scholarly journals OR15-05 Gain in Near Adult Height Using the Combination of an LHRH Analogue and an Aromatase Inhibitor in Early Maturing Girls with Compromised Growth. The “Gail” Study ISRCTN11469487

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dimitrios T Papadimitriou ◽  
Eleni Dermitzaki ◽  
Maria Papagianni ◽  
Kleanthis Kleanthous ◽  
George Mastorakos
Keyword(s):  
Adult Height ◽  
Combined Therapy ◽  
Final Height ◽  
Combined Treatment ◽  
Bone Age ◽  
Early Puberty ◽  
Lhrh Analogue ◽  
Early Maturing ◽  
Group A ◽  
Group B

Abstract Background. Third generation aromatase inhibitors (AI), as monotherapy, have never been used to increase predicted adult height in girls. Our previously published GAIL study has shown that the combination of anastrozole to an LHRH analogue for 24 months is safe and effective in ameliorating PAH in girls with early puberty +1.21 SDS (+7.51 cm) compared to inhibition of puberty alone +0.31 SDS (+1.92 cm), p=0.001 (1). Objective and Hypotheses. We assessed the final height of the girls who participated in the GAIL study compared to the predicted after 24 months of combined treatment and additionally the efficacy of anastrozole monotherapy after completion of the combined treatment in further improving final height. Methods. We measured adult (i.e. age 16.5 yrs) or near adult height (i.e. at bone age 14 yrs) of the 40 girls who participated in the GAIL study and were divided in two groups Group A (20 girls on anastrozole + leuprorelin) and Group B (20 girls on Leuprorelin alone). Group A was further randomized into two subgroups. Group A1 (10 girls), after completion of the combined therapy, received anastrozole 1 mg/day as monotherapy until bone age of 14 yrs with a 6-month follow-up. Group A2 (10 girls) had stopped the combined therapy at 24 months or 11 yrs of age and were recalled for adult (or near) height evaluation. Results. Adult or near adult height (NAH) exceeded the predicted at the completion of the initial phase of the GAIL study in all three groups but the result was statistically significant only in Group A1: NAH-PAH = Group A1: +3.85 cm (+0,62 SDS) p=0.001, Group A2: +1,6 cm (+0,26 SDS) p=0.26, Group B: +1,7 cm (+0,3 SDS) p = 0.09. Gain in Group A1 was significantly greater to that of Group A2 (p=0.046) and Group B (p=0.035). Conclusion. In early maturing girls with compromised growth, treatment for 2 yrs or until the age of 11 yrs with LHRH analogue plus anastrozole 1mg/day, the gain is +9.7cm in total when treated with anastrozole monotherapy until they reach NAH, whereas it is +7.4 cm if they do not continue with the monotherapy and only +3.6 cm when treated with an LHRHa only. As a result, the combination therapy continued with anastrozole monotherapy, ends in the shortest distance from target height. This implies that the addition of the anastrozole to an LHRHa apart from being safe, is effective in ameliorating substantially Near Adult Height making the intervention meaningful. Reference: (1) Papadimitriou DT, Dermitzaki E, Papagianni M, Papaioannou G, Papaevangelou V, Papadimitriou A. Anastrozole plus leuprorelin in early maturing girls with compromised growth: the “GAIL” study. Endocrinol Invest. 2016 Apr;39(4):439-46]

Combined treatment with growth hormone and gonadotropin-releasing hormone analogues in children with isolated growth hormone deficiency

1992 ◽  
Vol 127 (4) ◽  
pp. 307-312 ◽  
Author(s):  
Giuseppe Saggese ◽  
Graziano Cesaretti ◽  
Giuliana Andreani ◽  
Carla Carlotti
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Combined Therapy ◽  
Final Height ◽  
Combined Treatment ◽  
Bone Age ◽  
Height Velocity ◽  
Gnrh Analogue ◽  
Early Puberty ◽  
Gnrh Analogues

In subjects with an isolated GH deficiency the inhibition of puberty by GnRH-analogue administration may be attempted to delay the onset, or to prolong the duration, of pubertal maturation in order to improve final height. We report our experience on the matter in 10 subjects (6M, 4F) suffering from isolated GH deficiency with a chronological age ranging from 6.5 to 10.6 years at diagnosis. After a period of 1–5.1 years of GH treatment, GnRH-analogues (long-acting D-Trp-6-GnRH) were added to GH for 12 months, when six subjects were still prepubertal and four in early puberty. During combined therapy, a regression in pubertal development was shown in three out of four children in early puberty, while serum testosterone or estradiol decreased. Height velocity decreased (from 5.23±1.49 (mean±sd) to 4.12±0.67 cm/year; p<0.02), whereas height sd scores for bone age increased (from −0.75±0.42 to −0.47±0.55; p<0.02). During the year of combined therapy, bone age increased only 0.57±0.27 years. The values for predicted height (TW2 and Bayley-Pinneau method) after combined treatment were also higher than those after treatment with GH alone (p<0.02 and p<0.001, respectively). Our preliminary data showed that the addition of GnRH-analogues to GH in subjects with isolated GH deficiency reduces the effect of GH on height velocity, but determines an improvement in statural prognosis, although a proper answer will not be obtained until final height has been achieved.

