Sustained control of Graves' hyperthyroidism during long-term low-dose antithyroid drug therapy of patients with severe Graves' orbitopathy

Thyroid. 2011 Sep;21(9):951-6. doi: 10.1089/thy.2011.0039. Epub 2011 Aug 11.

Abstract

Background: Patients with severe Graves' orbitopathy often have hyperthyroidism that is difficult to treat and a high proportion of patients experience relapse of hyperthyroidism after a course of antithyroid drug (ATD) therapy of fixed duration. The aim of the study was to evaluate the feasibility of prolonged low-dose ATD therapy for attaining stable euthyroidism in patients with severe Graves' orbitopathy and hyperthyroidism.

Methods: We performed retrospective analyses of data collected during observation of a cohort of patients (n = 108) treated for severe Graves' orbitopathy and for hyperthyroidism using partial block with low-dose thionamide + replacement with levothyroxine (L-T4) for >2 years. The study was performed at a university hospital referral center for patients with severe Graves' orbitopathy.

Results: The median duration of thionamide therapy was 80 months (25-75 percentiles: 55-115 months); 101 patients received methimazole (median: 5 mg/day) without side effects during prolonged therapy, and 7 propylthiouracil (median: 200 mg/day); median L-T4 dose was 0.1 mg/day. Ninety percent of patients remained euthyroid throughout the period of therapy, and 65% of them had thyroid stimulating hormone (TSH) receptor antibodies in serum within the assay reference interval at the last observation. Only four (3.7%) developed episodes of hyperthyroidism during stable therapy, and 94% had serum TSH within 0.1-4.0 mU/L at the last observation. One patient developed reversible cutaneous vasculitis after 6 years of propylthiouracil therapy.

Conclusions: Prolonged partial block plus replacement therapy with low-dose ATD + L-T4 keeps the majority of patients with severe Graves' orbitopathy and hyperthyroidism stable and euthyroid.

MeSH terms

  • Adult
  • Antithyroid Agents / administration & dosage*
  • Antithyroid Agents / adverse effects
  • Biomarkers / blood
  • Denmark
  • Drug Administration Schedule
  • Feasibility Studies
  • Female
  • Graves Disease / diagnosis
  • Graves Disease / drug therapy*
  • Graves Disease / immunology
  • Graves Ophthalmopathy / diagnosis
  • Graves Ophthalmopathy / drug therapy*
  • Graves Ophthalmopathy / immunology
  • Hormone Replacement Therapy
  • Hospitals, University
  • Humans
  • Immunoglobulins, Thyroid-Stimulating / blood
  • Male
  • Methimazole / administration & dosage*
  • Methimazole / adverse effects
  • Middle Aged
  • Propylthiouracil / administration & dosage*
  • Propylthiouracil / adverse effects
  • Recurrence
  • Retrospective Studies
  • Severity of Illness Index
  • Thyroxine / administration & dosage
  • Time Factors
  • Treatment Outcome

Substances

  • Antithyroid Agents
  • Biomarkers
  • Immunoglobulins, Thyroid-Stimulating
  • thyrotropin-binding inhibitory immunoglobulin
  • Methimazole
  • Propylthiouracil
  • Thyroxine