Treatment of gonadotropin dependent precocious puberty due to hypothalamic hamartoma with gonadotropin releasing hormone agonist depot.

The gonadotropin releasing hormone (GnRH) secreting hypothalamic hamartoma (HH) is a congenital malformation consisting of a heterotopic mass of nervous tissue that contains GnRH neurosecretory neurons attached to the tuber cinereum or the floor of the third ventricle. HH is a well recognised cause of gonadotropin dependent precocious puberty (GDPP). Long term data are presented on eight children (five boys and three girls) with GDPP due to HH. Physical signs of puberty were observed before 2 years of age in all patients. At presentation with sexual precocity, the mean height standard deviation (SD) for chronological age was +1.60 (1.27) and the mean height SD for bone age was -0.92 (1.77). Neurological symptoms were absent at presentation and follow up. The hamartoma diameter ranged from 5 to 18 mm and did not change in six patients who had magnetic resonance imaging follow up. All patients were treated clinically with GnRH agonists (GnRH-a). The duration of treatment varied from 2.66 to 8.41 years. Seven of the eight children had satisfactory responses to treatment, shown by regression of pubertal signs, suppression of hormonal levels, and improvement of height SD for bone age and predicted height. One patient had a severe local reaction to GnRH-a with failure of hormonal suppression and progression of pubertal signs. It seems that HH is benign and that GnRH-a treatment provides satisfactory and safe control for most children with GDPP due to HH.     

促性腺激素释放激素类似物联合重组人生长激素对中枢性性早熟女童身高的影响

目的 研究促性腺激素释放激素类似物（GnRHa）与重组人生长激素（rhGh）联合治疗以及GnRHa单用对骨龄≥10岁的特发性中枢性性早熟（ICPP）女童成年身高的改善情况。方法 将6个医学中心确诊为ICPP符合研究条件的80例女童（年龄9.0±0.7岁,骨龄≥10岁）根据治疗方法分为GnRHa与rhGh联合治疗组（31例）及GnRHa单用组（49例）。观察治疗前后的预测成年身高、接近成年身高和身高净获等各项指标的变化。结果 两组在治疗后按骨龄的身高标准差分值均较治疗前有显著改善（P<0.01）,其中GnRHa与rhGh联合治疗组明显优于GnRHa单用组（P<0.01）。联合用药组接近成年身高（157±6 cm vs 157±4 cm）、身高净获（4.68 cm vs 3.89 cm）、停药时预测成年身高（161±5 cm vs 158±5 cm）、接近成年身高与遗传靶身高差值等指标均略高于GnRHa单用组,但差异无统计学意义（均P >0.05）。结论 GnRHa与rhGh联合治疗或GnRHa单用组均能改善骨龄≥10岁ICCP女童的成年身高,但两药联用优势不明显。对ICPP患儿预测成年身高的评估需要慎重,停药时的预测值偏高。     

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.     

Human growth hormone and gonadotropin releasing hormone analog combination therapy increases predicted height in short normal girls

The "short normal" child constitutes a real challenge for the pediatric endocrinologist. In a subgroup of short normal children, puberty starts at a normal age but with low height, and hence, the final height is expected to be quite compromised. Efforts to improve the outcome in this group have been made in the past with equivocal results. We present the growth data of 8 short girls with normal growth hormone values on provocative testing and low height at puberty initiation. At intervention the height and the stage of puberty were 129.3 +/- 5 cm and II to III, respectively, and the predicted height was 148.8 +/- 2.6 cm. Gonadotropin releasing hormone analog, triptorelin (3.6 +/- 0.5 microg/kg/day) and growth hormone (0.5 IU/kg/week) were used in different sequential order and simultaneously in each child. The mean total treatment period was 47.6 +/- 11.2 months. The mean predicted and the mean final height in the total group were 148.8 +/- 2.6 and 154.5 +/- 3.6 cm, respectively (p:0.028). The final height did not differ from the target height (154.8 +/- 8 cm versus 154.5 +/- 3.6 cm), while in 4 children, the final height was greater than the target height. The height gain (delta Final height - Predicted height) was 5.7 +/- 1.3 cm. If we analyze separately the girls in whom growth hormone was started first and gonadotropin releasing hormone analog followed versus those who started the analog first, the delta Final height - Predicted height was 8 +/- 3 cm in the former and 4.8 +/- 3.1 cm in the latter (p:0.03). It seemed that the difference was accounted for by duration of growth hormone therapy (51.3 +/- 10.6 months versus 28.6 +/- 10.6 months) (p:0.026), rather than by other factors. In conclusion, under the conditions of the present study, the combination of puberty arrest and growth hormone therapy significantly improved predicted height. The most significant determinant of the height gain was the duration of growth hormone therapy.     

