Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism
Bone loss is correlated to the severity of growth hormone deficiency in adult patients with hypopituitarism
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DOI：
10.1210/jc.84.6.1919
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发表时间：
1999-06-01
影响因子：
5.8
通讯作者：
Lombardi, G
中科院分区：
文献类型：
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作者：
Colao, A;Di Somma, C;Lombardi, G
据报道，骨密度（BMD）降低的患者孤立的生长激素缺乏症（GHD）或与多种垂体激素缺乏症（MPHD）。为了研究GHD的严重程度是否与骨量和骨转换障碍的程度相关，我们评估了腰椎和股骨颈的BMD;循环胰岛素样生长因子I（IGF-I）、IGF结合蛋白-3（IGFBP-3）和骨钙素水平，和尿I型胶原交联N-端肽（Ntx）水平在101名成人低血压患者和35名性别和年龄-根据精氨酸加GHRH对GH的反应，（ARG+GHRH）组41例，GH峰值低于3 μ g/L（0.9 +/- 0.08 μ g/L），定义为极重度GHD;第2组包括25例GH峰值在3.1-9 μ g/L之间的患者（4.7 ± 0.4 μ g/L），定义为重度GHD;第3组包括18例GH峰值在9.1-16.5 μ g/L之间的患者组4包括17名GH峰值高于16.5 μ g/L（28.3 +/- 4.3 μ g/L）的患者，定义为非GHD。在所有35个对照组（第5组）中，ARG+GHRH后的GH反应高于16.5 μ g/L（40.7 +/- 2.2 μ g/L）。在第1组患者中，循环IGF-I（P < 0.001），IGFBP-3（P < 0.05），骨钙素（P < 0.001），尿Ntx（P < 0.001）低于3-5组，但无显著性差异;腰椎的t评分（-1.99 ± 0.2）和股骨颈（-1.86 ± 0.3）低于第3组（分别为-0.5 +/-0.7，P < 0.01和-0.3 +/-0.7，P < 0.01），4（分别为-0.5 +/-0.2，P < 0.01和-0.3 +/-0.7，P < 0.01）和5（分别为-0.5 +/-0.2，P < 0.001和0.0 +/-0.02，P < 0.001）。在第2组患者中，循环IGF-I和IGFBP-3水平与第1组无差异，而腰椎t评分（-1.22 +/- 0.3）和股骨颈（-0.9 +/-0.3）分别显著高于和低于组1和组5血清骨钙素和尿Ntx水平显著高于第1组，低于第3-5组（P < 0.001）。MPHD患者根据其激素缺陷的数量进行细分，如全垂体功能减退症伴尿崩症（10例）或不伴尿崩症（31例），GHD伴1个或多个额外的垂体缺陷（36例），单纯GHD（7例），1-2个垂体激素缺陷（10例）不伴GHD，和垂体前叶功能正常（7例）。不同GH分泌水平亚组间腰椎和股骨颈t评分及骨转换生化指标差异无统计学意义; ARG+GHRH后GH峰值与IGF-I、骨钙素、尿Ntx水平及腰椎t评分相关，而与股骨颈水平相关性不显著。血浆IGF-I水平与腰椎和股骨颈t评分、血清骨钙素和尿Ntx之间也存在显著相关性。多元相关分析显示，血浆IGF-I水平对腰椎t评分的预测作用更强，而对股骨颈t评分的预测作用则不强ARG+GHRH组GH峰值显著高于对照组（t = 3.376; P < 0.005（t = -0.968; P = 0.338）。总之，仅在极重度或重度GHD患者中发现与骨转换参数异常相关的BMD显著降低，而非GHD低血糖患者的BMD值正常。无论是否存在额外的激素缺乏，这些异常在所有GHD患者中始终存在，表明GHD在骨质疏松患者的骨质减少发生中起着核心作用。
Reduced bone mineral density (BMD) has been reported in patients with isolated GH deficiency (GHD) or with multiple pituitary hormone deficiencies (MPHD). To investigate whether the severity of GHD was correlated with the degree of bone mass and turnover impairment, we evaluated BMD at the lumbar spine and femoral neck; circulating insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and osteocalcin levels, and urinary cross-linked N-telopeptides of type I collagen (Ntx) levels in 101 adult hypopituitary patients and 35 sex- and age-matched healthy subjects.On the basis of the GH response to arginine plus GHRH (ARG+GHRH), patients were subdivided into 4 groups: group 1 included 41 patients with a GH peak below 3 mu g/L (0.9 +/- 0.08 mu g/L), defined as very severe GHD; group 2 included 25 patients with a GH peak between 3.1-9 mu g/L (4.7 +/- 0.4 mu g/L), defined as severe GHD; group 3 included 18 patients with a GH peak between 9.1-16.5 mu g/L (11.0 +/- 0.3 mu g/L), defined as partial GHD; and group 4 included 17 patients with a GH peak