Pheochromocytoma: Adrenal Gland Tumors

Definition and Location

• Pheochromocytoma is a dusky-colored tumor derived from chromaffin cells.
• Most commonly located in the adrenal medulla, but can also occur in extraadrenal sites.

Symptoms and Effects

• 90% of pheochromocytomas cause massive norepinephrine production and release into systemic circulation.
• Epinephrine can also be the predominant catecholamine produced.
• Common triad of symptoms: headache, diaphoresis, and tachycardia.
• Excessive and prolonged alpha-1 receptor stimulation can lead to:
  • Intravascular volume depletion
  • Renal insufficiency
  • Hemorrhagic cerebral infarct
  • Myocardial irritability
  • Ischemia and infarction
  • Congestive heart failure and cardiomyopathy (if hypertension remains untreated)

Management and Anesthetic Concerns

• Preoperative management includes:
  • Adrenergic receptor blockade (alpha-receptor blockade followed by beta-receptor blockade)
  • Intravascular volume replacement
  • Assessment of end-organ damage
• Intraoperative surges in catecholamine release can occur during:
  • Laryngoscopy
  • Intubation
  • Manipulation of the tumor
  • Ligation of the adrenal vein
• Postoperative anesthetic concerns include:
  • Treating pain
  • Stabilizing blood pressure
  • Prompt diagnosis and treatment of:
    • Pneumothorax
    • Hypoglycemia
    • Hypoadrenocorticism

Pathophysiology

• Pheochromocytomas are catecholamine-secreting tumors that originate in the adrenal gland (90% of cases) or extraadrenal sites (paravertebral sympathetic chain).
• Tumors are composed of chromaffin cells that produce, store, and secrete catecholamines.
• Most extraadrenal pheochromocytomas occur in the abdominal cavity.
• Unilateral adrenal gland is most frequently affected, and most tumors are benign.
• Familial pheochromocytomas occur in bilateral adrenal glands (50% of cases) and are frequently benign.

Epidemiology

• Pheochromocytomas affect males and females equally.
• Most frequently manifest between 30 and 50 years of age.
• Associated with multiple endocrine neoplasia type II A and B, neurofibromatosis, tuberous sclerosis, Sturge-Weber syndrome, and von Hippel-Lindau disease.

Clinical Manifestations

• Sympathetic nervous system (SNS) stimulation causes a massive release of catecholamines, predominantly norepinephrine.
• Common clinical manifestations include:
  • Headache
  • Diaphoresis
  • Tachycardia
  • Arrhythmias with palpitations
  • Anxiety
  • Pallor
  • Hypertension
  • Hyperglycemia
  • Paresthesias to the extremities
  • Orthostatic hypotension
  • Polycythemia
  • Cerebral hemorrhage
  • Myocardial infarction
  • Cardiomyopathy
  • Congestive heart failure
  • Renal insufficiency

Surgical Procedure for Adrenalectomy

• Adrenalectomy is traditionally performed through an open transperitoneal approach, but laparoscopic adrenalectomy has become the most common surgical technique for removal of a pheochromocytoma.
• The patient is placed in the lateral decubitus position for maximal exposure to the surgical site in laparoscopic adrenalectomy.
• The adrenal vein is located and ligated, and the adrenal gland is then excised and removed.
• Laparoscopic approach has advantages, including small incision, decreased postoperative pain, and potential for developing a pneumothorax during the surgical dissection.

Signs and Symptoms of Pheochromocytoma

• A triad of signs and symptoms associated with a pheochromocytoma include headache, diaphoresis, and tachycardia.
• Other physiologic signs and symptoms include hypertension, arrhythmias, ST-segment changes, nervousness, and anxiety.
• Hypertension associated with tachycardia is most common, but the physiologic response is directly proportional to the concentration of catecholamines that are released.

Diagnosis of Pheochromocytoma

• The initial diagnosis of pheochromocytoma is difficult to make due to nonspecific symptoms, varying among individuals, and the rarity of the disease.
• Diagnostic tests include:
  • Plasma free metanephrines
  • Urine catecholamine and metanephrine levels
  • Clonidine suppression test
  • 24-hour urine test: three urine samples are collected within a 24-hour period, and the concentration of metanephrines is analyzed.
  • Imaging studies: CT scan, positron emission tomography (PET) scan, or magnetic resonance imaging (MRI) to identify the presence of a tumor and its size and location.
  • MIBG scintigraphy: a chemical with a high affinity for secretory granules present in chromaffin cells.

Preoperative Pharmacologic Preparation

• Preoperative pharmacologic management includes alpha-receptor blockade, beta-receptor blockade, and volume expansion.
• Alpha-receptor blockade is instituted before beta-receptor blockade, usually accomplished by the administration of phenoxybenzamine.
• Beta-receptor blockade is initiated once adequate alpha-receptor blockade is established, managed with beta-receptor blockade, most often propranolol.
• Volume expansion is achieved by a decrease of 5% from the baseline hematocrit level or orthostatic hypotension associated with a decline in the systolic blood pressure.

