Autoimmune Thyroid Disease and Pregnancy
- Author: Dotun A Ogunyemi, MD; Chief Editor: George T Griffing, MD more...
Thyroid disorders are the second most common endocrinologic disorders found in pregnancy. Overt hypothyroidism is estimated to occur in 0.3-0.5% of pregnancies. Subclinical hypothyroidism appears to occur in 2-3%, and hyperthyroidism is present in 0.1-0.4%.
Autoimmune thyroid dysfunctions remain a common cause of both hyperthyroidism and hypothyroidism in pregnant women. Graves disease accounts for more than 85% of all cases of hyperthyroid, whereas Hashimoto thyroiditis is the most common cause of hypothyroidism.
Postpartum thyroiditis (PPT) reportedly affects 4-10% of women. PPT is an autoimmune thyroid disease that occurs during the first year after delivery. Women with PPT present with transient thyrotoxicosis, hypothyroidism, or transient thyrotoxicosis followed by hypothyroidism. This presentation may be unrecognized, but is important because it predisposes the woman to develop permanent hypothyroidism.
Women with a past history of treated Graves disease or a thyrotoxic phase in early pregnancy are at increased risk of developing (Graves) hyperthyroidism postpartum.
Of interest, symptoms of autoimmune thyroid diseases tend to improve during pregnancy. A postpartum exacerbation is not uncommon and perhaps occurs because of an alteration in the maternal immune system during pregnancy. The improvement in thyroid autoimmune diseases is thought to be due to the altered immune status in pregnancy.
The defect that predisposes an individual to develop autoimmune thyroid disease is still unknown. Proposed mechanisms include a tissue-specific defect in suppressor T-cell activity, a genetically programmed presentation of a thyroid-specific antigen, and an idiotype/anti-idiotype reaction. Regardless of the cause, the common outcome is the production of 1 or more types of autoantibodies, which affect thyroid function positively or negatively.
Adams and Purves described the concept of Graves disease as an autoimmune dysfunction of the thyroid gland. These investigators noted that the sera of patients with Graves disease contained a factor that stimulated the murine thyroid gland. This factor had a longer duration of action than that of thyrotropin (ie, thyroid-stimulating hormone [TSH]), the long-acting thyroid stimulator.[3, 4, 5, 6]
Further studies revealed that these long-acting thyroid stimulators are autoantibodies directed against the TSH receptor. The activating versions of the TSH receptor are the thyroid-stimulating autoantibodies, which activate adenylate cyclase and which stimulate thyroid function.
In terms of histologic features, the thyroid glands of patients with Graves disease show follicular hypertrophy and hyperplasia (see Histologic Findings).
Hashimoto thyroiditis is also known as goitrous chronic thyroiditis. Almost all patients with this disease have positive test results for the thyroid peroxidase antibody (anti-TPO), an autoantibody against thyroid peroxidase enzyme. Of these patients, 50-70% also have positive results for antithyroglobulin antibodies.
Classic histologic findings of Hashimoto thyroiditis are extensive lymphocytic infiltration, follicular rupture, eosinophilia, various degrees of hyperplasia, and fibrosis (see Histologic Findings).
Atrophic chronic thyroiditis
Atrophic chronic thyroiditis is a rare autoimmune cause of hypothyroidism. This condition is characterized by the presence of blocking autoantibodies to the TSH receptors.
PPT is a variant of chronic autoimmune thyroiditis (Hashimoto thyroiditis). PTT is characterized by the presence of antimicrosomal antibodies. Histologic examination of PTT-affected thyroid glands affected reveals destructive lymphocytic thyroiditis (see Histologic Findings).
Hyperthyroidism affects 0.1-0.4% of pregnancies. Graves disease accounts for 85% of these cases. Hypothyroidism affects up to 2.2% of pregnant women and Hashimoto thyroiditis is the most common cause. Atrophic thyroiditis is less common. Postpartum thyroiditis has a prevalence ranging from 3.3-8.8% in the United States.
The most common cause of thyrotoxicosis in the postpartum period is postpartum thyroiditis. Specifically, the prevalence of postpartum thyrotoxicosis has been shown to be 4.1% vs 0.2% for thyrotoxicosis related to Graves disease.
