a case from the clinic
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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 - PowerPoint PPT PresentationTRANSCRIPT
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
PathophysiologyCirculating Blood Volume
Renal PerfusionPressure
Renin Release
Angiotensin I
AngiotensinogenAngiotensin II
Aldosterone Release
Na, K
PathophysiologyTubular Lumen
Peritubular Capillary
3Na
2K
Na
KAldosterone
Aldosterone
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/dlCortisol
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