Clinical Pearls:
- Subclinical hypothyroidism (SCH) is defined as elevated TSH levels with normal serum levels of thyroxine (T4). Recently ATA redefined the upper limit of TSH during pregnancy to 2.5 mIU/L during the first trimester and 3.0 mIU/L during the second and third trimesters
- The review confirms the association of SCH during pregnancy with multiple adverse maternal and neonatal outcomes, but there is not sufficient evidence to support the use of levothyroxine therapy to mitigate this association.
- Decision to start levothyroxine in such patients should be taken after an open and well informed discussion between patients and physicians.
Routine
screening of all pregnant women for hypothyroidism is debatable because of
conflicting data from previous studies. ACOG and American Thyroid Association (ATA)
recommends against universal first trimester screening of pregnant women.
Subclinical
hypothyroidism (SCH) is defined as elevated TSH levels with normal serum
levels of thyroxine (T4). Recently ATA redefined the upper limit of TSH during
pregnancy to 2.5 mIU/L during the first trimester and 3.0 mIU/L during the
second and third trimesters.[1]
When
screened according to the updated criteria’s, nearly 15% pregnant women in
United states have SCH, which is almost 5 times the previous prevalence.
Many studies
have reported adverse maternal and neonatal outcomes in pregnancy with SCH that
includes an array of problems like including recurrent pregnancy loss, preterm
delivery, gestational diabetes, gestational hypertension, preeclampsia,
placental abruption, premature rupture of membranes, intrauterine growth
restriction, low birth weight, small for gestational age, low Apgar score, and
neonatal death.
Some studies
also report increased risk of cognitive deficits with rising TSH levels.
Other
studies have not found any statistically significant association between SCH
and adverse pregnancy outcomes.
This systemic review and meta-analysis estimates the effect of SCH on pregnancy outcome with patients who are euthyroid and the effect of levothyroxine on preventing the
adverse pregnancy outcomes.
The study
was published in the April issue of Journal Thyroid.[2]
The main
outcome measures were pregnancy loss (miscarriage, IUD and fetal loss). Other
outcome measure included various other complications of pregnancy.
Comprehensive
search of data base from inception to January 2015, identified 1108 potentially
eligible studies, of which 18 cohort studies comprising of total 3995 pregnant
women with SCH were eligible.
After meta-analysis
and sensitivity analysis, it was seen that women with SCH were at higher risk
for pregnancy loss, placental abruption, PROM, and neonatal death compared with
euthyroid pregnant women.
The study
also showed the prevalence of inconsistencies in defining SCH in different
studies, absence of trimester specific range and cutoff that is used to start
treatment with levothyroxine.
The ATA
guidelines recommend treatment of pregnant women with SCH and positive TPO
antibodies (Level B, fair evidence—USPSTF), but found insufficient evidence to
recommend for or against universal levothyroxine treatment in pregnant women
with SCH and negative TPO antibodies (Level I—USPSTF).[3]
The
Endocrine Society panel recommends levothyroxine replacement in all pregnant
women with SCH (weak recommendation, low-quality evidence).[4]although
this will result in treating nearly 15% of pregnant women with levothyroxine,
the guidelines panel opine that it will gain the benefits of replacing levothyroxine
and reducing adverse effects as iatrogenic hyperthyroidism is unknown.
The review
stresses the importance and need of a large randomized trial to study the
effects of levothyroxine supplementation on patients with SCH.
To conclude,
the review confirms the association of SCH during pregnancy with multiple
adverse maternal and neonatal outcomes, but there is not sufficient
evidence to support the use of
levothyroxine therapy to mitigate this association.
Clinicians
and patients must have a frank and informed discussion with the patients on use
of levothyroxine in patients with SCH, while we wait for larger trials to be
conducted on patients with SCH and use and benefits of levothyroxine.
[1]A
Stagnaro-Green, M Abalovich, E Alexander, F Azizi, J Mestman, R Negro, A Nixon,
EN Pearce, OP Soldin, S Sullivan, W Wiersinga 2011 Guidelines of the American
Thyroid Association for the diagnosis and management of thyroid disease during
pregnancy and postpartum. Thyroid 21:1081–1125.
[2] Maraka
Spyridoula, Ospina Naykky M. Singh, O'Keeffe Derek T., Espinosa De Ycaza Ana
E., Gionfriddo Michael R., Erwin Patricia J., Coddington Charles C. III, Stan
Marius N., Murad M. Hassan, and Montori Victor M.. Thyroid. April 2016, 26(4):
580-590. doi:10.1089/thy.2015.0418.
[3] A
Stagnaro-Green, M Abalovich, E Alexander, F Azizi, J Mestman, R Negro, A Nixon,
EN Pearce, OP Soldin, S Sullivan, W Wiersinga 2011 Guidelines of the American
Thyroid Association for the diagnosis and management of thyroid disease during
pregnancy and postpartum. Thyroid 21:1081–1125.
[4] L De
Groot, M Abalovich, EK Alexander, N Amino, L Barbour, RH Cobin, CJ Eastman, JH
Lazarus, D Luton, SJ Mandel, J Mestman, J Rovet, S Sullivan 2012 Management of
thyroid dysfunction during pregnancy and postpartum: an Endocrine Society
clinical practice guideline. J Clin
Endocrinol Metab 97:2543–2565.
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