Thyroid Hormone Replacement in Pregnant Women With Subclinical Hypothyroidism Requires Revision of Recommended Guidelines

Highlights:

Hypothyroidism during pregnancy is harmful to both the mother and fetus.
Thyroid hormone replacement is associated with better outcome for both mother and the baby.
However, treatment can be associated with other adverse effects.
Current treatment recommendations on subclinical hypothyroidism in pregnancy may need revision.

A recent published study indicates that it is only necessary to treat a pregnant women with the thyroxine hormone tablets if their TSH concentrations is between 4.1-10 mIU/L and that too during the first three months of the pregnancy.

There is a requirement for a more scientific study on the subject and also the need to revise the current guidelines on thyroid hormone treatment in pregnant women with subclinical hypothyroidism.

Thyroid Tests During Pregnancy
Thyroid tests during pregnancy like TSH and free T4 can help to detect thyroid problems. Hypothyroidism is more common during pregnancy as compared to hyperthyroidism.

‘Treatment with thyroid hormone of pregnant women during the first trimester of pregnancy can prevent fetal loss.’

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Current Clinical Guidelines on Subclinical Hypothyroidism

According to American Thyroid Association guidelines, subclinical hypothyroidism is defined as elevated TSH levels greater than 2.5 mIU/L, in the presence of normal thyroid hormone concentrations.

As per these guidelines, approximately 15 percent of pregnant women in the US and Europe will have subclinical hypothyroidism, representing a fivefold increase compared to before these criteria were laid down (2-3%), raising the possibility of over-diagnosis of the condition.

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Symptoms of hypothyroidism are often general, unspecific changes in the body. Lethargy, weight gain, stiffness and cramping of muscles are some of the symptoms of hypothyroidism.

Insufficient evidence exists to indicate the net benefit of administering thyroid hormone during pregnancy. Despite this the current guidelines recommend giving levothyroxine hormone to treat subclinical hypothyroidism in pregnant women.

The degree to which these recommendations are being followed and implemented at present is not known.

New International Guidelines For Thyroid Disease in Pregnancy
The revised guidelines include recommendations regarding the interpretation of thyroid function tests in pregnancy, important fetal, neonatal considerations.

New Retrospective Study

The objective of the retrospective cohort study was to assess the prevalence, safety versus the risks and efficacy of administering thyroid hormone to pregnantwomen with subclinical hypothyroidism.

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The retrospective cohort study involved 5405 women with untreated subclinical hypothyroidism chosen from a large US administrative database. The participants were selected based on predetermined criteria. The study spanned five years from January 2010 to December 2014.

Among the participants, 843 women (16 percent) with a mean TSH value of 4.8 mIU/L were treated with thyroid hormone while 4562 women with a mean TSH concentration of 3.3 mIU/L were not treated.

The adverse outcomes assessed included primarily fetal loss (miscarriage and stillbirth). Secondary outcomes assessed included preterm labor and delivery, premature rupture of membranes, gestational diabetes, gestational hypertension, preeclampsia, placental abruption, and poor fetal growth.

The results from the study threw up the following observations –

Risk of fetal loss was lower in women treated with thyroxine compared to those who were not treated.
Treatment with thyroid hormone was associated with higher incidence of adverse outcomes such as preterm delivery, preeclampsia and gestational diabetes.
Thyroid hormone therapy did not affect the other adverse outcomes assessed such as premature rupture of membranes, poor fetal growth and placental abruption.
Among the treated women, the effect of reducing fetal loss was observed only among women who had pre-treatment TSH levels of 4.1-10.0 mIU/L, not those with concentrations of 2.5-4.0 mIU/L.

Policy Implications Following the Study Findings

Both physicians and patients are unsure about the overall benefit of thyroid hormone treatment on maternal and fetal outcome in pregnancy.

Based on the study findings, it appears reasonable to treat women with TSH concentrations between 4.1-10 mIU/L with thyroxine replacement. Since the efficacy of thyroid hormone replacement was not significant in women with TSH levels of 2.5-4 mIU/L and due to the occurrence of other adverse outcomes in general, treatment could be withheld in this group and policy guidelines revised.

In fact discussions at the 2016 Endocrine Society meeting have suggested increasing the cut-off limit of TSH levels to 4 mIU/L in the upcoming American Thyroid Association guidelines.

Also, results from large randomized trials like the TSH study and the pregnancy complication data from the Controlled Antenatal Thyroid Screening study are awaited and could possibly provide more scientific rationale for treatment of pregnancy associated subclinical hypothyroidism.

Strengths and Limitations of the Study

This study is the largest national study regarding thyroid hormone replacement in pregnant women with subclinical hypothyroidism.
The sample was not restricted to hospital centers and was racially and geographically diverse reflecting real life estimates in the US regarding thyroid hormone replacement in pregnant women with subclinical hypothyroidism.
The main limitations of this study would be its retrospective observational design and use of administrative claims information, with a possible lack of clinical detail, improper classification of treatment and confounders, and selection biases related to health plan enrolment, treatment choice and diagnostic testing.

Conclusions

Based on the study findings, it is recommended that physicians follow a policy of shared decision making approach with the patient to enable them to participate in decision making about their health and treatment that would be optimal for them.
The timing of thyroid hormone replacement also becomes important. If preventing fetal loss is the main aim of thyroid replacement, treatment could be restricted to the first trimester when the risk of fetal loss is the greatest.
If treatment is initiated, regular monitoring of thyroid function and dose adjustment is critical.

Further research is necessary to understand the causal association between fetal loss and hypothyroidism and to evaluate the safety of thyroid hormone replacement in pregnancy.

The results of such future studies would go a long way in helping both the physician and the patient make informed decisions regarding starting thyroid hormone replacement in pregnant women.

References

Spyridoula Maraka, Raphael Mwangi, Rozalina G McCoy, Xiaoxi Yao, Lindsey R Sangaralingham, Naykky M Singh Ospina, Derek T O’Keeffe, Ana E Espinosa De Ycaza, Rene Rodriguez-Gutierrez, Charles C Coddington III, Marius N Stan, Juan P Brito, Victor M Montori. Thyroid hormone treatment among pregnant women with subclinical hypothyroidism: US national assessment. The British Medical Journal (2017) doi: https://doi.org/10.1136/bmj.i6865
High prevalence of subclinical hypothyroidism during first trimester of pregnancy in North India - (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683205/)

Source-Medindia