THYROID Volume 2, Number 1, 1992 Mary Ann Liebert, Inc., Publishers
Postpartum Thyroid Dysfunction:
Comment
ULLA FELDT-RASMUSSEN
THEdysfunction provides interesting review BY
Learoyd
ET al. on
postpartum thyroid
study, Danish women developing significantly higher thyroid gland volume (3).
As in the Welsh
and important new information from recent studies on this often overlooked clinical entity. A few supplementary comments are given here. As indicated in the review, thyroid autoantibodies are wellknown predictors of postpartum thyroid dysfunction (PPTD). Among these, antimicrosomal (antiperoxidase) antibodies show the strongest predictability. These autoantibodies decrease during pregnancy and show a rebound during the postpartum period. Measurement of these autoantibodies a few days after delivery as described by Hayslip (ref. 24 in the review) seems insufficient. In a recent study (1), antiperoxidase levels at the end of pregnancy and 1 month postpartum were not different in women developing PPTD from those who did not. On the other hand, antiperoxidase was high in the first two trimesters of pregnancy and 6 months postpartum in women developing PPTD. The best periods for measuring autoantibody levels are during early pregnancy or several months postpartum. The latter period, however, is too late for prediction, since PPTD often has already developed at that time. Screening for thyroid autoantibodies to predict PPTD should thus be performed during the first two trimesters of pregnancy. The data presented in the review show several differences from a recent Danish study (2). In the Danish study, there was a significantly higher thyroid volume as measured by ultrasound in smokers compared to nonsmokers but no increase of PPTD in smokers (36%) compared to nonsmokers (32%), whereas the Welsh group found a definite increase in PPTD among smokers. Another important difference was that the increase in thyroid gland size through pregnancy did not parallel changes in TSH in the Danish study, since TSH was low throughout pregnancy. The reason for these differences is not clear, but the fact that completely normal women (no thyroid autoantibodies. no PPTD) in the Welsh study did not show any increase in thyroid gland size during pregnancy, whereas normal Danish women had a 32% increase in ultrasonically determined thyroid gland volume (3), indicated a population difference in factors, such as iodine economy, ethnic differences, or others. The increase in thyroid volume in normal women was of the same order as in women with thyroid autoantibodies not developing PPTD (3).
Department of Endocrinology P. University Hospital. Copenhagen.
PPTD had
The mechanism for the goitrogenic effect of pregnancy is understood. In some studies, TSH was elevated, but in others, it was low. Therefore. hCG has been proposed as the causative agent. The mechanism may be multifactorial, since the thyroid gland volume also is fluctuating during the menstrual cycle where no hCG is present (3). Only prospective long-term follow-up studies of women with PPTD can clarify the prevalence of permanent hypoth-yroidism. The development of thyroid failure is well known to be mainly a female problem, and a population study in Finland (4) showed a high prevalence of hypothyroidism when thyroid autoantibodies coexist with compensated hypothyroidism. In future studies, it would be interesting to clarify if this high incidence of thyroid failure is related to previous PPTD episodes. The impact of iodine on PPTD is still controversial. The statement that Japan and the USA have higher iodine intake than Sweden (indicated to be borderline iodine insufficient) is contradicted by a report by Gutekunst et al., who studied thyroid volume and iodine intake in children from Sweden compared to northern and southern Germany (5). Denmark is borderline iodine insufficient, as is Germany (but not Sweden), and demonstrates one of the lowest published prevalences of PPTD (3.3%). This suggests an effect of iodine. A recent study by Roti et al. (6) gave evidence for spontaneous permanent damage to the thyroid gland following PPTD and aggravation by iodine. Seven of 1 1 patients with PPTD 27 months earlier were shown to have a positive perchlorate test, and 5 had an abnormally high TSH response to TRH. Treatment with iodide for 90 days resulted in elevated basal or TRH-stimulated TSH in 8 of 11 compared to none of the nulliparous control women. This study is thus in disagreement with the assumption of Learoyd et al. that a low iodine intake should aggravate the hypothyroid phase. Another hypothesis could be that high iodine intake aggravates the autoimmune process, resulting in either hyperthyroidism or hypothyroidism or both. The recognition that PPTD often is associated with very few clinical symptoms is certainly important. The reasons for screening for PPTD presented in the review are follow-up for
poorly
Denmark.
