Pheochromocytoma Update Quan-Yang Duh Professor of Surgery - - PDF document

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Pheochromocytoma Update

Quan-Yang Duh Professor of Surgery University of California, San Francisco

Advances in Endocrine Metabolism PG Course, UCSF, March 19, 2016

Nothing to Declare

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Pheochromocytoma: Work up & Management

◆ Presentation ◆ Hereditary PPGL (pheo/paraganglioma) ◆ Diagnostic Testing ◆ Imaging ◆ Preop Preparation ◆ Laparoscopic Resection ◆ Pheo Crisis

Pheochromocytoma and Paraganglioma: 2014 Endocrine Society Clinical Practice Guideline

Jacques W.M. Lenders, Quan-Yang Duh, Graeme Eisenhofer, Anne-Paule Gimenez- Roqueplo, M. Hassan Murad, Mitsuhide Naruse, Karel Pacak, William F. Young, Jr.

Endocrine Society Practice Guidelines: pheochromocytoma/paraganglioma Lenders JW, et al. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42.

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An American President, a German Teenager, a Canadian Nun, and an Appalachian Family Feud Which is proven true?

◆ Lincoln

MEN 2B

◆ Eisenhower

Pheochromocytoma

◆ Kennedy

Adrenal Insufficiency

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Which is proven true?

◆ Lincoln

MEN 2B

◆ Eisenhower

Pheochromocytoma

◆ Kennedy

Adrenal Insufficiency

John G Sotos: The Physical Lincoln, 2008. Messerli FH, et al: The President and Pheochromocytoma, Am J Cardiol 99:1325-9, 2007 ◆ “wide swings in President’s

BP”, “headache”, 8 MI’s

◆ 1.5 cm left adrenal pheo Messerli FH, et al: Am J Cardiol 99:1325-9, 2007

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Pheochromocytoma: 1st description (Felix Frankel, Freiburg, 1886)

◆ Minna Roll, age 18. died in1884. ◆ 1 yr intermittent palpitation, anxiety, vertigo,

headache, vomiting, constipation.

◆ Pale, “goiter”, tachycardia, chest pain. ◆ Died from circulatory failure 9 days after adm. ◆ Autopsy showed bilateral adrenal tumors

(“sarcoma” & “angiosarcoma”), cardiac hypertrophy

Felix Frankel 1886, CA Cancer J Clin 1984;34:93-106. Neumann HP, et al. NEJM 2007; 357:1311-5

Pheochromocytoma: Minna Roll had MEN 2A

◆ ret c634w mutation

found in 4 affected relatives

Neumann HP, et al. NEJM 2007; 357:1311-5

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Family Tree of Minna Roll

Neumann HPH, et al. NEJM 2007; 357:1311-5

Pheochromocytoma: 1st successful operations

◆ Cesar Roux (Lausanne) Feb 25, 1926

§ Madame S, 33 yo, 2 years of nausea/vertigo § 13 cm R adrenal pheo resected § Well for at least 18 months

◆ Charles Mayo (Rochester) Oct 9, 1926

§ Mother Joachim

Vauthey JN, et al Surgery. 1992;112:946-50 Mayo CH: JAMA 1927; 89:1047-50 Van Heerden JA, Am J Surg. 1982;144:277-9

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Pheochromocytoma: 1st successful operations in the US

◆ Charles Mayo (Rochester) operated on Mother Joachim on Oct 9, 1926

– 30 yo Ursuline nun from Chattam, Ontario – 18 months of episodic N/V/HA. – Adm’d June 3, 1926, paroxysmal HTN (300/160) – 6 cm left adrenal tumor “enucleated and packed”,

• p time 1 hr 4 min. Discharged in December.

– No further symptoms, taught music at convent. – Died from “coronary thrombosis” at age 48

Mayo CH: JAMA 1927; 89:1047-50 Van Heerden JA, Am J Surg. 1982;144:277-9

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Hatfield & McCoy: A family feud fueled by pheo?

