Ignite Creation Date:
2024-05-06 @ 7:58 AM
Last Modification Date:
2024-10-26 @ 11:54 AM
Study NCT ID:
NCT02638922
Status:
UNKNOWN
Last Update Posted:
2016-04-06
First Post:
2015-12-13
Brief Title:
Evaluation and Treatment of Tall Statured Girls
Sponsor:
Rigshospitalet Denmark
Organization:
Rigshospitalet Denmark
Study Overview
Official Title:
Evaluation of 304 Danish Girls With Tall Stature Phenotypic Characteristics and Effects of Oral Administration of Natural 17β-Estradiol
Status:
UNKNOWN
Status Verified Date:
2016-04
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TallgirlsDK
Brief Summary:
Objective
To evaluate the phenotypic characteristics and diagnoses in a large cohort of 304 consecutive girls referred due to tall stature Furthermore to evaluate the effect of oral administration of 17β-estradiol on predicted adult height in constitutionally tall statured girls
Design
A single-centre retrospective observational study of 304 girls evaluated due to tall stature between 1993 and 2013
Setting
Tertiary referral centre for pediatric endocrinology
Participants
A total of 304 girls were evaluated for tall stature of whom 39 13 were excluded due to missing data reclassification overgrowth syndromes or associated comorbidities Another 58 19 girls did not fulfil auxological criteria for constitutionally tall stature CTS resulting in a total of 207 68 girls eligible for analysis
Main Outcome Measures
The effect of oral treatment with 17β-estradiol on height predicted adult height PAH final height and circulating hormones in constitutional tall statured girls
To evaluate the phenotypic characteristics and diagnoses in a large cohort of 304 consecutive girls referred due to tall stature Furthermore to evaluate the effect of oral administration of 17β-estradiol on predicted adult height in constitutionally tall statured girls
Design
A single-centre retrospective observational study of 304 girls evaluated due to tall stature between 1993 and 2013
Setting
Tertiary referral centre for pediatric endocrinology
Participants
A total of 304 girls were evaluated for tall stature of whom 39 13 were excluded due to missing data reclassification overgrowth syndromes or associated comorbidities Another 58 19 girls did not fulfil auxological criteria for constitutionally tall stature CTS resulting in a total of 207 68 girls eligible for analysis
Main Outcome Measures
The effect of oral treatment with 17β-estradiol on height predicted adult height PAH final height and circulating hormones in constitutional tall statured girls
Detailed Description:
17α-ethinylestradiol EE2 treatment of extreme tall stature has become increasingly debated and controversial In Sweden percutaneous epiphysiodesis operation is suggested as an alternative to EE2 treatment An alternative clinical practise was introduced 20 years ago when early treatment with oral administration of natural estrogens 17β-estradiol E2 was introduced in order to initiate or ensure rapid progression of puberty and epiphyseal closure in tall statured girls
A retrospective 20-year single center experience included evaluation of 304 tall statured girls and the possible clinical effects of oral administration of E2
Subjects and methods
Patients
The patient population consisted of girls who were referred with tall stature or overgrowth syndromes ICD10 344 and ICD10 DE874 DQ970 DQ873A DQ873B to the Department of Growth and Reproduction at Rigshospitalet in Copenhagen Denmark during a 20-years period between 1993 and 2013 A total of 304 patients were identified and the diagnoses were re-evaluated as part of the present study
Clinical data and medical history
Medical history was obtained using a structured review of patient record files Clinical data on pubertal development were obtained from each patient visit Puberty was evaluated by inspection and palpation of the breasts and s pubic hair according to Marshall and Tanner A wall-mounted stadiometer Holtain Ltd Crymych United Kingdom was used to measure standing height to the nearest 01 cm The girls were weighed on a digital electronic scale Seca delta model 707 Seca Hamburg Germany with a precision of 01 kg while wearing light clothing and no shoes BMI was calculated as weight kg divided by height m2 The Danish growth references published by Tinggaard et al was used in this study Boneage BA was calculated according to the methods of Greulich and Pyle GP using manual readings between 1993-2008 n368 and automated BA estimation from 2008-2013 n378 Target height was calculated as the sum of the mothers and fathers heights cm minus 13 cm divided by 2 Predicted Adult Height PAH was calculated using BoneXpert