Use of growth hormone and gonadotropin releasing hormone agonist in addition to L-thyroxine to attain normal adult height in two patients with severe Hashimoto's thyroiditis

AIM: We report two patients with severe acquired juvenile hypothyroidism who presented with compromised predicted adult height (PAH), and the successful use of growth hormone (GH) and gonadotropin releasing hormone agonist (GnRHa) in addition to L-thyroxine to attain normal adult height. PATIENTS AND RESULTS: Patient 1: 13 year-old girl who presented with pubertal delay, short stature (height SDS -4), and marked bone age retardation (BA 8 yr). Serum T4 was undetectable and TSH level was 1,139 mIU/l. After 1 year of treatment with L-thyroxine, growth rate improved from 1.0 cm/yr to 9.8 cm/yr but puberty progressed (Tanner 3 breast) and BA accelerated by 4 years, compromising predicted adult height (PAH) (144 cm vs mid-parental target height [MTH] of 163 cm). Combined use of GH and GnRHa for one year slowed BA progression, and catch-up growth (10.4 cm/yr) continued to attain a final height (FH) of 155 cm. Patient 2: 14 year-old boy with undetectable T4, TSH of 811 mIU/l in mid-puberty with poor growth rate (1.0 cm/yr), without any bone age delay (BA 14 years) but compromised PAH (163.8 cm vs MTH 174 cm). Because of the advanced puberty and poor growth rate, treatment with GH and GnRHa was initiated. Treatment for 2 years led to improvement of growth velocity (10.6 cm/yr), slowed BA progression to attain a FH equal to MTH. CONCLUSION: Combined use of GH and GnRHa improved the FH of two patients, with Hashimoto's thyroiditis: one with pubertal and bone age delay and the other with normal onset of puberty and normal bone age.     

促性腺激素释放激素激动剂治疗女童性早熟的不良反应探析

促性腺激素释放激素激动剂(gonadotropin releasing hormone agonist,GnRHa)是目前临床广泛应用的相对安全的性早熟治疗药物.患儿在停药后可以正常月经来潮、怀孕、生育.GnRHa不会降低青春期后的子宫体积,停药后的黄体生成素、卵泡刺激素及性激素水平可恢复至接近或超过停药前水平.研究提示促性腺激素释放激素拟似物可能会增加罹患雄激素过多症及多囊卵巢综合征的风险,但尚缺乏较高等级的证据.现有的研究不能提供充分证据表明GnRHa对骨矿物质密度有显著和不可逆的负面影响.GnRHa可能具有增加体质量指数(BMI)的不良反应,亦有研究表明GnRHa有助于降低BMI,或不会增加BMI.     

GnRHa治疗女性中枢性性早熟疗效及不良反应观察

目的观察促性腺激素释放激素类似物(GnRHa)治疗特发性中枢性性早熟对改善患者终身高的确切疗效,探讨GnRHa治疗的不良反应。方法23例女性特发性中枢性性早熟(ICPP)终止GnRHa治疗后随访(45.0±14.2)个月,观察终身高、月经初潮时间、月经规则程度、体质指数(BMI),比较了G-P图谱、TW3和身高曲线图三种方法预测终身高的精确度。结果GnRHa治疗(24.3±13.1)个月,平均终身高为(160.3±4.2)cm,与靶身高比较,从治疗前预测身高-1.58±2.02SD增加到-0.01±1.53SD。停止治疗后(11.5±5.5)个月出现或复现月经初潮,月经周期均规则。达终身高时BMI为20.81±2.08。停止治疗时G-P图谱和TW3预测值与实际终身高比较差异无统计学意义,均明显高于曲线法的预测值。结论GnRHa治疗ICPP能有效改善终身高,经随访无不良反应。     

Dual growth hormone (GH) response to repeated GH releasing hormone stimulus in children and adults