scholarly journals Exaggerated Premature Adrenarche in Boys: Comparative Study of a Therapeutic Intervention With the Aromatase Inhibitor Anastrozole Versus Morning Low Dose Hydrocortisone

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A666-A667
Author(s):  
Dimitrios T Papadimitriou ◽  
Eleni Dermitzaki ◽  
Kleanthis Kleanthous ◽  
Anastasios Papadimitriou ◽  
George Mastorakos
Keyword(s):  
Aromatase Inhibitors ◽  
Low Dose ◽  
Adult Height ◽  
Late Onset ◽  
Blood Lipid ◽  
Bone Age ◽  
Treated Group ◽  
Premature Adrenarche ◽  
Group A ◽  
Group B

Abstract Background: In boys, idiopathic premature adrenarche (IPA) is defined as the appearance of pubic or axillary hair/odor before the age of 9 yrs, not due to pathology of the adrenal glands. Exaggerated Adrenarche (EXAD), occurring in 10-15% of children with IPA, is characterized by an elevated &gt;10 DHEA/Δ4 ratio (theoretically indicating reduced 3-β-HSD activity) and accelerated bone age (BA) maturation, continuously increasing the projecting distance from the target height (TH) curve, beyond the one observed in the pattern of Constitutional Advancement of Growth (CAG), eventually leading to short stature (SS). It is traditionally successfully treated with a morning (6-8 am) low dose of hydrocortisone (8 mg/m2) in order to reduce the androgens produced and delay BA progression, similarly to the standard treatment of non-classical (late-onset) CAH. Third generation aromatase inhibitors (AI) have been shown to delay BA by inhibiting the peripheral aromatization of androgens and are being widely used off-label to treat short SS in boys. Aims: To evaluate the effectiveness of the AI anastrozole in delaying BA in boys with EXAD. Methods: 39 boys with advanced BA and a predicted adult height (PAH) &lt;170cm and &gt; -1SDS from TH) were included. Group-A (n=28) received anastrozole 1mg x 1 p.o. and group-B (n=11) low dose (8 mg/m2) hydrocortisone at 6-8 am for at least 3 yrs. All measurements were made on the same height meter by the same examiner. The two groups did not differ in terms of age at intervention onset: 8.6 in group A vs 8.74 yrs in group B, TH: 175.7 vs 175.7 cm, PAH: 168.4 vs 167.8 cm and BA advancement: +2.3 yrs in group A vs +2.4 yrs in group B. A 6-month follow-up included clinical examination, BA assessment, and laboratory tests (general blood, lipid chart, LH, FSH, TESTO, E2, E1, and complete calcium metabolism). Lumbar spine DEXA scan and X-Ray was performed on an annual basis. Results: Both groups had a statistically significant gain in PAH after 3yrs of treatment: Group A +10.3 cm (1.53 SD), p&lt;0.001, and group B +7.1 cm (1.06 SD), p=0.007. Thus, group A exceeded their TH by +3cm (0.45 SDS) and group B reached -0.8cm (-0.11 SDS) from their TH, p=0.03. The reduction of BA advancement was statistically significant in both groups (p&lt;0.05), with superiority of the anastrozole-treated group: at 3yrs in group A BA advancement was +0.48 yrs, and at group B +1.24 yrs (p&lt;0.001). No clinical adverse events or abnormal tests were noted in any of the groups. Bone density and vertebral morphology was not affected within or between groups. Conclusions: Aromatase Inhibitors may have a place in managing exaggerated adrenarche in boys, showing superiority to traditional low-dose hydrocortisone in improving predicted adult height and delaying bone age maturation, but notably by overcoming quality of life and compliance issues associated with hydrocortisone therapy (mandatory 6-8 am).

scholarly journals Anastrozole Improves Near Adult Height in Boys With Compromised Height Potential, as Monotherapy or in Combination With a GnRH Analogue

