Adrenal myeloma: diagnosis and medical treatment

2021-07-24 11:54 PM

Pheochromocytoma, a tumor of the adrenal medulla that secretes catecholamines, including adrenaline, and/or noradrenaline, and, more rarely, dopamine.

Catecholamine-secreting tumors arising from the chromaffin cells of the adrenal medulla and sympathetic ganglia are called "pheochromocytomas" and "catecholamine-secreting paragangliomas" ("pheochromocytomas"). Because tumors have similar clinical presentations and are treated with similar approaches, many clinicians use the term "pheochromocytoma" to refer to both adrenal pheochromocytomas and catecholamine-secreting paragangliomas. However, the distinction between pheochromocytoma and paraganglioma is an important one because of the associated tumors, risk of malignancy, and genetic testing.

Catecholamine-secreting tumors are rare tumors that may occur in less than 0.2% of patients with hypertension. It is estimated that the annual incidence of pheochromocytoma is about 0.8 per 100,000 persons per year. However, this may be an underestimate as 50 percent of pheochromocytomas were diagnosed at autopsy in a series. Although pheochromocytomas can occur at any age, they are most common between the ages of 40 and 50 and are equally common in men and women.

Most catecholamine-secreting tumors are sporadic. However, about 40 percent of patients develop the disease as part of a familial disorder; In these patients, catecholamine-secreting tumors were more likely to be bilateral pheochromocytomas or paragangliomas.

Hereditary catecholamine-secreting tumors usually present at a younger age than sporadic tumors. Sporadic pheochromocytoma is usually diagnosed based on symptoms or a random finding on computed tomography, whereas syndromic pheochromocytoma is often diagnosed early in the course of the disease by biochemical surveillance or genetic testing.

Pheochromocytoma is a tumor of the adrenal medulla that secretes catecholamines including adrenaline and/or noradrenaline, and, more rarely, dopamine. This is the cause of severe and dangerously high blood pressure. Fractures can be fatal if not diagnosed or treated incorrectly.

The disease occurs in both sexes, at all ages, and is usually diagnosed between the ages of 40 and 50.

About 80% of pheochromocytomas are unilateral, often following the 10% rule: 10% bilateral and 10% extra-adrenal, about 10% of pheochromocytoma are malignant, the site of metastasis is usually in retroperitoneum, lymph nodes, bones, liver, lungs, and mediastinum.

About 90% of cases are isolated in the population and 10% are familial (MEN lla and lib, VHL, Neurofibromatosis), bilateral adrenal medullomas are more common in these familial syndromes.

Clinical symptoms

About 10% of patients have no symptoms.

Acute or recurrent hypertension, possibly with malignant hypertensive crisis, often resistant to conventional therapy.

Accompanying symptoms are often headache, tachycardia, sweating, and paleness. Other symptoms may occur such as orthostatic hypotension, chest pain, shortness of breath, abdominal pain, nausea, hand tremors, nervousness, anxiety, panic...

Subclinical symptoms

Blood tests: little value

Quantification of blood catecholamines: total catecholamines > 11.8nM (2000μg/ml). This test has low sensitivity in patients with no symptoms or intermittent catecholamine secretion.

Plasma meta machine: is secreted continuously by adrenal myeloma, is a test that has both high sensitivity and specificity, meta machine level > 236 ng/l, normetanephrine > 400 ng/l to confirm the diagnosis.

Urine tests

Free Catecholamine in urine: diagnostic threshold: > 1480 nmol/24 hours (> 250 μg/24 hours).

Urine meta machine: diagnostic threshold: 2-3 times normal.

Prepare the patient for blood and urine tests.

Note: for the test to be valid, it is necessary to follow the correct specimen collection process as well as the necessary requirements. Should be done when the patient is symptomatic. This test can be done more than once.

Do not take the following medications for two weeks before the test:

+ Tricyclic antidepressants, MAO inhibitors.

+ Clonidine, levodopa, methyldopa, diuretics, theophylline.

+ Calcium channel blockers: nifedipine, amlodipine, ditiazem, verapamil.

+ Vasodilators: hydralazine, isosorbide.

+ Stimulants: coffee, tobacco, alcohol.

Do not conduct the test on patients with stroke, hypoglycemia, increased intracranial pressure.

