A Case From The Clinic

Paul J. Scheel, Jr., MD

Director Of Nephrology

The Johns Hopkins University School of Medicine

Patient W.T.

• 56 year old AA male

• Hypertension x 28 years

• Hypokalemia past 2 years during annual physical. ( 2.8,3.1, 3.0)

• Past Medical History : Negative

• Past Surgical History: Absent

Patient W.T.

• Current Meds:– Procardia XL 90 mg twice daily– Amiloride 10 mg orally each day– Metoprolol 100 mg twice daily– Clonidine 0.2 three times daily

Patient W.T.

• Family History: Mother and Father both deceased ( 64,59) both with hypertension, One of 7 children all with hypertension

• Social History: Recently retired from Federal Government. No Tob or Alcohol, No history of recreational drug use.

• Review of Systems: Occasional fatigue and erectile dysfunction.

Patient W.T.Physical Exam

• General: Appeared Well

• Vitals: BP 160/92, P 62, R 12 Wt 175 #

• HEENT: Normal Fundi

• Neck: No Bruits

• Back: No Buffalo Humping

• CV: Displaced PMI, S4, All peripheral pulses strong without bruits.

• Abdomen: No masses No striae, No Bruits

• Skin: No Echymoses

Patient W.T.Labs

143

3.2

108

25

26

0.9

U/A: Dip negative , No Cells

Hypertension and HypokalemiaDifferential Diagnosis

• Mineralocorticoid Excess– Hyperaldosteronism– Excess deoxycorticosterone

• Renal Vascular Disease

• Cushing’s

• Congenital Adrenal Hyperplasia

• Renin Secreting tumors

When to Evaluate

• Unexplained Hypokalemia ?

• Severe, Resistant Hypertension or a Change in BP Pattern ?

• Adrenal Incidentaloma

• Physical Exam Suggestive of Excess Cortisol.

• Hypertension Alone ?

Incidence Of HyperaldosteronismPAC/PRA > 30

Study Incidence N Comments

Gordon 9 % 199

Lim 9.2% 465

Fardella 9.5% 305 Normal K +

Loh 18% 359

Primary HyperaldosternoismPrevalence by JNC VI

0

2

4

6

8

10

12

14

Normal Stage 2

% PA

• I: BP 140-159/90-99• II: BP 160-179/100-

109• III BP > 180/>110

Pathophysiology

Circulating Blood Volume

Renal PerfusionPressure

Renin Release

Angiotensin I

AngiotensinogenAngiotensin II

Aldosterone Release

Na, K

PathophysiologyTubular Lumen

Peritubular Capillary

3Na

2K

Na

K

AldosteroneAldosterone

Receptor

Diagnosis

• Plasma Renin Activity

• Plasma Aldosterone

• Plasma Aldosterone: Renin Ratio

• 24 Hour Urine ( For What ?)

Plasma Aldosterone: Renin

• 8 am paired plasma Aldosterone + Renin

• For Diagnosis of Hyperaldosteronism Plasma Aldosterone > 20

• Patients must be off Aldactone for 6 weeks

• Calcium Channel Blockers, Alpha Blockers, Beta Blockers OK

• ACEI : May falsely elevate renin

Plasma Aldosterone : Renin

• Interpretation of Results:– Normal - 4-10– Hyperaldosteronism – 30-50

Must know lower limit of lab for plasma renin. Is is 0.6 or 0.1 ? May significantly affect ratios

PAC/PRA

• PAC > 20 and PAC/PRA > 30– Sensitivity and Specificity of 90% for diagnosis

of aldosterone producing adenoma

24 Hour Urine Collection

• Historically used to document K+ Wasting• Now more useful to document other

potential etiologies for low K +• 24 hour Urine should be sent for:

– K +– Na +– Creatinine– Aldosterone

24 Hour Urine CollectionResults

• In setting of hypokalemia– Inappropriate K + Wasting > 30 meq/day– < 30 meq /day suggest extra renal losses– Aldosterone > 14μg/day ( 39nmol/day)– 24 hour urine sodium must be > 200 meq/day– Must be accurate 24 hour collection (creatinine)

