PheochromocytomaPresented by Susie Clabots, Linnea

Cooper, and Stephen Coots

Pheochromoctoma: What is it?

• Tumor in the medulla of the adrenal gland.• Mostly benign• Often produces large amounts of

catecholamines.• Reported number of tumors vary widely.

Occurs in approximately 1 in 1000 people.• Estimated 800 new cases annually

(Mastropietro 1985)

Endocrine Glands and Hormones

• Posterior pituitary– Oxytocin- milk let down, contractions during childbirth– ADH- water balance

• Pituitary- MSH• Thyroid

– T3, T4, Calcitonin• Parathyroid

– PTH• Hypothalamus: controls hormone production in

pituitaryhttp://www.hormone.org/Endo101/

Adrenal glands• Outer- cortex

– Glucocorticoids• Control blood sugar, burning of protein and fat, response to

stress like illness or injury– Mineralcorticoids

• Aldosterone: control blood volume, regulate blood pressure by working on kidney

– Activation of R-A-A, as a result of dec blood flow to kidney, releases angiotension II

– Elevated potassium/low sodium leads to aldosterone secretion– Androgens

• Growth and development in both sexes• Stimulate pubic and axillary hair growth, sex drive in females

• Inner- medulla– Produces epinephrine, norepinephrine, dopamine

• Catecholamines are hormones when secreted by medulla but neurotransmitters when secreted by nerve cell.

www.mayoclinic.com

Cortisol

• Increases blood glucose – stimulation of hepatic gluconeogenesis– inhibiting protein synthesis – stimulate lipolysis in adipose tissue– Decrease peripheral glucose in fasting state.

• Anti-inflammatory action• Increase cortisol during times of stress to more

effectively deal with it.• Alter cell-mediated response

Negative feedback

• Endocrine system is regulated primarily by negative feedback.

• Glands respond by increasing or decreasing the amount of hormone produced based on the feedback it gets from body signals.

• When the levels of these hormones get to a certain level, the release of the hormones is shut off.

• http://www.hormone.org/Endo101/

Changes in the elderly

• Inc secretion of norepinephrine, no change in epinepherine.

• Decreased B-adrenergic receptor response to norepi.– Dec responsiveness to medications that work on b-

receptors– May account for increased prevalence of hypertension with aging

(Graber-Obrien 2007)

Chromaffin Cell tumor

• Chromaffin Cells are found in the adrenal medulla and the ganglia of the sympathetic nervous system.

• Cat release not initiated by neural impulses• They secrete norepinephrine, epinephrine,

dopamine.

A Primer on Chromaffin Cells http://webpages.ull.es/users/isccb12/ChromaffinCell/Primer.html

Who gets it?

• Less often diagnosed in African American• Equal occurrence in females and males• Can occur at any age. Most common in

people between 30 and 60• Usually on Right side• Incidence decreases with age(Hammer 2006)

Associated with…..

– Multiple endocrine neoplasia, type II (MEN-II)– Thyroid cancer (medullary)– Von Hippel-Lindau disease

• Rare multi-system disorder at higher risk for developing

– Neurofibromatosis• Includes: multiple tumors in the skin(neurofibromas),

pigmented skin spots, tumors of optic nerve, and bone lesions. Higher risk of having pheo.

www.mayoclinic.com

Von Hippel Lindau Syndrome (VHL)

• VHL tumor suppressor protein helps protect the body from tumors. When this protein is rendered inactive by a germline mutation malignant and benign tumors are more likely to occur, including pheo.

www.emedicine.com

Neurofibromatosis

• Autosomal dominant disorder• Comes in many different forms (eight or more

phenotypes and at least two different genetic disorders)

• Can effect the skin, bones, nervous system, and endocrine system.

• Most commonly effects the skin.• Increased chance of pheo

www.emedicine.com

Multiple Endocrine Neoplasia (MEN)

Definition: Two endocrine neoplasia tumor types occur in the body with evidence of either a causative mutation or hereditary transmission.

