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Thyroxine Requirement During Pregnancy

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Question

One of my patients underwent total thyroidectomy because of failure of drug treatment of Graves disease. One month postoperative she was pregnant. Under 150 mcg T4 the TSH was 3.6 mU/L in the first trimester. After 2 months it rose to 26 mU/L (under 170 mcg/d) and it was necessary to give more T4: The TSH normalised at the 6 month of pregnancy under 250 mcg/d (TSH 4.2 , fT4 18.6 pmol/l, fT3 3.5 pmol/l). Today, around term, she needs 5.8 mcg/kg effectve weight/d, or 7 mcg/kg prepartum weight/d) in order to achieve a TSH of 1.4 I have no doubt about compliance (the pharmacy confirms the correct amount of tablets). Normal weight, no symptoms, fetal growth normal. (P.S.-Prepartum weight 50 Kg and during pregnancy 57Kg). Is is an extreme form of physiological THR in pregnancy?

Many thanks for your answer.

Dr. Fabio Cattaneo, Lugano, Switzerland

Response

It is estimated that in almost all patients with thyroid deficiency (previously having received radioiodine, or operated, or with autoimmune thyroid disorders), the replacement dosage of l-T4 needs to be increased during pregnancy. The guidelines to carry out this dosage increment are as follows :1) it has to be done relatively rapidly during early gestation, and certainly within the first trimester;2) the dosage increment needs to be closely monitored during gestation, in order to avoid a rise in serum TSH. In our experience, changes in l-T4 dosages occurred until mid-gestation (5-6 months), and rarely in the last trimester (a platteau is reached at this stage); 3) percentage-wise, the dosage increment is approximately 30-60 % above baseline (preconception) daily doses. However, this is an average, but does not tell us anything about individual cases. Individually, l-T4 doses may have to be doubled (and even higher); in our own experience, one compliant patient required above 300 mcg/d during pregnancy; 4) the final dosage increment depends upon several factors that are difficult to predict: – The functional reserve of the thyroidal machinery : see the paper by Mike Kaplan, comparing pregnant patients with Hashimoto (requiring a lesser increase) and thyroid ablation for cancer, etc (requiring proportionally more); – The rise in TSH (when it has occurred, like in your case) is an additional difficulty, because then one often runs “behind” the actual events taking place and it is sometimes difficult to bring the TSH back to normal before the end of gestation (it seems that you succeeded); – Iodine deprivation : because of increased needs for iodine during pregnancy, and its reduced availability in the pregnant state, this may constitute an additional factor to complicate matters. Obviously, this factor will only play a role when the iodine nutritional status is limited, restricted, or deficient. Also, iodine deficiency will obviously play no role (as in your patient) when a total thyroidectomy has been performed previously; – Thyroxine absorption by the digestive tract : this has not been investigated so far, but we believe that some pregnant women may have “malabsorption” of thyroxine; – Changes in weight. I hope to have brought some light to your clinical problem, which is frequently encountered, and requires particular attention given the possibility that hypothyroxinemia in expecting mothers may have a deleterious role for the progeny’s final IQ (see Haddow, Pop, etc). Furthermore, the fact your patient already had a serum TSH of 3.6 mU/L in the first trimester (while taking 150 mcg) is an indication that she was slightly undertreated for this stage of early pregancy. It is therefore not surprizing that a few weeks later the TSH rose to 26 mU/L. As I indicated above, you “ran behind the cat”, and this can be shown by the fact that, at 6 months of gestation, the serum TSH was still too high (4.6 mU/L), despite giving 250 mcg/day.

Prof Daniel Glinoer