Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Gen Comp Endocrinol. 2013 Jul 1;188:282-7. doi: 10.1016/j.ygcen.2013.04.024. Epub 2013 May 4.
Acromegaly is an illness usually defined by excessively high growth hormone (GH) and insulin like growth factor 1 (IGF-1) levels, the latter mainly reflecting GH action on the liver. IGF-1, also known as somatomedin C, mediates several actions of GH. The diagnosis and management of acromegaly is relatively straight forward, but long-term follow-up of patients can be difficult, as elevated IGF-1 levels can occur in the presence of apparently normalised GH levels and late recurrence of acromegaly may arise despite previous suppression on oral glucose tolerance testing. Data suggest this applies especially to patients in whom the GH receptor lacks exon 3. In such patients, GH may not always be a useful marker of disease, and traditional GH cut-offs may be misleading. Recent data suggest that soluble Klotho (sKlotho), besides and in addition to IGF-1, may help monitor the activity of GH-producing adenomas (presumably reflecting GH action on the kidneys) and may be a useful supplementary tool.
GHR genotyping was performed in 112 patients with acromegaly. IGF-1 and sKlotho levels were measured in the sera of patients before and after transsphenoidal surgery, with emphasis on patients judged inconclusively cured by surgery or with small residual tumour masses shortly after surgery. Patients were assessed for recurrence of acromegaly with GH levels (random or nadir during an oGTT).
Of the 48 patients who underwent surgery between 2000 and 2009 and who had well-documented longer term follow-up at our institution, 29 had no biochemical evidence of residual disease activity after transsphenoidal surgery (marked reduction in IGF-1 and sKlotho levels, GH suppressible to <1 ng/ml) and were classified as in remission. 2 of these patients developed recurrent symptoms of acromegaly during follow-up with increasing levels of IGF-1 and sKlotho, and both patients were carriers of the d3-GHR genotype.
Acromegalic patients with the d3-GHR polymorphism might be - for a given low postsurgical GH level - at higher risk for recurrence and may require a lower GH nadir during oGTT to be classified as in remission. Soluble Klotho could be useful in the follow-up of acromegalic patients. The question arises whether sKlotho not only reflects the activity of GH-secreting pituitary adenomas but whether Klotho (ectodomain clipping?) could also mediate selected actions of GH.
肢端肥大症通常定义为生长激素 (GH) 和胰岛素样生长因子 1 (IGF-1) 水平过高，后者主要反映 GH 对肝脏的作用。IGF-1 又称 somatomedin C，介导 GH 的多种作用。肢端肥大症的诊断和治疗相对简单，但患者的长期随访可能很困难，因为即使 GH 水平正常，IGF-1 水平仍可能升高，并且尽管口服葡萄糖耐量试验已抑制，但肢端肥大症仍可能复发。有数据表明，这种情况尤其适用于缺乏外显子 3 的 GH 受体的患者。在这些患者中，GH 可能并不总是疾病的有用标志物，传统的 GH 截断值可能具有误导性。最近的数据表明，除了 IGF-1 之外，可溶性 Klotho (sKlotho) 可能有助于监测 GH 分泌腺瘤的活性（推测反映了 GH 对肾脏的作用），并且可能是一种有用的补充工具。
对 112 例肢端肥大症患者进行了 GHR 基因分型。在经蝶窦手术后，测量了患者血清中的 IGF-1 和 sKlotho 水平，重点关注手术结果不确定或术后短时间内仍有少量肿瘤残留的患者。通过 GH 水平（口服葡萄糖耐量试验期间的随机或最低点）评估患者的肢端肥大症复发情况。
在 2000 年至 2009 年间接受手术且在我们机构有详细长期随访的 48 例患者中，29 例患者在经蝶窦手术后无残留疾病活动的生化证据（IGF-1 和 sKlotho 水平显著降低，GH 抑制至<1ng/ml），被归类为缓解期。其中 2 例患者在随访期间出现肢端肥大症复发症状，IGF-1 和 sKlotho 水平升高，这 2 例患者均为 d3-GHR 基因型携带者。
携带 d3-GHR 多态性的肢端肥大症患者可能 - 对于给定的术后 GH 低水平 - 复发风险更高，并且可能需要在口服葡萄糖耐量试验期间的更低 GH 最低点才能被归类为缓解期。可溶性 Klotho 可能对肢端肥大症患者的随访有用。问题是 sKlotho 是否不仅反映 GH 分泌性垂体腺瘤的活性，而且 Klotho（外显子剪接？）是否也能介导 GH 的某些作用。