• Occurs by a mutation that renders MENIN, a tumor suppressor protein, inactive or by mutations to the RET gene

• Occurs twice as often in men as women.• Genetic disorders account for about 10% of pheos

www.emedicine.com

Malignant Pheochromocytoma• 3-36% of pheochromocytomas• Location of metastasis predicts survival

– Lung and liver worst, bone best• 5 year survival 34-60%• Less than 40% respond to therapy, reduction in

size lessens symptoms only• Chemotherapy: should be aware of potentially

fatal complications arising from excessive catecholamine release as tumor cells are destroyed (usually within the first 24 hr).

http://www.endotext.org/adrenal/adrenal34/ch01s07.html

Pheo Outside the Adrenal Glands

• About 10% of pheochromocytomas occur outside the adrenal glands. They are referred to as Paragangliomas (also extra-adrenal pheochromocytomas).

• Very rarely malignant.• Similar symptoms to pheochromocytomas.• Some extra symptoms depending on the location of

the tumor.• About 85% of paragangliomas occur in the abdomen

So you have an Adrenal Mass?

Clinical manifestation• Severe episodic hypertension*• Accompanied by: severe, pounding HA of sudden onset,

tachycardia/arrythmias, profuse sweating, anxiety, palpitations, unexplained abd or chest pain, pallor, weight loss, fever, hypertensive retinopathy, nausea, weakness, flushing and constipation.

• The syndrome can vary depending on the types of catecholamines being produced, the amount and frequency of their release into the circulation, and other factors (Onusko 2003).

• Massive catecholamine release can be induced by positional change– Average dec 14mmHg in pt opposed to 4mmHg in pt with essential

HTN (Hammer 2006)

Hypertensive Crisis

• Life-threatening, compromise vital organs• Results from increase in catecholamines from

the tumor.• BP >180/110 • Blood vessels become inflamed and leak fluid

– Heart not able to keep up with demand• Leads to: coronary artery disease, left

ventricular hypertrophy, heart failurewww.mayoclinic.com

Differential Dx

• Pt with pheo have mildly elevated baseline BP– present with HTN crisis with BPs 200/110 followed

by severe exhaustion• HTN not labile

– unable to equate it with stress or emotional distress

• Panic Attacks– Mildly elevated BP– Feeling of doom is primary sign

(Hammer 2003)

Attacks due to….

• SNS stimulation• Accompanied by anxiety. • Provoked by some medications:

antihypertensives, opiods, contrast dye, tricyclic antidepressants

• Lasts minutes to hours

Case study #1• 1. The Physician informs T.L. that an adrenal tumor is

causing his symptoms. T.L. is obviously upset with his diagnosis. He states he doesn’t understand how a tumor on top of his kidney can cause high BP. He asks whether this means he has cancer. How would you respond?

• Most pheo are benign and can be removed. Only 6-10% of pheos are cancerous and metastasize. Typically, they are limited to one local area and will not spread to other parts of the body. – Malignant (cancerous) tumors spread to neighboring

tissue and blood vessels and can metastasize to other parts of the body.

Case study #2

The physician advises T.L. to undergo an adrenalectomy. He is immediately started on phenoxybenzamine (Dibenzyline) 10mg PO g12h. This medication is titrated up q3d until T.L.’s supine BP is below 160/90 mmHg and his standing BP is above 85/40. Propranolol (Inderal) 20mg PO qid is added to control his tachyarrhythmia. What is the connection between these two drugs and the diagnosis?

Phenoxybenzamine (Dibenzyline)Class: long acting alpha adrenergic blockerIndications: Management of blood pressureAction: relaxes smooth muscle, causes BP to decreaseDosage: initially 10 mg twice daily. Can be increased every other day,

usually to 20-40 mg 2 or 3 times a day.Adverse side effects: Dizziness, drowsiness, fainting, lightheadedness.

(Alcohol, hot weather, exercise, and fever can increase these effects.). Postural hypotension, tahcycardia Also, pt should sit up or stand slowly, especially in the morning. Sit down at first sign of dizziness or weakness.

Interactions: Potentiates effect of medicines that stimulate both alpha and beta adrenergic receptors (i.e. epinephrine) and so exaggerrated hypotensive response and tachycardia can occur. Dibenzyline can blocks hyperthermia production by levarterenol and blocks hypothermia production by reserpine.

