Growth hormone treatment during suppression of early puberty in adopted girls

Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotropin-releasing hormone (GnRH) analogues. During such treatment decreased growth velocity is frequent. The aim of this investigation was to study whether the addition of growth hormone (GH) to GnRH analogue treatment improves height velocity and final height in girls with early or precocious puberty. Forty-six girls with early or precocious puberty adopted from developing countries were randomized for treatment with GnRH analogue or a combination of GH and GnRH analogue. After 2 y of treatment the mean growth in the GH/GnRH analogue group was significantly higher, 14.6 cm, compared to 10.9 cm in the control group. The increase in bone age did not differ, while the difference in predicted adult height increased by 2.7 cm in favour of the combination group. Although data on final height are not yet available, combined GH/GnRH analogue treatment for 2 y resulted in a higher growth velocity and predicted final height compared to GnRH analogue treatment alone.     

Combined therapy with GnRH analog plus growth hormone in central precocious puberty

GnRH analogues (GnRHa) arrest pubertal development, and slow growth velocity (GV) and bone maturation, thus improving adult height in central precocious puberty (CPP). In some patients, however, GV decreases to such an extent that it compromises the improvement in predicted adult height (PAH) and therefore the addition of GH is suggested. Of 20 patients with idiopathic CPP (treated with GnRHa [depot-triptorelin] at a dose of 100 microg/kg every 21 days i.m. for at least 2-3 yr) whose GV fell below the 25th percentile for chronological age (CA), ten received, in addition to the GnRHa, GH at a dose of 0.3 mg/kg/wk, s.c. 6 days weekly, for 2-4 yr. Ten patients matched for BA, CA, and duration of GnRHa treatment who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of the addition of GH. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean +/- SEM): 13.2 +/- 0.2 yr in GnRHa + GH vs 13.0 +/- 0.1 yr in the control group. At the conclusion of the study all the patients had achieved adult height. Adult height was considered to be attained when the growth during the preceding year was less than 1 cm, with a BA of over 15 yr. Patients of the group treated with GH + GnRHa showed an adult height significantly higher (p<0.001) than pretreatment PAH (160.6 +/- 1.3 vs 152.7 +/- 1.7 cm). Height SDS for BA significantly increased from -1.5 +/- 0.2 at start of GnRHa to -0.21 +/- 0.2 at adult height (p<0.001). Target height was significantly exceeded. The GnRH alone treated group reached an adult height not significantly higher than pretreatment PAH (157.1 +/- 2.5 vs 155.5 +/- 1.9 cm). Height SDS for BA did not change (from -1.0 +/- 0.3 at start of GnRHa to -0.7 +/- 0.4 at adult height). Target height was just reached but not significantly exceeded. The gain in centimeters obtained calculated between pretreatment PAH and final height was 7.9 +/- 1.1 cm in patients treated with GH combined with GnRH analogue while in patients treated with GnRH analogue alone the gain was just 1.6 cm +/- 1.2 (p=0.001). Furthermore, no side effects, bone age progression, or ovarian cysts, were observed in GnRHa + GH treated patients. In conclusion, a gain of 7.9 cm in adult height represents a significant improvement which justifies the addition of GH for 2-3 yr to conventional treatment with GnRH analogues in patients with central precocious puberty, and with a decrease in growth velocity so marked as to impair predicted adult height to below the third percentile.     

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.     

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.     

长效促性腺激素释放激素类似物和甲孕酮治疗对真性性早熟女孩预测身高影响的比较

目的观察促性腺激素释放激素类似物（ＧｎＲＨａ）和甲孕酮用于治疗真性性早熟女孩,对其抑制性发育,减慢骨成熟和生长速度,改善成人期预测身高的作用。方法分别使用两种药物治疗两组特发性真性性早熟女孩各９例,时间６～１２个月,观察治疗前后的身高、性发育情况、骨龄、成人期预测身高等,并进行综合比较。结果两组患儿经治疗后,性发育情况大多数得到抑制。甲孕酮治疗组骨龄年增长为１１岁,身高年增长为７６ｃｍ,成人期预测身高治疗前后无改变。长效ＧｎＲＨａ组骨龄年增长为０２岁,身高年增长为５６ｃｍ,成人期预测身高治疗６个月时增长３１ｃｍ,较治疗前明显改善（Ｐ＜００１）,治疗１年时增长６４ｃｍ,较治疗６个月时更为明显（Ｐ＜００５）。结论长效ＧｎＲＨａ与甲孕酮相比较,除可抑制性发育进程外,还可有效减慢骨成熟和生长速度,最终改善成人期预测身高,治疗时间愈长,效果愈明显     

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.     

