七、治疗和预后
中枢性甲减的治疗原则是恢复血清甲状腺激素的浓度。尽管在理论上，这些可以通过TSH或者TRH的替代得以实现，但是由于成本以及严格的适用性[9]，这些方法已经搁浅。因此，首选的中枢性甲减治疗方法是以L-T4的替代。Bunevicius R等报道配有甲状腺素以及三碘甲状腺原氨酸的治疗相比于甲状腺素单独治疗更有效[9]。但是，最近相关研究对患有CH的患者的研究未支持这一理论，并未见联合治疗的优越性[43-44]。在原发性疾病中，L-T4的治疗初期应该从较低剂量（例如，每天25μg）起始，尤其是那些长期患有甲状腺功能减退的患者，在治疗后期可以逐渐增加剂量，在接下来的几周中，不断增加，直至适合剂量为止。对患有CPHDs的患者，在开始L-T4治疗之前，必须排除肾上腺皮质功能不全，因为单纯给予L-T4可能会诱发肾上腺危象。如果在开始L-T4治疗之前不能评估肾上腺功能，建议使用糖皮质激素进行预防性治疗。
考虑到L-T4的日常使用剂量，近期有些文献研究了中枢性甲减患者的L-T4替代疗法，这些文献着重讨论了实现替代疗法易犯的错误。L-T4替代疗法对于原发性甲减很容易实现，只需要测定循环TSH水平，但是对于监测中枢性甲减患者L-T4疗法来说，这一指标的参考价值也有限。但是，在L-T4治疗期间，发现未被抑制的血清TSH水平表明了治疗不足。实际上，在Ferretti及其同事的报道中[34]，在大约80%的中枢性甲减患者中，一半的L-T4替代剂量足以抑制TSH分泌，但是大部分的血清FT4水平仍然处于甲减水平。与之类似，Carrozza及同事观察到，在L-T4治疗期间，135名中枢性甲减患者中大部分患者的血清TSH浓度不正常[45]。Shimon和同事证实了这些发现，并表示TSH水平高于1.0mIU/L清楚反映了L-T4替代治疗尚不足[46]。因此，评估循环游离甲状腺激素水平是监测中枢性甲减患者L-T4治疗的主要因素。毫无疑问，游离甲状腺激素测定的准确度要高于所有甲状腺激素的指标，其测定方法是通过平衡透析或者直接的两步法测FT4（在未受到不正常血清结合蛋白或者是抗T4/抗T3抗体的干扰下）。在原发性甲状腺疾病中，FT4在甲状腺功能减退症中具有很高的精确度，但是FT3的精确度更高。因此，如果在清晨测定FT4，在替代治疗之前抽取血液，那么较低的FT4可能表示治疗不足，而较高的FT3则表示治疗过度[34]。然而，血清FT4和FT3同时测量的必要性仍然存有争议，因为当前大部分FT3的测量方法是不准确的。这些指标的测量应该考虑到可能来自CPHD的影响，因为在很大程度上，这些参数大部分受到促生长激素细胞、性腺、肾上腺功能改变的影响[34-35]。由于缺乏敏感性和特异性，只有这些参数的纵向评估，例如性激素结合球蛋白（SHBG）、骨钙蛋白或胆固醇，可能有助于解释CH患者的治疗不足或过度。这些参数一般用于对于甲状腺功能亢进的评估，因此其敏感性更有助于解释CH患者的治疗过度。
最近，Koulouri和同事开始用一种新方法着手解决CH替代疗法的问题。他们使用其部门的临床信息系统检出患有甲状腺-垂体病变的患者，并且将他们进行了高风险和低风险的分类之后，他们将这些患者与患有原发性甲状腺功能不足的患者（足量的L-T4治疗中）比较，即那些在替代治疗期间循环TSH水平正常的人进行比较。结论是中枢性甲减的患者一般都治疗不足[47]。此外，他们建议FT4水平应该在16pmol/L左右（参考值范围为9～25pmol/L），这也许代表着中枢性甲减患者的一个合理数值。这一结论同之前许多学者的结论很相似。例如，将FT4调整到实验正常值范围的中间值。Ferretti和同事以及Alexopoulou及其同事分别指出，如果L-T4的日常用量为（1.5±0.3）μg/（kg·d）以及（1.6±0.5）μg/（kg·d），大多数接受治疗的中枢性甲减患者的FT4水平可以控制在一个合理范围。这些最优剂量同原发性甲减的报道也相似。对于原发性甲减，年轻的中枢性甲减患者需要更大的剂量。而且，L-T4的剂量也取决于CPHD的伴随治疗。研究表明，接受重组hGH（rhGH）替代疗法的患者需要更多的L-T4用量。因此，GH不足可能会遮盖CH的亚临床表现，而且CH只有在rhGH替代疗法之后才能显示出生化特征[48]。rhGH对下丘脑-垂体-甲状腺轴的影响，是仅对于那些甲状腺功能部分损坏的CPHD患者具有生物相关性，而对于那些仅仅患有GH缺乏，而甲状腺形态和功能未受损的患者，rhGH治疗不能诱导中枢性甲减[49]。据报道，雌激素可以增加甲状腺功能减退患者L-T4的需求量[50]。这可能是由甲状腺素结合球蛋白 （TBG）水平增加所致，故应该调整L-T4用量以增加血浆蛋白的T4结合能力。
对于新生儿或童年发病的中枢性甲减患者，其治疗策略是有所不同的。正常情况下，婴儿和儿童的游离甲状腺激素水平更高[51]。因此，针对甲状腺功能减退患儿，建议使用高剂量的L-T4，并且应该在开始时便使用足量剂量，尤其是新生儿发病，应该及时治疗以保证正常神经发育。指南建议新生儿疾病的治疗从10～15μg/kg L-T4开始，每隔2～4周测定FT4水平，以调整剂量目标范围，这应该是从对正常儿童中的观察中得到[51]。在儿童时期过渡到成年的过程中，逐步降低替代剂量。
总而言之，L-T4替代疗法如果满足以下条件可能达到最优效果：①排除肾上腺功能不全后再治疗。②在随访期间，每日摄入L-T4片之前，采血测FT4水平。③基于年龄和性别决定用药剂量（每天1.4～1.7μg/kg）。④使循环FT4水平维持在实验室参考值中间数值。⑤有其他垂体激素的同时替代时，重新评估L-T4剂量。⑥当TSH水平＞ 0.5mIU/L时，考虑替代剂量不足。⑦在碘缺乏的国家，考虑可能存在结节性甲状腺肿伴有自主甲状腺激素分泌，谨防L-T4过度治疗。
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