Dose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults.
Authors
Murray, Robert DSkillicorn, C J
Howell, Simon J
Lissett, Catherine A
Rahim, Asad
Shalet, Stephen M
Affiliation
Department of Endocrinology, Christie Hospital, Manchester, UK.Issue Date
1999-06
Metadata
Show full item recordAbstract
OBJECTIVE: 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.Citation
Dose titration and patient selection increases the efficacy of GH replacement in severely GH deficient adults. 1999, 50 (6):749-57 Clin. Endocrinol. (Oxf)Journal
Clinical EndocrinologyDOI
10.1046/j.1365-2265.1999.00722.xPubMed ID
10468947Type
ArticleLanguage
enISSN
0300-0664ae974a485f413a2113503eed53cd6c53
10.1046/j.1365-2265.1999.00722.x
Scopus Count
Collections
Related articles
- Influences on quality of life in GH deficient adults and their effect on response to treatment.
- Authors: Murray RD, Skillicorn CJ, Howell SJ, Lissett CA, Rahim A, Smethurst LE, Shalet SM
- Issue date: 1999 Nov
- Body composition and quality of life in adults with growth hormone deficiency; effects of low-dose growth hormone replacement.
- Authors: Ahmad AM, Hopkins MT, Thomas J, Ibrahim H, Fraser WD, Vora JP
- Issue date: 2001 Jun
- The influence of gender on the short and long-term effects of growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults: a 5-year study.
- Authors: Drake WM, Rodríguez-Arnao J, Weaver JU, James IT, Coyte D, Spector TD, Besser GM, Monson JP
- Issue date: 2001 Apr
- Spinal irradiation impairs the osteo-anabolic effects of low-dose GH replacement in adults with childhood-onset GH deficiency.
- Authors: Murray RD, Adams JE, Smethurst LE, Shalet SM
- Issue date: 2002 Feb
- Sustained reduction in circulating cholesterol in adult hypopituitary patients given low dose titrated growth hormone replacement therapy: a two year study.
- Authors: Florakis D, Hung V, Kaltsas G, Coyte D, Jenkins PJ, Chew SL, Grossman AB, Besser GM, Monson JP
- Issue date: 2000 Oct