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Surgical intervention helped with persistent symptoms of Hashimoto's disease, according to results of a randomized trial from Norway.

Among patients with euthyroid status on hormone replacement therapy, but who had persistent Hashimoto-related symptoms, total thyroidectomy significantly improved overall health 18 months after surgery compared with hormonal medical management (between-group difference: 29 points on Short Form-36 Health Survey, 95% CI 22-35 points), reported Ivar Guldvog, MD, PhD, of Telemark Hospital in Skien, and colleagues.

Patients who underwent surgery saw an average jump of 26 points in their general health score from baseline, they wrote in .

Other significant clinical improvements were also seen in patients who underwent a total thyroidectomy after 18 months, not seen in patients medically managed with hormones:

• Fatigue score: decreased from 23 to 14 points (between-group difference of 9.3 points, 95% CI 7.4-11.2 points)
• Chronic fatigue frequency: decreased from 82% to 35% (between-group difference of 39 percentage points, 95% CI 23-53 percentage points)
• Median serum anti-TPO antibody titers: decreased from 2,232 to 152 IU/mL (between-group difference of 1,148 IU/mL, 95% CI 1,080-1,304 IU/mL)

"Some patients with this disorder report symptoms despite adequate treatment with levothyroxine, and at baseline, patients in this trial exhibited clinically relevant impairment in health-related quality-of-life and fatigue scores compared with the general Norwegian population," Guldvog's group explained. They added that currently, "no specific treatment exists for patients whose symptoms persist despite adequate thyroid hormone replacement."

The randomized trial included 150 adult patients from one center in Norway, all of whom had chronic and persistent Hashimoto-related symptoms, such as extreme tiredness, sleep disturbance, and arthralgia or myalgia, despite being on hormone replacement therapy. All patients also had serum antithyroid peroxidase (anti-TPO) antibody titers >1,000 IU/mL and thyroid-stimulating hormone (TSH) levels >3.5 mIU/L before hormone replacement. To be eligible for the study, patients had to have severe enough symptoms to be interested in surgery.

At baseline, the surgical group was on a 618 μg (range 157 to 1450 μg) median weekly dose of levothyroxine compared with a 550 μg (range 88 to 1500 μg) weekly dose for the medical management group. During follow-up, levothyroxine dose was adjusted every third month if necessary to maintain euthyroid status.

Three patients (4.1%) of the surgical group experienced postsurgical infections, while another three experienced longstanding hypocalcemia. A few patients also experienced unilateral recurrent laryngeal nerve palsy a few months after surgery, although this improved by the end of the follow-up period.

The authors hypothesized the improvement in symptoms seen in the study was likely due to the normalization of serum anti-TPO antibody titers via two different pathways.

"First, serum anti-TPO antibodies may lead to cross-reaction with other tissues. In patients with oligoarthritis, anti-TPO antibodies have been detected in synovial fluid 1 year before appearing in serum, revealing Hashimoto disease," they wrote, adding that it's possible that "activated anti-TPO antibody-producing lymphocytes may leave the thyroid gland and invade other, distant tissue, contributing to inflammation and nonhypothyroid symptoms."

Guldvog and colleagues also pointed out that clearance of serum anti-TPO antibody might simultaneously occur with a reduction in other immunologic mediators, including T-lymphocyte-derived proinflammatory cytokines interferon-γ and tumor necrosis factor-α.

Study limitations included a relatively short 18-month follow-up period, and that the surgery itself could have produced "a strong placebo effect," they noted.

"Because symptom relief is the dominant goal for many patients, we encourage further studies using symptoms as the end point, with longer follow-up, and including differentiation among subgroups of patients with Hashimoto disease," the authors concluded, suggesting future research of immunologic mechanisms in Hashimoto patients after surgery.

Click for the American Association of Clinical Endocrinologists's clinical practice guidelines for adult hypothyroidism.

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