American Thyroid Association 87th Annual Meeting:

New Thinking Suggests Extending Medication Therapy for Pediatric Thyroid Diseases

With Catherine A. Dinauer, MD, and Andrew Bauer, MD, FAAP

For pediatricians and endocrinologists alike, diagnosing and managing patients with pediatric autoimmune thyroid disease (AITD) is an ongoing challenge,1 said Catherine A. Dinauer, MD, who spoke at the ATA Pediatric Thyroid Forum Satellite Program at the American Thyroid Association 87th Annual Meeting in Vancouver, BC, Canada.

While questions remain, much more is known about the ideal management for both Graves' disease and Hashimoto's thyroiditis in children,1 said Dr. Dinauer,  a pediatric endocrinologist at Yale University in New Haven, Connecticut, in her opening remarks.

One key to managing both conditions would be for physicians to discuss with parents the limitations of treatment and the likelihood of remission for Grave’s disease, which is low in some cases, starting when either of the autoimmune thyroid conditions is diagnosed.1

Dr. Dinauer also discussed new thinking about the appropriate length of time for medical therapy of Grave’s disease, which was, she said, the more difficult thyroid disease to manage in children.1

New recommendations for pediatric Grave's disease is to extend medication therapy. Best outcomes achieved when parents are informed of long-term prognosis and treatment options at the beginning of treatment..

Managing Pediatric Hashimoto Thyroiditis and Grave's Disease

To establish a full appreciation for the challenge endocrinologists and families are facing, Dr. Dinauer offered some statistics about the prevalence of both conditions, which she said in children are not easy to come by. Some surveys suggest that about 5% of teenagers in the United States have antibody evidence of Hashimoto's thyroiditis, although they do not necessarily have low thyroid function.2

For Graves' Disease in the pediatric population, estimates range from 1 in 5,000 to 1 in 10,000 in the US,2 she said.

Among the influencing factors that raise the risk for thyroid autoimmune disease in children are:1

  • Genetic predisposition
  • Exposure to environmental factors, including iodine, selenium, medications, infection, stress, pollution
  • Endogenous experiences such as rapid growth, puberty onset, pregnancy, menopause, aging, emotional vulnerability and female sex

Standard of Care for Managing Grave’s Disease

The preferred medical therapy for Grave’s disease is methimazole (MMI) since carbimazole (a precursor of MMI, not available in the US), and propylthiouracil (PTU) has a black box warning and therefore is not recommended for pediatric use,1 according to Dr. Dinauer.

“Medical therapy for pediatric Grave’s disease is purely palliative, not curative,” said Dr. Dinauer, and “ It's a message that bears repeating to patients and their parents.”

The recommended dosing strategy as suggested by Dr. Dinauer is as follows:1,3

  • Begin at 0.2 to 0.5 milligram per kilogram body weight per day, she says, and starting doses more than 30 mg a day should be avoided.
  • Once daily or twice a day (BID) dosing is appropriate.
  • TH levels can be expected to normalize in 4-12 weeks, after which the dose should be decreased once FT4 or total T4 normalize
  • "Block and replace" is not recommended

Medication side effects include rash, pruritus, arthralgia, nausea, transient granulocytopenia (1000 to 1500 mm3), increased liver enzymes. More major side effects include agranulocytosis (below 500 mm3), Stevens-Johnson syndrome, severe hepatitis/liver failure, MPO-ANCA-mediated vasculitis.4

"Many of the side effects are dose-related" with methimazole, Dr. Dinauer said.

Best Strategies to Achieve Remission

Parents, understandably, want to know the prognosis for Grave’s disease, especially the chance of remission, Dr. Dinauer said. Studies have presented a broad range of possibilities, so she recommends telling parents that they may expect, on average, that there is a 25% chance for remission. The likelihood of remission in Grave’s disease is much less than for adults, which may be as high as 45 to 50%.

"We really know why that is,'' Dr. Dinauer said, of the differences in remission rates between children and adults.

Dr. Dinauer urges clinicians to be more patient with the length of medical treatment. Traditionally, treatment for one to two years has been recommended due to the low likelihood of remission, and then the discussion must turn to more definitive next level treatment—radioactive iodine or surgery.1

However, currently, if children are doing ok on medication, the best approach is to keep them on it longer, really as long as possible, according to Dr. Dinauer. Determination of whether a pediatric patient can tolerate the medication to continue is dependent on several factors—It is appropriate provided the hyperthyroidism is well-controlled, there no evidence of toxicity, the patient is compliant, and the patient not ready for definitive treatment.3

Determining the Right Time to Initiate Definitive Treatment

“Discussion about definitive treatment should be ongoing,” said Dr. Dinauer, to enable patients and their families to become better informed about the pros and cons of radioactive iodine and surgery, particularly to avoid any surprise when medical treatment has stopped working and they are faced with having to make a sudden choice about which procedure is preferable.

She advised talking about fully exploring both options, radioactive iodine as well as surgery.

For radioactive iodine, the pros are:

  • Outpatient procedure
  • No scarring or cosmetic concerns
  • Patient does not need to become euthyroid
  • Safety record good with appropriate doses

For radioactive iodine, cons:

  • Need for 72 hours of isolation
  • Chance for failure
  • Variable time to hypothyroidism, worsening of GO, possible increase in TSIg
  • Not recommended for children under five years

For surgery, the pros:

  • Immediate relieve from hyperthyroidism
  • Relief from compressive symptoms
  • TSIg titer likely to decline or become normal

For surgery, the cons:

  • Surgical risks such as recurrent laryngeal nerve injury and hypoparathyroidism
  • Scarring and keloid risk

New Thinking on Length of Therapy for Pediatric Grave's Disease

"Taking care of [a patient with] Hashimoto's is much easier than Grave’s disease," Dr. Dinauer said, “That is because the symptoms are subtle and often happen gradually. Every now and then we see a child with very severe hypothyroidism," she says, where the growth rates have dropped off."

The child may be sluggish, but still functioning. Those with Grave’s disease, on the other hand, often have significant dysfunction—going from excellent grades to failing, for instance, and showing moodiness, anxiety, and anger. Parents often confuse these symptoms as typical teen angst, she said.

By the time pediatric patients are diagnosed, they often have had the symptoms for at least six months to a year.

“The points about new thinking on the length of medical therapy for Grave’s Disease is important for endocrinologists to take note of,” said Andrew J. Bauer, MD, FAAP, director of the Thyroid Center at the Children's Hospital of Philadelphia. The new approach of extending mediation for as long as possible is based on mounting evidence from research as well as practical experience.

"At least two studies suggest, backed by a trend in clinical practice, that [children] can be maintained on medication for much longer than two years," Dr. Bauer told EndocrineWeb. The cut point now, depending on the patient, is probably five to seven years, he said.

For pediatricians, the take-home message from the update, he said, is to have an ''index of suspicion" for hyperthyroidism. If in doubt? Run some labs, says Dr. Bauer, who is also an associate professor of pediatrics at the University of Pennsylvania Perelman School of Medicine. "At least get a TSH,'' he says. "It’s the simplest screening lab for both."

A video captures Dr. Bauer sharing other key highlights from the Pedidatric Satellite Forum.

Dr. Dinauer reports no disclosures; Dr. Bauer has no disclosures.

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