Beck-Peccoz P, Piscitelli G, Amr S, Ballabio M, Bassetti M, Giannattasio G, Spada A, Nissim M, Weintraub B D, Faglia G
J Clin Endocrinol Metab. 1986 Apr;62(4):704-11. doi: 10.1210/jcem-62-4-704.
A 40-yr-old man who had acromegaly and hyperthyroidism due to a GH/TSH-secreting pituitary adenoma is described. Serum free T4 was 2.8 ng/dl, free T3 was 1.1 ng/dl, and TSH was 1.2-1.5 microU/ml; the latter was measured in an immunoradiometric assay with a sensitivity of 0.07 microU/ml. Serum TSH was immunologically identical to standard TSH and did not decrease during a T3 suppression test. Serum free alpha-subunit and the molar alpha-subunit to TSH ratio were high (6.1 ng/ml and 31.2, respectively). TRH administration induced significant increases in both GH (+129%) and alpha-subunit (+156%) levels. Conversely, dopamine infusion resulted in a decrease in serum GH (-66%) and alpha-subunit (-43%) levels, and subsequent administration of the dopamine antagonist sulpiride induced significant increases in both GH and alpha-subunit (+393% and +106%, respectively). Similarly, somatostatin infusion inhibited GH (-43%) and alpha-subunit (-61%) secretion. Serum TSH levels were not affected by TRH, dopamine, or somatostatin. The biological to immunological activity ratio of serum TSH purified by immunoaffinity chromatography and measured in an adenylate cyclase assay was significantly increased compared to that in serum from hypothyroid or euthyroid subjects [biological to immunological activity ratio, 6.9 +/- 0.2 (+/- SD) vs. 4.4 +/- 1.1; P less than 0.001]. In gel chromatography, the apparent mol wt of the patient's TSH was smaller than that of the controls. After adenomectomy, all of the altered parameters of pituitary function became normal. Double gold particle immunostaining of the adenomatous tissue showed that all of the cells contained secretory granules positive for GH and alpha-subunit, while very few cells were positive for TSH beta as well as GH and alpha-subunit. These data indicate that in this patient serum TSH had an apparent mol wt smaller than that of normal TSH and an increased biological activity which, along with the autonomous TSH secretion, account for hyperthyroidism in the presence of low normal TSH levels; alpha-subunit originated from the same adenomatous cells that secreted GH but not TSH, thus explaining the in vivo observation that alpha-subunit responses to several agents were dissociated from TSH responses and parallel to GH responses; and TSH and GH were colocalized in a minority of the neoplastic cells.
本文描述了一名40岁男性，因生长激素/促甲状腺激素分泌型垂体腺瘤导致肢端肥大症和甲状腺功能亢进。血清游离T4为2.8 ng/dl，游离T3为1.1 ng/dl，促甲状腺激素（TSH）为1.2 - 1.5 μU/ml；后者采用灵敏度为0.07 μU/ml的免疫放射分析测定。血清TSH在免疫方面与标准TSH相同，且在T3抑制试验中未降低。血清游离α亚基及α亚基与TSH的摩尔比均较高（分别为6.1 ng/ml和31.2）。促甲状腺激素释放激素（TRH）给药后，生长激素（GH）水平（+129%）和α亚基水平（+156%）均显著升高。相反，多巴胺输注导致血清GH水平（-66%）和α亚基水平（-43%）降低，随后给予多巴胺拮抗剂舒必利可使GH和α亚基水平均显著升高（分别为+393%和+106%）。同样，生长抑素输注可抑制GH（-43%）和α亚基（-61%）分泌。血清TSH水平不受TRH、多巴胺或生长抑素影响。通过免疫亲和层析纯化并在腺苷酸环化酶分析中测定的血清TSH的生物学活性与免疫活性之比，与甲状腺功能减退或甲状腺功能正常受试者血清中的该比值相比显著升高[生物学活性与免疫活性之比，6.9±0.2（±标准差）对4.4±1.1；P＜0.001]。在凝胶层析中，患者TSH的表观分子量小于对照组。垂体腺瘤切除术后，垂体功能的所有改变参数均恢复正常。腺瘤组织的双金颗粒免疫染色显示，所有细胞均含有GH和α亚基阳性的分泌颗粒，而同时为TSHβ以及GH和α亚基阳性的细胞极少。这些数据表明，在该患者中，血清TSH的表观分子量小于正常TSH，且生物学活性增加，这与TSH的自主分泌一起，解释了在TSH水平略低于正常时出现的甲状腺功能亢进；α亚基源自分泌GH但不分泌TSH的同一腺瘤细胞，从而解释了体内观察到的α亚基对多种药物的反应与TSH反应分离且与GH反应平行的现象；TSH和GH共定位于少数肿瘤细胞中。
