THYROID DISEASE DURING PREGNANCY* GERARD N. BURROW** LA JOLLA
CLINICAL AND CLIMATOLOGICAL The pregnant woman undergoes a series of physiological adjustments to accommodate the fetus (1). Since the fetus carries a full complement of paternal antigens, the maternal immune system must be "dampened" to prevent rejection. The fetus elaborates cytokines which decrease the maternal immune response. As a consequence, pregnancy affects disease activity in a variety of autoimmune disorders like Graves' disease, rheumatoid arthritis, myasthenia gravis and idiopathic thrombocytopenic purpura. Classically, the autoimmune disease ameliorates during gestation accompanied by a rebound of disease activity in the postpartum period (Fig. 1). This flare of disease activity in the postpartum period has long been recognized in women with Graves' disease (2). Thyrotoxicosis tends to ameliorate during pregnancy with a recurrence of signs and symptoms in the postpartum period (3). The realization that as many as five percent of pregnant women may develop postpartum thyroiditis has generated great interest in this phenomenon where postpartum abnormalities of thyroid function occur in otherwise healthy women. Postpartum thyroiditis is considered part of the autoimmune thyroid disease spectrum of Hashimoto's thyroiditis (4). Hashimoto's thyroiditis occurs in eight to ten percent of women, and about half of these women develop postpartum thyroiditis (5). Since Hashimoto's disease has a genetic inheritance, postpartum thyroiditis is more common in women with a family history of thyroid disease (6). There is a higher incidence of postpartum thyroiditis in Type I patients with diabetes (7) where the prevalence of elevated TSH concentrations approximates twenty percent. Studies on the association between postpartum thyroiditis and HLA haplotypes have produced varying results with the HLA-DR3 and HLADR4 haplotypes associated with the condition (8).
From the Department of Medicine (Division of Endocrinology) University of California, San Diego. ** Address for reprints: G. N. Burrow, M.D., UCSD SCH MED (0602), 9500 Gilman Drive, La Jolla, CA 92093-0602. *
120
121
THYROID DISEASE DURING PREGNANCY Autoimmune activity
Autoimffxune thyroiditis +
Graves'thyrotoxicosis
Pregnancy Postpartum period
FIG. 1. The relation between pregnancy and disease activity as typically observed in women with autoimmune thyroid disorders. (Reproduced with permission.)
Characteristics of Postpartum Thyroidits In some patients with postpartum thyroiditis an initial phase of thyrotoxicosis precedes the development of postpartum hypothyroidism (Fig. 2). The thyrotoxic phase beings one-half to three months postpartum and may last four to eight weeks. The symptoms and signs of hyperthyroidism are less severe than in Graves' disease, although in some instances treatment may be warranted (Table 1). The most common manifestation of postpartum thyroiditis is hypothyroidism occurring three to six months following delivery (Table 2). The usual symptoms and signs of decreased energy, lethargy, cold intolerance, and constipation may be absent. Hayslip et al. have reported impaired memory, difficulty concentrating and depression (9). The hypothyroidism generally resolves by ten to twelve months postpartum i!4 I) V
0
X0
to
q5E0 Cal t' 10 I E us -,
E
o-V% o
DELIVERY
3
6
9
12
15
Time in Months FIG. 2. Thyroid function during postpartum thyroiditis. (Reproduced with permission.)
122
GERARD N. BURROW TABLE 1 Characteristics of transient postpartum thyrotoxicosis due to painless thyroiditis. Thyrotoxicosis (often abrupt onset and short duration) Low thyroid uptake of iodine Thyroidal pain and tenderness absent Lymphocytic thyroiditis on fine-needle biopsy Thyroid microsomal autoantibodies usually present Subsequent hypothyroid phase develops (Reproduced with permission.)
