Optimal Levothyroxine Doses for Hypothyroidism in Pregnancy

Marlene Busko

December 09, 2013

A new study has determined the correct initial doses of levothyroxine (LT4) to give pregnant women with newly discovered hypothyroidism, leading to prompt attainment of normal thyrotropin (TSH) levels. This should help minimize pregnancy complications, say the authors, led by Marcos Abalovich, MD, from Durand Hospital, Buenos Aires, Argentina.

Although recent recommendations give target TSH levels in pregnancy, the doses of levothyroxine needed to attain these levels are not specified, say Dr. Abalovich and his colleagues in their study, published online November 11 in Thyroid.

For example, the latest Endocrine Society guidelines "say that for the treatment of subclinical hypothyroidism diagnosed during pregnancy, a dose of 50 µg or more could be enough," Dr. Abalovich explained to Medscape Medical News in an email. But whether "over 50 µg" means 51 or 75 or 125 or some other number is unclear, he said.

The new study provides "the endocrinologist [with] precise orientation on how to approach the treatment of pregnant women with hypothyroidism diagnosed during pregnancy," he observed.

Impact of Subclinical Hypothyroidism: A Matter of Debate

Dr. Abalovich and colleagues explain that while it's well-established that overt hypothyroidism in pregnancy should be treated, the recommended levothyroxine doses for this indication "are variable and are based on expert opinion."

But when it comes to the subject of subclinical hypothyroidism, "the impact of treatment is debated." Although subclinical hypothyroidism is less frequent than overt hypothyroidism in pregnancy, it occurs in about 3% of pregnancies.

"Most studies have found that untreated subclinical hypothyroidism causes obstetrical complications for the mother and fetus," he explained, including some that indicate a possible negative effect on the neurointellectual coefficient of the child, although this is somewhat disputed.

Existing practice guidelines recommend TSH target levels of 2.5 mIU/L or less for the first trimester of pregnancy and 3 mIU/L or less for the subsequent trimesters for subclinical hypothyroidism, because of potential benefits, especially in patients with positive thyroid peroxidase autoantibodies.

The aim of the current study was to try to pinpoint the appropriate levothyroxine doses to normalize TSH levels in patients with newly discovered subclinical hypothyroidism during pregnancy and to correlate them with basal TSH levels.

The researchers retrospectively identified 77 women seen at their center who were aged 18 to 45 years and had hypothyroidism that was newly discovered during pregnancy.

A total of 64 women had subclinical hypothyroidism:

  • 31 women had TSH greater than 2.5 (or 3) to 4.2 mIU/L (group 1a).

  • 33 women had TSH greater than 4.2 to 10 mIU/L (group 1b).

The remaining 13 women had overt hypothyroidism (group 2).

All patients were treated with levothyroxine as soon as hypothyroidism was diagnosed and were monitored every 4 to 6 weeks. The levothyroxine dose was considered adequate when the patient had a TSH level of 2.5 mIU/L or less (first trimester) or 3 mIU/L or less (subsequent trimesters).

Baseline TSH Should Guide Levothyroxine Dose

The researchers discovered that the levothyroxine dose required to attain the TSH target levels varied significantly, depending on the baseline TSH level.

Adequate Levothyroxine Doses in Pregnant Women With Newly Diagnosed Hypothyroidism

Hypothyroidism Type Baseline TSH (mIU/L) LT4 dose (µg/d) LT4 dose (µg/kg/d)
Group 1aa (subclinical) 3.56 77.98 1.20
Group 1bb (subclinical) 5.43 95.35 1.42
Group 2 (overt) 40.33 147.08 2.33

a. TSH > 2.5 (or 3) to 4.2 mIU/L
b. TSH > 4.2 to 10 mIU/L
TSH = thyrotropin
LT4 = levothyroxine
The initial levothyroxine dose was the appropriate one in 89% of the women with subclinical hypothyroidism and 77% of the women with overt hypothyroidism.

Once the appropriate dose was prescribed, euthyroidism was confirmed in around the same number of weeks in both patients with overt hypothyroidism (mean, 5.3 weeks) as well as in those with subclinical hypothyroidism (mean, 6 weeks).

Gestational hypertension was the most common complication in subclinical hypothyroidism, found in 7.8% of these women.

While 56% of patient had positive thyroid peroxidase autoantibodies, there were no miscarriages or premature deliveries.

"When hypothyroidism is newly discovered during pregnancy, we suggest initiating the treatment with the following levothyroxine doses: 1.20 µg/kg/day for subclinical hypothyroidism with TSH less than 4.2 mIU/L, 1.42 µg/kg/day with TSH greater than 4.2 to 10, and 2.33 µg/kg/day for overt hypothyroidism," Dr. Abalovich and colleagues write.

"By taking this approach, patients will promptly attain the euthyroid state, avoiding additional increments and, probably, obstetric risks," they conclude.

Thyroid. Published online November 11, 2013. Abstract

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