Boyages S C, Halpern J P
Department of Clinical Endocrinology, Westmead Hospital, Sydney, Australia.
Thyroid. 1993 Spring;3(1):59-69. doi: 10.1089/thy.1993.3.59.
Based on our data, the clinical picture of endemic cretinism results from the product of two pathophysiological events. Both events share a common feature, namely iodine deficiency, but act at different points in time. The first event occurs in all cretins and represents the prenatal action of thyroid hormone deficiency on brain development, transmitted vertically from mother to fetus, resulting in the neurological disorder of endemic cretinism. A consistent pattern and intensity of neurological, intellectual, and audiometric deficit is common to and equally present in all types of endemic cretin. The nature of these deficits points to an intrauterine insult to the developing fetal nervous system around the time of the midtrimester. The second event represents the postnatal action of thyroid hormone deficiency on somatic as well as brain development. Whereas previous workers had attributed the differences in the clinical presentation of endemic cretinism to the presence or absence of neurological features (i.e. prenatal hypothyroidism), the distinction between the types of endemic cretin can be related to the length and severity of postnatal thyroid hormone deficiency. Endemic cretins with predominant neurological features have had only transient hypothyroidism in the postnatal period, evidenced by their near normal thyroid function and by a lack of hypothyroid clinical features. By contrast, cretins with marked myxedematous features were characterized by permanent and severe postnatal thyroid hormone deficiency. These cretins, in addition to signs of neurological damage, were typically dwarfed, sexually immature, with marked clinical features of myxedema. This second event, influenced by the thyroid gland's morphologic response to its environment (goiter or thyroid atrophy), dictates the final clinical outcome. In conclusion, our hypothesis states that the clinical expression of endemic cretinism is determined by the sum of two pathophysiologic processes. The first process is fetal hypothyroidism which results in the neurological damage of the disorder and the second process is the duration and magnitude of postnatal hypothyroidism which dictates the final clinical appearance.
根据我们的数据，地方性克汀病的临床表现是两种病理生理事件共同作用的结果。这两种事件都有一个共同特征，即碘缺乏，但作用于不同的时间点。第一个事件发生在所有克汀病患者身上，代表甲状腺激素缺乏对脑发育的产前影响，由母亲垂直传递给胎儿，导致地方性克汀病的神经障碍。所有类型的地方性克汀病都有一致的神经、智力和听力缺陷模式及严重程度，且同样存在。这些缺陷的性质表明，在妊娠中期左右，发育中的胎儿神经系统受到了宫内损伤。第二个事件代表甲状腺激素缺乏对躯体和脑发育的产后影响。以往的研究人员将地方性克汀病临床表现的差异归因于神经特征的有无（即产前甲状腺功能减退），而地方性克汀病类型之间的区别可能与产后甲状腺激素缺乏的持续时间和严重程度有关。以神经特征为主的地方性克汀病患者在出生后仅有短暂的甲状腺功能减退，这可从其甲状腺功能接近正常以及缺乏甲状腺功能减退的临床特征得到证明。相比之下，具有明显黏液性水肿特征的克汀病患者的特点是出生后永久性和严重的甲状腺激素缺乏。这些克汀病患者除了有神经损伤的体征外，通常身材矮小、性发育不成熟，并有明显的黏液性水肿临床特征。这第二个事件受甲状腺对其环境的形态学反应（甲状腺肿或甲状腺萎缩）影响，决定了最终的临床结果。总之，我们的假设是，地方性克汀病的临床表型由两个病理生理过程共同决定。第一个过程是胎儿甲状腺功能减退，导致该疾病的神经损伤，第二个过程是产后甲状腺功能减退的持续时间和严重程度，它决定了最终的临床外观。
