Disease Presentation and Remission Rate in Graves Disease Treated With Antithyroid Drugs

Is Gender Really a Factor?

Talia Diker-Cohen, MD, PhD; Hadar Duskin-Bitan, MD; Ilan Shimon, MD; Dania Hirsch, MD; Amit Akirov, MD; Gloria Tsvetov, MD; Eyal Robenshtok, MD


Endocr Pract. 2019;25(1):43-50. 

In This Article


Medical records of patients with Graves disease who were treated as outpatients at the endocrinology service of Rabin Medical Center between 2010 and 2015 were reviewed. Charts coded by "Graves disease" or "Graves ophthalmopathy" were screened. Diagnostic criteria for Graves disease included laboratory values consistent with overt hyperthyroidism confirmed by either positive anti–thyroid-stimulating hormone (TSH) receptor antibodies or diffuse uptake on thyroid scan. We included only a first episode of Graves' disease.

Major exclusion criteria were subclinical hyperthyroidism, GO with laboratory euthyroidism, onset of disease at <18 years of age, cases with insufficient data, and noncompliance with medical treatment or clinic visits as stated in the medical record. Patients were mostly started on methimazole 20 to 40 mg daily, and treatment was then individualized at the physician's discretion. Remission was defined according to the 2016 American Thyroid Association (ATA) hyperthyroidism guidelines [11] as laboratory euthyroidism 12 months after discontinuation of ATD therapy. At time of data cut-point, patients who were on ongoing treatment with an ATD (for longer than 18 months) were defined as no remission. Recurrence was defined as overt hyperthyroidism detected after at least 12 months of clinical and laboratory euthyroidism following ATD discontinuation in patients with previous documentation of remission. Patients were defined to have goiter as clinically assessed by physical examination during their office visits. Patients were defined to have GO in case of any of the following: (1) there were any signs of ophthalmopathy in the physical examination report per the European Group on Graves Orbitopathy criteria; (2) documentation of an imaging study (e.g., magnetic resonance imaging of orbital muscles) supporting the diagnosis of GO; (3) they received any treatment for GO; or (4) chart was coded by "Graves ophthalmopathy." Treatment of GO was defined according to use of drops, ointment, selenium, steroids, or surgery. No patient required external beam radiation. Menopause was defined based on the report in the medical chart, coding in the medical chart, age above 60 years, or laboratory tests of gonadotropins that were consistent with a menopausal status. The study was approved by the hospital's Institutional Review Board. Informed consent was not required for this retrospective analysis.

Serum TSH was measured by a two-site sandwich immunoassay using a direct chemiluminometric technology (normal range, 0.4 to 4.4 mIU/L), and free thyroxine (T4) and free triiodothyronine (T3) levels were measured by a competitive immunoassay (normal range, 10 to 20 pmol/L and 3.5 to 6.5 pmol/L, respectively) using a direct chemiluminescence technique (ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY). Anti–thyroid peroxidase antibodies were measured by a chemiluminescent sequential immunometric assay (Immulite 2000, Siemens Healthcare Diagnostics, Gwynedd, United Kingdom). TSH receptor antibodies were measured by enzyme-linked immunosorbent assay (ETI-Max 3000, DiaSorin, Saluggia, Italy).

Statistical Analysis

All statistical analyses were performed with SPSS, version 20.0 (IBM Corp, Armonk, NY). Associations between two categorical variables were examined using χ 2 test and Fisher's exact test; associations between continuous and quantitative variables were examined using the Mann-Whitney nonparametric U test. A two-sided P value of <.05 was considered statistically significant for all analyses.