PTH Circadian Rhythm and PTH Target-Organ Sensitivity Is Altered in Patients With Adult Growth Hormone Deficiency With Low BMD

Abstract

AGHD is associated with osteoporosis. We examined PTH circadian rhythmicity and PTH target-organ sensitivity in 23 patients with AGHD with low BMD and 20 patients with AGHD with normal BMD. Patients with low BMD had a blunted nocturnal rise in PTH concentration and reduced PTH target-organ sensitivity compared with patients with normal BMD; these factors may be important in the pathogenesis of AGHD-related osteoporosis. Adult growth hormone deficiency (AGHD) is associated with decreased BMD. Reduced parathyroid gland sensitivity to changes in calcium and reduced PTH target-organ sensitivity may underlie the pathogenesis of AGHD-related osteoporosis. A blunted nocturnal PTH rise has been reported in AGHD and may contribute to the reduction in BMD. We examined the difference in PTH concentration and markers of bone metabolism in patients with AGHD with normal and low BMD. Forty-three patients with AGHD consented to the study. Twenty-five patients were growth hormone (GH) naïve (GH-N, 13 had BMD femoral neck or lumbar spine T-score < -1.0), and 18 patients had received GH for >2 yr (GH-R, 10 had BMD T-score < -1.0). Patients were hospitalized for 24 h, where blood samples were collected every 0.5 h and urine samples were collected every 3 h for PTH, calcium, phosphate, NcAMP, 1,25-dihydroxyvitamin D [1,25(OH)(2)D], type-I collagen beta C-telopeptide (betaCTX), and procollagen type-I amino-terminal propeptide (PINP). Serum calcium was adjusted for albumin (ACa). Low BMD GH-N and GH-R patients exhibited a reduced nocturnal rise in PTH concentration compared with patients with normal BMD (p < 0.001). GH-N low BMD patients had significantly higher 24-h mean PTH (p < 0.001) than GH-N normal BMD patients, with significantly lower 24-h mean NcAMP, ACa, and 1,25(OH)(2)D (p < 0.01), suggesting a reduction in renal PTH sensitivity. GH-R low BMD patients had significantly lower 24-h mean PTH, NcAMP, ACa, and 1,25(OH)(2)D (p < 0.01) than GH-R normal BMD patients, suggesting reduced renal PTH action. Lower PTH concentration in the presence of lower ACa may reflect reduced sensitivity of the parathyroid calcium-sensing receptor to changes in ACa concentration in the GH-R low BMD patients. Low BMD in GH-N and GH-R AGHD patients may be a consequence of abnormalities in PTH circadian rhythmicity together with reduced parathyroid gland and target-organ sensitivity. Further studies are needed to determine the potential benefit of therapeutic manipulation of PTH rhythmicity and sensitivity on BMD.