Parathyroid hormone and phosphate circadian rhythms are altered in osteopaenic adult growth hormone deficient patients
HD White1, AM Ahmad1, F Joseph1, S Chandran1, P Corlett1, BH Durham2, WD Fraser2 & JP Vora1
Alterations in PTH circadian rhythmicity have previously been reported in Adult Growth Hormone Deficiency (AGHD) and may contribute to the pathogenesis of AGHD-related osteoporosis. However, changes in PTH circadian rhythm have not been correlated with bone mineral density (BMD) in AGHD. Serum phosphate is a likely determinant of PTH rhythm. We examined the PTH and phosphate circadian rhythms in AGHD patients with reduced (defined as femoral neck T-score <-1.0) and normal BMD, who were either GH naive (GHN) or optimally GH replaced (GHR).
25 GHN (13 reduced BMD (mean femoral neck T-score plus/minus standard error mean: -1.7plus/minus0.2), 12 normal BMD (1.0plus/minus0.3)) and 18 GHR (10 reduced BMD (-1.4plus/minus0.3), 8 normal BMD (0.9plus/minus0.4)) AGHD patients were consented to the study. Patients were hospitalised for 24 hours and half-hourly blood samples were collected for PTH and phosphate. Circadian rhythmicity was examined using cosinor analysis. Local Ethics Committee approval was obtained.
All patients had significant PTH and phosphate circadian rhythms (p<0.001). Analysis of the PTH and phosphate 24-hour profiles revealed that compared to GHN and GHR normal BMD patients, GHN and GHR reduced BMD patients had significantly reduced nocturnal PTH rise (3.5plus/minus1.9% versus 13.5plus/minus1.8% and 5.4plus/minus2.0% versus 21.6plus/minus2.3% for GHN and GHR reduced and normal BMD patients respectively, p<0.001) and phosphate rise (0.2plus/minus0.9% versus 10.3plus/minus0.9% and 4.4plus/minus1.0% versus 9.6plus/minus1.3% for GHN and GHR reduced and normal BMD patients respectively, p<0.001).
GHN and GHR AGHD patients with reduced BMD have alterations in PTH circadian rhythmicity which may contribute to the pathogenesis of AGHD-related osteoporosis. Differences in PTH circadian rhythmicity of osteopaenic patients may be a consequence of altered phosphate circadian rhythm. Therapeutic manipulation of the phosphate circadian rhythm may be of value in the treatment of osteopaenic AGHD patients.