AVS and IPSS: The Basics and the Pearlssyllabus.aace.com/2016/EU-2016/presentations/mon-thurs/17-Young.pdf · AVS and IPSS: The Basics and the Pearls William F. Young, Jr., MD, MSc

AVS and IPSS:

The Basics and the Pearls

William F. Young, Jr., MD, MSc

Professor of Medicine

Mayo Clinic College of Medicine

Rochester, MN, USA © 2016 Mayo Foundation for Medical Education and Research. All rights reserved.

DISCLOSURE*

Relevant Financial Relationship(s)

None

Off Label Usage

None

*A provider must disclose the above information to

learners prior to beginning of the educational activity (ACCME)

When Not to Do AVS

Patient without confirmed PA

Patient who does not want to pursue the surgical option

Young patient with marked PA and unilateral adrenal macroadenoma on CT (and normal appearing contralateral adrenal)

• APA clinical phenotype in a

young patient (<35 yr) with

unilateral adrenal macroadenoma

(>1-cm) – AVS not needed

Prevalence by Age -- Autopsy Data

Kloos et al., Endo Rev 16:460, 1995

The development of adrenocortical

nodules is, in part, a function of age 7%!

Algorithm that will be part of revised ES PA Guidelines – to be published in 2016

Lim V, Guo Q, Grant CS, Thompson GB, Richards ML, Farley DR, Young WF Jr.

Accuracy of adrenal imaging and adrenal venous sampling in predicting surgical

cure of primary aldosteronism. J Clin Endocrinol Metab. 2014 Aug;99(8):2712-9.

When to Do AVS

Patient with confirmed PA and:

o Who wants to pursue the surgical option and

o Who is >35 yrs old or <35 yrs old and lack of unilateral macroadenoma on CT

68-Year-Old Man Hypertension x 9 yrs: Intermittent spontaneous hypokalemia noted

on routine testing over the last 2 yrs

Asymptomatic – no spells

Suboptimal BP control on a CCB, ACE-I, central α-2 agonist, and β-adrenergic blocker

Also takes 40 mEq KCl/d

Physical exam: normal phenotype, BP = 140/83 mm Hg, HR 84 bpm, BMI 29.4

Initial labs: Na+ = 144 mEq/L, K+ = 4.0 mEq/L, creatinine = 1.0 mg/dL

PAC/PRA Ratio - PAC = 42 ng/dL (1165 pmol/L)

- PRA = <0.6 ng/mL/hr

PA Confirmatory Test

24-hr urine on ambient sodium diet:

- Sodium = 269 mEq

- Aldosterone = 34 mcg (94 nmol)

Adrenal CT: Radiologist report: “normal adrenals”

Adrenal Venous Sampling

Adrenal Vein Sampling*

Vein

RT Adrenal Vein

LT Adrenal Vein

IVC

A/C Ratio

Aldosterone Ratio

Aldosterone (A) ng/dL

Cortisol (C) mcg/dL

593

457

14

Step 1: Was cannulation of both AVs

successful?

AV [cortisol] should be >5-fold higher than

IVC [cortisol] from BOTH AVs

If successful, go to step 2. If not successful,

stop.


Vein

RT Adrenal Vein

LT Adrenal Vein

IVC

A/C Ratio

17.7

0.2

1.9

Aldosterone Ratio


10500

84

27

Cortisol (C) mcg/dL

593

457

14

Step 2: Where is Aldo coming from?

To correct for dilution (from inferior phrenic

vein) on the LT AV sample, divide each AV

[aldo] by it’s respective AV [cortisol] for the

“A/C Ratio”


Vein

RT Adrenal Vein

LT Adrenal Vein

IVC

A/C Ratio

17.7

0.2

1.9

Aldosterone Ratio

102 : 1


10500

84

27

Cortisol (C) mcg/dL

593

457

14

Step 3: Where is Aldo coming from? Unilateral if A/C ratio from the dominant adrenal is

>4-fold higher than A/C ratio from lower adrenal

Maybe unilateral or bilateral if aldosterone

lateralization ratio (ALR) is between 3:1 and 4:1

Bilateral if ALR is <3:1

1

10

100

APA (n=102) IHA (n=84) PAH (n=8) A

ldo

ste

ron

e L

ate

ralizati

on

Rati

o

Young WF, Stanson AW, Thompson GB, et al. Surgery. 2004;136:1227-35.

