Akita S, Hirano A, Fujii T
Department of Plastic and Reconstructive Surgery, Nagasaki University School of Medicine, Japan.
Plast Reconstr Surg. 1996 Jan;97(1):1-12. doi: 10.1097/00006534-199601000-00001.
Premature closure of cranial sutures has been known as one of the complications of juvenile or congenital hyperthyroidism. Thyroid hormone is an anabolic agent for bone formation in the early stages of childhood development. In children, excess thyroid hormone acts as an acceleration factor for the skeletal bone, whereas in adult hyperthyroidism, it causes bone mineral loss due to the high turnover rate of bone formation and consequently bone resorption. In addition, there are numerous literature descriptions concerning the interactions among bone metabolism, hormones, and growth factors, among which insulin-like growth factor I (IGF-I) is the most abundantly found growth factor in osteoblasts and in bone models in vivo. We therefore investigated whether or not the cranial sutures show accelerated closure and how the local growth factors or cytokines participate and function in local bone metabolism after administration of exogenous excess thyroid hormone in a rat model. A total of 60 female Wistar rats, aged 10 days, were divided into two groups, the triiodothyronine (T3)-treated group (n = 30, T3 0.1 microgram/gm of body weight per day) and the control group (n = 30, saline vehicle only), and were maintained and subsequently sacrificed at 15, 30, and 60 days. The parameters of cranial width derived from the morphologic measurements of the skull indicated that the lambda-asterion distance at 30 days and the pterion-bregma distance at 60 days in the T3-treated group were significantly decreased compared with those of the control group. Furthermore, the fluorescent histologic findings showed fluorescent labeling with no interruption along the suture edges, suggesting continuous bone formation, and displayed narrowing of the suture gap of the sagittal suture in the T3-treated group. Tartrate resistant acid phosphatase staining showed very little osteoclastic activity in the sagittal suture, especially in the T3-treated group. The intensity of immunohistochemical staining of IGF-I was markedly increased in the suture margins of the T3-treated group. There were no significant differences observed either in the skull base measurements or in the histologic and histochemical findings of the skull base or the coronal suture between the groups. More significantly, excess administration of thyroid hormone enhanced the cranial sagittal suture closure; therefore, it was proposed that local IGF-I plays an important role in sagittal sutural bone formation.
颅缝过早闭合一直被认为是青少年或先天性甲状腺功能亢进症的并发症之一。甲状腺激素是儿童发育早期骨骼形成的合成代谢剂。在儿童中，过量的甲状腺激素是骨骼生长的加速因子，而在成人甲状腺功能亢进症中，由于骨形成的高周转率以及随之而来的骨吸收，它会导致骨矿物质流失。此外，有大量关于骨代谢、激素和生长因子之间相互作用的文献描述，其中胰岛素样生长因子I（IGF-I）是成骨细胞和体内骨模型中发现最多的生长因子。因此，我们研究了在大鼠模型中给予外源性过量甲状腺激素后，颅缝是否显示加速闭合，以及局部生长因子或细胞因子如何参与并在局部骨代谢中发挥作用。总共60只10日龄的雌性Wistar大鼠被分为两组，即三碘甲状腺原氨酸（T3）治疗组（n = 30，每天每克体重给予0.1微克T3）和对照组（n = 30，仅给予生理盐水），并分别在15天、30天和60天时进行饲养并随后处死。从颅骨形态测量得出的颅宽参数表明，与对照组相比，T3治疗组在30天时的人字点-星点距离和在60天时的翼点-前囟距离显著减小。此外，荧光组织学结果显示沿缝线边缘有不间断的荧光标记，表明骨形成持续进行，并且T3治疗组矢状缝的缝线间隙变窄。抗酒石酸酸性磷酸酶染色显示矢状缝中破骨细胞活性非常低，尤其是在T3治疗组。T3治疗组缝线边缘IGF-I免疫组化染色强度明显增加。两组之间在颅底测量以及颅底或冠状缝的组织学和组织化学结果方面均未观察到显著差异。更显著的是，过量给予甲状腺激素会加速颅矢状缝闭合；因此，有人提出局部IGF-I在矢状缝骨形成中起重要作用。
