Endocrine surgery

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CHAPTER 57

Endocrine surgery

Thyroid

1. Using the Bethesda System, list the possible results of fine-needle aspiration (FNA) of thyroid nodules, and describe the appropriate surgical intervention.

2. A patient underwent thyroid lobectomy for a suspicious thyroid nodule, and the final pathology report revealed papillary carcinoma. How do you decide whether completion thyroidectomy is necessary?

3. Why not just do an intraoperative frozen section on indeterminate thyroid nodules to determine whether to perform lobectomy versus thyroidectomy?

4. What is the role for molecular testing of thyroid nodules?

Fifteen percent to 30% of thyroid nodules are cytologically indeterminate on FNA, and most of these patients undergo surgery to make a definitive diagnosis. However, most of these nodules turn out to be benign on final pathologic examination, in which case the surgery was unnecessary. The goal of molecular testing of thyroid nodules is to stratify the risk of malignancy further in those with indeterminate cytology to decrease the number of patients who undergo unnecessary surgery for benign disease. The most commonly analyzed mutations include those occurring in BRAF, RAS, and RET/PTC. There are commercially available tests that analyze for these and other mutations; however, it is very important to consider the positive and negative predictive values of these tests, as well as cost, when using them to guide clinical care.

5. What are the differences among total, near-total, and subtotal thyroidectomy?

6. What is the appropriate extent of thyroidectomy for differentiated thyroid carcinoma?

Most patients with differentiated thyroid carcinoma (papillary, follicular, Hürthle cell) should undergo total or near-total thyroidectomy. Several studies have shown that for larger tumors, total or near-total thyroidectomy compared with lesser resections results in lower recurrence rates and improved survival. There appears to be no difference in outcome between patients who undergo lobectomy and those who have near-total or total thyroidectomy when tumor size is less than 1 cm. However, for tumors larger than 1 cm, patients who undergo near-total or total thyroidectomy have lower recurrence and improved survival compared with those who undergo lobectomy. This improved outcome is seen even in the subset of patients with tumors 1 to 2 cm in size. Therefore, most patients should undergo total or near-total thyroidectomy.

7. What is the incidence of lymph node metastasis in well-differentiated thyroid cancer, and when is neck dissection indicated?

Differentiated thyroid cancer (predominantly papillary) involves cervical lymph nodes in 30% to 80% of cases. In most cases, the metastatic lymph nodes are not clinically evident; therefore, all patients should undergo a preoperative full neck ultrasound scan to assess for abnormal nodes. Unlike in many other malignant diseases, the presence of occult lymph node metastases does not worsen the outcome for most patients with differentiated thyroid cancer, and routine neck dissection does not clearly improve outcome except for patients in the high-risk group. Moreover, neck dissection may increase the risk of complications. For these reasons, the decision to perform neck dissection for differentiated thyroid cancer is somewhat controversial. The following are some general guidelines:

image All patients with clinically palpable nodes require compartment (central and/or lateral) dissection at the same time as thyroidectomy.

image Any suspicious nodes on ultrasound should undergo FNA and, if positive, should be removed via formal neck dissection as described earlier.

image Physical examination, ultrasound, and intraoperative assessment are insensitive in determining nodal metastasis in the central neck. Whether prophylactic central neck dissection at the time of thyroidectomy is indicated for papillary carcinoma is debated. The current American Thyroid Association Guidelines Taskforce state that prophylactic central neck dissection may be indicated in patients with advanced tumors (> 4 cm and/or grossly invasive), and that thyroidectomy alone may be appropriate for noninvasive tumors less than 4 cm.

8. What is central and modified radical neck dissection?

9. Describe the appropriate surgical management of medullary thyroid carcinoma.

Medullary thyroid carcinoma accounts for less than 5% of thyroid cancers but occurs as part of an inherited syndrome in 20% to 25% of cases. Thus, all patients with medullary thyroid carcinoma should be considered for genetic testing. If the patient has multiple endocrine neoplasia type 2 (MEN-2) syndrome, then prophylactic thyroidectomy is indicated; the specific RET gene mutation can help determine at what age the surgical procedure should occur. Patients with MEN-2 should also be screened for pheochromocytoma and primary hyperparathyroidism (HPT) so that these conditions can be surgically corrected before or concomitant with the thyroidectomy, respectively. Because medullary thyroid cancer is not sensitive to radioiodine or thyroid-stimulating hormone (TSH) suppression, total thyroidectomy is indicated. Given the high incidence of regional lymph node involvement, central neck dissection is performed at the time of thyroidectomy. Some surgeons also advocate routine bilateral modified neck dissection at the initial surgery; however, despite this aggressive approach, biochemical cure (normalization of calcitonin) is rare in patients with positive lymph nodes. Current guidelines recommend that lateral neck dissection should be performed selectively, based on clinically or ultrasonographically abnormal nodes.

