Growth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study.

2.50
Hdl Handle:
http://hdl.handle.net/10541/87919
Title:
Growth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study.
Authors:
Toogood, Andy; Shalet, Stephen M
Abstract:
Adults over the age of 60 yr with organic disease of the hypothalamic-pituitary axis have a 90% reduction in GH secretion. This is distinct from the hyposomatotropism associated with increasing age and results in a significant reduction in serum insulin-like growth factor I (IGF-I), an increase in fat mass, abnormal bone turnover, and an adverse lipid profile compared with those in healthy subjects of the same age. These findings suggest that the elderly with organic GH deficiency might benefit from GH replacement therapy. However, the dose of GH required to maintain serum IGF-I levels in the normal range while minimizing side-effects in this group of patients is unknown. We have studied 12 patients with organic GH deficiency, aged 62.4-85.2 (median, 67.9 yr), each treated with three doses of GH (0.167, 0.33, and 0.5 mg/day). Each dose was administered for 12 weeks. The serum IGF-I level rose in a dose-related manner over the course of the study (P < 0.0001). From a baseline median (range) IGF-I concentration of 101 (49-148) microg/L to 149 (49-227) microg/L at 12 weeks (P = 0.003 vs. baseline), 200 (70-453) microg/L at 24 weeks (P = 0.002 vs. baseline; P = 0.04 vs. 12 weeks), and 239 (122-502) microg/L at 36 weeks (P = 0.002 vs. baseline; P = 0.07 vs. 24 weeks). The age-specific IGF-I SD score exceeded normal in two subjects taking 0.33 mg/day and in six subjects taking 0.5 mg/day. Serum IGF-binding protein-3 also rose over the course of the study (P < 0.001); however, the greatest increase occurred during the first 12 weeks, after which the IGFBP-3 level plateaued. Body composition changed significantly during the study, with a fall in fat mass (P = 0.0003) and an increase in lean body mass (P = 0.0001). GH was well tolerated in this elderly group, all of whom completed the study. Three patients developed side-effects while taking 0.5 mg/day; two developed headaches, and one developed arthralgia. This study has demonstrated that the GH replacement dose in elderly subjects is considerably lower than that required by younger adults with GH deficiency. In 50% of the subjects a dose of 0.5 mg/day was excessive, whereas 83% maintained their serum IGF-I within normal limits while taking 0.33 mg/day. No patient exhibited a supranormal IGF-I level on 0.17 mg/day.
Affiliation:
Department of Endocrinology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.
Citation:
Growth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study. 1999, 84 (1):131-6 J. Clin. Endocrinol. Metab.
Journal:
The Journal of Clinical Endocrinology and Metabolism
Issue Date:
Jan-1999
URI:
http://hdl.handle.net/10541/87919
DOI:
10.1210/jc.84.1.131
PubMed ID:
9920073
Type:
Article
Language:
en
ISSN:
0021-972X
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorToogood, Andyen
dc.contributor.authorShalet, Stephen Men
dc.date.accessioned2009-12-14T16:27:59Z-
dc.date.available2009-12-14T16:27:59Z-
dc.date.issued1999-01-
dc.identifier.citationGrowth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study. 1999, 84 (1):131-6 J. Clin. Endocrinol. Metab.en
dc.identifier.issn0021-972X-
dc.identifier.pmid9920073-
dc.identifier.doi10.1210/jc.84.1.131-
dc.identifier.urihttp://hdl.handle.net/10541/87919-
dc.description.abstractAdults over the age of 60 yr with organic disease of the hypothalamic-pituitary axis have a 90% reduction in GH secretion. This is distinct from the hyposomatotropism associated with increasing age and results in a significant reduction in serum insulin-like growth factor I (IGF-I), an increase in fat mass, abnormal bone turnover, and an adverse lipid profile compared with those in healthy subjects of the same age. These findings suggest that the elderly with organic GH deficiency might benefit from GH replacement therapy. However, the dose of GH required to maintain serum IGF-I levels in the normal range while minimizing side-effects in this group of patients is unknown. We have studied 12 patients with organic GH deficiency, aged 62.4-85.2 (median, 67.9 yr), each treated with three doses of GH (0.167, 0.33, and 0.5 mg/day). Each dose was administered for 12 weeks. The serum IGF-I level rose in a dose-related manner over the course of the study (P < 0.0001). From a baseline median (range) IGF-I concentration of 101 (49-148) microg/L to 149 (49-227) microg/L at 12 weeks (P = 0.003 vs. baseline), 200 (70-453) microg/L at 24 weeks (P = 0.002 vs. baseline; P = 0.04 vs. 12 weeks), and 239 (122-502) microg/L at 36 weeks (P = 0.002 vs. baseline; P = 0.07 vs. 24 weeks). The age-specific IGF-I SD score exceeded normal in two subjects taking 0.33 mg/day and in six subjects taking 0.5 mg/day. Serum IGF-binding protein-3 also rose over the course of the study (P < 0.001); however, the greatest increase occurred during the first 12 weeks, after which the IGFBP-3 level plateaued. Body composition changed significantly during the study, with a fall in fat mass (P = 0.0003) and an increase in lean body mass (P = 0.0001). GH was well tolerated in this elderly group, all of whom completed the study. Three patients developed side-effects while taking 0.5 mg/day; two developed headaches, and one developed arthralgia. This study has demonstrated that the GH replacement dose in elderly subjects is considerably lower than that required by younger adults with GH deficiency. In 50% of the subjects a dose of 0.5 mg/day was excessive, whereas 83% maintained their serum IGF-I within normal limits while taking 0.33 mg/day. No patient exhibited a supranormal IGF-I level on 0.17 mg/day.en
dc.language.isoenen
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshBody Composition-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshFemale-
dc.subject.meshHormone Replacement Therapy-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshHypothalamo-Hypophyseal System-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 3-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshQuality of Life-
dc.titleGrowth hormone replacement therapy in the elderly with hypothalamic-pituitary disease: a dose-finding study.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie Hospital National Health Service Trust, Manchester, United Kingdom.en
dc.identifier.journalThe Journal of Clinical Endocrinology and Metabolismen

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