Triiodothyronine-predominant Graves' disease in childhood: detection and therapeutic implications

Abstract

Objective: To assess in a pediatric population, the clinical characteristics and management of triiodothyronine-predominant Graves' disease (T 3 -P-GD), a rare condition well known in adults, but not previously described in children. Design: We conducted a university hospital-based observational study. Methods: All patients with GD followed for more than 1 year between 2003 and 2013 (nZ60) were included. T 3 -P-GD (group I) was defined as high free T 3 (fT 3 ) concentration (O8.0 pmol/l) associated with a normal free thyroxine (fT 4 ) concentration and undetectable TSH more than 1 month after the initiation of antithyroid drug (ATD) treatment. Group II contained patients with classical GD without T 3 -P-GD. Results: Eight (13%) of the patients were found to have T 3 -P-GD, a median of 6.3 (3.0-10.5) months after initial diagnosis (nZ4) or 2.8 (2.0-11.9) months after the first relapse after treatment discontinuation (nZ4). At GD diagnosis, group I patients were more likely to be younger (6.8 (4.3-11.0) vs 10.7 (7.2-13.7) years) and had more severe disease than group II patients, with higher serum TSH receptor autoantibodies (TRAb) levels: 40 (31-69) vs 17 (8-25) IU/l, P!0.04, and with slightly higher serum fT 4 (92 (64-99) vs 63 (44-83) pmol/l) and fT 3 (31 (30-46) vs 25 (17-31) pmol/l) concentrations. During the 3 years following T 3 -P-GD diagnosis, a double dose of ATD was required and median serum fT 4 :fT 3 ratio remained lower in group I than in group II. Conclusion: Severe hyperthyroidism, with particularly high TRAb concentrations at diagnosis, may facilitate the identification of patients requiring regular serum fT 3 determinations and potentially needing higher doses of ATD dosage during follow-up.

MANAGEMENT OF ENDOCRINE DISEASE: Arguments for the prolonged use of antithyroid drugs in children with Graves’ disease

“…Once the ATD dose has been reduced, biochemical evaluations should be carried out every 3-4 months. However, approximately 10% of patients with fT3-predominant GD, have high serum fT3 concentrations after serum fT4 concentrations have returned to normal or subnormal levels (21). These patients therefore have a high fT3:fT4 ratio, making it necessary to determine serum free T3 concentrations in patients with long-term undetectable TSH levels, to identify cases with this presentation.…”

“…These patients therefore have a high fT3:fT4 ratio, making it necessary to determine serum free T3 concentrations in patients with long-term undetectable TSH levels, to identify cases with this presentation. These patients have larger thyroid glands and high serum titers of TRAb (21,22,23). They are more likely to be younger and require doses of ATD twice as high as those used in patients with classic GD, over long periods of time, although it remains unclear why the maintenance of high doses is required to overcome the resistance to ATD (21).…”

Therapy with propylthiouracil for T3-predominant neonatal Graves’ disease: a case report

“…T3-P-GD presents with prominently elevated type 1 iodothyronine deiodinase (D1) activity and type 2 iodothyronine deiodinase (D2) activity. In this case of Graves’ disease, FT3 was elevated; this is known to be difficult to manage in adults ( 6 , 7 , 8 ). Oral administration of PTU was initiated, as it suppresses D1 activity, and its pharmacological action suppresses conversion of T4 to T3 ( 9 ).…”

Basedow-Graves’ disease in a pediatric patient with Sticlker syndrome, a new endocrine finding to improve personalized treatment

“…GD diagnosis was based on detecting a suppression of serum TSH concentrations and the presence of anti-TSH receptor antibodies, according to the literature [8].…”

“…As indicated by the paediatric endocrinology consultant, she was treated with Methimazole (MMI) with an initial dose of a half a 5 mg tablet three times a day (0.45 mg/kg/day). Other drugs, such as β-blockers, were not added in absence of cardiological signs or symptoms, according to the literature [8].…”