scholarly journals Increased Final Height in Precocious Puberty after Long-Term Treatment with LHRH Agonists: The National Institutes of Health Experience

2001 ◽  
Vol 86 (10) ◽  
pp. 4711-4716 ◽  
Author(s):  
Karen Oerter Klein ◽  
Kevin M. Barnes ◽  
Janet V. Jones ◽  
Penelope P. Feuillan ◽  
Gordon B. Cutler Jr.

We report 98 children who have reached final adult height in a long-term trial of LHRH agonist treatment. These children were 5.3± 2.1 yr old at the start of treatment and were treated with either deslorelin (4 μg/kg·d sc) or histrelin (4–10 μg/kg·d) for an average of 6.1 ± 2.5 yr. Final height averaged 159.8 ± 7.6 cm in the 80 girls, which was significantly greater than pretreatment predicted height (149.3 ± 9.6 cm) but still significantly less than midparental height (MPH) (163.7 ± 5.6). Final height averaged 171.1 ± 8.7 cm in the 18 boys, which was significantly greater than pretreatment predicted height (156.1 ± 14.2 cm) but still significantly less than MPH (178.3 ± 5.2 cm). However, the average adult height of the 54 children who had less than a 2-yr delay in the onset of treatment was not significantly different from their MPH, and 21 children exceeded MPH. Final height sd score correlated positively with duration of treatment (P < 0.01), midparental height (P < 0.001), predicted height at the start of treatment (P < 0.001), and growth velocity during the last year of treatment (P < 0.001) and correlated inversely with delay in the onset of treatment (P < 0.001), age at the start of treatment (P < 0.001), bone age at the start of treatment (P < 0.001), bone age at the end of treatment (P < 0.001), breast stage at the start of treatment (P = 0.02), and bone age minus chronological age at the start of treatment (P = 0.001). We conclude that LHRH agonist treatment improves the final height for children with rapidly progressing precocious puberty treated before the age of 8 yr for girls or 9 yr for boys. Less delay in the onset of treatment, longer duration of treatment, and lower chronological and bone age at the onset of treatment all lead to greater final height. All children with onset of pubertal symptoms before age 8 in girls and age 9 in boys should be evaluated for possible treatment. Treatment is appropriate in children with rapidly progressing puberty, accelerated bone maturation, and compromise of adult height prediction, regardless of bone age or chronological age at time of evaluation. However, once treatment is considered appropriate, it should be initiated quickly, because longer delays lead to shorter final height. In addition, the longer the treatment is continued, the greater is the final height outcome.

Author(s):  
Carolina O. Ramos ◽  
Ana P M Canton ◽  
Carlos Eduardo Seraphim ◽  
Aline Guimarães Faria ◽  
Flavia Rezende Tinano ◽  
...  

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.


1999 ◽  
Vol 84 (10) ◽  
pp. 3575-3578 ◽  
Author(s):  
C. Bouvattier ◽  
J. Coste ◽  
D. Rodrigue ◽  
C. Teinturier ◽  
J. C. Carel ◽  
...  

Abstract GnRH agonists improve final height in girls with “true” precocious puberty. To test if a comparable effect can be obtained in older girls, we performed a long-term controlled study in 30 caucasian girls whose puberty started between 8.4 and 10 yr (9.4 ± 0.1 yr), a variant of normal called “advanced” puberty. At entry into trial, these girls had clinical, biological, and sonographic manifestations of puberty and a bone age greater than 10.9 yr. They were randomized 2:1 to receive 3.75 mg triptorelin im every 4 weeks for 2 yr (n = 20, group I) or no treatment (n = 10, group II). Mean height at inclusion was 135.2 ± 4.3 cm (+0.6 sds) in group I, 136.1 ± 4.2 cm (+0.8 sds ) in group II, with target height 157.6 ± 4.3 cm (group I) and 157.8 ± 4.7 cm (group II), and predicted height (Bayley-Pinneau) 154.1 ± 3.9 cm and 155.2 ± 3.7 cm. Although GnRH agonists transiently delayed sexual maturation as well as bone age and growth rate, they had no clear-cut long-standing effect, and final height was comparable in treated (157.6 ± 4.0 cm) and untreated girls (156.1 ± 5.3 cm) (NS).


1959 ◽  
Vol XXXII (IV) ◽  
pp. 563-574 ◽  
Author(s):  
H. Hortling ◽  
K. Wahlfors

ABSTRACT In 7 cases of dwarfism with markedly delayed closure of the epiphyses, methyltestosterone was administered sublingually in doses of 5–10 (25) mg daily in combination with thyroid hormone in doses of 25–120 mg daily for 2–7 years. At the institution of treatment the patients were 9, 11, 15, 15, 16, 17 and 20 years old and were 95, 125, 119, 124, 120, 135 and 125 cm in height respectively. The bone age was in all cases checked against Greulich & Pyle's radiographic tables (1950). During the first two years of therapy, 5 patients exhibited a more rapid increase of the bone age than was to be expected considering their chronological age. In 5 cases where the therapy was continued over a longer period of time, such a tendency was not demonstrable later, although the dosage of methyltestosterone was often somewhat increased. On the contrary, a retardation of the bone age development occurred, as compared with the chronological age. In none of the present cases have the epiphyses become closed, notwithstanding a considerable height increase in all cases, i. e. 15–29 cm depending on the length of the period of treatment, and the relatively advanced age of the patients at the time of writing when they are still under androgen therapy with or without thyroid medication. Provided that the bone age is continuously checked, it appears that methyltestosterone in small doses can safely be used in the treatment of dwarfism with delayed closure of the epiphyses. This trea[ill]ment proved to be of great importance from the point of view of the choice of a vocation as well as for the future life of the patients.