The reported range for the frequency of PPT is wide. In Thailand, as few as 2 in 100 postpartum women are affected. By comparison, some Canadian studies revealed a frequency of 2 per 10 postpartum women. These differences may be due to variations in diagnostic criteria, in genetic factors, and in iodine consumption.
Fetal and maternal outcomes improve when thyroid function returns to normal.
Uncontrolled hyperthyroidism, especially in the second half of pregnancy, can lead to numerous complications. Maternal complications include miscarriage, infection, preeclampsia, preterm delivery, congestive heart failure (CHF), thyroid storm, and placental abruption. Fetal and neonatal complications include prematurity, small size for gestational age, intrauterine fetal death, and fetal or neonatal goiter and/or thyrotoxicosis. Overtreatment may cause iatrogenic fetal hypothyroidism.
Maternal complications of untreated hypothyroidism include microcytic anemia, preeclampsia, placental abruption, postpartum hemorrhage, cardiac dysfunction, and miscarriage. Fetal or neonatal complications include prematurity, low birth weight, congenital anomalies, stillbirth, and poor neuropsychological development. Abalovich et al showed about 60% risk of fetal loss with inadequate treatment or detection of hypothyroidism. Leung et al noted a 22% risk of gestational hypertension in pregnancy associated with hypothyroidism, compared to controls. Allan et al demonstrated an increased risk of fetal death with hypothyroidism.
In particular, overt maternal hypothyroidism is associated with neonatal neurologic developmental delay because of the transplacental transfer of thyroid hormone in early pregnancy is inadequate. This process is required for brain development. The fetal thyroid does not begin to concentrate iodine until 10-12 weeks of gestation. Therefore, before this time, the mother must provide for all of the fetus' thyroxine (T4) requirements. Thus, the conclusion of all available evidence demonstrates that hypothyroidism is associated with significant adverse maternal and fetal sequelae.
Subclinical hypothyroidism may be associated with an increased risk of adverse pregnancy complications such as spontaneous abortions, fetal loss, and preterm labor. A study by Wilson et al found that women diagnosed with subclinical hypothyroidism during their pregnancy have an increased risk for severe preeclampsia. An association between maternal subclinical hypothyroidism and adverse fetal neurocognitive development is biologically plausible though not clearly demonstrated.
Approximately 10-15% of the population have thyroid antibodies. These antibodies have been linked to an increased risk of spontaneous abortion.
It is debated whether isolated hypothyroxinemia causes any adverse effects on the developing fetus; reports of decreased IQ in offspring have been criticized for methodological processes and the plausibility of the conclusion.
Complications associated with postpartum thyroiditis (PPT) are maternal, and depression is common. Permanent hypothyroidism occurs in as many as 30% of women. These patients are also at high risk for recurrent PPT with subsequent pregnancies.
Autoimmune thyroid diseases occur more often in women than in men. The female-to-male ratio is 5-10:1.
Autoimmune thyroid dysfunction most often affects women of reproductive age.
Abalovich M, Amino N, Barbour LA, Cobin RH, De Groot LJ, Glinoer D. Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2007 Aug. 92(8 Suppl):S1-47. [Medline].
Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011 Oct. 21(10):1081-125. [Medline]. [Full Text].
McGiven AR, Adams DD, Purves HD. A comparison of the heat stability of long-acting thyroid stimulator and human thyroid-stimulating hormone. J Endocrinol. 1965 Apr. 32:29-33. [Medline].
Adams DD, Kennedy TH, Purves HD, Siret NE. Failure of TSH antisera to neutralize long-acting thyroid stimulator. Endocrinology. 1962 Jun. 70:801-5. [Medline].
Adams DD. The presence of an abnormal thyroid-stimulating hormone in the serum of some thyrotoxic patients. J Clin Endocrinol Metab. 1958 Jul. 18(7):699-712. [Medline].
Adams DD. The pathogenesis of thyrotoxicosis the discovery of LATS. N Z Med J. 1975 Jan 8. 81(531):15-7. [Medline].
Wilson KL, Casey BM, McIntire DD, Halvorson LM, Cunningham FG. Subclinical thyroid disease and the incidence of hypertension in pregnancy. Obstet Gynecol. 2012 Feb. 119(2 Pt 1):315-20. [Medline].
Friedrich N, Schwarz S, Thonack J, John U, Wallaschofski H, Völzke H. Association between parity and autoimmune thyroiditis in a general female population. Autoimmunity. 2008 Mar. 41(2):174-80. [Medline].
