General Introduction
Surgical excision of endocrine tumors ranges from relatively common thyroid cancer surgery to rare conditions such as removal of pheochromocytoma and hypophysectomy for pituitary adenoma.
A comprehensive evaluation of the perioperative management of all endocrine tumors is beyond the scope of this chapter. Therefore this chapter focuses on the perioperative management of the following endocrine tumors:
Thyroid tumors
Pheochromocytoma
Cushing’s disease
Carcinoid syndrome
Hypophysectomy for pituitary adenomas
Perioperative Management of Thyroid Tumor Resection
Epidemiology
Thyroid cancer is now the most common endocrine malignancy worldwide. The incidence increased from 1.5 cases per 100,000 in 1953 to 7.5 cases per 100,000 in 2002. Developments in diagnostic capabilities, including neck ultrasonography, fine needle aspiration, computed tomography, and magnetic resonance imaging, may have contributed to this apparent increase in the diagnosis of thyroid cancer. Ninety percent of all thyroid tumors are indolent, with the estimated mortality rate at just 0.6 deaths per 100,000 person years. Benign thyroid disease requires treatment only in the presence of dysfunction or local compressive symptoms.
Preoperative Management
A comprehensive history and examination should assess for signs of severe hypothyroidism hyperthyroidism, or complications of thyroid disease, as outlined in Table 28.1 .
| Pathology | Signs and Symptoms |
| Hypothyroidism | Low respiratory rate, hypothermia Weight gain, atrial fibrillation, myxedematous facies, delayed reflexes |
| Hyperthyroidism | Hyperthermia, atrial fibrillation, tachyarrhythmias, sweating, anxiety, weight loss, diarrhea |
| Large Goiter (may be hypo- or hyper thyroid) | Positional dyspnea or dysphagia, neck swelling |
Enlarged thyroid glands or goiters as seen in Fig. 28.1 can lead to tracheal compression and difficult airway management. Airway assessment should include thyromental distance, assessment of neck movement, and visualization of pharyngeal structures.
Investigations recommended prior to thyroid surgery are outlined in Table 28.2 .
| Investigation | Indication |
| Full blood count | Antithyroid medications can cause agranulocytosis and aplastic anemia. Hypothyroidism may be associated with anemia of chronic disease |
| Urea and electrolytes | Hyperthyroidism can lead to diarrhea that can result in electrolyte abnormalities |
| Liver function tests | Antithyroid medications can cause hepatitis |
| Thyroid function test | Hypothyroidism: high TSH, low T4 Hyperthyroidism: low TSH, high T4 |
| Chest x-ray | Assessing for tracheal compression or deviation |
| CT scan | Assessing for a retrosternal goiter and tracheal compresssion |
| Laryngoscopy | Assessing for vocal cord dysfunction |
Interpretation of the Thyroid Function Test
Euthyroid Sick Syndrome
Significant physiological stress, such as critical illness, starvation, or surgery, results in hypothalamic adjustment of thyroid homeostasis.
Thyroid function tests reveal a decreased triiodothyronine (T3) level occasionally accompanied by a fall in circulating thyroxine (T4); however, thyroid stimulating hormone (TSH) levels remain within normal limits. Of note, patients remain clinically euthyroid throughout. As this is an adaptive response to physiological stress, no treatment is needed.
Clinical judgment is thus required in the interpretation of abnormal thyroid results in patients with a significant acute or chronic illness.
Corticosteroids
High doses of glucocorticoids inhibit the deiodination of T4 to T3, resulting in a decrease in circulating T3 levels. Corticosteroids also act on the hypothalamic-hypophyseal-thyroid axis by suppressing the pituitary’s production of TSH.
These interactions result in abnormal thyroid function tests and the administration of high-dose or long-term exogenous glucocorticoids. Such changes rarely reach clinical significance, with patients for the most part remaining euthyroid throughout their treatment course.
Intraoperative Management
Thyroid surgery is almost always performed under general anesthesia with tracheal intubation. General anesthesia may be induced in a standard manner. Awake fiberoptic intubation should be considered with a large goiter if it is causing tracheal compression, or in a retrosternal goiter with compressive symptoms, or vocal cord dysfunction.
Regarding the endotracheal tube itself, as the surgical field is focused on the head and neck, a simple endotracheal tube could potentially be at risk of kinking under the pressure of surgical handling in the upper neck. For this reason, some anesthesiologists prefer to use a wire-reinforced endotracheal tube, but there is no evidence that this affects patient outcomes.