17β-Estradiol treatment
The decision to initiate treatment with E2 was determined individually and made by the physician together with the patient and her parents depending on height SDS age PAH and target height Oral E2 was administered in increasing doses depending on age and pubertal stage The starting doses ranged between 02 mg E2 to 4 mg E2 The speed of dose increment depended on the individual girl age bone BA maturity pubertal stage and PAH The treatment consisted of 17β-estradiol supplemented with norethisteronacetat after 1-2 years of E2 or after the first menstrual bleeding Oral E2 treatment was administered in the form of Trisekvens Novo Nordisk Scandinavia AB Copenhagen Denmark Trisekvens Forte Novo Nordisk Scandinavia AB Copenhagen Denmark andor Femanest Sandoz AS Copenhagen Denmark Clinical and biochemical values were recorded at baseline and at each year thereafter The treatment was generally terminated when the X-ray showed closed epiphyseal lines at final or near-final 2 cmyear height
Laboratory analysis
Blood samples were drawn from the antecubital vein between 8 AM and 1 PM in the non-fasting state Blood samples were clotted and centrifuged and serum was stored at -20 Celsius until hormone analyses were performed Serum follicle-stimulating hormone FSH and luteinising hormone LH were measured by time-resolved immunofluorometric assays Delfia Wallac Turku Finland The detection limits dL for FSH and LH were 006 and 005 IUl respectively Intra- and interassay coefficients of variation CV were 5 in both gonadotropin assays Testosterone was measured by radioimmunoassay RIA Coat-a-count Diagnostic Products Corporation Los Angeles CA with a dL of 023 nmolL and intra- and interassay CV both 10 Serum sex hormone-binding globulin SHBG was measured by time-resolved immunofluorometric assays Delfia Wallac Turku Finland with a dL of 020 nmoll and intra- and interassay CVs of 58 and 64 respectively Serum insulin-like growth factor I IGF-I was measured using a highly sensitive in-house RIA as previously described by Juul et al The intra- and interassay CV were 39 and 87 respectively From 2008 IGF-I levels were determined by conventional immunoassays IMMULITE 2000 IGF-1 Siemens Healthcare Diagnostics Los Angeles CA USA on automated IMMULITE 2000 Siemens The CV were less than 4 and 9 respectively Serum insulin-like growth factor-binding protein 3 IGFBP-3 was measured by RIA as previously described by Blum et al The intraassay CV was 24 and the interassay CV was 107 Between 1993 and 2013 serum inhibin B was measured using one of two double antibody enzyme immunometric assays Inhibin B DSL or Oxford Bio-Innovation Inhibin B both with a dL of 20 pgml and intra- and interassay CV 16 Estradiol was measured by RIA Pantex Santa Monica CA before 1998 distributed by Immuno Diagnostic Systems Bolton UK with a dL of 18 pmolL and intra- and interassay CVs 8 and 13 respectively Only assays for IGF-I changed during the 20-year study period and we compared the two assays rigorously and ensured that they yielded similar results before changing the assay
Statistical analysis
Data are displayed as the median with interquartile range 25th75th percentiles andor the range min - max Results of treatment effect and IGF-I SD are displayed as the mean SD Hormone values below the dL of the assay were assigned a value corresponding to the dL2 The Mann-Whitney U test and students test was used to determine significance when comparing clinical auxological and laboratory data between groups and students t-test was used when comparing the effect of treatment within the group of girls treated with oral E2 All statistical analyses were performed using SPSS software IBM Corporation Armonk NY version 22
A retrospective 20-year single center experience included evaluation of 304 tall statured girls and the possible clinical effects of oral administration of E2
Subjects and methods
Patients
The patient population consisted of girls who were referred with tall stature or overgrowth syndromes ICD10 344 and ICD10 DE874 DQ970 DQ873A DQ873B to the Department of Growth and Reproduction at Rigshospitalet in Copenhagen Denmark during a 20-years period between 1993 and 2013 A total of 304 patients were identified and the diagnoses were re-evaluated as part of the present study
Clinical data and medical history