Several authors have demonstrated that plasma growth hormone (GH) levels as response to acute GH releasing hormone (GHRH) stimulation in adults are decreased by a previous GHRH injection whereas they are maintained in children. Probably the most accepted hypothesis for this finding is the increase in the somatostatinergic tone. The aim of the present study was to evaluate the dual GH response to repeated GHRH stimuli to clarify the possible influence of somatostatinergic activity in the type of response. Eighteen healthy prepubertal children, mean age 9.2 years (range: 6.0-12.9 years) and 19 healthy adult volunteers, mean age 25.5 years (range: 17-35 years) were studied with the GHRH test. An additional group of 10 normal adults with similar characteristics (mean age 31 years, range 25-35 years) were also recruited as a control group for somatostatinergic assessment. The GH response to the first GHRH bolus was similar in both children and adults. However, while children showed a preserved response to the second stimulus, it was diminished in adults. As expected, thyroid stimulating hormone (TSH) was within the normal range in all subjects. When the evolution of TSH was compared between the group of non-responders and the control group, no significant differences were found either at basal time or at 120 min, showing a similar decreasing trend for serum TSH level. The variation of TSH levels were also expressed as the proportion of TSH response after 2 hours compared to the basal level (TSH-120/TSH-0) but no significant differences were found (GHRH non-responders group mean: 73.6%, range: 51.3-93.7; control group mean: 70.7%, range: 62.9-92.5). In conclusion, the results confirm that in adults but not in children, the somatotrope responsiveness to GHRH is inhibited by a previous bolus of GHRH. The finding that the plasma TSH level diminishes in a similar manner in both non-responders and the control group is in agreement with the rejection of the hypothesis of the influence of somatostatin.     

Growth hormone secretion in response to the administration of thyrotropin releasing hormone (TRH) in children with insulin-dependent diabetes mellitus]

In this study the Authors examined the response in growth hormone (GH) to thyrotrophin releasing hormone (TRH) administration in a group composed of 29 children (17 males, 12 females) suffering from insulin-dependent diabetes mellitus (IDDM) (group 1). All subjects were prepubertal, had a chronological age of 8.82 +/- 1.76 years (m +/- SD), a bone age of 8.60 +/- 1.65 years; the time elapsed since the diagnosis was 2.45 +/- 1.51 years, glycosylated hemoglobin (HbA1c) was 7.33 +/- 1.80%. Some of the same subjects (all those with a response in GH to TRH higher than 4 ng/ml; no. 11; group 2) were examined again 12-18 months later; as controls, 13 short children were also examined (group 3). All the subjects of the three groups showed a TSH peak ranging from 10-25 microU/ml, whereas GH peak resulted higher than 4 ng/ml ("paradoxical" response) in 6 subject of the group 1 and in an only subjects of the group 2. All the responders of the 3 groups showed a value in HbA1c higher than 8%. A significant difference was not present between males and females in GH and TSH values. Cortisol levels and glycaemia remained almost constant during the performance of the tests. By considering all the groups, TSH and GH values during TRH-test were not correlated with glycaemia, chronological age, bone age, the time elapsed since the diagnosis, height, height velocity, HbA1c values. In conclusion, our data demonstrated that "paradoxical" response in GH to TRH administration was present only in some subjects and particularly in those with a poor metabolic control of the disease.     

Adult height in advanced puberty with or without gonadotropin hormone releasing hormone analog treatment

Advanced puberty is defined as the onset of puberty in girls at 8-10 years of age and in boys at 9-11 years. This study analyzes adult height in 57 children with advanced puberty to evaluate the results of treating children (9 girls and 8 boys) with gonadotropin hormone releasing hormone (GnRH) analog and the impact of advanced puberty on adult height in untreated children (31 girls and 9 boys). For treated girls, adult height predicted at the onset of treatment (151.9+/-1.7 cm) was similar to the final adult height (155.3+/-1.4 cm), but lower than target height (157.2+/-1.6 cm, p = 0.04). For untreated girls, adult height predicted at the initial evaluation (156.7+/-1 cm) was also similar to adult height (157+/-1 cm), but lower than the target height (157.6+/-1 cm, p = 0.03). The adult heights of both treated and untreated girls were similar to their target heights. For treated boys, adult height predicted at the onset of treatment (173.2+/-3.1 cm) was greater than the final adult height (164.1+/-2.1 cm, p = 0.01), which was lower than target height (170.4+/-1.2 cm, p = 0.01). For untreated boys, adult height predicted at the initial evaluation (170.8+/-2.7 cm) was similar to both the adult height (169.1+/-1.9 cm) and target height (170.2+/-1.2 cm). Height gains between the onset of puberty and adult height were similar in treated (29.9+/-2.3 cm in girls and 29.8+/-1.7 cm in boys) and untreated (28.6+/-1 and 33.1+/-2 cm) children. When expressed as SD, the adult height was significantly shorter than that at 4 years in treated girls (difference 1 SD, p = 0.03), in untreated girls (difference 0.9 SD, p = 0.0002) and in treated boys (difference 0.9 SD, p = 0.02), but it was similar to that in untreated boys. Adult height was below target height by >5 cm in seven girls (two of them treated) and five boys (four of them treated). In conclusion, treating advanced puberty did not change the adult height reached by girls, and was associated with reduced growth potential in boys. The adult heights of untreated children were similar to those predicted at the initial evaluation and to target heights, but in girls they were 1 SD lower than the height at 4 years. These data suggest that advanced puberty decreases the growth potential by about 5 cm, and that GnRH analog treatment does not prevent this.     