TABLE 2 Characteristics of postpartum hypothyroidism. Hypothyroidism, usually transient develops 4-8 months postpartum Thyrotoxic phase is often observed 1-2 months prior to hypothyroidism Goiter with lymphocytic infiltration is most prominent at time of hypothyroidism Thyroid microsomal autoantibodies are present and titres are highest at time of maximal hypothyroidism Fatigue, loss of initiative, weight gain and mild psychic discomfort are most frequent symptoms Recurrence of similar intensity usually occurs after a subsequent pregnancy (Reproduced with permission.)
although permanent hypothyroidism may occur in five to seven percent of women with postpartum thyroiditis (10, 11). Postpartum thyroiditis tends to occur with subsequent pregnancies and hypothyroidism may eventually occur in most patients with the condition. Diagnosis The diagnosis of postpartum thyroiditis is based on the same tests of thyroid function utilized in the non-gravid state. Thyrotoxicosis in the postpartum period may also represent Graves' disease. The radioactive iodine uptake is elevated in Graves' disease while the uptake is suppressed in postpartum thyroiditis. Suppression of the radioiodine uptake is due either to the release of excess thyroid hormone which suppressed TSH or to the inflammation reaction which interferes with the iodine trapping mechanism. Iodine ingestion resulting in the Iod Basedow phenomenon would give a similar picture of thyrotoxicosis with a decreased radioiodine thyroid uptake. Iodine is excreted in breast milk and this should be considered when ordering a radioactive iodine thyroid uptake on a nursing mother (12). Hypothyroidism is diagnosed by the presence of an elevated serum TSH concentration and low serum thyroxine. Postpartum hypophysitis occurs much less commonly with a low serum thyroxine and decreased serum TSH concentration. Most patients with postpartum
THYROID DISEASE DURING PREGNANCY
123
thyroiditis have positive thyroid antibodies, especially microsomal. In fact, the absence of antibodies should lead the physician to question the diagnosis. In most instances the clinical diagnosis of the thyrotoxic phase of postpartum thyroiditis is very difficult. The only thyrotoxic symptoms noted in a significantly greater number of instances in affected women versus postpartum controls were fatigue and palpitations (13). These symptoms are common in postpartum women as are the lethargy and constipation found in the hypothyroid woman with postpartum thyroiditis (Table 3). Treatment In most instances treatment for postpartum thyroiditis is unnecessary. Probably the majority of patients are not brought to clinical attention. The thyrotoxic phase is usually mild and self-limited. Beta-blocking agents may provide symptomatic relief. However, anti-thyroid drugs are rarely indicated. If treatment is instituted, discontinuance after three to four months with reassessment of thyroid function is reasonable in view of the self-limited nature of the disease. Treatment of hypothyroidism in postpartum thyroiditis is more common. Thyroxine replacement therapy may markedly improve symptoms like lethargy and fatigue which could easily be attributed to the "new mother syndrome." A course of treatment for six months is indicated with reassessment of thyroid function six weeks after discontinuing thyroxine. Normal thyroid function is usually restored but if not, thyroxine therapy should be reinstituted (14). Five to
TABLE 3 Clinical presentation of post-partum thyroid disease Thyrotoxic phase 2-4 months post-partum Usually mild symptoms or asymptomatic Transient elevation of FT4 or FT3 Low radioiodine uptake Negative TSAb Hypothyroid phase 4-8 months post-partum Symptomatic. Psychiatric symptoms Clinically hypothyroid. Goitre with lymphocytic infiltration High titres of anti TPO antibodies Treatment with T4 often required Recurrence of disease in subsequent pregnancy Long-term hypothyroidism may occur in 25% (Reproduced with permission.)
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GERARD N. BURROW
seven percent of women will remain hypothyroid and require treatment (10, 11). Postpartum thyroiditis will recur in subsequent pregnancies in as many as twenty-five percent of pregnancies (14). Many of these women will eventually become hypothyroid and should be kept under endocrine surveillance.
