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There are three main treatments for Hürthle cell adenomas. Once the adenoma is detected most often the nodules removed to prevent the cells from later metastisizing. A total thyroidectomy is often performed, this results in a complete removal of the thyroid. Some patients may only have half of their thyroid removed, this is known as a thyroid lobectomy. Another treatment option includes pharmacological suppression of thyroid hormone. The thyroid gland is responsible for producing the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Patients with suppressed thyroid function often require oral thyroid replacement (e.g. levothyroxine) in order to maintain normal thyroid hormone levels. The final treatment option is RAI abaltion (radioactive iodine ablation). This treatment option is used to destroy infected thyroid cells after total thyroidectomy. This treatment does not change prognosis of disease, but will diminish the recurrence rate. Also, Hürthle cells do not respond well to RAI. However, often doctors suggest this treatment to patients with Hürthle cell adenoma and Hürthle cell carcinoma because some Hürthle cells will respond and it will kill remaining tissue.
Most of these tumors are treated with surgical removal. It is non recurrent.
Treatment may include the following:
- Surgery with or without radiation
- Radiotherapy
Fast neutron therapy has been used successfully to treat salivary gland tumors, and has shown to be significantly more effective than photons in studies treating unresectable salivary gland tumors.
- Chemotherapy
A non-minimally invasive Hürthle cell carcinoma is typically treated by a total thyroidectomy followed by radioactive iodine therapy. A Hürthle cell adenoma or a minimally invasive tumor can be treated by a thyroid lobectomy, although some surgeons will perform a total thyroidectomy to prevent the tumor from reappearing and metastasizing.
A modified radical neck dissection may be performed for clinically positive lymph nodes.
Clinical trials of protein kinase inhibitors, which block the abnormal kinase proteins involved in the development and growth of medullary cancer cells, showed clear evidence of response in 10-30% of patients. In the majority of responders there has been less than a 30% decrease in tumor mass, yet the responses have been durable; responses have been stable for periods exceeding 3 years. The major side effects of this class of drug include hypertension, nausea, diarrhea, some cardiac electrical abnormalities, and thrombotic or bleeding episodes.
Vandetanib, trade name Caprelsa, was the first drug (April 2011) to be approved by US Food and Drug Administration (FDA) for treatment of late-stage (metastatic) medullary thyroid cancer in adult patients who are ineligible for surgery.
Cabozantinib, trade name Cometriq, was granted marketing approval (November 2012) by the U.S. FDA for this indication. Cabozantinib which is a potent inhibitor of RET, MET and VEGF was evaluated in a double-blind placebo controlled trial. It was shown to improve overall survival by 5 months for the treated cohort vs. placebo, which was not statistically significant. However, cabozantinib was particularly effective in patients with the RET M918T mutation, extending overall survival by roughly 2 years, doubling survival vs. untreated patient (4 years vs. 2 year). Treatment with cabozantinib did require many dose reduction to mitigate side effects. It has been suggested that the trial dose of 140 mg was excessive, particularly in lower body mass patients. Ongoing trials have been scheduled to identify more optimal dosing regimes. Activity has been observed, in practice at doeses of 1.2 mg/kg.
Surgery and radiation therapy have been the major treatments for medullary thyroid carcinoma.
Management of MEN2 patients includes thyroidectomy including cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved and selective resection of pathologic parathyroid glands for primary hyperparathyroidism.
Familial genetic screening is recommended to identify at risk subjects who will develop the disease, permitting early management by performing prophylactic thyroidectomy, giving them the best chance of cure.
Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC indicating the necessity of a complete thyroid surgery for index cases with MTC and the early thyroidectomy for screened at risk subjects.
The main treatment modalities are surgery, embolization and radiotherapy.
Most patients with thyroid adenoma can be managed by watchful waiting (without surgical excision) with regular monitoring. However, some patients still choose surgery after being fully informed of the risks. Regular monitoring mainly consists of watching for changes in nodule size and symptoms, and repeat ultrasonography or needle aspiration biopsy if the nodule grows.
Some benign tumors need no treatment; others may be removed if they cause problems such as seizures, discomfort or cosmetic concerns. Surgery is usually the most effective approach and is used to treat most benign tumors. In some case other treatments may be of use. Adenomas of the rectum may be treated with sclerotherapy, a treatment in which chemicals are used to shrink blood vessels in order to cut off the blood supply. Most benign tumors do not respond to chemotherapy or radiation therapy, although there are exceptions; benign intercranial tumors are sometimes treated with radiation therapy and chemotherapy under certain circumstances. Radiation can also be used to treat hemangiomas in the rectum. Benign skin tumors are usually surgically resected but other treatments such as cryotherapy, curettage, electrodesiccation, laser therapy, dermabrasion, chemical peels and topical medication are used.
