成人生长激素缺乏症的诊断(Diagnosis of Adult Growth Hormone Deficiency)
成人生长激素缺乏症的诊断你需要知道的
直到几年前，生长激素刺激测试（GHST），测量脑垂体产生生长的能力，被认为是诊断AGHD的主要生化测试。在过去几年中，GHST确定一个人是否患有AGHD的准确性受到越来越多的质疑，因为测试变异性以及对IGF-I具有重大诊断价值的接受程度，以及GHST，表型（身体和心理特征，病史，如上所述;而且，在缺乏明确界定的AGHD有机原因的情况下，对GHGHD的接受程度越来越高。，被评估的每个人的独特生理，使AGHD的诊断复杂和多样。
Until several years ago, the growth hormone stimulation test (GHST), which measures the capacity of the pituitary to produce growth, was considered the principal biochemical test for the diagnosis of AGHD. During the past several years, the accuracy of the GHST to determine whether a person has AGHD has been increasingly questioned because of test variability and increasing acceptance of IGF-I being of significant diagnostic value in combination with the GHST, the phenotype (physical and mental characteristics, the medical history, as described above; and, increased understanding that, in the absence of a clearly defined organic cause for AGHD, the unique physiology of each person being evaluated, makes the diagnosis of AGHD complex and varied.
成人生长激素缺乏 （GHD） 是一种多因素障碍，其中与垂体腺瘤或治疗相关的垂体功能障碍起主要作用。部分GHD的概念，多年来被儿科内分泌学家所认可，现在正在成人中检查下丘脑-垂体疾病与代谢和人体测量异常之间的关联。然而，部分GHD在肥胖、年龄增加和缺乏额外的垂体激素缺陷的情况下变得更加难以诊断。
Adult growth hormone deficiency (GHD) is a multifactorial disorder in which pituitary dysfunction associated with pituitary adenomas or their treatment plays a major role. The concept of partial GHD, recognized by pediatric endocrinologists for many years, is being now being examined in adults for an association between hypothalamic-pituitary disease and metabolic and anthropometric abnormalities in persons whose GH range from severe GHD to non-GHD levels. Partial GHD, however, becomes more difficult to diagnosis in the presence of obesity, increasing age, and in the absence of additional pituitary hormone deficits.
Adults with GHD can have a variety of signs and symptoms, which include abnormality body composition with increased fat mass (especially central adiposity), decreased lean muscle mass, extracellular fluid volume, diminished muscle strength, physical energy and stamina, lack of motivation, lethargy, lability (changes in mood), depression, and impairment of cognitive functions.
全面的生化测试可能揭示以下条件，也是AGHD的标志：脂质失衡，动脉硬化，肥胖，增加低密度脂蛋白胆固醇和降低胰岛素敏感性，和代谢综合征。MRI扫描可能揭示大脑的结构异常或肿瘤。肺功能测试可能显示肺呼吸肌肉能力下降。DEXA（双能量X射线吸收）扫描可能揭示骨质疏松症和骨折风险增加。所有这些条件都符合AGHD。低血压和 GHD 与死亡率增加有关。
Comprehensive biochemical testing may reveal the following conditions that are also markers for AGHD: lipid imbalance, atherosclerosis, obesity, increased LDL cholesterol and reduced insulin sensitivity, and metabolic syndrome. An MRI scan may reveal a structural abnormality or tumor in the brain. A pulmonary function test may reveal diminished lung respiratory muscle capacity. A DEXA (dual-energy X-ray absorptiometry) scan may reveal osteoporosis and increased risk of fracture. All those conditions are consistent with AGHD. Hypopituitarism and GHD are associated with increased mortality.
综合生化测试最初包括但不限于：完整的血计数（CBC）与差异血小板，综合代谢面板，甲状腺面板，IGF-I，HbA1c，叶黄素激素，卵泡刺激激素，睾酮，雌激素（仅供女性使用），DHEAS，和罗斯蒂尼。生化测试还可以揭示甲状腺素、睾酮和雄激素类固醇（DHEAS 和雄激素）的缺乏性、代谢疾病和紊乱，以及可能干扰 GH 和 IGF-I 分泌、吸收和利用的遗传缺陷。
Comprehensive biochemical testing initially includes but is not limited to: complete blood count (CBC) with differential platelets, comprehensive metabolic panel, thyroid panel, IGF-I, HbA1c, luteinizing hormone, follicle stimulating hormone, testosterone, estrogen (for women only), DHEAS, androstenedione. Biochemical testing can also reveal deficiencies in thyroxin, testosterone, and androgenic steroids (DHEAS and androstenedione), diseases and disorders of metabolism, and genetic defects that can interfere with the secretion, uptake, and utilization of GH and IGF-I.
