Pheochromocytoma Final Word

8/3/2019 Pheochromocytoma Final Word

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CLINICAL SEMINAR ON PHEOCHROMOCYTOMA

Introduction

Pheochromocytoma is a tumor that is usually benign and originates from the chromaffin cells of the

adrenal medulla. In 85% of patients , the tumor arises in the medulla; in the remaining patients, it occurs

in the extra-adrenal chromaffin tissue located in or near the aorta, ovaries, spleen, or other organs. Those

arising from extra-adrenal tissue are commonly known as paragangliomas.Paragangliomas are divided in

to two groups; those that arise from parasympathetic associated tissues (most commonly along the cranianerves and vagus (eg. glomus tumors,chemodectoma,and carotid body tumor ) and those that arise from

sympathetic associated chromaffin tissue(often designated as extra adrenal pheochromocytomas)

The name pheochromocytoma proposed by Pick in 1912 comes from the Greek wordsphaios (dusky) and

chroma(color);it refers to the staining that occurs with tumors when they are treated with chromium

salts.

Anatomy and Physiology

There are two adrenal glands in the human, each attached to the upper portion of a kidney. Eachadrenal gland is, in reality, two endocrine glands with separate, independent functions. The adrenamedulla at the center of the gland secretes catecholamines, and the outer portion of the gland, the

adrenal cortex, secretes steroid hormones .

The secretion of hormones from the adrenal cortex is regulated by the hypothalamicpituitary-adrenal axis. The hypothalamus secretes corticotropinreleasing hormone (CRH), which in turn

stimulates the pituitary gland to secrete ACTH. ACTH then stimulates the adrenal cortex to secrete

glucocorticoid hormone (cortisol). Increased levels of the adrenal hormone then inhibit the

production or secretion of CRH and ACTH. This system is an example of a negative feedback

mechanism

Functions of Adrenal Medulla

The adrenal medulla functions as part of the autonomic nervous system. Stimulation of preganglionicsympathetic nerve fibers, which travel directly to the cells of the adrenal medulla, causes release of the

catecholamine hormones epinephrine and norepinephrine.

About 90% of the secretion of the human adrenal medulla is epinephrine (also called adrenaline).

Catecholamines regulate metabolic pathways to promote catabolism of stored fuels to meet caloricneeds from endogenous sources. The major effects of epinephrine release are to prepare to meet a

challenge (fight-or-flight response).

Secretion of epinephrine causes decreased blood flow to tissues that are not needed in emergencysituations, such as the gastrointestinal tract, and causes increased blood flow to tissues that are

important for effective fight or flight, such as cardiac and skeletal muscle.

Catecholamines also induce the release of free fatty acids, increase the basal metabolic rate,and elevate the blood glucose level.

In the healthy physiologic state, hormone concentration in the bloodstream is maintained at arelatively constant level. When the hormone concentration rises, further production of that

hormone is inhibited. When the hormone concentration falls, the rate of production of that

hormone increases. This mechanism for regulating hormone concentration in the bloodstream is

called negative feedback, which is important in the regulation of many biologic processes.

Epidemiology


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Pheochromocytoma is estimated to occur in 28 out of 1 million persons per year, and about 0.1% of

hypertensive patients harbor a pheochromocytoma. Autopsy series reveal prevalence figures of 0.2%.

The mean age at diagnosis is about 40 years, although the tumors can occur from early childhood until latin life.

The "rule of tens" for pheochromocytoma states that about 10% are bilateral, 10% are extra adrenal, and

10% are malignant. However, these percentages are higher in the inherited syndromes.

Etiology And Pathogenesis

Pheochromocytomas and paragangliomas are well-vascularized tumors that arise from cells derived from

the sympathetic (e.g., adrenal medulla) or parasympathetic (e.g., carotid body, glomus vagale) para gangli

The namepheochromocytoma reflects the black-colored staining caused by chromaffin oxidation of

catecholamines. Although a variety of nomenclatures have been used to describe these tumors, most

clinicians use the termpheochromocytoma to describe symptomatic catecholamine-producing tumors,including those located in extra adrenal retroperitoneal, pelvic, and thoracic sites.

The termparaganglioma is used to describe catecholamine-producing tumors in the head and neck, as

well as tumors that arise from the parasympathetic nervous system, which may secrete little or no

catecholamines.