Atuk NO, et al, J Clin Endocrin Metab 1998, 83:117-120

HOUSE, MD

(Princeton-Plainsboro Teaching Hospital)

◆ Season 2 episode 1

– “acceptance” – Clarence, a prisoner on death row – Pheo as potential cause for his rage

◆ Season 4 episode 2

– “the right stuff” – Greta, an air force captain training to be an astronaut – Diagnosed with VHL and pheo

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Grey’s Anatomy

(Seattle Grace Mercy West Hospital)

◆ Season 7 episode 10

– Dr. Teddy Altman (cardiac surgeon) married Henry Burton (who has VHL) so he can have health insurance to have his adrenalectomy for pheochromocytoma

◆ Season 8 episode 9

– Henry died intraoperatively from a bleeding malignant pulmonary carcinoid tumor.

Pheochromocytoma: Presentation

Autopsy Eisenhower Crisis Minna Roll Classic Mother Joachim, Madame S Genetic McCoy, Minna Roll Incidentaloma

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Case: young man with chest pain

◆ 30 year-old man seen in ER for “rule out MI”

– Chest tightness, tachycardia, coughing, for 3 months – Sweating and sense of impending doom

◆ PMH

– Diabetic for 3 years, on insulin 20 u each morning – Anxiety disorder – Tremor since age 14

◆ Family History

– Father died of MI at age 49

◆ BP 160/95, P 125 ◆ MI ruled out. Treated with propranolol 20 mg BID

Case: young man with chest pain

◆ Non-contrast CT ◆ L adre tumor, heterogen. ◆ 13 cm x 8 cm x 6.5 cm ◆ FNA suggested

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Case: young man with chest pain

◆

Neck exam found a palpable 1.4 cm right jugular node

◆

Ultrasound also found non- palpable thyroid nodules 1.3x1.1x0.9 cm on the right and 1.7x1.0x0.9 cm

• n the left.

◆

Plasma calcitonin 1138 pg/ mL (nl < 10). Ret 634+.

Pheochromocytoma/UCSF: Clinical Presentation

UCSF, Jan 1994 - June 2009 102 patients (50 men, age 47 ± 16), 108

• perations (5 bilateral)

◆ Classical (41%) – HTN w/HA, sweating, palp. ◆ Incidentaloma (33%) ◆ “Pheo crisis” (14%) – multisystem organ

failure

◆ Screening for familial syndromes (7%) ◆ Prior operation elsewhere (4%) Shen WT et al, Arch Surg. 2010 Sep;145(9):893-7

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Pheochromocytoma No longer a “10% tumor” (30-35% familial, 15-20% malignant) Pheochromocytoma/Paraganglioma familial syndromes, UCSF

◆ 15/102 (15%) patients had familial syndromes:

– 8 MEN-2A – 3 von-Hippel Lindau (VHL) – 2 neurofibromatosis type 1 (NF1) – 1 each MEN-2B, Osler-Weber-Rendu, SDHB

◆ Routine genetic counseling /screening

started only recently

Shen WT et al, Arch Surg. 2010 Sep;145(9):893-7

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Pheochromocytoma: Germ-line Mutations are Common

◆ Excluded those with known syndromes ◆ Overall 24% (66/271) had mutations

– 30 VHL, 13 RET, 11 SDHD, 12 SDHB

◆ If multifocal, 84% ◆ If < 18 year-old, 59% ◆ If Extra-adrenal, 93% Neumann et al: NEJM 346: 1459, 2002

Clinically Guided Genetic Screening: Italian Pheochromocytoma Network

◆ 501 patients, for MEN2, VHL, PGL, NF1 ◆ Germline mutation found in 32.1% ◆ 11.6% for single tumor and no family history ◆ 38.8% if multiple or recurrence. ◆ 91.2% if positive family history. ◆ 100% if has associated syndromic lesions. Mannelli M, et al: JCEM 94:1541-1547, 2009

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Succinate Dehydrogenase (SDH) Subunits Mutations

◆ SDHB: abdm extra-adrenal; malignancy ◆ SDHD: adreanl; head & neck; multiple Neumann et al: JAMA 292:943, 2004

