1. Intern Case Report
Matt Jepson, DO

2. E.A. is a 44 F CC: Chest pain, shortness of breath HPI:
Constant, 7/10, sharp pain at xiphoid process radiating straight to her back
Started suddenly at 02:00, worsened by movement, improved with lying down
Denies diaphoresis, headache, palpitations, nausea, vomiting, fevers, chills

3. History
PMH
Positive for: HTN, CHF, hypothyroidism, iron deficiency anemia, depression, anxiety, and PULMONARY EMBOLI
PSH
None
Social hx: non-contributory. (no tobacco, no alcohol, no elicit drug use, married, lives at home)
Family hx: non-contributory.

4. Imaging …CT with PE protocol showed pulmonary emboli
Tx: Re-started on Xarelto
She had not been taking it previously.
BUT WAIT, THERE’S MORE…

5. Home Medications
Clonazepam 2 mg TID (1 mg daily is target dose for anxiety)
Clonidine 0.4 mg BID
Levothyroxine 75 mcg daily
Lisinopril 40 mg BID
Lopressor 100 mg BID
Venlafaxine 150 mg daily
…she’s 44 years old… ?

6. Review of systems
ROS:
Positive: episodic diaphoresis, palpitations, weakness, lightheadedness, syncope and severe headaches, depression, anxiety, persistent episodic HTN despite medications
Negative: fever, chills, weight loss, vision changes, cough, vomiting, abdominal pain, diarrhea, seizures

7. Physical Exam
Vitals: Afebrile, HR 101, RR 16, BP 175/99, O2 97%, 7/10 pain
Gen: AOx4, NAD, well-developed, obese, appears distressed
HEENT: NCAT, trachea midline, no adenopathy, EOMI, PERRL, no icterus, no JVD, no thyromegaly
CV: Tachycardic, regular rhythm, no gallop, 2/6 systolic crescendo-decrescendo murmur at 2nd right ICS, DPP and equal in bilateral upper and lower extremities, no carotid bruits
Pulm/chest: normal effort, CTAB, not tachypneic, no distress, no w/r/r, TTB over LLSB
Abd: BS normal, obese but not distended, non-tender
Neuro: CN 2-12 intact, no focal deficits, normal tone, normal gait, normal reflexes
Psychiatric: anxious, distressed, otherwise normal affect
Skin: dry, warm, no diaphoresis or erythema. No rashes.

8. Labs
8.5
8.7
28.5
325
140
4.1
109 22 12
0.8
112
AST: 24
ALT: 17
Alk phos: 114
INR: 1.0
TSH 3.69
Troponin: below assay limit
EKG: sinus tachycardia

9. Labs/imaging Urine catecholamines (24 hour):
epinephrine – not elevated
dopamine – not elevated
norepinephrine ratio to creatinine – 214 (normal <45)
CT abdomen/pelvis (without contrast): 1.8 cm nodule is noted in the left adrenal gland with average Hounsfield units of 5 and a small calcification compatible with an adrenal adenoma.

11. Follow-up
Re-hospitalized a few months later for spells of unconsciousness while in clinic
During that admission, Endocrinology was consulted and they ordered 24-hour urine metanephrines
Normetanephrine: 1566 (normal )
Total metanephrines: 1737 (normal )

12. Let’s be clear…
The MAJORITY of patients with paroxysmal HTN do NOT have pheochromocytomas (1:300)

13. Pheochromocytoma
Catecholamine-producing tumor located within the adrenal gland
Extra-adrenal are paragangliomas
Distinction is important due to implications for associated neoplasms, risk for malignancy, and genetic testing
Less than 0.2 percent of patients with hypertension have catecholamine-producing tumors

14. Demographics Incidence: 0.8 per 100,000 person years
This may be underestimated…
In one series, 50% of pheochromocytomas were diagnosed at autopsy
Usually occur in fourth to fifth decade
Equally common in men and women

15. Clinical Presentation
Symptomatic patient
Discovery of an incidental adrenal mass
Family history in a patient with familial disease
One report had the average age at diagnosis of 47 years; average tumor size was 4.9 cm

16. Clinical Presentation
Classical triad
Headache, sweating, and tachycardia
Whether or not they have hypertension, should be evaluated for pheochromocytoma
Patients with “spells” of paroxysmal hypertension should be evaluated via 24-hour urine catecholamines and metanephrines
Other symptoms
Forceful palpitations, tremor, pallor, dyspnea, generalized weakness, and panic attack-type symptoms

17. - Anti-hypertensives are OK
- Tricyclic antidepressants
24-hour urine fractionated catecholamines:
Norepi : creatinine - 214
- Nmet 1566
- 1.8 cm nodule on left adrenal

18. Diagnostic criteria
A positive case-detection test for a catecholamine-secreting tumor includes one or more of the following findings:
Norepinephrine >170 mcg/24 hour
Epinephrine >35 mcg/24 hour
Dopamine >700 mcg/24 hour
Normetanephrine >900 mcg/24 hour or metanephrine >400 mcg/24 hour
Mayo Medical Laboratories, the diagnostic cutoffs are >400 mcg for metanephrines, >900 mcg for normetanephrines, and >1000 mcg for total metanephrines

19. Which comes first?
Biochemical confirmation of the diagnosis should be followed by radiological evaluation to locate the tumor, not the other way around.

