EVALUATION AND MANAGEMENT OF THE ADRENAL MASS handout.pdf-50% of mets are from melanoma, breast, kidney, lung-Adrenal mass represents mets in 50%-If no other known mets you need to

9/30/2019

1

EVALUATION AND MANAGEMENT OF THE

ADRENAL MASS

Dr Robert Elgin

Michigan Institute of UrologyClinical Professor of Urology

Wayne State UniversityMichigan State University

Todays Overview

-Anatomy

-Basic physiology

-Incidentaloma

-Adenoma

Fat Rich vs Fat Poor

-Evaluation of the functional mass

-Pheo

-Conn’s

-Cushings

-ACC

-Mets

Anatomy

Size

Length 3-5cm

Width 2.5-3cm

Weight 3-5 gm

Fetal adrenal tissue involutes after birth, ratio of adrenal to kidney weight:

Neonate 1:3

Adult 1:30

9/30/2019

2

Anatomy

Location

Retroperitoneal

In its own sub compartment of Gerotas Fascia

Ant / Sup / Med to kidney

Anatomy

Arterial Supply

-7cc/gm/minute

Superior- Inferior phrenic artery, majority of blood supply

Middle- Aorta

Inferior- Renal artery

9/30/2019

3

Anatomy

Venous Drainage

Right vs Left

Right- single short vein, into the IVC. Gland is often under the IVC. Scary.

Left- major vein into the renal vein, can have phrenic drainage

Anatomy

Nerve Supply

Medulla- sympathetic supply T10-L1.

Mediates Epi / Norepi

Cortex- no known innervation

Lymphatics

-Lateral aortic nodes, from diaphragm to renal hilum toaorta. Different from renal lymphatics.

9/30/2019

4

Adrenal Physiology

Cortex

-Mesoderm origin.

-3 zones GFR

Glomerulosa (outer)- Aldosterone

Fasiculata (middle)- Cortisol

Reticularis (inner)- Androgen

Nope, not gonna do it.

Adrenal Physiology

Aldosterone

-Principal cells, collecting duct

-Na-K pump in nephron, resulting in water retention and isosmotic volume expansion.

Aldosterone Stimulants

Primary- Angiotensin II

Secondary- ACTH, hyponatremia, hyperkalemia

Aldosterone Antagonist

-ANP

9/30/2019

5

Adrenal Physiology

Cortisol

-Does lots of stuff

-CRH (corticotropin releasing hormone) secreted from thehypothalamus, stimulates ACTH, causing adrenal cortisol release.

-ACTH and cortisol result in negative feedback on CRH

Adrenal Physiology

Androgen

-Sex steroid production is stimulated by ACTH

-Physiologic impact is minimal except in disease state

9/30/2019

6

Adrenal Physiology

Medulla

-Neuroectoderm origin

Catecholamines- dietary phenylalanine and tyrosine are precursors

Norepi- 73%

Epi- 14%

Dopamine- 13%

PNMT- Phenylethanolamine-N-Methyl Transferase, only found in the medulla. Noepi Epi.

-pheo vs paraganglioma

Adrenal Physiology

Norepi / Epi

Adrenal Physiology

Epi / Norepi

-T1/2 is 20 seconds

Metabolism- COOMT, Catechol-O-methyltransferase monoamine oxidase.

-metabolite is urinary VMA, metanephrine, nometanephrine.

9/30/2019

7

Adrenal Physiology

Incidentaloma / Adenoma Fun Facts

Adrenal mass >1cm found incidentally without sign or symptom of adrenal disorder.

-Incidence is age related, 7% of those >70 years, 0.2% of those <29 years

-Roughly 85% are non-functional

N = 2005

Non-functional = 82%

Cushings= 5%

Pheo= 5%

Conn’s= 1%

ACC= 4%

Incidentaloma

Questions to ask

Is it functional?

Physical signs and characteristics?

Biochemical evidence?

Is this a malignancy?

History of another malignancy?

9/30/2019

8

Incidentaloma

Where to begin?