Succinate Dehydrogenase “Mitochondrial tumor-suppresser genes”

◆ SDHx: subunit ABCD ◆ Complex II of ETC

mitochondria

◆ TCA (glycolysis) cycle ◆ SDHx dysfunction or

mutation increases ROS and succinate

Gottlieb E, Tomlinson IPM: Nature Rerviews Cancer 5:857-866, 2005

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Pheo/PGL Germ-line Mutations

◆ RET ◆ VHL ◆ NF1 ◆ TMEM127 ◆ MAX ◆ HIF2A ◆ SDHx (A,B,C,D,FA2) Crona J, et al: JCEM 98:E1266-1271, 2013 Dahia PLM: JCEM 98:2679-2681, 2013

Pheo/PGL Genetic Testing

◆ All patients with pheo/PGL should be referred

for genetic testing/counselling. (1⏐⊕⊕⊕O).

◆ Priority and sequence depends on syndromic

features, family history, age at diagnosis, multifocal and metastatic presentation, tumor location and biochemical phenotype

– Malignant pheo – Test for SDHB – All paraganglioma – Test for SDHx

Endocrine Society Practice Guidelines: pheochromocytoma/paraganglioma Lenders JW, et al. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42.

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Diagnosis of Pheochromocytoma

Biochemical Diagnosis of Pheochromocytoma: Which test is best?

Lenders et al: JAMA 287: 1427, 2002 ◆ Plasma metanephrines

– Best negative predictive v

❖ More false positives ❖ Screen familial disease

◆ Urinary metanephrines

– Best positive predictive v

❖ Fewer false positives ❖ All other patients

◆ (CT/MRI characteristics)

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Pheo/PGL Biochemical Diagnosis

◆ Pheos (vs. nerve) ↑COMT↓MAO

– Catechols (COMT) →met/normet – Catechols (MAO) → DHPG

◆ Plasma free normetanephrine &

metanephrine most sensitive.

– Best if done supine, rest > 30 min

◆ Urinary fractionated metanephrines

more specific

Eisenhoefer G, et al. Kindney International 67:668-77, 2005 Lenders JW, et al. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42.

Drugs interfere with Diagnosis of PPGL

◆ Acetaminophen ◆ Benzodiazepines ◆ Buspirone ◆ Catecholamines and

related drugs

◆ Diuretics ◆ Levodopa ◆ Sympathomimetics ◆ Tricyclic

antidepressants

◆ Vasodilators

Neary NM, et al: NEJM 364:2268-70, 2011 Westphal SA: Am J Med Sci 329: 18-21, 2005

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Italian Society of Endocrinology Retrospective Multicenter Study

◆ 26 centers, 1980-1995, questionnaire ◆ 1004 pts, age 58 (15-86), 420 men, 3 (0.5-25) cm

– 85% non-functioning, 15% functioning – 9.2% subclinical Cushing’s – 4.2% pheochromocytomas – 1.6% aldosteronoma

◆ 380 operated

– 52% adenoma, 11% pheo – 12% carcinoma, 3/42 < 4 cm

F Mantero, et al (Ancona): JCEM 2000;85:637-44. A Angeli, et al (Torino) Horm Res. 1997;47:279-83 .

Swedish Prospective Multicenter Study for Adrenal Incidentaloma

◆ 381 patients, 33 hospitals, 1996-2001

– 164 men, 217 women, age 64 (18-84), 3 (1-20) cm

◆ Operative criteria:

– > 3-4 cm or hypersecreting hormone

◆ 85/381 (22%) operated

– 20 (5%) hypersecreting benign tumors (15 pheos) – 14 (4%) malignant (10 adrenal cortical ca)

❖ 10 (4-16) cm

B Bulow & B Ahren (Lund): J Intern Med. 2002;252:239-46.