20. Imaging
CT versus MRI
Both sensitive, but only 70% specific due to high prevalence of incidentalomas
MRI better at distinguishing incidentaloma versus pheochromocytoma
T2-weighted images show them as hyperintense whereas other tumors are isointense
Most pheochromocytomas are 3 cm or larger in diameter
If tumor is not visualized with CT or MRI and diagnosis is still highly suspected
123-I-metaiodobenzylguanidine (MIBG) scintigraphy
MIBG is a compound resembling norepinephrine that is taken up by adrenergic tissue.
Can detect tumors not detected by CT or MRI or multiple tumors when CT or MRI is positive

21. Treatment Alpha-blockers
Phenoxybenzamine, start at 10 mg daily with target of mg daily
For metastatic disease, selective alpha-1 blockers are preferred (terazosin, prazosin, etc)
Start at least days pre-operatively, longer if recent MI, catecholamine CM, refractory HTN, catecholamine-induced vasculitis
Day 2-3 of alpha-blockade, start high-sodium diet
Due to volume contraction from catecholamines and orthostatic changes with alpha blockage

22. Treatment Beta-blockers Alternative agents
Start about 2-3 days pre-operatively
NEVER start without alpha-blockers on board
Caution with asthmatics or CHF patients
Start low the first day (10 mg propranolol q6H), then increase to daily dosing as tolerated with goal HR bpm
Alternative agents
CCB’s, especially when alpha-blockers are not tolerated or alpha + beta-blockade still not controlling BP
Metyrosine: catecholamine synthesis inhibitor – short-term course titrated over 4 days preop, main symptom is sleeping
Prolonged use can lead to depression, anxiety, nightmares, crystalluria, urolithiasis, galactorrhea, and EPS
Used more when difficult resection, malignant lesions to be destroyed
Laparoscopic adrenalectomy (for <8 cm diameter)

23. Follow-up Genetic testing – 24% have inherited syndromes MEN2 VHL
30% have bilateral disease
50% of patients with unilateral will develop contralateral disease within 10 years
Therefore, bilateral partial (cortical-sparing) adrenalectomy
VHL
Less diffuse medullary disease
More likely to have recurrence with partial adrenalectomy
VHL type 2A has high malignancy rate

24. Follow-up Surgical removal of benign tumor is not always curative
In 176 patients, 16% (29 patients) had recurrence and of those, 15 were malignant recurrences
More common in familial syndromes, right adrenal tumors or extra-adrenal tumors

25. References
Bissell, M.g. "A Comparison of Plasma-free Metanephrines with Plasma Catecholamines in the Investigation of Suspected Pheochromocytoma." Yearbook of Pathology and Laboratory Medicine 2013 (2013): Web. 11 May 2014.
Young, Wiliam F., MD, Norman M. Kaplan, MD, and Electron Kebebew, MD, FACS9. "Treatment of Pheochromocytoma in Adults." UpToDate. N.p., 9 Apr Web. 11 May 2015.
Young, William F., MD, and Norman M. Kaplan, MD. "Clinical Presentation and Diagnosis of Pheochromocytoma." UpToDate. N.p., 12 May Web. 11 May 2015.
Pacak K, Eisenhofer G, Ilias I. Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. Hormones (Athens) Apr-Jun;8(2): Review. PubMed PMID:
Tischler AS. Pheochromocytoma and extra-adrenal paraganglioma: updates. Arch Pathol Lab Med Aug;132(8): doi: / (2008)132[1272:PAEPU]2.0.CO;2. Review. PubMed PMID:
Amar L, Servais A, Gimenez-Roqueplo AP, Zinzindohoue F, Chatellier G, Plouin PF. Year of diagnosis, features at presentation, and risk of recurrence in patients with pheochromocytoma or secreting paraganglioma. J Clin Endocrinol Metab Apr;90(4): Epub 2005 Jan 11. PubMed PMID:
Young WF Jr, Maddox DE. Spells: in search of a cause. Mayo Clin Proc Aug;70(8): Review. PubMed PMID:

26. Questions?