Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment.

GH state and auxological data after completion of GH therapy are reported in 131 patients (79 males, 52 females). They were treated from 1980-1994 for partial (n = 98) or complete (n = 33) GH deficiency (GHD), either idiopathic (n = 121) or organic (n = 10). A single stimulation test (clonidine+betaxolol) was used, and only 50 patients (38%) maintained a blunted response (GH peak below 10 micrograms/L). Although 9 of the 10 patients with organic GHD had an abnormal low GH peak, 67% of patients with idiopathic GHD normalized their GH secretion. This was particularly true of partial GHD patients (71% vs. 36% of complete GH-deficient patients). Based on a retest GH peak below 5 micrograms/L, only 23% of the patients were considered to be GH deficient and therefore candidates for GH treatment during adulthood. We found no significant difference between hormonal state at completion of treatment and initial GH deficiency, pubertal state, or sex, although we did find a significantly lower GH peak value before and after treatment in patients with elevated body mass index. Of the 14 obese children who were treated, 50% had an abnormally low serum insulin-like growth factor-I level, arguing for true GHD, and only two children remained obese at cessation of treatment. Auxological data showed that with a mean duration of treatment of 3.6 +/- 2.0 yr, patients classified as having complete GHD before treatment had significantly greater catch-up growth as expressed in SDS for height than patients with partial GHD (0.6 +/- 1.1 vs. 1.1 +/- 0.7 SDS, P < 0.05), and that boys grew better than girls (1.4 +/- 0.8 vs. 1.6 +/- 0.6 SDS) for height, P < 0.01). That catch-up growth was not correlated with the result of GH peak after cessation of treatment.

Effect of overnight constant infusion of human growth hormone (GH)-releasing hormone-(1-44) on 24-hour GH secretion in children with partial GH deficiency.

A continuous infusion (0.5 or 1 microgram/kg X h) of GH-releasing factor-(1-44) [GHRH-(1-44)] was administered from 2000-0800 h to 16 children with GH deficiency, defined as a maximum peak plasma GH less than 11 ng/ml in response to 2 provocative tests [first test; mean, 7.4 +/- 2.6 (+/- SD) ng/ml; second test; mean, 8.4 +/- 2.4 ng/ml]. Eight were boys and 8 girls; their average age was 10 yr, 5 months; and growth was retarded in all [mean, -3 +/- 0.6 (+/- SD)]. Polygraphic monitoring was carried out during the night, and blood samples for plasma GH measurements were drawn every 20 min during the night and the following day. A control study had been carried out in the preceding months with the same children. During GHRH infusion, a significant increase in nocturnal GH secretion occurred; the mean maximum peak increased from 17.5 +/- 3.4 (+/- SD) to 38.7 +/- 3.2 ng/ml, the mean area under the curve from 2243 +/- 459 to 5348 +/- 710 ng/ml, the mean integrated concentration from 4.2 +/- 0.8 to 9.9 +/- 1.3 ng/ml X min, and the mean number of peaks above 5 ng/ml from 2.7 +/- 0.3 to 4.7 +/- 0.4. During GHRH infusion, the 16 children had 2 peaks during the first 4 h of sleep and a third peak at the end of the night. Plasma GH levels the day after the infusions were not significantly increased. We conclude that continuous nocturnal GHRH infusion increases pulsatile sleep GH secretion throughout the night in children with partial GH deficiency.

Can some growth hormone (GH)-deficient children benefit from combined therapy with gonadotropin-releasing hormone analogs and GH? Results of a retrospective study.

Recombinant GH (rGH) treatment does not invariably correct height deficits in GH-deficient children once puberty has begun. The addition of GnRH analogs (GnRHa) to delay puberty has been advocated, but published results are few and sometimes conflicting. We retrospectively compared GH-deficient children treated with rGH and GnRHa for at least 1 yr after entering puberty and having attained their final height (n = 23) with a matched control group treated only with rGH. Overall, combined therapy did not significantly increase final height relative to rGH alone. However, the shortest girls at the onset of puberty (<25th percentile) benefited more than the tallest (>75th percentile) in both final height relative to predicted height and pubertal catch-up growth. In the control group, patients having experienced intrauterine growth retardation (IUGR) attained a lower mean final height than patients without IUGR (difference significant in boys, but not in girls). In the combined therapy group, IUGR did not affect the final height of either sex. Our results suggest that two populations might benefit most from combined GnRHa and rGH therapy: girls particularly short at the onset of puberty and patients who had experienced IUGR. Further prospective studies are required to confirm these preliminary hypothesis.