Management of puberty in growth hormone deficient children

The pubertal growth spurt accounts for approximately one-eighth of adult height and is regulated by complex hormonal interactions involving the somatotropic and gonadal axes. The observation that children with growth hormone deficiency (GHD) may fail to achieve an appropriate pubertal growth spurt led to the development of strategies to optimize GH therapy during puberty. In one strategy the dosage of GH is increased during puberty to support pubertal growth and in keeping with the physiological increase in serum levels of the hormone seen at that age. A different approach is to combine a GnRH analog (GnRHa) to GH to stop pubertal development, delaying epiphyseal fusion and prolonging peripubertal growth. Both strategies require caution. As regards the first strategy, too high doses of GH may shorten the pubertal time for growth; we found a small, nonsignificant, improvement in final height by increasing the dose by less than half. Preliminary results on the second strategy are more encouraging. However, manipulation of puberty should be limited to selected patients who show a statural height SDS for bone age unfavorable in terms of height prognosis.     

Combined Treatment with Gonadotropin-releasing Hormone Analog and Anabolic Steroid Hormone Increased Pubertal Height Gain and Adult Height in Boys with Early Puberty for Height

Twenty-one boys with a height of 135 cm or less at onset of puberty were treated with a combination of GnRH analog and anabolic steroid hormone, and their pubertal height gain and adult height were compared with those of untreated 29 boys who enter puberty below 135 cm. The mean age at the start of treatment with a GnRH analog, leuprorelin acetate depot (Leuplin^®) was 12.3 yr, a mean of 1.3 yr after the onset of puberty, and GnRH analog was administered every 3 to 5 wk thereafter for a mean duration of 4.1 yr. The anabolic steroid hormone was started approximately 1 yr after initiation of treatment with the GnRH analog. The mean pubertal height gain from onset of puberty till adult height was significantly greater in the combination treatment group (33.9 cm) than in the untreated group (26.4 cm) (p<0.0001). The mean adult height was significantly greater in the combination treatment group (164.3 cm) than in the untreated group (156.9 cm) (p<0.0001). The percentage of subjects with an adult height of 160 cm or taller was 90.5% (19/21) in the combination treatment group, and it was 13.8% (4/29) in the untreated group (p<0.0001). Since growth of the penis and pubic hair is promoted by the anabolic steroid hormone, no psychosocial problems arose because of delayed puberty. No clinically significant adverse events appeared. Combined treatment with GnRH analog and anabolic steroid hormone significantly increased height gain during puberty and adult height in boys who entered puberty with a short stature, since the period until epiphyseal closure was extended due to deceleration of the bone age maturation by administration of the GnRH analog and the growth rate at this time was maintained by the anabolic steroid hormone.     

Effect of combined treatment with gonadotropin releasing hormone analogue and growth hormone in patients with central precocious puberty who had subnormal growth velocity and impaired height prognosis

Growth hormone-insulin-like growth factor-I status and response to growth hormone therapy (0.6 IU/kg/week sc, six times a week for 12 months) were evaluated in 12 girls (chronological age 9.4 ± 1.6 years) suffering from central precocious puberty with growth velocity less than 4 cm/year and no substantial increase or decrease in predicted adult height during gonadotropin releasing hormone (Gn-RH) analogue treatment (D-Trp⁶-LH-RH, 60 μg/kg im/28 days). At baseline, large variations were observed in nocturnal growth hormone (GH) means (pathological values (< 3.6μg/l) 33.3%), stimulated levodopa GH peaks (pathological values (<10.0 μg/I) 28.6%) and serum insulin-like growth factor-I (IGF-I) levels. Neither GH nor IGF-I levels were correlated with growth velocity. During recombinant GH therapy, growth velocity increased significantly (baseline 3.0 ± 0.9 cm/year; 6 months 6.4 ± 1.9cm/year, p < 0.001 versus baseline; 12 months 6.0 ± 1.3cm/year, p < 0.001 versus baseline). There was a significant increase in height SDS for bone age (baseline –1.6 ±0.5 SDS; 12 months -1.04 ± 0.6SDS; p < 0.002) and in predicted adult height (baseline 152.0 ± 3.6cm; 12 months 155.9 ± 3.4cm; p < 0.002). Our results suggest that combined therapy with Gn-RH analogues and recombinant GH can improve growth velocity and predicted adult height in girls with central precocious puberty and impaired height prognosis during Gn-RH analogue treatment.     

