Jansson J O, Svensson J, Bengtsson B A, Frohman L A, Ahlman H, Wängberg B, Nilsson O, Nilsson M
Research Centre of Endocrinology and Metabolism (RCEM), Sahlgrenska University Hospital, Göteborg, Sweden.
Clin Endocrinol (Oxf). 1998 Feb;48(2):243-50. doi: 10.1046/j.1365-2265.1998.3471213.x.
A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.
一名50岁男性患者，患有糖尿病和库欣综合征，伴有巨大纵隔肿块。血清皮质醇水平升高（1500 - 1800 nmol/l），且无昼夜变化。血浆促肾上腺皮质激素（ACTH）水平（200 - 250 ng/l）及尿皮质醇排泄量也增加。这些激素水平在促肾上腺皮质激素释放激素（CRH）刺激或高剂量地塞米松抑制下均无变化。患者基础生长激素（GH）水平升高（7.3 mU/l），8份血浆样本中免疫反应性生长激素释放激素（GHRH）水平显著升高（600 - 1500 ng/l）。胰岛素样生长因子-1（IGF-1）、嗜铬粒蛋白A和神经肽Y（NPY）的循环水平也升高。计算机断层扫描和奥曲肽闪烁扫描显示有巨大纵隔肿瘤及左锁骨上窝转移灶。在奥曲肽治疗期间，基础GH水平下降（至4.4 mU/l），而GH脉冲高度未变。手术切除大部分肿瘤组织后，血清基础GH水平进一步下降至治疗前水平的约20%（1.6 mU/l），而脉冲高度和平均GH受影响程度较小。术后，皮质醇和IGF-1的循环水平下降，患者临床症状改善。组织学检查显示为神经内分泌肿瘤，其特征与胸腺来源的前肠类癌一致。在80 - 90%的肿瘤细胞中检测到免疫反应性GHRH、ACTH和NPY，但未检测到免疫反应性GH，且这三种肽似乎共定位。在原代培养中，该肿瘤细胞对GHRH或生长激素释放肽-6（GHRP-6）有钙内流反应，而另一个不产生GHRH、ACTH或NPY的类癌细胞则无此反应。这些结果证实了一例罕见的异位分泌GHRH、ACTH和NPY的病例，并表明肿瘤细胞对GHRH、GHRP-6以及奥曲肽有反应。
