How to use thionamide anti-thyroid drug in the young– what’s new?

Abstract

The excess thyroid hormone secretion that characterises Graves’ disease (GD) is generated when stimulatory antibodies bind to the thyroid stimulating hormone receptor on the follicular cell of the thyroid gland.This underlying mechanism cannot easily be abolished and the mainstay of Graves’ disease (GD) management in the young remains thionamide anti-thyroid drug (ATD). Unfortunately, GD will usually recur after a 2 or 3 year course of ATD, even when the stimulatory antibody titres have fallen. The diagnosis of GD therefore usually signals the start of a lengthy period of out-patient assessments and associated venepuncture. Careful, more protracted administration of ATD may increase the likelihood of longer-term remission and reduce the likelihood of the patient developing ATD side-effects. An understanding of how best to use ATD and an awareness of the less well-known consequences of GD and its’ treatment - such as excessive weight-gain and long-term hypothyroidism – are also of fundamental importance.Recent clinical studies have shed light on how best to manage the young patient with GD and the associated new information will help to answer some of the questions posed by the young person and their family at diagnosis. This new knowledge is the focus of this article about ATD therapy in the young.

Remission in pediatric Graves’ disease treated with antithyroid drug and the risk factors associated with relapse

“…However, the thionamide effect of a decrease in TRAb level has an unknown mechanism. Commonly accepted theories include altering antigen presentation or a direct immunomodulatory action by ATDs [ 20 ]. In vitro data suggest that thionamide inhibits thyroid autoantibody production in cultured lymphocytes [ 20 - 22 ].…”

“…Commonly accepted theories include altering antigen presentation or a direct immunomodulatory action by ATDs [ 20 ]. In vitro data suggest that thionamide inhibits thyroid autoantibody production in cultured lymphocytes [ 20 - 22 ]. However, other accumulating evidence suggests otherwise [ 23 , 24 ].…”

Graves’ disease: moving forwards

“…26 Most side effects occur within the first 3 months of treatment, 27 although the rare but potentially fatal side effect agranulocytosis (absolute neutrophil count of <0.5×10 9 /L) can arise after many years. 28 It is essential that when ATD is prescribed, the young person and their family are counselled about the importance of stopping the medication in the event of a sore throat or fever until they have an FBC checked. If agranulocytosis develops, alternative treatment should be initiated.…”

“…Rarely, hepatic dysfunction can develop which is cholestatic in nature, and unlike with PTU, will resolve on stopping treatment 26. Most side effects occur within the first 3 months of treatment,27 although the rare but potentially fatal side effect agranulocytosis (absolute neutrophil count of <0.5×10 9 /L) can arise after many years 28…”

“… 26 Most side effects occur within the first 3 months of treatment, 27 although the rare but potentially fatal side effect agranulocytosis (absolute neutrophil count of <0.5×10 9 /L) can arise after many years. 28 …”