Comparison between spontaneous gonadotropin concentration profiles and gonadotropin response to low-dose gonadotropin-releasing hormone in prepubertal and early pubertal boys and patients with hypogonadotropic hypogonadism: assessment by using ultrasensitive, time-resolved immunofluorometric assay.

To assess whether nocturnal gonadotropin concentration profiles in children could be predicted by measurement of peak gonadotropin levels after gonadotropin-releasing hormone (GnRH) administration, we measured spontaneous gonadotropin levels every 20 min and the gonadotropin responses to low-dose GnRH using an ultrasensitive, time-resolved immunofluorometric assay in 61 boys with short stature and/or delayed puberty. Spontaneous nocturnal LH pulses were observed in 58 out of 61 patients. After GnRH administration in a dose of 25 ng/kg, all of the 61 patients had significant LH and FSH responses, and GnRH-stimulated peak LH and FSH levels were highly correlated with maximal spontaneous nocturnal LH and FSH levels, respectively (r = 0.83 for LH and r = 0.91 for FSH; p less than 0.00001). Analysis of individual subjects revealed that GnRH-stimulated peak LH levels were almost identical to maximal nocturnal LH levels in the subjects whose GnRH-stimulated peak LH levels were between 5 and 10 IU/L, whereas GnRH-stimulated peak LH levels tended to be higher than maximal nocturnal levels in the subjects whose GnRH-stimulated peak LH levels were 5 IU/L or lower. To determine if there were any parameters in the gonadotropin response to GnRH that might be useful in distinguishing early pubertal boys from prepubertal boys, we evaluated the gonadotropin response to GnRH in 44 prepubertal and 10 early pubertal normal short boys. Although maximal nocturnal LH levels did not overlap between prepubertal and pubertal groups, GnRH-stimulated LH peak levels overlapped considerably between the two groups. Even the GnRH-stimulated peak LH to peak FSH ratio overlapped between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Estimation of GnRH pulse amplitude during pubertal development

Fourteen children between 2.5 and 16 years of age were studied to provide a quantitative estimate of the changes in gonadotropin-releasing hormone (GnRH) pulse amplitude in hypophysial portal plasma during puberty. Responses to physiologic doses of synthetic GnRH were measured [induced luteinizing hormone (delta LH) and induced follicle-stimulating hormone (delta FHS)] and compared with spontaneous fluctuations in gonadotropins [spontaneous luteinizing hormone (delta sLH) and spontaneous follicle-stimulating hormone (delta FHS)]. One to four low-dose (0.0125 or 0.025 microgram/kg IV) pulses of GnRH were given every 2 hr between 0800 ad 1600 or 2200 and 0400 hr. Maximal peripheral plasma concentrations of GnRH one min after pulses averaged 107 +/- 25 pg/ml (S.E.) (0.0125 microgram/kg dose) and 218 +/- 33 pg/ml (0.025 microgram/kg dose). In early pubertal children the maximal delta LH was similar to or less than the maximal nocturnal delta sLH (maximum, delta LH 7.0 +/- 0.2 versus maximum delta sLH 7.0 +/- 1.3 mIU/ml in boys, 7.0 +/- 1.2 versus 16.0 +/- 3.0 mIU/ml in girls). Luteinizing hormone (LH) responses were low or undetectable in children whose bone ages were less than 10 years. When discernible, LH pulse frequency was similar during daytime and nighttime sampling periods in early pubertal boys. However, two hourly injections of GnRH given during the day did not simulate the initial nocturnal rise in LH. Overall mean delta FSH and delta sFSH were similar in three prepubertal female patients (3.0 +/- 0.2 versus 2.8 +/- 0.2 mIU/ml). delta FSH was greater than delta sFSH in two patients with gonadal dysgenesis (bone ages, 2.5 and 5 years) and in one prepubertal girl. The gonadotropin responses seen in early pubertal children suggests that the amplitude of nocturnal GnRH pulses is equal to or greater than that previously reported in normal men.     

