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, n = 11) or thyroidectomy (n = 5). All patients had been advised by their obstetricians to take prenatal vitamins enriched with iron ( approximately 90mg/tablet) and calcium ( approximately 200 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 mIU/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, n = 5 v 0.41 +/- 0.017, n = 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.