Differential regulation of serum growth hormone (GH)-binding protein during continuous infusion versus daily injection of recombinant human GH in GH-deficient children.

Serum GH-binding protein (GHBP) was evaluated in 2 randomly divided groups of prepubertal children presenting with idiopathic GH deficiency and receiving recombinant human GH, either continuously by sc infusion (group 1) or as 1 daily sc injection (group 2). After the first 6 months, group 1 switched from continuous infusion to daily injections for the following 6 months. There was no significant difference in clinical data, GH values, or GHBP levels between the 2 groups before treatment. During the first 6 months, GHBP levels increased in all except 1 of the 8 children in group 1 from 8.6% to 16.9% after 3 months and 22.5% after 6 months. The increment factor ranged from 1.1-7.9, with wide individual variations. In group 2, the mean variation in GHBP was from 8.3-8.2% after 3 months and 10.7% after 6 months. Only 2 of the 10 children in this group showed a significant increase in GHBP levels. During the second period, group 1 maintained their GHBP levels, whereas the 2 children in group 2 tended to a continued increase in their GHBP levels. There was no correlation with the increase in growth velocity, as children in both groups grew equally well, but higher insulin-like growth factor-I levels were found in group 1, although the difference between the two groups was not significant. These data show that GH can increase GHBP levels and that there is a differential effect depending on the mode of GH administration, although the reason for and the role of such regulation remains to be explained.

Combined hypothalamic-pituitary-gonadal defect in a hypogonadic man with a novel mutation in the DAX-1 gene.

We have studied a 20-yr-old male patient with adrenal hypoplasia congenita and hypogonadotropic hypogonadism (HH) due to a C to A transversion at nucleotide 825 in the DAX-1 gene, resulting in a stop codon at position 197. The same mutation was detected in his affected first cousin (adrenal hypoplasia congenita and HH) and in a heterozygous state in their carrier mothers. The patient had had acute adrenal insufficiency at the age of 2 yr and 6 months, bilateral cryptorchidism corrected surgically at the age of 12 yr, and failure of spontaneous puberty. Plasma testostereone (T) was undetectable (<0.30 nmol/L), gonadotropin levels were low (LH, <0.4 IU/L; FSH, 1.5 IU/L) and not stimulated after i.v. injection of 100 microg GnRH. The endogenous LH secretory pattern was apulsatile, whereas free alpha-subunit (FAS) levels depicted erratic pulses, suggesting an incomplete deficiency of hypothalamic GnRH secretion. During i.v. pulsatile GnRH administration (10 microg/pulse every 90 min for 40 h), each GnRH pulse induced a LH response of low amplitude (0.54 +/- 0.05 UI/L), whereas mean LH (0.45 +/- 0.01 IU/L) and FAS (63 +/- 8 mU/L) levels remained low. Amplitude of LH peaks (0.83 +/- 0.09 IU/L), mean LH (0.53 +/- 0.02 IU/L), and FAS (161 +/- 18 mU/L) levels increased (P < 0.01), whereas the T concentration remained low (0.75 nmol/L) when the pulsatile GnRH regimen was raised to 20 microg/pulse for a 40-h period, suggesting a partial pituitary resistance to GnRH. Thereafter, plasma T levels remained in prepubertal value after three daily im injections of 5000 IU hCG (3.6 nmol/L) and after 1-yr treatment with weekly i.m. injections of 1500 IU hCG (1.2 nmol/L), implying Leydig cell resistance to hCG. The patient had a growth spurt, bone maturation, progression of genital and pubic hair stages, and normalization of plasma T level (15.8 nmol/L) after a 12-month treatment with twice weekly injections of hCG and human menopausal gonadotropin (75 IU International Reference Preparation 2) preparations, suggesting that, in presence of FSH, a Sertoli cell-secreted factor stimulated Leydig cell production of T. In conclusion, we report a novel mutation in the DAX-1 gene in patients with AHC and HH. Our results suggest that the hypogonadism is due to a combined hypothalamic-pituitary-gonadal defect and imply that the DAX-1 gene may play a critical role in human testicular function.

Results of 1-year growth hormone (GH)-releasing hormone-(1-44) treatment on growth, somatomedin-C, and 24-hour GH secretion in six children with partial GH deficiency.

