Comparison of empiric versus individualized levothyroxine (LT4) dose adjustment in hypothyroid women during pregnancy: interim data analysis

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 437-470-Non-neoplastic Thyroid Disorders
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-439
Geanina Popoveniuc*1, Kenneth Burman2, Jacqueline Jonklaas3, Uha Prabhakar Reddy4 and Shannon Danielle Sullivan2
1Georgetown University Hospital, Washington, DC, 2MedStar Washington Hospital Center, Washington, DC, 3Georgetown Univ Med Ctr, Washington, DC, 4Georgetown University, Washington, DC
Intro: Maternal hypothyroidism is associated with adverse maternal and fetal pregnancy outcomes, thus among women dependent on LT4 replacement, precise regulation of maternal TSH is crucial for achieving optimal pregnancy outcomes.  In general, LT4 requirements increase during pregnancy due to increased maternal and fetal demand, however, there are no established standards for monitoring and adjusting LT4 therapy in hypothyroid women during pregnancy.

Methods: We designed a prospective, randomized study comparing 2 methods of LT4 dose adjustment in hypothyroid women during pregnancy for efficacy in maintaining goal TSH. Women age 18-45 with hypothyroidism of any etiology, who achieve pregnancy naturally, have pre-pregnancy TSH≤ 4.5 mIU/L and are ≤10 weeks’ gestation are eligible.  Subjects are randomized to either Group 1) empiric LT4 dose adjustment, in which LT4 dose is increased by 2 pills/week at enrollment followed by adjustments by #pills/week, or Group 2) individualized LT4 dose adjustment based on TSH at enrollment, followed by adjustments by #mcg/day. TSH monitoring is performed q2 wks in Trimester (T)1 and T2, and q4 wks in T3. In both groups, LT4 dose is adjusted using algorithms designed to maintain TSH≤2.5 uIU/mL in T1, 0.5-2.5 uIU/mL in T2, and 0.5-3.0 uIU/mL in T3.  Student’s T-tests were performed to examine differences between groups, P<0.05.

Results: To date, 13 women (G1, n = 6; G2, n = 7) have enrolled and 8 (61.5%, G1, n =4; G2, n =4) have completed pregnancy. All pregnancies are singleton except 1 twin pregnancy in G2. Etiology of hypothyroidism is not different between groups (thyroid cancer: G1, n=4, G2, n=3; primary hypothyroidism: G1, n=2; G2, n=3). There are no differences between groups in maternal age (33±3.0 yrs, G1 vs 33±1.7 yrs, G2), week of gestation (7±2 wks, G1 vs 5±1 wks, G2), or LT4 dose (109±36 mcg/day, G1 vs 123±25 mcg/d, G2) at enrollment. TSH at enrollment was lower in G1 (0.43mIU/L±0.4, G1 vs 1.01±0.6, G2, P=0.067), trending toward significance.  There were no differences in free T4 or total T3 (ng/dl) between the groups at enrollment (fT4: 1.5±0.3, G1 vs 1.6±0.2, G2; TT3: 117±21, G1 vs 106±28 ng/dl, G2). TSH throughout the study period was higher in G2 (1.1±1.4 mIU/L, G1 vs 1.7±1.8 mIU/L, G2, P<0.05). % of TSH values outside goal range per participant (22%±21, G1 vs 33%±24, G2) and % of TSH values requiring LT4 dose changes per individual (41.5%±24, G1 vs 46%±14.5, G2) were not statistically different between groups.

Conclusion: Frequent (q2-4 wk) monitoring of thyroid function during pregnancy is crucial to maintain optimal maternal TSH levels.  Our data suggest that empiric and individualized LT4 dose adjustment strategies using algorithms to maintain trimester-specific goal TSH are equally effective in the management of hypothyroid women during pregnancy.

Nothing to Disclose: GP, KB, JJ, UPR, SDS

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