当IGF-I低时，有必要进一步调查以确定低IGF-I的原因，其中可能包括（1）IGF-II和IGF结合蛋白的测试;（2）生长激素刺激试验，以确定垂体是否具有产生生长激素的能力;（3） 锌、镁和氦的水平，这些矿物质对于某些酶的正常运作是必要的，这些酶对于IGF-I及其各种结合蛋白的代谢过程至关重要;和，可能测试代谢疾病和紊乱。
When the IGF-I is low, further investigation is warranted to determine the cause of the low IGF-I, which can include (1) the testing of IGF-II, and the IGF binding proteins; (2) growth hormone stimulation tests to determine whether the pituitary has the capacity to produce growth hormone; (3) the levels of zinc, magnesium, and selenium, which minerals are necessary for the proper functioning of certain enzymes that are essential for the metabolic processes involved in with IGF-I and its various binding proteins; and, possibly testing for metabolic diseases and disorders.
AGHD 的诊断往往具有挑战性，因为缺乏生长参数作为诊断因素，以及成人随着时间的推移获得的其他疾病的影响。因此，需要其他标记来识别患有 GHD 并可能受益于 GH 替代疗法的成年人。成人GHD诊断和治疗的共识指南包括有下脑垂体脑病或紊乱证据的患者、儿童病患GHD患者和经颅骨消融或有头部创伤史的患者。在其他垂体激素缺陷的情况下，对GHD的怀疑也加剧。GHD 测试包括进行生长激素刺激测试 （GHST） 时对 GH 的测量，这些刺激剂具有高灵敏度和敏感性，包括但不限于胰岛素耐受性测试 （ITT）。Ghrh 加上精氨酸或 Ghrh 和 Ghrp - 6 。多项研究发现，非刺激性血清或尿液对GH水平的测量不能可靠地预测成人的缺乏症。此外，ITT 在管理中存在一些潜在风险，其可重复性值得怀疑，这促使了上述测试的发展。因此，在 ITT 是禁忌或无定论的情况下，精氨酸和 GHRH 的组合是一种有效的选择。
The diagnosis of AGHD is often challenging because of the absence of growth parameters as diagnostic factors in addition factor, and the effects of other disorders that adults acquire over time. Other markers are therefore needed to identify adults who have GHD and could potentially benefit from GH replacement therapy. Consensus guidelines for the diagnosis and treatment of adult GHD include patients who have evidence of hypothalamic-pituitary disease or disorder, patients with childhood-onset GHD, and patients who have undergone cranial ablation or have a history of head trauma. Suspicion of GHD is also heightened in the presence of other pituitary hormone deficits. Tests for GHD include measurement of GH upon conducting growth hormone stimulation tests (GHSTs) with provoking agents that have high sensitivity and sensitivity including, but not limited to, the insulin tolerance test (ITT). GHRH plus arginine or GHRH and GHRP-6. The results of several studies have found that non-stimulated serum or urine measurements of GH levels do not reliably predict deficiency in adults. Also, the ITT has some potential risks involved in its administration and is of questionable reproducibility, which has prompted the development of the previously mentioned tests. Thus, in cases where ITT is contraindicated or inconclusive, the combination of arginine and GHRH is an effective alternative.
生长激素缺乏的迹象和症状可以掩盖睾酮或甲状腺素， 或由这些激素的缺乏或其他激素功能障碍或代谢紊乱.在这种情况下， rhGH 可能会导致其他激素缺乏.例如，皮质醇，或与男性睾酮联合，可通过激素红细胞生成素导致继发性多细胞血症，导致严重甚至严重的疾病，如血红蛋白增多症、心肌梗死、中风和瘫痪、肝脏损伤。rhGH 也可以刺激前血蛋白的凝固和激活部分血栓铂时间在 GHD 成人。过量的 GH/rhGH 也会导致癌症和癌症和糖尿病复发的风险显著增加。
The signs and symptoms of growth hormone deficiency can be masked by testosterone or thyroxin, or caused by deficiencies in those hormones or by other hormone dysfunction or by metabolic disorders. In such cases, rhGH can cause other hormone deficiencies. For example, cortisol, or in combination with testosterone in males, can cause secondary polycythemia via the hormone erythropietin, resulting in serious and even grave conditions, such as hemochromotosis, cardiac infarction, stroke and paralysis, liver damage. rhGH can also stimulate coagulation of prothrombin and activated partial thromboplastin time in GHD adults. Excessive GH/rhGH also causes a significant increase in the risk of cancer and the recurrence of cancer and diabetes mellitus.
因此，在诊断和治疗 GHD/AGHD 之前，必须确定和排除任何此类情况。患者的病史，以及体格检查，生化检查和适当的脑部扫描，是诊断和治疗患者的AGHD的关键。
It is, therefore, important to identify and rule out any such conditions before diagnosing and treating GHD/AGHD. The patient’s medical history, as well as physical examination, biochemical testing and appropriate scans of the brain, are critical to the diagnosis and treatment of the patient for AGHD.
主要信息来源Principal Source of Information
1. 美国临床内分泌学家协会（AACE）成人和儿童生长激素使用临床实践指南 - 2003年最新更新
American Association of Clinical Endocrinologists (AACE) Guidelines for the Clinical Practice for Growth Hormone Use in Adults and Children - 2003 update
2. 儿童生长激素使用指南更新：劳森·威尔金斯儿科学会
Update of Guidelines for the Use of Growth Hormone in Children: The Lawson Wilkins Pediatric Society
3. 内分泌学会药物和治疗委员会
Endocrinology Society Drug and Therapeutics Committee