Some studies have shown that thyroglobulin (Tg) testing combined with neck ultrasound is more productive in finding disease recurrence than full- or whole-body scans (WBS) using radioactive iodine. However, current protocol (in the USA) suggests a small number of clean annual WBS are required before relying on Tg testing plus neck ultrasound. When needed, whole body scans consist of withdrawal from thyroxine medication and/or injection of recombinant human Thyroid stimulating hormone (TSH). In both cases, a low iodine diet regimen must also be followed to optimize the takeup of the radioactive iodine dose. Low dose radioiodine of a few millicuries is administered. Full body nuclear medicine scan follows using a gamma camera. Scan doses of radioactive iodine may be I or I.
Recombinant human TSH, commercial name Thyrogen, is produced in cell culture from genetically engineered hamster cells.
Treatment of a thyroid nodule depends on many things including size of the nodule, age of the patient, the type of thyroid cancer, and whether or not it has spread to other tissues in the body.
If the nodule is benign, patients may receive thyroxine therapy to suppress thyroid-stimulating hormone and should be reevaluated in 6 months. However, if the benign nodule is inhibiting the patient's normal functions of life; such as breathing, speaking, or swallowing, the thyroid may need to be removed.
Sometimes only part of the thyroid is removed in an attempt to avoid causing hypothyroidism. There's still a risk of hypothyroidism though, as the remaining thyroid tissue may not be able to produce enough hormones in the long-run.
If the nodule is malignant or has indeterminate cytologic features, it may require surgery. A thyroidectomy is a medium risk surgery that can result complications if not performed correctly. Problems with the voice, nerve or muscular damage, or bleeding from a lacerated blood vessel are rare but serious complications that may occur. After removing the thyroid, the patient must be supplied with a replacement hormone for the rest of their life. This is commonly a daily oral medication prescribed by their endocrinologist.
Radioactive iodine-131 is used in patients with papillary or follicular thyroid cancer for ablation of residual thyroid tissue after surgery and for the treatment of thyroid cancer. Patients with medullary, anaplastic, and most Hurthle cell cancers do not benefit from this therapy. External irradiation may be used when the cancer is unresectable, when it recurs after resection, or to relieve pain from bone metastasis.
Levothyroxine is a stereoisomer of thyroxine which is degraded much slower and can be administered once daily in patients with hypothyroidism.
Without treatment, persons with MEN2B die prematurely. Details are lacking, owing to the absence of formal studies, but it is generally assumed that death in the 30s is typical unless prophylactic thyroidectomy and surveillance for pheochromocytoma are performed (see below). The range is quite variable, however: death early in childhood can occur, and it is noteworthy that a few untreated persons have been diagnosed in their 50s. Recently, a larger experience with the disease "suggests that the prognosis in an individual patient may be better than previously considered."
Thyroidectomy is the mainstay of treatment, and should be performed without delay as soon as a diagnosis of MEN2B is made, even if no malignancy is detectable in the thyroid. Without thyroidectomy, almost all patients with MEN2B develop medullary thyroid cancer, in a more aggressive form than MEN 2A. The ideal age for surgery is 4 years old or younger, since cancer may metastasize before age 10.
Pheochromocytoma - a hormone secreting tumor of the adrenal glands - is also present in 50% of cases. Affected individuals are encouraged to get yearly screenings for thyroid and adrenal cancer.
Because prophylactic thyroidectomy improves survival, blood relatives of a person with MEN2B should be evaluated for MEN2B, even if lacking the typical signs and symptoms of the disorder.The mucosal neuromas of this syndrome are asymptomatic and self-limiting, and present no problem requiring treatment. They may, however, be surgically removed for aesthetic purposes or if they are being constantly traumatized.
Surgery remains the mainstay of treatment for papillary thyroid cancer. The Revised 2009 American Thyroid Association guidelines for papillary thyroid cancer state that the initial procedure should be near-total or total thyroidectomy. Thyroid lobectomy alone may be sufficient treatment for small (<1 cm), low-risk, unifocal, intrathyroidal papillary carcinomas in the absence of prior head and neck irradiation or radiologically or clinically involved cervical nodal metastasis.
- Minimal disease (diameter up to 1.0 centimeters) - hemithyroidectomy (or unilateral lobectomy) and isthmectomy may be sufficient. There is some discussion whether this is still preferable over total thyroidectomy for this group of patients.
- Gross disease (diameter over 1.0 centimeters) - total thyroidectomy, and central compartment lymph node removal is the therapy of choice. Additional lateral neck nodes can be removed at the same time if an ultrasound guided FNA and thyroglobulin TG cancer washing was positive on the pre-operative neck node ultrasound evaluation.
