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
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1 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.
2 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)
3 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)
4 APA clinical phenotype in a young patient (<35 yr) with unilateral adrenal macroadenoma (>1-cm) AVS not needed
5 Prevalence by Age -- Autopsy Data The development of adrenocortical nodules is, in part, a function of age 7%! Kloos et al., Endo Rev 16:460, 1995
6 Algorithm that will be part of revised ES PA Guidelines to be published in 2016
7 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 Aug;99(8):
8 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
9 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
10 PAC/PRA Ratio - PAC = 42 ng/dl (1165 pmol/l) - PRA = <0.6 ng/ml/hr
11 PA Confirmatory Test 24-hr urine on ambient sodium diet: - Sodium = 269 meq - Aldosterone = 34 mcg (94 nmol)
12 Adrenal CT: Radiologist report: normal adrenals
13 Adrenal Venous Sampling
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. Adrenal Vein Sampling* Vein RT Adrenal Vein LT Adrenal Vein Aldosterone (A) ng/dl Cortisol (C) mcg/dl A/C Ratio Aldosterone Ratio IVC 14
15 Adrenal Vein Sampling* Vein RT Adrenal Vein LT Adrenal Vein Aldosterone (A) ng/dl Cortisol (C) mcg/dl A/C Ratio Aldosterone Ratio IVC 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
16 Adrenal Vein Sampling* Vein RT Adrenal Vein LT Adrenal Vein Aldosterone (A) ng/dl Cortisol (C) mcg/dl A/C Ratio Aldosterone Ratio 102 : 1 IVC 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
17 Aldosterone Lateralization Ratio 100 APA (n=102) IHA (n=84) PAH (n=8) The patient I am presenting 10 ALR = 4:1 1 Young WF, Stanson AW, Thompson GB, et al. Surgery. 2004;136:
18 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 divided by 1.9 = 0.1 Adrenal Vein Sampling* Vein RT Adrenal Vein LT Adrenal Vein Aldosterone (A) ng/dl Cortisol (C) mcg/dl A/C Ratio Aldosterone Ratio 102 : 1 IVC
19 Contralateral A/C ratio 100 APA (n=102) IHA (n=84) PAH (n=8) Contralateral A/C ratio divided by the IVC A/C ratio Young WF, Stanson AW, Thompson GB, et al. Surgery. 2004;136:
20
21 Follow-up 9 Months Postop: - Hypokalemia resolved and BP = 125/65 mm Hg on low-doses of 2 BP meds
22
23
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25 AVS Summary 203 patients; % success rate Based on CT: o 46 patients (24%) would have been bypassed for surgery o 42 pts (22%) would have had unnecessary surgery CT accuracy = 53% Surgery 136: , 2004.
26 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 = > hr urine aldo (high Na + diet): 16 mcg (Na + = 418 meq) CT: 6-mm LT nodule KKM019
27
28 AVS Case 2: Results of Bilateral Adrenal Venous Sampling Vein R adrenal vein L adrenal vein Inferior vena cava Aldosterone (A), ng/dl Cortisol (C), g/dl A:C ratio *L adrenal vein A:C ratio divided by R adrenal vein A:C ratio. Aldosterone ratio* 15.5 KKM019
29 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)
30 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
31
32 AVS Case 3: Results of Bilateral Adrenal Venous Sampling Vein R adrenal vein L adrenal vein Inferior vena cava Aldosterone (A), ng/dl Cortisol (C), g/dl A:C ratio *L adrenal vein A:C ratio divided by R adrenal vein A:C ratio. Aldosterone ratio* 2.7 DHY261
33 AVS Case 3: 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)
34 AVS Case 3: Results of Bilateral Adrenal Venous Sampling Vein R adrenal vein L adrenal vein Inferior vena cava Aldosterone (A), ng/dl Cortisol (C), g/dl A:C ratio Aldosterone ratio* 2.7 DHY261
35 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
36
37 AVS Case 4: Results of Bilateral Adrenal Venous Sampling Vein R adrenal vein L adrenal vein Inferior vena cava Aldosterone (A), ng/dl Cortisol (C), g/dl A:C ratio *R adrenal vein A:C ratio divided by L adrenal vein A:C ratio. Aldosterone ratio* 22.1 GQH 042
38 AVS Case 4: 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)
39
40 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.
41 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 pituitarydependent 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
42 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
43 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
44 41-Year-Old Woman
45 41-Year-Old Woman Do we need IPSS here? No, we need a pituitary surgeon Lost 30# of wt BP meds D/C
46 Confirmed Cushing s Syndrome (CS) Serum ACTH Undetectable Adrenal CT Mid-normal to increased Pituitary MRI Unilateral adrenal mass: Adenoma Carcinoma Bilateral adrenal masses: AIMAH PPNAD Bilateral cortisolsecreting adenomas Definite pituitary tumor IPSS usually not needed if clinical picture fits pituitary CS Normal or if clinical picture fits ectopic CS IPSS
47 Confirmed Cushing s Syndrome (CS) Serum ACTH Mid-normal to increased Pituitary MRI Definite pituitary tumor If clinical picture fits with pituitary-dependent CS (eg, female, slow onset, mild to moderate CS, UFC <600 mcg) then IPSS usually not needed Normal or if clinical picture fits ectopic CS IPSS
48 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
49 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
50 64-Year-Old Woman
51 64-Year-Old Woman Do we need IPSS here? No, we need a cross sectional imaging + octreotide scintigraphy or FDG-PET
52 FDG-PET
53
54 Confirmed Cushing s Syndrome (CS) Serum ACTH Mid-normal to increased Pituitary MRI Definite pituitary tumor If clinical picture fits with pituitary-dependent CS (eg, female, slow onset, mild to moderate CS, UFC <600 mcg) then IPSS usually not needed Normal or if clinical picture fits ectopic CS IPSS
55 When to Do IPSS Patient with confirmed ACTHdependent 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
56 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?
57
58 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
59 Pituitary MRI shows a full sella, but no tumor
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61 PV IPSS Cortisol ACTH with CRH increased Post Pre CRH: from / / to to = 356% 97 = % Time RT IPS LT IPS PV PV ACTH ACTH ACTH cortisol -5 min min min min min min min min If concerned about adequacy of IPSS, check PRL levels
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63 IPSS Case 2: 50-year-old man with severe ACTH-dependent CS (note: + PRL gradient) Time RT IPS LT IPS PV PV ACTH ACTH ACTH cortisol -5 min min min min min min min min
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