Subclinical Hypothyroidism in Women Planning Conception and During Pregnancy

Who Should Be Treated and How?

Spyridoula Maraka; Naykky M. Singh Ospina; George Mastorakos; Derek T. O'Keeffe

Disclosures

J Endo Soc. 2018;2(6):533-546. 

In This Article

Abstract and Introduction

Abstract

Subclinical hypothyroidism (SCH), a mild form of hypothyroidism defined as elevated TSH with normal free thyroxine levels, is a common diagnosis among women of reproductive age. In some, but not all, studies, it has been associated with infertility, an increased risk of adverse pregnancy and neonatal outcomes, and possibly with an increased risk of neurocognitive deficits in offspring. Despite well-established recommendations on treatment of overt hypothyroid pregnant women, a consensus has not yet been reached on whether to treat women with SCH. This review focuses on examining the evidence informing the clinical strategy for using levothyroxine (LT4) in women with SCH during pregnancy and those who are planning conception. A crucial first step is to accurately diagnose SCH using the appropriate population-based reference range. For pregnant women, if this is unavailable, the recommended TSH upper normal limit cutoff is 4.0 mIU/L. There is evidence supporting a decreased risk for pregnancy loss and preterm delivery for pregnant women with TSH > 4.0 mIU/L receiving LT4 therapy. LT4 treatment has been associated with better reproductive outcomes in women with SCH undergoing artificial reproductive techniques, but not in those who are attempting natural conception. Thyroid function tests need to be repeated throughout pregnancy to monitor LT4 therapy. In addition to potential harms, LT4 contributes to treatment burden. During a consultation, clinicians and patients should engage in a careful consideration of the current evidence in the context of the patients' values and preferences to determine whether LT4 therapy initiation is the best next step.

Introduction

Subclinical hypothyroidism (SCH) is a mild form of hypothyroidism defined as an elevated TSH concentration in conjunction with normal free thyroxine (FT4) levels.[1] It is a common diagnosis among women of reproductive age (4% to 8%) and as such it can affect women planning conception and pregnant women.[2] Owing to the nonspecific nature of the hypothyroidism-related symptoms (e.g., fatigue), the diagnosis of SCH is based on laboratory testing.[1]

In contrast to the known negative impact on conception and pregnancy of overt hypothyroidism (e.g., increased risk of pregnancy loss, premature birth, lower offspring intelligence quotient), in which TSH is elevated and the FT4 level is below normal, the impact of SCH remains unclear. In some studies, it has been associated with infertility,[3] an increased risk of adverse pregnancy and neonatal outcomes,[4–14] and possibly with an increased risk of neurocognitive deficits in the offspring.[15] However, other studies have not found an association of SCH with adverse outcomes.[16–19]

The recommended treatment of maternal overt hypothyroidism is administration of oral levothyroxine (LT4). The question that clinicians are called to answer is the following: Is SCH also a disease requiring treatment or is it just a biochemical diagnosis of no clinical consequences? Although there are a few observational studies suggesting a beneficial effect of LT4 treatment in pregnant women with SCH,[20] results from large randomized trials suggest the opposite.[21,22]

This review discusses the evidence informing the clinical strategy for using LT4 in women with SCH during pregnancy and those who are planning conception, focusing on the benefits and risks of treatment. We also consider issues related to the monitoring and duration of treatment.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....