A study of over 3000 thyroidectomies found that difficult intubation occurred in 6% of cases. Patients undergoing thyroid surgery are at risk of injury to the recurrent laryngeal nerve.
Short acting muscle relaxants can be used to facilitate tracheal intubation and allow for recurrent laryngeal nerve monitoring during the surgery.
Patients are positioned for surgery in neck extension with a head-up table tilt of 25% to reduce blood loss. As visualizing the patient’s face is often not possible intraoperatively, careful attention must be paid to securing the endotracheal tube and protecting the eyes.
Intraoperative monitoring of blood loss is required, via regular assessment of estimated blood loss and weighted swabs, especially in patients with large goiters.
Surgical technique involves raising of skin flaps, muscle retraction, superior pedicle mobilization, ligation and dissection of vessels, and hemostasis and wound closure.
Complications include the following.
Recurrent Laryngeal Nerve Damage
This can occur via ischemia, contusion, or inadvertent dissection. Incidence of recurrent laryngeal nerve (RLN) damage and vocal cord dysfunction ranges from 0% to 7.2% of all patients undergoing thyroidectomies. There is a higher incidence of RLN injury during repeat surgery for recurrent goiter or surgery for thyroid malignancy. Signs of vocal cord dysfunction, including stridor, dyspnea, and hoarseness, should be monitored in the postoperative period. Intraoperative electromyography can be used to protect the RLN from inadvertent surgical injury, whereby intramuscular vocal cord electrodes are placed into the laryngeal muscles and connected to the neuromonitoring device, which emits sound and displays graphics, so the surgical team remain aware of their proximity to the RLN.
Postoperatively vocal cords may be visualized directly using laryngoscopy. Visualization of both vocal cords moving is reassuring that RLN function is preserved, but this can be difficult to achieve safely in the reemerging patient. Surgical experience remains the most effective prognostic indicator of preservation of RLN. A vocal cordectomy may be necessary if vocal cord dysfunction does not improve after 4–6 weeks.
Cervical Hematoma
Signs include stridor (abnormal high-pitched breath sounds, especially on inspiration) occurring within 6 hours of tracheal extubation. Bleeding leads to compression of the trachea and potentially acute airway obstruction. Intraoperative Valsalva maneuvers can identify potential sites of early postoperative bleeding for the surgical team. Management of a suspected postoperative hematoma involves reexploring the cervical incision with removal of the hematoma, local hemostasis, and surgical revision. In this circumstance, tracheal reintubation may be extremely difficult because of airway tissue edema from venous congestion.
Hypocalcemia
Due to the small size of the parathyroid glands and firm adherence to the thyroid, patients undergoing thyroidectomy are at high risk of parathyroid gland disruption or removal, leading to postoperative hypocalcemia. Signs include numbness in the hands, feet and lips, muscle cramps, and rarely, seizures occurring within 36 hours postoperatively. Postoperative monitoring of serial calcium and parathyroid hormone levels is crucial. Reimplantation of at least one of the parathyroid glands intraoperatively, combined with supplemental calcium and vitamin D in the postoperative period, can reduce the risk of hypocalcemia.
Postoperative Management
Measures should be undertaken to prevent straining on tracheal extubation where possible, because this can cause venous engorgement of airway tissues and hence airway edema. It can also rupture small blood vessels directly, leading to hematoma formation and airway compromise. Options to prevent this include tracheal extubation under deep anesthesia, topical use of lidocaine, and the use of an intravenous narcotic such as remifentanil.
Pheochromocytoma
Epidemiology
A Danish population-based study found that the incidence of pheochromocytomas has doubled in the last two decades (0.2 per 100,000 person years to 0.4 per 100,000 person years). Similarly, a systematic review in the Netherlands found that the incidence rate increased from 0.29 to 0.46 per 100,000 over the same time period, while age at diagnosis increased. These trends are likely related to improved diagnosis, including imaging studies and advances in biochemical testing, with up to 40% of all pheochromocytomas now diagnosed incidentally on imaging.