Propanolol (Inderal) Class: AntiarrhythmicsPharmacologic: beta blockersIndications: Management of arrhythmias. Management of HTN.Manage pheochromocytoma. Action: Blocks stimulation of beta1 (myocardial) and beta2 (pulmonary, vasular and uterine) – adrenergic receptor sites. Therapeutic effects: Decreases HR and BP, suppression of arrhythmias, prevention of MI.Dosage: for adjunct management of pheochromocytoma 20mg 2 to 3 times a day concurrently with alpha-blocking therapy.Adverse effects: fatigue, weakness, dizziness, drowsiness, impotence, arrythmias, bradycardia, CHF, pulmonary edema, bronchospasmInteractions: General anesthesia, IV phenytoin, and verapamil (can cause additive myocardial depression). Additive hypotensive effects with other

antihypertensives, acute ingestion of alcohol, or nitrates. Concurrent use of amphetamines, cocaine, ephedrine, epi, norepi, may result in unopposed alpha-adrenergic stimulation (excessive HTN, bradycardia).

Diagnostic Procedures• Only 0.1% of HTN• Plasma Metanephrine (High sensitivity, lower specificity)

– >236 ng/L confirms dx • Measurement of urinary fractioned metanephrines (catecholimine

metabolites) as well as fractionated catecholamines and creatinine• Done as 24 hr urine

– Sometimes tumor doesn’t produce enough catecholamines to elicit a reading

– SNS nerve fibers also produce catecholamines• Vanillylmandelic acid (VMA) 24 hr urine, less sensitive• Plasma catecholamines/stimulation test• CT/MRI for tumor location• Clonidine suppression test(Hammer 2003)

Plasma catecholamines collection• Drugs, diet and stress can all raise levels• Acetaminophen interferes- stop taking 5 days

prior.• Caffeine, nicotine interfere with results• Emotional stress interferes• Interfering medications should be stopped 2

weeks prior: tricyclic antidepressants, antipsychotics, levadopa, ethanol, phenoxybenzamine, withdrawing from clonidine

• Supine position for draw, after night fast(Hammer 2003)

Labs drawn

• Routine urinalysis, • Complete blood cell count, • blood chemistry profile (potassium, sodium,

creatinine, fasting glucose, fasting lipid levels),• 12-lead electrocardiogram are recommended

for all patients with hypertension.

(Onusko 2003)

Treatment

• Surgical removal of tumor– Laparoscopic adrenalectomy

If surgery not option: metyrosine used to diminish catecholamine production and simplify chronic management

• Preoperatively : alpha-adrenergic blockers• Sympathetic blocking agens (minipress) –HTN

and other symptoms• B-blockers

Laproscopic Transperitoneal Surgery

• Currently standard of practice• 2” incision• Reduced post op pain• Reduced length of stay• Earlier return to regular activities• Decreased postop complications

– 2/61 patients• Essential preoperative alpha an beta-blockers and tight

BP control intraoperatively.(Jaroszewski 2003)

Interventions

• Preoperatively: calm environment, rest– Assess: observe for classic triad: severe headache,

tachycardia, profuse sweating. – Orthostatic hypotension- SE of meds and surgery• Intraoperative: • monitor for hypovolemia and hypotension• monitor glucose levels

• Postoperatively:– Case manage: refer to health care provider

Nursing Diagnosis• Anxiety r/t symptoms from increased catelcholamines-

headache, palpitations, sweating, nervousness, N/V, syncope

• Disturbed sleep pattern r/t high levels of circulating catelcholamines

• Ineffective Health Maintenance r/t deficient knowledge regarding treatment and self-care

• Nausea r/t increased catelcholamines

• Risk for ineffective tissue perfusion cardiopulmonary and renal r/t episodes of hypertension

Anxiety r/t symptoms from increased catelcholamines- headache, palpitations, sweating, nervousness, N/V,

syncope

Outcome: Pt will have vital signs that reflect a baseline or decreased sympathetic stimulation.