Evaluation of gonadotropin responses to synthetic gonadotropin-releasing hormone in girls with idiopathic hypopituitarism.

We hypothesized that prepubertal girls with gonadotropin deficiency would produce less follicle-stimulating hormone (FSH) in response to synthetic gonadotropin-releasing hormone (GnRH) than would gonadotropin-sufficient children. To test this hypothesis, we performed 103 GnRH tests serially in 21 children who had idiopathic hypopituitarism with growth hormone deficiency. We tried to predict whether puberty would occur in the 17 girls with bone ages of 8 years or less. Of these 17 girls, 4 failed to have spontaneous secondary sexual characteristics by age 16 1/2 years, and 12 had spontaneous complete pubertal development. One girl had incomplete pubertal maturation with partial gonadotropin deficiency; her results were combined with those of the girls who had no spontaneous pubertal development. With increasing bone age, the girls with complete pubertal development had a decrease in the increment of FSH released in response to GnRH, although basal gonadotropin concentrations did not change. For GnRH tests performed at bone ages of 8 years or less, basal luteinizing hormone (LH) values did not differ between girls with complete puberty and those with absent or incomplete puberty. However, basal FSH and the incremental response of LH and FSH to GnRH were greater in those with complete puberty. Only two girls with prepubertal bone ages at the time of testing, who subsequently had complete puberty, had incremental FSH responses to GnRH that were less than 5 IU/L. Individual incremental LH responses to GnRH did not discriminate well between groups. None of the girls with adrenocorticotropic hormone deficiency, either originally or subsequently, had spontaneous puberty, but 4 of 12 girls with thyrotropin deficiency, either originally or subsequently, had complete puberty. We conclude that a significant increase in GnRH-stimulated FSH suggests that spontaneous pubertal development will occur in girls with idiopathic hypopituitarism. However, a low FSH response to GnRH may not be diagnostic of gonadotropin deficiency.     

Height prognosis of children with true precocious puberty and growth hormone deficiency: effect of combination therapy with gonadotropin releasing hormone agonist and growth hormone.

We evaluated height prognosis and therapeutic efficacy of long-term, combination therapy with gonadotropin releasing-hormone agonist and growth hormone (GH) in five children (three girls) with coexistent precocious puberty and GH deficiency. Their clinical characteristics and growth response were compared with those of 12 girls with idiopathic true precocious puberty and eight prepubertal GH-deficient children (one girl). Precocious GH-deficient subjects were older than the precocious GH-sufficient children (9.5 +/- 1.8 years vs 6.5 +/- 1.3 years; mean +/- SD), but bone ages were comparable (12 +/- 3.7 years vs 10 +/- 0.9 years); their chronologic age was similar to that of the prepubertal GH-deficient children (9.6 +/- 2.1 years), but bone age was significantly more advanced (6.9 +/- 2.3 years). The mean height velocity of the prepubertal GH-deficient children (3.8 +/- 1.5 cm/yr) was lower than that of the precocious GH-deficient subjects (6.7 +/- 1.6 cm/yr) and the precocious GH-sufficient children (9.5 +/- 2.9 cm/yr). Baseline adult height prediction z scores were significantly lower in the precocious GH-deficient children (-3.7 +/- 1.0) than in either the precocious GH-sufficient children (-2.2 +/- 1.0) or the prepubertal GH-deficient subjects (-1.5 +/- 0.8). During therapy with gonadotropin releasing-hormone agonist, growth rates slowed to an average of 3.7 cm/yr in the precocious GH-deficient children but increased after the addition of GH to 7.4 cm during the first year of combination therapy. After 2 to 3 years of combination therapy, height predictions increased an average of 10 cm, compared with an increase of 2.8 cm in the precocious GH-sufficient group treated with gonadotropin releasing-hormone agonist alone. We conclude that combination treatment with gonadotropin releasing-hormone agonist and GH improves the height prognosis of children with coexistent true precocious puberty and GH deficiency, but falls short of achieving normal adult height potential.     

