Matt Jepson, DO Intern Case Report - PowerPoint Presentation

Matt Jepson, DO Intern Case Report

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

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.

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…

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… ?

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

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 2 nd 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.

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

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.

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 119-451) Total metanephrines : 1737 (normal 156-561)

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

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

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

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

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

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

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

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

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

Treatment Alpha-blockers Phenoxybenzamine , start at 10 mg daily with target of 20-100 mg daily For metastatic disease, selective alpha-1 blockers are preferred (terazosin, prazosin , etc ) Start at least 10-14 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

Treatment Beta-blockers 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 60-80 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 destroyedLaparoscopic adrenalectomy (for <8 cm diameter)

Follow-up Genetic testing – 24% have inherited syndromes MEN2 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

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

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): 325-26. 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. 2014. Web. 11 May 2015. Young, William F., MD, and Norman M. Kaplan, MD. "Clinical Presentation and Diagnosis of Pheochromocytoma." UpToDate. N.p., 12 May 2014. Web. 11 May 2015. Pacak K, Eisenhofer G, Ilias I. Diagnosis of pheochromocytoma with special emphasis on MEN2 syndrome. Hormones (Athens). 2009 Apr-Jun;8(2):111-6. Review. PubMed PMID: 19570738 .Tischler AS. Pheochromocytoma and extra-adrenal paraganglioma : updates. Arch Pathol Lab Med. 2008 Aug;132(8):1272-84. doi : 10.1043/1543-2165(2008)132[1272:PAEPU]2.0.CO;2. Review. PubMed PMID: 18684026 .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. 2005 Apr;90(4):2110-6. Epub 2005 Jan 11. PubMed PMID: 15644401.Young WF Jr, Maddox DE. Spells: in search of a cause. Mayo Clin Proc. 1995 Aug;70(8):757-65. Review. PubMed PMID: 7630214.

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