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The role of danazol in the management of precocious puberty.

The management, investigation and treatment of 12 children with precocious puberty is described. Danazol, a synthetic derivative of ethisterone, has been used over a period of 3 1/2 years. Its clinical, endocrine and biochemical effects have been evaluated. Danazol ha a very useful clinical effect in controlling the development of secondary sexual features but does not modify the rapid linear growth and skeletal maturity seen in this condition.

17-Ketosteroids↗

Lack of adrenarche in two children with precocious puberty secondary to hypothalamic hamartoma.

Adrenarche, which occurs earlier than gonadarche in normal children, is marked by increases in plasma dehydroepiandrosterone and its sulfate (DHAS). Adrenarche and gonadarche can be dissociated in various situations, e.g. central precocious puberty, indicating that they are controlled by independent mechanisms. This report concerns 2 children with central precocious puberty secondary to hypothalamic hamartoma. Their plasma basal DHAS values, compared to other cases with central precocious puberty not secondary to hamartoma, remained low for chronological age and bone age over a follow-up of 6.3 (case 1) and 9.2 9.2 years (case 2): in case 1 (boy), DHAS was 9 micrograms/dl at chronological age 7.7 and bone age 13 years; in case 2 (girl), DHAS was 11 micrograms/dl for chronological age 10.5 and bone age 13.5 years. GH secretion was normal. Basal plasma cortisol levels as the levels during hypoglycemia and after corticotropin stimulation were all normal. These data suggest that hypothalamic hamartoma may affect the central control of adrenarche. They may also contribute to the diagnosis of hypothalamic hamartoma.

Adrenal Glands↗

Long-term results of GnRH analogue (Buserelin) treatment in girls with central precocious puberty.

The GnRH analogue Buserelin was given for one year to six girls with central precocious puberty in a daily subcutaneous dose of 20 micrograms/kg/day. A decrease of plasma estradiol and vaginal maturation index to prepubertal values was obtained in 5 out of 6 cases. Bone maturation decreased and final predicted adult height improved significantly. This analogue of GnRH appears to be an effective medication for gonadotropin dependent precocious puberty in girls.

Buserelin↗

[Clinical study of subcutaneous administration of gonadotropin-releasing hormone agonist every six weeks in girls with idiopathic central precocious puberty].

OBJECTIVE: Gonadotropin-releasing hormone agonist (GnRHa) is widely used for the treatment of precocious puberty, but there was no identical regime for the dosage and the interval of administration. The aim of this study was to assess the feasibility of subcutaneous administration of Triptorelin with a prolonged interval (six weeks) for the suppression of pituitary-gonadal axis and clinical signs in girls with idiopathic central precocious puberty (ICPP). METHODS: Forty-six girls with ICPP were enrolled in this trial and were divided into two groups at random, with 26 patients in group A and 20 in group B. There were no significantly differences in chronological age, height, weight, age at clinical onset of puberty and bone age between the two groups before treatment. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6 weeks intervals in group A or intramuscularly (IM) at 4 weeks intervals in group B. Both forms were given for more than 12 months consecutively. During the period of treatment, the clinical parameters including height, weight, pubertal stage, bone age, uterine volume and ovarian size were documented. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E(2)) were monitored using immunoenzymometric assay. RESULTS: Both treatment regimes can completely suppressed the pituitary-gonadal axis. The clinical signs of pubertal development regressed or stabilized in all patients. Breast developments, as reflected by Tanner staging, were regressed. Uterine volume decreased after treatment, however, this decrease did not reach statistical significance. Mean ovarian volume did not change significantly during treatment. The height velocity was significantly decreased from a pretreatment value of 6.3 +/- 1.4 cm/year to 5.8 +/- 1.2 cm/year in group A and 6.7 +/- 1.3 cm/year to 5.4 +/- 1.0 cm/year in group B, respectively. The rate of skeletal maturation was reduced significantly during treatment. The ratio of bone age/chronological age was 1.2 +/- 0.2 or 1.3 +/- 0.3 at the onset of therapy and decreased significantly after the treatment to 0.7 +/- 0.2 or 0.9 +/- 0.1, respectively. The predicted adult height increased significantly and progressively during therapy. The levels of serum LH, FSH and E(2) were returned to the prepubertal condition after 6 - 8 weeks treatment and remained suppressed for the duration of treatment. No significantly side effects of therapy were noted. The most common adverse event during SC treatment was that a non-irritating, 1 cm in diameter mass can be palpated at the site of subcutaneous injection in the abdominal wall of group A patients. It gradually decreased in size, and disappeared after 8 - 12 weeks. Two girls had minimal withdrawal virginal bleeding episodes after the first injection. CONCLUSION: Both IM and SC triptorelin administration were clinically effective. They can induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6 weeks intervals at a dosage of 3.75 mg was a safe and acceptable regime for ICPP with good efficacy.

Body Height↗

Prostate specific antigen in boys with precocious puberty before and during gonadal suppression by GnRH agonist treatment.

UNLABELLED: In healthy boys, the pituitary-gonadal axis exhibits diurnal variation in early puberty. Serum testosterone levels are higher during the night and low or immeasurable during the day. These fluctuating levels of circulating androgens in early pubertal boys are difficult to monitor. Prostate specific antigen (PSA) is a marker of the androgen-dependent prostatic epithelial cell activity and it is used in the diagnosis and surveillance of adult patients with prostatic cancer. We have measured PSA concentrations in serum from boys with precocious puberty before and during gonadal suppression with GnRH agonists to evaluate the effect of normal and precocious puberty on PSA levels and to study the correlation between testosterone and PSA in boys. METHODS: PSA was measured by an ultrasensitive immunofluorometric assay with a detection limit of 0.03 microgram/l. Testosterone was measured by an RIA with a sensitivity of 0.23 nmol/l, and sex hormone binding globulin was measured by a time-resolved immunofluorescence assay (sensitivity 0.23 nmol/l). Five boys with central precocious puberty (CPP) were studied before and after 12 months of GnRH agonist treatment. Sixty healthy boys (12 in each Tanner stage of puberty) and 37 healthy young males served as controls. RESULTS: PSA levels were immeasurable in all prepubertal boys, whereas PSA levels increased with increasing stage of pubertal maturation. There was a significant correlation between PSA and testosterone and free androgen indices (r = 0.61 and r = 0.65 respectively, both P < 0.001). All 5 boys with CPP had significantly elevated PSA levels which decreased to very low or immeasurable levels after GnRH agonist treatment. CONCLUSION: PSA may be a useful marker of testosterone activity in boys with normal or precocious puberty.

Adolescent↗

Hypothalamic hamartoma causing precocious puberty treated by surgery: case report.

A 6-year-old girl was treated for precocious puberty secondary to a hypothalamic hamartoma by resection of the tumor. When she was six months old, her parents noticed incipient pubic hair and menses accompanied by breast development. Computed tomography was judged as normal. The girl was treated with monthly gonadotropin-releasing hormone analogue injections until 6 years of age, when magnetic resonance imaging (MRI) demonstrated a pedunculated isodense mass below the tuber cinereum. The hamartoma was totally removed using microsurgery. The symptoms and signs of precocious puberty disappeared after surgery. Follow-up MRI 1 year later showed no remaining tumor.

Child↗