Outcome: Pt is able to identify and verbalize symptoms and possible causes of anxietyOutcome: Pt is able to verbalize and demonstrate techniques that can help control

anxiety.

Interventions: Nurse will assess pt’s level of anxiety and physical reactions to anxiety. To get a baseline understanding.

Nurse can educate pt about signs/symptoms of excessive sympathetic stimulation. So pt can understand and self-monitor for s/sx.

Nurse will educate pt regarding lifestyle changes that can help decreased the number of triggers. (more important pre-operatively, but still important post-op, esp. if HTN remains).

Nurse will discuss with pt activities that promote relaxation and also stress reduction techniques.

Nurse will intervene when necessary. Anxiety is a normal response to actual or perceived danger; if the threat is removed, the response will stop. So if pt gets sudden severe headache, palpitations, diaphoresis…the nurse can attend to him and reassure him, explain what is happening, get him to sit down.

Case study, #3• Some people experience paroxysmal, or sudden, periodic attacks of HTN

that correspond to the release of epinephrine and/or norepinephrine. Under what circumstances would T.L. most likely experience a paroxysmal hypertensive event?

• At work- his position as a supervisor• Don’t know much about him

– Kids, family? Elderly parents? Job stress?– Being in hospital– Paying bill– Exercise– Caffeine– B-blockers and anesthesia can increase secretion of catecholamines

• Excessive ingestion of tyrosine-containing foods (aged cheese, red wine, beer, yogurt)– If on MAOI

Case study #4

• What measures to prevent a paroxysmal hypertensive event should you teach T.L.?

• HTN resulting from an identifiable, correctable cause

– Avoid tyrosine containing foods (if on MAOI)– Avoid stress, exercise (until after the surgery), palpating adrenal

glands– Meds should be evaluated to see if they aggravate his condition– Stop/limit smoking– Avoid extreme excitement– Teach stress reduction techniques/limit work/take time outs

1

(Onusko 2003)

Case study #5

• Following the surgery, T.L. is taken directly to the ICU. The anesthesiologist gives the admitting nurse the following report: surgery went well, and T.L. should wake up shortly; his VS have been running 180/90, 88, 16, 96.1 F; he’s got a left subclavian Swan-Ganz catheter and two large-bore peripheral IVs with D5W running at a total of 125mL/h; urine output during OR was 200mL. What additional data should the ICU nurse elicit from the anesthesiologist?

Case study #5….

• How did he handle surgery?• Family here?• What drugs did you give him?

– For BP– Potential interactions of anesthesia and drugs

Case study, #6Identify three postoperative issues R/T T.L.’s care.

• Blood glucose- can lead to DM– Monitor– Proper diet– After tumor removal, immediately start D5W and continue for several hours (Pecak 2008)

• Htn can persist (10-30%): stress importance of follow up care– Establish pcp, teach importance, teach s/s htn crisis

• Orthostatic hypotension– Give fluids right away (Pecak 2008)– Teach to get up slow, safety measures– SE of many meds

• Good nutrition, sleep• Control stress• Pain- post-op• Biochemical testing should be repeated after about 14-28 days from surgery in order to check for

remaining disease• On long term follow-up about 17% of tumors recur, with about 50% of these showing signs of

malignancy. (Pecak 2008)

Case study, #7

For each issue identified in question 6, outline two to three interventions/measures.

• Assess the patient for pain• Administer pain medication as ordered. • Administer fluids as ordered.• Tell the patient you’d like to be in the room when he

gets out of bed.• Monitor blood pressure frequently.• Assess neurological status• Instruct the patient to shift positions slowly and give

himself time between each shift.• Teach stress reduction techniques

Case study #8

• During shift assessment (second post operative day), the nurse notes that T.L. seems less alert, his grip strength is markedly weaker than yesterday, and his mucous membranes are dry. The previous nurse reported that he had vomited twice in the last hour. The cardiac monitor shows peaked T waves and a widened QRS complex. VS are 120/72, 94, 14, 101 F. What conclusions can you draw from the foregoing data?– All these findings suggest adrenal insufficiency

Adrenal insufficiency• Result of removal of adrenal gland• Aldosterone no longer being released