1999 ◽  
Vol 84 (2) ◽  
pp. 449-452 ◽  
Author(s):  
Anna Maria Pasquino ◽  
Ida Pucarelli ◽  
Maria Segni ◽  
Marco Matrunola ◽  
Fabio Cerrone

GnRH analogues (GnRHa) represent the treatment of choice in central precocious puberty (CPP), because arresting pubertal development and reducing either growth velocity (GV) or bone maturation (BA) should improve adult height. However, in some patients, GV decrease is so remarkable that it impairs predicted adult height (PAH); and therefore, the addition of GH is suggested. Out of twenty subjects with idiopathic CPP (treated with GnRHa depot-triptorelin, at a dose of 100 μg/kg im every 21 days, for at least 2–3 yr), whose GV fall below the 25th percentile for chronological age, 10 received, in addition to GnRHa, GH at a dose of 0.3 mg/kg·week sc, 6 days weekly, for 2–4 yr; and 10 matched for BA, chronological age, and duration of GnRHa treatment, who showed the same growth pattern but refused GH treatment, served to evaluate the efficacy of GH addition. No patient showed classical GH deficiency. Both groups discontinued treatment at a comparable BA (mean ± sem): 13.2 ± 0.2 in GnRHa plus 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 plus GnRHa showed an adult height significantly higher (P &lt; 0.001) than pretreatment PAH (160.6 ± 1.3 vs. 152.7 ± 1.7 cm). Target height (TH) was significantly exceeded. The group treated with GnRH alone reached an adult height not significantly higher than pretreatment PAH (157.1 ± 2.5 vs. 155.5 ± 1.9 cm). TH 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 GnRHa; whereas in patients treated with GnRHa alone, the gain was just 1.6 ± 1.2 cm (P = 0.001). Furthermore, no side effects have been observed either on bone age progression or ovarian cyst appearance and the gynecological follow-up in the GH-treated patients (in comparison with those treated with GnRHa alone). 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 during the conventional treatment with GnRHa, especially in patients with CPP, and a decrease in GV so marked as to impair PAH, not allowing it to reach even the third centile.


1996 ◽  
Vol 75 (4) ◽  
pp. 292-297 ◽  
Author(s):  
W Oostdijk ◽  
B Rikken ◽  
S Schreuder ◽  
B Otten ◽  
R Odink ◽  
...  

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A679-A679
Author(s):  
Gerhard Binder ◽  
Akie Nakamura ◽  
Roland Schweizer ◽  
Tsutomu Ogata ◽  
Maki Fukami ◽  
...  

Abstract Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. Long-term treatment effects of aromatase inhibitors are unknown. Retrospectively we collected data from file records of 7 boys (three sibling pairs and one sporadic case) with AEXS. Genetic analysis revealed upstream of CYP19A1 a 165,901 bp deletion in 4 German cousins, a 198,662 bp deletion in 2 Japanese brothers and a 387,622 bp tandem duplication in a Japanese boy. All boys developed prepubertal gynecomastia, at 9.0 yr of age (median; range: 7.0 - 11.0). Height was +1.20 SDS (-0.24 - +1.98); predicted adult height was -1.29 (-3.29 - +1.09 SDS). Four boys were treated with anastrozole 1.0 mg daily, while three reached adult height untreated. Treatment with anastrozole was stopped after 5.6 yr (4.0 - 6.8). Three treated boys exceeded height prognosis by 2.4, 6.9 and 8.1 cm; while one untreated fell below prognosis by 8.6 cm. One treated with a low dose and two untreated reached their prognosis. Adult heights were -0.91 SDS with anastrozole (-2.86 - -0.29) and -0.15 SDS without (-2.31 - -0.03). Distance to target height was -0.22 SDS with anastrozole (-1.72 - +0.52) and +0.54 SDS without treatment (+0.23 - +1.30). Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by aromatase inhibitor anastrozole (1 mg daily) promotes adult height in boys with AEXS.


Author(s):  
Gerhard Binder ◽  
Akie Nakamura ◽  
Roland Schweizer ◽  
Tsutomu Ogata ◽  
Maki Fukami ◽  
...  

