trelstar and Adrenal-Hyperplasia--Congenital

Topics: 11-beta-Hydroxysteroid Dehydrogenases; Adrenal Hyperplasia, Congenital; Body Height; Bone Development; Child; Dwarfism; Female; Hirsutism; Hormones; Humans; Hydrocortisone; Leuprolide; Physical Examination; Prognosis; Puberty, Precocious; Triptorelin Pamoate; Ultrasonography

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

Polycystic ovary syndrome (PCOS) and congenital adrenal hyperplasia (COH) are heterogeneous disorders, in which excess of androgens may be caused by improper function of ovaries and/or adrenals. In many cases an overlap between ovarian and adrenal type of functional hyperandrogenism has been observed. The relationship between adrenal and ovarian metabolism in hyperandrogenic women is not totally known and etiologic diagnosis of female hyperandrogenism is often difficult. The aim of the present study was to evaluate the usefulness of combined Dexamethasone-Triptoreline testing in distinguishing ovarian and adrenal type of functional hyperandrogenism, and checking if the test could be shortened in order to economise it.. We have examined 57 women with androgen excess divided into two groups: ovarian (n = 42) and adrenal (n = 15) and 20 women with idiopathic hirsutism. There was also one patient suffering from Morris syndrome taken under examination just for curiosity. The blood for hormonal assay was taken in baseline conditions at 8.00 a.m. for LH, FSH, PRL, cortisol, T, DHEAS, 17OHP, E2. Dx was given for 4 days 0.5 mg p.o. every 6 hours. 8 hours after the last Dx administration, the blood was taken for 17OHP and T. Immediately after that Triptorelin 100 mg was given s.c. Then the blood was collected every 4 hours during 24 hours for 17OHP estimation.. Decrease in T levels (from 1.65 +/- 0.52 to 0.73 +/- 0.25 ng/ml) after Dexamethasone administration was observed in adrenal group, which indicates adrenal glands as a source of excessive androgen production. No significant differences were seen in ovarian group. But in women from ovarian group supranormal 17OHP response after Triptoreline administration was seen: (ng/ml): at 8.00 am-0.68 +/- 0.44, 12.00--1.21 +/- 0.7*, 16.00--1.71 +/- 1.19*, 20.00--2.39 +/- 1.81*, 24.00--3.41 +/- 2.64*, 4.00--3.91 +/- 2.82*, 8.00--6.06 +/- 2.43* (*p < 0.01, **p < 0.001). Such a response is typical for women with well defined PCOS and other forms of functional ovarian hyperandrogenism and indicates ovary as a source of androgens. Significant differences were also noticed in idiopathic group: 8.00--0.31 +/- 0.09, 12.00--0.38 +/- 0.17, 16.00--1.41 +/- 0.62*, 20.00--1.52 +/- 0.97*, 24.00--1.89 +/- 0.83*, 4.00--2.17 +/- 0.83*, 8.00--1.83 +/- 0.71** (*p < 0.01). 17OHP levels did not change significantly during the whole test in adrenal group: 8.00--1.83 +/- 1.24, 12.00--1.91 +/- 1.37, 16.00--1.95 +/- 0.86, 20.00--2.19 +/- 0.93, 24.00--2.63 +/- 1.58, 4.00--2.56 +/- 1.78, 8.00--237 +/- 0.94. But patients from this group had exaggerated 17OHP response to ACTH (from 4.32 +/- 1.31 to 15.34 +/- 4.1 ng/ml). In patient suffering from Morris syndrome, after Triptoreline, serum 17OHP levels reminded on the same level as they were before drug administration.. Combined Dx-Triptorelin test can be very useful to distinguish ovarian and adrenal type of functional hyperandrogenism. The number of times of blood collection for 17OHP can be reduced to 4 times a day (during 24 hours): at 8.00, 20.00, 24.00, 8.00.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Dexamethasone; Drug Administration Schedule; Female; Follicle Stimulating Hormone; Hirsutism; Humans; Luteinizing Hormone; Luteolytic Agents; Ovary; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Testosterone; Triptorelin Pamoate; Ultrasonography