10. Discuss the role of surgery in anaplastic carcinoma of the thyroid.

Anaplastic carcinoma of the thyroid accounts for less than 1% of thyroid cancers but is one of the most aggressive solid tumors known and is rarely curable. At the time of diagnosis, 50% of patients harbor distant metastases, and 95% have local invasion precluding curative resection. Thus, surgery is usually restricted to a diagnostic or palliative role. Palliative surgical debulking and tracheostomy should be reserved for symptoms of dysphagia or airway compromise, respectively, because they do not prolong survival. An attempt at curative resection should be reserved for younger patients without distant disease and only when all gross cervical and mediastinal disease can be resected without excessive morbidity. In this select subgroup of patients, curative-intent surgery combined with adjuvant external beam radiation and/or chemotherapy has been shown to prolong survival compared with patients treated with adjuvant therapy alone.

11. When is surgery indicated for recurrent thyroid cancer?

Suspected recurrent disease in the neck should be evaluated by FNA. Confirmed nodal recurrence should be treated with formal dissection of the involved neck compartment. Recurrence in a neck compartment that has already been subjected to formal neck dissection can be challenging because of scarring of the tissue planes that renders repeat formal neck dissection virtually impossible. In these situations, the risks and benefits of additional surgery must be carefully considered because the risk of complications increases and the likelihood of cure decreases with each subsequent surgical procedure for disease recurrence. Observation may be the best option for patients with low-risk disease. When indicated, nodal recurrences that are palpable can be locally excised. If these recurrences are not palpable, intraoperative ultrasound can be used to guide the excision. For patients who are poor surgical candidates or have had multiple neck operations, percutaneous ethanol injection of nodal metastases is an alternative. Radioiodine is the standard therapy for distant metastatic disease, but isolated metastases can occasionally be surgically resected or treated with external beam radiation.

12. How many times should a thyroid cyst be aspirated if it reaccumulates fluid?

13. List the indications for thyroidectomy in hyperthyroidism.

In the United States, thyroidectomy is not commonly performed for hyperthyroidism unless the condition is secondary to a single hyperfunctioning adenoma or to a toxic multinodular goiter that is associated with compressive symptoms or contains a suspicious nodule. Despite the excellent success rate, low recurrence rate, safety, and more rapid return to a euthyroid state, fewer than 10% of patients with hyperthyroidism undergo thyroidectomy. Possible indications for thyroidectomy in patients with hyperthyroidism include:

image Failure of antithyroid medications

image Large goiter and low iodine uptake

image Compression symptoms, such as dysphagia, stridor, or hoarseness

image Nodules suggestive of cancer

image Children

image Pregnant patients who are difficult to treat medically

image Young female patients who want to become pregnant in the near future

image Noncompliance

image Cosmetic concerns

image Severe Graves’ ophthalmopathy

14. How should patients with hyperthyroidism be prepared for surgery?

It is important to render patients euthyroid before surgery for hyperthyroidism, to avoid perioperative thyroid storm. Antithyroid medications administered for 4 weeks preoperatively are usually adequate. Some surgeons use saturated solution of potassium iodide (SSKI) or Lugol’s solution, 3 to 5 drops three times a day for 3 to 5 days before surgery, to decrease the vascularity of the goiter and reduce the risk of bleeding. Patients who are very symptomatic may benefit from preoperative beta-blockade. For more rapid induction of a euthyroid state, patients may also be given dexamethasone, which can return thyroxine (T4) and triiodothyronine (T3) levels to within the normal range in less than 7 days. In cases of severe, refractory hyperthyroidism, plasmapheresis may occasionally be indicated.

15. What are the complications of thyroidectomy?

16. What is the significance of a “hot” thyroid nodule incidentally discovered on a positron emission tomography (PET) scan?

17. What is the appropriate therapy for an intrathoracic (substernal) goiter?

Intrathoracic goiters are typically cervical goiters with mediastinal extension. Although they are commonly asymptomatic, up to 40% of patients present with compressive symptoms resulting from impingement on the airway, esophagus, vascular structures, or nerves. There is general agreement that medical therapy (thyroid hormone suppression and/or radioiodine) is ineffective for intrathoracic goiters. Whether there is an increased risk of malignancy in intrathoracic compared with cervical goiters is controversial; however, when cases of microcarcinoma are excluded, there does not appear to be an increased risk of malignancy in intrathoracic goiters. Even so, the presence of an intrathoracic goiter is considered by many as an indication for thyroidectomy. Because the arterial supply of intrathoracic goiters originates in the neck, most of these tumors can be resected through a cervical approach. Extension into the posterior mediastinum, malignancy, or compression of the vena cava may necessitate a combined cervical and sternotomy approach, although this is required in less than 5% of cases.

