These women should have their thyroid-stimulating immunoglobulin (TSI) levels measured at the beginning of pregnancy and again at 24-26 weeks. The results may help confirm a suspicion of fetal hyperthyroidism or prompt further analysis, she said at the meeting, sponsored by the University of California, San Francisco.

In most laboratories, a normal background TSI titer will be less than 130%. A TSI of 350% with a fetal heart rate below 160 beats per minute suggests a low risk for fetal hyperthyroidism, but continued monitoring in these cases is prudent, said Dr. Block of the university.

A fetal heart rate above 160 beats per minute typically characterizes the disease.

A TSI of 350%-500% puts the fetus at moderate risk for hyperthyroidism, and a TSI of more than 500% puts the fetus at high risk.

Fetal hyperthyroidism complicates 1% of pregnancies in U.S. women with a history of Graves’ disease. With active maternal disease, most fetuses will be protected by their mothers’ antithyroid medication.

Physicians should be especially careful to look for fetal hyperthyroidism in women with a history of Graves’ disease who are on thyroid hormone replacement therapy but have discontinued antithyroid medication. These women may still have thyroid-stimulating hormone (TSH)-receptor antibodies, which puts them at highest risk for fetal hyperthyroidism, she said.

In general, a maternal TSH-receptor antibody titer above 350% increases the likelihood that the fetus has hyperthyroidism.

Diagnosis is based on clinical symptoms and ultrasound findings. Ultrasound studies should be ordered for women with a history of Graves” disease to look for fetal, goiter or a hyperextended fetal neck that could indicate goiter.

Growth retardation, increased fetal motility, or accelerated fetal bone maturation also can be signs of fetal hyperthyroidism. If the woman had a previous pregnancy complicated by fetal hyperthyroidism, this also increases the risk for the disease in the current pregnancy.

In rare cases, obtaining a sample of fetal cord blood may be necessary to make the diagnosis, but this procedure carries a 1% risk of fetal loss.

Physicians should therefore weigh the risks and benefits carefully and consult a pediatric endocrinologist before performing this procedure.

Related posts:

1. Graves’ eye Disease Uncommon after Radioiodine
2. Smoking may Boost Dermopathy Risk in Graves’ Disease
3. Graves’ Disease in Pregnancy

A small study presented at the annual meeting of the American Association of Clinical Endocrinologists found that 31 of 39 patients with acropachy (79%), 81 of 102 patients with dermopathy (79%), and 13 of 46 patients with Hasbimoto’s thyroiditis (28%) had a history smoking.

More than half of patients with dermopathy or acropachy reported that they were current smokers, compared with 9% of patients with Hashimoto’s thyroiditis.

“Several reports have indicated that tobacco use is a risk factor for Graves’ ophthalmopathy,” noted Dr. Vahab Fatourechi of the Mayo Clinic, Rochester, Minn., in a poster presented at the meeting.

But the frequency of tobacco use in patients with even more severe manifestations of Graves’ disease had never been studied. These manifestations include acropachy, an inflammatory disorder of connective tissue that involves clubbing of the fingers and toes and can lead to elephantiasis, and dermopathy, also known as pretibial or localized myxedema, which is an infiltrative condition of the dorsum of the legs and feet characterized by hyperpigmented patches and plaques.

Dr. Fatourechi and coinvestigator Mitra M. Fatourechi, a medical student at the University of Minnesota, Minneapolis, compared age- and sex-matched patients with acropachy, dermopathy, or Hashimoto’s thyroiditis, finding a striking association between the more severe conditions and current or past tobacco use.

“Although the pathogenesis of this association is unclear and suggested modification of the immune process by smoking needs further confirmation, a strong case can be made for considering tobacco use as a risk factor for severity of autoimmune manifestations of Graves’ disease,” Dr. Fatourechi said. “Patients with Graves’ disease should be strongly advised against smoking.”

Related posts:

1. Graves’ eye Disease Uncommon after Radioiodine
2. Graves’ Disease in Pregnancy
3. Graves’ disease – Screen for Fetal Hyperthyroidism

Graves’ ophthalmopathy affects up to 30% of patients with Graves’ disease, with severe effects reported in 3%-5%.

The influence of radioiodine therapy on the development of Graves’ ophthalmopathy is not clear and is considered a controversial area.

Randomized data of good quality are not available, and no reliable clinical or laboratory predictors of the development of Graves’ ophthalmopathy following radioiodine therapy have been identified, although tobacco use has been suggested as a possible risk factor, said Dr. Hallanger-Johnson of the Mayo Clinic, Rochester, Minn., and her associates.

At the clinic, radioiodine therapy is the first choice of treatment for hyperthyroid adult Graves’ patients, regardless of the presence or severity of ophthalmopathy.

For the study, the investigators reviewed the charts of 592 such patients who had received their first radioiodine therapy between 1990 and 1993.

Most of the patients were women (76.9%), and the group had a mean age of 49 years. The majority (63.2%) had a history of smoking, 45.7% were current smokers, and 19.9% had taken antithyroid medication before being referred to Mayo.

Graves’ ophthalmopathy was present prior to radioiodine therapy in 17.7% (105) of the patients, comprising 21% of the smokers and 14% of the nonsmokers.