The patient I

am presenting

ALR = 4:1


Vein

RT Adrenal Vein

LT Adrenal Vein

IVC

A/C Ratio

17.7

0.2

1.9

Aldosterone Ratio

102 : 1


10500

84

27

Cortisol (C) mcg/dL

593

457

14

Step 4: Consider contralateral suppression

The A/C ratio from the nondominant adrenal

should be less than the A/C ratio from the

IVC

In this case example 0.2 is less than 1.9

0.2 divided by 1.9 = 0.1

0.1

1

10

100

APA (n=102) IHA (n=84) PAH (n=8) C

on

trala

tera

l A

/C r

ati

o

Young WF, Stanson AW, Thompson GB, et al. Surgery. 2004;136:1227-35.

Contralateral A/C ratio

divided by the IVC A/C ratio

Follow-up

9 Months Postop:

- Hypokalemia resolved and BP = 125/65 mm Hg on low-doses of 2 BP meds

AVS Summary 203 patients; 1990 -- 2003

96% success rate

Based on CT:

o46 patients (24%) would have been bypassed for surgery

o42 pts (22%) would have had unnecessary surgery

Surgery 136:1227-35, 2004.

CT accuracy = 53%

AVS Case 2: 35-yr-old woman with new onset hypertension

Normal serum potassium

BP treated with ACE-I

PAC = 16 ng/dL

PRA = <0.6 ng/mL/hr

ARR = > 26

24-hr urine aldo (high Na+ diet):

16 mcg (Na+ = 418 mEq)

CT: 6-mm LT nodule

KKM019

LH 730

AVS Case 2: Results of Bilateral Adrenal Venous Sampling

Vein

R adrenal vein

L adrenal vein

Inferior vena cava

A:C ratio

0.2

3.09

0.89

Aldosterone ratio*

15.5

Aldosterone (A), ng/dL

4

1300

23

Cortisol (C), g/dL

20

421

26

*L adrenal vein A:C ratio divided by R adrenal vein A:C ratio.

KKM019

AVS Case 2: The best next step in this case is:

1. RT adrenalectomy

2. LT adrenalectomy

3. Bilateral adrenalectomy

4. Repeat AVS

5. Option “5” (something else)

AVS Case 3: 57-yr-old woman with BP x 20 yrs &

accelerated x 2 yrs; spontaneous hypokalemia x 2 yrs

BP treated with CCB, ACE-I, ARB & KCL 80 mEq/d

PAC = 37 ng/dL

PRA = <0.6 ng/mL/hr

ARR = > 45

CT: 11-mm RT nodule

DHY261

LH 730


Vein

R adrenal vein

L adrenal vein

Inferior vena cava

A:C ratio

0.36

0.96

1.22

Aldosterone ratio*

2.7


8.6

503

33

Cortisol (C), g/dL

24

522

27

*L adrenal vein A:C ratio divided by R adrenal vein A:C ratio.

DHY261

1. RT adrenalectomy

2. LT adrenalectomy


4. Repeat AVS




Vein

R adrenal vein

L adrenal vein

Inferior vena cava

A:C ratio

0.36

0.96

1.22

Aldosterone ratio*

2.7


8.6

503

33

Cortisol (C), g/dL

24

522

27

DHY261

AVS Case 4: 39-yr-old woman with poorly controlled BP

on 3 drugs

Spontaneous hypokalemia

PAC = 41 ng/dL

PRA = <0.6 ng/mL/hr

ARR = > 68

CT: 9-mm RT nodule & 8-mm LT nodule

GQH042


Vein

R adrenal vein

L adrenal vein

Inferior vena cava

A:C ratio

0.39

8.62

4.46

Aldosterone ratio*

22.1


250

4267

98

Cortisol (C), g/dL

647

495

22

*R adrenal vein A:C ratio divided by L adrenal vein A:C ratio.

GQH 042

1. RT adrenalectomy

2. LT adrenalectomy


4. Repeat AVS



AVS and IPSS:

The Basics and the Pearls

William F. Young, Jr., MD, MSc

Professor of Medicine

Mayo Clinic College of Medicine

Rochester, MN, USA © 2016 Mayo Foundation for Medical Education and Research. All rights reserved.

When Not to Do IPSS Patient without confirmed CS—

IPSS does NOT diagnose CS; IPSS only tells you where ACTH is coming from

Patient with “typical pituitary-dependent CS presentation” + definite pituitary adenoma on MRI

Patient with obvious ectopic ACTH and tumor is co-localized with cross sectional imaging and octreotide scintigraphy or FDG-PET

41-Year-Old Woman • Slowly developing

symptoms over 5 yrs:

Dx with DM 4 yrs ago

Dx with hypertension 2 yrs ago

Osteoporosis with 2 nontraumatic stress fractures

Gained 100# over past 3 yrs

Proximal muscle weakness; hirsutism

Irritable – “I am always freaking out”

• BMI 48.8 kg/m2

41-Year-Old Woman • Lab:

Serum cortisol: 26 mcg/dL 8 AM; 19 mcg/dL 4 PM

Midnight salivary cortisol = 296 ng/dL (N <100)

24-hr UFC = 63 and 97 mcg (N <45)

1-mg overnight DST = 12 mcg/dL

ACTH = 63 pg/mL (N <60)

• Head MRI

41-Year-Old Woman

41-Year-Old Woman

• Do we need IPSS here?