Six children with short stature and partial GH deficiency in response to two pharmacological tests received GHRH for 12 months (10 micrograms/kg X day, sc) each evening. Twenty-four-hour GH secretion was studied before and after 3 and 12 months of treatment, and GHRH tests (2 micrograms/kg, iv) were done before and after 6 months of treatment. Plasma somatomedin-C was measured before and after 1.5, 3, 6, 9, and 12 months of treatment. Statural growth was measured at 3-month intervals. Mean growth velocity increased from 4.2 to 8.6 cm/yr, with a good result in five children and no response in the other. The growth response was substantial during the first 3 months. It was maintained during the following 6 months, and then decreased during the last 3 months. The peak plasma GH level in response to GHRH increased from 34.5 +/- 14.2 (+/-SD) ng/mL before treatment to 47.8 +/- 3.4 ng/mL after 6 months of treatment. Twenty-four-hour GH secretion increased in all parameters at 3 months (maximum peak, area under the curve, integrated concentration, and number of peaks) and at 12 months (with the exception of the maximum peak). Nycthemeral secretory profiles became normal, with reappearance of secretory pulses in two children, slight increases in three children, and no change in one child. Plasma somatomedin-C levels rose from 0.8 +/- 0.3 U/mL before treatment to 2.0 +/- 1.0 U/mL at 3 months, then decreased to 1.3 +/- 0.6 U/mL at 12 months. These results indicate that GHRH administered by sc injection for a 1-yr period stimulated growth and GH secretion. However, a decrease in activity was noted during the last 3 months of treatment. Tests for anti-GHRH antibodies were positive in the only child who did not respond to treatment.

A 5-year prospective study of growth hormone (GH)-deficient children treated with GH before the age of 3 years. French Serono Study Group.

The aim of the study was to assess the efficacy of GH therapy in GH-deficient children treated before the age of 3 yr. A noncomparative multicenter prospective study included 49 children (22 girls and 27 boys) with isolated GH deficiency (n = 19) or multiple pituitary hormone deficiency (n = 30) treated with daily s.c. injections (0.6 U/kg.week) for 3-5 yr. They were divided into two groups according to their height SD score for chronological age (CA) at the initiation of therapy: group A consisted of 8 patients presenting an initial height within the normal range (< 2 SD below the mean) followed for 2-5 yr, and group B consisted of 25 children followed for 5 yr among 41 patients with initial growth retardation. In group A, the mean height SD score increased from -1.1 +/- 0.6 to 0.35 +/- 1.0 SD (P < 0.001) in the first year and remained in the normal range throughout the following 4 yr. In group B after 4 yr of treatment, the mean height SD score for age had increased from -3.6 +/- 1.0 SD (time zero) to -0.9 +/- 1.2 SD. During the fourth year of therapy, the mean height gain of 0.2 +/- 0.2 SD was significant (P < 0.001). After 5 yr of treatment, a plateau was reached with a corresponding height SD score (CA) of -0.8 +/- 1.2 SD (95% confidence interval between -1.3 and -0.2 SD). This value remained significantly below normal for age (P < 0.001), indicating that catch-up growth was incomplete. Only four patients (16%) remained below -2SD for CA. The 5-yr height gain was negatively correlated with the height SD score at the start of treatment (r = -0.6; P < 0.005) and the first year height gain was the most predictive parameter. There was no significant influence of intrauterine growth retardation, body mass index and age at the start of treatment, or parental target height. Bone maturation was significantly retarded over CA by a mean value of 1.1 +/- 0.9 yr (P < 0.0001), with a mean bone age/CA ratio of 0.8 +/- 0.2 after a mean treatment duration of 5.1 +/- 1.1 yr. In conclusion, the rapid and almost complete return to normal height obtained in this study supports the need for GH treatment in early diagnosed GH-deficient children. The present dosage may be considered the minimum to obtain satisfactory catch-up growth ensuring a favorable outcome for these children. In addition, it allowed growth at a rate normal for age in patients diagnosed before growth retardation.

Once daily subcutaneous growth hormone-releasing hormone therapy accelerates growth in growth hormone-deficient children during the first year of therapy. Geref International Study Group.