Arguments for total thyroidectomy are:
- Reduced risk of recurrence, if central compartment nodes are removed at the original surgery.
- 30-85% of papillary carcinoma is multifocal disease. Hemithyroidectomy may leave disease in the other lobe. However, multifocal disease in the remnant lobe may not necessarily become clinically significant or serve as a detriment to patient survival.
- Ease of monitoring with thyroglobulin (sensitivity for picking up recurrence is increased in presence of total thyroidectomy, and ablation of the remnant normal thyroid by low dose radioiodine 131 after following a low iodine diet (LID).
- Ease of detection of metastatic disease by thyroid and neck node ultrasound.
- Post-operative complications at high-volume thyroid surgery centers with experienced surgeons are comparable to that of hemithyroidectomy.
Arguments for hemithyroidectomy:
- Most patients have low-risk cancer with an excellent prognosis, with similar survival outcomes in low-risk patients who undergo total thyroidectomy versus hemithyroidectomy.
- Less likelihood of patient requiring lifelong thyroid hormone replacement after surgery.
Thyroid total body scans are less reliable at finding recurrence than TG and ultrasound.
Papillary tumors tend to be more aggressive in patients over age 45. In such cases, it might be required to perform a more extensive resection including portions of the trachea. Also, the sternocleidomastoid muscle, jugular vein, and accessory nerve are to be removed if such procedure allows apparently complete tumor resection. If a significant amount of residual tumor is left in the neck, external radiotherapy has been indicated and has proven useful especially in those cases when the residual tumor does not take up radioiodine.
After surgical thyroid removal, the patient waits around 4–6 weeks to then have radioiodine therapy. This therapy is intended to both detect and destroy any metastasis and residual tissue in the thyroid. The treatment may be repeated 6–12 months after initial treatment of metastatic disease where disease recurs or has not fully responded.
Patients are administered hormone replacement levothyroxine for life after surgery, especially after total thyroidectomy. Chemotherapy with cisplatin or doxorubicin has proven limited efficacy, however, it could be helpful for patients with bone metastases to improve their quality of life. Patients are also prescribed levothyroxine and radioiodine after surgery. Levothyroxine influences growth and maturation of tissues and it is involved in normal growth, metabolism, and development. In case of metastases, patients are prescribed antineoplastic agents which inhibit cell growth and proliferation and help in palliating symptoms in progressive disease.
After successful treatment, 35 percent of the patients may experience a recurrence within a 40-year span. Also, patients may experience a high incidence of nodule metastasis, with 35 percent cases of cervical node metastases. Approximately 20 percent of patients will develop multiple tumors within the thyroid gland.
There is ongoing discussion regarding the best management regarding the optimal surgical procedure for papillary thyroid cancer. Prognosis of patients with papillary thyroid cancer is found to be dependent on the patient's age, the size of the tumor, presence of metastatic disease, and the presence of tumor invasion into adjacent tissues near the thyroid gland. Recent studies have examined a more conservative approach to surgery and have demonstrated that hemithyroidectomy may be acceptable for patients with low-risk papillary thyroid cancer with tumor size 1 cm to 4 cm with no presence of invasion to tissues surrounding the thyroid or metastasis. Studies examining large databases of patients with papillary thyroid cancer have concluded that there is no survival advantage for patients with stage I papillary thyroid cancer size 1–4 cm receiving total thyroidectomy versus hemithyroidectomy. In light of this data, choosing the optimal course of surgical and medical management of papillary thyroid cancer should involve shared decision making from patient, endocrinologists, and surgeons.
An alternative using high intensity focused ultrasound or HIFU has recently proved its effectiveness in treating benign thyroid nodules. This method is noninvasive, without general anesthesia and is performed in an ambulatory setting. Ultrasound waves are focused and produce heat enabling to destroy thyroid nodules.
Focused ultrasounds have been used to treat other benign tumors, such as breast fibroadenomas and fibroid disease in the uterus.
The role of external beam radiotherapy (EBRT) in thyroid cancer remains controversial and there is no level I evidence to recommend its use in the setting of differentiated thyroid cancers such as papillary and follicular carcinomas. Anaplastic thyroid carcinomas, however, are histologically distinct from differentiated thyroid cancers and due to the highly aggressive nature of ATC aggressive postoperative radiation and chemotherapy are typically recommended.
The National Comprehensive Cancer Network Clinical Practice Guidelines currently recommend that postoperative radiation and chemotherapy be strongly considered. No published randomised controlled trials have examined the addition of EBRT to standard treatment, namely surgery. Radioactive iodine is typically ineffective in the management of ATC as it is not an iodine-avid cancer.