To determine the role of heterozygosity for mutations in the 21-hydroxylase gene (CYP21) in the pathogenesis of hyperandrogenism.. Controlled clinical study.. Tertiary care institutional hospital.. Forty hirsute women and 13 healthy control women.. The source of androgen excess was determined by the changes in serum testosterone levels in response to a single 3.75-mg i.m. dose of triptorelin.. CYP21 molecular genetic analysis and serum 17-hydroxyprogesterone levels.. Eight patients and one control were heterozygous carriers of CYP21 mutations. Two patients with adrenal hyperandrogenism and one patient with ovarian hyperandrogenism, who carried the V281L mutation had an increased ACTH-stimulated 17-hydroxyprogesterone level (>4.1 ng/mL) that persisted during gonadal suppression. Another patient with adrenal hyperandrogenism carried the V281L mutation, and her ACTH-stimulated 17-hydroxyprogesterone level was elevated only during gonadal suppression. Four patients (three with idiopathic hirsutism, one with ovarian hyperandrogenism) and one control were carriers of CYP21 mutations typically associated with classic congenital adrenal hyperplasia but had normal basal and ACTH-stimulated 17-hydroxyprogesterone levels. Nine patients without CYP21 mutations had increased ACTH-stimulated 17-hydroxyprogesterone levels; these decreased to normal in six of the patients during gonadal suppression.. The response of serum 17-hydroxyprogesterone to ACTH does not predict CYP21 carrier status. No clear concordance was found between the CYP21 genotype and the functional origin of androgen excess.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adrenocorticotropic Hormone; Adult; Dehydroepiandrosterone Sulfate; Female; Genotype; Heterozygote; Hirsutism; Humans; Hyperandrogenism; Mutation; Phenotype; Reference Values; Sex Hormone-Binding Globulin; Steroid 21-Hydroxylase; Testosterone; Triptorelin Pamoate

To determine the effectiveness of GnRH-agonist (GnRH-a) treatment in women with late onset congenital adrenal hyperplasia.. Prospective assessment of GnRH-a treatment in six women with documented late-on-set congenital adrenal hyperplasia who were not preselected. Comparisons were made to previous responses in the same patients receiving dexamethasone. Eight age- and weight-matched ovulatory women served as controls.. Academic medical center.. Baseline blood determinations before and after i.v. ACTH, before and after 6 months of GnRH-a treatment. Estrogen and progestin replacement was begun in all women after the 3rd month of treatment.. Serum 17-hydroxyprogesterone (17-OHP), gonadotropin, and androgen levels before and after GnRH-a treatment. Responses of 17-OHP and androgens to ACTH assessment of hirsutism using a modified Ferriman-Gallwey score.. Gonadotropins, estrogen, androgen, and 17-OHP were suppressed with GnRH-a treatment. Levels were similar before and after estrogen and progestin replacement. Responses of 17-OHP after ACTH were blunted but still were elevated compared with responses in controls. Ferriman-Gallwey scores decreased significantly (-8 +/- 1; mean +/- SE). This response was greater than that observed previously with 6 months of dexamethasone (-2 +/- 0.3).. Suppression of the ovary with GnRH-a treatment was beneficial in these patients with late-onset congenital adrenal hyperplasia. An ovarian influence on the clinical and biochemical findings of the disorder is suggested.