The efficacy and safety of 1 yr of GH-releasing hormone [GHRH-(1-29)] therapy in GH-deficient children were determined. One hundred and ten previously untreated prepubertal GH-deficient children were treated for up to 1 yr in a multicenter, open label study with 30 micrograms/kg GHRH-(1-29)/day, sc, given at bedtime. Eighty-six of the 110 patients were eligible for efficacy analysis. The main outcome measures, monitored every 3-6 months, were linear growth enhancement (height velocity), bone age progression, and safety measures including clinical chemistry. The mean height velocity for the group increased from 4.1 +/- 0.9 cm/yr at baseline to 8.0 +/- 1.5 and 7.2 +/- 1.3 cm/yr after 6 and 12 months of therapy, respectively. At 6 months, 74% of the children were considered to have a good response to GHRH. The ratio of the change in bone age to height age was not significantly different from unity at 12 months (1.04 +/- 0.58; P = 0.63). No adverse changes in general biochemical or hormonal analyses were noted. No change in fasting glucose concentration or excessive generation of insulin-like growth factor I occurred, and overall GHRH was well tolerated. We conclude that GHRH administered as a once daily dose of 30 micrograms/kg GHRH.(1-29), s.c., was effective in increasing height velocity in GH-deficient children.

Human growth hormone receptor: cloning and expression of the full-length complementary DNA after site-directed inactivation of a cryptic bacterial promoter.

Growth hormone receptor is a cytokine-type receptor which is required for normal somatic growth and for numerous metabolic processes. Its complementary DNA (cDNA) has been isolated in various species leading to intensive studies to elucidate the mechanism of action of the growth hormone. However, serious difficulties have been reported in cloning in Escherichia coli, an intact full-length human cDNA. In this study, the cDNA is shown to contain a cryptic bacterial promoter driving inappropriate expression of a part of human growth hormone (hGH) receptor which is toxic for E. coli growth. Identification of this promoter and its inactivation by changing only one nucleotide led us to obtain stable bacterial clones containing a high copy number of full-length coding sequences. This molecular clone was used in a baculovirus/insect cell system to produce large amounts of glycosylated recombinant receptor. Binding studies with 125I-labelled hGH revealed an affinity constant of 2.8 x 10(9) M(-1), similar to that reported for the native liver receptor. This report described a general method of cloning which could be applied to similar unclonable cDNA fragments.

Expression of a recombinant human growth hormone binding protein in baculovirus/insect cell system.

An eucaryotic recombinant human growth hormone binding protein (rGHBP) was expressed in baculovirus-infected insect cells and purified by affinity chromatography from culture supernatant. This mannose-rich 34-kDa protein specifically bound human growth hormone (hGH) with the same affinity (kDa = 0.42 x 10(-9) M) than the 51.5 kDa GHBP we purified and characterised from human plasma (kDa = 1.1 x 10(-9) M). A high molecular form of the rGHBP was detected by silver-stained SDS-PAGE, Western blot (mAb 263), affinity cross-linking and Western ligand blot with 125I-hGH. Reduction experiments with beta-mercaptoethanol suggested that this form involved a disulfide bound between two rGHBPs.

Heterozygous mutation in the WSXWS equivalaent motif of the growth hormone receptor in a child with poor response to growth hormone therapy.

Besides complete GH insensitivity syndrome (GHIS) described by Laron, clinical and molecular evidences have accumulated concerning partial GHIS. We studied GH receptor (GHR) gene in children who show poor response to GH treatment and detected a patient with a heterozygous mutation in exon 7 leading to the Y222H substitution. This missense mutation, located in the YGEFS motif of the GHR equivalent to the WSXWS motif highly conserved throughout all members of the cytokine receptor family, has not been described so far. Although we cannot conclude on the deleterious effect of this mutation, there are several lines of evidence suggesting that it could account for the partial GH insensitivity: (i) hormonal data including IGF-I generation test; (ii) molecular data - no other mutation was identified in the coding sequence, the father who has the same mutation is short, the brother did not inherit the mutated allele and was of normal height.

Intensive dance practice. Repercussions on growth and puberty.

To determine the effect of intensive sports training on growth and puberty, we studied a group of 97 young female dancers longitudinally for 5 years. We studied the changes in their heights, weights, and pubertal developments and compared these findings with those of a control group. We found that 15 (16%) dancers who started dance training had noticeably decreased growth velocity during the prepuberty stage after the beginning of ballet practice compared with the control group. This group had the same average training time compared with the other dancers, but these dancers were the slimmest and had the most inadequate nutritional intake. Puberty in dancers was delayed compared with the controls. We found that moderately intensive dance practice can lead to eating disorders and weight control early in childhood, with consequences that are poorly known. Weight and height statistics of children who practice individual sports involving body aesthetics must be monitored to detect early anomalies.

Gonadotropin treatment of hypogonadotropic hypogonadal adolescents.