Imbalances in age, sex, completeness of surgical excision, histological type and stage, between patients receiving and not receiving EBRT, confound retrospective studies. Variability also exists between treatment and non-treatment groups in the use of radio-iodine and post-treatment thyroid stimulating hormone (TSH) suppression and treatment techniques between and within retrospective studies.
Some recent studies have indicated that EBRT may be promising, though the number of patients studies has been small.
Clinical trials for investigational treatments are often considered by healthcare professionals and patients as first-line treatment.
A recommend surveillance program for Multiple Endocrine Neoplasia Type 1 has been suggested by the International Guidelines for Diagnosis and Therapy of MEN syndromes group.
In the absence of extracervical or unresectable disease, surgical excision should be followed by adjuvant radiotherapy. In the 18–24% of patients whose tumour seems both confined to the neck and grossly resectable, complete surgical resection followed by adjuvant radiotherapy and chemotherapy could yield a 75–80% survival at 2 years.
There are a number of clinical trials for anaplastic thyroid carcinoma underway or being planned.
The different manifestations of Birt–Hogg–Dubé syndrome are controlled in different ways. The fibrofolliculomas can be removed surgically, through curettage, shave excision, skin resurfacing, or laser ablation; however, this is not a permanent solution as the tumors often recur. The renal and pulmonary symptoms are managed preventatively: CT scans, ultrasounds, or MRIs of the kidneys are recommended regularly, and family members are advised not to smoke. MRIs are the preferred method for surveillance of the kidneys in people with BHD because they do not carry the same risk of radiation complications as CT scans and are more sensitive than ultrasounds. Smokers with Birt–Hogg–Dubé have more severe pulmonary symptoms than non-smokers. Though nephrectomy is sometimes indicated, kidney tumors in cases of Birt–Hogg–Dubé are often removed without taking the whole kidney, in a procedure called partial nephrectomy. Knockout mouse studies have shown that administration of rapamycin may mitigate the effects of FLCN mutations on kidneys and improve renal cancer prognoses because of folliculin's interaction with the mTOR pathway.
Based on overall cancer staging into stages I to IV, papillary thyroid cancer has a 5-year survival rate of 100 percent for stages I and II, 93 percent for stage III and 51 percent for stage IV.
The usual treatment is surgery. The surgery usually is a fertility-sparing unilateral salpingo-oophorectomy. For malignant tumours, the surgery may be radical and usually is followed by adjuvant chemotherapy, sometimes by radiation therapy. In all cases, initial treatment is followed by surveillance. Because in many cases Sertoli–Leydig cell tumour does not produce elevated tumour markers, the focus of surveillance is on repeated physical examination and imaging. Given that many cases of Sertoli–Leydig cell tumor of the ovary are hereditary, referral to a clinical genetics service should be considered.
The prognosis is generally good as the tumour tends to grow slowly and usually is benign: 25% are malignant. For malignant tumours with undifferentiated histology, prognosis is poor.
Surgery is the only cure for parathyroid adenomas. It is successful about 95% of the time. Parathyroidectomy is the removal of the affected gland(s). The standard of treatment of primary hyperparathyroidism was formerly a surgical technique called bilateral neck exploration, in which the neck was opened on both sides, the parathyroids were identified, and the affected tissue was removed. By the 1980s, unilateral exploration became more common. Parathyroidectomy can now be performed in a minimally invasive fashion, mainly because imaging techniques can pinpoint the location of the tissue. Minimally invasive techniques include smaller open procedures, radio-guided and video-assisted procedures, and totally endoscopic surgery.
Before surgery is attempted, the affected glandular tissue must be located. Though the parathyroid glands are usually located on the back of the thyroid, their position is variable. Some people have one or more parathyroid glands elsewhere in the neck anatomy or in the chest. About 10% of parathyroid adenomas are ectopic, located not along the back of the thyroid but elsewhere in the body, sometimes in the mediastinum of the chest. This can make them difficult to locate, so various imaging techniques are used, such as the sestamibi scan, single-photon emission computed tomography (SPECT), ultrasound, MRI, and CT scans. sometimes parathyroid adenomas can be ablated by ethanol injection, guided by ultrasound.
Renal oncocytoma is considered benign, cured by nephrectomy. There are some familial cases in which these tumors are multicentric rather than solitary. However, they may be resected to exclude a malignant tumor, e.g. renal cell carcinoma.
In terms of treatment/management one should observe what signs or symptoms are present and therefore treat those as there is no other current guideline. The affected individual should be monitored for cancer of:
- Thyroid
- Breast
- Renal