Screening for Postpartum Thyroiditis As has been described, the clinical diagnosis of postpartum thyroiditis is difficult and screening procedures are necessary if indicated. An elevated thyroid microsomal antibody titer during the first trimester of pregnancy has a significant correlation with the development of postpartum hypothyroiditis (5). The microsomal antibody titer falls during gestation and therefore the screening test should be done early in pregnancy or in the late postpartum period. Screening has been recommended for any woman with a personal or family history of thyroid disease (15). This approach would decrease the number of screening tests which is a real financial burden. If the antibody titer is diagnostic of Hashimoto's disease, then thyroid function tests should be done to rule out the possibility of hypothyroidism during pregnancy. Arguments against screening include the cost and the apparent mild nature of postpartum thyroiditis. The question arises as to whether postpartum psychiatric disorders could be due to thyroid abnormalities. Postpartum psychosis develops within two weeks following delivery and tends to recur in subsequent pregnancies (16). The problem is complicated by the fact that hyperthyroxinemia has been observed in acute psychiatric disorders (17). Stewart and her colleagues reported a significantly higher free thyroxine index and decreased serum TSH concentration during the first postpartum year although both values were within the normal range (18). Microsomal antibodies were present in only five percent of these women indicating that acute immune thyroid disease is probably not responsible for the alterations of thyroid function. Postpartum depression occurs in ten to fifteen percent of women and is usually diagnosed four to five months postpartum. Thyroxine administration has been credited with successfully alleviating postpartum depression. Whether postpartum thyroiditis contributes to postpartum psychiatric disease is not clear (18). Certainly patients with depression in the postpartum period should have thyroid function evaluated. Prevention Screening with microsomal antibodies identifies patients at risk to develop postpartum thyroiditis but does not alleviate the disease. Jansson and co-workers noted that the administration of 0.15 mg of thyroxine to
THYROID DISEASE DURING PREGNANCY
125
hypothyroid patients with Hashimoto's disease caused a significant decrease in antibody titers (19). Chiovato et al. reported similar findings in hypothyroid patients but not in euthyroid patients with Hashimoto's thyroiditis (20) (Fig. 3). They attributed the decrease in thyroid antibodies during thyroxine administration to reduced antigen availability secondary to the decreased serum concentration TSH. Jansson and his coworkers gave thyroxine to eighteen women for forty weeks postpartum who had moderate to high titers of peroxidase (microsomal) antibody (21). The peroxidase antibodies decreased in all the women during pregnancy with a transient rise postpartum. However, thyroxine therapy had no effect on the antibody concentration and did not appear to alter the course of the postpartum thyroiditis. In a recent article, the administration of thyroxine to patients with Graves' disease who were being treated with antithyroid drugs resulted in only one person with a recurrence of the hyperthyroidism compared to seventeen patients in the placebo group (22). Thyroid antibody fall under L-thyroxine
120.. 100j
._
50 0 la
50
A
._C
E0 U,
0
.E
O.1 r
0
,
. . 12 24 months of therapy
6
. 36
48
FIG. 3. Microsomal antibody changes in 9 hypothyroid patients with Hashimoto's thyroiditis treated with suppressive doses of L-thyroxine. Results are expressed as percent of the pretreatment Mab value. (Reproduced with permission.)
126
GERARD N. BURROW
Discussion One in twenty pregnant women will develop postpartum thyroiditis. Clinical diagnosis is difficult and screening with peroxidase antibodies is necessary in early pregnancy to identify patients at risk. About half these women will develop postpartum thyroiditis. Whether all pregnant women should be screened depends on whether conditions like postpartum depression are associated with the thyroiditis. The majority of these patients will ultimately become hypothyroid. Whether thyroxine therapy will decrease the TSH stimulation of antigen production and possibly ameliorate the hypothyroidism remains to be evaluated. REFERENCES 1. Seely BL, Burrow GN. Thyrotoxicosis in pregnancy. The Endocrinologist. 1991;1:409 2. Burrow GN, Ferris F. Medical Complications during Pregnancy. Philadelphia: W. B. Saunders Company; 1988. 3. Becks GP, Burrow GN. Thyroid Disease and Pregnancy. Med Clin North Am 1991; 75: 121. 4. Stuenkel CA, Burrow GN. Postpartum thyroiditis. In: Lee RV, ed. Current Obstetric Medicine. Chicago: Mosby Year Book, Inc.; In Press. 5. Jansson R, Bernander S, Karlson A, et al. Autoimmune thyroid dysfunction in the postpartum period. J Clin Endocrinol Metab 1984; 58: 681. 6. Nikolai TF, Turney SL, Roberts RC. Postpartum lymphocytic thyroiditis. Prevalence, clinical course, and long-term follow-up. Arch Intern Med 1987; 147: 221. 7. Gray RS, Borsey DQ, Seth J, et al. Prevalence of subclinical thyroid failure in insulindependent diabetes. J Clin Endocrinol Metab 1980; 50: 1034. 8. Jansson R, Safwenberg J, Dahlberg PA. Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis. J Clin Endocrinol Metab 1985; 60: 168. 9. Hayslip CC, Fein HG, O'Donnell VM, et al. The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction. Am J Obstet Gynecol 1988; 159, 203. 10. Amino N, Miyai K, Kuro R, et al. Transient postpartum hypothyroidism: fourteen cases with autoimmune thyroiditis. Ann Intern Med 1977; 87: 155. 11. Fein HG, Goldman JM, Weintraub BD. Postpartum lymphocytic thyroiditis in American women: a spectrum of thyroid dysfunction. Am J Obstet Gynecol 1980; 138: 504. 12. Dydek GJ, Blue PW: Human breast milk excretion of iodine-131 following diagnostic and therapeutic administration to a lactating patient with Graves' disease. J Nucl Med 1988; 29: 407. 13. Amino N, Mori H, Iwatani Y, et al. High prevalence of transient postpartum thyrotoxicosis and hypothyroidism. N Engl J Med 1982; 306: 849. 14. Walfish PG, Chan JYC. Postpartum hyperthyroidism. Clin Endocrinol Metab 1985; 14: 417. 15. Ramsay I: Postpartum thyroiditis-an underdiagnosed disease. Br J Obstet Gynaecol 1986; 93: 1121. 16. Hamilton JA. Postpartum Psychiatric Problems. St. Louis: CV Mosby; 1962. 17. Spratt DI, Pont A, Miller MB, et al. Hyperthyroxinemia in patients with acute psychiatric disorders. Am J Med 1982; 73: 41.