Tamoxifen treatment of progressive precocious puberty in a patient with McCune-Albright syndrome

Treatment of progressive precocious puberty in patients with McCune-Albright syndrome (MAS) has traditionally been with aromatase inhibitors, such as testolactone. However, the use of these agents has been characterized by problems with both efficacy and compliance. We report a case of MAS in which tamoxifen proved to be a successful alternative in the treatment of progressive precocious puberty. An African-American female presented with MAS at 2-5/12 years. Frequent menses, skeletal maturation and growth acceleration prompted initiation of therapy with testolactone at 22 mg/kg/d. Over the next 13 months, the patient's puberty advanced unchecked, despite progressive increases in the dose of testolactone. At age 4 years, medication was discontinued due to treatment failure. At 4-6/12 years, bone age was 10 years, predicted adult height was 137 cm, and monthly bleeding continued. Tamoxifen was then begun on an experimental basis. In response, the patient experienced immediate cessation of menses, and had an abrupt decrease in the rates of pubertal progression and linear growth. This patient has now been maintained on tamoxifen for over three years with no apparent adverse effects. GnRH analogue therapy was begun when the onset of central precocious puberty was noted. Predicted adult height has improved to 154 cm and growth velocity and skeletal maturation remain stable. Our results suggest that tamoxifen may have a valuable role in the treatment of precocious puberty in patients with MAS and may lead to superior results compared with those achieved with aromatase inhibitors.     

11beta-hydroxylase deficiency: improvement of final height with growth hormone and gonadotropin-releasing hormone analog

Steroid 11beta-hydroxylase deficiency is the second most common cause of congenital adrenal hyperplasia. 11beta-hydroxylase intervenes in cortisol synthesis and its deficiency leads to accumulation of adrenal androgens--producing prenatal virilization and, subsequently, hyperandrogenism--as well as 11-deoxycorticosterone, leading to the development of hypertension. We describe a 7-year-old girl who was referred for pubarche and accelerated skeletal maturation due to 11beta-hydroxylase deficiency. Because the patient's predicted height was below her target height, the combination of gonadotropin-releasing hormone analog and growth hormone was added to oral glucocorticoid therapy. With this therapeutic strategy, the patient's predicted height improved significantly and the girl reached a final height in agreement with her target height at the age of 13 years and 6 months.     

Diagnosis and management of precocious puberty

The onset of pubertal development before the age of 8 years in girls or 9 years in boys constitutes precocious puberty. There are numerous causes of precocious puberty, which can be classified as central or peripheral precocious puberty. Central precocious puberty results from premature activation of the hypothalamic-pituitary-gonadal axis and thus presents with physical and hormonal findings similar to those found in normal puberty. Peripheral precocious puberty results from extrapituitary gonadotropin secretion or secretion of sex steroids independent of pituitary gonadotropins. All types of precocious puberty are characterized by rapid growth and advancement of skeletal age, leading to the paradox of the tall child becoming a short adult as a result of premature epiphyseal fusion. Long-acting GnRH agonists afford effective, selective, and reversible therapy of central precocious puberty without significant toxicity. GnRH agonists are not effective in managing the premature sexual maturation associated with peripheral precocious puberty, but a number of other agents have been used with some success. These agents include testolactone, ketoconazole, and medroxyprogesterone acetate. GnRH agonist treatment leads to an increase in predicted final height. To determine the true benefit of any of these agents in increasing ultimate height, there is a need for continuing studies in treated cohorts to follow growth patterns until adult stature is achieved.     

Predictive factors for the effect of gonadotrophin releasing hormone analogue therapy on the height of girls with idiopathic central precocious puberty

The factors influencing the final height of central precocious puberty patients treated with gonadotrophin releasing hormone (GnRH) analogues remain a critical issue. This study compares the predicted final height before and after GnRH analogue therapy to identify predictive factors for final height. Fourteen girls with idiopathic central precocious puberty were treated with a GnRH analogue. All had an active non-regressive form before therapy, full and permanent suppression of oestrogenic activity during therapy (duration >2 years, 3.1±0.3 years, mean ±SEM), and the pubertal pituitary-ovarian axis had normalized in all of them 1 year after the cessation of therapy. The mean predicted final height increased from 152±1.8 cm before therapy to 162.2±1.2 cm (P<0.01) at the last evaluation performed 4.5±0.3 years after the onset of therapy. The mean gain in predicted final height between the onset of therapy and the last evaluation was 10.2±1.1 cm. It was correlated with the following data recorded at the onset of therapy: bone age advance over chronological age (r=0.66,P<0.02), predicted final height at the onset of therapy (r=–0.76,P<0.001), and the difference between the target height and the predicted height at onset of therapy (r=0.76,P<0.001). We conclude that GnRH analogue therapy is more likely to improve final height prognosis in girls who initially present with a markedly advanced bone age and a great difference between their target and predicted heights. Both these parameters reflect the severity of the disease at diagnosis.This work was presented in part at the international symposium on GnRH analogues in cancer and human reproduction, Geneva, November 1990. Abstract, Gynecol Endocrinol 4 [Suppl 2]:101 (1990)     

