McDermott M T, Ridgway E C
Division of Endocrinology, University of Colorado Health Sciences Center, Denver, USA.
Endocrinol Metab Clin North Am. 1998 Mar;27(1):187-203. doi: 10.1016/s0889-8529(05)70306-6.
Central hyperthyroidism is a rare condition in which thyrotoxicosis results from primary overproduction of TSH by the pituitary gland with subsequent thyroid enlargement and hyperfunction. The two known causes of central hyperthyroidism are TSH-producing pituitary tumors (TSHomas) and the syndrome of PRTH. Both of these entities are characterized by clinical thyrotoxicosis, diffuse goiters, elevated circulating levels of free T4 and T3, and a nonsuppressed serum TSH. It is critical to distinguish central hyperthyroidism from the much more common types of primary hyperthyroidism, all of which have undetectable TSH values. TSHomas and PRTH can usually be differentiated from one another by measuring the serum alpha-subunit and the TSH response to intravenous TRH or exogenous thyroid hormone, and by pituitary imaging studies. TSHomas are usually benign adenomas arising from the monoclonal expansion of neoplastic thyrotropes. Causative oncogenes have not yet been convincingly identified. PRTH is a nonneoplastic disorder caused by inherited mutations in the gene for the thyroid hormone receptor beta; it is a poorly understood variant of GRTH. For unclear reasons, in PRTH, the pituitary gland is resistant to the feedback inhibitory effects of circulating thyroid hormones while peripheral tissues respond normally, causing patients to experience the toxic peripheral effects of thyroid hormone excess. TSHomas are best treated by transphenoidal surgical removal. Radiotherapy is indicated for inoperable or incompletely resected tumors. Octreotide administration is a useful adjunct for preoperatively reducing tumor size and for the medical management of surgical treatment failures. PRTH is ideally treated by chronically suppressing TSH secretion with medications such as D-thyroxine, TRIAC, octreotide, or bromocriptine. If such therapy is ineffective or unavailable, thyroid ablation with radioiodine or surgery may be employed with subsequent close monitoring of both thyroid hormone status and pituitary gland size.
中枢性甲状腺功能亢进是一种罕见的疾病，其甲状腺毒症是由垂体原发性过度分泌促甲状腺激素（TSH），随后导致甲状腺肿大和功能亢进引起的。中枢性甲状腺功能亢进的两个已知病因是分泌TSH的垂体肿瘤（TSH瘤）和垂体抵抗性甲状腺激素过多综合征（PRTH）。这两种疾病的特征均为临床甲状腺毒症、弥漫性甲状腺肿、游离T4和T3的循环水平升高以及血清TSH未被抑制。将中枢性甲状腺功能亢进与更为常见的原发性甲状腺功能亢进类型区分开来至关重要，所有原发性甲状腺功能亢进类型的TSH值均无法检测到。TSH瘤和PRTH通常可通过测量血清α亚基、TSH对静脉注射促甲状腺激素释放激素（TRH）或外源性甲状腺激素的反应以及垂体成像研究来相互鉴别。TSH瘤通常是由肿瘤性促甲状腺细胞的单克隆扩增引起的良性腺瘤。尚未令人信服地确定致病致癌基因。PRTH是一种非肿瘤性疾病，由甲状腺激素受体β基因的遗传突变引起；它是广义抵抗性甲状腺激素过多综合征（GRTH）中了解较少的一种变体。原因不明的是，在PRTH中，垂体对循环甲状腺激素的反馈抑制作用具有抵抗性，而外周组织反应正常，导致患者出现甲状腺激素过量的毒性外周效应。TSH瘤最好通过经蝶窦手术切除治疗。对于无法手术或切除不完全的肿瘤，需进行放射治疗。使用奥曲肽是术前缩小肿瘤大小以及对手术治疗失败进行药物管理的有用辅助方法。PRTH的理想治疗方法是使用D-甲状腺素、三碘甲状腺乙酸（TRIAC）、奥曲肽或溴隐亭等药物长期抑制TSH分泌。如果这种治疗无效或无法进行，可以采用放射性碘或手术进行甲状腺消融，随后密切监测甲状腺激素状态和垂体大小。