Preoperative Cardiovascular Criteria

• The goal of preoperative therapy is to control excessive catecholamine release that causes extreme physiologic aberrations.
• The following criteria must be met before surgical intervention and anesthesia administration:
  • Blood pressure must remain less than 160/90 mm Hg within 48 hours before surgery.
  • Orthostatic hypotension must occur, but the blood pressure must be greater than 80/45 mm Hg.
  • The ECG must not have ST/T-wave abnormalities for at least 1 week and have no more than one PVC within 5 minutes.
  • Adequate hydration is achieved by a decrease in the hematocrit by approximately 5% from the baseline value.

Factors that Increase Morbidity and Mortality

• Factors that increase the potential for morbidity and mortality include:
  • The activity of the pheochromocytoma
  • Inadequate preoperative alpha-receptor and then beta-receptor blockade
  • Advanced end-organ damage (cardiovascular, renal failure)
  • Whether the pheochromocytoma is malignant or benign
  • Prolonged surgical duration

Intraoperative Period

• Medications that increase blood pressure or heart rate or cause histamine release should be avoided during intraoperative management.
• Alternative drugs that stimulate the release or inhibit the breakdown of catecholamines should be used.
• General anesthesia and endotracheal intubation are necessary for patients with pheochromocytoma.
• An epidural placed preoperatively can be used to provide anesthesia during surgery and analgesia during the postoperative period.

Anesthetic Considerations

• Two large-bore peripheral intravenous lines are indicated due to the risk of rapidly developing hemorrhage.
• Arterial line placement is required for blood pressure monitoring.
• A central line is indicated to monitor central venous pressure and assess the patient's volume status.

Anesthetic Management

• Preoperative sedation is necessary to decrease anxiety and sympathetic nervous system (SNS) activity.
• An adequate anesthetic depth should be achieved before direct laryngoscopy to avoid an exaggerated SNS response.
• Nitrous oxide should be avoided due to concerns regarding pneumothorax development.
• Succinylcholine administration is controversial due to its potential to increase catecholamine release.

Blood Pressure Management

• Hypertension is most common during intubation, incision, tumor manipulation, and ligation of the venous drainage of the affected adrenal gland.
• Hypertension can be managed by:
  • Increasing the concentration of inhalation anesthetic agent
  • Administering narcotics/dexmedetomidine
  • Using sodium nitroprusside as an intravenous drip
  • Administering clevidipine
  • Administering magnesium sulfate
• Hypotension is most common after tumor removal and can be treated by:
  • Decreasing the anesthetic depth
  • Administering crystalloids, colloids, or packed red blood cells
  • Administering a direct-acting vasopressor such as phenylephrine

Blood Glucose Management

• Blood glucose should be assessed preoperatively and throughout the surgical procedure.
• Hyperglycemia can occur before tumor removal due to SNS predominance and glycogenolysis.
• Hypoglycemia can develop rapidly during the postoperative period.

Intraoperative Course

• Alpha- and beta-adrenergic blockade may not prevent hypertension and heart rate variability during induction, endotracheal intubation, and epidural catheter placement.
• Surgical manipulation of the pheochromocytoma can cause an abrupt increase in blood pressure.
• Ligation of the venous drainage from the adrenal gland can cause a rapid decrease in blood pressure.

Postoperative Complications after Adrenalectomy for Pheochromocytoma

• Hypertension can occur due to residual pheochromocytoma, pain, hypoglycemia, hypervolemia, and hypoxia.
• Hypotension may result from residual alpha-adrenergic receptor blockade, hypovolemia, myocardial ischemia or infarction, bleeding, or sepsis.
• Pneumothorax is a potential complication.
• Hemorrhage is a possible postoperative complication.
• Sepsis is a potential complication after adrenalectomy for pheochromocytoma.
• Hypoglycemia is a possible postoperative complication.
• Hypoadrenocorticism is a potential complication after adrenalectomy for pheochromocytoma.
• Acute renal failure is a possible postoperative complication.

Anesthetic Medications to Avoid in Pheochromocytoma Patients

• Desflurane should be avoided due to its sympathomimetic effects
• Pancuronium should be avoided due to its sympathomimetic effects
• Atracurium should be avoided due to histamine release
• Succinylcholine should be avoided as it causes fasciculation, leading to catecholamine release
• Morphine should be avoided due to histamine release
• Droperidol should be avoided due to its antidopaminergic effects, which can lead to neuroleptic malignant syndrome
• Metoclopramide should be avoided due to its antidopaminergic effects, which can lead to neuroleptic malignant syndrome
• Phenothiazines should be avoided due to their antidopaminergic effects, which can lead to neuroleptic malignant syndrome
• Ephedrine should be avoided due to its sympathomimetic effects
• Ketamine should be avoided due to its sympathomimetic effects
• Atropine should be avoided as it produces tachycardia
• Naloxone hydrochloride should be avoided due to its sympathetic nervous system predominance

Signs and Symptoms of Pheochromocytoma

• Headache is a common symptom
• Diaphoresis is a common symptom
• Tachycardia is a common symptom
• Chest pain is a common symptom
• Bradycardia is a possible symptom
• Anxiety is a common symptom
• Blurred vision is a possible symptom
• Seizures are a possible symptom