Final height after combined growth hormone and GnRH analogue treatment in adopted girls with early puberty

Background: Girls adopted from developing countries often have early or precocious puberty, requiring treatment with gonadotrophin-releasing hormone (GnRH) analogues. During such treatment, decreased growth velocity is frequent. Aim: To study whether the addition of growth hormone (GH) to GnRH analogue treatment improves final height in girls with early or precocious puberty. Methods: Forty-six girls with early or precocious puberty (age ≤9.5 y) adopted from developing countries were randomized for treatment for 2-4 y with GnRH analogue, or with a combination of GH and GnRH analogue. Results: During treatment, the mean growth velocity in the GH/GnRH analogue group was significantly higher compared to the control group. Combined GH/GnRH analogue treatment resulted in a higher final height: 158.9 cm compared to 155.8 cm in the GnRH analogue-treated group. Three out of 24 girls (13%) in the combined group and nine of the 22 girls (41%) treated with GnRH analogue alone attained a final height below -2 standard deviation scores (SDS).

Conclusion: The difference between the two groups is statistically significant, and possibly of clinical importance. A future challenge is to identify a subgroup with clinically significant advantage of GH addition to GnRH analogue treatment. Being very short on arrival in Sweden and being short and young at start of treatment are possible indicators.     

Treatment with a gonadotropin-releasing-hormone analog and attainment of full height potential in a male monozygotic twin with gonadotropin-releasing hormone-dependent precocious puberty

We report on a pair of male monozygotic twins, one unaffected and the other affected with gonadotropin-releasing hormone (GnRH)-dependent precocious puberty, and discuss the role of treatment with a GnRH analog in the attainment of full height potential in GnRH-dependent precocious puberty. At 1.6 years of age, the affected twin was studied for tall stature (+3.8 SD), and was diagnosed as having GnRH-dependent precocious puberty due to a hypothalamic hamartoma of the tuber cinereum. He was treated with oral cyproterone acetate (110–170 mg/m² daily) from 1.8 through 5.0 years of age, with oral cyproterone acetate and intranasal buserelin acetate (700–900 μg/m² daily) from 5.0 through 7.5 years, and with intranasal buserelin acetate alone (1100– 1400 μg/m² daily) from 7.5 through 12.6 years. He attained a final height of 171.0 cm at 14.9 years of age (+0.10 SD) and his twin 170.0 cm at 15.3 years of age (−0.10 SD), with their target height being 174.5 ± 9.0 cm. Conclusion This study indicates that GnRH analog treatment may preserve near full height potential in some patients with GnRH-dependent precocious puberty. Received: 30 March 1999 / Accepted: 31 May 1999     

Prolongation of growth by treatment of 11-hydroxylase deficiency with depot-leuprolide, growth hormone, and hydrocortisone

A 4-10/12 year-old boy presented with tall stature and advanced secondary sexual characteristics. His bone age was 13 years giving him a height prediction of 147 cm. An initial 11-deoxycortisol level of 13,770 ng/dl and associated hypertension suggested the diagnosis of 11-hydroxylase deficiency, which was confirmed by dexamethasone suppression and genotyping. Treatment strategy was based on the premise that known hypothalamic priming resulting in early pubertal development could be averted by delaying puberty with leuprolide; also that effects of hydrocortisone and leuprolide on attenuating growth could be counteracted by growth hormone. The combined treatment resulted in a final height at age 12 years which was 25.4 cm greater than predicted, and bone density above average. We conclude that delaying puberty until an appropriate age, offsetting growth suppression, and improving bone mineralization can be effectively achieved using glucocorticoids, leuprolide and growth hormone in patients with 11-hydroxylase deficiency.     

