessment, serum FSH, LH, testosterone, oestrogen, pelvic ultrasound, GnRH stimulation test, MRI brain, MRI adrenals, genetic testing and TSH/FT4.
  • Intervention aims to conserve adult height, reduce psychosocial stresses, and treat the underlying cause.

References

Uptodate.com. Definition, etiology, and evaluation of precocious puberty [Internet]. 2015 [cited 19 March 2015]. Available from: http://www.uptodate.com/contents/definition-etiology-and-evaluation-of-precocious-puberty?source=search_result&search=precocious+puberty&selectedTitle=1~100

Uptodate.com. Treatment of precocious puberty [Internet]. 2015 [cited 19 March 2015]. Available from: http://www.uptodate.com/contents/treatment-of-precocious-puberty?source=search_result&search=precocious+puberty&selectedTitle=2~100

Bestpractice.bmj.com. BMJ Best Practice – Precocious Puberty [Internet]. 2015 [cited 19 March 2015]. Available from: http://bestpractice.bmj.com/best-practice/monograph/1127.html

Marcdante K, Kliegman R. Nelson essentials of pediatrics. Philadelphia, PA: Saunders/Elsevier; 2015

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About 

Lindsay Holland is a medical student at the University of Newcastle, currently enjoying his first hospital placement. Discovering how little free time he is now left with, Lindsay practices writing fiction, flailing around with paintbrushes and listening to his friend, when he's able to.

2 Responses to "Precocious puberty"

  1. James
    James 2 years ago .Reply

    Thanks for the summary, Lindsay! I thought it really highlighted the important points and those easy to get lost in the whole picture, in particular an understanding of normal and the variations of normal, as well as the indications for and goals of treatment.
    Please write more!

    • Tessa Davis
      Tessa Davis 2 years ago .Reply

      Glad you like it James. All contributions are always welcome.

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