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:
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–
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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
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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
108
3.2
25
26
0.9
U/A: Dip negative , No Cells
Hypertension and Hypokalemia
Differential Diagnosis
• Mineralocorticoid Excess
– Hyperaldosteronism
– Excess deoxycorticosterone
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•
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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 Hyperaldosteronism
PAC/PRA > 30
Study
Incidence
N
Gordon
9%
199
Lim
9.2%
465
Fardella
9.5%
305
Loh
18%
359
Comments
Normal K +
Primary Hyperaldosternoism
Prevalence by JNC VI
• I: BP 140-159/90-99
• II: BP 160-179/100109
• III BP > 180/>110
14
12
10
8
% PA
6
4
2
0
Normal
Stage 2
Pathophysiology
Na, K
Circulating Blood Volume
Renal Perfusion
Pressure
Aldosterone
Release
Angiotensin II
Angiotensinogen
Angiotensin I
Renin Release
Tubular
Lumen
Pathophysiology
Na
Peritubular
Capillary
3Na
2K
Aldosterone
Receptor
K
Aldosterone
Diagnosis
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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:
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K+
Na +
Creatinine
Aldosterone
24 Hour Urine Collection
Results
• In setting of hypokalemia
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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
PRA
PRA
PAC
PAC
PAC
Secondary
Hyperaldosteronism
Renovasular Disease
Diuretic Use
Renin Tumor
Hyperaldosteronism
Work Up
CAH
DOC-Tumor
Cushings Syndrome
Hyperaldosteronism
Confirmatory Evaluation
• Increased PAC:PRA
• Confirmatory Testing Requires
– High Sodium Diet followed by 24 hr urine
OR
– Saline Suppression Test with repeat of PAC:PRA
OR
– Fludrocortisone Suppression ( 0.2 mg b.i.d. x 2 days)
Aldosterone level on day 3 > 5 confirmatory
Hyperaldosteronism
Classification
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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 Treatment
Aldactone 100 mg- 200mg
Adrenal Vein Sampling
Medical Therapy
• Aldactone: Usual therapeutic dose is 100200mg in divided doses per day.
• Amiloride or Triamtene, ? Eplerenone
• Lifestyle Modification
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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 Treatment
Aldactone 100 mg- 200mg
Adrenal Vein Sampling
Adrenalectomy
Adrenal Vein Sampling
Patient W.T.
Aldosterone
39 ng/dl
Aldosterone
3229 ng/dl
Cortisol
Cortisol
1062 mcg/dl
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