Endocrine Abstracts (2004) 7 P5

Growth hormone replacement is important for the restoration of PTH circadian rhythmicity in older adult growth hormone deficient patients

HD White1, AM Ahmad1, F Joseph1, VKB Prabhakar1, A Patwala1, P Whittingham1, BH Durham2, WD Fraser2 & JP Vora1

1Department of Diabetes and Endocrinology, Royal Liverpool University Hospital, Prescot Street, Liverpool, UK; 2Department of Clinical Chemistry, Duncan Building, Royal Liverpool University Hospital, Daulby Street, Liverpool, UK.

Adult Growth Hormone Deficiency (AGHD) is associated with osteoporosis. PTH circadian rhythmicity is important for bone remodelling. Abnormalities in PTH circadian rhythms, including a blunted nocturnal rise, have been reported in AGHD and may contribute to osteoporosis development. GH replacement (GHR) results in improvement of PTH circadian rhythmicity and bone mineral density (BMD). In health, increasing age is associated with declining GH secretion and the appropriateness of GHR in older AGHD patients has been debated. We examined the effect of age on PTH circadian rhythm response to GHR.

22 AGHD patients (12 <55 years (younger patients), 10 >55 years (older patients)) were consented to the study. Patients were hospitalised for 24 hours before then 1, 3 and 6 months following GHR. Half-hourly blood samples were taken for PTH. Circadian rhythmicity was examined using cosinor analysis. Local Ethics Committee approval was obtained.

All patients achieved target IGF1 by 1 month. PTH circadian rhythms were significant in all patients at each visit (p<0.001). At baseline, there was no significant difference in mean PTH concentration between 1400-2300h and 2330-0800h in either age group (4.43plus/minus0.12pmol/L versus 4.68plus/minus0.11pmol/L, respectively for younger patients, p=0.43 and 4.49plus/minus0.13pmol/L versus 4.88plus/minus0.13pmol/L for older patients, p=0.09). Mean PTH concentration between 1400-2300h and 2330-0800h became significantly different following 1 month of GHR in younger patients (4.10plus/minus0.12pmol/L versus 4.60plus/minus0.11pmol/L, p=0.002) and 6 months in older patients (4.25plus/minus0.14pmol/L versus 4.62plus/minus0.14pmol/L, p=0.01). The nocturnal rise in PTH concentration increased significantly 3 months following GHR in younger patients (29.7%, p=0.007) but not until 6 months in older (20.8%, p=0.03) patients.

Older AGHD patients do derive benefit from GHR in terms of PTH circadian rhythmicity improvement. Their response, however, appears delayed compared to younger patients which should be taken into account when designing studies examining long-term BMD responses to GHR.

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