– Normally acts on kidneys, gut, and salivary/sweat glands to affect electrolyte balance

• Cortisol– Responds to stress, immune system, cv function, insulin balance

• s/s: Weakness (99%) • Pigmentation of skin (98%) • Weight loss (97%) • Abdominal pain (34%) • Salt craving (22%) • Diarrhea (20%) • Constipation (19%) • Syncope (16%) http://www.emedicine.com/emerg/topic16.htm

Case study #9

• What treatment measures would you anticipate for adrenal insufficiency?– Steroid replacement therapy (normally should

only be used in Cushing syndrome or bilateral adrenalectomy)

– Fluids – Electrolyte replacement

http://archsurg.ama-assn.org/cgi/content/full/141/8/771?ck=nck

Case study #10

• Outline four measures that are critical during this period.– Ensure IV line patency and insertion site and

maintain adequate fluid infusion rate to prevent further dehydration from vomiting

– Monitor VS q 1 hr– Administer antipyretics– Start steroid therapy per physician

Case study #11

• T.L. is stabilized and is scheduled to be discharged home. During discharge teaching, T.L. asks whether he will require medication for the rest of his life. How should you respond to T.L.?– Life long therapy is generally needed quality of life

is able to be maintained.

Reference• Hammer, G and Nguyen-Martin, M (2006). Pheochromocytoma: An Update on Risk

Groups, Diagnosis, and Management. Hospital Physician. Turner White Communications, Inc: Wayne, PA. pp 17-26.

• The Hormone Foundation (2008). ENDO 101: The Endocrine System. Retrieved April 26, 2008 from http://www.hormone.org/Endo101/

• Medline Plus (2008). Endocrine Diseases. Retrieved April 26, 2008 from http://www.nlm.nih.gov/medlineplus/endocrinediseases.html.

• Banakik, J. & Copstead, L. (2005). Pathophysiology, 3rd Edition. St. Louis, Missouri: Elsevier, Inc.

• Ackley, B. & Ladwig, G. (2006). Nursing Diagnosis Handbook: A Guide to Planning Care, 7th Edition. St. Louis, Missouri: Mosby, Inc.

• Graber O’Brien, P., Ruff Dirksen, S., Lewis, S. L., McLean Heirkemper, M., Bucher, L. (2007). Medical-Surgical Nursing: Assessment and Management of Clinical Problems, 7th Edition. St. Louis, Missouri: Mosby Elsevier, Inc.

• Onusko, Edward. (2003). Diagnosing Secondary Hypertension. American Family Physician. 67(1):67-74

• Jaroszewski, Dawn, et al. (2003). Laparoscopic Adrenalectomy for Pheochromocytoma. Mayo Clin Proc 2003;78:1501-1504

References…• Daub, K. F. (2007, March) Pheochromocytoma: challenges in diagnosis and nursing

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• Shen, W.T., Lee, J., Kebebew, E., Clark, O.H., Quan-Yang, D (2006, August) Selective Use of Steroid Replacement After Adrenalectomy: Lessons from 331 Consecutive Cases. Archives of Surgery. 141(8). 771-776. Retrieved April 27th, 2008 from Archives of Surgery.

References.• Carmichael, S & Winkler, H. A Primer on Chromaffin Cells. Retried April

27th, 2008, from The Chromaffin Cell Web site: http://webpages.ull.es/users/isccb12/ChromaffinCell/Primer.html

• National Cancer Institute. (2008) Pheochromocytoma Treatment. Retrieved April 27th, 2008 from National Cancer Institute. Web site: http://www.cancer.gov/cancertopics/pdq/treatment/pheochromocytoma/HealthProfessional/page1

• The Endocrine System: How it Functions. Retrieved from http://www.youtube.com/watch?v=rS7SM4vzs18 on April 27, 2008

• Pecak, Karel. (2008). Management of Pheochromocytoma. Retrieved April 26, 2008 from http://www.endotext.org/adrenal/adrenal34/ch01s07.html

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• eMedicine. (2007). Adrenal Insufficiency and Adrenal Crisis. Retrieved on April 27, 2008 from http://www.emedicine.com/emerg/topic16.htm.