Diagnosis and Treatment of Central Precocious Puberty-Can Final Height Be Improved?

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Abstract
Central precocious puberty is characterized by premature activation of the hypothalamic gonadotrophin-releasing hormone (GnRH) pulse generator, resulting in accelerated growth and bone maturation with clinical signs of gonadarche before the age of 8 years in girls and 9 years in boys. In rapidly progressing central precocious puberty, the plasma luteinizing hormone (LH) response to exogenous GnRH exceeds the reference range for sex and stage of puberty, and the ratio of LH:follicle-stimulating hormone after GnRH is usually above 1 [1]. Short adult stature, with unfavourable body proportions, i.e. an increased upper:lower segment ratio, is probably the only handicap of idiopathic central precocious puberty that persists into adulthood. This cannot be avoided by treatment with either medroxyprogesterone or cyproterone acetate. Following the first report of pituitary-gonadal suppression in a 2-year-old girl with central precocious puberty using daily injections of the gonadotrophin-releasing hormone (GnRH) agonist deslorelin [2], various short-acting GnRH agonists have been studied in children with central precocious puberty. Some of the older patients treated for shorter periods have now reached adult or near-final height. By 1985, slow-release (depot) GnRH agonists, such as triptorelin and later leuprorelin, were available. These are injected only once every 4 weeks instead of daily or given by nasal spray six times daily, making long-term treatment much more acceptable to patients and their parents. Moreover, suppression of gonadarche is more complete with long-acting (e.g. triptorelin) compared with short-acting (e.g. buserelin) agonists, resulting in significantly slower bone age progression and, thus, greater improvement in predicted, and probably also in achieved, final height [3]. A multicentre trial of depot triptorelin organized by the German/Dutch Central Precocious Puberty Study Group enrolled 104 children. Pubertal development was arrested or regressed, behaviour improved markedly and menstruation ceased in all the girls receiving the drug. Pathological increase of height velocity and bone maturation normalized, and the predicted adult height increased significantly by a mean of 1.5 cm/treatment year. After cessation of depot triptorelin treatment, the mean height prediction decreased slightly and the approximate adult height remained comparable with the predicted height at the start of treatment (in most cases slightly below genetic target height), due to a reacceleration of bone maturation. This is similar to the results obtained with short-acting GnRH agonists. After treatment, normal puberty and, in girls, cyclic ovarian function, returned progressively. No side-effects or antibodies were observed [4]. Depot GnRH agonists appear to be the treatment of choice for long-term therapy of central precocious puberty. Not only is long-term compliance good, but also, because of their superior suppressive effects on bone maturation, the previously severely compromised adult height of such patients can be avoided. Whether additional treatment with growth hormone will improve final height in a subgroup of patients with a pathologically low final height prediction and/ or target height remains to be studied in a sufficiently large number of children on a long-term basis.

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