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

Disclosures

Endocr Pract. 2019;25(1):43-50. 

In This Article

Results

A total of 316 medical records coded by "Graves disease" or "Graves ophthalmopathy" were screened (231 female subjects, 82 male subjects) (Figure 1). A total of 80 cases were excluded for either insufficient data (n = 38), diagnosis of subclinical hyperthyroidism (n = 7), GO with laboratory euthyroidism (n = 7), onset of disease in childhood (n = 10), noncompliance with medical treatment (n = 12), or other causes (n = 6). The final analysis included data of 235 patients (171 females, 64 males). Males comprised 27% of the study cohort.

Figure 1.

Case selection process.

Patient Characteristics at Disease Presentation

Men and women had similar age at disease presentation, 41.4 ± 14 years for men and 40 ± 15 years for women, and similar duration of follow-up with 6.6 ± 7 years for men and 7.6 ± 6 years for women (P = .06) (Table 1). Active smoking was twice more prevalent among male subjects (31% male vs. 15% female; P = .009). Rates of GO were similar (31% vs. 28%; P = .62), and the rate of GO necessitating treatment was also comparable (25% vs. 21%; P = .75).

Nonthyroidal autoimmune comorbidities were present in both groups: male subjects had type 1 diabetes mellitus (n = 3), celiac disease (n = 3), and pernicious anemia (n = 2). Female subjects presented with type 1 diabetes mellitus (n = 5), celiac disease (n = 1), pernicious anemia (n = 8), and other diseases (1 myasthenia gravis, 1 rheumatoid arthritis, 1 Bechcet disease, 1 Crohn disease, 1 systematic lupus erythematosus, 2 immune thrombocytopenic purpura cases); nonetheless, the overall rate of comorbid autoimmune diseases did not differ between study groups (13% in men, 12% in women, P = .98).

Laboratory data showed slightly higher values of free T4 at presentation among male subjects (46.9 ± 21.9 pmol/L vs.4.07 ± 17.5 pmol/L; P = .06), but no significant difference in values of free T3 (16.8 ± 6.5 pmol/L vs. 15.6 ± 6.7 pmol/L; P = .35) or positivity of anti-TSH receptor antibodies (90% vs. 85%; P = .61).

Treatment of Graves Patients

All male patients and 168 of 171 female patients were treated with ATDs as first line for a median time of 24 and 20 months, respectively (P = .55) (Table 2). Only 3 females (1.7% of female subjects) and none of the male patients received radioactive iodine as the initial treatment modality; reasons for prescribing iodine therapy in these cases were pregnancy planning (n = 1), baseline neutropenia (n = 1) and patient preference (n = 1). No patient underwent thyroidectomy as first-line therapy.

Outcome Data

Remission rates after the first course of ATD were comparable, with 47% in men and 58% in women (P = .14), after a mean follow-up of 9 ± 21 years and 6 ± 6 years, respectively. Men had lower rates of adverse effects (9% vs. 18%; P = .09) and discontinuation of ATD treatment (5% vs. 16%; P = .02) compared to women (Table 2). Adverse events in men included rash or pruritus in 3 subjects and elevated liver enzymes in 3 subjects. Adverse events in women included the following: rash or pruritus (n = 16), elevated liver enzymes (n = 7), neutropenia (n = 2), gastrointestinal intolerance (n = 2), arthritis (n = 1), arthralgia (n = 1), and thrombocytopenia (n = 1). Recurrence rates were comparable in men and women (14% vs. 20%; NS), as well as time to recurrence (58 ± 71 months vs. 51 ± 78 months; NS), and radioiodine treatment (20% vs. 23%, NS) (Table 2).

Predictors for Remission on ATD Therapy

Overall, 126 patients (54%) had remission (96 females, 30 males). Male subjects represented 34% of those who failed to achieve remission and 24% of those who did achieve remission with ATDs. Gender was not a predictor of remission in univariate analysis of the full study cohort (P = .124) (Table 3). Also, neither age at diagnosis of Graves disease, menopause, smoking, personal history of other autoimmune diseases, ophthalmopathy, blood levels of thyroid hormone, nor antithyroid antibodies predicted treatment success with ATD. Duration of therapy predicted remission (P = .003), as patients who achieved remission were treated for shorter periods of time compared to patients without remission (mean 27 ± 42 months vs. 45 ± 43 months). A second predictor for remission was report of adverse effects (P<.001), as more adverse events predicted lower rates of remission.

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