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A673-A673
Author(s):  
Dimitrios T Papadimitriou ◽  
Eleni Dermitzaki ◽  
Maria Papagianni ◽  
Kleanthis Kleanthous ◽  
Anastasios Papadimitriou ◽  
...  
Keyword(s):  
Adult Height ◽  
Bone Age ◽  
Height Velocity ◽  
Gnrh Analogue ◽  
Cytochrome P450 Enzyme ◽  
Bone Maturation ◽  
X Ray ◽  
Group A ◽  
Group B

Abstract Background: Bone maturation depends mainly on locally produced estrogens by aromatization. Third generation aromatase inhibitors (AIs) are being widely used off-label to improve predicted adult height (PAH) in boys as well as in girls, either as monotherapy or in combination with growth hormone and/or puberty inhibition. They induce reverse binding inhibiting the activity of aromatase (a cytochrome P450 enzyme), which catalyzes the conversion of androstenedione and testosterone to estrone and estradiol, respectively. While numerous studies have shown that AIs delay bone maturation and improve PAH, data on near-adult height (NAH) of children treated with AIs are lacking. Aims: To compare results on NAH of boys treated with anastrozole either as monotherapy or in combination with pubertal inhibition (for at least 1yr at onset). Methods: 159 boys with advanced bone age (BA) and PAH &lt;170 cm that received anastrozole 1 mg/day p.o. either as monotherapy (n=76, group A) or as co-therapy with a GnRH analogue for at least 1yr and then as monotherapy (n=83, group B) until bone age of 15-16 yrs were included. Data on boys that reached NAH (BA at least 16 yrs with height velocity &lt;2 cm/yr) were analyzed: group A, n=16 with PAH 167.3 and TH 170.9 and group B, n=10 with PAH 165.5 and TH 171.7 cm. Measurements were made on the same height meter by the same examiner. The choice of therapeutic intervention was made randomly. Groups A and B did not differ in terms of age at intervention onset, TH or PAH. During treatment, they underwent a 6-month follow-up that included clinical examination, BA, and laboratory tests at 8:00 hrs (general blood count, lipid chart, LH, FSH, testosterone, estradiol, estrone, and complete calcium metabolism), with lumbar spine DEXA (Dual Energy X-ray Absorptiometry) and X-ray performed annually. Results: The duration of anastrozole treatment was 3.9 yrs in group A, and 4.6 yrs in group B (where the GnRHa was administered for at least 1 yr) and the median age at intervention onset was 11.04 and 11.8 yrs, respectively. Both groups had a statistically significant gain in NAH with no difference between them: for group A 3.6 cm (+0.53 SD, p=0.002) and for group B 4.8 cm (+0.71 SD, p=0.0007). Thus, distance from TH was finally 0 cm for group A and -1.5 cm (0.19 SD) for group B. According to the definition of NAH, the adult height of the two groups is expected to be about 2% higher. Follow-up showed no side effects on their biochemical or lipid profile, bone density and vertebral architecture. Conclusions: Anastrozole therapy is safe and effective in improving adult height in boys with advanced puberty and poor height prediction, either as monotherapy or in combination with pubertal inhibition.

scholarly journals Comparison of Two Different Dosing Regimens with Lymecycline, in Association with Adapalene, in Inflammatory Acne

2005 ◽  
Vol 3 (2) ◽  
pp. 89-95 ◽  
Author(s):  
G.A. Vena ◽  
N. Cassano ◽  
G. Alessandrini ◽  
G. Carrieri ◽  
D. Fai ◽  
...  
Keyword(s):  
Combined Therapy ◽  
Combined Treatment ◽  
High Dose ◽  
Acne Lesion ◽  
Dosage Regimens ◽  
Therapeutic Value ◽  
Dosing Regimens ◽  
Group A ◽  
Group B

Combined treatment with oral lymecycline and topical adapalene has been shown to induce greater and faster improvement of acne than monotherapy with lymecycline. We wanted to evaluate the effects of combined therapy with topical adapalene (cream or gel) plus oral lymecycline used at different dosages (group A: 300mg/day for 2 weeks and then 150mg/day for 14 weeks; group B: 300mg/day for 16 weeks) in 242 patients with inflammatory acne. Both dosage regimens were well tolerated in the majority of patients and significantly improved both the acne lesion count and seborrhoea. There was a trend towards a greater reduction of seborrhoea and nodules in patients of group B. After the initial 16-week phase, patients entered an 8-week follow-up phase, consisting of the use of adapalene monotherapy. The results obtained after this phase confirm the therapeutic value and the favourable tolerability of adapalene as maintenance treatment after successful treatment of inflammatory acne. At the same time, a significantly reduced count of comedones was observed in patients of group B as compared with group A, suggesting that prolonged use of high-dose lymecycline may have a more pronounced influence on comedogenesis.

