Hurthle Cell Carcinoma Treatment & Management

Updated: Jun 08, 2016
  • Author: Serhat Aytug, MD; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment

Medical Care

Surgical excision is the main treatment for patients with Hürthle cell carcinoma. Postoperative iodine-131 (131I) scanning is usually performed 4-6 weeks after surgery. No thyroid hormone treatment is administered to the patient in the interim. If uptake occurs in the thyroid bed or other sites, a treatment dose of 131I is administered, and another total body scan is obtained 4-7 days later.

Radioactive iodine-131 treatment

This treatment is usually administered if postoperative iodine scanning shows uptake, in the thyroid bed or elsewhere.

131I therapy is used after surgery for three reasons. First, radioactive iodide destroys any remaining normal thyroid tissue, thereby enhancing the sensitivity of subsequent 131I total-body scanning and increasing the specificity of measurements of serum thyroglobulin for the detection of persistent or recurrent disease. Second, 131I therapy may destroy occult microscopic carcinoma. Third, the use of a large amount of 131I allows for total-body scanning, which is a more sensitive test for detecting persistent carcinoma.

Compared with other thyroid carcinomas, Hürthle cell cancer has a lower avidity for 131I; therefore, treatment with radioactive iodide has limited efficacy. Reportedly, approximately 10% of metastases take up radioiodine, compared with 75% of metastases from follicular carcinoma; thus, radioactive iodide treatment, which is the most useful nonsurgical therapy for recurrent well-differentiated thyroid carcinoma, is not always useful in patients with Hürthle cell carcinoma. This causes difficulty in the treatment of recurrences. Nevertheless, radioactive iodide treatment is used for most patients with Hürthle cell cancers after total and near-total thyroidectomy and in the treatment of patients with recurrent and metastatic Hürthle cell carcinoma.

Jillard et al reported that post-thyroidectomy 131I therapy improves survival in patients with Hürthle cell carcinoma. In their review of 1909 cases, patients who received 131I (n=1162) had superior 5-year and 10-year survival compared with patients who did not (88.9 vs. 83.1% and 74.4 vs. 65.0%, respectively, p <0.001). These authors conclude that their finding suggest that radioactive iodine therapy should be advocated for patients with  tumors >2 cm, and those with nodal and distant metastatic disease. [25]

There is limited evidence in the literature that redifferentiation therapy with retinoic acid may restore 131I uptake in some thyroid carcinomas that have lost their capability for radioiodine concentration; however, the benefits of this approach remain uncertain. [26, 27] Retinoic acid therapy also may be considered in patients with Hürthle cell carcinoma that does not take up radioactive iodide, although this is not yet a standard form of therapy.

Levothyroxine treatment

The growth of thyroid tumor cells is controlled by thyroid-stimulating hormone (TSH), and the inhibition of TSH secretion with levothyroxine (T4) lowers recurrence rates and improves survival; therefore, T4 should be administered to all patients with thyroid carcinoma, regardless of the extent of thyroid surgery and other treatments.

Levothyroxine treatment is started after the treatment dose of 131I is administered. The effective dose of T4 in adults is 2.2-2.8 mcg/kg; children require higher doses. The adequacy of therapy is monitored by measuring serum TSH about 8-12 weeks after the treatment begins. The initial goal is a serum TSH concentration of 0.1 µU/mL or less and a serum triiodothyronine concentration within the reference range. When these guidelines are followed, T4 therapy does not have deleterious effects on the heart or bone.

External radiotherapy

Hürthle cell carcinoma is considered a radiosensitive tumor. Radiation therapy may provide palliative relief from symptomatic metastases, control recurrent tumors, and prevent recurrence of advanced resected tumors. [28]

External radiotherapy to the neck and mediastinum is indicated only in patients in whom surgical excision is incomplete or impossible. This therapy can also be considered for tumors that do not take up 131I.

Chemotherapy

Chemotherapy for metastatic differentiated thyroid cancer is usually ineffective. However, some experimental trials have yielded promising results

Over the past decade, good progress has been made in understanding molecular mechanisms of thyroid cancer; accordingly, multiple medications are being developed to target various molecules involved in the development of differentiated thyroid cancer. These targets are present both in the tumor cell as well as at the vascular endothelial cells providing blood supply to the tumor. The drugs include multikinase inhibitors, selective kinase inhibitors, and combination therapies. Examples include sorafenib, gefitinib, axitinib, motesanib, sunitinib, and pazopanib. Sorafenib is approved by the US Food and Drug Administration (FDA) for advanced differentiated thyroid cancer. [29]

Younes et al have studied antivascular therapy in mouse models with bone metastasis from follicular thyroid cancer. [30, 31] In these studies, a novel dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGFR) was used alone and in combination with paclitaxel. These studies showed suppression of tumor growth, with promising outcomes.

A treatment algorithm can be viewed at the National Comprehensive Cancer Network’s Thyroid Carcinoma clinical practice guideline. See Thyroid Cancer Treatment Protocols for summarized information.

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Surgical Care

Surgery is the main treatment for patients with Hürthle cell carcinoma. Surgical treatment is aimed at removal of the entire cancer, thereby minimizing the risk of locally persistent or recurrent disease, providing adequate staging information, minimizing risk without compromise to optimal cancer management, improving efforts for postoperative adjunctive treatment (eg, radioactive iodide), and facilitating follow-up care.

Total thyroidectomy is usually recommended for patients with Hürthle cell carcinomas, whereas patients with Hürthle cell adenomas are generally treated with a thyroid lobectomy.

Although total thyroidectomy is generally considered the treatment of choice for Hürthle cell carcinoma, a lobectomy is usually performed first; if histologic sections show Hürthle cell carcinoma, as evidenced by vascular and/or capsular invasion, then a complete thyroidectomy is performed in a second surgery. In clinically high-risk cases and in some institutions, a total thyroidectomy is performed as the first surgery based on frozen section results. Unfortunately, the majority of series have insufficient numbers of patients to allow statistically valid conclusions regarding which of those approaches should become the standard.

Intraoperative frozen section examination of the thyroid gland has variable diagnostic value, based on institutional experience. This procedure requires processing of an average of 6-15 slides per patient, which is impractical in many institutions. Other limitations include the following:

  • Sampling error
  • Variable thickness
  • Irregularity of the capsule
  • Freezing artifact
  • Difficulty in distinguishing capsular entrapment from invasion
  • Freezing-induced distortion and collapse of the blood vessels.

Frozen section provides no additional value in most studies. However, in one study, the diagnosis of malignant follicular or Hürthle cell carcinoma was established correctly in 78% of cases, thereby permitting immediate definitive surgical management and eliminating the need for two-stage operations. [32]

Standard surgical wound care is usually appropriate. Postoperative care includes careful monitoring for the following:

  • Infection
  • Hematoma
  • Signs of recurrent laryngeal nerve injury (eg, hoarseness)
  • Airway compromise
  • Signs of hypoparathyroidism and hypocalcemia
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Consultations

Management of thyroid cancer is a team effort, and the following consultations should be obtained:

  • Endocrinologist
  • Surgeon
  • Nuclear medicine specialist
  • Pathologist
  • Radiation oncologist
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Diet and Activity

No particular diet is recommended, but an iodide-free diet is recommended at least 1 week prior to scanning to minimize the interference. Activity may be performed as tolerated.

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