Toxicological considerations for antithyroid drugs in children

Abstract

The FDA recently reported that use of PTU is associated with a higher risk for clinically serious or fatal liver injury compared to MMI in both adult and pediatric patients. They also found that congenital malformations were reported approximately three times more often with prenatal exposure to MMI compared with PTU and especially with the use of MMI during the first trimester of pregnancy. The authors believe that PTU should not be used in pediatric patients unless the patient is allergic to or intolerant of MMI, and there are no other treatment options available. That being said, PTU may be the treatment of choice during, and just before, the first trimester of pregnancy.

Management of Neonates Born to Mothers With Graves’ Disease

“…Subsequent American Thyroid Association guidelines recommend that PTU should be offered only as a short course in case of thyroid storm or severe adverse reactions to MMI treatment, other than agranulocytosis, when treatment options such as radioactive iodine or thyroidectomy are not available. 67,68 Because a response to ATDs is seen only once thyroid hormone stores are depleted, it can take several days to weeks before clinical and biochemical effects are noticeable. In symptomatic patients, nonselective β-adrenergic blockers such as propranolol can decrease sympathetic hyperactivity.…”

“…72 The most common side effects are mild, such as transient elevations of liver enzymes, mild and transient leukopenia, skin rashes, gastrointestinal symptoms, arthralgia, and myalgia. 68,72 Serious side effects (0.5% of children) include agranulocytosis, liver injury, vasculitis and Stevens-Johnson syndrome. 68,72 Agranulocytosis most commonly presents with fever, sore throat, or mouth sores.…”

“…68,72 Serious side effects (0.5% of children) include agranulocytosis, liver injury, vasculitis and Stevens-Johnson syndrome. 68,72 Agranulocytosis most commonly presents with fever, sore throat, or mouth sores. Parents should be instructed to stop ATDs immediately if these occur, consult a physician, and obtain a complete blood count.…”

Propylthiouracil-induced mitochondrial dysfunction in liver and its relevance to drug-induced hepatotoxicity

“…Mice (n=42) were treated with PTU (10,20,40,80, and 160 mg/kg, i.p). The control animals received PTU vehicle (Normal saline, 5 ml/kg, i.p).…”

“…6,7 PTU also causes serious adverse effects such as agranulocytosis and liver failure. [8][9][10] Several cases of PTU-induced hepatotoxicity have been reported. 4,[11][12][13][14][15][16] Pediatrics seems to be more vulnerable to PTU-induced hepatotoxicity.…”