S3
84
FELDT-RASMUSSEN
progression to thyroid failure, counseling in relation to present PPTD and to future pregnancies and. if necessary treatment of a hypothyroid phase. It has been shown that the neonates of women developing PPTD have a lower gain in weight and length in the first month postpartum, despite a normal birth weight and normal thyroid function (7). Several questions concerning PPTD still remain controversial unanswered: Should all pregnant women be screened for anti-TPO and TgAb in early pregnancy? Should all women who had PPTD be followed to diagnose future permanent hypothyroidism? Do the neonates of women prone to develop PPTD need extra food supplementation for fully normal growth? The eventual answers to these questions can be clarified only by further follow-up studies and analyses. or
Rasmussen NG. Horness PJ. Hegedüs L, Feldt-Rasmussen U 1989 Serum thyroglobulin during the menstrual cycle, during pregnancy and postpartum. Acta Endocrinol (Copenh) 121:168-173. Gordin A. Lamberg B-A 1981 Spontaneous hypothyroidism in symptomlcss autoimmune thyroiditis. A long-term follow-up study. Clin Endocrinol (Oxf) 15:537-543. Gutekunst R, Smolarek H. Hasenpusch U. Stubbe P. Friedrich H-J. Wood WG. Scribe PC 1986 Goitre epidemiology: Thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden. Acta Endocrinol (Copenh) 112:494-501. Roti E. Minelli R. Gardini E. Braverman LE 1991 Iodine-induced hypothyroidism in euthyroid women with a previous episode of
postpartum thyroiditis. Thyroid Ksuppl l):S-25. Bech K. Hertel J. Rasmussen NG, Hegedüs L, Horness PJ, FeldtRasmussen U, Hoier-Madsen M 1991 Effect of maternal thyroid autoantibodies and post-partum thyroiditis on the fetus and neonate. Acta Endocrinol (Copenh) 125:146-149.
REFERENCES 1. Feldt-Rasmussen U. H0ier-Madscn M, Rasmussen NG, Hegedüs L, Horncss P 1990 Antithyroid peroxidase antibodies during pregnancy and postpartum. Relation to postpartum thyroiditis. Autoimmunity
6:211-214. 2. Rasmussen NG. Horness PJ. H0ier-Madscn M, Feldt-Rasmussen U. Hegedüs L 1990 Thyroid size and function in healthy pregnant women with thyroid autoantibodies. Relation to development of postpartum thyroiditis. Acta Endocrinol (Copenh) 123:395-401.
Address reprint requests to: Ulla Feldt-Rasmussen
Department of Endocrinology P University Hospital Blegdamsvej 9 DK-2100 Copenhagen Denmark
Postpartum Thyroid Dysfunction:
Comment
ULLA FELDT-RASMUSSEN
THEdysfunction provides interesting review BY
Learoyd
ET al. on
postpartum thyroid
study, Danish women developing significantly higher thyroid gland volume (3).
As in the Welsh
and important new information from recent studies on this often overlooked clinical entity. A few supplementary comments are given here. As indicated in the review, thyroid autoantibodies are wellknown predictors of postpartum thyroid dysfunction (PPTD). Among these, antimicrosomal (antiperoxidase) antibodies show the strongest predictability. These autoantibodies decrease during pregnancy and show a rebound during the postpartum period. Measurement of these autoantibodies a few days after delivery as described by Hayslip (ref. 24 in the review) seems insufficient. In a recent study (1), antiperoxidase levels at the end of pregnancy and 1 month postpartum were not different in women developing PPTD from those who did not. On the other hand, antiperoxidase was high in the first two trimesters of pregnancy and 6 months postpartum in women developing PPTD. The best periods for measuring autoantibody levels are during early pregnancy or several months postpartum. The latter period, however, is too late for prediction, since PPTD often has already developed at that time. Screening for thyroid autoantibodies to predict PPTD should thus be performed during the first two trimesters of pregnancy. The data presented in the review show several differences from a recent Danish study (2). In the Danish study, there was a significantly higher thyroid volume as measured by ultrasound in smokers compared to nonsmokers but no increase of PPTD in smokers (36%) compared to nonsmokers (32%), whereas the Welsh group found a definite increase in PPTD among smokers. Another important difference was that the increase in thyroid gland size through pregnancy did not parallel changes in TSH in the Danish study, since TSH was low throughout pregnancy. The reason for these differences is not clear, but the fact that completely normal women (no thyroid autoantibodies. no PPTD) in the Welsh study did not show any increase in thyroid gland size during pregnancy, whereas normal Danish women had a 32% increase in ultrasonically determined thyroid gland volume (3), indicated a population difference in factors, such as iodine economy, ethnic differences, or others. The increase in thyroid volume in normal women was of the same order as in women with thyroid autoantibodies not developing PPTD (3).
Department of Endocrinology P. University Hospital. Copenhagen.
