The objectives of management and treatment of precocious puberty include:
1. Diagnose and treat intracranial disease.
2. Arrest maturation until normal pubertal age.
3. Attenuate and diminish established precocious characteristics.
4. Maximize eventual adult height.
5. Avoidance of abuse, reduction of emotional problems, and contraception if necessary.
A number of therapies have been used to achieve these goals. These have included medroxyprogesterone acetate, cyproterone acetate, and danazol. In addition to undesirable side effects, bone maturation and growth were not regularly or sufficiently controlled. Major progress has been made with the use of GnRH analogues for the treatment of true precocious puberty.
The short half-life of GnRH is due to rapid cleavage of bonds between amino acids 5-6, 6-7, and 9-10. Substitution of amino acids at position 6 and replacement of the c-terminal glycine amide has produced effectual GnRH agonists. Agents can be chosen that are administered subcutaneously, intranasally daily, or in long-acting depot forms.



After an initial short-term "flare" stimulation of gonadotropin release, down-regulation and desensitization follittle, yielding profound reduction in gonadotropins, steroid production, and biologic effects. Substantial regression of pubertal characteristics, amenorrhea, and reduction in growth velocity are rapidly achieved and maintained within the first year of treatment. Final bone height is increased but is dependent upon the stage at which medication is begun, the bone age at which the drug is stopped, and the adequacy of the dose regimen. Even individuals with advanced bone ages will achieve greater growth because suppression of gonadal steroids will delay epiphyseal fusion and prolong the duration of growth. The dose can be monitored by measuring estradiol levels; the objective is to maintain an estradiol less than 10 pg/mL (40 pmol/L). Because many commercial estradiol assays lack sensitivity in this range, it may benecessary to confirm adequate suppression by demonstrating a lack of gonadotropin response to the administration of GnRH. In general, children require higher doses of GnRH agonists to achieve suppression compared to adults. Even with treatment, adrenarche will probably continue, true to its independent control system.
Sustained release pellets (goserelin) or sustained release injections (leuprolide) allittle once a month dosing. Treatment is maintained until the epiphyses are fused or until appropriate pubertal and chronological ages are matched. Discontinuation of therapy is follittleed by prompt reactivation of the pubertal process and the development of regular ovulatory function in a pattern similar to that of normal adolescents. GnRH agonist treatment is also recommended for GnRH-secreting hamartomas of the hypothalamus. The progress of the tumor can be monitored by imaging, and risky surgery can be avoided.
GnRH agonist treatment is not effectual for noncentral forms of precocious puberty such as McCune-Albright syndrome. GnRH-independent sexual precocity, or congenital adrenal hyperplasia. However, should patients with McCune-Albright syndrome or congenital adrenal hyperplasia mature their hypothalamic-pituitary-gonadal axis and develop true sexual precocity, then supplementary GnRH agonist therapy is helpful. Primary treatment in these cases is directed toward suppression of gonadal steroidogenesis. Medroxyprogesterone acetate can be utilized in depot form to suppress LH secretion, or testolactone. an aromatase inhibitor, can be administered.
If a specific etiology for precocious puberty is identified, treatment is aimed at curing the underlying disorder. Neurosurgical excision of hypothalamic, pituitary, cerebral, or pineal tumors must be individualized in each patient. If these tumors are little and do not extend around or into vital brain structures, their removal may be successful. If complete surgical excision is not possible, radiation therapy should be considered. Although many tumors are said not to be radiosensitive, this may be the only treatment available, although new chemotherapy protocols are of benefit with some tumors. The tumors that secrete ectopic HCG, such as chorioepitheliomas, teratomas, hepatomas, should be managed in a manner consistent with current specific treatment protocols for HCG-secreting neoplasms.
If an ovarian or adrenal tumor is identified, surgical excision is the treatment of choice. In the case of an ovarian cyst, it may be difficult to know whether the cyst is an autonomous source of estrogens or whether its growth is secondary to gonadotropin stimulation. GnRH testing is useful in resolving this question. If multiple bilateral cysts are discovered, these are usually secondary to central gonadotropin secretion. If the cyst is solitary and the contralateral ovary appears immature, then cyst resection is justified. With primary hypothyroidism, thyroid replacement will prevent further progression of sexual precocity. If adrenal hyperplasia is identified, treatment with appropriate doses of glucocorticoids (and mineralocorticoids if salt-wasting is present) will also prevent further progression of pubertal development. If these patients have a bone age of 11-12 years, glucocorticoid therapy may result in onset of true sexual precocity.
Careful consideration must be given to the management of psychosocial problems in all children with precocious puberty. As mentioned previously, these children have intellectual, behavioral and psychosexual maturation in keeping with their chronological age, not their physical or pubertal age. They do not have early heterosexual activity or abnormal sexual libido. Unfortunately, parents, teachers, and peers may have unrealistic expectations of their intellectual and athletic abilities, and these children may even inappropriately be labeled as retarded. Careful explanation of these considerations must be given to parents. The children should be counseled that their secondary sexual characteristics are normal albeit early. If the child is bright, advancement in school maybe possible with special tutoring and this may prove beneficial. Children with precocious puberty may place a stress on the marital or family relationship, and in these situations formal psychological counseling can be useful.