I would like to ask for help and advice on the management of a 22 y/o female with Graves’ disease who is currently 33 weeks pregnant. She presented with severe symptoms of thyrotoxicosis and was diagnosed with Graves’ disease last summer 6 months after she delivered her first child. Her T4 and T3 were extremely elevated and she was placed on tapazole but developed agranulocytosis (she was referred to hematology who agreed that tapazole was the likely cause of her neutropenia and her neutrophils normalized rather quickly after tapazole was discontinued). RAI treatment was recommended at that time but she refused and she wanted to seek a second opinion at a nearby academic center. She was lost to followup until this Spring when she presented to our office approximately 12 weeks pregnant with untreated hyperthyroidism. She was referred for subtotal thyroidectomy during her 2nd trimester at two nearby academic facilities but refused their recommendations regarding surgery. The fetus is small but the fetus has no evidence of fetal hyperthyroidism or a goiter based on a recent ultrasound. The decision was made to induce her at least by 39 weeks if she does not go into labor earlier. She is on propranolol (1400 mg daily in divided doses) and her heart rate is approximately 102 bpm and though she is feeling fatigue she has no other symptoms of thyrotoxicosis and has been gaining weight. Her most recent free T4 is 2.85 (upper limit of normal of 2.19) and total T3 is 370 (upper limit of normal 196) How should I manage her for the next several weeks and what should I do once she goes into labor. Thank you so much for your consideration and I appreciate this ability to ask the experts! about such difficult cases.
Rita R. Gonzalez, MD
Prior to recommending a therapeutic intervention, it is important to discuss the clinical status of the fetus with MFM. The fetus was described as small, without sonographic features of fetal thyrotoxicosis. It is important to ascertain that although perhaps small, the fetus is growing appropriately without fetal growth restriction and that there is no evidence of advanced bone age. If the fetus is growing appropriately along a trajectory, then maternal hyperthyroidism is being tolerated. Also, it is important to exclude the concern for fetal thyrotoxicosis, which if present, would lead to a different recommendation. A significant number of women with Graves’ disease will experience clinical remission as pregnancy progresses. In fact, since Rita initially contacted ENDOTEXT, the Mom’s TFTS further improved so that her FT4 is just above the upper normal non-pregnant limit (so appropriate for the Graves’ therapeutic target in pregnancy) and the TT3 was now in the mid 200s. Based upon what appears to be normal fetal development and improvement in maternal TFTs, no therapeutic intervention is required now. In fact, the Mom’s TFTs may continue to improve as pregnancy progresses. If therapy were needed, she has already experienced agranulocytosis with MMI, and there are no data that have explored the frequency of cross reactivity of this life threatening adverse event with PTU. So, PTU is not really an option. There is a very relevant paper by Naoko Momotani (J Clin Endocrinol Metab 1992 75:738-744). In this paper, pregnant women with Graves’ disease received chronic therapy with low dose iodine (only 6-40mg/day, so about 1 drop of SSKI/day) without significant untoward effects in the offspring, and with careful monitoring of maternal TFTS to the appropriate pregnancy targets. However, hopefully this will not be necessary, based upon her course. In addition, at this time given improvement in maternal TFTS, the beta blocker dose can be decreased with monitoring of HR.
Susan J. Mandel, MD MPH