GONADOTROPIN RESPONSIVENESS TO LUTEINIZING HORMONE RELEASING HORMONE IN PREPUBERTAL AND PUBERTAL PATIENTS WITH GROWTH HORMONE DEFICIENCY

ABSTRACT. Gonadotropin response to 100 μg/m² LHRH was determined in 31 patients with growth hormone deficiency. According to their bone ages the patients were divided into a "prepubertal" ( n =18) and a "pubertal" ( n =13) group. The results were compared with the LHRH tests from 16 healthy prepubertal boys and girls and 32 healthy adult probands, respectively. The maximum increment of LH and FSH was evaluated. In the "prepubertal" group five patients had an insufficient rise of LH and FSH, four of them having additional anterior pituitary hormone deficiencies. In the "pubertal" group nine patients were found to be gonadotropin deficient, all of them had additional hormone deficiencies, TSH being the most frequently affected hormone. Only one of 14 gonadotropin-deficient patients had no other than growth hormone deficiency in addition. An isolated decreased FSH increment without LH deficiency was found in 6 male and 2 female patients and is not thought to be of diagnostic value. No influence of growth hormone treatment or growth velocity on the gonadotropin responsiveness was found. Patients with an additional thyreotropic defect could be classified as pituitary or hypothalamic disorder due to their reaction in the TRH test. These groups could not be differentiated by a single bolus LHRH test, indicating the need of prolonged stimulation to recover the pituitary hyporesponsiveness. Due to methodological problems the diagnosis of gonadotropin deficiency in an individual patient of the prepubertal age group might be questioned. However, a normal gonadotropin response to LHRH can be expected in prepubertal patients with growth hormone deficiency and may indicate a normal gonadotropin function.     

Ovarian function following chemotherapy for childhood brain tumours

Pubertal development, basal gonadotrophin, and oestradiol levels were assessed in 21 girls who had received neuroaxis irradiation for a brain tumour followed by adjuvant chemotherapy with carmustine (BCNU) or lomustine (CCNU) and procarbazine. Thirteen received chemotherapy before the age of 11 years. Ten remained prepubertal at their last assessment, nine of whom showed biochemical evidence of primary ovarian failure. The remaining three were pubertal or adult, and although basal follicle-stimulating hormone (FSH) and luteinising hormone (LH) levels were normal, all had shown abnormalities of gonadotrophin secretion previously. Eight girls received chemotherapy after 11 years of age. Only three girls exhibited an elevated basal FSH level or exaggerated FSH response to GnRH. Elevated basal FSH values had been noted previously in two of the other five girls. All girls entered or progressed through puberty spontaneously. Seven experienced menarche at an appropriate age. However in four, gonadotrophin levels, which had been elevated, were now within the normal range. In two, menses had continued throughout with normal midfollicular oestradiol levels, whilst the other two developed secondary amenorrhoea associated with radiation-induced gonadotrophin deficiency. The majority of girls showed evidence of primary ovarian dysfunction. This did not prejudice pubertal development or the timing of menarche. Ovarian function may return to normal in the years after treatment, indicating a potential for fertility.     

Spontaneous and GnRH-provoked gonadotropin secretion and testosterone response to human chorionic gonadotropin in adolescent boys with thalassaemia major and delayed puberty

