What is a Pheochromocytoma?

Pheochromocytoma is a tumor that originates from chromaffin tissue of the neuroectoderm and mainly secretes catecholamines. Paraganglioma is classified into parasympathetic paraganglioma (including chemoreceptor tumors, carotid arteries) according to whether the tumor is from the sympathetic nerve or parasympathetic nerve. Body tumors, etc.) and sympathetic paraganglioma (including paraperitoneal, pelvic, and mediastinal paraganglioma). In some patients, severe heart, brain, and kidney damage caused by long-term hypertension or crisis caused by sudden severe hypertension can be life-threatening, but it is a curable follow-up if diagnosis and treatment can be obtained in time and early. Essential hypertension.

Basic Information

English name

pheochromocytoma

Visiting department

Endocrinology, Surgery

Common locations

Adrenal, extraperitoneal, paraabdominal aorta

Common causes

unknown

Common symptoms

High blood pressure, headache, palpitations, high metabolic status, high blood sugar, sweating, etc.

Contagious

no

Causes of pheochromocytoma

The prevalence of pheochromocytoma in patients with hypertension is 0.05% to 0.2%, and the peak incidence is 20 to 50 years old. 80% to 90% of pheochromocytomas are located in the adrenal glands, and most of them are unilateral; extraadrenal tumors are mainly located outside the peritoneum and beside the abdominal aorta. More benign and malignant accounted for 10%. As with most tumors, the etiology of sporadic pheochromocytoma remains unclear. Familial pheochromocytoma is genetically related.

Clinical manifestations of pheochromocytoma

The clinical manifestations of this disease vary greatly from individual to individual, with sudden occurrence of malignant hypertension, heart failure or cerebral hemorrhage. About 10% of pheochromocytomas are extraadrenal, 10% are malignant, 10% are familial, 10% occur in children, 10% tumors are bilateral, and 10% are multiple. Clinical symptoms and signs are related to excessive catecholamine secretion, manifested as hypertension, headache, palpitations, high metabolic status, hyperglycemia, and sweating. Its common symptoms and signs are as follows:

Cardiovascular system

(1) The main and characteristic manifestations of hypertension are symptoms, which can be intermittent or persistent. Typical paroxysmal episodes usually show a sudden rise in blood pressure, which can reach 200-300 / 130-180mmHg, with severe headache, sweating throughout the body, palpitations, tachycardia, arrhythmia, and a sense of urgency in the precardiac area and upper abdomen , Pain, anxiety, fear or dying, pale skin, nausea, vomiting, abdominal or chest pain, blurred vision, diplopia, severe cases can cause acute left heart failure or cardiovascular and cerebrovascular accidents.

(2) Hypotension and shock Hypotension or orthostatic hypotension may occur in this disease, and even shock or hypertension and hypotension appear alternately.

(3) A large amount of catecholamines in heart disease can cause catecholaminergic heart disease, and arrhythmias may occur such as precontractual contraction, paroxysmal tachycardia, and ventricular fibrillation. Some cases can cause myocardial damage such as myocardial degeneration, necrosis, and inflammatory changes, and heart failure can occur. Long-term, persistent hypertension can cause left ventricular hypertrophy, enlarged heart, and heart failure.

2. Metabolic Disorders

High concentrations of epinephrine act on the central nervous system, especially the sympathetic nervous system, which increases oxygen consumption, and increased basal metabolic rate can cause fever and weight loss. Accelerated liver glycogen breakdown and suppressed insulin secretion result in impaired glucose tolerance and increased liver gluconeogenesis. A few can occur hypokalemia, or hypercalcemia due to tumor secretion of parathyroid hormone-related peptides.

