source: Endocrine Society
Albert Hsieh, Stephen Adelstein, Susan McLennan, Paul F Williams, Stephen Morris Twigg, Elizabeth Lian Chua
One of the greatest challenges in managing Graves’ disease (GD) is the high recurrence of hyperthyroidism after achieving remission. Approximately 50-80% of individuals with GD who do not have definitive treatment with either radioactive iodine or thyroidectomy will experience disease recurrence. Although some evidence suggests that male gender, smoking, and geographical variation may contribute to the risk of recurrence, the factors that affect recurrence have not been fully explored (1). We performed a review of the Royal Prince Alfred Hospital Thyroid Clinic adult database from 2000 to 2012 inclusive, examining the factors associated with GD recurrence. Recurrence was defined as developing thyrotoxicosis after achieving American Thyroid Association defined remission, i.e. having “normal serum TSH, FT4, and T3 for 1 year after discontinuation of anti-thyroid therapy” (2). If patients developed thyrotoxicosis within 12 months of delivery, they were excluded from the analysis.
There were 183 patients with GD who had both clinical and biochemical hyperthyroidism. Forty out of 183 had a GD recurrence. Among the 40 patients, 80% were female; 55% had East and South East Asian ancestry and 32.5% of patients had European ancestry; 60% had a family history of thyroid disorder; 22.5% were active smokers and 5% were ex-smokers.
Univariate analysis showed that age of GD onset < 30 years was significantly associated with the risk of recurrence (P=0.02) while gender, ancestry, family history, and smoking history were not. Age of GD onset was divided into 4 subgroups: ≤ 20, 21 to 30, 31 to 40, and > 40 years. The percentage of recurrence was 40%, 29%, 21% and 11% in each age group, respectively. Multivariate logistic regression showed a strong inverse relationship of GD recurrence with initial age of diagnosis. The odds ratios for recurrence in ascending order of age groups using > 40 years as the reference group, were 6.5 (95% CI 1.3-33.1), 3.6 (95% CI 1.2-11.0), and 2.3 (95% CI 0.7-7.2).
Using less stringent criteria of recurrence, defined as development of thyrotoxicosis at any time after cessation of medication, having had at least 12 months of anti-thyroid therapy or during the post-partum period, 49.2% of the 183 patients recurred. The significant inverse relationship of GD recurrence with age of onset <30 years was again observed. (P<0.001)
In conclusion, this analysis demonstrates the novel finding that earlier age of GD onset is significantly and progressively associated with disease recurrence. We recommend taking age of GD onset into account in decisions about GD treatment, monitoring, and planning for definitive therapy.
Royal Prince Alfred Hospital, Australia; University of Sydney, Australia