To elucidate whether the cause of sexual maturation arrest in thalassaemia is of gonadal or pituitary etiology, 10 males with thalassaemia and delayed puberty and 10 with constitutional delay of growth and pubertal maturation (CSS) were extensively studied. Their spontaneous nocturnal gonadotropin secretion and gonadotropin response to intravenous 100 micrograms gonadotropin-releasing hormone (GnRH) were evaluated. Circulating testosterone concentration and clinical response were evaluated after 3 days, 4 weeks and 6 months of intramuscular administration of human chorionic gonadotropin (HCG) (2500 U/m2/dose). Thalassaemic boys had significantly lower circulating concentrations of testosterone compared to those with constitutional delay of growth and sexual maturation (CSS) at the same pubertal stage. Short- and long-term testosterone response to administrations of HCG was markedly decreased in thalassaemic boys. After 6 months of HCG administration 50 per cent (5/10) of the boys did not show significant testicular enlargement or genital changes. Despite the low circulating concentrations of testosterone, none of the patients had high basal or exaggerated gonadotropin response to gonadotropin releasing hormone (GnRH) stimulation. Luteinizing hormone (LH) peak responses to GnRH were significantly lower as compared to controls. Follicle-stimulating hormone (FSH) peak responses to GnRH did not differ among the two study groups. The mean nocturnal LH and FSH secretion was significantly decreased in all thalassaemic boys as compared to boys with CSS at the same pubertal stage (testicular volume). These data proved that hypogonadotropic hypogonadism is the main cause of delayed/failed puberty in adolescents with thalassaemia major. MRI studies revealed complete empty sella (n = 5), marked diminution of the pituitary size (n = 5), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 8) in thalassaemic patients, denoting a high incidence of structural abnormalities (atrophy) of the pituitary gland. Moreover, in many of the thalassaemic boys, the defective testosterone response to long-term (6 months) HCG therapy denoted significant testicular atrophy and/or failure secondary to siderosis. It appears that testosterone replacement might be superior to HCG therapy in these patients. This therapy should be introduced at the proper time in these hypogonadal patients to induce their sexual development and to support their linear growth spurt and bone mineral accretion.     

The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty

OBJECTIVES: To assess the value of gonadotrophin releasing hormone (GnRH) stimulation test in identifying intracranial abnormality in girls with central precocious puberty (CPP). PATIENTS AND METHODS: A study of 67 girls diagnosed with CPP who underwent cranial MRI scans. Patients were not receiving any therapy and there were no neurological signs or symptoms at presentation. Patients underwent evaluation of GnRH stimulation test and plasma oestradiol levels at presentation. RESULTS: Mean age at onset of puberty was 6.2 years (range 2.0 to 8.0 years). Intracranial abnormalities were present in 10 (15%) patients, while 57 girls (85%) had no abnormalities. No significant difference was shown between girls with intracranial abnormality and girls without intracranial abnormality in basal LH or FSH values, peak LH or FSH values, LH/FSH peak ratios, peak LH/basal LH ratios, peak FSH/ basal FSH ratios at presentation. CONCLUSION: GnRH stimulation test does not identify those with underlying intracranial abnormality at presentation. MRI imaging remains necessary in all cases of central precocious puberty in girls.     

血清促性腺激素基础值在性早熟女童诊断中的价值

目的：探讨血清促性腺激素基础值在性早熟女童诊断中的价值。方法：以促性腺激素释放激素（GnRH）激发试验结果作为性早熟诊断的金标准,将77例性早熟女童分为中枢性性早熟（CPP,n=45）和单纯性乳房早发育（IPT,n=32）两组,分别比较两组黄体生成素（LH）、卵泡刺激素（FSH）基础值及LH/FSH比值的差异;并采用受试者工作特征（ROC）曲线分析LH、FSH基础值及LH/FSH比值诊断性早熟的准确性。结果：CPP组患儿血清基础LH、FSH水平及LH/FSH比值均高于IPT组（P<0.01）;两组患儿LH基础值与GnRH激发试验中LH峰值存在正相关;LH、FSH和LH/FSH比值诊断CPP的曲线下面积（AUC）进行比较,AUCLH大于AUCFSH和AUCLH/FSH（均P＜0.05）,而AUCFSH和AUCLH/FSH之间比较差异无统计学意义。当血清LH基础值为0.62 IU/L时,敏感度为0.778,特异度为0.906,Youden指数最大（0.684）;当切割值为1.5 IU/L时,诊断敏感度下降为0.311,但特异度为1.0。结论：血清LH基础值诊断CPP的价值优于LH/FSH比值及FSH基础值,可用于性早熟女童门诊的初步诊断,但存在一定的误诊和漏诊率;对于LH基础值大于1.5 IU/L的患儿,结合临床表现可明确诊断,无需另行GnRH激发试验。     

Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation

A new triptorelin 11.25 mg long depot formulation is now available for the treatment of central precocious puberty (CPP). The aim of our study was to evaluate the efficacy of triptorelin 11.25 mg administered every 90 days to suppress gonadotropin and sex steroid secretion and pubertal signs in children with CPP during 2 years of treatment. Inclusion criteria were clinical pubertal development before the age of 8 years in girls or 9 years in boys, advanced bone age and a pubertal LH response (peak >5 mIU/ml) to GnRH. We studied 20 patients (19 girls and 1 boy), with a median age at entry into the study of 7.5 +/- 0.2 years for girls, and 9 years for the boy. The basal and GnRH-stimulated serum levels of LH and FSH decreased significantly from baseline to 3 months of therapy (p <0.0001). All patients had a GnRH-stimulated peak below 3 mIU/ml between 6 and 24 months of treatment. The pituitary-gonadal axis recovered adequately after discontinuation of therapy. These results suggest that 3-month depot triptorelin is a satisfactory alternative for the therapy of children with CPP. The longer interval between injections may increase acceptability and compliance with treatment.     

Nocturnal integrated gonadotropin concentrations in evaluating pubertal transition in girls

We assessed the utility of measuring the physiological levels of gonadotropins as a diagnostic tool for pubertal onset in girls. Two methods of gonadotropin measurements were compared: the standard frequent sampling method, in which blood samples were drawn every 20 min, and the multiple integrated sampling method, in which samples were obtained continuously at 30 min intervals by a withdrawal pump. The two methods were examined simultaneously overnight in a group of eight girls at different stages of puberty. The following parameters of both LH and FSH secretion, calculated by PULSAR program, were highly correlated between these methods: area under the curve (AUC), mean levels, mean from smoothed baseline and mean peak height. The diagnostic value of multiple integrated sampling of gonadotropins (performed over 6 h) was then assessed in five prepubertal girls and six girls at early puberty (Tanner stages 2 and 3), in whom peak gonadotropins levels in response to GnRH stimulation test were in the prepubertal range. Several parameters of LH (but none of FSH) were significantly higher (p<0.05) in early pubertal compared to prepubertal girls: AUC (5.61 +/- 2.40 vs 2.39 +/- 1.41), mean levels (0.52 +/- 0.21 vs 0.23 +/- 0.14), smoothed mean level (0.43 +/- 0.18 vs 0.18 +/- 0.11) and peak area (0.27 +/- 0.08 vs 0.11 +/- 0.06). We conclude that the technically simple method of multiple integrated sampling is useful in detecting pubertal transition and is superior to the GnRH-stimulation test. This method can be used in selective cases when the stimulation test yields equivocal results.     

Sleep-related gonadotropin rhythms in children following treatment of acute leukemia: recovery of the hypothalamo-pituitary-gonadal axis after chemotherapy and CNS-irradiation

Twelve children (5 girls and 7 boys, between the ages of 6 and 20 years) in complete remission from previous ALL who had completed their entire anti-leukemic treatment program and who had been off all chemotherapy for at least one year, were included in a study of sleep-related prolactin and gonadotropin rhythms. All the patients had received prophylactic CNS-irradiation. The patients in early puberty showed a sleep-dependent FSH rhythm. Patients in middle-to-late puberty had sleep-related FSH and LH rhythms, and estradiol and testosterone plasma concentrations were normal for their pubertal stage, suggesting recovery of the hypothalamo-pituitary-gonadal feedback system. We conclude that the neuro-endocrine axis is not permanently injured by CNS-irradiation and anti-leukemic therapy.     

Hypothalamic-pituitary-ovarian function in menstruating women with Turner syndrome (45,X)