above 16.5 mu g/L (28.3 +/- 4.3 mu g/L), defined as non-GHD. In all 35 controls (group 5), the GH response after ARG+GHRH was above 16.5 mu g/L (40.7 +/- 2.2 mu g/L). In patients in group 1, circulating IGF-I (P < 0.001), IGFBP-3 (P < 0.05), osteocalcin (P < 0.001), and urinary Ntx levels (P < 0.001) were lower than those in group 3-5, which were not different from each other; the t score at the lumbar spine (-1.99 +/- 0.2) and that at the femoral neck (-1.86 +/- 0.3) were lower than those in groups 3 (-0.5 +/- 0.7, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), 4 (-0.5 +/- 0.2, P < 0.01 and -0.3 +/- 0.7, P < 0.01, respectively), and 5 (-0.5 +/- 0.2, P < 0.001 and 0.0 +/- 0.02, P < 0.001, respectively). In patients in group 2, circulating IGF-I and IGFBP-3 levels were not different from those in group 1, whereas the t scores at the lumbar spine (-1.22 +/- 0.3) and femoral neck (-0.9 +/- 0.3) were significantly higher and lower, respectively, than those in groups 1 and 5 (P < 0.05) but not those in groups 3 and 4, and serum osteocalcin and urinary Ntx levels were significant higher than those in group 1 and lower than those in groups 3-5 (P < 0.001).To evaluate the effect of isolated GHD us. MPHD, patients were subdivided according to the number of their hormonal deficits, such as panhypopituitarism with (10 patients) or without (31 patients) diabetes insipidus, GHD with 1 or more additional pituitary deficit(s) (36 patients), isolated GHD (7 patients), 1-2 pituitary hormone deficit(s) without GHD (10 patients), and normal anterior pituitary function (7 patients). The t score at the lumbar spine and femoral neck and the biochemical parameters of bone turnover were not significantly different among the different subgroups with similar GH secretions.A significant correlation was found between the GH peak after ARG+GHRH and IGF-I, osteocalcin, urinary Ntx levels, and the t score at the lumbar spine, but not that at the femoral neck level. A significant correlation was also found between plasma IGF-I levels and the t score at the lumbar spine and femoral neck, serum osteocalcin, and urinary Ntx. Multiple correlation analysis revealed that the t score at the lumbar spine, but not that at the femoral neck, was more strongly predicted by plasma IGF-I levels (t = 3.376; P < 0.005) than by the GH peak after ARG+GHRH (t = -0.968; P = 0.338).In conclusion, a significant reduction of BMD associated with abnormalities of bone turnover parameters was found only in patients with very severe or severe GHD, whereas normal BMD values were found in non-GHD hypopituitary patients. These abnormalities were consistently present in all patients with GHD regardless of the presence of additional hormone deficits, suggesting that GHD plays a central role in the development of osteopenia in hypopituitary patients.