H&P

PE

Basic Endocrine Evaluation

Search for occult malignancy

-CXR

-Hemoccult

-Mammogram

Endocrine Evaluation

1- Serum K if hypertensive

R/O aldosteronoma, unlikely if not hypertensive

2- Plasma free metanephrines

99% sensitivity, 89% specificity

3- Cortisol screening

24 hour cortisol

low dose dex suppression test

late night salivary cortisol

Adrenal Adenoma

Diagnostic Criteria

<10 HU on non-con CT

>60% reduction in density on contrasted imaging at 15 minutes

CT density <10 HU - 71% sens 98% spec

CT washout >60% - 100% sens and spec

MRI T2 intensity <0.8 compared to liver - 80% sens and spec

Loss of signal on chemical shift MRI - 95% sens 100% spec

9/30/2019

9

Adrenal Adenoma

What if HU >10 on non-con?

-Don�t freak out

-Get contrasted study with 15min delay.

Lipid Poor Adenoma

-HU > 10 but has >60% washout.

-If <60% washout its ACC / mets

What if non-functional? Do we care?

-Uncertain progression of non-functional adenomas

-5-25% will increase in size

-1.7% can develop hormonal production (controversial)

Current Recs

-Annual hormonal eval for 4 years

-Repeat imaging at 6 / 12 / 24 months.

-Annual imaging after?? Probably.

Incidentaloma Size

Size Criteria

65% of lesion > 6cm are ACC

CT underestimates size by 20%, therefore recommendation is adrenalectomy at 5cm.

-5cm, regardless of enhancement.

9/30/2019

10

Pheo Fun Facts

-90% are symptomatic. Classic triad (HA, tachy, sweaty)

-Can have orthostatic hypotension, volume depleted

-Anywhere in the paraganglion system

-Catecholamine induced cardiomyopathy, high mortality rate if uncorrected

Rule of 10’s..... Except in kids (25% bilat / extra-adrenal)

-Bilateral

-Familial

-extra-adrenal

-malignant

-normotensive

-multiple (MIBG)

Paraganglioma

9/30/2019

11

Pheo Radiographic Diagnosis

Pheo Diagnosis

Screening- Plasma free metanephrine

Confirmatory- 24 hour urine catecholamine

Inconclusive results =

Clonidine Suppression Test

0.3mg Clonidine and check plasma metanephrine

-no suppression of metanephrine = Pheo

9/30/2019

12

Pheo Radiographic Diagnosis

CT- 98% sens 70% spec

MRI- 100% sens, 67% spec, T2 bright, “lightbulb”

MIBG- 86-100% sens, 85-99% spec

PET (fluoro)- 99% sens, 95% spec

MIBG- exam of choice for extra-adrenal, or if unable to localize on conventional imaging.

Pheo Radiographic Diagnosis

Perioperative Management

Phenoxybenzamine- non-selected alpha blockade. Generally started 2 weeks before surgery to allow for volume expansion.

Beta-Blocker- must be given after alpha blockade in order toreduce tachycardia and prevent cardiac ischemia. Propranolol is commonly used.

Metyrosine- Tyrosine hydroxylase inhibitor, can be helpful in reducing catecholamine synthesis pre-op.

Volume Expansion- aggressive IVF.

9/30/2019

13

Adrenal Physiology

Norepi / Epi

Intraoperative Management

-Good idea to warn your anesthesia department

-Ligate vein first

-Intraop HTN control; esmolol, phentolamine, nitroprusside

-Expect post op hypoglycemia, due to increased insulin release

Drugs to Avoid- halothane, pancuronium, propofol

Pheo Outcomes

Malignant Recurrence – 10%

Surveillance- Yep. Even if benign. 16% recurrence at 10 years. Even in those without familial syndromes.

-Current recommendation is yearly biochemical evaluation.

9/30/2019

14

Familial Syndromes

Primary Hyperaldosteronism “Conn’s Syndrome”

Clinical Features

-HTN

-Hypokalemia

-Muscle weakness / tetany

-Worsening hypokalemia with diuretics

Conn’s Fun Facts

-0.5% of all refractory HTN

-Middle aged white dudes

-Path is 70% aldosteronoma, 30% bilateral adrenal hyperplasia

Pathophysiology

-Autonomous aldosterone secretion from adrenal gland

-Suppression of Renin

-Salt retention, volume expansion, K wasting

9/30/2019

15

Conn’s Fun Facts

Conn’s Diagnosis

Screening- serum K < 3.0

-Plasma Renin <2

-Plasma Aldosterone >15

-Aldosterone : Renin Ratio > 20:1

Confirmatory- Sodium loading test

-high salt diet for 3 days then check 24 hour urine.