Testosterone substitution, needed for normal physical development in male hypogonadal adolescents, does not induce testicular growth. We treated 37 hypogonadal adolescents with gonadotropins (hCG/hMG), to obtain complete virilization during the first two years of treatment, to avoid psychological sequellae and to allow normal sexual development. Testicular volume increased significantly during therapy (from 1.98 +/- 1.2 to 9 +/- 3.3 ml), while testosterone rose from 0.26 +/- 0.04 to 5.3 +/- 0.8 ng/ml, with worse results in adolescents with cryptorchidism. hCG/hMG treatment had a better outcome than testosterone during the induction of puberty, avoiding psychological problems induced by atrophic testes. Further long term studies are necessary to evaluate whether early hCG/hMG treatment facilitates later spermatogenesis even in patients with cryptorchidism.

[Progressive external ophthalmoplegia and disorders of ventricular conduction. Apropos of 3 recent cases]. / Ophtalmoplégie externe progressive et troubles de la conduction ventriculaire. A propos de 3 nouvelles observations.

The authors report 3 cases with an association of progressive external ophthalmoplegia (OEP) and disordered intracardiac conduction. These cases, and the twenty or so similar ones reported in the literature, show that this association is important for two reasons:--there is a therapeutic importance in that the condition affects young patients, who are at risk from sudden death due to the conduction defect; for this reason electrocardiographic follow-up must be regular, and an intracavitary pacemaker must be introduced definitively at the least indication;--there is a physiopathological importance in that the effect of the myopathies on the myocardium is well known, but most information relates to the diffuse cardiomyopathies, and in only 10% of cases are there conduction defects. By contrast, the conductive tissue appears to be involved in all cases of OEP, while cardiac failure is rare. It seems likely, therefore, that cases of OEP have a pathogenesis different from that of the diffuse myopathies, whether or not these involve the external occular muscles.

Growth hormone (GH) profiles in response to continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 in children with GH deficiency.

Six children presenting with partial growth hormone (GH) deficiency (mean GH peak in two different tests, 8.0 +/- 1.3 micrograms/l) aged 8-10.3 years (mean, 2.7 +/- 0.9 years) were treated for 6 months by continuous subcutaneous infusion of GH-releasing hormone(1-29)-NH2 (GHRH(1-29)-NH2); 24-hour GH profiles and height velocity were measured. A biphasic effect of GHRH(1-29)-NH2 infusion was observed. After an early substantial increase in the 24-hour integrated concentration of GH, from 1.6 +/- 0.1 to 3.5 +/- 0.7 micrograms/l/minute, a subsequent consistent decrease occurred by 3 months, which was more pronounced after 6 months (mean 24-hour integrated concentration of GH, 1.9 +/- 0.9 micrograms/l/minute). This effect reflects modification of both pulse amplitude and frequency of GH secretion. At the end of the study, one child had complete suppression of GH secretion and two others showed only one peak above 5 micrograms/l during a 24-hour period. No correlation was found between these changes and height velocity. Three children did not grow significantly; the other three children who had a growth response to GHRH(1-29)-NH2 were those with the lowest 24-hour integrated GH concentration at the end of the study. The possible mechanisms involved in this biphasic effect, including GHRH antibodies, changes in somatostatin levels and/or desensitization of pituitary GHRH receptors, have been investigated.

[Creutzfeldt-Jakob disease after treatment with human extracted growth hormone. A clinicopathological study]. / Maladie de Creutzfeldt-Jakob après traitement par l'hormone de croissance extractive humaine: étude clinico-pathologique.

This report describes the pathological changes observed in the brain of a 18-year-old patient who died with Creutzfeldt-Jakob disease (CJD) of the ataxic and panencephalopathic type. Clinically, the disease began at age 17 with a rapidly progressive cerebellar syndrome, associated with myoclonus and mental deterioration. Cranial CT scan and MRI showed minor abnormalities. EEG demonstrated non specific changes. The patient became progressively demented, bedridden and died 10 months after the onset. Nine years earlier, he had been operated upon for craniopharyngioma and subsequently treated with cadaver-derived human growth hormone. Post-mortem examination of the brain revealed mild diffuse atrophy. Histology showed congophilic amyloid plaques found in both gray and white matters of the cerebrum and cerebellum, associated with spongiosis, mainly in the basal ganglia and cerebellum, and gliosis. They were immunostained with antiprion protein antibody using the immunoperoxidase method on paraffin embedded sections. The clinical findings in this case were similar to those of other cases of human growth hormone-associated CJD. However, this case is unusual because of the great number of amyloid plaques, which have been only rarely found in previous reports.

