A Case From The Clinic

1
A Case From The Clinic

• Paul J. Scheel, Jr., MD
• Director Of Nephrology
• The Johns Hopkins University School of Medicine

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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

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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

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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.

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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

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Patient W.T.Labs
26
143
108
25
3.2
0.9
U/A Dip negative , No Cells
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Hypertension and HypokalemiaDifferential
Diagnosis

• Mineralocorticoid Excess
• Hyperaldosteronism
• Excess deoxycorticosterone
• Renal Vascular Disease
• Cushings
• Congenital Adrenal Hyperplasia
• Renin Secreting tumors

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When to Evaluate

• Unexplained Hypokalemia ?
• Severe, Resistant Hypertension or a Change in BP
  Pattern ?
• Adrenal Incidentaloma
• Physical Exam Suggestive of Excess Cortisol.
• Hypertension Alone ?

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Incidence Of HyperaldosteronismPAC/PRA gt 30
Study Incidence N Comments
Gordon 9 199
Lim 9.2 465
Fardella 9.5 305 Normal K
Loh 18 359
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Primary HyperaldosternoismPrevalence by JNC VI

• I BP 140-159/90-99
• II BP 160-179/100-109
• III BP gt 180/gt110

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Pathophysiology
Circulating Blood Volume
Na, K
Renal Perfusion Pressure
Aldosterone Release
Renin Release
Angiotensinogen
Angiotensin II
Angiotensin I
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Pathophysiology
Tubular Lumen
Peritubular Capillary
Na
3Na
2K
Aldosterone Receptor
Aldosterone
K
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Diagnosis

• Plasma Renin Activity
• Plasma Aldosterone
• Plasma Aldosterone Renin Ratio
• 24 Hour Urine ( For What ?)

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Plasma Aldosterone Renin

• 8 am paired plasma Aldosterone Renin
• For Diagnosis of Hyperaldosteronism Plasma
  Aldosterone gt 20
• Patients must be off Aldactone for 6 weeks
• Calcium Channel Blockers, Alpha Blockers, Beta
  Blockers OK
• ACEI May falsely elevate renin

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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
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PAC/PRA

• PAC gt 20 and PAC/PRA gt 30
• Sensitivity and Specificity of 90 for diagnosis
  of aldosterone producing adenoma

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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

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24 Hour Urine CollectionResults

• In setting of hypokalemia
• Inappropriate K Wasting gt 30 meq/day
• lt 30 meq /day suggest extra renal losses
• Aldosterone gt 14µg/day ( 39nmol/day)
• 24 hour urine sodium must be gt 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

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Hypertension and Hypokalemia
Plasma Renin and Plasma Aldosterone
PRA
PRA
PRA
PAC
PAC
PAC
Secondary Hyperaldosteronism
Hyperaldosteronism Work Up
CAH DOC-Tumor Cushings Syndrome
Renovasular Disease Diuretic Use Renin Tumor
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HyperaldosteronismConfirmatory Evaluation

• Increased PACPRA
• Confirmatory Testing Requires
• High Sodium Diet followed by 24 hr urine
• Saline Suppression Test with repeat of PACPRA
• Fludrocortisone Suppression ( 0.2 mg b.i.d. x 2
  days) Aldosterone level on day 3 gt 5 confirmatory

OR
OR
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HyperaldosteronismClassification

• Adrenal Hyperplasia
• Adrenal Adenoma
• Adrenal Carcinoma
• Familial Hyperaldosteronism I II

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Radiologic Testing

• CT or MRI
• Unilateral Adrenal Mass gt 5 cm Carcinoma
• Can Identify Adenomas gt 1 cm
• Bilateral Abnormal Glands or Normal Bilateral
  Glands Suggest Hyperplasia

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Radiologic Testing

• Adrenal Vein Sampling
• Selective Catheterization of Adrenal Veins
• gt 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

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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

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Confirmed Hyperaldosteronism
Negative CT
Empiric Treatment Aldactone 100 mg- 200mg
Adrenal Vein Sampling
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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 ( lt 100 mEq/day)

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Negative CT

• Adenomas lt 1 cm will be missed
• Sensitivity compared to adrenal vein sampling
  with subsequent surgery and histologic
  confirmation of adenoma as low as 53 .

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Confirmed Hyperaldosteronism
Negative CT
Empiric Treatment Aldactone 100 mg- 200mg
Adrenal Vein Sampling
Adrenalectomy
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Adrenal Vein SamplingPatient W.T.
Aldosterone 3229 ng/dl
Aldosterone 39 ng/dl
Cortisol 1062 mcg/dl
Cortisol 598 mcg/dl
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Confirmed Hyperaldosteronism
Adrenal Adenoma
Laparoscopic Adrenalectomy
Adrenal Vein Sampling
Medical Therapy
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Patient W.T.
32
Patient W.T.

• Patient Now 3 months S/p Adrenalectomy
• Bp 127/71 on Atenolol 50 mg once daily

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Conclusions

• Hyperaldosteronism suspected in a patient with
  hypertension and unexplained hypokalemia or
  Severe Hypertension alone
• Screen with PACPRA
• Confirmatory Testing with Saline Suppression Test
  or Salt loading followed by 24 hr Urine.

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Conclusions

• CT or MRI can detect lesions gt 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