THYROID Volume 2, Number 2, 1992 Mary Ann Liebert, Inc., Publishers
Commentary
Monitoring Thyroxine Treatment During Pregnancy P. REED LARSEN
that the requirement for thyroxine patients with primary hypothyroidism is remarkably decreasing only as patients reach the seventh or eighth decade. There are only a few exceptions to this rule. For example, the institution of anticonvulsant therapy with carbamazepine or phénobarbital may accelerate T4 metabolism. Cholestyramine inhibits T4 absorption and amiodarone inhibits conversion of T4 to the active hormone 3,5,3'-triiodothyronine (T3). Any of these changes may increase T4 dosage requirements in a hypothyroid patient. It is now apparent that pregnancy is another condition during which there may be a 50%-100% increase in T4 requirement. This careful study by Dr. Kaplan and results from our own and other thyroid clinics have clearly
IT (T4) stable,
has long been taught
in
established that this is the case (1,2). Why was such a significant change not recognized earlier? The answer is relatively straightforward. It is a direct result of the reduction in T4 dose consequent to our improved capacity to assess what is the physiologic T4 replacement dose. This, in turn, has derived from the availability of sensitive TSH assays (now almost routine) that can discriminate between the lower limit of normal and a suppressed value. By monitoring serum TSH concentrations in patients with primary hypothyroidism, we can adjust the T4 dose to a level appropriate to the individual patient. This is evidenced by a restoration of the serum TSH concentration to a normal value of 1-2 p,U/mL. Using this criterion, we have recognized that the previously recommended dose of T4 was excessive. Thus, the typical replacement dose in the young female with primary hypothyroidism is approximately 88-112 p-g. When women with severe hypothyroidism who are stabilized on physiologic replacement doses of T4 become pregnant, I suspect that nearly all will require an increase in their
daily requirement. The large number of patients available for Kaplan's evaluation has allowed further insights into the clinical aspects of this phenomenon. Most importantly, it is clear from his report that individuals with total thyroid ablation have a greater and a more consistent increase in T4 requirement than do individuals with
Department of Medicine,
Harvard Medical School, and
Hashimoto's thyroiditis, who presumably have some residual thyroid function. This would seem to make sense. Presumably, the more severe the hypothyroidism associated with this condition, the more likely it would be that such patients would show an increased thyroxine requirement. Our initial report included 12 patients, 9 of whom had Hashimoto's disease as the cause of their hypothyroidism (2). However, our pretreatment data did not allow a conclusion as to the severity of the condition in each case. A second important observation derived from Kaplan's study is that although it is not uncommon to find an increase in TSH by 8 weeks gestation in these patients, this change may be delayed until as late as 6 months. Thus, although a first trimester increase in T4 requirement seems to be the rule, one cannot assume that such an increased requirement is not going to occur if it has not done so by the end of the first trimester. Third, much higher levels of TSH (up to 70 p,U/mL) were noted in some of Kaplan's patients. We may conclude from this result that there is considerable individual variation in the required increment in T4, which can range from
Commentary
Monitoring Thyroxine Treatment During Pregnancy P. REED LARSEN
that the requirement for thyroxine patients with primary hypothyroidism is remarkably decreasing only as patients reach the seventh or eighth decade. There are only a few exceptions to this rule. For example, the institution of anticonvulsant therapy with carbamazepine or phénobarbital may accelerate T4 metabolism. Cholestyramine inhibits T4 absorption and amiodarone inhibits conversion of T4 to the active hormone 3,5,3'-triiodothyronine (T3). Any of these changes may increase T4 dosage requirements in a hypothyroid patient. It is now apparent that pregnancy is another condition during which there may be a 50%-100% increase in T4 requirement. This careful study by Dr. Kaplan and results from our own and other thyroid clinics have clearly
IT (T4) stable,
has long been taught
in
established that this is the case (1,2). Why was such a significant change not recognized earlier? The answer is relatively straightforward. It is a direct result of the reduction in T4 dose consequent to our improved capacity to assess what is the physiologic T4 replacement dose. This, in turn, has derived from the availability of sensitive TSH assays (now almost routine) that can discriminate between the lower limit of normal and a suppressed value. By monitoring serum TSH concentrations in patients with primary hypothyroidism, we can adjust the T4 dose to a level appropriate to the individual patient. This is evidenced by a restoration of the serum TSH concentration to a normal value of 1-2 p,U/mL. Using this criterion, we have recognized that the previously recommended dose of T4 was excessive. Thus, the typical replacement dose in the young female with primary hypothyroidism is approximately 88-112 p-g. When women with severe hypothyroidism who are stabilized on physiologic replacement doses of T4 become pregnant, I suspect that nearly all will require an increase in their
daily requirement. The large number of patients available for Kaplan's evaluation has allowed further insights into the clinical aspects of this phenomenon. Most importantly, it is clear from his report that individuals with total thyroid ablation have a greater and a more consistent increase in T4 requirement than do individuals with
Department of Medicine,
Harvard Medical School, and
Hashimoto's thyroiditis, who presumably have some residual thyroid function. This would seem to make sense. Presumably, the more severe the hypothyroidism associated with this condition, the more likely it would be that such patients would show an increased thyroxine requirement. Our initial report included 12 patients, 9 of whom had Hashimoto's disease as the cause of their hypothyroidism (2). However, our pretreatment data did not allow a conclusion as to the severity of the condition in each case. A second important observation derived from Kaplan's study is that although it is not uncommon to find an increase in TSH by 8 weeks gestation in these patients, this change may be delayed until as late as 6 months. Thus, although a first trimester increase in T4 requirement seems to be the rule, one cannot assume that such an increased requirement is not going to occur if it has not done so by the end of the first trimester. Third, much higher levels of TSH (up to 70 p,U/mL) were noted in some of Kaplan's patients. We may conclude from this result that there is considerable individual variation in the required increment in T4, which can range from
