Incidental Adrenal Nodules Differential Diagnosis

Transcription

1 Adrenal Stuff Richard J. Auchus, MD, PhD, FACE Division of Metabolism, Endocrinology & Diabetes Departments of Internal Medicine & Pharmacology University of Michigan/VA Ann Arbor

2 Incidental Adrenal Nodules Differential Diagnosis Nonfunctioning Cortical Adenoma Cortisol-Producing Adenoma/Nodular Disorders Aldosterone- or DOC-Producing Adenoma Adrenocortical Carcinoma Pheochromocytoma Myelolipoma Cyst Metastatic Carcinoma Lymphoma Infection/Granuloma Hemorrhage Congenital Adrenal Hyperplasia

3 Incidental Adrenal Nodules Non-Adrenal Tumors Renal Cysts and Masses Accessory Spleen Gastric Duplication Ganglioneuromas Retroperitoneal Tumors

4 Three Parts Of The Evaluation Look at the Scan Size, Imaging Characteristics The OTHER Adrenal Interview & Examine the Patient History, Physical Exam, Recent Changes Laboratory Evaluation Routine & Directed Testing

5 Part 1: Imaging Data Size: <2, 2-4, >4 cm Useful Gauge Noncontrasted CT Density <10 HU = Lipid-Rich Adrenocortical Tumor Might Cause Hormone Excess Homogeneity or Lack Thereof Contrast Enhancement Amount, Pattern, Washout Other Suspicious Features Lymph Nodes, Invasion, IVC Thrombus

6 Part 1: Ancillary Imaging Data MRI: Signal Loss on Out-of-Phase Images = High Lipid Content Not Routinely Necessary High Signal on T2-Wtd = Pheo, Other 123 I-MIBG, 111 In-Pentotreotide Should Follow Biochemical Testing 18 F-FDG PET Question of CA, Metastasis Preferable to Biopsy Most Cases 10% of Benign Tumors PET-Avid (Pheo)

7 Incidental Adrenal Nodules Part 2: History & Physical Known Malignancy? Weight Change? HTN? Paroxysms? Myopathy? DM? Bruising? Cushing Stigmata: SC/DC Fat Pads, Thin Skin & Bruising, Muscle Weakness, Plethora Androgen Excess (Women)?

8 Incidental Adrenal Nodules Part 3: Basic Laboratory Evaluation Screen For Hypercortisolemia 1 mg ONDST, <1.8 μg/dl = 50 nmol/l 24 h UFC Poor Sensitivity For Mild Hypercortisolemia Additional Testing if Suspicious: ACTH, DHEAS Screen For Pheochromocytoma 24 h Urine or Plasma Metanephrines Screen For Primary Aldo if HTN &/or Low K

9 Cushing Syndrome Discriminatory Features Proximal Muscle Weakness/Myopathy Osteoporosis Wide, Purple Striae Easy Bruising Moderately Specific: Supraclavicular Fat Pads Facial & Upper Chest Plethora Nonspecific Features Way More Common Fatigue, Weight Gain, Depression, Etc

10 Cushing Syndrome Principles of Testing Cortisol Production is Elevated Urinary Free Cortisol The Diurnal Rhythm is Blunted Serum/Saliva Cortisols at Night Cortisol Production Not Suppressible Dexamethasone Suppression Tests Distinguish From Pseudocushing State ACTH-Dependent or Independent

11 Subclinical Cushing Syndrome Mild ACTH-Independent Hypercortisolism ~25% Subtle Cortisol Excess (SCS) Evident On Careful Testing 90% Have Hypertension 50% Have DM, Dyslipidemia, Obesity 10% Progress to Overt Cushing Syndrome Prevalence Higher if >2.5 cm

12 Adrenal Incidentaloma Hypercortisolism Testing Overnight 1 mg DST Can Use 3 mg Suppress ACTH Plasma ACTH Must Be Done By 0830, Low Stress Serum DHEAS Useful in Patients <65 YO Corroborates Low ACTH Repeat Equivocal Labs In 6-12 Weeks