• No, we need a pituitary surgeon

• Lost 30# of wt

• BP meds D/C

Bilateral adrenal

masses:

• AIMAH

• PPNAD

• Bilateral cortisol-

secreting

adenomas

Normal

or if

clinical picture

fits ectopic CS

IPSS

Confirmed Cushing’s Syndrome (CS)

Unilateral

adrenal

mass:

• Adenoma

• Carcinoma

Adrenal CT

Undetectable

Serum ACTH

Definite

pituitary

tumor

Pituitary MRI

Mid-normal to

increased

IPSS usually not

needed if clinical

picture fits pituitary CS

Normal

or if

clinical picture

fits ectopic CS

IPSS


Serum ACTH

Definite

pituitary

tumor

Pituitary MRI

Mid-normal to

increased

If clinical picture fits with pituitary-dependent CS

(eg, female, slow onset, mild to moderate CS,

UFC <600 mcg) then IPSS usually not needed

64-Year-Old Woman • Well until 5 months ago:

Severe reflux and preop Nissen labs showed serum K+ = 2.2 mEq/L

Has noticed redness and rounding of the face; scalp hair thinning; easy bruising

New onset DM

• BMI 25.2 kg/m2

64-Year-Old Woman • Lab:

Serum cortisol: 46 mcg/dL 8 AM; 43 mcg/dL 4 PM

Midnight salivary cortisol = ND

24-hr UFC = 1084 mcg (N <45)

1-mg overnight DST = ND

ACTH = 151 pg/mL (N <60)

• Head MRI

64-Year-Old Woman

64-Year-Old Woman

• Do we need IPSS here?

• No, we need a cross sectional imaging + octreotide scintigraphy or FDG-PET

FDG-PET

Normal

or if

clinical picture

fits ectopic CS

IPSS


Serum ACTH

Definite

pituitary

tumor

Pituitary MRI

Mid-normal to

increased

If clinical picture fits with pituitary-dependent CS

(eg, female, slow onset, mild to moderate CS,

UFC <600 mcg) then IPSS usually not needed

When to Do IPSS

Patient with confirmed ACTH-dependent CS and:

o Has rapid onset and severe CS and negative cross sectional imaging

o Has mild or intermediate degree CS, but negative pituitary MRI

50-Year-Old Woman

Signs & symptoms of CS slowly developed over 10 yrs:

80 pound central weight gain (130# to 210#)

Dorsocervical & supraclavicular fat pads

Easy bruising

Decreased proximal muscle strength

New onset hypertension & diabetes

Patient says: “I am trapped in a fat cocoon . . who am I and where did I go?”

50-Year-Old Woman

Serum cortisols =

36 mcg/dL a.m.

36 mcg/dL p.m.

24-hr UFC = 531 mcg

ACTH = 151 pg/mL

Na+ = 139 mEq/L; K+ = 3.7 mEq/L

Pituitary MRI shows a full

sella, but no tumor

IPSS with CRH

Time RT IPS ACTH

LT IPS ACTH

PV ACTH

PV cortisol

-5 min 11490 1387 119 24

- 1 min 10480 352 90 25

+ 2 min 54600 1280 87 22

+ 5 min 190000 6040 125 23

+ 10 min 147000 2870 190 21

+ 30 min 523 32

+ 45 min 435 38

+ 60 min 467 41

Post CRH: 190000/125 = 1520 Pre CRH: 11490/119 = 97 PV ACTH increased from 105 to 479 = 356% PV Cortisol increased from 24.5 to 39.5 = 61%

If concerned about adequacy of IPSS, check PRL levels

IPSS Case 2: 50-year-old man with severe ACTH-dependent CS (note: + PRL gradient)

Time RT IPS ACTH

LT IPS ACTH

PV ACTH

PV cortisol

-5 min 110 120 119 38

- 1 min 122 132 90 40

+ 2 min 140 139 110 36

+ 5 min 146 90 133 39

+ 10 min 130 100 140 42

+ 30 min 130 44

+ 45 min 150 39

+ 60 min 120 40

Documents

AVS and IPSS: The Basics and the Pearlssyllabus.aace.com/2016/EU-2016/presentations/mon-thurs/17-Young.pdf · AVS and IPSS: The Basics and the Pearls William F. Young, Jr., MD, MSc