Thyroidectomy Versus Medical Management for Euthyroid Patients With Hashimoto Disease and Persisting Symptoms: A Randomized Trial

Ann Intern Med. 2019 Apr 2;170(7):453-464. doi: 10.7326/M18-0284. Epub 2019 Mar 12.


Background: Hashimoto disease is a chronic autoimmune thyroiditis. Despite adequate hormone substitution, some patients have persistent symptoms that may be the result of immunologic pathophysiology.

Objective: To determine whether thyroidectomy improves symptoms in patients with Hashimoto thyroiditis who still have symptoms despite having normal thyroid gland function while receiving medical therapy.

Design: Randomized trial. ( NCT02319538).

Setting: Secondary care hospital in Norway.

Patients: 150 patients aged 18 to 79 years with persistent Hashimoto-related symptoms despite euthyroid status while receiving hormone replacement therapy and with serum antithyroid peroxidase (anti-TPO) antibody titers greater than 1000 IU/mL.

Intervention: Total thyroidectomy or medical management with hormone substitution to secure euthyroid status in both groups.

Measurements: The primary outcome was general health score on the Short Form-36 Health Survey (SF-36) at 18 months. Secondary outcomes were adverse effects of surgery, the other 7 SF-36 subscores, fatigue questionnaire scores, and serum anti-TPO antibody titers at 6, 12, and 18 months.

Results: During follow-up, only the surgical group demonstrated improvement: Mean general health score increased from 38 to 64 points, for a between-group difference of 29 points (95% CI, 22 to 35 points) at 18 months. Fatigue score decreased from 23 to 14 points, for a between-group difference of 9.3 points (CI, 7.4 to 11.2 points). Chronic fatigue frequency decreased from 82% to 35%, for a between-group difference of 39 percentage points (CI, 23 to 53 percentage points). Median serum anti-TPO antibody titers decreased from 2232 to 152 IU/mL, for a between-group difference of 1148 IU/mL (CI, 1080 to 1304 IU/mL). In multivariable regression analyses, the adjusted treatment effects remained similar to the unadjusted effects.

Limitation: Results are applicable only to a subgroup of patients with Hashimoto disease, and follow-up was limited to 18 months.

Conclusion: Total thyroidectomy improved health-related quality of life and fatigue, whereas medical therapy did not. This improvement, along with concomitant elimination of serum anti-TPO antibodies, may elucidate disease mechanisms.

Primary funding source: Telemark Hospital.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antibodies / blood
  • Drug Therapy, Combination
  • Fatigue / prevention & control
  • Female
  • Follow-Up Studies
  • Hashimoto Disease / immunology
  • Hashimoto Disease / physiopathology*
  • Hashimoto Disease / surgery
  • Hashimoto Disease / therapy*
  • Hormone Replacement Therapy*
  • Humans
  • Iodide Peroxidase / immunology
  • Male
  • Middle Aged
  • Patient Reported Outcome Measures
  • Postoperative Complications
  • Quality of Life
  • Thyroid Gland / physiology*
  • Thyroidectomy* / adverse effects
  • Thyroxine / therapeutic use*
  • Triiodothyronine / therapeutic use
  • Young Adult


  • Antibodies
  • Triiodothyronine
  • Iodide Peroxidase
  • Thyroxine

Associated data