PPTD had
The mechanism for the goitrogenic effect of pregnancy is understood. In some studies, TSH was elevated, but in others, it was low. Therefore. hCG has been proposed as the causative agent. The mechanism may be multifactorial, since the thyroid gland volume also is fluctuating during the menstrual cycle where no hCG is present (3). Only prospective long-term follow-up studies of women with PPTD can clarify the prevalence of permanent hypoth-yroidism. The development of thyroid failure is well known to be mainly a female problem, and a population study in Finland (4) showed a high prevalence of hypothyroidism when thyroid autoantibodies coexist with compensated hypothyroidism. In future studies, it would be interesting to clarify if this high incidence of thyroid failure is related to previous PPTD episodes. The impact of iodine on PPTD is still controversial. The statement that Japan and the USA have higher iodine intake than Sweden (indicated to be borderline iodine insufficient) is contradicted by a report by Gutekunst et al., who studied thyroid volume and iodine intake in children from Sweden compared to northern and southern Germany (5). Denmark is borderline iodine insufficient, as is Germany (but not Sweden), and demonstrates one of the lowest published prevalences of PPTD (3.3%). This suggests an effect of iodine. A recent study by Roti et al. (6) gave evidence for spontaneous permanent damage to the thyroid gland following PPTD and aggravation by iodine. Seven of 1 1 patients with PPTD 27 months earlier were shown to have a positive perchlorate test, and 5 had an abnormally high TSH response to TRH. Treatment with iodide for 90 days resulted in elevated basal or TRH-stimulated TSH in 8 of 11 compared to none of the nulliparous control women. This study is thus in disagreement with the assumption of Learoyd et al. that a low iodine intake should aggravate the hypothyroid phase. Another hypothesis could be that high iodine intake aggravates the autoimmune process, resulting in either hyperthyroidism or hypothyroidism or both. The recognition that PPTD often is associated with very few clinical symptoms is certainly important. The reasons for screening for PPTD presented in the review are follow-up for
poorly
Denmark.
S3
84
FELDT-RASMUSSEN
progression to thyroid failure, counseling in relation to present PPTD and to future pregnancies and. if necessary treatment of a hypothyroid phase. It has been shown that the neonates of women developing PPTD have a lower gain in weight and length in the first month postpartum, despite a normal birth weight and normal thyroid function (7). Several questions concerning PPTD still remain controversial unanswered: Should all pregnant women be screened for anti-TPO and TgAb in early pregnancy? Should all women who had PPTD be followed to diagnose future permanent hypothyroidism? Do the neonates of women prone to develop PPTD need extra food supplementation for fully normal growth? The eventual answers to these questions can be clarified only by further follow-up studies and analyses. or
Rasmussen NG. Horness PJ. Hegedüs L, Feldt-Rasmussen U 1989 Serum thyroglobulin during the menstrual cycle, during pregnancy and postpartum. Acta Endocrinol (Copenh) 121:168-173. Gordin A. Lamberg B-A 1981 Spontaneous hypothyroidism in symptomlcss autoimmune thyroiditis. A long-term follow-up study. Clin Endocrinol (Oxf) 15:537-543. Gutekunst R, Smolarek H. Hasenpusch U. Stubbe P. Friedrich H-J. Wood WG. Scribe PC 1986 Goitre epidemiology: Thyroid volume, iodine excretion, thyroglobulin and thyrotropin in Germany and Sweden. Acta Endocrinol (Copenh) 112:494-501. Roti E. Minelli R. Gardini E. Braverman LE 1991 Iodine-induced hypothyroidism in euthyroid women with a previous episode of
postpartum thyroiditis. Thyroid Ksuppl l):S-25. Bech K. Hertel J. Rasmussen NG, Hegedüs L, Horness PJ, FeldtRasmussen U, Hoier-Madsen M 1991 Effect of maternal thyroid autoantibodies and post-partum thyroiditis on the fetus and neonate. Acta Endocrinol (Copenh) 125:146-149.
REFERENCES 1. Feldt-Rasmussen U. H0ier-Madscn M, Rasmussen NG, Hegedüs L, Horncss P 1990 Antithyroid peroxidase antibodies during pregnancy and postpartum. Relation to postpartum thyroiditis. Autoimmunity
6:211-214. 2. Rasmussen NG. Horness PJ. H0ier-Madscn M, Feldt-Rasmussen U. Hegedüs L 1990 Thyroid size and function in healthy pregnant women with thyroid autoantibodies. Relation to development of postpartum thyroiditis. Acta Endocrinol (Copenh) 123:395-401.
Address reprint requests to: Ulla Feldt-Rasmussen
Department of Endocrinology P University Hospital Blegdamsvej 9 DK-2100 Copenhagen Denmark