Circulating immunoreactive growth hormone releasing hormone concentrations and growth hormone response to growth hormone releasing hormone in short children

To study the role of peripheral immunoreactive growth hormone releasing hormone (ir-GHRH) concentrations and the GHRH test in the evaluation of growth hormone (GH) secretion in short stature, 46 children with a mean age of 9.4 years (range 1.6–16.3 years) and a mean relative height score of –3.2 SD (range –5.0–2.1 SD) were investigated. The children were divided into prepubertal (n=35) and pubertal (n=11) and the prepubertal children further into three groups based on their maximal GH responses to insulin-induced hypoglycaemia (IIH) and clonidine: (1) GH deficient subjects (maximal GH<10 g/l in both test); (2) discordant responders (maximal GH<10 g/l in one test and 10 g/l in the other); and (3) normal responders (maximal GH10 g/l in both test). Peripheral ir-GHRH concentrations were measured during the IIH test by radioimmunoassay after purification of plasma samples on Sep-pak cartridges. Among the prepubertal children 10 fell into group 1, 16 into group 2 and 9 into group 3. Children in group 1 were older, than those in group 3. There were no significant differences in relative heights and weights or absolute and relative growth velocities between the groups. Subjects in groups 1 and 2 had lower maximal GH responses to GHRH than those in group 3. There were no significant differences in the basal plasma ir-GHRH concentrations between the groups. Nine children (19.6%) had somatotrophs with a poor response to a single dose of exogenous GHRH (maximal GH<10 g/l). These subjects had increased basal plasma ir-GHRH concentrations. All of them had a decreased GH response to IIH and/or clonidine. Pubertal children had higher circulating ir-GHRH levels than the prepubertal subjects. There was an inverse correlation (r=–0.46;P<0.001) between the maximal GH response to GHRH and calendar age in the whole series. These observations suggest that: (1) a substantial proportion of short children have a heterogenous GH response to pharmacological stimuli necessitating complementary evaluation of their spontaneous GH secretion; (2) a poor response to exogenous GHRH is associated with increased ir-GHRH levels in the peripheral circulation; (3) all children with normal GH responses in pharmacological tests respond normally to GHRH and (4) the pituitary sensitivity to GHRH decreases with increasing age. Peripheral ir-GHRH concentrations do not differentiate between short children with growth hormone deficiency (GHD) and those with undefined short stature. The GHRH test is of limited value in the diagnosis of GHD, since a normal GH response does not exclude GHD, although a subnormal response appears to reflect dysfunctional GH secretion.     

Growth, growth hormone and sex steroid secretion in girls with central precocious puberty treated with a gonadotrophin releasing hormone (GnRH) analogue

We have treated 14 girls with central precocious puberty for a mean period of 2.3 years (range, 0.5-3.9) with intranasal (D-Ser6) GnRH analogue administered in a mean dose of 28 micrograms/kg/day (range, 15-56). With the onset of treatment there was an initial increase in sitting height compared to subischial leg length, but overall there was no significant change in height standard deviation score for bone age. In this respect our results were indistinguishable from untreated children with central precocious puberty. There was a decrease in physiological GH secretion, associated with decreased sex steroid secretion, which probably accounts for the growth deceleration which has been described during GnRH analogue therapy. The effect of this growth deceleration combined with slowing of the rate of epiphyseal maturation may explain the absence of alteration in height prognosis.     