18. When should thyroglossal duct cysts be removed? Describe the operation.

During the embryologic development of the thyroid, a diverticulum forms from the foramen cecum at the base of the tongue and descends as the thyroglossal duct to the future anatomic position of the thyroid overlying the anterolateral surface of the upper tracheal rings. The thyroglossal duct normally disappears during further development but in rare cases persists as a patent duct or as a thyroglossal duct cyst. Patients may complain of infection, pain, or compressive symptoms, or they may have cosmetic concerns. Because of the risk of infection, thyroglossal duct cysts should be removed; this requires excision of the entire cyst and cyst tract from the origin at the foramen cecum down to the cyst itself. Because the tract nearly always passes through the hyoid bone, the center of the hyoid should be resected to lower the risk of recurrence; this causes no disability and requires no repair.

Parathyroid

19. Which patients with primary HPT should undergo parathyroidectomy?

Patients with classic symptoms of HPT (nephrolithiasis, severe bone disease or fractures, or overt neuromuscular syndrome) should undergo parathyroidectomy; however, most patients with HPT do not have the classic symptoms. The National Institutes of Health (NIH) established criteria to assist clinicians in determining which patients with “asymptomatic” HPT should undergo surgery. In the absence of any of these criteria, continued surveillance is a reasonable option; however, if the patient meets any one of the criteria, then surgery is recommended:

image Calcium greater than 1.0 mg/dL above normal

image Creatinine clearance reduced by more than 30%

image Bone mineral density reduced more than 2.5 standard deviations below mean peak adult value (T score)

image Age less than 50 years

image Patients who do not desire or cannot undergo surveillance

Nonspecific symptoms, such as fatigue, mental slowing, musculoskeletal aches and pains, and depression, were not included in the NIH indications for surgery but are commonly reported by patients. Compared with controls (patients undergoing thyroid surgery), patients with HPT score significantly lower on preoperative quality of life questionnaires. Several studies indicate improvement in these patient-reported outcomes following parathyroidectomy.

20. When should preoperative parathyroid localization studies be performed?

An experienced parathyroid surgeon does not require preoperative localization before initial bilateral neck exploration. However, most patients with primary HPT have a single parathyroid adenoma, so preoperative localization is commonly performed and, when successful, enables minimally invasive parathyroidectomy. Patients with a prior history of neck surgery and certainly all patients with persistent or recurrent HPT should undergo preoperative localization studies before planned re-exploration. The best localization study available is the technetium-99m sestamibi scan, although ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and parathyroid venous sampling with or without arteriography may all be useful in certain situations, especially persistent or recurrent HPT.

21. What is the best treatment for a 45-year-old woman with primary HPT but negative preoperative localization studies?

22. Define minimally invasive parathyroidectomy.

Conventional parathyroidectomy entails bilateral neck exploration, identification of all four glands, and removal of the grossly enlarged gland or glands. The development of accurate preoperative localization studies and a rapid intraoperative parathyroid hormone (ioPTH) assay fostered the development of minimally invasive approaches to parathyroidectomy. A directed unilateral approach uses preoperative imaging to limit the dissection to one side. The abnormal gland is found and removed; after 10 to 15 minutes, a postexcision blood sample is drawn, and the PTH level is compared with a preexcision blood sample. A reduction of the PTH to 50% of the preoperative level and into the normal range predicts successful removal of all hyperfunctioning glands, and the surgical procedure is terminated. If the PTH does not drop appropriately, then all four glands must be identified because the patient likely has multiglandular disease.

23. What is minimally invasive radioguided parathyroidectomy (MIRP)?

MIRP is a second alternative to conventional parathyroidectomy and involves a technetium-99m sestamibi scan the morning of the surgery. An incision is made, either unilateral or bilateral neck exploration is performed, and the abnormal parathyroid glands are removed. A small, hand-held gamma probe is then used to measure the ex vivo radioactive counts of the excised parathyroid to determine whether the gland is hyperfunctioning. Biopsy of normal or borderline enlarged parathyroid glands can also be performed. The ex vivo radioactive counts can be used to confirm that the biopsy represents parathyroid tissue and to determine whether the gland is hyperfunctioning, in which case the rest of the parathyroid is resected. Contrary to common perception, the gamma probe is not used to localize the abnormal parathyroid. An ioPTH assay can also be used to exclude the possibility of multiglandular disease further (5%–10%).

24. Summarize the advantages of minimally invasive approaches.

25. How is the ioPTH assay used in parathyroid surgery?

The half-life of PTH is 3 to 5 minutes, and this allows for a rapid assay for ioPTH to be used intraoperatively to assess the functional success of the operation. This test is performed by drawing a sample of blood before the operation and 10 minutes after removal of the suspected abnormal gland or glands. A reduction of the ioPTH by 50% predicts successful removal of all hyperfunctioning glands, and the surgical procedure is terminated. The rate of residual multiglandular disease is approximately 5% when ioPTH is used to determine the completeness of resection, whereas the rate is 10% to 35% when conventional parathyroidectomy is performed (i.e., bilateral neck exploration and removal of grossly enlarged parathyroids). Therefore, the use of ioPTH may prevent the unnecessary removal of glands that appear enlarged but are not hyperfunctional.

26. What is the expected success of surgery for primary HPT?

27. Describe the appropriate management of a “missing” parathyroid.

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