The hypothalamic-pituitary-ovarian hormone secretion patterns were evaluated in two women with 45,X Turner syndrome, spontaneous sexual development, and monthly menstrual periods. Each women had serum gonadotropin and sex steroid determinations during two or more menstrual cycles. During the follicular phase of a menstrual cycle, both women received 100 micrograms gonadotropin-releasing hormone (GnRH) s.c., and serum LH and FSH responses were determined. In addition, one woman collected daily overnight urine specimens for 40 consecutive days, spanning two menstrual periods, for the measurement of LH, FSH, estriol, and free progesterone. The randomly measured hormone results showed low serum progesterone concentrations during luteal phases, consistent with the interpretation of anovulation or inadequate corpus luteum function. At the time of the GnRH stimulation tests, baseline serum FSH concentrations and FSH responses to GnRH were within normal limits, whereas baseline LH levels and LH responses to GnRH were low. The pituitary gonadotropin secretion patterns were more consistent with patterns seen during early puberty than in the perimenopausal state. This interpretation was further confirmed by the urinary excretion patterns of gonadotropins, which were not significantly elevated. Furthermore, the urinary hormone profiles revealed that, although the intermenstrual period was of normal length, the follicular phase was prolonged, with normal levels of LH, FSH, and estriol excreted. The menstrual cycle studied was ovulatory but had a short luteal phase. The hormone results indicated that the dysgenetic ovary of women with 45,X Turner syndrome is capable of producing sufficient quantities of sex steroids and other regulatory factors to maintain gonadotropin secretion patterns that are reminiscent of early puberty.(ABSTRACT TRUNCATED AT 250 WORDS)     

SLEEP-RELATED GONADOTROPIN RHYTHMS IN CHILDREN FOLLOWING TREATMENT OF ACUTE LEUKEMIA: RECOVERY OF THE HYPOTHALAMO-PITUITARY-GONADAL AXIS AFTER CHEMOTHERAPY AND CNS-IRRADIATION

ABSTRACT. Twelve children (5 girls and 7 boys, between the ages of 6 and 20 years) in complete remission from previous ALL who had completed their entire anti-leukemic treatment program and who had been off all chemotherapy for at least one year, were included in a study of sleep-related prolactin and gonadotropin rhythms. All the patients had received prophylactic CNS-irradiation. The patients in early puberty showed a sleep-dependent FSH rhythm. Patients in middle-to-late puberty had sleep-related FSH and LH rhythms, and estradiol and testosterone plasma concentrations were normal for their pubertal stage, suggesting recovery of the hypothalamo-pituitary-gonadal feedback system. We conclude that the neuro-endocrine axis is not permanently injured by CNS-irradiation and anti-leukemic therapy.     

Central precocious puberty and growth hormone deficiency in a boy with Prader-Willi syndrome

In Prader-Willi syndrome (PWS) hypothalamic dysfunction is the cause of hormonal disturbances, such as growth hormone deficiency (GHD), hypogonadism, and delayed or incomplete puberty. Only a few cases of central precocious puberty (CPP) have been reported. We describe an 8.8-year-old PWS boy, with microdeletion of chromosome 15q, who developed CPP. On admission, height was 131.1 cm (+0.17 SD), BMI 26.2 kg/m², pubic hair (Ph) 2, and testis 4.5 ml. We found increased growth velocity (7 cm/year), high testosterone levels, pubertal response to GnRH test, and advanced bone age (10.6 years). An evaluation of growth hormone (GH) secretion revealed a deficiency. Pituitary MRI was normal. LHRH analogue therapy (Leuproreline 3.75 mg/28 days i.m.) was started at 8.9 years and discontinued at 11.3 years, when the patient had bone age of 13 years. During therapy, growth velocity, testosterone, FSH, and LH peak decreased significantly, with no pubertal progression. Growth hormone therapy (0.24 mg/kg/week) was started at 9.5 years and discontinued at 15.3 years because the patient had bone age of 17 years. After interrupting LHRH therapy the patient demonstrated spontaneous pubertal progression with pubertal gonadotropin and testosterone. At 16.3 years, height was 170 cm (−0.48 SDS), BMI 36.3 kg/m², Ph 4, testis volume 10 ml and there was a combined hypothalamic and peripheral hypogonadism hormonal pattern (normal LH even with low testosterone and undetectable inhibin B with high FSH). To our knowledge this is the fourth male patient with genetically-confirmed PWS demonstrating CPP and GHD and the first with a long follow-up to young adulthood.     

Suppressed responsiveness to gonadotropin-releasing hormone in girls with unsustained isosexual precocity.