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Western Sweden Adrenal Study Group: Incidentaloma

◆ Population 1.7 millions, 18 months, 19 radiology Depts, consecutive, prospective ◆ 34,044 scans, 534 assessed (1.6 %) ◆ 226 pts included, 15 operated (6.6%)

– 3 aldo, 1 pheo, 1 metastasis – 10 non-functioining large adenoma (>3 cm) – No additional disease diagnosed at 2 yr f/u

Muth A, et al. Br J Sur; 2011;98:1383-91

Imaging

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Pheochromocytoma

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131I MIBG Treatment for Malignant Pheo

Atlas of Clinical Oncology: Endocrine Surgery, 2003

PET and PET-CT

◆ [18F]fluoro-

deoxyglucose (FDG)

◆ [18F]fluorodopamine ◆ [18F]fluorodihydroxy-

phenylalanine

◆ [11C]hydroxyephedrine ◆ [11C]epinephrine Atlas of Clinical Oncology: Endocrine Surgery, 2003 Ioannis & Pacak:JCEM 89:479, 2004

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PET vs MIBG for Pheo/PGL

◆ 28 studies, 852 patients compared various

PET scans to MIBG

◆ [11C]HED, [18F]DA, [18F]DOPA, [18F]FDG,

[Ga68] somatostatin analogs

◆ PET better than MIBG, especially for familial,

extra-adrenal and metastatic diseases.

◆ MIBG used to select candidate for high-dose

therapeutic I131-MIBG treatment

Rufini B, et al, Q J Nucl Med Mol Imaging 57:122-33, 2013

Pheo/PGL Localization

◆ CT scan

– No FNA

◆ MRI better for skull base and neck ◆ 18F-FDG PET/CT for SDHB or metastasis ◆ 123I-MIBG functional imaging for metastasis

• r potential for 131I-MIBG treatment

Endocrine Society Practice Guidelines: pheochromocytoma/paraganglioma Lenders JW, et al. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42.

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Pheochromocytoma: Avoid FNA

◆ Mayo clinic,

1995-2005, 20 FNA

◆ 14 complications ◆ 6 hematoma ◆ 5 incorrect dx ◆ 2 recurrences Vanderveen KA, et al (Thompson GB), Surgery; 2009; 146:1158-66

There is no such thing as medullary hyperplasia! Adrenal vein sampling can not lateralize pheochromocytoma

◆ 18 pts: AVS to

evaluate cortisol secreting tu, no pheo

◆ Wide range of

catecholamine (R>L 2:1)

◆ AVS not useful Freel EM, et al (Young WF), JCEM 2010; 95:1328-32

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Pheochromocytoma: Medical Management Medical Management of Pheochromocytoma

◆ Treat hypertension

– Alpha blocker: phenoxybenzamine

◆ Expand intravascular volume ◆ Control arrhythmia

– Beta blocker: propranolol

◆ Intraoperative control

– phentolamine, nitroprusside, monitoring

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Alpha Adrenergic Blocker

◆ Phenoxybenzamine

– start 10 mg/d up to 300 mg/d, Q 8-24hr doses – side effects: orthostatic hypotension, tachycardia, nasal congestion, nausea, abdominal pain

◆ Increase alpha blocker dosage until

– supine BP <160/90, orthostatic BP (but > 80/45) – development of side effects

◆ Two weeks preoperatively

Other Antihypertensive Drugs

◆ Doxazocin (alpha-1 competitive blocker) ◆ Prazosin (alpha blocker)

– 2-5 mg Q6-8 hr, shorter acting, avoid postop hypotension, but may be less potent

◆ Labetalol (alpha and beta blocker)

– 400-1600 mg/d – difficult to differentially control alpha v. beta block

◆ Calcium channel blockers ◆ ACE inhibitors

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Pheo/PGL Medical Treatment

◆ Alpha-adrenergic blockade

– Phenoxybenzamine – Doxazocin

◆ Preop volume expansion Endocrine Society Practice Guidelines: pheochromocytoma/paraganglioma Lenders JW, et al. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42.

