H. D. White

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

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.

Gender variation in PTH sensitivity and rhythmicity following growth hormone replacement in adult growth hormone‐deficient patients

background  Adult GH deficiency (AGHD) is associated with osteoporosis and reduced bone turnover; factors improved by GH replacement (GHR), with men gaining greater benefit than women. Reduction in sensitivity of bone and kidney to the effects of PTH may underlie AGHD changes in bone turnover. We determined the gender difference in PTH target‐organ sensitivity following GHR in AGHD patients.

Effect of Oral Phosphate and Alendronate on Bone Mineral Density When Given as Adjunctive Therapy to Growth Hormone Replacement in Adult Growth Hormone Deficiency

BACKGROUND Adult GH deficiency (AGHD) is associated with osteoporosis, which occurs as the result of reduced sensitivity of the bone and kidney to the effect of PTH. AIM The aim of the study was to examine the effect of oral phosphate and alendronate therapy on PTH sensitivity, bone turnover, and bone mineral density (BMD) in AGHD patients. METHODS Forty-four AGHD patients were hospitalized for 24 h, and half-hourly blood and 3-hourly urine samples were collected for PTH, nephrogenous cAMP (marker of renal PTH activity), procollagen type-I amino-terminal propeptide, and type-I collagen β C-telopeptide. Patients were randomized to one of six groups: patients who were previously naive to GH were randomized to receive GH replacement (GHR) alone, GHR+alendronate, or GHR+phosphate-sandoz, whereas patients already receiving GHR were randomized to continue GHR alone, GHR+alendronate, or GHR+phosphate-sandoz. Study visits were repeated after 1, 3, 6, and 12 months in the previously GH-naive group and after 12 months in the previously GH-replaced group. BMD was measured at 0 and 12 months. RESULTS Patients receiving GHR+phosphate had greater increases in nephrogenous cAMP and bone markers than patients receiving GHR alone (P < 0.01), and this was associated with greater increases in BMD (P < 0.01). In the GHR+alendronate groups, type-I collagen β C-telopeptide decreased (P < 0.001), and BMD increases were greater than in those receiving GHR alone (P < 0.05). The greatest increases in BMD were seen in patients receiving GHR+phosphate. CONCLUSIONS Phosphate and alendronate therapy given in combination with GHR confer advantage in terms of BMD increase. Phosphate appears to exert its effect by increasing PTH target-organ action, whereas alendronate acts primarily through reduction in bone resorption.

Correlation of serum-adjusted calcium with ionized calcium over a 24-h period in patients with adult growth hormone deficiency before and after growth hormone replacement

Background Difficulties associated with measuring ionized calcium in clinical practice have led to the use of total calcium, with or without adjustment for albumin concentration, as an estimate of calcium metabolism. We examined the correlation between ionized and total/adjusted calcium over a 24-h period in patients with adult growth hormone deficiency (AGHD), a group of patients with previously reported alterations in calcium metabolism. Methods Four patients with AGHD were consented to the study. They were hospitalized for 24 h where half-hourly blood samples were collected for ionized calcium, total calcium, albumin and creatinine, before and one month after the commencement of growth hormone replacement. Total calcium concentration was adjusted for serum albumin. Results Strong correlations were found between ionized calcium and adjusted calcium (r 2 = 0.840 and 0.766 for visits 1 and 2, respectively, P < 0.001), and between ionized calcium and total calcium (r 2 = 0.828 and 0.731 for visits 1 and 2, respectively, P < 0.001). Correlations remained significant during the day (ionized versus adjusted calcium: r 2 = 0.847 and 0.780 for visits 1 and 2, respectively; ionized versus total calcium: r 2 = 0.860 and 0.792 for visits 1 and 2, respectively, all P < 0.001) and at night (ionized versus adjusted calcium: r 2 = 0.831 and 0.802 for visits 1 and 2, respectively; ionized versus total calcium: r 2 = 0.767 and 0.722 for visits 1 and 2, respectively, all P < 0.001). Conclusion The results of our study suggest that total calcium and serum-adjusted calcium can be used in place of ionized calcium as a reliable indicator of calcium metabolism over a 24-h period in patients with AGHD.