Bevan J S, Burke C W, Esiri M M, Adams C B, Ballabio M, Nissim M, Faglia G
Department of Endocrinology, Radcliffe Infirmary, Oxford, UK.
Clin Endocrinol (Oxf). 1989 Jul;31(1):59-70. doi: 10.1111/j.1365-2265.1989.tb00454.x.
Of 22 previously reported patients with TSH-secreting pituitary adenomas challenged with dopamine agonists, 18 showed no decrease in serum TSH. There have been few in-vitro studies of these rare tumours so the mechanism of the dopaminergic resistance has remained obscure. We describe two further patients with thyrotrophinomas; the first was thyrotoxic (T3 6.1 nmol/l, TSH 7 mU/l) and the second was diagnosed after radioiodine for presumed Graves' disease. The second patient had an alpha-subunit: TSH molar ratio less than unity (0.27). In-vivo TSH responses to TRH, bromocriptine and domperidone were compared with those of the resected tumour cells in vitro, the latter studied using a continuous perifusion system. Dopamine receptors were sought in membranes from each tumour using a radioreceptor assay employing 3H-spiperone. Patient 1 showed significant increases in serum TSH (7 to 13 mU/l) and alpha-subunit (18.7 to 385 ng/ml) after 200 micrograms TRH (i.v.) but patient 2 showed no such increases (TSH: 69 to 72 mU/l, alpha-subunit: 4.9 to 5.2 ng/ml). Neither patient showed a change in serum TSH following bromocriptine 2.5 mg (orally) or domperidone 10 mg (i.v.), though serum PRL responded normally. Serum TSH from patient 1 was of apparently normal molecular size but increased bioactivity (B/I ratio 3.8) and that from patient 2 was of increased molecular size but reduced bioactivity (B/I ratio 0.1). Tumour cells from each patient immunostained for TSH beta and alpha-subunit, and secreted TSH in vitro. The first showed dose-dependent TSH release after TRH (1-100 ng/ml) which could not be inhibited by dopamine (5 mumol/l) but the second was unresponsive to TRH in vitro. Neither tumour showed inhibition of TSH release by dopamine (5 mumol/l) or bromocriptine (0.01-10 nmol/l) and neither contained membrane-bound dopamine receptors. The results suggest that the dopaminergic resistance typical of most TSH-secreting pituitary adenomas may be due to altered or absent membrane-bound dopamine receptors.
在先前报道的22例接受多巴胺激动剂刺激的促甲状腺激素分泌型垂体腺瘤患者中，18例患者的血清促甲状腺激素未降低。针对这些罕见肿瘤的体外研究很少，因此多巴胺抵抗的机制仍不清楚。我们描述了另外两名促甲状腺素瘤患者；第一例有甲状腺毒症（T3 6.1 nmol/l，促甲状腺激素7 mU/l），第二例在接受放射性碘治疗疑似格雷夫斯病后被诊断出来。第二例患者的α亚基：促甲状腺激素摩尔比小于1（0.27）。将体内促甲状腺激素对促甲状腺激素释放激素（TRH）、溴隐亭和多潘立酮的反应与体外切除的肿瘤细胞的反应进行比较，后者使用连续灌流系统进行研究。使用3H-螺哌隆放射受体分析法在每个肿瘤的膜中寻找多巴胺受体。患者1静脉注射200微克TRH后血清促甲状腺激素（从7 mU/l升至13 mU/l）和α亚基（从18.7 ng/ml升至385 ng/ml）显著升高，但患者2未出现此类升高（促甲状腺激素：从69 mU/l升至72 mU/l，α亚基：从4.9 ng/ml升至5.2 ng/ml）。两名患者口服2.5毫克溴隐亭或静脉注射10毫克多潘立酮后血清促甲状腺激素均无变化，尽管血清催乳素反应正常。患者1的血清促甲状腺激素分子大小明显正常，但生物活性增加（B/I比值为3.8），患者2的血清促甲状腺激素分子大小增加但生物活性降低（B/I比值为0.1）。两名患者的肿瘤细胞均对促甲状腺激素β和α亚基进行免疫染色，并在体外分泌促甲状腺激素。第一例在TRH（1 - 100 ng/ml）后显示出剂量依赖性促甲状腺激素释放，且不能被多巴胺（5 μmol/l）抑制，但第二例在体外对TRH无反应。两个肿瘤均未显示多巴胺（5 μmol/l）或溴隐亭（0.01 - 10 nmol/l）对促甲状腺激素释放的抑制作用，且均未含有膜结合多巴胺受体。结果表明，大多数促甲状腺激素分泌型垂体腺瘤典型的多巴胺抵抗可能是由于膜结合多巴胺受体改变或缺失所致。