13 CRH CRH ACTH ACTH Cortisol DHEA-S Cortisol DHEA-S Cortisol DHEA-S Cortisol DHEA-S

14 Case 37-yo WF, New Onset HTN, IFG CT: 2.3 cm Left Adrenal Mass Mild Weight Gain, Regular Menses PE: Mild Facial Plethora, Moon Facies, Dermal Atrophy, SC Fat Pads, Central Obesity 10/2013 5/ /2014 ACTH DHEAS ONDST

15 Case 4: CT Scan 10/ cm

16 Case 4: CT Scan 11/ cm

17 Primary Aldosteronism Whom To Screen? HTN + Hypokalemia Patients With Resistant HTN Or Controlled With 4 Drugs Patients With HTN At Age < 40 Or FH HTN or CVA Age <40 Considering Secondary Causes Sustained BP >150/100 mmhg HTN + Known Adrenal Mass or OSA HTN + First-Degree Relative With PA

18 Primary Aldosteronism Screening Procedure: Stop Drugs? Most Drugs OK for Screening Most Drugs PRA & Aldo (b-blockers PRA) If PRA is Suppressed, Screen is Valid Up to 4 Wk: Spironolactone, Eplerenone BUT STILL OK if PRA Suppressed Best: a 1 -Blocker + Verapamil Can Always Rescreen After Off Drugs

19 Primary Aldosteronism Screening Tests Random PAC/PRA or ARR Ambulatory Test PAC >10 ng/dl AND PRA <1 ng/ml h or DRC <10 pg/ml **PAC/PRA Dominated By Low PRA ( 0) 24 h Urine Na, K Adequate Na Intake, NO K Supplements K > meq/d + Na > 100 meq/d Useful if Hypokalemic

20 ARR Sensitivity & Specificity Nishizaka 2005 Am J Hypertens 18:805

21 Who Has Primary Aldo? ARR Interpretation Serum Aldo PRA Potassium (ng/dl) (ng/ml/hr) ARR (meq/l) Interpretation Low ARR, not PA, stop Low aldo, not PA, stop Positive screen for PA, go to confirmatory testing Probably PA, supplement K, rescreen Probably PA, stop meds and rescreen

22 Funder et al 2016 JCEM 101:1889

23 Primary Aldosteronism Confirmatory Tests Forego PRA <0.6 ng/ml/h, Aldo >20 ng/dl 24 h Urine Na, Aldosterone Aldo >14 mg + Na >200 meq + Nl Plasma K Higher Aldo Suggests Adenoma Saline Suppression Test Aldo >10 ng/dl After 2 L Normal Saline Seated Better Than Supine (?) Fludrocortisone Suppression Test 1000 Aldo >6 ng/dl Captopril Challenge No Fall in Aldo; >10 ng/dl (?)

24 Consider Renovascular Disease PRA >20 ng/ml/h DRC >250 pg/ml PRA 1-20 ng/ml/h DRC pg/ml Meets Screening Criteria Plasma Renin Serum Aldosterone Hypertension With Any of the Following: Resistant Hypertension Hypokalemia FH Hypertension or CVA age <40 Known Adrenal Tumor Controlled on 4 Drugs BP >150/100 Sleep Apnea First-degree Relative PA Consider MR Antagonist PRA <1 ng/ml/h DRC <10 pg/ml Aldo <10 ng/dl Aldo ng/dl Aldo >20 ng/dl MR Antagonist Therapy Possible PA PA Referral For Confirmation & Subtyping Byrd et al 2018 Circulation 138:823

25 Medical Management of PA Start With Spironolactone mg/d Wait 4-6 Weeks Before Doubling Monitor K & Cr Before Raising Titrate to Normal Renin IF POSSIBLE Eplerenone Instead Of Spironolactone Men: Gynecomastia, ED Women: Spotting, Fertility Double Dose of Spironolactone, BID Dosing Amiloride During Pregnancy, 5-20 mg/d Dihydropyridine CCB Add-on