45,X Turner综合征合并中枢性性早熟1例报告并文献复习

目的总结Turner综合征(TS)合并中枢性性早熟的诊断和治疗经验,提高对该病的认识。方法报道1例45,X TS合并中枢性性早熟诊断、治疗和随访病例,对相关文献进行复习。结果患儿,女,7.5岁,因"乳房增大半年"就诊。身高117.9 cm(P_(7.2)),体重32.5 kg,肥胖外观,无高腭弓、颈蹼、盾形胸和肘外翻,乳房Tanner分期Ⅱ期,心肺查体未见异常,外阴阴毛Tanner分期Ⅰ期。辅助检查:促性腺激素释放激素(LHRH)激发试验峰值:黄体生成素(LH)11.9 U·L~(-1),卵泡刺激素(FSH)34.2 U·L~(-1),雌二醇(E2)39.3 ng·L~(-1)。盆腔超声示卵巢增大。骨龄9.7岁。应用促性腺激素释放激素类似物(GnRHa)治疗2.7年后,身高131.4 cm,骨龄12岁,联合重组人生长激素(rh GH)继续治疗2.3年,身高148.4 cm,骨龄13岁。停药1年半后身高154.2 cm,接近遗传靶身高,检测LH 11.9 U·L~(-1),FSH 50.5 U·L~(-1),E2 38.9ng·L~(-1),染色体:45,X。系统文献检索国外仅有6例TS合并中枢性性早熟的病例报告,其中5例染色体为嵌合体,1例为1条X染色体的片段缺失。结论单体型TS可出现中枢性性早熟,GnRHa联合rh GH治疗能够改善患儿成年终身高。     

Accelerated versus slowly progressive forms of puberty in girls with precocious and early puberty. Gonadotropin suppressive effect and final height obtained with two different analogs

OBJECTIVES: To distinguish which children with precocious puberty (PP) and early puberty (EP) should be treated and which followed without therapy. To determine the effect of GnRH analog treatment on the final height of treated patients and compare the effect of two different analogs on gonadotropin suppression and final height. STUDY DESIGN: Sixteen females with PP or EP with a mean chronological age (CA) of 8.8 +/- 1.4 years and a mean bone age (BA) of 10.8 +/- 1.3 years were treated for a mean of 2.7 +/- 1.0 years with a GnRH analog (triptorelin or leuprolide acetate; group A), while 21 girls with a mean CA of 8.5 +/- 1.0 years, a mean BA of 9.7 +/- 1.4 years and a predicted adult height of >155 cm were followed without therapy (group B). Criteria for treatment were one of: a. predicted adult height (PAH) of <155 cm initially or at any time during follow up; b. PAH over 155 cm with a dramatic decrease in PAH over a 6-month follow-up period; c. advanced and rapidly progressing breast development for age (Tanner 3 before the age of 9 years). RESULTS: GnRHa therapy suppressed gonadotropins in group A, while gonadotropins increased gradually in group B. Height velocity (HV) decreased in group A, while it remained accelerated in group B; BA increased a mean of 1.7 +/- 0.5 years in group A and 3.2 +/- 0.3 years in group B. This resulted in a height increase in group A from a baseline PAH of 153.7 +/- 1.2 cm to a final height (FH) of 160.9 +/- 4.0 cm (p <0.001), clearly above their target height (TH) of 157.7 +/- 4.2 cm. The height of group B children did not change over time (164.1 +/- 4.1 cm before therapy and 166.0 +/- 6.0 cm at FH), both above their TH. The mean leuprolide acetate dose utilized in this study decreased during treatment, while both the initial and final triptorelin dose remained unchanged. Adequate gonadotropin suppression (peak level of LH and FSH of <2 IU/l after i.v. GnRH stimulation) was noted with both leuprolide acetate and triptorelin, although LH suppression was slightly more pronounced with triptorelin. BA advanced 1.8 +/- 0.4 years during leuprolide acetate treatment and 1.5 +/- 0.3 years with triptorelin, so that FH increased a mean of 5.5 +/- 1.3 cm with leuprolide acetate and 8.7 +/- 2.2 cm with triptorelin. CONCLUSIONS: PAH of <155 cm before or during therapy, PAH of >155 cm with a dramatic decrease in predicted height over a 6-month follow-up period and/or advanced and rapidly progressing breast development in girls with PP or EP were useful parameters in deciding which patients to treat. GnRHa therapy suppressed gonadotropins, HV and bone maturation in children with an accelerated form of PP or EP, resulting in a significant height increase. Final height remained stable over time in untreated patients. Adequate gonadotropin suppression was noted with both analogs, although with the doses of analog used in our study, LH and BA suppression were more pronounced with triptorelin, resulting in a larger height gain.     

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.     

促性腺激素释放激素类似物在儿童中枢性性早熟中的应用

促性腺激素释放激素(GnRH)依赖性性早熟/中枢性性早熟(GDPP/CPP)是儿科内分泌系统的常见病之一,促性腺激素释放激素类似物(GnRHa)是国际上治疗CPP的主要药物,其通过抑制下丘脑-垂体-性腺轴的活动和性激素分泌,减缓CPP患儿骨龄进展、改善成年身高。在临床实践中,仍需要不断探索GnRHa治疗的获益人群,探讨...