• Woman 10-12 mg/kg body wt/24 hrs

• Men: 12-15 mg/kg/body wt/24 hrs

Hypertension and Hypokalemia

Plasma Renin and Plasma Aldosterone

PRA

PAC

SecondaryHyperaldosteronism

Renovasular DiseaseDiuretic UseRenin Tumor

PRA

PAC

HyperaldosteronismWork Up

PRA

PAC

CAHDOC-Tumor

Cushings Syndrome

HyperaldosteronismConfirmatory Evaluation

• Increased PAC:PRA• Confirmatory Testing Requires

– High Sodium Diet followed by 24 hr urine

– Saline Suppression Test with repeat of PAC:PRA

– Fludrocortisone Suppression ( 0.2 mg b.i.d. x 2 days) Aldosterone level on day 3 > 5 confirmatory

OR

OR

HyperaldosteronismClassification

• Adrenal Hyperplasia

• Adrenal Adenoma

• Adrenal Carcinoma

• Familial Hyperaldosteronism I + II

Radiologic Testing

• CT or MRI – Unilateral Adrenal Mass > 5 cm Carcinoma– Can Identify Adenomas > 1 cm– Bilateral Abnormal Glands or Normal Bilateral

Glands Suggest Hyperplasia

Radiologic Testing

• Adrenal Vein Sampling:– Selective Catheterization of Adrenal Veins– > 5x PAC From One Side Unilateral

Disease– Must Also Measure After ACTH Stimulation

Measuring both Aldosterone and Cortisol.– Cortisol Should be 10x Cortisol From

Peripheral Vein

Patient W.T

• Plasma Aldosterone 25, PRA 0.63 Ratio 40

• Saline Suppression PAC 21, PRA 0.4 Ratio 52.5

• CT Scan: No abnormality

• Dexamethasone Suppression PAC 17, PRA 0.4 , Ratio 42.5

Confirmed Hyperaldosteronism

Negative CT

Empiric TreatmentAldactone 100 mg- 200mg

Adrenal Vein Sampling

Medical Therapy

• Aldactone: Usual therapeutic dose is 100-200mg in divided doses per day.

• Amiloride or Triamtene, ? Eplerenone

• Lifestyle Modification– Ideal Body Wt– Exercise– Smoking Cessation– Moderation of Alcohol Consumption– Sodium Restriction ( < 100 mEq/day)

Negative CT

• Adenomas < 1 cm will be missed

• Sensitivity compared to adrenal vein sampling with subsequent surgery and histologic confirmation of adenoma as low as 53 % .

Confirmed Hyperaldosteronism

Negative CT

Empiric TreatmentAldactone 100 mg- 200mg

Adrenal Vein Sampling

Adrenalectomy

Adrenal Vein SamplingPatient W.T.

Aldosterone

39 ng/dl

Aldosterone

3229 ng/dl

Cortisol

1062 mcg/dl

Cortisol

598 mcg/dl

Confirmed Hyperaldosteronism

Adrenal Adenoma

Laparoscopic Adrenalectomy

Adrenal Vein Sampling

Medical Therapy

Patient W.T.

Patient W.T.

• Patient Now 3 months S/p Adrenalectomy

• Bp 127/71 on Atenolol 50 mg once daily

Conclusions:

• Hyperaldosteronism suspected in a patient with hypertension and unexplained hypokalemia or Severe Hypertension alone

• Screen with PAC:PRA

• Confirmatory Testing with Saline Suppression Test or Salt loading followed by 24 hr Urine.

Conclusions:

• CT or MRI can detect lesions > 1 cm• Normal CT or MRI does not rule out

microadenoma• Adrenal Vein sampling is difficult to

perform but is crucial to differentiating unilateral vs bilateral disease

• Surgical Therapy = Adrenalectomy• Medical Therapy = Aldactone, ? Eplerenone