During the monitoring period for testing, if the blood pressure is elevated and requires treatment, an alpha-adrenergic receptor blocker can be selected: phenoxyben antagonists are the best, starting with a dose of 10mg/ day or alpha 1 (selective inhibitor - Doxazosin - Carduran 2mg).

Image analyzation

Help locate the tumor when the diagnosis is confirmed and help find metastases if present in the case of malignancy.

The tumor can be intra-adrenal or extra-adrenal (Paraganglioma): CT scan and MRI are the first choices.

Abdominal ultrasound: detect large tumor.

MRI (Magnetic Resonance): look for adrenal tumors, extra-adrenal tumors in the abdomen, find tumors around the blood vessels or near the heart. The application of choice for children, pregnant patients or when allergic to contrast. 90% have tumor image hyperintense on T-2.

Computed tomography: look for tumors > 0.5 - 1 cm in size in the adrenal gland and metastases > 1 - 2 cm in the abdomen and pelvis. Twisted CT is used to look for smaller tumors. Small tumors are usually homogeneous, strongly enhanced after contrast injection, large tumors > 4cm parenchyma are heterogeneous, may have cysts, hemorrhage or necrosis in the mass.

Note: Contrast-enhanced CT can cause hypertensive crisis.

MIBG scintigraphy (Metaiodobenzyl guanidine bound 123l or 131l): is a useful next test to help localize tumors, especially those with abnormal location, recurrent or metastatic tumors in the retroperitoneum, lymph nodes, and bones. , liver, lung mediastinum, ovary, bladder.

PET scan (Positron emission tomography scanner): gives accurate information about the number and location of tumors.

Treatment

Surgery is the first choice, but preoperative medical treatment is very important for a successful operation.

Internally medical treatment

Alpha-adrenergic receptor blockers:

Reduces vasoconstrictor effect of catecholamines, increases blood flow.

Non-selective inhibitors: phenoxybenzamine is best. Start with 10mg/day, gradually increase dose by 10-20mg/day until blood pressure is controlled and no exacerbations appear. Maintain dose of 40-80mg/day.

Alpha 1 antagonist (selective inhibitor - Doxazosin - Cardura 2mg); not as good, but it also helps to prevent exacerbations. Initially 1mg, as a single dose over 1-2 weeks, dose may be increased gradually by 2mg, 4mg, 8mg and up to 16mg depending on patient response, titrated every 1-2 weeks, usual dose 2 - 4mg X 01 time/day.

Beta-blockers:

Use only after alpha-blockers have been established. Helps reduce tachycardia that may occur with alpha-blockers and prevent arrhythmias. The drug of choice is propranolol at a starting dose of 20mg/day, gradually increasing the dose every 3-7 days to achieve effectiveness.

Calcium channel blockers:

Well tolerated, there is a greater effect on cardiovascular manifestations due to increased catecholamines than on tumor-induced catecholamine secretion. The drug of choice is nicardipine (Loxen) starting at 10 mg, gradually increasing the dose after at least 3 days to 20 mg/day in 2 divided doses or 30 mg/day in 3 divided doses until blood pressure is controlled. In cases where blood pressure is still not controlled with tablets or malignant hypertension, nicardipine (Loxen 20mg) should be administered intravenously at an initial dose of 5 mg/hour, increasing by 2.5 mg/hour every 15 minutes. According to blood pressure, the highest dose should not exceed 15mg/hour when the patient's blood pressure responds to treatment, reduce dose by 3mg/hour, monitor and consider dose necessary to achieve stable blood pressure.

Surgical treatment

It is the treatment of choice for most cases.

Principle: remove the tumor and the entire ipsilateral adrenal gland to prevent recurrence and limit metastasis if malignant.

During surgery, there is a very important point to note: when performing vascular clamping and tumor removal, hypotension may occur, if hypotension is mild, EĆ­edrine (ephedrine) dose can be used. 10-20mg intravenously, adjusted according to the patient's blood pressure. If the condition is severe, adrenaline (epinephrine) can be administered intravenously with an electric pump at a dose of 1-4 mcg/min, adjusting the dose according to the patient's response.

Difficulty: the cytological criteria for adrenal medulloblastoma are difficult to define, so it is necessary to follow up over time in all patients with adrenal medulloblastoma.

Monitoring

Check urinary catecholamine 2 weeks after surgery to determine the success of the surgery.

Check every year for catecholamines or whenever symptoms recur.