Signs And Symptoms

The signs and symptoms of a pheochromocytoma are those ofsympathetic nervous system hyperactivity,

including:

SYMPTOMS

Headache Palpitations Sweating Anxiety/nervousness Nausea/emesis Pain in chest or abdomen Weakness/fatigue Dizziness Heat intolerance Paresthesias Constipation Dyspnea Visual disturbances Seizures, grand malSIGNS

Hypertension Tachycardia/reflex bradycardia Postural hypotension(another clue to the presence of pheochromocytoma is orthostatic

hypotension (a fall in systolic blood pressure greater than 20 mmHg or a fall in diastolic blood

pressure greater than 10 mmHg upon standing)
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Hypertension, paroxysmal Weight loss Pallor Hyper metabolism fasting hyperglycemia(due primarily to catecholamine stimulation of lipolysis (breakdown of

stored fat) leading to high levels of free and the subsequent inhibition of glucose uptake by muscle

cells. Further, stimulation of beta-adrenergic receptors leads to glycogenolysis and

gluconeogenesis and thus elevation of blood glucose levels). tremor increased RR decreased GI motility psychosis(rare) flushing, paroxysmal(rare)

Not all patients experience all of the signs and symptoms listed

The dominant sign is hypertension. Classically, patients have episodic hypertension, but sustained

hypertension is also frequent. Catecholamine crises can lead to heart failure, pulmonary edema,arrhythmias, and intracranial hemorrhage.

During episodes of hormone release, which can occur at very divergent intervals, patients are anxious and

pale, and they experience tachycardia and palpitations. These paroxysms generally last less than an hour

and may be precipitated by surgery, positional changes, exercise, pregnancy, urination (particularly

bladder Pheochromocytomas), and various medications (e.g., tricyclic antidepressants, opiates,

metoclopramide)s

Among the presenting symptoms, episodes of palpitations, headaches, and profuse sweating are typical

and constitute a classic triad.

COMPLICATIONS

Syncope,Cardiac dysrhythmias (sinus tachycardia, superior ventricular arrhythmias, prematurecontraction),Angina even in absence of CAD,Myocardial infarction,Prominent U wave,

Cardiomyopathy ,Heart failure / ARF ,Aneurysm / stroke,Fatal paroxysms

Diagnosis

The diagnosis is based on documentation of catecholamine excess by

o biochemical testing and localization of the tumor byo imaging.

Testing

Blood Tests: analysis of free meta nephrine in blood plasma. High levels are indicative ofpheochromocytoma.

Urine Tests: Although this test is slightly less effective than plasma testing it is still considered highlyeffective in diagnosis. Usually the metabolites ofnorepinephrine and epinephrine, vanillylmandelic

acid (VMA) and homovanillic acid (HVA) are found in relatively small amounts in normal humans. The

increased intermittent excretion of these metabolites is indicative of the disease, but does not

completely rule out other diseases which may cause the same excretion values.
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Other Tests: One diagnostic test used in the past for a pheochromocytoma is to administerclonidine, a

centrally-acting alpha-2 agonist used to treat high blood pressure. Clonidine mimics

catecholamines in the brain, causing it to reduce the activity of the sympathetic nerves controlling

the adrenal medulla. A healthy adrenal medulla will respond to the clonidine suppression testby

reducing catecholamine production; the lack of a response is evidence of pheochromocytoma. The suppression test is based on the principle that catecholamine levels are normally increased

through the activity of the sympathetic nervous system. In pheochromocytoma, increasedcatecholamine levels result from the diffusion of excess catecholamine into the circulation,

bypassing normal storage and release mechanisms. Therefore, in patients with

pheochromocytoma, clonidine does not suppress the release of catecholamines.

The results of the test are considered normal if 2 to 3 hours after a single oral dose of clonidine, thetotal plasma catecholamine value decreases at least 40% from baseline. Patients with

pheochromocytoma exhibit no change in catecholaminelevels. False-positive results, however,may occur in patients with primary hypertension.

Another test is for the clinician to press gently on the adrenal gland. A pheochromocytoma willoften release a burst of catecholamines, with the associated signs and symptoms quickly following

This method is NOT recommended because of possible complications arising from a potentiallymassive release of catecholamines.

Diagnostic Imaging

CECT. MRI with gadolinium contrast Radioactive tracers including 131I- or 123I-metaiodobenzylguanidine (MIBG), 111In-somatostatin

analogues, or 18F-dopa (or dopamine) positron-emission tomography (PET). Because these agents

exhibit selective uptake in paragangliomas, nuclear imaging is particularly useful in the hereditary

syndromes.

Measurements of urine and plasma levels of catecholamines are the most direct and conclusivetests for over activity of the adrenal medulla. Measurements of urinary catecholamine

metabolites (metanephrines [MN] and vanillylmandelic acid [VMA]) or free catecholamines are

the standard diagnostic tests used in the diagnosis of pheochromocytoma. Levels can be as high

as three times normal limits .

A 24-hour specimen of urine is collected for determining free catecholamines, MN, and VMA;the use of combined tests increases the diagnostic accuracy of testing.