THYROID DISEASE DURING PREGNANCY
127
18. Stewart DE, Addison AM, Robinson GE, et al. Thyroid function in psychosis following childbirth. Am J Psychiatry 1988; 145: 22. 19. Jansson R, Karlsson A, Dahlberg PA. Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto's thyroiditis. Brit Med J 1985; 290: 11. 20. Chiovato L, Marcocci C, Mariotti S, et al. L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibodies in idiopathic myxedema and in hypothyroid, but not in euthyroid Hashimoto's thyroiditis. J Endocrinol Invest 1986; 9: 299. 21. Kampe 0, Jansson R, Karlsson FA. Effects of L-thyroxine and iodide on the development of autoimmune postpartum thyroiditis. J Clin Endocrinol Metab 1990; 70: 1014. 22. Hashizume K, Ichikawa K, Sakurai A, et al. Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N Engl J Med 1991; 324: 947.
CLINICAL AND CLIMATOLOGICAL The pregnant woman undergoes a series of physiological adjustments to accommodate the fetus (1). Since the fetus carries a full complement of paternal antigens, the maternal immune system must be "dampened" to prevent rejection. The fetus elaborates cytokines which decrease the maternal immune response. As a consequence, pregnancy affects disease activity in a variety of autoimmune disorders like Graves' disease, rheumatoid arthritis, myasthenia gravis and idiopathic thrombocytopenic purpura. Classically, the autoimmune disease ameliorates during gestation accompanied by a rebound of disease activity in the postpartum period (Fig. 1). This flare of disease activity in the postpartum period has long been recognized in women with Graves' disease (2). Thyrotoxicosis tends to ameliorate during pregnancy with a recurrence of signs and symptoms in the postpartum period (3). The realization that as many as five percent of pregnant women may develop postpartum thyroiditis has generated great interest in this phenomenon where postpartum abnormalities of thyroid function occur in otherwise healthy women. Postpartum thyroiditis is considered part of the autoimmune thyroid disease spectrum of Hashimoto's thyroiditis (4). Hashimoto's thyroiditis occurs in eight to ten percent of women, and about half of these women develop postpartum thyroiditis (5). Since Hashimoto's disease has a genetic inheritance, postpartum thyroiditis is more common in women with a family history of thyroid disease (6). There is a higher incidence of postpartum thyroiditis in Type I patients with diabetes (7) where the prevalence of elevated TSH concentrations approximates twenty percent. Studies on the association between postpartum thyroiditis and HLA haplotypes have produced varying results with the HLA-DR3 and HLADR4 haplotypes associated with the condition (8).
From the Department of Medicine (Division of Endocrinology) University of California, San Diego. ** Address for reprints: G. N. Burrow, M.D., UCSD SCH MED (0602), 9500 Gilman Drive, La Jolla, CA 92093-0602. *
120
121
THYROID DISEASE DURING PREGNANCY Autoimmune activity
Autoimffxune thyroiditis +
Graves'thyrotoxicosis
Pregnancy Postpartum period
FIG. 1. The relation between pregnancy and disease activity as typically observed in women with autoimmune thyroid disorders. (Reproduced with permission.)