Non-classical 21-hydroxylase deficiency in infancy and childhood: the effect of time of initiation of therapy on puberty and final height

1997 ◽  
Vol 136 (2) ◽  
pp. 188-195 ◽  
Author(s):  
Naomi Weintrob ◽  
Zvi Dickerman ◽  
Elliot Sprecher ◽  
Avinoam Galatzer ◽  
Atalia Pertzelan
Keyword(s):  
Final Height ◽  
Bone Age ◽  
Peak Height ◽  
Height Velocity ◽  
Peak Height Velocity ◽  
Hydroxylase Deficiency ◽  
Group A ◽  
Parental Height ◽  
Group B ◽  
21 Hydroxylase Deficiency

Abstract Objective: To review the characteristics of children with non-classical 21-hydroxylase deficiency (NC-21-OHD) diagnosed during infancy and childhood, and to evaluate the relationship of pubertal and bone age maturation at initiation of glucocorticoid therapy with the course of puberty and final height. Design: We retrospectively compared the course of puberty, growth pattern and final height in two groups of patients: group A (two males, six females), hydrocortisone (HC) treatment 7·5–15 mg/m2 per 24 h, initiated ≥1 year before onset of true puberty and group B (seven females), treatment started with the first signs of true puberty present. Participants: Thirteen girls and two boys with NC-21-OHD diagnosed at age range 0·5–10·6 years were followed-up for 9·0 ± 3·8 years (mean±s.d.). Therapy with HC was initiated because of signs of hyperandrogenism, accelerated growth and bone maturation, or true precocious puberty. The HC dose was adjusted according to linear growth and basal plasma androgen levels. Results: Puberty and peak height velocity developed significantly earlier in the girls of group B: gonadarche at 7·9 ± 1·4 years and peak height velocity at 9·2 ± 1·4 years vs 10·2 ± 0·4 years (P = 0·002) and 11·5 ± 0·7 years (P = 0·006) in group A. Menarche, however, occurred only slightly earlier in group B (12·0 ± 1·1 vs 12·8 ±0·5 years, P = 0·068). All eight children in group A achieved a final height within the range of their mean parental height standard deviation scores (SDS) in comparison with only 1/7 in group B (P = 0·0014). Seven of eight patients who started therapy before a bone age of 9 years achieved a final height within the parental height SDS range, compared with 2/7 who started therapy later (P = 0·041). The final height SDS was significantly better for group A (0·05 ± 0·19, mean ± s.e.m.) than group B (−1·63 ± 0·23, P = 0·0007), even when adjusted for a significant effect of the mean parental height SDS (A, −0·63 ± 0·28; B, −0·89 ± 0·31, P = 0·0245, ANCOVA). Conclusion: Every child with signs of excess androgen activity or early puberty should be studied for the possibility of NC-21-OHD. Screening programs for populations with a high frequency of the gene for NC-21-OHD would facilitate early diagnosis and treatment. Pubertal stage and bone age at the introduction of therapy dictate height prognosis. Initiation of therapy before puberty with careful follow-up and HC dose adjustment can assure the achievement of genetic adult height. European Journal of Endocrinology 136 188–195

Height Increment and Laboratory Profile of Boys Treated With Aromatase Inhibitors With or Without Growth Hormone

2017 ◽  
Vol 49 (10) ◽  
pp. 778-785 ◽  
Author(s):  
Ludmila Pedrosa ◽  
Joice de Oliveira ◽  
Paula Thomé ◽  
Cristiane Kochi ◽  
Durval Damiani ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Aromatase Inhibitors ◽  
Adult Height ◽  
Final Height ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Bone Age ◽  
Height Loss ◽  
Retrospective Data Analysis ◽  
Height Gain

AbstractAromatase inhibitors (AIs) have been used to recover height loss due to their capacity to delay growth plate closure. Long-term studies describing final heights are needed to determine the efficacy and safety profiles of these drugs for the treatment of impaired growth. This study aims to identify the therapeutic efficiency of AIs in improve growth and to describe potential adverse effects during treatment. Retrospective data analysis of 96 adolescents, among which 22 patients already attained near-final height, were followed at outpatient clinics of two referral centers. Patients were all in puberty and present idiopathic decrease in predicted adult height. Patients were treated with Anastrozole (ANZ: 1 mg/day) or Letrozole (LTZ: 2.5 mg/day) with/without recombinant human growth hormone (0.05 mg/kg/day) for 1.0 to 3.5 years (2.1±1.2 years). Height gain, body mass index, lipid, liver enzyme, gonadotropins and testosterone levels were described before and at the end of treatment. Predicted adult height (PAH) and NF height were compared with the TH. The height SDS (adjusted to bone age) significantly increased (p<0.05) in all groups [0.8±0.7 (ANZ), 0.7±0.7 (ANZ+GH), 0.3±0.5 (LTZ), and 1.2±0.8 (LTZ+GH)]; the latter group exhibited the highest increment of PAH and growth recovery to the TH (p<0.004). No significant side effects were observed. AI treatment, especially when used in association with GH was able to improve growth and the attainment of familial target height.

