Background Conflicting data have been reported on the association between IFN- therapy of multiple sclerosis (MS) patients and thyroid disease development.

Aims To assess the actual occurrence of thyroid dysfunction and autoimmunity during long-term IFN- therapy; to establish the possible presence of predictive factors for thyroid dysfunction development and duration; to suggest an effective follow-up protocol for patients receiving long-term IFN- therapy.

Study protocol 106 MS patients (76 women) underwent IFN- 1a or 1b therapy for up to 84 months (median 42). Thyroid function and autoimmunity were assessed at baseline and every 3-6 months throughout the treatment course.

Results Baseline thyroid autoimmunity was detected in 8.5% of patients and hypothyroidism in 2.8%. Thyroid dysfunction (80% hypothyroidism, 92% subclinical, 56% transient) developed in 24% (68% with autoimmunity) of patients and autoimmunity in 22.7% (45.5% with dysfunction), without significant differences between the two cytokines; 68% of dysfunctions occurred within the first year. Autoimmunity emerged as the only predictive factor for dysfunction development (RR 8.9), while sustained disease was significantly associated with male gender (P < 0.003).

Conclusions Both incident thyroid autoimmunity and dysfunction frequently occur in MS patients during IFN- therapy, particularly within the first year of treatment. Thyroid dysfunction is generally subclinical and transient in over than half of cases; preexisting or incident autoimmunity emerged as the only significant predictive factor for thyroid dysfunction development. Thyroid function and autoimmunity assessment is mandatory within the first year of IFN- therapy thereafter, serum TSH measurement only in patients with thyroid disease could be sufficient.