trelstar and Hamartoma

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin se

Topics: Adrenal Glands; Adrenal Hyperplasia, Congenital; Bone Development; Child; Child, Preschool; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Gonadotropin-Releasing Hormone; Growth Hormone; Hamartoma; Humans; Hypothalamic Neoplasms; Insulin-Like Growth Factor I; Luteinizing Hormone; Male; Pituitary Hormone-Releasing Hormones; Puberty, Precocious; Testosterone; Triptorelin Pamoate

Very few abnormalities in endocrine function have been reported during long term gonadotropin-releasing hormone agonist (GnRHa) treatment in girls. Most authors agree that this therapy is safe and effective. We present an unusual outcome of long term GnRHa therapy in two girls with central precocious puberty(CPP) of idiopathic or organic origin. They have received monthly depot injections of triptorelin acetate for a time period of 8 years. Thyroid function was examined by measuring serum levels of thyrotropin (TSH), thyroxine (T4), thyroid antibodies, and ultrasound of the thyroid gland. One of the girls was at the age of 8.5 years, having elevated thyroid antibodies, mild goitier and an abnormal ultrasound of the thyroid gland, suggesting autoimmune thyroiditis. Another girl with a hypothalamic hamartoma developed diabetes mellitus at the age of 9 years. Both of these girls were early diagnosed for CPP, at 6 months and 8 months respectively, and given GnRHa treatment. So far, it is not known whether these autoimmune diseases are related to the GnRHa treatment or are simply a coincidence. However, we suggest a closer monitoring of girls with CPP who have had a long period of treatment.

Topics: Child; Diabetes Mellitus, Type 1; Female; Hamartoma; Humans; Luteolytic Agents; Pituitary Diseases; Puberty, Precocious; Thyroiditis, Autoimmune; Triptorelin Pamoate

Hypothalamic hamartomas (HH) are rare congenital lesions of the tuber cinereum presenting with the classic triad of gelastic epilepsy, central precocious puberty (CPP) and developmental delay. In light of the important and diverse consequences of precocious puberty for affected children and their families, a correct diagnosis without delay is imperative. We present here a rare case of a 7-month-old infant girl with CPP and HH who was successfully treated with depot gonadotropin-releasing hormone (GnRH) analogue is presented.

Topics: Delayed-Action Preparations; Estradiol; Female; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Infant; Injections, Intramuscular; Luteinizing Hormone; Luteolytic Agents; Magnetic Resonance Imaging; Puberty, Precocious; Triptorelin Pamoate

Topics: Child; Female; Hamartoma; Humans; Hypothalamic Diseases; Luteolytic Agents; Puberty, Precocious; Triptorelin Pamoate

Childhood epileptic syndrome characterized by early onset gelastic seizures, hypothalamic hamartoma and precocious puberty is well recognized though rare. We report association of agenesis of corpus callosum, Dandy-Walker complex and heterotopic gray matter with this childhood epileptic syndrome which is hitherto an unreported association. The child showed a satisfactory response to gonadotropin releasing hormone agonist.

Topics: Agenesis of Corpus Callosum; Cerebral Cortex; Corpus Callosum; Dandy-Walker Syndrome; Epilepsies, Partial; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Neoplasms; Infant; Luteolytic Agents; Magnetic Resonance Imaging; Male; Nervous System Malformations; Puberty, Precocious; Treatment Outcome; Triptorelin Pamoate

Although the GnRH agonist analogs have become an established treatment for precocious puberty, there have been few long term studies of reproductive function and general health after discontinuation of therapy. To this end, we compared peak LH and FSH after 100 microg sc GnRH, estradiol, mean ovarian volume (MOV), age of onset and frequency of menses, body mass (BMI), and incidence of neurological and psychiatric problems in 2 groups of girls: those with precocious puberty due to hypothalamic hamartoma (HH; n 18) and those with idiopathic precocious puberty (IPP; n = 32) who had been treated with deslorelin (4-8 microg/kg x day, s.c.) or histrelin (10 microg/kg x day, s.c.) for 3.1-10.3 yr and were observed at 1, 2, 3, and 4-5 yr after discontinuation of treatment. The endocrine findings were also compared to those in 14 normal perimenarcheal girls. There were no differences between the HH and IPP groups in age or bone age at the start of treatment, at the end of treatment, or during GnRH analog therapy. We found that whereas the peak LH level was higher in HH than in IPP girls before (165.5 +/- 129 vs. 97.5 +/- 55.7; P < 0.02) and at the end (6.8 +/- 6.0 vs. 3.9 +/- 1.8 mIU/mL; P < 0.05) of therapy, this difference did not persist at any of the posttherapy time points. LH, FSH, and estradiol rose into the pubertal range by 1 yr posttherapy in both HH and IPP. However, the mean posttherapy peak LH levels in both HH and IPP groups tended to be lower than normal, whereas the peak FSH levels were not different from normal, so that the overall posttherapy LH/FSH ratio was decreased compared to that in the normal girls (HH, 2.7 +/- 0.3; IPP, 2.6 +/- 0.1; normal, 5.2 +/- 4.8; P < 0.05). The MOV was larger in HH than IPP at the end of treatment (3.7 +/- 3.5 vs. 2.0 +/- 1.2 mL; P < 0.05) and tended to increase in both groups over time to become larger than that in normal girls by 4-5 yr posttherapy (HH, 14.9 +/- 12.9; IPP, 7.6 +/- 2.2; normal, 5.4 +/- 2.5 mL; P < 0.05). Whereas the onset of spontaneous menses varied widely in both groups, once menses had started, the HH group had a higher incidence of oligomenorrhea. Pelvic ultrasonography revealed more than 10-mm hypoechoic regions in 4 HH patients, 15 IPP patients, and 3 normal girls, all of whom were reporting regular menses. Live births of normal infants were reported by 2 HH and 2 IPP patients, and elective terminations of pregnancy were reported by 1 HH and 2 IPP patients. BMI was greater than normal in HH