3. Other performance

Excessive catecholamines weaken intestinal peristalsis and tension, so it can cause constipation, intestinal dilatation, proliferative or occlusive arteritis of blood vessels in the gastrointestinal wall, cause intestinal necrosis, bleeding or perforation; weakened gallbladder contraction, Oddi sphincter tone Enhancement can cause bile retention and gallstones. Elderly patients with severe disease can cause renal failure. Patients with paraganglioma in the bladder can induce elevated blood pressure when urinating. The redistribution of blood cells under the action of a large amount of epinephrine increases the white blood cell count in peripheral blood and sometimes increases red blood cells. In addition, the disease may be part of type multiple endocrine adenoma syndrome (MEN), and may be associated with medullary thyroid carcinoma, parathyroid adenoma or hyperplasia, adrenal adenoma or hyperplasia.

Pheochromocytoma examination

1. Determination of blood, urine catecholamines and their metabolites

(1) Urine catecholamines, vanillyl mandelic acid, 3-methoxyadrenaline (MN) and methoxynorepinephrine (NMN) and their total (TMN) can all be increased.

(2) Determination of plasma catecholamines and DHPG: Plasma catecholamine values were significantly higher than normal when the disease persisted or paroxysmal attacks. It only reflects the instant blood catecholamine levels in blood samples, so its diagnostic value is not more meaningful than the determination of catecholamine levels in urine during the 24-hour period of the onset.

2. Adrenal CT scan

Is preferred. When performing CT examination, since the change of body position or the injection of intravenous contrast agent can induce hypertension, you should first use -adrenergic receptor blockers to control hypertension, and prepare phentolamine at any time during the scan for urgent needs .

3. Magnetic resonance imaging (MRI)

Can show the anatomical relationship and structural characteristics of tumors and surrounding tissues.

4.B ultrasound

The sensitivity is not as good as CT and MRI, and it is not easy to find smaller tumors. Can be used as a means of preliminary screening and positioning.

5. ¹³¹ -m-iodobenzylamine (MIBG) scintigraphy, somatostatin receptor and PET imaging

It has qualitative and positioning significance.

Pheochromocytoma diagnosis

Qualitative diagnosis

The diagnosis of pheochromocytoma is based on the determination of blood, urine catecholamines, and their metabolites.

2. Positioning diagnosis

The use of various imaging studies can assist in the positioning of pheochromocytomas to guide treatment.

(1) B-ultrasound can detect tumors with a diameter greater than 2 cm in the adrenal gland. Generally, the tumor has an envelope, the edge echo is enhanced, and the interior is homogeneous with low echo. If the tumor is large, there is hemorrhage, necrosis or cystic change when the growth is fast, and the ultrasound shows no echo area. However, B ultrasound cannot be displayed for tumors that are too small or in special parts outside the adrenal gland (such as the neck and chest).

(2) CT is currently the preferred method of positioning inspection. Pheochromocytoma mostly appears as a round-like mass on CT, with uneven density, high density of bleeding areas or calcifications, and the tumor is substantially strengthened during enhanced scanning, while the necrotic area is not or slightly enhanced. The sensitivity of CT in the diagnosis of intra-adrenal pheochromocytoma is 93% to 100%, but the specificity is not high, only 70%. For extra-adrenal pheochromocytoma, such as small and scattered tumors in the abdominal cavity, it is not easy to distinguish from the section of the intestinal cavity, so it may be missed.

(3) The intensity of T1-weighted solid tumors in MRI is similar to that of liver parenchyma, and the signal of T2-weighted solid tumors is higher. The necrotic and cystic regions showed a low signal at T1 and a high signal at T2. The sensitivity and specificity of MRI in the diagnosis of pheochromocytoma is similar to that of CT. The advantage of MRI is that it is three-dimensional imaging, which is beneficial to observe the anatomical relationship between tumors and surrounding organs and blood vessels.

(4) Isotopic ¹³¹ I-labeled MIBG scan MIBG (m-iodobenzylguanidine) is a physiological analog of norepinephrine, which can be taken up and stored in pheochromocytoma. After being labeled with isotopic ¹³¹ I, it can show the tumor.

Differential diagnosis of pheochromocytoma

Many diseases have symptoms similar to pheochromocytoma, so differential diagnosis is important.

Essential hypertension

Some patients with essential hypertension show high sympathetic nerve excitability, which is manifested as palpitations, sweating, anxiety, and increased cardiac output. But the patient's urine catecholamines were normal. Especially urinary catecholamine measurement during anxiety attacks can help to rule out pheochromocytoma.

