Grasberger Helmut, Ringkananont Usanee, Croxson Michael, Refetoff Samuel
Department of Medicine, University of Chicago, Chicago, Illinois, USA.
Thyroid. 2005 Jul;15(7):730-3. doi: 10.1089/thy.2005.15.730.
We report a patient with the unusual coincidence of two rare congenital disorders, lingual ectopy of the thyroid gland and resistance to thyroid hormone (RTH), resulting in impaired thyroid hormone production and action, respectively. The proposita had a positive thyrotropin (TSH) newborn screening test (350 mU/L, confirmed) with normal thyroxine (T4) and no clinical signs of hypothyroidism. A scintiscan revealed lingual but no orthotopic thyroid tissue. Levothyroxine (LT4) replacement failed to reduce TSH and was discontinued after four months owing to significantly elevated free T4. Her physical and mental development was unremarkable, and she was considered to be clinically euthyroid throughout childhood, even though she received either no T4 or a dose insufficient to lessen hyperthyrotropinemia. At the age of 15 years, T4 was gradually increased to a supraphysiological dose of 300 microg/d, resulting in the normalization of the serum TSH level, and subjective improvements in her ability to concentrate. The proposita's mother was clinically euthyroid, had a palpable diffuse goiter, and thyroid function tests consistent with RTH. This diagnosis was confirmed by detection of a heterozygous mutation (R320H) in the thyroid hormone receptor-beta (TR-beta) gene found in both the proposita and her mother. Under the high-dose T4 regimen, the patient's TSH and free T4 values resembled those of untreated patients with TRbeta R320H mutation, suggesting that a compensated state could be achieved, at least at the pituitary level. In the proposita, treatment of hyperthyrotropinemia is clearly mandatory because of potential complications inflicted by TSH-stimulated growth of the lingual tissue. To our knowledge, this represents the first report of congenital hypothyroidism secondary to thyroid dysgenesis complicated by coincidental RTH.
我们报告了一名患者，其罕见地同时患有两种先天性疾病，即甲状腺舌异位和甲状腺激素抵抗（RTH），分别导致甲状腺激素产生和作用受损。该患者促甲状腺激素（TSH）新生儿筛查结果呈阳性（350 mU/L，已确认），甲状腺素（T4）正常，且无甲状腺功能减退的临床体征。闪烁扫描显示甲状腺位于舌部，但无正常位置的甲状腺组织。左甲状腺素（LT4）替代治疗未能降低TSH，4个月后因游离T4显著升高而停药。她的身体和智力发育正常，尽管未接受T4治疗或接受的剂量不足以减轻促甲状腺激素血症，但在整个儿童期都被认为临床甲状腺功能正常。15岁时，T4逐渐增加至超生理剂量300 μg/d，血清TSH水平恢复正常，其注意力集中能力也有主观改善。该患者的母亲临床甲状腺功能正常，可触及弥漫性甲状腺肿，甲状腺功能检查结果与RTH一致。通过检测患者及其母亲甲状腺激素受体-β（TR-β）基因中的杂合突变（R320H），确诊了该诊断。在高剂量T4治疗方案下，患者的TSH和游离T4值与未治疗的TRβ R320H突变患者相似，表明至少在垂体水平可实现代偿状态。对于该患者，由于TSH刺激舌部组织生长可能带来潜在并发症，因此明确必须治疗促甲状腺激素血症。据我们所知，这是首例因甲状腺发育异常继发先天性甲状腺功能减退并合并RTH的报告。