The patients with Graves’ ophthalmopathy at baseline had significantly higher levels of thyroid-stimulating immunoglobulin. Those patients also were more likely to have been taking antithyroid medication (36.2% vs. 16.9%), suggesting that the referring physicians were under the impression that radioiodine therapy might have adverse effects on Graves’ ophthalmopathy, the investigators noted.

The rate of new-onset Graves’ ophthalmopathy was 5% in the first year after radioiodine therapy, rising to 19.6% at 10 years, the investigators reported.

Patient survival free of Graves’ ophthalmopathy was 94.9% at 1 year, 86.3% at 3 years, 85.8% at 5 years, and 80.4% at 10 years.

The development of new-onset Graves’ ophthalmopathy was not associated with gender, smoking status, serum thyroxine concentrations, thyroid weight, patient age, or the need for a second dose of radioactive iodine.

However, development of new-onset Graves’ ophthalmopathy was marginally related to higher concentrations of thyroid-stimulating immunoglobulin, the investigators reported.

The purported adverse effects of radioiodine therapy and the increase in thyroid-stimulating hormone receptor antibodies typically occur in the first few months after radioiodine therapy.

The fact that new cases of Graves’ ophthalmopathy occurred in just 5% of study patients in the first year, with the rate remaining steady for the first 3 years, makes it unlikely that radioiodine therapy has an adverse effect on patients who do not already have Graves’ ophthalmopathy at baseline, Dr. Hallanger-Johnson and her associates pointed out.

The study did not address the course of eye disease among the 17% of patients who already had Graves’ ophthalmopathy at baseline, the investigators noted.

Related posts:

1. Graves’ Disease in Pregnancy
2. Smoking may Boost Dermopathy Risk in Graves’ Disease
3. Graves’ disease – Screen for Fetal Hyperthyroidism

Propylthiouracil (PTU) has been the preferred therapy for Graves’ disease during pregnancy, especially during first-trimester organogenesis, because methimazole (MMI) and carbimazole have been associated with aplasia cutis and rare embryopathy including choanal atresia, esophageal atresia, tracheoesophageal fistula, and athelia.

None of these congenital anomalies has been reported with the use of PTU, Dr. Mandel said at an American Thyroid Association–sponsored meeting. Dr. Mandel is associate chief of the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia.

Last month, the Food and Drug Administration issued a warning about the risk of severe liver injury associated with the use of PTU with the treatment of Graves’ disease. “After analyzing adverse event reports, the FDA has identified an increased risk of liver injury with propylthiouracil, compared with an alternative treatment for Graves’ disease, methimazole,” Dr. Amy Egan, deputy director for safety, division of metabolism and endocrinology products, FDA Center for Drug Evaluation and Research, said in a statement.

“Health care professionals should carefully consider which drug to initiate in a patient recently diagnosed with Graves’ disease. If PTU therapy is chosen, the patient should be closely monitored for symptoms and signs of liver injury, especially during the first 6 months after initiating therapy.”

The FDA is advising health care professionals to reserve PTU for patients in their first trimester of pregnancy or those who are intolerant of or allergic to methimazole.

The FDA statement, posted on the agency’s MedWatch Web site, said that 32 cases of serious liver injury were reported to the FDA from 1969, when the agency’s adverse event reporting program was established, through October 2008. Of these cases, 22 were in adults, and included 12 fatalities and 5 liver transplants. Among the 10 pediatric cases, there were 6 reports of liver transplants and 1 fatality, according to the statement.

On the basis of an analysis of these reports, the FDA has determined that the risk of hepatotoxicity is greater with PTU than with MMI. The FDA received only five reports of serious liver injury associated with MMI, which was approved in 1950.

The FDA announced plans to change the prescribing information for PTU to reflect the hepatotoxicity warning

Concerns about PTU’s hepatotoxicity have come largely from the pediatric community. Last year, the National Institute of Child Health and Human Development (NICHD) held a conference on “hepatic toxicity following treatment for pediatric Graves’ disease.” And most recently, Dr. Scott A. Rivkees of Yale University, New Haven, Conn., and Dr. Donald R. Mattison of NICHD called for an end to the use of PTU in children.

In a letter to the editor published in the April 9 issue of the New England Journal of Medicine (2009;360:1574-5), Dr. Rivkees and Dr. Mattison said that PTU-induced liver failure may occur in 1 in 2,000 to 1 in 4,000 treated children, with nearly 10 times that range developing reversible PTU-induced liver injury.

In the context of Graves’ disease in pregnancy, Dr. Mandel said, “it may be that we should be rethinking, what are the relative risks of hepatotoxicity with PTU versus the very rare embryopathy reported with methimazole [and carbimazole].”

Because the changes apparently caused by MMI “all occur by 8-10 weeks’ gestation, and some even earlier, there may be a rationale” to using PTU into early pregnancy and then switching to methimazole afterwards,” added Dr. Mandel, also professor of medicine and radiology at the University of Pennsylvania.

The original recommendations to use PTU in pregnancy–before the teratogenic effects of MMI were reported–came from studies suggesting that PTU was less likely to cross the placenta. More recent data acquired through the use of newer measurement techniques have challenged this, demonstrating a similar degree of transplacental passage with both drugs, she noted.

Related posts:

1. Smoking may Boost Dermopathy Risk in Graves’ Disease
2. Graves’ eye Disease Uncommon after Radioiodine
3. Graves’ disease – Screen for Fetal Hyperthyroidism