Urinary aldosterone >14mcg

Adrenal Vein Sampling – Who needs it?

Endocrine Guidelines

-Age >40

-Bilateral findings on imaging

Young et al 2004

-22% of patients would not have been offered adrenalectomy, 25% of patients would have been offered wrong side surgery without vein sampling.

9/30/2019

16

Primary Hyperaldosteronism Management

Bilateral Adrenal Hyperplasia

-HTN and hypokalemia are less severe than those withsecreting adenoma

-Medical mgmt with spirololactone

-Expect painful gynecomastia / ED

Unilateral Adrenal Adenoma

-Lap / robot adrenalectomy

Cushing’s Syndrome / Disease

Syndrome- Glucocorticoid excess

Disease- Pituitary hypersecretion of ACTH.

-ACTH dependent in 82% of all glucocorticoid excess

-ACTH independent, cortisol mediated. eg- adrenal adenoma, ACC, adrenal hyperplasia

Cushing’s Syndrome / Disease

9/30/2019

17

Cushing’s Fun Facts

-Obesity 90%

-Muscle weakness 80%

-HTN 80%

-DM 80%

-Striae 70%

-Moon Face 60%

Cushing’s Diagnosis Step 1

Screening- Establish hyper cortisolism

1. 24 hour urine cortisol. >100mg/day is diagnostic.

2. If equivocol then, low dose dexamethasone suppression test

-1mg dexamethasone at 11pm, check cortisol at 8am

-No suppression = Cushing’s syndrome

-Normal is cortisol < 5ng/ml

Cushing’s Diagnosis Step 2

Establish relationship of cortisol and ACTH.

-Check late afternoon ACTH

>50 pg/ml = ACTH dependent.

2 options: Cushing’s disease or ectopic ACTH

<5 pg/ml = ACTH independent. Primary adrenal Cushing’s Syndrome.

9/30/2019

18

Cushing’s Diagnosis Step 3

-Where is the ACTH coming from? Within the HPA or not?

High-dose Dexamethasone Suppression Test

-8mg dexamethasone at 11pm, check cortisol at 8am.

<50% reduction = Ectopic ACTH production

>50% reduction= Cushing’s disease, pituitary secretion.

Cushing’s Syndrome Management

Bilateral Adrenal Hyperplasia

Nelson’s Syndrome

Bilateral adrenalectomy for Cushing’s Syndrome

-Incidence is 15%

-Resulting hypersecretion of ACTH

-Headaches

-Tan

-Visual disturbance

Adrenal Cortical Carcinoma

-Bad news bears

-Rare 1 in 1.7 million

-0.02% of all cancers

-80% are functional

-Majority > 6cm

-PET has high sens/spec

-Will be bright on T2, don�t get fooled

9/30/2019

19

Adrenal Cortical Carcinoma

Weiss Diagnostic Criteria

-High mitotic index > 5 per hpf

-Atypical mitotic figures

-Eosinophilic cytoplasm

-Necrosis

-Microscopic invasion

ACC Management

Surgery is only real treatment

-65% of all adrenal masses > 6cm

-Open, en-bloc resection

-5 year survival of organ confined disease 50%

-Needs regional lymphadenectomy and subtotal / total excision ofadjacent structures.

Metastatic / Recurrent Disease

-6 month survival

-Mitotane is chemo of choice, but is palliative only

ACC Management

9/30/2019

20

Adrenal Metastasis

-50% of mets are from melanoma, breast, kidney, lung

-Adrenal mass represents mets in 50%

-If no other known mets you need to do complete functional workup

-Consider FNA IR biopsy, rule out pheo first.

Adrenal Confusing “M’s”

Mitotane- Palliative chemo for ACC

Metyrosine- Tyrosine hydroxylase inhibitor, pheo surgery pretreatment

Metyrapone- 11 Beta hydroxylase inhibitor, can be used in the diagnosis of adrenal insufficiency, HPA axis.

9/30/2019

21