Intracranial disease

When intracranial disease is associated with high intracranial pressure, severe headaches such as pheochromocytoma can occur. Patients usually have signs of other neurological damage to support the primary disease. But we should also be alert to pheochromocytoma complicated with cerebral hemorrhage and so on.

3. Neuropsychiatric disorders

Anxiety attacks, especially with hyperventilation, are easily confused with pheochromocytoma attacks. But blood pressure is usually normal during anxiety attacks. If blood pressure also rises, it is necessary to measure blood and urine catecholamines to help identification.

4. Epilepsy

Seizures are also similar to pheochromocytoma. Sometimes blood catecholamines can be elevated, but urine catecholamines are normal. There are threats before seizures, abnormal EEG, and effective antiepileptic treatment to help exclude pheochromocytoma.

5. Menopause syndrome

Women in the menopausal transition period will experience various symptoms caused by estrogen deficiency, such as hot flashes, sweating, irritability, and uncontrollable mood swings, which are similar to the onset of pheochromocytoma. By understanding the history of menstruation, sexual hormones and catecholamines Determination can help identification.

6. Other

Hyperthyroidism presents with high metabolic symptoms, accompanied by hypertension. But the diastolic blood pressure is normal, and the catecholamine does not increase. The onset of coronary heart disease and angina pectoris and acute myocardial infarction need to be distinguished from pheochromocytoma. Generally speaking, it can be distinguished from the changes in the electrocardiogram at the time of the attack and the improvement of the treatment of myocardial blood supply. The most critical thing is the determination of urinary catecholamines.

Pheochromocytoma complications

Cardiovascular complications

Catecholaminergic heart disease, arrhythmia, shock.

2. Brain complications

Stroke, transient ischemic attack (TIA), hypertensive encephalopathy, and mental disorders.

3. Other

Such as diabetes, ischemic enterocolitis, cholelithiasis and so on.

Pheochromocytoma treatment

Once the pheochromocytoma is diagnosed and localized, the tumor should be removed in time, otherwise the tumor may secrete a large amount of catecholamines and cause a potential danger of hypertension crisis. In recent years, with the development of biochemical tests and imaging technology, the qualitative and localized diagnosis technology of pheochromocytoma has been greatly improved, so the success rate of surgery has been improved. Preoperatively, alpha blockers should be used to reduce blood pressure, reduce the burden on the heart, and expand the originally reduced blood vessel volume to ensure the success of the operation.

Drug treatment

(1) Once the qualitative and localized diagnosis of pheochromocytoma is clear, it should be controlled with drugs immediately to prevent emergent hypertension. The main medications are long-acting alpha blockers, including phenoxybenzamine and prazosin.

(2) In the case of hypertensive emergency, phentolamine can be given intravenously. If the effect is not good, intravenous sodium nitroprusside can be given.

2. Preoperative preparation and medication

(1) Alpha-adrenergic receptor blocker phentolamine: It is used for the differential diagnosis of hypertension, and to control the blood pressure during the onset of hypertension or surgery. Phenylbenzamine: It is usually used for preoperative preparation and taken orally before surgery until the blood pressure is close to normal. During the medication, the changes in the horizontal and vertical blood pressure and heart rate should be closely monitored. prazosin, terazosin, doxazosin: are selective post-synaptic ₁ adrenergic receptor blockers. It is easy to cause severe orthostatic hypotension when applied, so it should be taken before bedtime and stay in bed as much as possible. Uladil (Bunidine): can block ₁ and ₂ receptors, and can activate the central serotonin 1A receptor, reducing the sympathetic feedback effect of the medullary cardiovascular regulatory center, so it does not reduce blood pressure at the same time. Increase your heart rate.

(2) -adrenergic receptor blockers Because of the use of -blockers, -receptor excitability increases and tachycardia, cardiac contractility, and myocardial oxygen consumption increase. -receptors Blockers improve symptoms.