Pheochromocytoma is NOT a Surgical Emergency (It may a medical emergency)

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Pheochromocytoma Crisis Is Not a Surgical Emergency

◆ 25 /137 (18%) UCSF pheo presented in crisis

– Alpha-adrenergic blockade at least 10 days – 10 urgent, 15 elective, no emergency operation – No death

◆ 33/97 pheo crisis pts had emergency operations

– Death 6/33 vs 0/64 (emergent vs urgent/elective) – Intraop complications 80% vs 42% – Postop complications 71% vs 33 %

Scholten, et al: J Clin Endocrinol Metab 98:581-591, 2013.

Laparoscopic Resection

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Laparoscopic Resection of Pheochromocytoma

Postoperative Care

◆ If well alpha-blocked, patients will have

minimally hemodynamic changes.

◆ High dose pressors may be needed after

tumor removal. Consider vasopressin (ADH).

◆ No need for ICU if stable for 4 hours in PAR. ◆ Anticipate next day discharge.

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Pheochromocytoma/UCSF: Operations

◆ 97 Laparoscopic resections (91%) ◆ 7 open operations (6%) ◆ 4 converted (3%)

– 3 converted to open – 1 converted to hand-assist

◆ 10 paragangliomas (7 laparoscopic, 3 open) ◆ 6 bilateral operations (5 laparoscopic) ◆ 3 subtotal cortex-sparing (all laparoscopic)

Shen et al, Arch Surg. 2010 Sep;145(9):893-7

Pheochromocytoma/UCSF: Operations

◆ Mean operating time: 3.1 ± 1.5 hours (range 1.25 -

9 hours)

◆ 13 patients (12%) required postop pressors

– Phenoxybenzamine preparation for 2 or more weeks

◆ 5 patients (5%) required blood transfusions ◆ Mean hospital stay: 2.5 ± 3.0 days (1-21 days) ◆ Mean tumor size : 5.3 ± 2.8 cm (range 1-15 cm)

Shen et al, Arch Surg. 2010 Sep;145(9):893-7

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Pheochromocytoma/UCSF: Recurrence

◆ 7 patients (6%) developed recurrence

requiring further operation

– Mean time between operation and recurrence 6 years (range 6 months to 17 years) – No “pheochromocytomatosis”. – 2 incomplete resection, 2 genetic, 3 cancers

◆ 3 patients died of disease

– Mean time between last operation and death 3.5 years (range 1-7 years)

Shen et al, Arch Surg. 2010 Sep;145(9):893-7

Pheochromocytomatosis

Li M, et al. Surgery 1309:1072-7, 2001

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Partial Adrenalectomy for Pheochromocytoma in VHL patients

◆ 36 partial adrenalectomy in 26 patients at

NCI, 1995-2003. > 5 year follow up.

◆ “demedullation” operation ◆ 3 (11%) had 5 recurrences ◆ 3 (11%) req’d contralateral adrenalectomy ◆ 3 (11%) became steroid dependent Benhammou JN et al: J Urol 184:1855-9, 2010

Cortex Sparing Adrenalectomy for Hereditary Pheochromocytoma

◆ 39 patients (55 cortical-sparing adrenalectomy)

– 4 recurrences (7%) – 1 acute adrenal insufficiency (3%) – 21 of 27 (78%) steroid independent

◆ 25 total adrenalectomy

– 5 acute adrenal insufficiency (20%).

Grubbs EG, et al: JACS 216:280-9, 2013

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Cortex Sparing Adrenalectomy for Hereditary Pheochromocytoma

◆ Genotype-pheotype association for recurrence? Grubbs EG, et al: JACS 216:280-9, 2013

Adrenal Crisis (Addisonian)

◆ Prospective study of 423 patients (221

primary, 202 secondary) for 2 years. 64 AC.

◆ 8.3 crisis per 100-pt-yr

– 1 crisis per 12 pt-years – GI infection, fever, emotional distress: each 20%

◆ 6% death from adrenal crisis

– 1 death in 16 adrenal crisis – 0.5 AC death per 100-pt-yr (0.5% per year risk)

Hahner S, et al: JCEM 100:407-416, 2015

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Pheo/PGL Surgical Options

◆ Pheo: Lap adrenal unless large or invasive

– Partial adrenalectomy may be justified on the second side (trading recurrence vs Addison’s)

◆ PGL: Open unless small and easy Endocrine Society Practice Guidelines: pheochromocytoma/paraganglioma Lenders JW, et al. J Clin Endocrinol Metab. 2014 Jun;99(6):1915-42.