A number of medications and foods (eg, coffee, tea, bananas, chocolate, vanilla, aspirin) mayalter the results of these tests; therefore, careful instructions to avoid restricted items mustbe given to the patient.

Urine collected over a 2- or 3-hour period after an attack of hypertension can be assayed forcatecholamine content.

Total plasma catecholamine (epinephrine and norepinephrine) concentration is measured withthe patient supine and at rest for 30 minutes. To prevent elevation of catecholamine levels by

the stress of venipuncture, a butterfly needle, scalp vein needle, or venous catheter may be

inserted 30 minutes before the blood specimen is obtained.
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Factors that may elevate catecholamine levels must be controlled to obtain valid results; thesefactors include consumption of coffee or tea, use of tobacco, emotional and physical stress, and

use of many prescription and over-the-counter medications (eg, amphetamines, nose drops or

sprays, decongestant agents, and bronchodilators).

Normal plasma values of epinephrine are 100 pg/mL (590 pmol/L); normal values of norepinephrine are generally less than 100 to 550 pg/mL (590 to 3,240

pmol/L).

Values of epinephrine greater than 400 pg/mL (2,180 pmol/L) or norepinephrine valuesgreater than 2,000 pg/mL (11,800 pmol/L) are considered diagnostic of pheochromocytoma

MALIGNANT PHEOCHROMOCYTOMA

About 510% of pheochromocytomas and paragangliomas are malignant. tumors with distant metastases, most commonly found in lungs, bone, or liver, suggesting a

vascular pathway of spread.

Because hereditary syndromes are associated with multifocal tumor sites, these features should beanticipated in patients with germ-line mutations of RET, VHL, SDHD, or SDHB.

Treatment options include tumor mass reduction; alpha blockers for symptoms; chemotherapy; and nuclear medicine

radiotherapy.

The prognosis of metastatic pheochromocytoma or paraganglioma is variable, with a 5-yearsurvival of 3060%.

Pheochromocytoma in Pregnancy Pheochromocytomas are occasionally diagnosed in pregnancy. Endoscopic removal, preferably in

the forth to sixth month of gestation, is possible and can be followed by uneventful childbirth.

Regular screening in families with inherited pheochromocytomas provides an opportunity to

identify and remove asymptomatic tumors in women of reproductive age.

Pheochromocytoma-Associated Syndromes

1) Neurofibromatosis type 1 (NF 1) (Von Recklinghausen's Disease): was the first described

pheochromocytoma-associated syndrome . Neurofibromas are benign peripheral nerve tumors composeof proliferating Schwann cells and fibroblasts.

They present as multiple, palpable, rubbery, cutaneous tumors.

They are generally asymptomatic; however, if they grow in an enclosed space, e.g., the intervertebral

foramen, they may produce a compressive radiculopathy or neuropathy. Aqueductal stenosis withhydrocephalus, scoliosis, short stature, hypertension, epilepsy, and mental retardation may also occur

NF1 is characterized by

cutaneous neurofibromas, pigmented lesions of the skin called caf au lait spots, freckling in non-sun-exposed areas such as the axilla, hamartomas of the iris termed Lisch nodules, and


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Pseudoarthrosis of the tibia.Patients with NF1 are at increased risk of developing nervous system neoplasms, including plexiform

neurofibromas, optic pathway gliomas, ependymomas, meningiomas, astrocytomas, and

pheochromocytomas.Neurofibromas may undergo secondary malignant degeneration and become

sarcomatous.

Mutation of the NF1 gene on chromosome 17 causes von Recklinghausen's disease. The NF1 gene is atumor-suppressor gene; it encodes a protein, neurofibromin, which modulates signal transductionthrough the ras GTPase pathway.

Pheochromocytomas occur in only about 1% of these patients and are located predominantly in the

adrenals. Malignant pheochromocytoma is not infrequent.

2)Von HippelLindau Syndrome: consists of retinal, cerebellar, and spinal hemangioblastomas, whichare slowly growing cystic tumors. Hypernephroma, renal cell carcinoma, pheochromocytoma, and benign

cysts of the kidneys, pancreas, epididymis, or liver may also occur.

Erythropoietin produced by hemangioblastomas may result in polycythemia. Mutation of the von HippelLindau (VHL) gene on chromosome 3p, a tumor-suppressor gene, causes this disorder. VHL encodes aprotein with multiple functions, including modulation of signal transduction in response to cellular

hypoxia

3) Multiple endocrine neoplasia type 2A and type 2B (MEN 2A, MEN 2B)

Autosomal dominant disorder It consists of pheochromocytoma, medullary carcinoma of thyroid, and hyperparathyroidism. Both types of MEN 2 are caused by mutations in RET (rearranged in transfection), which encodes

tyrosine kinase

MEN 2A is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, anhyperparathyroidism

MEN 2B also includes MTC and pheochromocytoma, as well as multiple mucosal neuromas, thoughit typically lacks hyperparathyroidism

Patients with MEN2-related pheochromocytoma often lack hypertension or other symptombecause they secrete epinephrine.

