Repeated Miscarriages in a Young Woman with Hashimoto’s Thyroiditis and Antibodies

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Question

This is a 32 yr old female who first saw me 3/7/7 when she was 8 weeks IUP, G4M3. First pregnacy was 5yrs ago FTND. Subsequent 3 miscarriages at 6-8wks IUP. Hypothyroidism diagnosed 3yrs ago, not treated for reasons unclear. 6/06 she was started on LT4 50 mcg, gradually increased to 100mcg by 2/07. When I saw her 3/7/7 - TSH was 6.9 (1st trim N- 0.3-4.5), FT4-1.3, TPO> 1000, TGAb>3000, TSI - 132 (N<125), TBII -30%(n<16%). I increased her LT4 to 112mcg, but she went on to have a miscarriage 5/07 at 12 weeks IUP. Her TSH on f/u post miscarriage was - 0.03, FT41.8, T3 185, TPO> 1000, TGAb1050. I reduced her LT4 back to 100mcg/day.

She also had a tennis ball sized fibroid which was subsequently removed. She has also had extensive testing by her reproductive endo, for etiology for her miscarriages, all which seem negative.

She wants to conceive again.

Since 11/07 her TFT have been normal on LT4 88mcg/day. 2/07 - TSH- 2.87, FT4 1.4, T3-122, TPO>1000, TGAb> 3000.

She weighs 123lbs, and was hyperthyroid on 100mcg LT4.So, I have not changed her current dose.

Is she a candidate for IVIG? Is there anything else I can do from endo standpoint to reduce her risk for miscarriage? What would you advice her?

Radha Reddy, MD
Rancho Cucamonga CA

Response

I am not too familiar with the medical phraseology used in the U.S. when presenting case histories, but I think I understood correctly that this patient has been pregnant 4 times, with three previous miscarriages, and a fourth - and last miscarriage - during her most recent pregnancy in 2007. Obviously, she also has chronic autoimmune thyroiditis, with hypothyroidism diagnosed a couple of years ago. It is not clear to me whether the 3 previous miscarriages took place while she was an untreated hypothyroid patient or whether the obstetrical history occurred before that period (where, by the way, she may also have already been hypothyroid, without a diagnosis). In her most recent pregnancy, the patient received L-thyroxine 'almost' from the onset of gestation. However, and despite increasing her l-T4 dosage, the "best" TSH obtained was still clearly suboptimal in the first trimester (6.9 mU/L). After that, she miscarried once again. Finally, the antibody data indicate high titers of anti-Tg (>1000-3000) and anti-TPO (>1000) Abs and a positive TBII value (30% TSH binding inhibition).

Comments:

1) This is the sad - but not unusual - story of those patients who miscarry early (in the first trimester) and repeatedly, who have autoimmune thyroiditis and a not well-controlled thyroid function. Most studies on recurrent abortion in such 'thyroid' cases indicate that the best that can be done to help them is to make sure that their thyroid function is perfectly equilibrated before they become pregnant (serum TSH below 2.5 mU/L is probably the best target). In my own practice, I tend to titrate them even 'higher', to obtain a serum TSH around 1 mU/L. As soon as they become pregnant (spontaneously or medically-assisted), their thyroid function tests need to be monitored extremely closely to make sure that thyroid function remains entirely normal. This can only be achieved by sequential monitoring (every three-four weeks) of serum free T4 and TSH, with rapid (or even anticipated, as I like to do) increments in L-T4 dosage, and a close follow up until 24 weeks gestation, at least.

2) If this Hashimoto patient also has TSH-receptor antibodies (again from my understanding of the data presented), she may well be one of those rare cases with blocking-type TSHR-Abs. In principle, this should not affect the mother other than enhancing the risk of hypothyroidism, but could constitute a risk for fetal thyroid function during the second half of pregnancy (if she ever gets to that point !).

3) She may well be a candidate for IVIG (in addition to L-T4?). This decision is usually taken by our Ob-Gyn colleagues. The rate of pregnancy success with IVIG in the study by E. Vaquero (Amer J Reproductive Immunology in 2000) was improved (54.5%) but less than with l-T4 administration (81.2%). However, that study was not randomized nor controlled and the number of cases in each branch was small (see my Editorial with this article on pages 202-203).

4) I have followed personally a small number of women with the similar difficult medical conditions. Some have undergone medically-assisted procreation, some have even eventually adopted children, and despite these heavy antecedents, we have witnessed a few (but remarkable) successes since some women finally achieved natural conception and successful outcome of pregnancy (after many failed attempts) by treating adequately their Hashimoto's disease. Thus, there is still hope since the patient is only 32 years of age, but this of course is not to say that success is obtained in all those cases !!

I hope my comments will be helpful to you.

Prof Daniel Glinoer
University of Brussels