Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Thyroid. 2012 Oct;22(10):1080-3. doi: 10.1089/thy.2011.0521. Epub 2012 Sep 4.
Ring chromosome 18 [r18] is a rare constitutional chromosomal aberration syndrome, characterized by dysmorphic face, hypoactivity, short stature, and delayed development. Autoimmune thyroiditis and immunoglobulin (Ig) A deficiency are occasionally associated with chromosome-18 deletion syndromes.
Here, we report a 2-year-old male child with r(18) syndrome and a selective IgA deficiency (<1.6 mg/dL, reference range [rr]: 20-149), who developed hypothyroidism and liver dysfunction. Thyroid function tests (thyroid-stimulating hormone [TSH]: 1031 μIU/mL, rr 0.43-4.0; free triiodothyronine: 0.52 pg/mL, rr 2.37-4.65; free thyroxine: 0.11 ng/dL, rr 1.03-2.00) and positive thyroid antibodies (anti-TSH receptor 1.7 IU/L, cut-off index [coi]: <1.0, antithyroid peroxidase 171 IU/mL, coi <0.3, and antithyroglobulin 2.8 IU/mL, coi <0.3) indicated autoimmune hypothyroidism. Elevated levels of aspartate aminotransferase (AST, 240 IU/L, rr 17-39) and alanine aminotransferase (ALT, 315 IU/L, rr 4-23), but negative antibodies against LKM and mitochondrial M2, suggested no autoimmune hepatitis. Transaminase levels became normalized after he was given levothyroxine therapy to achieve the euthyroid state, but they repeatedly became elevated when levothyroxine was inadvertently discontinued (peak AST=409 IU/L; peak ALT=390 IU/L). A maintenance dose of levothyroxine has effectively maintained the euthyroid state and normalized liver function tests despite no immunosuppressive therapy.
The r18 patient with autoimmune hypothyroidism and IgA deficiency suffered from idiopathic hepatitis. The liver dysfunction was associated with hypothyroidism that resolved with thyroid hormone treatment. While the former combination has been described, the latter has not. The reason for the development of hepatitis in association with hypothyroidism is unexplained. However, we postulate that it might be related, in ways that are not clear, to the deleted genes of r18.
环状染色体 18[r18] 是一种罕见的遗传性染色体异常综合征，其特征为面部畸形、活动力低下、身材矮小和发育迟缓。自身免疫性甲状腺炎和免疫球蛋白（Ig）A 缺乏症偶尔与 18 号染色体缺失综合征相关。
本研究报道了一例 2 岁男性患儿，患有 r（18）综合征和选择性 IgA 缺乏症（<1.6mg/dL，参考范围[rr]：20-149），该患儿出现甲状腺功能减退和肝功能障碍。甲状腺功能检测（促甲状腺激素[TSH]：1031μIU/mL，rr 0.43-4.0；游离三碘甲状腺原氨酸：0.52pg/mL，rr 2.37-4.65；游离甲状腺素：0.11ng/dL，rr 1.03-2.00）和阳性甲状腺抗体（抗 TSH 受体 1.7IU/L，截断指数[coi]：<1.0，抗甲状腺过氧化物酶 171IU/mL，coi<0.3，抗甲状腺球蛋白 2.8IU/mL，coi<0.3）提示自身免疫性甲状腺功能减退。天冬氨酸转氨酶（AST，240IU/L，rr 17-39）和丙氨酸转氨酶（ALT，315IU/L，rr 4-23）升高，但 LKM 和线粒体 M2 抗体阴性，提示无自身免疫性肝炎。在给予左甲状腺素治疗以使患儿达到甲状腺功能正常状态后，转氨酶水平恢复正常，但当无意中停止左甲状腺素治疗时，转氨酶水平再次升高（AST 峰值=409IU/L；ALT 峰值=390IU/L）。尽管未进行免疫抑制治疗，但左甲状腺素维持剂量有效地维持了甲状腺功能正常状态和肝功能检测正常。
患有自身免疫性甲状腺功能减退和 IgA 缺乏症的 r18 患者患有特发性肝炎。肝功能障碍与甲状腺功能减退有关，甲状腺功能减退在甲状腺激素治疗后得到缓解。虽然前者的组合已有描述，但后者尚未描述。与甲状腺功能减退相关的肝炎的发生原因尚不清楚。然而，我们推测这可能与 r18 缺失的基因有关，但具体机制尚不清楚。