Prophylactic thyroidectomy is being performed in many carriers of RET mutationspheochromocytomas should be excluded before surgery in these patients.

Medical Management

During an episode or attack of hypertension, tachycardia, anxiety, and the other symptoms ofpheochromocytoma, the patient is placed on bed restwith the head of the bed elevated to promote anorthostatic decrease in blood pressure

PHARMACOLOGIC THERAPY The patient may be moved to the intensive care unit for close monitoring of ECG changes and

careful administration of alpha adrenergic blocking agents (eg, phentolamine ) or smooth muscle

relaxants (eg, sodium nitroprusside) to lower the blood pressure quickly.

Phenoxy benzamine, a long-acting alpha-blocker, may be used when the blood pressure is stable tprepare the patient for surgery. Beta-adrenergic blocking agents, such as propranolol, may be used

in patients with cardiac dysrhythmias or those not responsive to alpha-blockers.


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Alpha adrenergic and beta-adrenergic blocking agents must be used with caution because patientswith pheochromocytoma may have increased sensitivity to them. Still other medications that may

be used preoperatively are catecholamine synthesis inhibitors, such as alpha-methyl-p-tyrosine .

These are occasionally used when adrenergic blocking agents do not reduce the effects of

catecholamines.

SURGICAL MANAGEMENT

The definitive treatment of pheochromocytoma is surgical removal of the tumor, usually withadrenalectomy.

Transabdominal approach: for familial disease Flank approach: for solitary tumor Laproscopic: if tumor


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Hypertensive nephropathy Hypertensive retinopathy Myocarditis Increased platelet aggregation Stroke Heart failure

Postoperative Management Volume replacement is treatment of choice if hypo tension occur either during sx or in the

postoperative period. The volume offluid required is often large (.5 to 1.5 times the patients total blood volume) during

the first 24 to 48 hrs. after removal of the tumor Any attempt to collect specimens for a residual tumor should be delayed atleast 5 to 7 days post

surgery to be certain that the large increase in both plasma and urinary catecholamines produced

by surgery have dissipated.COMPLICATIONS

Intraoperative: Extreme rise in BP,Cardiac dysrhythmias

Postoperative:Extreme fall in BP

PrognosisThe long term survival of patients after successful removal of a benign pheochromocytoma is

essentially the same as that of age related normal.

Approximately 25% of patients remain hypertensive ,but this is usually easily controlled with

medication.

NURSING MANAGEMENT

Risk for fluid volume deficit r/t hypotension hemorrhage & shock

Monitor vital signs shock, hemorrhage Give IV fluids as prescribed Administer IV vasopressors as prescribed Carefully measure hourly urine output Assess the client closely for manifestations of adrenal insufficiency

Fear & anxiety related to impending surgery

Assess the level of anxiety of client Establish trusting relationships Encourage ventilation of feelings Explain about surgery in simple words

Provide reinforcement regarding prognosis & assist in attaining goals Explain purpose of corticosteroidsRisk for altered nutrition r/t high metabolic rate

promoting rest & relief from stress providing diet high in vitamins minerals & calories. Encourage fluid intake Prohibiting beverages containing caffeine Administering prescribed sedatives

Knowledge deficit r/t disease management


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Assess the knowledge level of the patient Explain about disease complication management & prognosis Provide explanation in simple words Clarify doubts Teach post operative care

Acute pain r/t surgery , headache

Assess nature intensity & location of pain Provide comfortable position Avoid tension on suture line Splint the incision while coughing& turning. Teach relaxation technique Monitor vital signs Provide a calm & quiet environment Administer analgesics as per order

Ineffective family coping related to diagnosis of disease

Assess the familys perception of disease Identify any misconceptions guilt fear etc Determine degree of emotional or financial stress Include family members in client care Provide opportunity for family group sessions Encourage for screening

CONCLUSION

Disease with frightening symptoms. Continuous support during the therapy. Due to its familial predisposition, other family members should be evaluated for the disease Regular follow up is necessary as it can recur.

REFERENCESBrunner & Suddarths , textbook of Medical Surgical Nursing, 10th edition

Black MJ, Medial Surgical Nursing 3rd edition

www.pubmed.com

www.wikepedia.org,www.emedicine.com

Harrisons principals of internal medicine, 15th edition

GF Mccarkle, frank Sternberg , cancer nursing, 2nd edition

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