Wahid Shahid T, Marbach Peter, Stolz Barbara, Miller Margaret, James Robert Andrew, Ball Steve G
Endocrine Unit, Royal Victoria Infirmary, Newcastle Hospitals NHS Trust and University of Newcastle, Newcastle upon Tyne, NE1 4LP, UK.
Eur J Endocrinol. 2002 Mar;146(3):295-302. doi: 10.1530/eje.0.1460295.
Somatostatin (SST) analogues are a key option in the management of a variety of conditions, including acromegaly. Tachyphylaxis to SST analogues is not documented in acromegaly. We describe such a phenomenon.
A 74-year-old female with acromegaly previously treated with (90)Y implant, external radiotherapy and thrice daily s.c. octreotide had stable GH levels of 19 mU/l. GH progressively rose following switches to lanreotide and depot octreotide as Sandostatin LAR: from 29 to 126 mU/l. Magnetic resonance imaging and (111)In-pentetreotide scanning revealed no tumour growth or alteration in SST receptor (SSTR) status. Tachyphylaxis to SST analogues was considered. Therapy was discontinued and re-introduced in daily 200 microg/24 h increments by continuous s.c. infusion, to a maximum of 1000 microg/24 h, and maintained over 3 weeks with daily, followed by weekly, GH profiles. Competitive (125)I-octreotide radioligand binding assays measured in vitro bio-activity of anti-SST analogue antibodies. In vitro SSTR binding studies utilised SSTR-expressing rat cortex membrane.
Median GH fell by 93% from 504 to 39.5 mU/l and rose reproducibly on continued infusion to 120 mU/l. Octreotide withdrawal for 16 h produced a 64% increase in sensitivity. High-affinity IgG anti-lanreotide (IC(50)=187 pmol/l) and anti-octreotide (IC(50)=82 nmol/l) antibody, with no crossreactivity with natural SST, was demonstrated. In vitro inhibition of (125)I-octreotide SSTR binding by anti-SST analogue crossreacting antibody was observed at 1:1 serum dilution.
This is the first report of tachyphylaxis to SST analogues in acromegaly. We believe that the short time course of resensitisation following acute octreotide withdrawal is suggestive of an effect(s) on receptor function or on the receptor signal transduction cascade at sites further downstream, rather than an immune-mediated phenomenon.
生长抑素（SST）类似物是治疗包括肢端肥大症在内的多种病症的关键选择。肢端肥大症中未记录到对SST类似物的快速减敏现象。我们描述了这样一种现象。
一名74岁的肢端肥大症女性患者，先前接受过（90）Y植入、外照射放疗以及每日三次皮下注射奥曲肽治疗，其生长激素（GH）水平稳定在19 mU/l。在换用兰瑞肽和长效奥曲肽（善龙）后，GH水平逐渐升高：从29 mU/l升至126 mU/l。磁共振成像和（111）In-喷曲肽扫描显示无肿瘤生长或SST受体（SSTR）状态改变。考虑存在对SST类似物的快速减敏。停止治疗，然后通过持续皮下输注以每日200 μg/24 h的增量重新开始治疗，最大剂量为1000 μg/24 h，并持续3周，期间每日随后每周检测GH水平。通过竞争性（125）I-奥曲肽放射性配体结合试验测定抗SST类似物抗体的体外生物活性。体外SSTR结合研究使用表达SSTR的大鼠皮质膜。
GH中位数从504 mU/l降至39.5 mU/l，下降了93%，在持续输注时可重现性地升至120 mU/l。停用奥曲肽16小时后敏感性增加了64%。证实存在高亲和力的抗兰瑞肽IgG（IC50 = 187 pmol/l）和抗奥曲肽IgG（IC50 = 82 nmol/l）抗体，且与天然SST无交叉反应。在血清稀释度为1:1时观察到抗SST类似物交叉反应抗体对（125）I-奥曲肽SSTR结合的体外抑制作用。
这是肢端肥大症中对SST类似物快速减敏的首例报告。我们认为，急性停用奥曲肽后短时间内重新致敏提示其对受体功能或更下游位点的受体信号转导级联产生了影响，而非免疫介导现象。
Zotero 插件