Eleven girls, ages 10/12 to 76/12 years, were evaluated because of early and rapid breast development. Initial clinical presentations and serum gonadotropin or estradiol determinations did not differentiate patient types. However, patients could be divided into two groups based on their responses to synthetic gonadotropin-releasing hormone: Group A consisted of seven girls with suppressed or prepubertail-type responses, and Group B consisted of four girls with pubertal or adult-type responses. Subsequent evaluation revealed that Group A patients had intermittent or unsustained isosexual precocity, whereas Group B patients had isiopathic prococious puberty. During initial evaluation, increased serum or urinary estrogen values were noted in ten of ten patients who were studied. The greatest serum E2 values (162 and 117 pg/ml) were noted in two Group A patients; three months and two years later, those patients had normal prepubertal responses to GnRH and serum E2 values of less than 4 and 14 pg/ml, respectively. Unsustained sexual precocoity in girls may be secondary to autonomous ovarian production of estrogens, and the GnRH test may be useful in evaluation of girls with isosexual precocity.     

Effect of synthetic luteinizing hormone-releasing hormone on the release of gonadotropins in hypophysogonadal disorders of children and adolscents. VII. Constitutional delay of puberty in males.

Serum gonadotropins (LH and FSH) were measured by radioimmunoassay before and after intravenous injection of 0.1 mg/m2 of synthetic luteinizing hormone-releasing hormone in 20 male patients, aged 15 to 18 years, with constitutional delay of puberty. Basal plasma levels of LH and FSH were in the prepubertal range. After administration of LH-RH, the increase in LH was significantly high than in prepubertal control subjects, aged 1 to 13 years; the difference between test patients and pubertal control subjects was not significant. The increase in FSH was in the prepubertal range, significantly lower than that in pubertal control subjects. This discrepancy between LH and FSH responses to LH-RH is similar to that observed in normal boys at the late prepubertal stage and suggests that an elevation of readily releasable pituitary stores of LH correlates with the first step of pubertal onset in males, even if puberty is delayed.     

Children with sickle cell disease: growth and gonadal function after hematopoietic stem cell transplantation

The aim of this study is to describe the growth, pubertal development, and gonadal function of a cohort of 30 sickle cell disease children who underwent bone marrow transplantation. They all received the standard pretransplant conditioning regimen of busulfan (14 or 16 mg/kg) and cyclophosphamide (200 mg/kg). Growth was normal both before and after transplant. Seven out of 10 girls had severe ovarian failure and requirement for estrogen replacement. Three out of 10 girls recovered some ovarian function posttransplant, with spontaneous pubertal development, menses, and 1 successful normal pregnancy. Follicle-stimulating hormone (FSH) serum levels were very high during spontaneous puberty and slowly normalized thereafter in these 3 patients. The 3 girls with ovarian function recovery differed from the 7 others by the lower busulphan dose of the conditioning regimen they received (14 rather than 16 mg/kg). All boys showed spontaneous pubertal development. However, most of them had small testis and elevated serum FSH levels, reflecting germinal epithelium damage. Testosterone level was low normal and luteinizing hormone elevated, reflecting Leydig cell insufficiency. In conclusion, 7/10 girls had complete gonadal failure and most of the boys had spontaneous puberty but germinal epithelial failure. Serum FSH levels showed important variations over time in the same patient.     

Acute gonadotropin response to the gonadotropin releasing hormone agonist (decapeptyl) in girls with pubertal pathology

The aim of the study was to assess the effect of a single injection of the GnRH agonist decapeptyl on gonadotropin secretion in girls with different pubertal disorders. The test was performed in two groups of girls with premature thelarche (younger and older than 2 years of age), girls with premature adrenarche and postmenarcheal girls with policystic ovaries. The GnRH agonist decapeptyl stimulated gonadotropins secretion in pre- and postmenarcheal girls. The responsiveness of LH was increased significantly in puberty. FSH response was exaggerated in the girls with premature thelarche before the age of 2, but in older premenarcheal girls with the same disorder it was not different than in girls with premature adrenarche. It is concluded that a single dose of the GnRH agonist decapeptyl is a safe and efficacious test for assessment of the function of the pituitary gland in pre-and postmenarcheal girls.     