Characteristics of Postpartum Thyroidits In some patients with postpartum thyroiditis an initial phase of thyrotoxicosis precedes the development of postpartum hypothyroidism (Fig. 2). The thyrotoxic phase beings one-half to three months postpartum and may last four to eight weeks. The symptoms and signs of hyperthyroidism are less severe than in Graves' disease, although in some instances treatment may be warranted (Table 1). The most common manifestation of postpartum thyroiditis is hypothyroidism occurring three to six months following delivery (Table 2). The usual symptoms and signs of decreased energy, lethargy, cold intolerance, and constipation may be absent. Hayslip et al. have reported impaired memory, difficulty concentrating and depression (9). The hypothyroidism generally resolves by ten to twelve months postpartum i!4 I) V
0
X0
to
q5E0 Cal t' 10 I E us -,
E
o-V% o
DELIVERY
3
6
9
12
15
Time in Months FIG. 2. Thyroid function during postpartum thyroiditis. (Reproduced with permission.)
122
GERARD N. BURROW TABLE 1 Characteristics of transient postpartum thyrotoxicosis due to painless thyroiditis. Thyrotoxicosis (often abrupt onset and short duration) Low thyroid uptake of iodine Thyroidal pain and tenderness absent Lymphocytic thyroiditis on fine-needle biopsy Thyroid microsomal autoantibodies usually present Subsequent hypothyroid phase develops (Reproduced with permission.)
TABLE 2 Characteristics of postpartum hypothyroidism. Hypothyroidism, usually transient develops 4-8 months postpartum Thyrotoxic phase is often observed 1-2 months prior to hypothyroidism Goiter with lymphocytic infiltration is most prominent at time of hypothyroidism Thyroid microsomal autoantibodies are present and titres are highest at time of maximal hypothyroidism Fatigue, loss of initiative, weight gain and mild psychic discomfort are most frequent symptoms Recurrence of similar intensity usually occurs after a subsequent pregnancy (Reproduced with permission.)
although permanent hypothyroidism may occur in five to seven percent of women with postpartum thyroiditis (10, 11). Postpartum thyroiditis tends to occur with subsequent pregnancies and hypothyroidism may eventually occur in most patients with the condition. Diagnosis The diagnosis of postpartum thyroiditis is based on the same tests of thyroid function utilized in the non-gravid state. Thyrotoxicosis in the postpartum period may also represent Graves' disease. The radioactive iodine uptake is elevated in Graves' disease while the uptake is suppressed in postpartum thyroiditis. Suppression of the radioiodine uptake is due either to the release of excess thyroid hormone which suppressed TSH or to the inflammation reaction which interferes with the iodine trapping mechanism. Iodine ingestion resulting in the Iod Basedow phenomenon would give a similar picture of thyrotoxicosis with a decreased radioiodine thyroid uptake. Iodine is excreted in breast milk and this should be considered when ordering a radioactive iodine thyroid uptake on a nursing mother (12). Hypothyroidism is diagnosed by the presence of an elevated serum TSH concentration and low serum thyroxine. Postpartum hypophysitis occurs much less commonly with a low serum thyroxine and decreased serum TSH concentration. Most patients with postpartum
THYROID DISEASE DURING PREGNANCY
123
thyroiditis have positive thyroid antibodies, especially microsomal. In fact, the absence of antibodies should lead the physician to question the diagnosis. In most instances the clinical diagnosis of the thyrotoxic phase of postpartum thyroiditis is very difficult. The only thyrotoxic symptoms noted in a significantly greater number of instances in affected women versus postpartum controls were fatigue and palpitations (13). These symptoms are common in postpartum women as are the lethargy and constipation found in the hypothyroid woman with postpartum thyroiditis (Table 3). Treatment In most instances treatment for postpartum thyroiditis is unnecessary. Probably the majority of patients are not brought to clinical attention. The thyrotoxic phase is usually mild and self-limited. Beta-blocking agents may provide symptomatic relief. However, anti-thyroid drugs are rarely indicated. If treatment is instituted, discontinuance after three to four months with reassessment of thyroid function is reasonable in view of the self-limited nature of the disease. Treatment of hypothyroidism in postpartum thyroiditis is more common. Thyroxine replacement therapy may markedly improve symptoms like lethargy and fatigue which could easily be attributed to the "new mother syndrome." A course of treatment for six months is indicated with reassessment of thyroid function six weeks after discontinuing thyroxine. Normal thyroid function is usually restored but if not, thyroxine therapy should be reinstituted (14). Five to
TABLE 3 Clinical presentation of post-partum thyroid disease Thyrotoxic phase 2-4 months post-partum Usually mild symptoms or asymptomatic Transient elevation of FT4 or FT3 Low radioiodine uptake Negative TSAb Hypothyroid phase 4-8 months post-partum Symptomatic. Psychiatric symptoms Clinically hypothyroid. Goitre with lymphocytic infiltration High titres of anti TPO antibodies Treatment with T4 often required Recurrence of disease in subsequent pregnancy Long-term hypothyroidism may occur in 25% (Reproduced with permission.)