Pheochromocytoma: Work up & Management

◆ Presentation

Incidentaloma

◆ Hereditary PPGL

RET, VHL, SDHx

◆ Diagnostic Testing

Normet/metanephrine

◆ Imaging

PET, MIBG

◆ Preop Preparation

Alpha-blockade

◆ Lap Adrenalectomy

Most pheos

◆ Pheo Crisis

Medical emergency

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Thank You

Pheochromocytoma: RET mutations

◆ MEN 2B: codon 918 (exon 16).

kinase

◆ MEN 2A: codons 609, 611,

618, 620 (exon 10) and 634 (exon 11, predispd. to pheo). cys

◆ Sporadic pheos: most overexp.

ret mRNA. No rearrang. or

• amplification. 5-10% ret

mutation.

◆ No GDNF (glial cell line-derived

neurotrophic factor, a ligand for RET) mutation

JF Moley in Clark & Duh Textbook of Endocrine Surgery, 1997 Dahia: Ca Res 57:310, 1997

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MEN 2B Neurofibromatosis

◆ NF1 (von Recklinghausen disease)

– Café-au-lait, neurofibroma, axiallary-groin freckles, optic nerve glioma, iris harmatoma – Primary hyperpara, duodenal NET – Pheochromocytoma (2%)

◆ NF-1 encodes neurofibromin (homologous to

ras/GTPase-activating protein, GAP, turns off p21ras MAPK pathway)

◆ Some pheos have loss of NF1 expression

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von Hippel-Lindau Disease

◆ VHL is a tumor suppressor gene. ◆ pVHL complex degrades transcription factors, HIF-1

and 2 (regulate hypoxia-inducible genes, eg. VEGF)

Elder et al: J Surg Oncol 89:193-201, 2005

SDH, VHL & HIF1α “Pseudo-hypoxic pathway”

◆ Succinate inhibits PHD,

which hydroxylates HIF1α

◆ pVHL mediates HIF1α

polyubiquitylation

◆ Both degrades HIF1α ◆ HIF-1α increases tumor

growth & angiogenesis

Gottlieb E, Tomlinson IPM: Nature Rerviews Cancer 5:857-866, 2005

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Cyanotic Congenital Herat Disease: Increases Risk of PPGL 6-fold

Opotowski AR, et al. J Clin Endocrinol Metab 100:1325-34, 2015

◆ high-altitude, aggressive,

recurrent HN-PGL

◆ Loss of SDHB

immunohistochemical staining

Cerecer-Gil NY, et al: Clin Cancer Res 16:4148-4154, 2010.

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Fakhry N, et al: Eur Arch Otorhinolaryngol 265:557-563, 2008. Yes, 8 of 23 patients had SDHx mutations

Carney’s

◆ Carney’s Complex

– myxomas (cardiac endocrine, cutaneous, neural) – pigmented skin and mucosal lesions – prim pigmented nodular adrenocortical disease

◆ Carney Triad

– GIST (leiomyosarcoma) – Pulmonary chondroma (teratoma) – Paragangliomoa – Adrenal cortical adenoma (some subc Cushing)

Carney JA, Stratakis CA, Young WF : Am J Surg Path 37:1140-9, 2013

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Biochemical Diagnosis of Pheochromocytoma: Which test is best?

◆ Plasma metanephrines

– sensitivity 97% (H) 99% (S) – specificity 96% (H) 82% (S)

◆ Urinary metanephrines

– sensitivity 96% (H) 97% (S) – specificity 82% (H) 45% (S)

◆ Cohort, 4 centers, 214 with and 664

without pheo

◆ ROC curves best for plasma

metanephrines

– Overnight fast, indwelling catheter, supine, no Tylenol Lenders et al: JAMA 287: 1427, 2002

“Incidentaloma”

“Adrenal incidentalomas are tumours of the adrenal gland that are discovered incidentally when imaging studies are done for purpose

• ther than searching for adrenal pathology.”

