A Case From The Clinic Paul J. Scheel, Jr., MD Director Of Nephrology The Johns Hopkins University School of Medicine.

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Presentation transcript:

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 U/A: Dip negative, No Cells

Hypertension and Hypokalemia Differential 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 Hyperaldosteronism PAC/PRA > 30 StudyIncidenceNComments Gordon9 %199 Lim9.2%465 Fardella9.5%305Normal K + Loh18%359

Primary Hyperaldosternoism Prevalence by JNC VI I: BP /90-99 II: BP / III BP > 180/>110

Pathophysiology Circulating Blood Volume Renal Perfusion Pressure Renin Release Angiotensin I Angiotensinogen Angiotensin II Aldosterone Release Na, K

Pathophysiology Tubular Lumen Peritubular Capillary 3Na 2K Na K 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 –Hyperaldosteronism – 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 Collection Results 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 mg/kg body wt/24 hrs Men: mg/kg/body wt/24 hrs

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

Hyperaldosteronism Confirmatory 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

Hyperaldosteronism Classification 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 mg 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 Treatment Aldactone 100 mg- 200mg Adrenal Vein Sampling Adrenalectomy

Adrenal Vein Sampling Patient 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 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