Brent GA. Maternal thyroid function: interpretation of thyroid function tests in pregnancy. Clin Obstet Gynecol. 1997 Mar. 40(1):3-15. [Medline].
FDA MedWatch Safety Alerts for Human Medical Products. Propylthiouracil (PTU). US Food and Drug Administration. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm. Accessed: June 3, 2009.
ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 37, August 2002. (Replaces Practice Bulletin Number 32, November 2001). Thyroid disease in pregnancy. Obstet Gynecol. 2002 Aug. 100(2):387-96. [Medline].
Alexander EK, Marqusee E, Lawrence J, Jarolim P, Fischer GA, Larsen PR. Timing and magnitude of increases in levothyroxine requirements during pregnancy in women with hypothyroidism. N Engl J Med. 2004 Jul 15. 351(3):241-9. [Medline].
American Academy of Pediatrics Committee on Drugs. Transfer of drugs and other chemicals into human milk. Pediatrics. 1989 Nov. 84(5):924-36. [Medline].
Amino N, Mori H, Iwatani Y, Tanizawa O, Kawashima M, Tsuge I. High prevalence of transient post-partum thyrotoxicosis and hypothyroidism. N Engl J Med. 1982 Apr 8. 306(14):849-52. [Medline].
Amino N, Tanizawa O, Mori H, Iwatani Y, Yamada T, Kurachi K. Aggravation of thyrotoxicosis in early pregnancy and after delivery in Graves' disease. J Clin Endocrinol Metab. 1982 Jul. 55(1):108-12. [Medline].
Anonymous. Dangers of iodides in pregnancy. Lancet. 1970 Jun 13. 1(7659):1273-4. [Medline].
Azizi F. Treatment of post-partum thyrotoxicosis. J Endocrinol Invest. 2006 Mar. 29(3):244-7. [Medline].
Becks GP, Burrow GN. Thyroid disease and pregnancy. Med Clin North Am. 1991 Jan. 75(1):121-50. [Medline].
Belfiore A, Garofalo MR, Giuffrida D, Runello F, Filetti S, Fiumara A. Increased aggressiveness of thyroid cancer in patients with Graves' disease. J Clin Endocrinol Metab. 1990 Apr. 70(4):830-5. [Medline].
Browne-Martin K, Emerson CH. Postpartum thyroid dysfunction. Clin Obstet Gynecol. 1997 Mar. 40(1):90-101. [Medline].
Bungard TJ, Hurlburt M. Management of hypothyroidism during pregnancy. CMAJ. 2007 Apr 10. 176(8):1077-8. [Medline].
Burrow GN. The management of thyrotoxicosis in pregnancy. N Engl J Med. 1985 Aug 29. 313(9):562-5. [Medline].
Canaris GJ, Manowitz NR, Mayor G, Ridgway EC. The Colorado thyroid disease prevalence study. Arch Intern Med. 2000 Feb 28. 160(4):526-34. [Medline].
Casey BM, Dashe JS, Spong CY, McIntire DD, Leveno KJ, Cunningham GF. Perinatal significance of isolated maternal hypothyroxinemia identified in the first half of pregnancy. Obstet Gynecol. 2007 May. 109(5):1129-35. [Medline].
Chattaway JM, Klepser TB. Propylthiouracil versus methimazole in treatment of Graves' disease during pregnancy. Ann Pharmacother. 2007 Jun. 41(6):1018-22. [Medline].
Chopra IJ, Baber K. Treatment of primary hypothyroidism during pregnancy: is there an increase in thyroxine dose requirement in pregnancy?. Metabolism. 2003 Jan. 52(1):122-8. [Medline].
Cooper DS. Clinical practice. Subclinical hypothyroidism. N Engl J Med. 2001 Jul 26. 345(4):260-5. [Medline].
Davis LE, Lucas MJ, Hankins GD, Roark ML, Cunningham FG. Thyrotoxicosis complicating pregnancy. Am J Obstet Gynecol. 1989 Jan. 160(1):63-70. [Medline].
Dayan CM, Daniels GH. Chronic autoimmune thyroiditis. N Engl J Med. 1996 Jul 11. 335(2):99-107. [Medline].