Topics: Adolescent; Child; Child, Preschool; Estradiol; Female; Follicle Stimulating Hormone; Follow-Up Studies; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Luteinizing Hormone; Pregnancy; Puberty, Precocious; Reproduction; Triptorelin Pamoate

Hypothalamic hamartoma, a rare cause of true sexual precocity, may develop slowly so that its diagnosis may be late.. A 7 1/2-month-old girl was admitted because she suffered from development of physical pubertal changes. Laboratory tests were consistent with premature activation of the hypothalamic-pituitary axis. Initial neuroradiological investigation failed to find any cause. The patient was given medroxyprogesterone that resulted in regression of secondary sexual characteristics but growth rates and skeletal maturity remained accelerated. For that reason, the patient was given triptorexine, LH-RH analogue, 18 months later that resulted in a deceleration of puberty growth rate and skeletal maturity. MRI performed at the age of 9 years showed a small hypothalamic hamartoma and the LH-RH analogue was stopped at the age of 10 years.. MRI is now the best technique for investigating the hypothalamo-hypophyseal area.

Topics: Dose-Response Relationship, Drug; Female; Hamartoma; Humans; Hypothalamic Diseases; Infant; Magnetic Resonance Imaging; Puberty, Precocious; Triptorelin Pamoate

Between 1979 and 1983, 129 children (95 girls) with precocious puberty were referred to the National Institutes of Health and received treatment for at least 6 months with the long-acting LHRH analogue D-Trp6-Pro9-NEt-LHRH. The majority (107 of 129) of the children had central precocious puberty mediated by activation of the hypothalamic-pituitary-gonadal axis in association with hypothalamic hamartomas (24 of 107) or other central nervous system lesions (21 of 107), or idiopathic precocious puberty (62 of 107). Hypothalamic hamartomas or other central nervous system lesions were a frequent cause of central precocious puberty in girls (27 of 87), but idiopathic precocious puberty was still the most frequent diagnosis (63%). Idiopathic precocious puberty was uncommon in boys (6%). The patients with peripheral precocious puberty included six girls with McCune-Albright syndrome and six boys with familial male precocious puberty. These children had peripheral sex steroid secretion in the absence of hypothalamic-pituitary-gonadal axis maturation. The children with combined peripheral and central precocious puberty included nine children with congenital adrenal hyperplasia and one girl with a virilizing adrenal tumor. In the patients with central precocious puberty or combined peripheral and central precocious puberty, LHRHa therapy caused suppression of gonadotropin and sex steroid levels (P less than 0.001), stabilization or regression of secondary sexual characteristics, and decreases in growth rate and in the rate of bone age maturation (P less than 0.005). Patients with peripheral precocious puberty, however, had no significant change in gonadotropin or sex steroid levels, growth rate, or the rate of bone age maturation, and no improvement in secondary sexual characteristics. Thus, LHRHa is an effective treatment of central precocious puberty and combined peripheral and central precocious puberty, but is ineffective in the therapy of peripheral precocious puberty.

Topics: Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Delayed-Action Preparations; Estradiol; Female; Fibrous Dysplasia, Polyostotic; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth; Hamartoma; Humans; Hypothalamic Neoplasms; Luteinizing Hormone; Male; National Institutes of Health (U.S.); Puberty, Precocious; Sex Characteristics; Sex Factors; Testosterone; Triptorelin Pamoate; United States

A long-acting analog of LRH (LRHa) has been shown to suppress pituitary gonadotropin and estradiol secretion to prepubertal levels in girls with idiopathic true precocious puberty. We treated six boys, aged 1-6 yr, with true precocious puberty due to hypothalamic hamartoma for 6-24 months with daily sc injections of LRHa. The patients had enlarged testes (6-25 ml), Tanner stage II-IV pubic hair, facial and axillary hair, increased growth rate, and an advanced bone age. Frequent erections occurred in all patients. Computed tomography of the head showed abnormalities characteristic of hypothalamic hamartoma (0.5-3 cm in diameter) in each boy. Each patient had measurable LH and FSH levels, with pulsed nocturnal secretion, and pubertal LH and FSH responses to LRH. Serum testosterone was in the range for normal adult men (200-600 ng/dl). LRHa significantly decreased basal LH (P less than 0.005) and FSH levels (P less than 0.01), LRH-stimulated gonadotropin levels (P less than 0.005), and serum testosterone levels (P less than 0.005). Testis size decreased significantly (P less than 0.005). Annualized growth velocity (centimeters per yr) decreased significantly compared to the pretreatment growth rate (P less than 0.01). Bone age advancement per yr slowed significantly during the course of LRHa treatment (P less than 0.01). Pubic hair, facial hair, and erections decreased in all patients. LRHa is an effective treatment for boys with precocious puberty associated with hypothalamic hamartoma. Chronic therapy will be required, however, to assess the ultimate effect of LRHa.

Topics: Bone Development; Child, Preschool; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth; Hamartoma; Humans; Hypothalamic Neoplasms; Infant; Luteinizing Hormone; Male; Puberty, Precocious; Testosterone; Triptorelin Pamoate