EPIDIMOLOGI

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%.[1] 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. 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.

Pathophysiology
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. A study by Thangaratinam concluded that the presence of maternal thyroid autoantibodies in women with normal thyroid function is strongly associated with serious conditions, including preterm delivery and miscarriage.[2]

Graves disease
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
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.

Postpartum thyroiditis
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).

Epidemiology
Frequency
United States

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.[1]
International

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.

Mortality/Morbidity
Fetal and maternal outcomes improve when thyroid function returns to normal.

Hyperthyroidism

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.
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. 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. Approximately 10-15% of the population has thyroid antibodies. These antibodies have been linked to an increased risk of spontaneous abortion. Subclinical hypothyroidism also has been associated with spontaneous abortion and with preterm labor.
Postpartum thyroiditis

Complications associated with 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.

Sex
Autoimmune thyroid diseases occur more often in women than in men. The female-to-male ratio is 5-10:1.[7]

Age
Autoimmune thyroid dysfunction most often affects women of reproductive age.

Screening maternal hypertiroidsm

October 28, 2011 (Indian Wells, California) The universal screening of pregnant women for thyroid disease is highly cost-effective in light of the variety of potential adverse events for the mother and child, according to research presented here at the American Thyroid Association (ATA) 2011 Annual Meeting. Although the American Academy of Clinical Endocrinologists endorsed universal screening of pregnant women for thyroid dysfunction in 2002, other major organizations, including the ATA and the Endocrine Society, currently recommend screening only for high-risk women, despite numerous risks associated with the disease, said lead author Chrysoula Dosiou, PhD, from the Stanford University School of Medicine Division of Endocrinology in Palo Alto, California. "About 11% of women of reproductive age are anti-thyroid peroxidase (anti-TPO) antibodypositive, while about 2.2% of pregnant women have [elevated] thyroid-stimulating hormone (TSH)," she said. "Meanwhile, screening only high-risk women has been shown to miss at least 30% of women with overt or subclinical hypothyroidism who could benefit from treatment." Potential adverse obstetric outcomes associated with hypothyroidism include spontaneous miscarriage and preterm delivery, while levothyroxine treatment has been shown to improve these outcomes, Dr. Dosiou said. Dr. Dosiou, along with researchers with the University of Illinois at Chicago, the V. Fazzi Hospital, in Lecce, Italy, and George Washington University School of Medicine and Health Sciences, in Washington, DC, compared the 3 screening strategies of universal screening beginning in the first trimester of pregnancy, risk-based screening, and no screening.

The approaches were each evaluated in a statistical model to compare the lifetime cost per quality-adjusted life-year (QALY), which reflects the quality of life and the quantity of life. Under the model, a positive screening test result was assumed to lead to follow-up testing and treatment for hypothyroidism when indicated. Various potential adverse outcomes for the pregnancy, the lifetime outcomes for the mother and child, and the cost of treatment were also considered. Other factors included the age at pregnancy (mean, 25 years); disease prevalence (11.2% for anti-TPO antibody positivity); the cost of screening ($21 for anti-TPO antibodies and $25 for TSH), annual levothyroxine cost ($170), and other variables. As a general rule, a screening strategy is considered effective when it has an incremental costeffectiveness ratio of less than $50,000/QALY, Dr. Dousiou explained, and the results showed universal screening to be cost-effective compared with risk-based screening, with an incremental cost-effectiveness of $7258/QALY. Compared with no screening at all, risk-based and universal screening were each more costeffective, with incremental cost-effectiveness ratios of $6753/QALY and $7119/QALY, respectively. The researchers evaluated several scenarios, including one that assumed a detrimental effect of untreated maternal overt and subclinical hypothyroidism on child IQ, and improvement of the effects with treatment of levothyroxine. Under the scenario, screening proved to be particularly beneficial. "[In considering the child's IQ], screening became cost-saving, in terms of risk-based as well as universal screening, meaning it cost less to screen than the alternative strategy," Dr. Dosiou said. The findings suggest that the universal screening pregnant women for thyroid disease provides benefits that, as with some of the other most prominent screening efforts, are well worth the effort and cost, Dr. Dosiou emphasized. "The cost-effectiveness of screening pregnant women for autoimmune thyroid disease compares very favorably to the cost-effectiveness of other well-accepted screening practices in women, such as hypertension, mammography and fecal occult blood screening," she said. "Based on the results, we feel the medical community should strongly consider incorporating a TSH and anti-TPO antibody levels to the test of the first prenatal visit." Marco Centanni, MD, an associate professor of endocrinology at the University of Rome, in Latina, Italy, said he supported the need for universal screening, and suggested that efforts should be made to in fact try to begin screening before pregnancy. "Usually a woman may not get an exam for 4 to 6 weeks after discovering she is pregnant, and that is an enormous amount of time to lose if she is hypothyroid," he said.

"The screening should perhaps be offered even before the pregnancy," Dr. Centanni advised. He also indicated that testing for free thyroxine should also be performed in addition to TSH. "TSH is a marker that may be biased by several drugs and conditions," he observed. Dr. Dosiou noted, however, that additional testing may, among other things, increase the cost. "For the sake of cost, I think you have to take a limited number of tests for your initial screen and then turn to further testing if there are abnormalities," she said. "Yes there are a lot of things that affect TSH, but we are more concerned about the things that can falsely elevate TSH probably than those that would lower it, so I think overall TSH and TPO give a good combination that is reasonable from a cost standpoint." Dr. Dosiou and Dr. Centanni have disclosed no relevant financial relationships. American Thyroid Association (ATA) 2011 Annual Meeting; Abstract #10. Presented October 27, 2011