Central Precocious Puberty

Central Precocious Puberty
This is known as central, idiopathic or gonadotrophin-dependent precocious puberty. The pattern of sexual development is indistinguishable from normal puberty and investigations reveal LH predominance to a GnRH stimulation test and a multicystic ovarian morphology on pelvic ultrasonography. This may be associated with low-dose cranial irradiation, especially in girls and when irradiation is given at a young age.

Once the initial investigations have indicated that the sexual maturation is gonadotrophin dependent, then imaging of the hypothalamic pituitary region is essential. It used to be considered that most girls with central precocious puberty had ‘idiopathic’ precocious puberty, whereas with the availability of high-resolution CT scanning, it was appreciated that many such girls had hypothalamic lesions which were most commonly hamartoma. Recent studies in much larger numbers from both Italy and France have shown that there is a significant risk of any girl with central precocious puberty having a hypothalamic/pituitary tumour with sexual precocity being the only abnormal sign. Although reinforcing the original findings of Cacciari et al. that young girls with central precocious puberty usually have a hypothalamic hamartoma, tumours such as astrocytoma may present with central precocious puberty in girls between the ages of 5 and 7 years, and it is extremely important not to miss such an underlying aetiology at an early stage of the tumour’s growth.

These findings reinforce the clinical guideline that all girls with central precocious puberty should have neuroradiological imaging of the hypothalamic pituitary region. It is interesting that some tumours of the hypothalamic region, such as hamartoma, optic nerve glioma and astrocytoma, commonly produce precocious puberty, whereas others, such as craniopharyngioma, Langerhans’ cell histiocytosis and germinoma, only rarely cause precocious puberty despite involving the same anatomical site.

Hamartomata are the commonest hypothalamic tumours found in girls with central precocious puberty. Any surgical excision which may be indicated for intractable fits, would not cause a resolution of the precocious puberty. Interestingly, relatively high LH concentrations, not related to an LH surge, are often an indication of the presence of a tumour in the hypothalamic pituitary region.

Since 1980, older treatments with cyproterone acetate or medroxyprogesterone have been superseded by the use of GnRH analogues. These suppress gonadotrophin pulsatility and gonadotrophin secretion, and initially suppress and, hopefully, regress sexual maturation. They are relatively free of side effects and are effective. They can be given either as daily subcutaneous injections, intranasal sprays 2–3 times a day, or by depot injections lasting between 1 and 3 months. If puberty is well advanced and there is an endometrial echo of more than 4mm in thickness, then it is usually appropriate to use cyproterone acetate in conjunction with a GnRH analogue for the first 3 weeks in order to prevent a uterine withdrawal bleed associated with the initial stimulatory phase of the GnRH analogue’s action.

The indications for treating girls with central precocious puberty are to suppress sexual maturation and to help with psychological difficulties. Certainly, GnRH analogue treatment is effective for both of these sequelae, but it is also important to have an expert psychologist available to give appropriate support.

When GnRH analogues were initially introduced, there was a promise of increasing final height prognosis. However, there is no convincing evidence that there is an improvement in final height with the exception of 1 or 2cm. It is probable that the reasons why it was initially considered that height prognosis was improved was the inclusion of patients with thelarche variant (see below) into the cohort of patients considered to have central precocious puberty. There has been some evidence that adding biosynthetic human growth hormone to gonadotrophin-releasing analogue therapy may improve final stature.

 

Provided by ArmMed Media
Revision date: June 20, 2011
Last revised: by Janet A. Staessen, MD, PhD