Aromatase excess syndrome in a Chinese boy due to a novel duplication at 15q21.2

2019 ◽  
Vol 32 (1) ◽  
pp. 85-88 ◽  
Author(s):  
Xinrui Tan ◽  
Xiaochuan Wu ◽  
Jie Chen ◽  
Yan Wu ◽  
Shijun Li ◽  
...  
Keyword(s):  
Adult Height ◽  
Linear Growth ◽  
De Novo ◽  
Final Height ◽  
Clinical Manifestations ◽  
Bone Age ◽  
Autosomal Dominant Disorder ◽  
Case Presentation ◽  
Growth Promoting ◽  
Pubertal Gynecomastia

Abstract Background Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder caused by CYP19A1 overexpression. Clinical manifestations of AEXS include pre- or peri-pubertal gynecomastia, advanced bone age and compromised adult height. Case presentation Here we report an 8-year-old boy diagnosed with AEXS by chromosomal array that revealed a 1.1 Mb novel de novo duplication at 15q21.2, with a predicted final height of 157.4 cm. We prescribed letrozole and growth hormone (GH) to maximize his linear growth. Without further bone age advancement, his height increased from 137.7 cm to 144 cm after an 8-month treatment period. Conclusions We identified a novel duplication at 15q21.2 in AEXS, and found that aromatase inhibitor (AI) plus GH might provide a better growth-promoting approach for AEXS patients.

Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency

1982 ◽  
Vol 99 (2) ◽  
pp. 166-173 ◽  
Author(s):  
M. Zachmann ◽  
D. Tassinari ◽  
W. Sorgo ◽  
G. U. Exner ◽  
B. Kempken ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Single Dose ◽  
Growth Hormone Deficiency ◽  
Bone Age ◽  
Urine Samples ◽  
Hormone Deficiency ◽  
Cortisol Response ◽  
Transient Impairment ◽  
Group A ◽  
Group B

Abstract. Twentythree boys with delayed adolescence (age 15.7 ± 2.0, bone age 12.4 ± 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirtyseven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 ± 8 μg/m2/12 h) and 13 with an insufficient (191 ± 16 μg/m2/12 h) THS response. Values in the second and third sample were higher, indicating a dealyed response. In 12 tests (group B), the results were normal (1016 ± 143 μg/m2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.

scholarly journals EFFECTIVENESS OF C1-C2 SUSTAINED NATURAL APOPHYSEAL GLIDE COMBINED WITH DRY NEEDLING ON PRESSURE POINT THRESHOLD AND HEADACHE DISABILITY IN CERVICOGENIC HEADACHE.

2018 ◽  
Vol 11 (1) ◽  
pp. 171 ◽  
Author(s):  
Ramesh Chandra Patra ◽  
Patitapaban Mohanty ◽  
Ajay P Gautam
Keyword(s):  
Therapy Group ◽  
Combined Treatment ◽  
Cervicogenic Headache ◽  
Dry Needling ◽  
Pressure Point ◽  
Cervicogenic Headaches ◽  
Group A ◽  
The Mean ◽  
Headache Disability ◽  
Group B

 Objective: The main objective of this study was to evaluate the effectiveness of dry needling and mulligan C1-C2 sustained natural apophyseal glides (SNAGs) in increasing pressure point threshold and reducing headache disability in patients with CGH.Methods: This study was conducted on 150 patients. They were divided into three groups for the purpose of the study. Group A was referred to as the dry needling group. They were subjected to dry needling for treating the pain. Group B was the manual therapy group. The patients in this group were subjected to C1-C2 SNAGs. Group C was the combined group. Patients belonging to this group were given C1-C2 SNAGs along with dry needling.Results: Statistical analysis paired t-test was used for comparison of the mean within every group where it showed significant improvement in all the parameter (p<0.05).Conclusion: There was a consistent reduction in tenderness and improvement in disability of the patients belonging to all groups. However, Group C, where the patients were subjected to combined treatment, showed better results. Results of this study indicate that dry needling along with mulligan C1-C2 SNAGs is more beneficial in patients suffering from cervicogenic headaches.

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