Medical history was obtained using a structured review of patient record files Clinical data on pubertal development were obtained from each patient visit Puberty was evaluated by inspection and palpation of the breasts and s pubic hair according to Marshall and Tanner A wall-mounted stadiometer Holtain Ltd Crymych United Kingdom was used to measure standing height to the nearest 01 cm The girls were weighed on a digital electronic scale Seca delta model 707 Seca Hamburg Germany with a precision of 01 kg while wearing light clothing and no shoes BMI was calculated as weight kg divided by height m2 The Danish growth references published by Tinggaard et al was used in this study Boneage BA was calculated according to the methods of Greulich and Pyle GP using manual readings between 1993-2008 n368 and automated BA estimation from 2008-2013 n378 Target height was calculated as the sum of the mothers and fathers heights cm minus 13 cm divided by 2 Predicted Adult Height PAH was calculated using BoneXpert
17β-Estradiol treatment
The decision to initiate treatment with E2 was determined individually and made by the physician together with the patient and her parents depending on height SDS age PAH and target height Oral E2 was administered in increasing doses depending on age and pubertal stage The starting doses ranged between 02 mg E2 to 4 mg E2 The speed of dose increment depended on the individual girl age bone BA maturity pubertal stage and PAH The treatment consisted of 17β-estradiol supplemented with norethisteronacetat after 1-2 years of E2 or after the first menstrual bleeding Oral E2 treatment was administered in the form of Trisekvens Novo Nordisk Scandinavia AB Copenhagen Denmark Trisekvens Forte Novo Nordisk Scandinavia AB Copenhagen Denmark andor Femanest Sandoz AS Copenhagen Denmark Clinical and biochemical values were recorded at baseline and at each year thereafter The treatment was generally terminated when the X-ray showed closed epiphyseal lines at final or near-final 2 cmyear height
Laboratory analysis
Blood samples were drawn from the antecubital vein between 8 AM and 1 PM in the non-fasting state Blood samples were clotted and centrifuged and serum was stored at -20 Celsius until hormone analyses were performed Serum follicle-stimulating hormone FSH and luteinising hormone LH were measured by time-resolved immunofluorometric assays Delfia Wallac Turku Finland The detection limits dL for FSH and LH were 006 and 005 IUl respectively Intra- and interassay coefficients of variation CV were 5 in both gonadotropin assays Testosterone was measured by radioimmunoassay RIA Coat-a-count Diagnostic Products Corporation Los Angeles CA with a dL of 023 nmolL and intra- and interassay CV both 10 Serum sex hormone-binding globulin SHBG was measured by time-resolved immunofluorometric assays Delfia Wallac Turku Finland with a dL of 020 nmoll and intra- and interassay CVs of 58 and 64 respectively Serum insulin-like growth factor I IGF-I was measured using a highly sensitive in-house RIA as previously described by Juul et al The intra- and interassay CV were 39 and 87 respectively From 2008 IGF-I levels were determined by conventional immunoassays IMMULITE 2000 IGF-1 Siemens Healthcare Diagnostics Los Angeles CA USA on automated IMMULITE 2000 Siemens The CV were less than 4 and 9 respectively Serum insulin-like growth factor-binding protein 3 IGFBP-3 was measured by RIA as previously described by Blum et al The intraassay CV was 24 and the interassay CV was 107 Between 1993 and 2013 serum inhibin B was measured using one of two double antibody enzyme immunometric assays Inhibin B DSL or Oxford Bio-Innovation Inhibin B both with a dL of 20 pgml and intra- and interassay CV 16 Estradiol was measured by RIA Pantex Santa Monica CA before 1998 distributed by Immuno Diagnostic Systems Bolton UK with a dL of 18 pmolL and intra- and interassay CVs 8 and 13 respectively Only assays for IGF-I changed during the 20-year study period and we compared the two assays rigorously and ensured that they yielded similar results before changing the assay
Statistical analysis
Data are displayed as the median with interquartile range 25th75th percentiles andor the range min - max Results of treatment effect and IGF-I SD are displayed as the mean SD Hormone values below the dL of the assay were assigned a value corresponding to the dL2 The Mann-Whitney U test and students test was used to determine significance when comparing clinical auxological and laboratory data between groups and students t-test was used when comparing the effect of treatment within the group of girls treated with oral E2 All statistical analyses were performed using SPSS software IBM Corporation Armonk NY version 22
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None