Pelvic ultrasonography in normal girls and in girls with pubertal precocity

This prospective study sought to evaluate the role of pelvic ultrasonography in differentiating between various types of pubertal precocity. A control group of 117 normal girls (aged 1.1-15.6) was studied and compared with 87 girls with premature sexual maturation (aged 1.1-9.2y). Of these patients 19 had central precocious puberty (CPP), 48 had isolated premature thelarche (IPT) and 20 had premature adrenarche (IPA) Pelvic ultrasound variables evaluated were: (i) uterus: longitudinal diameter (uterine length), cross-sectional area (CSA) and fundo-cervical ratio; and (ii) ovaries: volume and morphology. Ovarian morphology was subdivided in 6 different appearances: solid, microcystic, paucicystic, multicystic, macrocystic, and major isolated cyst. In normal control girls, uterine length and CSA increased with age, although no cut-off values could be defined between different age ranges, and they were correlated with breast stage; fundo-cervical ratio was stable through childhood and increased after age 9. Ovarian volume was significantly greater in pubertal girls with breast stage 2 than in those with only pubic and/or axillary hair. There was a clear predominance of solid ovarian appearances in the age range 2-7, with the multicystic appearance being seen only after age 7, a minority being macrocystic. After age 10 all the different patterns were observed, and after age 13 the frequency of a macrocystic pattern increased. Significantly more mature ovarian appearances were observed in subjects with breast development compared with those without, independently of the presence of pubic hair. Patients with IPT had no significant differences in pelvic ultrasound measurements when compared with age-matched controls. All the different morphological ovarian appearances were observed in IPT, in contrast to age-matched controls, where only the less mature patterns (solid, micro- and paucicystic) were seen. Patients with CPP had significantly more mature patterns of ovarian morphology compared with age-matched controls, but did not differ from pubertal pre-menarcheal controls. Those patients with IPA differed from age-matched controls only in having significantly greater uterine length and CSA. Comparison of the pelvic ultrasound parameters between patient groups (IPT, CPP, IPA) and age-matched controls revealed significantly higher values in CPP for uterine length, uterine CSA and ovarian volume. Ovarian volume was also greater in IPT than in IPA. Ovarian morphology was significantly different in patients (IPT, CPP, IPA) compared with age-matched controls, but none of the ovarian morphological appearances was exclusive to a single condition. In conclusion: (i) pelvic ultrasound parameters increase progressively from birth to maturity, but no clear cut-off values can be established between age ranges; (ii) pelvic ultrasound variables reach adult values during puberty, with differences in the timing that may reflect geographical variations; (iii) the multicystic ovarian appearance occurs just before the onset of puberty; (iv) pelvic ultrasonography cannot always differentiate clearly between different disturbances of puberty and therefore cannot supersede other observations and investigations in the evaluation of pubertal disorders; and (v) in this study we propose a more detailed pelvic ultrasound terminology that can avoid apparent confusion in defining ovarian ultrasound appearance.     

Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency

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.     

Growth hormone response to growth hormone releasing factor in sickle cell disease

Many children with sickle cell disease (SCD) have impaired growth during childhood and adolescence, with patterns of growth consistent with constitutional delay in growth and pubertal development (CDGD). We evaluated the growth hormone (GH) response to a rapid intravenous (i.v.) infusion of growth hormone releasing factor (GRF, 1-44, 1 microgram/kg) in six children with SCD whose growth patterns and bone ages were consistent with CDGD. The peak GH response of the SCD patients to GRF (29.2 +/- 14.3 ng/ml, mean +/- SD, n = 6) was not statistically significantly different from the peak GH response of the control children (29.0 +/- 6.3 ng/ml, mean +/- SD, n = 7). These findings suggest that pituicyte GH response to GRF is intact and is not the cause of the observed impaired growth in patients with SCD.     

NELL2及其在促性腺激素释放激素分泌中的作用

机体的青春发育及生殖过程受下丘脑-垂体-性腺轴的调控.下丘脑促性腺激素释放激素(GnRH)神经元活化导致GnRH分泌增多是青春期启动的触发因素.GnRH神经元功能活动的调节机制非常复杂,有多种因子影响GnRH的分泌.谷氨酸作为最主要的兴奋性神经递质,可以通过多种机制促进GnRH的分泌.近年来有研究发现NELL2可能通过...     

Anabolic steroid and gonadotropin releasing hormone analog combined treatment increased pubertal height gain and adult height in two children who entered puberty with short stature

We studied the effect of gonadal suppression treatment in combination with anabolic steroid on pubertal height gain and adult height in two children who entered puberty with short stature. Patient 1 was a female with idiopathic short stature. She received combined treatment with an anabolic steroid (stanozolol) and a gonadotropin releasing hormone analog (leuprorelin acetate). Her pubertal height gain was 28.5 cm, which is greater than that in normal height girls (20-25 cm). Patient 2 was a male with Aarskog syndrome. Although his growth hormone (GH) secretion was normal, he received GH treatment. Since GH administration did not accelerate his growth, he received combined treatment with stanozolol and leuprorelin acetate. His pubertal height gain was 27.0 cm, which is greater than that observed in GH deficient boys treated with GH alone (21.9 cm). Combined treatment with stanozolol and leuprorelin acetate appears to be effective in increasing pubertal height gain and adult height in children who enter puberty with short stature.