Subclinical hypothyroidism and gestational hypertension: causal or coincidence?

Abstract

Thyroid hormone is critical in maintaining systemic homeostasis, as is demonstrated by the myriad of effects caused by thyroid hormone deficiency. Overt hypothyroidism can significantly disturb the cardiovascular system, resulting in alterations in left ventricular function, decreased cardiac output, and increased systemic vascular resistance. The effects of subclinical hypothyroidism, defined as an elevated thyroid-stimulating hormone (TSH) level with normal serum thyroxine (T4) levels, on the cardiovascular system are less clear. While subclinical hypothyroidism has been linked to an increased risk of hypertension and cardiovascular mortality in some observational studies, other studies have found no difference in blood pressure between euthyroid subjects and subjects with subclinical hypothyroidism. 1,2 The treatment in nonpregnant adults is also controversial. The most recent consensus guidelines from two major endocrinology societies recommend levothyroxine therapy for a TSH level of greater than 10, but that at levels lower than 10, treatment decisions should be made based on patient symptoms and other risk factors, such as the presence of anti-thyroperoxidase (TPO) antibodies. 3 There is no strong evidence to support treating patients with subclinical hypothyroidism and hypertension solely to improve blood pressure control. Several alterations occur in thyroid hormone metabolism during pregnancy, making the diagnosis and management of hypothyroidism in pregnancy more complex. Serum thyroid-binding globulin levels increase in pregnancy and women with preexisting hypothyroidism need escalating doses of levothyroxine due to the excess in thyroidbinding globulin. Human chorionic gonadotropin, in addition, weakly stimulates TSH receptors, resulting in a transient, physiologic increase in T4 and triiodothyronine (T3) concentrations, peaking at around 20 weeks gestation. The thresholds for abnormal TSH are, therefore, lower in pregnancy due to these physiologic changes. 3 Subclinical hypothyroidism is quite common in pregnancy, occurring in up to 15% of pregnancies, while overt hypothyroidism is still rare (0.2%), likely due to the anovulation and diminished fertility seen with this condition. 4 Several case reports have described a preeclampsia-like syndrome in the setting of overt hypothyroidism, associated with very poor fetal outcomes. 5,6 In a case series of pregnancy outcomes in women with both subclinical (n ¼ 12) and overt hypothyroidism (n ¼ 16), the authors found that preeclampsia occurred frequently in pregnancies complicated by overt hypothyroidism (n ¼ 7), but less commonly in women with subclinical hypothyroidism (n ¼ 2). A recent meta-analysis demonstrated that women with subclinical hypothyroidism were at an increased risk for adverse pregnancy outcomes, including pregnancy loss and neonatal death, but they were not at an increased risk for gestational hypertension or preeclampsia. 7