124
GERARD N. BURROW
seven percent of women will remain hypothyroid and require treatment (10, 11). Postpartum thyroiditis will recur in subsequent pregnancies in as many as twenty-five percent of pregnancies (14). Many of these women will eventually become hypothyroid and should be kept under endocrine surveillance.
Screening for Postpartum Thyroiditis As has been described, the clinical diagnosis of postpartum thyroiditis is difficult and screening procedures are necessary if indicated. An elevated thyroid microsomal antibody titer during the first trimester of pregnancy has a significant correlation with the development of postpartum hypothyroiditis (5). The microsomal antibody titer falls during gestation and therefore the screening test should be done early in pregnancy or in the late postpartum period. Screening has been recommended for any woman with a personal or family history of thyroid disease (15). This approach would decrease the number of screening tests which is a real financial burden. If the antibody titer is diagnostic of Hashimoto's disease, then thyroid function tests should be done to rule out the possibility of hypothyroidism during pregnancy. Arguments against screening include the cost and the apparent mild nature of postpartum thyroiditis. The question arises as to whether postpartum psychiatric disorders could be due to thyroid abnormalities. Postpartum psychosis develops within two weeks following delivery and tends to recur in subsequent pregnancies (16). The problem is complicated by the fact that hyperthyroxinemia has been observed in acute psychiatric disorders (17). Stewart and her colleagues reported a significantly higher free thyroxine index and decreased serum TSH concentration during the first postpartum year although both values were within the normal range (18). Microsomal antibodies were present in only five percent of these women indicating that acute immune thyroid disease is probably not responsible for the alterations of thyroid function. Postpartum depression occurs in ten to fifteen percent of women and is usually diagnosed four to five months postpartum. Thyroxine administration has been credited with successfully alleviating postpartum depression. Whether postpartum thyroiditis contributes to postpartum psychiatric disease is not clear (18). Certainly patients with depression in the postpartum period should have thyroid function evaluated. Prevention Screening with microsomal antibodies identifies patients at risk to develop postpartum thyroiditis but does not alleviate the disease. Jansson and co-workers noted that the administration of 0.15 mg of thyroxine to
THYROID DISEASE DURING PREGNANCY
125
hypothyroid patients with Hashimoto's disease caused a significant decrease in antibody titers (19). Chiovato et al. reported similar findings in hypothyroid patients but not in euthyroid patients with Hashimoto's thyroiditis (20) (Fig. 3). They attributed the decrease in thyroid antibodies during thyroxine administration to reduced antigen availability secondary to the decreased serum concentration TSH. Jansson and his coworkers gave thyroxine to eighteen women for forty weeks postpartum who had moderate to high titers of peroxidase (microsomal) antibody (21). The peroxidase antibodies decreased in all the women during pregnancy with a transient rise postpartum. However, thyroxine therapy had no effect on the antibody concentration and did not appear to alter the course of the postpartum thyroiditis. In a recent article, the administration of thyroxine to patients with Graves' disease who were being treated with antithyroid drugs resulted in only one person with a recurrence of the hyperthyroidism compared to seventeen patients in the placebo group (22). Thyroid antibody fall under L-thyroxine
120.. 100j
._
50 0 la
50
A
._C
E0 U,
0
.E
O.1 r
0
,
. . 12 24 months of therapy
6
. 36
48
FIG. 3. Microsomal antibody changes in 9 hypothyroid patients with Hashimoto's thyroiditis treated with suppressive doses of L-thyroxine. Results are expressed as percent of the pretreatment Mab value. (Reproduced with permission.)