1-5% of abdominal imaging studies identify unanticipated adrenal tumor

Geelhoed GW, Druy EM. Surgery 92: 866-874, 1982 Duh QY. Br J Surg 89:1347, 2002

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NIH State-of-the-Science Conference on the Clinically Inapparent Adrenal Mass

◆ 1-mg Dex suppression ◆ Plasma free metanephr ◆ Resect all pheo, clinical

Cushing, aldo and others

◆ Surgery or observation for

subclinical Cushing

◆ Resect > 6 cm ◆ Observe < 4 cm ◆ Q 6 m imaging x 2 ◆ Q y hormonal study x 4

NIH Consens State Sci Statements. 2002 Feb 4-6;19(2):1-25

Is this incidentaloma a pheo? (borderline metanephrines)

5 10 15 20 25 Normal 1-2 x elev >2x ur metanephrines No Pheo

Lee JA et al: Arch Surg 142:870, 2007 UCSF 1996-2005, 42 patients

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Alpha-adrenergic Blockade

◆ Treat hypertension ◆ Prevent and treat crisis ◆ Preoperative preparation

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Intraoperative Care

◆ Hemodynamic monitoring

– CVP (volume), arterial line (BP), urinary catheter – PA (Swan-Ganz) line if patient is at risk for congestive failure or has coronary artery disease

◆ Minimize anesthetic stress

– slow induction – use less cardiac depressive inhalation agents (isoflurane, enflurane) and muscle relaxants

Intraoperative Care

◆ Antihypertensives

– phentolamine (short acting alpha blocker) – nitroprusside (instantaneous, but build up cyanide) – nitroglycerine

◆ Antiarrhythmics

– esmolol for tachycardia (short acting beta blocker) – lidocaine for ventricular arrhythmia

◆ “Ligate adrenal vein first” is a myth ◆ Communication (surgeon, anesthesiologist)

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Hemodynamic Instability During Resection: Laparoscopic is better

◆ Largest increase in catecholamine level is

during manipulation of tumor

– Lap:  epinephrine x17.4, norepi x8.6 – Open:  epinephrine x34.2, norepi x13.7

◆ Cardiovascular instability occurred only during

traditional open resection.

Fernandez-Cruz L, et al. World J Surg 20:762, 1996

Lap Convert to Open Adrenalectomy

◆ 8/261 converted (4 to open, 4 to hand-assist),

because of size or concern for malignancy

◆ 3/85 pheos, w/o obvious ca at time of operation, but

later (6 m, 1 yr, 2 yr) developed metastatic disease

Shen et al: World J Surg 28:1176, 2004

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Recurrent Paraganglioma

◆ 25 yo m, s/p R adr pheo

resection age 14

◆ Bilateral recurrence

Paraganglioma: re-resection

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Variation of Right Adrenal Veins

Scholten A, et al: JAMA Surg 148:378-383, 2013

Variation of Left Adrenal Veins

Scholten A, et al: JAMA Surg 148:378-383, 2013

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Cortex-Sparing Adrenalectomy (“take the peanut butter and leave the bread”)

◆ Always leave some

medullary tissue behind

◆ Balancing risk for

tumor recurrence (re- growth, seeding or malignancy) versus enough cortex for function.

Painting by SONYA MAHNIC http//:www.bu.edu/histology

Partial Adrenalectomy (more accurate than “cortex-sparing”)

◆ Extent of resection is determined by the size and

location of the tumor.

◆ Remnant can recur (15-20% over 10-15 years)

and fractured-tumor can seed.

◆ Minimal bleeding; use ultrasonic or bipolar sealer. ◆ Remnant survives even with ligated adrenal vein. ◆ Avoid leaving remnant on IVC/difficult areas. ◆ Need 1/2 to 1/3 of one gland to avoid steroid. ◆ May need extra steroid during extreme stress.