(3) Calcium channel blocker (CCB) CCB can be used for preoperative combined therapy, especially for patients with coronary heart disease or catecholamine cardiomyopathy, or long-term antihypertensive treatment with and receptor blockers. Nifedipine is commonly used.

(4) Angiotensin-converting enzyme inhibitors (ACEI) such as captopril.

(5) Vasodilators Sodium nitroprusside is a powerful vasodilator, which is mainly used in patients with pheochromocytoma who have an onset of hypertension crisis or a continuous increase in blood pressure during surgery. Monitor blood pressure closely, adjust medication doses to prevent sudden drops in blood pressure, and monitor blood drug concentrations of cyanide.

(6) Catecholamine synthesis inhibitor -methyl para-tyrosine is a competitive inhibitor of tyrosine hydroxylase, blocking catecholamine synthesis. Adjust the dose according to blood pressure and blood and urine catecholamine levels, which can be gradually increased. Common side effects include drowsiness, depression, gastrointestinal symptoms, and extrapyramidal symptoms such as Parkinson's disease. The above symptoms can quickly disappear after reduction or withdrawal.

3. ¹³¹ -MIBG treatment

It is mainly used for malignant and unresectable pheochromocytoma.

4.Treatment of hypertensive crisis caused by pheochromocytoma

The head of the bed should be raised first and phentolamine should be injected intravenously immediately. Closely monitor blood pressure and stop injection when blood pressure drops to around 160 / 100mmHg. Followed by a slow drip.

5. Postoperative management

After the tumor was removed, the patient's blood pressure dropped quickly. If persistent hypertension persists after surgery, the tumor may not have been removed completely or it may be accompanied by essential hypertension or renal hypertension. Catecholamines return to normal levels 7 to 10 days after surgery. Therefore, catecholamine or its metabolites should be measured at 1 week after surgery to determine whether the tumor has been completely removed.

For patients who cannot be operated or patients with malignant tumors, long-term medication can be used. Most tumors grow slowly. Adrenergic receptor blockers and long-term treatment with alpha methyltyrosine can effectively inhibit catecholamine synthesis.

6. Treatment of Malignant Pheochromocytoma

Malignant pheochromocytoma can recur after peritoneum or metastasize to bone, lung, and liver. Relapses may occur years or decades after the first postoperative period and require long-term follow-up observation. Although radiotherapy is not very effective, it is good for controlling bone metastases. Can be combined with cyclophosphamide, vincristine, dacarbazine (metazamine) chemotherapy.

7. Management of familial pheochromocytoma

Familial pheochromocytoma is usually multiple or involves both adrenal glands and has a high recurrence rate. The alternatives include follow-up observation of small, non-functional tumors, adrenalectomy on the tumor side, and prophylactic bilateral adrenalectomy. Long-term corticosteroid replacement should be noted after bilateral adrenalectomy.

8. Management of pheochromocytoma during pregnancy

Pheochromocytoma is more difficult to manage during pregnancy. Transvaginal childbirth without any preparation often causes great harm to the mother and baby. The location of the tumor is suitable for MRI. Once the diagnosis is clear, alpha blockers should be taken to control symptoms. If it is in the early and middle stages of pregnancy, surgery should be performed immediately after preparation before surgery. Termination of pregnancy is not required after surgery, but surgery may increase the probability of miscarriage. If the diagnosis is already in late pregnancy, cesarean section can be performed with pheochromocytoma surgery at term. If the fetus is not yet mature, medications should be continued and closely monitored until surgery is appropriate.

Prognosis of pheochromocytoma

1. If early diagnosis can be made, the prognosis can be significantly improved.

2. The mortality of the operation is significantly reduced when the preoperative preparation is sufficient.

3. Because the recurrence rate of familial pheochromocytoma is high, it is recommended to review it once a year. If the measured value is abnormal, further imaging inspection is performed. The 5-year survival rate of malignant pheochromocytoma is less than 50%.

4. About 70% of patients with complete tumor resection and high blood pressure are cured. The rest still have persistent hypertension or hypertension recurrence, which may be primary hypertension or renal hypertension. Generally, antihypertensive drugs can control blood pressure well.