Reference: Ann Intern Med. 2019 Apr 2 (level 2 [mid-level] evidence)
Hashimoto Thyroiditis (HT) is considered the most common autoimmune disease worldwide (Autoimmun Rev. Apr-May 2014). First-line symptomatic management for primary and permanent hypothyroidism seen in HT is administration of synthetic levothyroxine. Surgery is typically performed when a goiter causes significant compression of the surrounding cervical structures or if there is concern for carcinoma (Autoimmun Rev. Apr-May 2014). Thyroid hormones have profound effects on many organs and tissues and signs and symptom of HT are numerous and variable. Patients often report profound fatigue, poor sleep quality, muscle and joint tenderness, and dry mouth and eyes (Ann Intern Med. 2019 Apr 2). There is currently no additional treatment for patients whose symptoms persist despite adequate thyroid hormone replacement (Ann Intern Med. 2019 Apr 2). Persistent symptoms are thought to be related to autoimmune disease rather than to inadequate hormone replacement (Ann Intern Med. 2019 Apr 2). In the study to be reviewed, complete removal of the antigenic tissue via total thyroidectomy was studied to assess effectiveness in relieving symptoms compared to medical management (Ann Intern Med. 2019 Apr 2).
A recent randomized unblinded controlled trial was performed to evaluate the outcomes of total thyroidectomy compared to medical therapy alone in 150 adults (mean age 49 years, 91% women) with persistent HT-related symptoms, as described above, despite euthyroid status while receiving hormone replacement therapy. All patients had serum antithyroid peroxidase (anti-TPO) antibody titers > 1,000 units/mL and thyroid-stimulating hormone > 3.5 milliunits/L before hormone replacement. The primary outcome was general health-related quality of life, measured on the Short form-36 Health Survey (SF-36) questionnaire (score range 0-100 points, with higher scores indicating better health-related quality of life) at 18 months. Secondary outcomes included serum anti-TPO antibody titers, the other 7 sub-scores of the SF-36 Health Survey, total fatigue (assessed by fatigue questionnaire; score range 0-33 points, with higher scores indicating greater fatigue), and chronic fatigue (defined as ≥ 4 points for duration of 6 months; score range 0-11 points, with higher scores indicating greater fatigue). Baseline symptom values were similar between groups.
For the primary outcome at 18 months, mean SF-36 general health score improved from 38 points to 64 points with surgery compared to a decline with medical management, from 38 points to 35 points (95% CI for difference 15-26 points higher, p < 0.001). For secondary outcomes at 18 months, mean total fatigue score improved from 23 points to 14 points with surgery compared to worsening with medical management, from 23 points to 24 points (95% CI for difference 7.4-11.2 points lower), chronic fatigue in 35% of patients in the surgery group compared to 74% of patients in the medical management group (p < 0.001, number needed to treat [NNT] of 3), and median serum antithyroid peroxidase antibody 152 units/mL with surgery compared to 1,300 units/mL with medical management (p < 0.001).
Surgical complications were low in this study. In the total thyroidectomy group, adverse events included postsurgical infections in 3 patients (4.1%), hypocalcemia in 3 patients (4.1%), and unilateral recurrent laryngeal nerve palsy in 4 patients (5.5%). In the medical management group, 1 patient experienced a stroke.
Overall, this trial demonstrated that total thyroidectomy led to improvement in health-related quality of life, fatigue, and normalization of serum anti-TPO antibody titers. One theory for the positive effect of thyroidectomy with normalization of anti-TPO antibodies is that anti-TPO antibodies lead to cross-reactions with other tissues and that clearing of anti-TPO antibodies may occur in parallel with a reduction in other immunologic mediators (Ann Intern Med. 2019 Apr 2).
While the results of this study are significant, there are several limitations including small sample size, a homogenous patient population, and lack of blinding with potential placebo effect favoring surgical intervention. In addition, the patient reported outcome measure (PROM) parameters were subjective in nature. Further, there is a known diagnosis of post-thyroidectomy fatigue syndrome, and with follow-up being limited to 18 months, it may not have been long enough to assess long-term effects (Langenbecks Arch Surg.2017 Nov). While SF-36 has been deemed an effective method to evaluate quality of life, it may not be applicable to this specific disease state. Including a more disease-specific PROM instrument, such as Thy-PRO (thyroid-related patient-reported outcome) would have been preferable (Ann Intern Med. 2019 Apr 2).
Physicians need to carefully consider the risks and benefits when referring a patient for the invasive procedure of thyroidectomy. Patients with HT are thought to be particularly prone to recurrent nerve palsy and hypocalcemia after surgery (Ann Intern Med. 2019 Apr 2). Further studies with longer term follow-up and assessment of complications would be of benefit. Ultimately, this study presents evidence in support of a possible treatment for symptomatic euthyroid autoimmune HT and offers another possible therapy for a disease with limited treatment options.
For more information, see the Hashimoto Thyroiditis topic in DynaMed.
Dr. Ashley Blasi is a Family Medicine PGY-1 at Memorial Health University Medical Center in Savannah, GA. She is originally from Clarks Summit, Pennsylvania. She attained her undergraduate degree from Marywood University and then traveled to North Carolina to earn her medical degree from Campbell University School of Osteopathic Medicine. She continues to move south for more days of sunshine allowing for plenty of kayaking and hiking with her pup, Jaxon. In her free time, she also loves to travel and has visited Paris, London, Italy, Spain, and Croatia (with hope that next on the agenda will be Greece)! Dr. Blasi has a particular interest in home-health medicine, direct primary care, and work with underserved populations.
Faculty contributions by Dr. Marvin Sineath