Approximately 40% of pheochromocytomas are hereditary and more likely to be bilateral and present at a younger age. The 5-year survival rate for localized and metastatic pheochromocytomas is 95% and 60%, respectively. Biochemical diagnosis and precise tumor localization are required, and the definitive treatment is complete surgical excision (see Table 28.3 ).
| Biochemical testing | Plasma free metanephrines 24-hour urinary fractionated metanephrines and catecholamines |
| Imaging | High-resolution computed tomography to localize tumor |
Preoperative Management
Pheochromocytomas cause symptoms in approximately 50% of patients. A comprehensive history and clinical exam should include the following :
- •
Signs and symptoms of a pheochromocytoma
- •
Episodic headaches
- •
Diaphoresis
- •
Abdominal pain
- •
Vomiting or diarrhea
- •
Weakness
- •
Weight loss
- •
- •
Cardiorespiratory signs of pheochromocytomas
- •
Tachycardia
- •
Dyspnea
- •
Palpations
- •
Hypertension
- •
Orthostatic hypotension
- •
Preoperative investigations and their clinical indications are included in Table 28.4 .
| Investigations | Indication |
| Full blood count | To assess for anemia |
| Blood pressure | Hypertension is often encountered in this cohort |
| Blood glucose | Hyperglycemia is common due to excess catecholamines |
| Chest x-ray | To rule out pulmonary edema and cardiomegaly |
| Electrocardiogram | Left ventricular hypertrophy can occur due to prolonged hypertension |
| Echocardiography | Where clinical suspicion of cardiomyopathy is high |
Preoperative Medical Management
Alpha-adrenoceptor Blockade
Catecholamine excess leads to alpha-1 mediated vasoconstriction and hypertension. These effects must be negated with a nonselective, irreversible alpha receptor antagonist such as phenoxybenzamine. This therapy may lead to hypotension, therefore in-hospital monitoring for side effects, such as orthostatic hypotension, tachycardia, dizziness, headaches, and drowsiness, is indicated. ,
Beta-adrenoceptor Blockade
Adrenergic beta-1 mediated tachycardia and ionotropy requires appropriate beta-receptor blockade with agents such as metoprolol or bisoprolol. This must only be initiated after establishing reliable alpha blockade. Alpha blockade causes vasodilation, which reduces arterial blood pressure, and so requires a degree of increased cardiac output in compensation. Introducing beta blockade before alpha blockade could inhibit compensatory cardiac output and lead to acute cardiac insufficiency, syncope, or pulmonary edema.
Vascular Expansion
To counteract the vasodilation caused by alpha-1 blockade, intravenous crystalloids are to be administered until serum hematocrit has decreased by 5%–10%. ,
In total, in-patient preoperative preparation may take up to 5–10 days.
Preoperative hemodynamic and hematological goals of pheochromocytoma treatment are outlined in Table 28.5 .
| Vital Sign | Aim |
| Systolic blood pressure | <130 mmHg |
| Diastolic blood pressure | <80 mmHg |
| Mean arterial pressure | <100 mmHg |
| Heart rate | <80 bpm |
| Hematocrit | 45 |
Intraoperative Management
Endotracheal intubation is advised in all patients undergoing surgical removal of a pheochromocytoma because of the extent and duration of surgery and its intraabdominal location. Preoperative alpha and beta blockade regimens should be continued. Laparoscopic adrenalectomy is sufficient in up to 95% of patients; however, large (>6 cm) or invasive tumors may require open resection. , Where open surgical technique is utilized, epidural anesthesia attenuates intraoperative stress-mediated catecholamine surges and postoperatively reduces pain.
Surgical Technique
Surgery comprises complete tumor resection and minimal tumor manipulation with appropriate control of vascular supply.
Up to 50% of patients will become hemodynamically unstable with tumor manipulation; therefore invasive blood pressure monitoring is essential. Central venous access allows for the administration of rapid fluid resuscitation and vasoactive medication as required.
Case reports describe the use of intraoperative transesophageal echocardiography to guide fluid management; however, level 1 evidence-based clinical trials have not shown any patient-centered benefit to intraoperative goal-directed fluid therapy. In patients diagnosed with catecholamine-induced cardiomyopathy a pulmonary artery catheter may allow for closer monitoring of cardiac index.
Common Intraoperative Issues
Hypertension
Noradrenaline (norepinephrine)-induced alpha-1 vasoconstriction can lead to hypertension intraoperatively. Short-acting potent vasodilators such as sodium nitroprusside and nitroglyceride (nitroglycerine) can be used to manage this effectively.
Tachyarrhythmias
Catecholamine secretions can result in arrhythmias, which may be effectively managed with a short acting beta-blocker if supraventricular in origin or lidocaine if ventricular. ,
Hypotension
Causes of intraoperative hypotension include a reduction in catecholamine levels, residual preoperative alpha blockade, blood loss, or myocardial dysfunction. Fluid replacement, blood products, or vasoactive medication may be required to stabilize the patient.
Postoperative Management
Postoperatively patients require a high dependency bed to monitor blood pressure, heart rate, and blood glucose levels. Some of the common complications that may occur are outlined in Table 28.6 .
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