126
GERARD N. BURROW
Discussion One in twenty pregnant women will develop postpartum thyroiditis. Clinical diagnosis is difficult and screening with peroxidase antibodies is necessary in early pregnancy to identify patients at risk. About half these women will develop postpartum thyroiditis. Whether all pregnant women should be screened depends on whether conditions like postpartum depression are associated with the thyroiditis. The majority of these patients will ultimately become hypothyroid. Whether thyroxine therapy will decrease the TSH stimulation of antigen production and possibly ameliorate the hypothyroidism remains to be evaluated. REFERENCES 1. Seely BL, Burrow GN. Thyrotoxicosis in pregnancy. The Endocrinologist. 1991;1:409 2. Burrow GN, Ferris F. Medical Complications during Pregnancy. Philadelphia: W. B. Saunders Company; 1988. 3. Becks GP, Burrow GN. Thyroid Disease and Pregnancy. Med Clin North Am 1991; 75: 121. 4. Stuenkel CA, Burrow GN. Postpartum thyroiditis. In: Lee RV, ed. Current Obstetric Medicine. Chicago: Mosby Year Book, Inc.; In Press. 5. Jansson R, Bernander S, Karlson A, et al. Autoimmune thyroid dysfunction in the postpartum period. J Clin Endocrinol Metab 1984; 58: 681. 6. Nikolai TF, Turney SL, Roberts RC. Postpartum lymphocytic thyroiditis. Prevalence, clinical course, and long-term follow-up. Arch Intern Med 1987; 147: 221. 7. Gray RS, Borsey DQ, Seth J, et al. Prevalence of subclinical thyroid failure in insulindependent diabetes. J Clin Endocrinol Metab 1980; 50: 1034. 8. Jansson R, Safwenberg J, Dahlberg PA. Influence of the HLA-DR4 antigen and iodine status on the development of autoimmune postpartum thyroiditis. J Clin Endocrinol Metab 1985; 60: 168. 9. Hayslip CC, Fein HG, O'Donnell VM, et al. The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction. Am J Obstet Gynecol 1988; 159, 203. 10. Amino N, Miyai K, Kuro R, et al. Transient postpartum hypothyroidism: fourteen cases with autoimmune thyroiditis. Ann Intern Med 1977; 87: 155. 11. Fein HG, Goldman JM, Weintraub BD. Postpartum lymphocytic thyroiditis in American women: a spectrum of thyroid dysfunction. Am J Obstet Gynecol 1980; 138: 504. 12. Dydek GJ, Blue PW: Human breast milk excretion of iodine-131 following diagnostic and therapeutic administration to a lactating patient with Graves' disease. J Nucl Med 1988; 29: 407. 13. Amino N, Mori H, Iwatani Y, et al. High prevalence of transient postpartum thyrotoxicosis and hypothyroidism. N Engl J Med 1982; 306: 849. 14. Walfish PG, Chan JYC. Postpartum hyperthyroidism. Clin Endocrinol Metab 1985; 14: 417. 15. Ramsay I: Postpartum thyroiditis-an underdiagnosed disease. Br J Obstet Gynaecol 1986; 93: 1121. 16. Hamilton JA. Postpartum Psychiatric Problems. St. Louis: CV Mosby; 1962. 17. Spratt DI, Pont A, Miller MB, et al. Hyperthyroxinemia in patients with acute psychiatric disorders. Am J Med 1982; 73: 41.
THYROID DISEASE DURING PREGNANCY
127
18. Stewart DE, Addison AM, Robinson GE, et al. Thyroid function in psychosis following childbirth. Am J Psychiatry 1988; 145: 22. 19. Jansson R, Karlsson A, Dahlberg PA. Thyroxine, methimazole, and thyroid microsomal autoantibody titres in hypothyroid Hashimoto's thyroiditis. Brit Med J 1985; 290: 11. 20. Chiovato L, Marcocci C, Mariotti S, et al. L-thyroxine therapy induces a fall of thyroid microsomal and thyroglobulin antibodies in idiopathic myxedema and in hypothyroid, but not in euthyroid Hashimoto's thyroiditis. J Endocrinol Invest 1986; 9: 299. 21. Kampe 0, Jansson R, Karlsson FA. Effects of L-thyroxine and iodide on the development of autoimmune postpartum thyroiditis. J Clin Endocrinol Metab 1990; 70: 1014. 22. Hashizume K, Ichikawa K, Sakurai A, et al. Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism. N Engl J Med 1991; 324: 947.
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