Department of Pediatrics, University of Maryland, Baltimore, Maryland 21201, USA.
Thyroid. 2013 Jul;23(7):892-7. doi: 10.1089/thy.2012.0332. Epub 2013 Jun 21.
Typically, newborns with congenital hypothyroidism are asymptomatic at birth, having been exposed to euthyroid mothers. However, hypopituitarism may be associated with central hypothyroidism, preserved fertility, and autosomal dominant inheritance, requiring increased attention to thyroid management during pregnancy.
A woman with a history of growth hormone deficiency and central hypothyroidism gave birth to a term male neonate appropriate for gestational age. Due to low thyrotropin (TSH) in the second trimester, the levothyroxine dose was decreased by the obstetrician, and free T4 was low throughout the latter half of pregnancy. The neonatal laboratory evaluation showed central hypothyroidism with a low T4 of 2.1 μg/dL (4.5-11.5) and an inappropriately normal TSH of 0.98 uIU/mL (0.5-4.5); undetectable growth hormone, IGF-I, and IGFBP3; a normal cortisol level; and a normal gonadotropin surge. After initiation of levothyroxine in the first week, both tone and feeding tolerance improved. However, the patient was found to have hearing loss, gross motor delay, and speech delay.
In this report, we review a case of vertical transmission of a dominant negative POU1F1 mutation in which fetal abnormalities due to the hypothyroxinemic state during gestation may have been exacerbated by a decrease in the mother's levothyroxine dose based on a low TSH in early gestation. Both mother and fetus were unable to synthesize sufficient thyroid hormone, which may be responsible for the patient's clinical presentation.
This case underscores several important points in the management of women with hypopituitarism. First, it is important that patients and clinicians are both aware of the differences in etiology, as well as appropriate screening and treatment, of primary versus central hypothyroidism. Second, it is necessary to monitor the thyroid hormone status closely during pregnancy to prevent fetal sequelae of maternal hypothyroidism. Third, genetic screening of patients with combined pituitary hormone deficiency is necessary, so that prenatal genetic counseling may be an option for expecting parents.
通常情况下，患有先天性甲状腺功能减退症的新生儿在出生时没有症状，因为他们的母亲甲状腺功能正常。然而，垂体功能减退症可能与中枢性甲状腺功能减退症、生育能力保留和常染色体显性遗传有关，这就需要在怀孕期间更加关注甲状腺的管理。
一位患有生长激素缺乏症和中枢性甲状腺功能减退症的女性足月分娩了一名男婴。由于在妊娠中期促甲状腺激素（TSH）较低，产科医生减少了左甲状腺素的剂量，并且整个妊娠后半期游离 T4 水平较低。新生儿实验室检查显示中枢性甲状腺功能减退，四碘甲状腺原氨酸（T4）水平为 2.1μg/dL（4.5-11.5），促甲状腺激素（TSH）水平不适当正常为 0.98uIU/mL（0.5-4.5）；生长激素、胰岛素样生长因子-1（IGF-1）和胰岛素样生长因子结合蛋白 3（IGFBP3）均无法检测到；皮质醇水平正常；促性腺激素激增正常。在出生后第一周开始使用左甲状腺素后，患儿的张力和喂养耐受性均得到改善。然而，该患者被发现存在听力损失、粗大运动发育迟缓以及言语发育迟缓。
在本报告中，我们回顾了一例垂直传播的显性负 POU1F1 突变病例，由于妊娠期间的甲状腺素不足，胎儿可能出现了异常，而母亲根据妊娠早期 TSH 水平降低而减少左甲状腺素剂量可能加重了这种情况。母亲和胎儿都无法合成足够的甲状腺激素，这可能是导致该患者临床表现的原因。
该病例强调了在管理垂体功能减退症女性患者时需要注意的几个重要问题。首先，患者和临床医生都应该意识到原发性甲状腺功能减退症和中枢性甲状腺功能减退症在病因、以及适当的筛查和治疗方面的差异。其次，在怀孕期间必须密切监测甲状腺激素状态，以防止母亲甲状腺功能减退症对胎儿造成的后果。第三，对于合并垂体激素缺乏症的患者需要进行基因筛查，以便为有生育需求的父母提供产前遗传咨询。