Abstract Context Aromatase excess syndrome (AEXS) is a very rare disorder characterized by prepubertal gynecomastia, bone age acceleration, and early growth arrest. Heterozygote submicroscopic rearrangements within the promotor of CYP19A1 result in overexpression of aromatase and enhanced aromatization of androgens. Objective The objective was to study long-term treatment effects of an aromatase inhibitor. Methods Data from 7 boys with AEXS were retrospectively collected. Genetic analysis revealed upstream of CYP19A1 a 165 901 bp deletion in 4 German cousins, a 198 662 bp deletion in 2 Japanese brothers, and a 387 622 bp tandem duplication in a Japanese boy. Results All boys developed prepubertal gynecomastia, at median 9.0 years of age (range: 7.0-11.0). Height was +1.20 standard deviation score (SDS) (–0.24 to +1.98); predicted adult height was -1.29 SDS (-3.29 to +1.09). Four boys were treated with 1.0 mg of anastrozole daily, while 3 reached adult height untreated. Treatment with anastrozole was stopped after 5.6 years (4.0-6.8). Three treated boys exceeded their prognosis by 2.4, 6.9, and 8.1 cm, while 1 untreated boy fell below the prognosis by 8.6 cm. One treated with a low dose and 2 untreated reached their prognosis. Adult heights were –0.91 SDS with anastrozole (–2.86 to –0.29) and –0.15 SDS without (–2.31 to –0.03). Distance to target height was –0.22 SDS with anastrozole (–1.72 to +0.52) and +0.54 SDS without (+0.23 to +1.30). Conclusion Spontaneous growth in AEXS varied, even in the same family. Our data suggest that early started, long-term inhibition by anastrozole promotes adult height in boys with AEXS.


1991 ◽  
Vol 73 (6) ◽  
pp. 1235-1240 ◽  
Author(s):  
KAREN E. OERTER ◽  
PENELOPE MANASCO ◽  
KEVIN M. BARNES ◽  
JANET JONES ◽  
SUVIMOL HILL ◽  
...  

1979 ◽  
Vol 92 (3) ◽  
pp. 385-397 ◽  
Author(s):  
Kazue Takano ◽  
Naomi Hizuka ◽  
Kazuo Shizume ◽  
Yoko Hasumi

ABSTRACT Eighteen patients with pituitary dwarfism were treated for 1 7/12 to 6 years with human growth hormone (hGH) at a dose of 0.19–0.62 unit (U) per kg of body weight per week. The mean increment in height was 2.0 ± 0.4 and 8.8 ± 0.5 cm/year before and the first year after treatment of hGH, respectively. A significant positive correlation was observed between serum levels of somatomedin A and growth rate, especially in children with bone age below 10 and a duration of treatment of less than one year (r = 0.66, P < 0.005). Long-term treatment with hGH was accompanied by a decreasing response. However, the serum levels of somatomedin A did not decrease significantly. Therefore, decreased growth increment in these situations was not due to decreased serum levels of somatomedin A.


2014 ◽  
Vol 99 (11) ◽  
pp. 4086-4093 ◽  
Author(s):  
E. Kirk Neely ◽  
Rajiv B. Kumar ◽  
Sydney L. Payne ◽  
Sayali A. Ranadive ◽  
Diane I. Suchet

Context: Aromatase inhibitors are used off-label to treat short stature in peripubertal boys. Objective: To investigate short- and long-term hormonal and auxologic differences in short pubertal boys treated with letrozole (L) or anastrozole (A). Design: Patients are seen for laboratory evaluation and physical examination every 6 months, bone age yearly, DEXA and spine film every 2 years. They will be followed until they reach their final height. This is a preliminary report after 1 year of treatment. Setting: A single academic children's hospital outpatient clinic. Patients: Boys with age &gt;10 years, bone age ≤14 years, clinical and hormonal evidence of central puberty, and either height &lt; fifth percentile or predicted adult height (PAH) more than 10 cm below mid-parental height (MPH). Intervention: Letrozole (2.5 mg) or anastrozole (1 mg) was administered orally each day. Main Outcome Measures: Hormonal and clinical parameters, growth velocity, and change in bone age and PAH. Results: Thirty-nine boys have completed 1 year of treatment. Baseline means were age 14.1 years, PAH 166 cm, and testosterone 198 ng/dL. At 1 year, letrozole resulted in higher LH (L 6.1 ± 2.5 vs A 3.2 ± 1.7 IU/L) and testosterone (1038 ± 348 vs 536 ± 216 ng/dL) with lower estradiol (2.8 ± 2.8 vs 5.6 ± 2.9 pg/mL) and IGF-1 (237 ± 51 vs 331 ± 79 ng/mL). First year growth velocities were identical (7.2 cm/year), but an increase in PAH was greater in the anastrozole group (4.2 ± 3.5 vs 1.4 ± 4.4 cm, p = 0.03) after 1 year. Conclusions: We present first-year data from a direct comparison of anastrozole and letrozole for height augmentation in short pubertal boys. Letrozole was more potent in hormonal manipulation than anastrozole. First-year growth velocities were comparable, but improvement in PAH was greater in the anastrozole group. It remains to be seen if positive PAH trends will translate to increase in final height in either group.


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