Primary hyperaldosteronism resident survival guide

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Causes

Common Causes

Common causes of Conn's Syndrome may be divided into:

• Adrenal causes:
  • Aldosterone-secreting adrenal adenoma (APA-benign tumor, 50-60%)
  • Idiopathic hyperaldosteronism (IHA-Bilateral hyperplasia of the adrenal gland, 40-50%)
• Extra-adrenal causes
  • Ectopic secretion of aldosterone (Ovaries and Kidneys)

Less Common Causes

• Familial hyperaldosteronism type I (glucocorticoid-remediable aldosteronism [GRA])
• Familial hyperaldosteronism II (the familial occurrence of APA or bilateral idiopathic hyperplasia or both)
• Familial hyperaldosteronism type III (associated with the germline mutation in the KCNJ5 potassium channel)
• Pure aldosterone-producing adrenocortical carcinomas
• Unilateral adrenal hyperplasia

Diagnosis and Treatment

The Management of Primary hyperaldosteronism including case detection, diagnosis, and treatment according to the "Endocrine Society Clinical Practice Guidlines" is as follows:

• Preferred Screening Population:
  • Blood pressure > 160 / 100 particularly (< 50 years)
  • Resistant hypertension or refractory hypertension (use of > 3 anti-hypertensives and poor control of blood pressure)
  • Hypokalemia (provoked by diuretic therapy or unprovoked)
  • Hypertension and incidentally discovered adrenal adenoma
  • Hypertension with a family history of early-onset hypertension (< 20 years) or cerebrovascular accident at age less than 40 years
  • Hypertensive first-degree relatives of patients with PA
• Confirmatory tests:
  • Fludrocortisone supression test (Positive test= Aldosterone > 6 ng / dl and simultaneous PRA levels < than 1.0 ng / ml / hour)- Gold standard
  • Intravenous saline load testing (Positive test= Aldosterone more than 10 ng / dl)
  • Oral sodium loading test (Positive test= 24-hour urinary aldosterone excretion > 12 μg / day)
  • Captopril challenge test (Positive test= PAC / PRA > 30, measured two hours after the administration of 25 mg or 50 mg of captopril)

Focused Initial Rapid Evaluation

Preparation:

1. Attempt to correct hypokalemia. Measure plasma potassium in blood collected slowly with a syringe and needle [preferably not a Vacutainer to minimize the risk of spuriously raising potassium]. During collection, avoid fist clenching, wait at least 5 seconds after tourniquet release (if used) to achieve insertion of needle, and ensure separation of plasma from cells within 30 minutes of collection. A plasma [K+] of 4.0 mmol/L is the aim of supplementation.

2. Encourage patient to liberalize (rather than restrict) sodium intake.

3. Withdraw agents that markedly affect the plasma aldosterone to renin ratio (ARR) for at least 4 weeks:

• Spironolactone, eplerenone, amiloride, and triamterene
• Potassium-wasting diuretics
• Products derived from licorice root (eg, confectionary licorice, chewing tobacco)

4. If the results of ARR after discontinuation of the above agents are not diagnostic, and if hypertension can be controlled with relatively noninterfering medications, withdraw other medications that may affect the ARR for at least 2 weeks, such as:

• β-Adrenergic blockers
• Central α-2 agonists (eg, clonidine, α-methyldopa)
• Nonsteroidal anti-inflammatory drugs
• Angiotensin-converting enzyme inhibitors
• Angiotensin receptor blockers
• Renin inhibitors
• Dihydropyridine calcium channel antagonists

5. If necessary to maintain hypertension control, commence other antihypertensive medications that have lesser effects on the ARR (e.g. verapamil slow-release, hydralazine with verapamil slow-release, to avoid reflex tachycardia), prazosin, doxazosin, terazosin.

B. Blood collection

1. Collect blood mid morning, after the patient has been up (sitting, standing, or walking) for at least 2 hours and seated for 5–15 minutes.

2. Collect blood carefully, avoiding stasis and hemolysis.

3. Maintain sample at room temperature (and not on ice, as this will promote conversion of inactive to active renin) during delivery to laboratory and prior to centrifugation and rapid freezing of plasma component pending assay.

C. Factors affecting interpretation of results

1. Age: in patients aged >65 years, renin can be lowered more than aldosterone by age alone, leading to raised ARR.

2. Gender: premenstrual, ovulating females have higher ARR levels than age-matched men, especially during the luteal phase of the menstrual cycle, during which false positives can occur, but only if renin is measured as DRC and not as PRA (220).

3. Time of day, recent diet, posture, and length of time in that posture

4. Medications

5. Method of blood collection

6. Level of potassium

7. Level of creatinine (renal failure can lead to false-positive ARR)

Preferred screening population

Plasma Renin Activity/Aldosterone Ratio

Normal or High Renin (Plasma Renin/Aldosterone ratio <10

Suppressed Renin (Plasma Renin/Aldosterone ratio >20

•Renin-secreting tumors •Diuretic use •Renovascular hypertension •Coarctation of aorta •Malignant phase hypertension

Urinary aldosterone

Elevated

Normal

Low

Conn's syndrome (Primary aldosteronism)

Profound K+ depletion

• 17 alpha hydroxylase deficiency • 11 beta hydroxylase deficiency • Liddle's syndrome • Licorice ingestion •Deoxycorticosterone producing tumor

Do confirmatory tests

Add Mineralocrticoid antagonist for 8 weeks

BP response

No BP response

Subtype classification

• Deoxycorticosterone excess( Tumor, 17 alpha hydroxylase and 11 beta hydroxylase deficiency) • Licorice ingestion •Glucocorticoid resistance

Liddle's syndrome)

Adrenal CT scan

Normal, micornodularity, bilateral masses or unilateral atypical mass

Unilateral hypodense nodule >1cm and <2cm in the setting of marked primary hyperaldosteronism

Surgery not desired

Surgery desired

Surgery desired

Surgery not desired

> 35 years consider

< 35 years consider

Glucocorticoid-remediable aldosteronism (GRA) OR Idiopathic hyperaldosteronism (bilateral hyperplasia): • Preferred regimen-Spironolactone 12.5mg to 25mg QD or Eplerenone 25mg BID • Alternative regimen-Amiloride 5mg BID plus chlorthalidone/hydrochlorothiazide 12.5mg to 25mg QD

No Lateralization with Adrenal Venous Sampling

Lateralization with Adrenal Venous Sampling

Aldosterone Producing Adenoma (APA) OR Primary Adrenal Hyperplasia (PAH): Unilateral laproscopic adrenalectomy

• Preferred regimen-Spironolactone 12.5mg to 25mg QD or Eplerenone 25mg BID • Alternative regimen-Amiloride 5mg BID plus chlorthalidone/hydrochlorothiazide 12.5mg to 25mg QD