Thyroidectomy for Graves’ disease
Department of Surgery
Skåne University Hospital
University Hospitals of Geneva
Carolyn D. Seib
Department of Surgery
Stanford University School of Medicine
16 September 2021
Graves’ disease (GD) is an autoimmune disease in which thyroid receptor stimulating antibodies cause the thyroid to overproduce thyroid hormone, leading to hyperthyroidism. Untreated hyperthyroidism can lead to adverse clinical outcomes, including severe hypertension, cardiac arrhythmias and death. Graves’ disease is named after the Irish surgeon Robert James Graves, who was the first to identify the hallmark clinical features of GD, which include symptoms of hyperthyroidism associated with a diffuse goitre, thyroid eye disease, and pretibial myxoedema.
Public figures with GD include the British Comedian Marty Feldman, singer-songwriter Missy Elliott, former U.S. president George H.W. Bush and his wife, former first lady Barbara Bush. Marty Feldman, Missy Elliot, and Barbara Bush all had thyroid eye disease or Graves’ ophthalmopathy, which occurs in up to 25% of patients with GD.1,2 Graves’ ophthalmopathy is caused by autoantibody stimulation of orbital fibroblasts and adipocytes, which leads to inflammation due to cell proliferation and the local accumulation of glycosaminoglycans.3
Guidelines by the European Thyroid Association (ETA), the American Thyroid Association (ATA) and the American Association of Endocrine Surgeons (AAES) state that antithyroid drugs , radioiodine ablation (RAI), and thyroidectomy are treatment options for GD.4-6 The administration of drugs, most commonly methimazole, results in remission in approximately 50% of patients with GD, but is associated with adverse events including pruritic rash, agranulocytosis, and hepatotoxicity.7, 8 Given the majority of adverse events occur early in the medical treatment of GD, long-term treatment is safe and may lead to higher rates of remission.9,10 The ETA and ATA recommend total thyroidectomy for GD with ophthalmopathy, large goitres, co-existing primary hyperparathyroidism, suspected or proven thyroid cancer, and current or planned pregnancy.4,5. Relative contraindications include significant patient comorbidity and/or limited life expectancy, prior neck surgery and/or irradiation.4
Total thyroidectomy offers rapid resolution of hyperthyroidism and avoids adverse side effects associated with RAI and drugs. However, it carries a low but non-negligible risk of serious morbidity, including injury to the recurrent laryngeal nerves, neck haematoma, and hypoparathyroidism following incidental removal of the parathyroid glands and/or damage to their delicate blood supply. These risks are lower in the hands of high-volume thyroid surgeons.11 Total thyroidectomy is associated with a lower risk of recurrent hyperthyroidism than subtotal thyroidectomy without any difference in risk of complications, and is the operative technique of choice for GD in developed countries.12 Recent data from Hong Kong suggest that patients with GD treated with thyroidectomy have more favorable long-term outcomes than those treated with drugs or RAI.13 Further, a Swedish study found better quality of life after surgery compared to RAI and/or medication.14
Regional practice patterns have a significant influence on the primary treatment for GD, and rates of thyroidectomy differ substantially between countries. In the U.S., endocrinologists historically favoured RAI as the initial treatment of choice for GD,15 although recent publications suggest a trend towards increasing use of first-line and longer-term medical therapy.16,17 Thyroidectomy is used more selectively in the U.S. for patients with Graves’ ophthalmopathy and at specific high-volume centres.16,18 In Europe, drugs are favoured as first-line treatment, reserving thyroidectomy for those who fail this treatment.5,19
The bloodless, extracapsular dissection technique in thyroid surgery was pioneered by the father of thyroid surgery, Professor Theodor Kocher in Bern, who in 1909 was awarded the Nobel Prize for his contributions to the understanding and management of thyroid disease. Early on, surgeons recognized the importance of the recurrent laryngeal nerves and parathyroids. In the 1990s, intraoperative nerve monitoring (IONM) was introduced to help surgeons identify and preserve the recurrent and superior laryngeal nerves. Although randomized trial data are lacking, there is evidence from observational studies that IONM reduces the risk of nerve injury.20 Further reductions might be achieved with continuous nerve monitoring, whereby a soft silicone electrode is attached to the vagus nerve, constantly stimulating the nerve, warning the surgeon of impending damage to the recurrent laryngeal nerve.21 IONM not only helps the surgeon identify and preserve the nerve, it can also predict nerve damage and allow for staging of contralateral thyroid lobectomy to prevent bilateral vocal cord injury and tracheostomy.
Hypoparathyroidism, previously thought to be rare, has recently been shown to be both common and morbid, causing significant impairment in quality of life.22 Persistent hypoparathyroidism, defined based on the need for calcium and active vitamin D for more than 6 months postoperatively, has been associated with increased morbidity and mortality following thyroidectomy.23,24 Measuring parathyroid hormone levels postoperatively can identify patients at risk of postoperative hypocalcaemia and define the need for calcium and vitamin D supplementation.25
A team led by the engineer Anita Mahadevan-Jansen at Vanderbilt University showed that the parathyroids exhibit fluorescence, i.e. when illuminated with light of a specific wavelength (specifically 785 nm, in the near-infrared light) they reflect light back with a different wavelength (820 nm).26 This property, near-infrared autofluorescence (NIRAF), has been used in devices that help surgeons identify the parathyroids in situ. Further, with angiography of the parathyroid glands, their delicate vasculature can be delineated and preserved. NIRAF has been shown in at least two randomized controlled trials to decrease the rate of early postoperative hypocalcaemia.27, 28 Having at least one well-perfused gland decreases the risk of hypoparathyroidism. Hence, NIRAF with angiography shows promise to replace postoperative measurement of parathyroid hormone to predict normocalcaemia.29,30 Autofluorescence is rapidly gaining acceptance with both probe-based and image-based devices commercially available.
Due to concerns about the adverse impact of scar appearance in select patient populations, surgeons have explored endoscopic techniques to remove the thyroid. Arguably, the remote access method with the most promise is the transoral endoscopic thyroidectomy vestibular approach (TOETVA), whereby the thyroid is accessed via small incisions under the lower lip in the oral vestibule.31
Although this technique is offered to patients with GD at high-volume centers with reported low rates of complications,32 remote access thyroid surgery for GD should only be performed in carefully selected patients at centers with experience performing these operations in patients with GD.
Conflicts of Interest
None to declare.
No funding was received for this blog article.
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