Franklyn JA, Davis JR, Gammage MD, Littler WA, Ramsden DB, Sheppard MC. Amiodarone and thyroid hormone action. Clin Endocrinol (Oxf). 1985 Mar. 22(3):257-64. [Medline].
Furmaniak J, Smith BR. Immunity to the thyroid-stimulating hormone receptor. Springer Semin Immunopathol. 1993. 14(3):309-21. [Medline].
Gerstein HC. How common is postpartum thyroiditis? A methodologic overview of the literature. Arch Intern Med. 1990 Jul. 150(7):1397-400. [Medline].
Haddow JE, Palomaki GE, Allan WC, Williams JR, Knight GJ, Gagnon J. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N Engl J Med. 1999 Aug 19. 341(8):549-55. [Medline].
Hayslip CC, Fein HG, O'Donnell VM, Friedman DS, Klein TA, Smallridge RC. The value of serum antimicrosomal antibody testing in screening for symptomatic postpartum thyroid dysfunction. Am J Obstet Gynecol. 1988 Jul. 159(1):203-9. [Medline].
Houck JA, Davis RE, Sharma HM. Thyroid-stimulating immunoglobulin as a cause of recurrent intrauterine fetal death. Obstet Gynecol. 1988 Jun. 71(6 Pt 2):1018-9. [Medline].
Jansson R, Bernander S, Karlsson A, Levin K, Nilsson G. Autoimmune thyroid dysfunction in the postpartum period. J Clin Endocrinol Metab. 1984 Apr. 58(4):681-7. [Medline].
Jansson R, Dahlberg PA, Winsa B, Meirik O, Säfwenberg J, Karlsson A. The postpartum period constitutes an important risk for the development of clinical Graves' disease in young women. Acta Endocrinol (Copenh). 1987 Nov. 116(3):321-5. [Medline].
Kvetny J, Poulsen H. Transient hyperthyroxinemia in newborns from women with autoimmune thyroid disease and raised levels of thyroid peroxidase antibodies. J Matern Fetal Neonatal Med. 2006 Dec. 19(12):817-22. [Medline].
Lazarus JH, Ammari F, Oretti R, Parkes AB, Richards CJ, Harris B. Clinical aspects of recurrent postpartum thyroiditis. Br J Gen Pract. 1997 May. 47(418):305-8. [Medline].
Lazarus JH, Kokandi A. Thyroid disease in relation to pregnancy: a decade of change. Clin Endocrinol (Oxf). 2000 Sep. 53(3):265-78. [Medline].
Leung AS, Millar LK, Koonings PP, Montoro M, Mestman JH. Perinatal outcome in hypothyroid pregnancies. Obstet Gynecol. 1993 Mar. 81(3):349-53. [Medline].
Lucas A, Pizarro E, Granada ML, Salinas I, Roca J, Sanmartí A. Postpartum thyroiditis: long-term follow-up. Thyroid. 2005 Oct. 15(10):1177-81. [Medline].
Mandel SJ, Larsen PR, Seely EW, Brent GA. Increased need for thyroxine during pregnancy in women with primary hypothyroidism. N Engl J Med. 1990 Jul 12. 323(2):91-6. [Medline].
Martino E, Aghini-Lombardi F, Lippi F, Baschieri L, Safran M, Braverman LE. Twenty-four hour radioactive iodine uptake in 35 patients with amiodarone associated thyrotoxicosis. J Nucl Med. 1985 Dec. 26(12):1402-7. [Medline].
Milham S Jr. Scalp defects in infants of mothers treated for hyperthyroidism with methimazole or carbimazole during pregnancy [letter]. Teratology. 1985 Oct. 32(2):321. [Medline].
Momotani N, Noh J, Oyanagi H, Ishikawa N, Ito K. Antithyroid drug therapy for Graves' disease during pregnancy. Optimal regimen for fetal thyroid status. N Engl J Med. 1986 Jul 3. 315(1):24-8. [Medline].
Nachum Z, Rakover Y, Weiner E, Shalev E. Graves' disease in pregnancy: prospective evaluation of a selective invasive treatment protocol. Am J Obstet Gynecol. 2003 Jul. 189(1):159-65. [Medline].
Neto LV, De Almeida CA, Da Costa SM, Vaisman M. Prospective evaluation of pregnant women with hypothyroidism: implications for treatment. Gynecol Endocrinol. 2007 Mar. 23(3):138-41. [Medline].
