Treatment of primary hypothyroidism during pregnancy: Is there an increase in thyroxine dose requirement in pregnancy?

We studied the dose requirements of thyroxine (T-4) and serum concentrations of thyrotropin-stimulating hormone (TSH) and free T-4 in 16 pregnant women with primary hypothyroidism due to autoimmune thyroid disease (ATD, In = 11) or thyroidectomy (n = 5). All patients had been advised by their obstetricians to take prenatal vitamins enriched with iron (90mg/tablet) and calcium (similar to200 mg/tablet), known to inhibit absorption of T-4. We asked patients to take their vitamins 4 hours after ingesting T-4 in the morning. The mean T-4 dose of 0.10 +/- 0.01 (mean +/- SEM, mg/d) during pregnancy did not differ significantly from that (0.09 +/- 0.005) before or after (0.10 +/- 0.01) pregnancy. Similarly, mean serum TSH of 2.7 +/- 0.28 mlU/L during pregnancy did not differ significantly from that before (2.2 +/- 0.47) or after (3.2 +/- 1.31) pregnancy. The mean serum free T-4 concentration during pregnancy (16 +/- 0.97 pmol/L) was significantly (P<.05) lower than that (22 +/- 1.5) before or after (23 2.2) pregnancy and similar to that observed with our free T-4 measurement technique in normal (healthy) pregnant women. We next examined the data separately in patients with ATD and thyroidectomy. The mean T-4 dose (0.08 +/- 0.009) and TSH (2.4 +/- 0.29) during pregnancy in 11 ATD patients did not differ appreciably from those before (T-4 dose, 0,08 +/- 0.0006; TSH, 2.7 +/- 0.54) or after (T-4 dose 0.09 +/- 0.0063; TSH, 4.1 +/- 1.91) pregnancy. Similarly, the mean T-4 dose (0.12 +/- 0.022, n = 5) during pregnancy in thyroidectomized patients was similar to that before (0.12 +/- 0.017, n = 3) or after (0.12 0.022) pregnancy. However, serum TSH increased significantly, albeit within the normal range, during pregnancy in thyroidectomized patients (3.2 +/- 0.62, In = 5 v 0.41 +/- 0.017, In = 3, P<.05) and it (1.3 +/- 0.60) decreased significantly (P<.05) after pregnancy. Our data suggest that (1) the dose requirement of T-4 does not change systematically in pregnancy in most hypothyroid women. There may occur a modest increase in T-4 dose requirement during pregnancy in some thyroidectomized patients; (2) diminished absorption of T-4 possibly related to ingestion of exogenous agents (eg, iron, calcium, vitamins), may have contributed to previous suggestions of substantial increased T-4 requirement in pregnancy; (3) ingestion of T-4 dose absorption-inhibiting agents some 4 hours away from T-4 markedly diminishes or obviates their effect in many patients, Although many hypothyroid patients may not require an adjustment in their T-4 dose during pregnancy, it is prudent to monitor all such patients carefully as the consequences of inadequate therapy may be very important. Copyright 2003, Elsevier Science (USA). All rights reserved.