Nobels F R, Kwekkeboom D J, Coopmans W, Hoekstra R, De Herder W W, Bouillon R, Lamberts S W
Department of Medicine, Erasmus University, Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 1993 Sep;77(3):784-9. doi: 10.1210/jcem.77.3.7690365.
We tested the hypothesis of whether chromogranin-A (CGA), an immunohistochemical marker of neuroendocrine tumors, could serve as a serum marker for clinically nonfunctioning pituitary adenomas. Basal and TRH-stimulated concentrations of LH, FSH, alpha-subunit, and CGA were measured in 22 patients with clinically nonfunctioning pituitary adenomas and in 20 control patients with other pituitary tumors. The control group consisted of 9 patients with PRL- and/or GH-secreting adenomas and 11 patients with nonendocrine tumors [5 craniopharyngiomas, 2 (dys)germinomas, 1 astrocytoma, 1 meningioma, 1 neurinoma of the acoustic nerve, and 1 dermoid cyst]. Immunohistochemical staining for CGA was performed on tumor tissue obtained at transsphenoidal surgery in 18 study and 12 control patients. Tissue from 19 of the 22 clinically nonfunctioning adenomas was cultured, and concentrations of LH, FSH, alpha-subunit, and CGA were measured. Immunohistochemical staining for CGA was positive in 15 of 18 clinically nonfunctioning adenomas and negative in all examined control tumors (n = 12). CGA was present in the culture medium of 16 of 18 adenomas in vitro. In 3 adenomas it was present in the absence of detectable amounts of gonadotropins or alpha-subunit. Basal serum levels of gonadotropins and/or alpha-subunit were elevated in 7 of 22 patients with clinically nonfunctioning adenomas and in 4 of 9 control patients with PRL- and/or GH-secreting adenomas. Basal CGA was elevated in 2 study patients and 1 prolactinoma patient. Significant increases in serum gonadotropin and/or alpha-subunit levels in response to TRH occurred in 14 of 21 patients with clinically nonfunctioning adenomas and in 13 of 20 control patients. A significant CGA peak after TRH administration was demonstrated in 6 patients with clinically nonfunctioning pituitary tumors and in none of the controls. We conclude that 1) immunohistochemical staining for CGA is an excellent tool to prove the endocrine origin of clinically nonfunctioning pituitary tumors; 2) in vivo, the gonadotroph origin can be recognized in only a minority of patients who have elevated basal levels of LH, FSH, or alpha-subunit; 3) examination of the effect of TRH on CGA release is a rather insensitive, but specific, diagnostic test, allowing differentiation from nonendocrine pituitary tumors; and 4) the responses of gonadotropins and alpha-subunit to TRH, although more sensitive, are not specific for clinically nonfunctioning pituitary adenomas and are probably only reliable in cases of total hypopituitarism.
神经内分泌肿瘤的免疫组化标志物嗜铬粒蛋白A（CGA）能否作为临床无功能垂体腺瘤的血清标志物。对22例临床无功能垂体腺瘤患者和20例患有其他垂体肿瘤的对照患者，测定了基础状态下以及促甲状腺激素释放激素（TRH）刺激后的促黄体生成素（LH）、促卵泡生成素（FSH）、α亚基和CGA的浓度。对照组包括9例分泌催乳素（PRL）和/或生长激素（GH）的腺瘤患者以及11例非内分泌肿瘤患者[5例颅咽管瘤、2例（生殖）细胞瘤、1例星形细胞瘤、1例脑膜瘤、1例听神经神经瘤和1例皮样囊肿]。对18例研究患者和12例对照患者经蝶窦手术获取的肿瘤组织进行了CGA免疫组化染色。对22例临床无功能腺瘤中的19例组织进行了培养，并测定了LH、FSH、α亚基和CGA的浓度。18例临床无功能腺瘤中有15例CGA免疫组化染色呈阳性，所有检测的对照肿瘤（n = 12）均为阴性。18例腺瘤中有16例在体外培养的培养基中检测到CGA。在3例腺瘤中，CGA在未检测到促性腺激素或α亚基的情况下出现。22例临床无功能腺瘤患者中有7例基础血清促性腺激素和/或α亚基水平升高，9例分泌PRL和/或GH的腺瘤对照患者中有4例升高。2例研究患者和1例催乳素瘤患者基础CGA升高。21例临床无功能腺瘤患者中有14例、20例对照患者中有13例在给予TRH后血清促性腺激素和/或α亚基水平显著升高。6例临床无功能垂体肿瘤患者在给予TRH后出现显著的CGA峰值，而对照组均未出现。我们得出以下结论：1）CGA免疫组化染色是证明临床无功能垂体肿瘤内分泌起源的极佳工具；2）在体内，只有少数基础LH、FSH或α亚基水平升高患者可识别出促性腺激素细胞来源；3）检测TRH对CGA释放的影响是一项不太敏感但具有特异性的诊断试验，可用于与非内分泌垂体肿瘤相鉴别；4）促性腺激素和α亚基对TRH的反应虽然更敏感，但对临床无功能垂体腺瘤不具有特异性，可能仅在全垂体功能减退的情况下可靠。
