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dc.contributor.authorMurray, Robert D
dc.contributor.authorSkillicorn, C J
dc.contributor.authorHowell, Simon J
dc.contributor.authorLissett, Catherine A
dc.contributor.authorRahim, Asad
dc.contributor.authorShalet, Stephen M
dc.date.accessioned2009-12-14T15:39:12Z
dc.date.available2009-12-14T15:39:12Z
dc.date.issued1999-06
dc.identifier.citationDose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults. 1999, 50 (6):749-57 Clin. Endocrinol. (Oxf)en
dc.identifier.issn0300-0664
dc.identifier.pmid10468947
dc.identifier.doi10.1046/j.1365-2265.1999.00722.x
dc.identifier.urihttp://hdl.handle.net/10541/87905
dc.description.abstractOBJECTIVE: Previous studies of GH replacement in adults have used unselected cohorts of GH deficient (GHD) adults and weight-based dosing regimens resulting in supraphysiological serum IGF-I levels and a high frequency of side-effects and withdrawal from these studies. By choosing patients with a high level of morbidity at baseline and using a low dose GH titration regimen we aimed to avoid over-replacement and increase the efficacy of treatment. DESIGN: An open study of GH replacement, initiating treatment with a dose of 0. 8 U/day and titrating the dose by 0.4 U increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age-related normal range. PATIENTS: 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), 25 males, of mixed adult and childhood-onset and mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. MEASUREMENTS: Height, weight, waist and hip circumference were measured to allow calculation of body mass index (BMI) and waist-hip ratio (WHR). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DEXA). Serum haemoglobin A1C (HbA1C), lipid profile and insulin like growth factor 1 (IGF-I) were measured. The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires (SRQ) were used to assess quality of life. RESULTS: Baseline characteristics were consistent with those previously described in severely GHD adults; mean IGF-I SDS - 2.4 (+/- 2.7), BMI 28.8 (+/- 5. 4) kg/m2, total cholesterol 6.17 (+/- 1.2) mmol/l, reduced BMD z-scores at the lumbar spine (- 0.8 +/- 1.2) and femoral neck (- 0. 44 +/- 1.4), and SRQ scores considerably lower than reported in previous studies of GH deficient adults and normal controls. Following initiation of GH serum IGF-I SDS was increased significantly from baseline to a mean level of 0.15 +/- 2.7 (P < 0. 001) and 0.31 +/- 2.0 (P < 0.001) at three and eight months, respectively. The mean PGWB score increased from 59.7 +/- 19.9 to 75. 8 +/- 15.0 (P < 0.001) and 73.7 +/- 19.5 (P = 0.001) at three and eight months, respectively. An increase of 14 points represents the largest improvement in quality of life, using this index, that has been reported in GHD adults. The mean AGHDA score also demonstrated considerable improvement, falling from 15.3 +/- 6.0 to 10.4 +/- 6.2 (P < 0.001) and 9.8 +/- 6.5 (P < 0.001) at three and eight months, respectively. The changes observed in both the PGWB and AGHDA scores between baseline and at both three and eight months were shown to correlate significantly with the respective baseline score. A significantly greater improvement was observed in the PGWB following GH replacement in those with a baseline PGWB score of < 60 than in those with a score > 60. This observation was significant at both three (27.1 vs 6.7, P = 0.0001) and eight (25.6 vs 3.3, P = 0.0003) months. All PGWB subscales showed significant improvement though that of vitality was of greatest magnitude. A strong correlation was observed between the generic and disease-specific SRQ (r = - 0.73, P < 0.001). CONCLUSIONS: The observed improvement in quality of life in GH deficient adults is proportional to the degree of impairment before commencing therapy. The use of low-dose titration and selection of a population with greater morbidity reduces the occurrence of over-replacement and increases the efficacy of treatment. This allows direction of resources to those in greatest need.