Monthly urinary LH and FSH secretory patterns in normal children and patients with sexual disorders

Urinary gonadotropin concentrations were determined by polyclonal double antibody RIA after ammonium sulfate extraction. Good correlation was observed between urinary gonadotropin/creatinine ratios in first morning voided and full 24-h urine collections. Using consecutive 30-d first morning voided urine specimens from normal children and from patients with sexual disorders, we have studied the monthly patterns of nighttime gonadotropin secretion. In normal prepubertal girls, the levels of urinary LH were low with few variations and those of urinary FSH were higher with episodic fluctuations. In early pubertal girls, the levels of urinary LH increased with striking, rhythmic fluctuations. The same changes were seen in urinary FSH. A single big surge of urinary gonadotropins was observed in postmenarcheal girls. In normal boys, the secretory patterns of urinary gonadotropins were similar to those of normal girls, but varied less. In patients with idiopathic precocious puberty, the patterns of urinary gonadotropins were similar to those of normal subjects matched for sexual stage. The measurement of 30-d first morning voided urinary gonadotropins can provide a simple and physiologic test of gonadotropin function in children.     

Evaluation of gonadotrophin insufficiency in thalassemic boys with pubertal failure: spontaneous versus provocative test

The objective of this study was to determine whether iron toxicity in blood transfusion dependent beta-thalassemic patients with pubertal failure was associated with gonadotrophin (GTH) insufficiency as assessed by spontaneous and dynamic tests. Gonadotrophin-releasing-hormone (GnRH)-GTH secretory dynamics were studied by serial ultradian GTH profiles and a 100 microg i.v. GnRH bolus test (GBT) in 28 male beta-thalassemia major patients with failed puberty (FP group). Five healthy, non thalassemic prepubertal males were studied for comparative purposes. According to the pulse profile, patients in the FP group were subdivided into apulsatile (no FSH and LH pulses, n = 16; AFP group) and pulsatile (defective pulse profile, n = 12; PFP group) subsets. The FP group had lower basal FSH (p < 0.01), LH (p < 0.01) and GnRH stimulated FSH (p < 0.001) and LH levels (p < 0.001) than the controls. However, basal and GnRH-stimulated FSH (p < 0.01 for basal and p < 0.001 for peak) and LH (p < 0.01 for both basal and peak) levels were lower in the AFP than the PFP group. Serum ferritin levels in GnRH-non-responders were higher than those in the responders (9,052.63 +/- 579.14 mg/l vs 5,933.33 +/- 1,819.65 mg/l; p < 0.05). Similarly, symptomatic organ damage was higher in the AFP than the PFP patients (81% vs 42%; p < 0.001). In conclusion, this study suggests that iron overloaded thalassemic patients with failed puberty had abnormal GnRH-GTH secretory dynamics. The severity of the defect was heterogeneous, ranging from very severe (apulsatile) to less severe (pulsatile) subsets. Comparison between spontaneous and dynamic test levels showed that there was concordance between the degree of pulse defect and magnitude of LH response to GBT. However, ultradian GTH profile was a more reliable method for identifying the degree of GTH insufficiency than GBT. Our data also showed that iron toxicity was the major cause of GnRH-GTH deficiency in thalassemic patients. Such information may be useful for better understanding of the pathophysiology of hypogonadotrophic hypogonadism (HH), thereby promoting therapeutic options for induction of puberty and spermatogenesis.     

Gonadotrophin response to LH-RH in boys with delayed growth and adolescence.

Plasma luteinising hormone (LH) and follicle-stimulating hormone (FSH) concentrations were measured before and after intravenous luteinising hormone-releasing hormone (LH-RH) in 33 boys with growth delay. Eighteen were prepubertal and 15 pubertal. Basal LH and FSH levels were low in both groups with mean increments after LH-RH of 3.2 +/- 0.8 U/l (mean +/- SEM) and 2.6 +/- 0.4 U/l respectively in the prepubertal and 7.4 +/- 0.7 U/l and 2.0 +/- 0.3 U/l in the pubertal boys. The LH increment showed a positive correlation with increasing bone age (r = 0.71, P less than 0.001); FSH did not. The LH-RH response thus appeared normal in relation to the stage of maturity.