C. Ernould

Treatment of central precocious puberty with an intranasal analogue of GnRH (Buserelin)

One boy and 13 girls with central precocious puberty were treated for 1 year using Buserelin, a GnRH analogue, given intranasally (0.3 mg, four times a day). After 1, 3 and 12 months of therapy, the gonadotropin responses to GnRH were abolished in all the patients whereas mean basal serum concentrations of luteinizing hormone (LH) remained similar to those of pubertal controls. During Buserelin treatment, genital development in the boy and breast development in the girls showed no further progress or some regression. In the boy, serum testosterone levels returned to prepubertal values. In the girls, serum oestradiol levels were variable and, in four of them, vaginal smears showed the persistence of a slight oestrogenic effect during therapy. Pelvic ultrasonography did not show any significant variation in ovarian and uterine lengths. Among the 14 patients, 3 had some progression of pubic hair development, irrespective of serum dehydroepiandrosterone sulphate (DHEAS) levels. In eight patients previously treated with cyproterone, elevated prolactin levels were observed before and during the first month of Buserelin administration. During treatment, mean height velocity was markedly reduced from 11.6 to 6.1 cm/year and mean bone age velocity (±1 SD) was 0.85±0.38 year/year. After 1 year of treatment, the differences in predicted adult height ranged between −0.74 and +1.04 SDS (standard deviation score). These differences were inversely related (r=−0.72) to the prognosis of adult height calculated before treatment. We conclude that, in central precocious puberty, intranasal administration of Buserelin, 1.2 mg/day, may arrest sexual development and reduce height velocity and bone maturation. Improvement of adult height prognosis may occur, especially when it was markedly impaired before treatment.

Pubertal Growth as a Determinant of Adult Height in Boys with Constitutional Delay of Growth and Puberty

In boys with constitutional delay of growth and puberty, adult height may be inconsistent with parental (target) height. We aimed at studying which period of growth was important to account for adult height being above or below target height. In this retrospective study, adult height measured after 20 years in 39 patients was compared with target height and height data obtained at about 6 and 12 years of age and at diagnosis of delayed puberty (mean 14.6 years). Twenty-eight patients were untreated while 11 received testosterone enanthate (50 or 100 mg/month for 6 months). The growth data from both groups were pooled since they were not different. On average, the adult height standard deviation score (–0.6 ± 0.8, mean ± SD) was similar to target height (–0.5 ± 0.6). There were, however, marked individual differences since adult height varied between 1.7 SD (11 cm) below target height and 1.4 SD (9.5 cm) above target height. Multiple regression analysis showed that the most significant determinant of the difference between adult height and target height was height catch up during puberty (p < 0.002). We conclude that the magnitude of height catch up during puberty is a significant determinant of adult height in boys with constitutional delay of growth and puberty. Thus, optimizing pubertal growth may be a relevant therapeutic aim for adult height in boys with short stature and delayed puberty.

GROWTH PROMOTING EFFECT OF GROWTH HORMONE AND LOW DOSE ETHINYL ESTRADIOL IN GIRLS WITH TURNER SYNDROME: FINAL HEIGHT RESULTS

In 1987 a multicenter trial was started to evaluate the effect of daily s.c. rhGH treatment (0.15 IU/kg/day Genotonorm, Kabi Pharmacia, Sweden) in 40 girls with Turner syndrome (TS) (mean±SD age: 11.3±2.6 yrs). Twenty randomly selected girls received in addition 25 ng/kg/day ethinylestradiol (EE2) orally. From the 3rd year of treatment puberty was induced with 100 ng/kg/day EE2 in the girls with a bone age older than 11 years. Thirty-six patients have been followed for 5 years. Except early breast budding in 9 out of 20 girls treated with rhGH and 25 ng/kg/day EE2, no differences were found between the patients treated with rhGH alone and those also treated with low dose EE2. In 28 patients with a bone age above 13 yrs, height attained 5 years after the start of rhGH treatment is 150.5±4.4 cm. This is higher (P<0.001) than the adult height of 144.8±5.8 cm of 43 untreated TS girls. In these 28 girls, the difference in height attained after 5 years of treatment and corrected mid parental height is 10.8±4.8 cm, which is less (P<0.001) than in untreated adult TS patients (16.2±4.8 cm). These results provide further evidence that treatment with rhGH increases final height in TS girls.

Pubertal Growth and Final Height in Hypopituitary Boys Are Not Related To Bone-age At Onset of Puberty

Hypopituitary boys (n=29) treated with hGH (18 to 24 IU/week) were studied before and during spontaneous puberty (SP, n=9) or puberty induced with testosterone enanthate, 100 mg/month (TIP, n=20). At onset of puberty, bone age (BA, TW2) varied between 11.2 and 15.4 yrs. Total height gain during puberty (mean : 17.2 cm) was not significantly related (r=-0.38) to BA ot onset of puberty. In contrast, BA increment (ΔBA) during puberty was negatively related (r=-0.92) to BA at onset of puberty. Final height (FH) was attained in 21 out of 29 patients. Mean FH was 157.2 cm after SP and 165.5 cm after TIP. FH was a direct function of parents height (r=0.61). After allowing for parents height, FH was found to be significantly related to height at onset of puberty (r=0.71) and adult height predicted (TW mark II) at onset of puberty (r=0.81). In contrast, FH did not change in relation to BA at onset of puberty (r=0.28). At the end of growth, a decreased height velocity (HV) can be expected from previous HV (r=0.57) and from height achieved as a percentage of predicted FH (r=-0.56) but not from BA at that time.We conclude that, in hypopituitary boys with SP and TIP, 1.BA at onset of puberty does not primarily influence HV during puberty and FH, 2. at onset of puberty, FH may be predicted although somewhat underestimated, 3. besides parents height, the major factor influencing FH is patients height at onset of puberty.

Assessment of Gonadotropin-deficiency in Pituitary Dwarfism

Fifty three patients with idiopathic (45) and organic (8) hypopituitarism, 43 boys and 10 girls, were studied during treatment with hGH. The gonadotrophin responses to GnRH (25 μg/m2) and serum levels of DHEA-s were measured yearly ; 15 patients remained prepubertal whereas 38 patients were studied before and during puberty occuring either spontaneously (11) or induced (27) by testosterone propionate (100 mg/mth) or ethinyloestradiol (10 μg/day)Gonadarche and adrenarche were dissociated in some patients : among the 11 patients with spontaneous gonadarche, 2 had no previous biological adrenarche ; among the 27 gonadotrophin deficient (G.D.) patients, 9 had spontaneous adrenarche.In prepubertal patients who were subsequently confirmed to be G.D., 27 GnRH tests were performed ; 23/27 integrated responses (I.R.) of FSH were found to be markedly lower than those observed in prepubertal controls of both sexes. In 9/27, I.R. of LH were below the control range. However, when in boys, I.R. of LH were analyzed according to bone age, 17/19 were below the lower limit of the control range.These data might stress the importance of calculating I.R. of FSH to GnRH in hypopituitary patients in order to predict gonadotrophin deficiency.