Ordookhani A, Mirmiran P, Walfish PG, Azizi F. Transient neonatal hypothyroidism is associated with elevated serum anti-thyroglobulin antibody levels in newborns and their mothers. J Pediatr. 2007 Mar. 150(3):315-7, 317.e2. [Medline].
Poppe K, Velkeniers B, Glinoer D. Thyroid disease and female reproduction. Clin Endocrinol (Oxf). 2007 Mar. 66(3):309-21. [Medline].
Pruyn SC, Phelan JP, Buchanan GC. Long-term propranolol therapy in pregnancy: maternal and fetal outcome. Am J Obstet Gynecol. 1979 Oct 15. 135(4):485-9. [Medline].
Roti E, Emerson CH. Clinical review 29: Postpartum thyroiditis. J Clin Endocrinol Metab. 1992 Jan. 74(1):3-5. [Medline].
Salvi M, How J. Pregnancy and autoimmune thyroid disease. Endocrinol Metab Clin North Am. 1987 Jun. 16(2):431-44. [Medline].
Simsek M, Mendilcioglu I, Mihci E, Karagüzel G, Taskin O. Prenatal diagnosis and early treatment of fetal goitrous hypothyroidism and treatment results with two-year follow-up. J Matern Fetal Neonatal Med. 2007 Mar. 20(3):263-5. [Medline].
Singer PA, Cooper DS, Levy EG, Ladenson PW, Braverman LE, Daniels G. Treatment guidelines for patients with hyperthyroidism and hypothyroidism. Standards of Care Committee, American Thyroid Association. JAMA. 1995 Mar 8. 273(10):808-12. [Medline].
[Guideline] Stagnaro-Green A, Abalovich M, Alexander E, Azizi F, Mestman J, Negro R, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011 Oct. 21(10):1081-125. [Medline]. [Full Text].
Tachi J, Amino N, Tamaki H, Aozasa M, Iwatani Y, Miyai K. Long term follow-up and HLA association in patients with postpartum hypothyroidism. J Clin Endocrinol Metab. 1988 Mar. 66(3):480-4. [Medline].
Tagami T, Hagiwara H, Kimura T, Usui T, Shimatsu A, Naruse M. The incidence of gestational hyperthyroidism and postpartum thyroiditis in treated patients with graves' disease. Thyroid. 2007 Aug. 17(8):767-72. [Medline].
Tamaki H, Amino N, Aozasa M, Mori M, Tanizawa O, Miyai K. Serial changes in thyroid-stimulating antibody and thyrotropin binding inhibitor immunoglobulin at the time of postpartum occurrence of thyrotoxicosis in Graves' disease. J Clin Endocrinol Metab. 1987 Aug. 65(2):324-30. [Medline].
Degroot LJ, Larsen PR, Henneman G, eds. The Thyroid and Its Diseases. 6th ed. New York, NY: Churchill Livingstone; 1996.
Van Dijke CP, Heydendael RJ, De Kleine MJ. Methimazole, carbimazole, and congenital skin defects. Ann Intern Med. 1987 Jan. 106(1):60-1. [Medline].
Vargas MT, Briones-Urbina R, Gladman D, Papsin FR, Walfish PG. Antithyroid microsomal autoantibodies and HLA-DR5 are associated with postpartum thyroid dysfunction: evidence supporting an autoimmune pathogenesis. J Clin Endocrinol Metab. 1988 Aug. 67(2):327-33. [Medline].
Walfish PG, Chan JY. Post-partum hyperthyroidism. Clin Endocrinol Metab. 1985 May. 14(2):417-47. [Medline].
Weetman AP. Graves' disease. N Engl J Med. 2000 Oct 26. 343(17):1236-48. [Medline].
Widerhorn J, Bhandari AK, Bughi S, Rahimtoola SH, Elkayam U. Fetal and neonatal adverse effects profile of amiodarone treatment during pregnancy. Am Heart J. 1991 Oct. 122(4 Pt 1):1162-6. [Medline].
Wing DA, Millar LK, Koonings PP, Montoro MN, Mestman JH. A comparison of propylthiouracil versus methimazole in the treatment of hyperthyroidism in pregnancy. Am J Obstet Gynecol. 1994 Jan. 170(1 Pt 1):90-5. [Medline].