Topics: 17-alpha-Hydroxyprogesterone; Adolescent; Adrenal Hyperplasia, Congenital; Adult; Age of Onset; Androgens; Dexamethasone; Endocrine Glands; Female; Gonadotropins; Hirsutism; Humans; Hydroxyprogesterones; Ovary; Prospective Studies; Triptorelin Pamoate

Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

Topics: Adrenal Hyperplasia, Congenital; Body Height; Bone Development; Child, Preschool; Drug Therapy, Combination; Follow-Up Studies; Gonadotropin-Releasing Hormone; Growth Hormone; Humans; Male; Puberty, Precocious; Triptorelin Pamoate

A 7.3-year-old boy was presented at out-patient clinic because of tallness and premature puberty. His height was 150.2cm (+ 4.74 standard deviation score for chronological age), body mass index 18.4 kg/m2, pubic hair stage 3 (after Tanner), testicular volume of 5.0 ml each. Bone age was accelerated by 6.5 years (SD -1.55 for height according to bone age). Expected final height was 166 cm, mean genetic target height 180 cm.. Basal serum concentration of 17-hydroxyprogesterone was 142.1 ng/ml (normal: < 1.9) and testosterone of 93 ng/dl (normal: < 11). 24-hour urine showed an increased excretion of pregnantriol of 8280 micrograms/d (normal < 500). Gonadotropine-releasing hormone test (GnRH), blood collected at 0 and 30 min, showed an increased rise of the serum LH concentration of 0.6 to 8.2 mU/ml (normal < 0.3 and < 3.6, respectively) and a normal FSH increase of 1.3 to 3.2 mU/ml (normal < 1.3 and < 4.0, respectively). The diagnosis of adrenogenital syndrome (AGS) with 21-hydroxylase defect was confirmed by molecular genetic testing.. The boy was treated with hydrocortisone (average dose 18.3 mg/m2 body surface area). Because of the premature puberty and the poor growth endprognosis treatment with the GnRH agonist Decapeptyl Depot, 3.75 mg every 4 weeks i.m., was started.. The correct diagnosis should have been made in the neonatal period on the basis of the family history (15-year-old brother with AGS) and at the latest on correct interpretation of the clinical signs during early childhood.

Topics: 17-alpha-Hydroxyprogesterone; Adrenal Hyperplasia, Congenital; Anti-Inflammatory Agents; Child; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Luteinizing Hormone; Luteolytic Agents; Male; Pregnanetriol; Puberty, Precocious; Testosterone; Time Factors; 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

Topics: Adrenal Hyperplasia, Congenital; Child; Child, Preschool; Delayed-Action Preparations; Female; Fludrocortisone; Gonadotropin-Releasing Hormone; Humans; Hydrocortisone; Male; Puberty, Precocious; Steroid Hydroxylases; Triptorelin Pamoate

Congenital adrenal hyperplasia (CAH) is a recognized cause of precocious pseudopuberty. Some children with CAH also develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen four such children (three boys and one girl) who had the diagnosis of CAH made between the ages of 3 and 6 yr. These patients were treated with standard doses of hydrocortisone and fludrocortisone. A diagnosis of true precocious puberty was made because of testicular enlargement in the boys, breast development in the girl, progressive pubic hair development, rapid growth, and rapid bone age maturation. Plasma steroid levels were elevated for age, and gonadotropin levels were within the normal pubertal range, both basally and in response to LHRH stimulation. We treated these children with daily sc injections of a LHRH analog (LHRHa) for 6-18 months in addition to the standard hydrocortisone and fludrocortisone therapy for CAH. LHRHa significantly decreased basal plasma LH and FSH, peak LH and FSH responses to native LHRH, and testosterone levels. Testis size decreased in the males, and breast development regressed in the female. LHRHa therapy led to significant decreases in linear growth rate, ulnar growth rate, and rate of bone age advancement. These results suggest that LHRHa is an effective adjunct to hydrocortisone and fludrocortisone in the treatment of true precocious puberty complicating CAH.

Topics: Adrenal Hyperplasia, Congenital; Bone Development; Child; Drug Therapy, Combination; Estradiol; Female; Fludrocortisone; Gonadotropin-Releasing Hormone; Gonadotropins; Growth; Humans; Hydrocortisone; Male; Puberty, Precocious; Testis; Testosterone; Triptorelin Pamoate