Long-term results of growth hormone treatment in France in children of short stature: population, register based study.

OBJECTIVES: To describe the growth of children treated with growth hormone and to evaluate the prognostic factors for height at the end of treatment. DESIGN: Register based cohort study. SETTING: French national register of all children treated with growth hormone. SUBJECTS: 3233 short stature children (3165 of whom were deficient in growth hormone) who were treated with growth hormone (excluding children with Turner's syndrome) and whose treatment started between 1973 and 1989, last data being recorded in December 1993. MAIN OUTCOME MEASURES: Annual changes in height, and height at the end of treatment. RESULTS: Mean height SD score at the end of treatment, after a mean of 4.3 years, was -2, corresponding to gain in mean height SD score of 1 and to a height SD score of 1.1 below target height. In all, 923 children prematurely stopped taking growth hormone treatment, mainly because of insufficient response (insufficient growth) or tiredness. Variables that predicted height at the end of treatment were age, target height, aetiology of short stature, use of puberty inhibitors, and type of growth hormone. CONCLUSIONS: The outcome of children of short stature with growth hormone deficiency who were treated with growth hormone has been less favourable than initially assumed. Growth hormone treatment has not restored normal growth to these children. The highly demanding nature and high costs of this treatment require an optimised prescription, and this remains to be determined.

[The TRH test in 60 depressed adolescents]. / Etude du test à la TRH chez 60 adolescents déprimés.

Thyroid-stimulating hormone (TSH) and triiodothyronine (T3) responses to thyrotropin-releasing hormone (TRH) were compared in sixty depressed adolescents and sixty normal controls. A significant difference was found for baseline and peak values of T3 and TSH levels. There was no correlation between TSH blunting and DSM III categories of depression.

[Androgen test: comparison of a low test and a high test in the development of the penis in male pseudohermaphroditism]. / Le test aux androgénes: comparaison d'un test faible et d'un test fort sur le développement du pénis dans les pseudohermaphrodismes masculins.

BACKGROUND: The androgen sensitivity test used in male pseudohermaphroditism for clinical assessment of the androgen sensitivity and prediction of penile development is an important element in choice of gender. However, there is a wide range of testosterone dosage and no standardized test. METHODS AND PATIENTS: Two doses (2.5 mg and 100 mg) of testosterone heptylate were used in six cases of male pseudohermaphrodism with sexual ambiguity and small penis (ages 6 to 18 months). The clinical results were compared with those of the study of androgen receptors. RESULTS: In two cases, both low-dose and high-dose tests resulted in only minimal changes in the penis. In two cases, the low-dose test gave a good result which was confirmed by the high-dose test; on the other hand, in two cases, the low-dose test was considered to be negative whereas the high-dose test led to the development of a normal-sized penis. In all cases except one, there was good concordance between the results of study of androgen receptors and those of the clinical test. CONCLUSION: The high-dose androgen test is thus useful in both diagnosis and treatment and facilitates the gender assignment.

[Precocious puberty and polycystic ovarian syndrome: apropos of 13 cases]. / Puberté précoce et syndrome des ovaires polykystiques: à propos de 13 observations.

BACKGROUND: Precocious puberty and polycystic ovarian syndrome are two different entities which appear at different stages of ovarian development. Their association is uncommon. POPULATION: Thirteen girls presented idiopathic central precocious puberty with sexual development before the age of 8 years; menstruations were seen at the age of 9.5 years in one patient. Nine of them were given medroxyprogesterone or cyproterone acetate and two patients LHRH analog. Menarche occurred at a mean age of 11.8 +/- 1.5 years. After a mean free interval of 22 months, these thirteen patients developed hirsutism with irregular menstruations (eight patients) and weight gain (seven patients). The diagnosis of polycystic ovarian syndrome was confirmed by increased plasma testosterone (mean 91.1 +/- 14 ng/dl) and LH levels during LHRH test and by ultrasonography or coelioscopy. The treatment included cyproterone acetate plus 17 beta oestradiol; it was discontinued in eleven cases after 2 years of treatment. Plasma testosterone levels were normal 6 months later in association with regular menstruations. But three patients presented clinical and hormonal recurrence one year later, requiring repeated treatment. CONCLUSION: This association seems to be related to the same gonadotropin dysfunction. It is necessary to regularly follow patients treated for precocious puberty.