Abnormal Thyroid Function During Pregnancy

Zachary T Bloomgarden, MD


July 09, 2003

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Jorge H Mestman, MD, Keck School of Medicine, University of Southern California, Los Angeles, discussed the common findings of abnormal thyroid function during pregnancy.[1]

Between 1% and 16% of pregnant women have postpartum thyroiditis; maternal thyroid deficiency during pregnancy may adversely affect subsequent neuropsychological development of the child, and there is a relationship between miscarriage and thyroid dysfunction. Ten percent to 15% of pregnant women have abnormal thyroid function during the first half of pregnancy, and may be hypothyroid, hyperthyroid, or have gestational thyrotoxicosis.

Estrogen stimulates thyroid binding globulin (TBG) formation and increases its half life, with maximal TBG levels around 20 weeks, leading to increases in serum thyroxine levels. In addition, because of the increased glomerular filtration rate during pregnancy, renal iodine loss may occur, potentially causing both maternal and fetal hypothyroidism in geographic areas of low dietary iodine. This may be important in the United States, because there is evidence of decreased iodine uptake among US women over the past decade. Women who are euthyroid, or have subclinical hypothyroidism with chronic thyroiditis, or receive thyroxine replacement therapy may not compensate for the increased thyroid demand. Therefore, particularly close monitoring is required during pregnancy, and approximately half of women will require an increase in thyroxine replacement.

Dr. Mestman suggested that hypothyroidism is seen in 2% of women during the first trimester of pregnancy, and that there may be particular difficulty during pregnancy in women with inconsistent compliance with replacement treatment. The fetal thyroid takes up iodine by 10 to 12 weeks and produces T4 and T3 between 15 and 18 weeks of gestation, with the fetal pituitary producing TSH beginning around this time. There had been controversy as to whether maternal transfer of T4 to the fetus occurs prior to fetal thyroid hormone synthesis, but recent studies suggest this does appear to occur, as amniotic fluid free T4 at 6 to 12 weeks' gestation is approximately half that in maternal serum.[2] This is the only source of thyroid hormone during early fetal life, and it is important to maintain normal maternal thyroid status for brain maturation of the developing child.[3]

Levels of human chorionic gonadotropin (hCG) increase during the first trimester, peaking between 7 and 13 weeks. hCG has mild TSH-like activity, leading to slightly high free T4 during early pregnancy. In most women, this leads to a feedback decrease in TSH with balanced thyroid function. Dr. Mestman commented that, as a result, during early pregnancy the upper limit of normal TSH is lower than in nonpregnant women, and therapeutic decisions should be adjusted accordingly. In patients with increased hCG or increased biological activity of hCG, clinical or subclinical hyperthyroidism develops.[4]

The syndrome of gestational thyrotoxicosis, seen in 10% to 15% of pregnant women during early pregnancy,[5] is characterized by mildly increased free T4 and suppressed TSH early in pregnancy. The condition is not due to intrinsic thyroid pathology. It usually is characterized by mild or no symptoms, and resolves spontaneously by the second half of pregnancy. To establish the diagnosis, there should be no evidence of thyroid autoimmunity, either with elevated thyroid peroxidase antibodies or thyroid-stimulating immunoglobulins.

In a study of 689 pregnant women, 18% of the 338 who were assessed during the first trimester had TSH < 0.2, showing inverse correlation with hCG.[6] Both asymptomatic and symptomatic gestational thyrotoxicosis occurs more frequently with twin or multiple pregnancies, and is associated with hyperemesis gravidarum, which occurs in 0.05% to 1% of pregnant women. The condition is characterized by severe nausea and vomiting beginning around 4 to 6 weeks of gestation and usually subsiding around 16 to 20 weeks of gestation. However, TSH may remain low to the end of pregnancy in these women, in which case they often require hospitalization and occasionally parenteral nutrition.[7] In severe cases, abnormal liver function and electrolyte abnormality may be seen. The pathogenesis of the vomiting is not clear. Management with antiemetics and beta-blockers may be useful, but there is no evidence that antithyroid treatment is beneficial. The infants of these women are healthy, although they usually show some degree of intrauterine growth retardation. Milder forms of this disorder may explain variations in the severity of the "morning sickness" experienced during pregnancy, which correlates with the degree of elevation in free T4 and suppression of TSH.[8] Gestational hyperthyroidism may also be associated with trophoblastic disease,[9] mutation in the TSH receptor,[10] luteoma of pregnancy, or hyperplacentosis.

  1. Mestman JH. Do abnormal thyroid function tests in pregnancy always mean thyroid abnormality? Program of the American Association of Clinical Endocrinologists 12th Annual Meeting and Clinical Congress; May 14-18, 2003; San Diego, California.

  2. Calvo RM, Jauniaux E, Gulbis B, et al. Fetal tissues are exposed to biologically relevant free thyroxine concentrations during early phases of development. J Clin Endocrinol Metab. 2002;87:1768-1777. Abstract

  3. Haddow JE, Palomaki GE, Allan WC, et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999;341:549-555. Abstract

  4. Goodwin TM, Montoro M, Mestman JH, Pekary AE, Hershman JM. The role of chorionic gonadotropin in transient hyperthyroidism of hyperemesis gravidarum. J Clin Endocrinol Metab. 1992;75:1333-1337. Abstract

  5. Yeo CP, Khoo DH, Eng PH, Tan HK, Yo SL, Jacob E. Prevalence of gestational thyrotoxicosis in Asian women evaluated in the 8th to 14th weeks of pregnancy: correlations with total and free beta human chorionic gonadotrophin. Clin Endocrinol (Oxf). 2001;55:391-398. Abstract

  6. Glinoer D, De Nayer P, Robyn C, Lejeune B, Kinthaert J, Meuris S. Serum levels of intact human chorionic gonadotropin (HCG) and its free alpha and beta subunits, in relation to maternal thyroid stimulation during normal pregnancy. J Endocrinol Invest. 1993;16:881-888. Abstract

  7. Bouillon R, Naesens M, Van Assche FA, et al. Thyroid function in patients with hyperemesis gravidarum. Am J Obstet Gynecol. 1982;143:922-926. Abstract

  8. Mori M, Amino N, Tamaki H, Miyai K, Tanizawa O. Morning sickness and thyroid function in normal pregnancy. Obstet Gynecol. 1988;72:355-359. Abstract

  9. Rodien P, Bremont C, Sanson ML, et al. Familial gestational hyperthyroidism caused by a mutant thyrotropin receptor hypersensitive to human chorionic gonadotropin. N Engl J Med. 1998;339:1823-1826. Abstract

  10. Ginsberg J, Lewanczuk RZ, Honore LH. Hyperplacentosis: a novel cause of hyperthyroidism. Thyroid. 2001;11:393-396. Abstract


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