Poster Presentation ESA-SRB Conference 2015

Subclinical hypothyroidism in pregnancy related to TSH receptor blocking antibodies: An unique clinical conundrum  (#238)

Shao Feng Mok , TZE PING LOH 1 , DODDABELE SRINIVASA DEEPAK 1 , E SHYONG TAI 1 2
  1. NATIONAL UNIVERSITY HOSPITAL SINGAPORE, Singapore, SINGAPORE
  2. SAW SWEE HOCK SCHOOL OF PUBLIC HEALTH, NATIONAL UNIVERSITY OF SINGAPORE , SINGAPORE

TSH receptor auto-antibodies (TrAb) belong to a heterogeneous group of auto-antibodies that may stimulate or inhibit TSH receptors. Most commonly, they exhibit an overall stimulatory effect and are associated with Grave's disease. Rarely, they may exert a greater inhibitory effect, giving rise to hypothyroidism (1,2).

TSH binding inhibition immunoglobulin (TBII) assays are competitive immunoassays, which measure TrAb concentration. They do not inform about the biological effects of TrAb. Overall biological effects of TrAb are determined by their ability to stimulate cyclic AMP generation in thyroid stimulating immunoglobulin (TSI) bioassays. The behavior and proportion of these auto-antibodies may fluctuate with time and in response to treatment, changing the patient’s thyroid status. 

Here, we describe a middle-aged Chinese lady with subfertility related to subclinical hypothyroidism due to blocking TrAb. She was treated with levothyroxine for 1 year before achieving TSH normalization and successful conception via in-vitro fertilization (Table 1).

Serial thyroid function monitoring during pregnancy revealed primary hyperthyroidism. Levothyroxine was stopped at 18 weeks of gestation with normalization of thyroid function (Table 2). At this time, the TrAb showed predominantly stimulating effects on TSI bioassay, which concurred with the switch in thyroid function.

The patient delivered a healthy and euthyroid child via normal vaginal delivery at 39 weeks of gestation. Six months post-partum, her thyroid function revealed symptomatic primary hyperthyroidism. She was started on thiamazole 10mg OM for Graves’ thyrotoxicosis (Table 3). 

Our patient mirrors previously described cases of hyperthyroidism resulting from a switch of TrAb from blocking to stimulating nature amongst middle-aged Japanese females (3–6). The proposed mechanisms include polarization of dendritic cells after levothyroxine treatment with impairment of regulatory T cells and emergence of stimulating autoantibodies. Additionally, there may be a switch in T cell populations due to possible preferential clearance of blocking over stimulating antibodies in pregnancy (6–8).

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