dc.language.isoenen
dc.subjectHaemoglobinsen
dc.subject.meshAdolescent
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshBody Mass Index
dc.subject.meshBone Density
dc.subject.meshCholesterol
dc.subject.meshDrug Administration Schedule
dc.subject.meshFemale
dc.subject.meshGrowth Hormone
dc.subject.meshHemoglobins
dc.subject.meshHumans
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshPatient Selection
dc.subject.meshProspective Studies
dc.subject.meshPsychiatric Status Rating Scales
dc.subject.meshQuality of Life
dc.subject.meshStatistics, Nonparametric
dc.titleDose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital, Manchester, UK.en
dc.identifier.journalClinical Endocrinologyen
html.description.abstractOBJECTIVE: Previous studies of GH replacement in adults have used unselected cohorts of GH deficient (GHD) adults and weight-based dosing regimens resulting in supraphysiological serum IGF-I levels and a high frequency of side-effects and withdrawal from these studies. By choosing patients with a high level of morbidity at baseline and using a low dose GH titration regimen we aimed to avoid over-replacement and increase the efficacy of treatment. DESIGN: An open study of GH replacement, initiating treatment with a dose of 0. 8 U/day and titrating the dose by 0.4 U increments to normalize the IGF-I SDS between - 2.0 and + 2.0 SD of the age-related normal range. PATIENTS: 65 severely GHD patients (peak GH < 9 mU/l to provocative testing), 25 males, of mixed adult and childhood-onset and mean age 38.7 (range 17-72) years. Inclusion criterion was that of subjectively poor quality of life on clinical interview. MEASUREMENTS: Height, weight, waist and hip circumference were measured to allow calculation of body mass index (BMI) and waist-hip ratio (WHR). Bone mineral density (BMD) was measured by dual X-ray absorptiometry (DEXA). Serum haemoglobin A1C (HbA1C), lipid profile and insulin like growth factor 1 (IGF-I) were measured. The Psychological General Well-Being Schedule (PGWB) and Adult Growth Hormone Deficiency Assessment (AGHDA) self-rating questionnaires (SRQ) were used to assess quality of life. RESULTS: Baseline characteristics were consistent with those previously described in severely GHD adults; mean IGF-I SDS - 2.4 (+/- 2.7), BMI 28.8 (+/- 5. 4) kg/m2, total cholesterol 6.17 (+/- 1.2) mmol/l, reduced BMD z-scores at the lumbar spine (- 0.8 +/- 1.2) and femoral neck (- 0. 44 +/- 1.4), and SRQ scores considerably lower than reported in previous studies of GH deficient adults and normal controls. Following initiation of GH serum IGF-I SDS was increased significantly from baseline to a mean level of 0.15 +/- 2.7 (P < 0. 001) and 0.31 +/- 2.0 (P < 0.001) at three and eight months, respectively. The mean PGWB score increased from 59.7 +/- 19.9 to 75. 8 +/- 15.0 (P < 0.001) and 73.7 +/- 19.5 (P = 0.001) at three and eight months, respectively. An increase of 14 points represents the largest improvement in quality of life, using this index, that has been reported in GHD adults. The mean AGHDA score also demonstrated considerable improvement, falling from 15.3 +/- 6.0 to 10.4 +/- 6.2 (P < 0.001) and 9.8 +/- 6.5 (P < 0.001) at three and eight months, respectively. The changes observed in both the PGWB and AGHDA scores between baseline and at both three and eight months were shown to correlate significantly with the respective baseline score. A significantly greater improvement was observed in the PGWB following GH replacement in those with a baseline PGWB score of < 60 than in those with a score > 60. This observation was significant at both three (27.1 vs 6.7, P = 0.0001) and eight (25.6 vs 3.3, P = 0.0003) months. All PGWB subscales showed significant improvement though that of vitality was of greatest magnitude. A strong correlation was observed between the generic and disease-specific SRQ (r = - 0.73, P < 0.001). CONCLUSIONS: The observed improvement in quality of life in GH deficient adults is proportional to the degree of impairment before commencing therapy. The use of low-dose titration and selection of a population with greater morbidity reduces the occurrence of over-replacement and increases the efficacy of treatment. This allows direction of resources to those in greatest need.


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