26 AVS With Spironolactone LI CI Comparison of LI and CI between patients exposed & those not exposed to MRA at the time of AVS Unilateral N= [ ] 0.2 [ ] MRA N=51 Bilateral N= [ ] 0.7 [ ] Unilateral N= [ ] 0.2 [ ] No MRA N=140 Bilateral N= [ ] 1.1 [ ] p value MRA vs. no MRA Unilateral * Bilatera l* Complete biochemical success: +MRA: 22 (95.7%) No MRA: 37 (90.2%) Lateralization in 35 patients taking MRA throughout PA diagnostic testing Suppressed PRA N=24 Unilateral, N=26 Bilateral, N=8 Unsuppressed PRA N=2 Case 1 Case 2 Suppressed PRA N=8 p value (Unilat vs. Bilat) LI 14.4 [ ] [ ] < CI 0.2 [ ] [ ] PAC (ng/dl) 40 [21-69] [25-47] >0.9 PRA (ng/ml/h) 0.2 [ ] [ ] 0.07 Hypokalemia 83% % 0.02 DDD index 6.7 [ ] [ ] 0.6 Spironolactone Dose (mg) (N) Eplerenone Dose (mg) (N) (19) (5) (6) (2) Nanba JCEM (in press)

27 Time to Play What Lab Test Do You Want?

28 53 YO LAM, Hypertension, Post-Contrast CT Scan 24 h Urine Normetanephrine 5,100 mg/24 h (Metanephrine Nl) Bilateral Pheochromocytoma Von Hippel-Lindau (VHL Mutation)

29 Incidentally Discovered Pheochromocytoma CT Scan

30 Pheochromocytoma MRI Scans

31 46 YO WM, Took Some Medicines As A Child 17-Hydroxyprogesterone 32,000 ng/dl Classic 21-Hydroxylase Deficiency Bilateral Myelolipomas

32 Adrenal Myelolipoma

33 63 YO WM, Not Feeling Well, Weight Loss Cortisol <0.5 mg/dl; PPD Negative Granulomatous Adrenalitis/Adrenal Insufficiency Histoplasmosis

34 36 YO LAF, Really Not Feeling Well, Weight Loss Cortisol <0.5 mg/dl; Anti-21OHD Ab Pos 83 U (nl <1) Autoimmune Adrenalitis/Adrenal Insufficiency APS-2

35 18 YO AAM, Weight Gain, Bruising, ACTH <5 pg/ml 24 h Urine Free Cortisol 280 mg; DST Cortisol 25 mg/dl Micronodular Adrenocortical Hyperplasia (PPNAD) Carney Complex

36 52 YO G6P3 WF, Worsening Hirsutism After Menopause 17-Hydroxyprogesterone 1,200 ng/dl; T 121 ng/dl Nonclassic 21-Hydroxylase Deficiency

37 29 YO LAF, Amenorrhea, Hirsutism, Hypertension DHEAS 1,700 mg/dl; Testosterone 180 ng/dl Adrenocortical Cancer

38 72 YO WM, S/P Hip Surgery, Warfarin, Bilateral Flank Pain Cortisol <1 mg/dl Bilateral Adrenal Hemorrhage?Anti-Phospholipid Syndrome

39 35 YO WF, Weight Gain, Hypertension, IFG DST Cortisol 3.5 mg/dl; ACTH 8 pg/ml Macronodular Adrenocortical Hyperplasia

40 67 YO AAM, Weight Loss, Night Sweats, Fevers Endocrine Labs Normal Biopsy Atypical Lymphocytes Adrenal Lymphoma

41 82 y/o white man ref onc clinic for bilateral adrenal masses and non-suppressible T. Dx with prostate cancer 2013, followed by XRT to prostate and initiation of ADT in Dec 2016 for elevated PSA of 14.2, but despite months of GnRH therapy (leuprolide) T remained in 100s. Began bicalutamide T still not suppressed; LH, FSH both <1 IU/L and TT 220 ng/dl.

42 Plasma Metanephrines Nl; 1 mg ONDST Cortisol <1 μg/dl ACTH 39 pg/ml; PM Cortisol 5.6 μg/dl; DHEAS 312 μg/dl 4 PM 17OHP 4910 ng/dl Androstenedione 317 ng/dl; T 119 ng/dl (Non)classic 21-Hydroxylase Deficiency!

43 Adrenals Are Life; The Rest is Just Details