II. Epidemiology

  1. Represents under 6% of Hypertension Causes
    1. Most common cause of drug Resistant Hypertension
  2. Peak age 30-50 years
  3. More common in women

III. Pathophysiology

  1. Inappropriate Aldosterone Hypersecretion
    1. Primary Hyperaldosteronism (See Causes below)
      1. Increased Aldosterone is initiating event
      2. Results in Sodium retention and volume increase
      3. Renin decreases
    2. Secondary Hyperaldosteronism (See Causes below)
      1. Decreased circulating volume is initiating event
      2. Results in increased renin and Aldosterone
      3. Results in Sodium retention
  2. Physiologic response to Aldosterone Excess
    1. Increased renal distal tubular Sodium reabsorption
      1. Increased total body Sodium content
      2. Increased water retention
    2. Escape phenomenon
      1. Compensatory increased ANF secretion
      2. Hypertension may not be solely volume expansion
    3. Increased Peripheral Vascular Resistance
      1. Hypokalemia: Potassium lost in distal renal tubule (Potassium wasting)
      2. Alkalosis: Ammoniagenesis
    4. Hydrogen Ion loss (avid Sodium retention)
    5. Polyuria: Decreased renal concentrating ability
    6. Plasma renin suppressed
      1. Unresponsive to intravascular volume depletion

IV. Causes

  1. Primary Hyperaldosteronism (Conn's Disease)
    1. Solitary Adrenal Adenomas (80-90%)
    2. Bilateral adrenal hyperplasia (10-20%)
      1. Idiopathic Hyperaldosteronism
      2. Accounts for 50% of cases at some referral centers
    3. Adrenal Carcinoma (rare)
    4. Unilateral Adrenal Hyperplasia (very rare)
  2. Secondary Hyperaldosteronism
    1. Hypertensive States
      1. Primary Reninism (rare renin producing tumor)
      2. Secondary reninism due to decreased renal perfusion
    2. Edematous States
      1. Cirrhosis
      2. Nephrotic Syndrome
    3. Miscellaneous causes
      1. Excessive Growth Hormone (Acromegaly)

V. Symptoms

  1. Often Asymptomatic
  2. Frontal Headache
  3. Muscle Weakness to Flaccid Paralysis (Hypokalemia)
  4. Polyuria and Polydipsia (Carbohydrate intolerance)

VI. Signs

  1. Hypertension
    1. May be severe
    2. Rarely malignant
  2. Motor Exam with decreased Muscle Strength

VII. Labs

  1. Serum Electrolytes
    1. Serum Potassium decreased (Hypokalemia)
      1. Hypokalemia is the most prominent feature of Hyperaldosteronism
      2. However, Potassium is normal in 50% of Hyperaldosteronism causes
    2. Serum Sodium increased (Mild)
    3. Metabolic Alkalosis
  2. Morning Aldosterone to PRA ratio
    1. Ratio over 20-25 (esp if >100) suggests Hyperaldosteronism
    2. Aldosterone >15 ng/dl and plasma renin low
      1. Serum Aldosterone alone may be normal in 25% of Hyperaldosteronism patients
    3. Technique
      1. Obtain 2 hours after waking and in upright position
      2. Stop Spironolactone, Eplerenone, Amiloride, Triamterene, Potassium-wasting Diuretics 4 weeks before test
      3. Consider stopping antihypertensives and NSAIDs before test
        1. May use Verapamil XR, Hydralazine or Alpha Adrenergic Antagonist for Blood Pressure control
  3. Saline suppression
    1. IVF: 300-500 cc/hour for 4 hours
    2. Normal response
      1. Aldosterone usually under 0.28
      2. Renin usually suppressed

VIII. Differential Diagnosis: Hypertension with Hypokalemia

  1. Cushing's Disease
    1. Low Aldosterone and Low Plasma Renin
  2. Renal Artery Stenosis or other renal cause
    1. High Aldosterone and High Plasma Renin

IX. Management

  1. Adrenal Adenoma
    1. Surgical excision
  2. Adrenal Hyperplasia
    1. First-Line Agents
      1. Spironolactone (Aldactone)
    2. Alternative agents if Gynecomastia develops on Spironolactone
      1. Eplerenone (Inspra)
      2. Amiloride (Midamor)
    3. Precautions
      1. Follow Serum Potassium and Serum Creatinine every 6 months with these agents

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Related Studies

Ontology: Hyperaldosteronism (C0020428)

Definition (NCI) Overproduction of aldosterone by the adrenal glands, which may lead to hypokalemia and/or hypernatremia.(NICHD)
Definition (MSH) A condition caused by the overproduction of ALDOSTERONE. It is characterized by sodium retention and potassium excretion with resultant HYPERTENSION and HYPOKALEMIA.
Definition (CSP) abnormality of electrolyte function caused by excessive secretion of aldosterone by the adrenal cortex.
Concepts Disease or Syndrome (T047)
MSH D006929
ICD9 255.10, 255.1
ICD10 E26 , E26.9
SnomedCT 88213004, 190506003, 154709005, 190509005, 267484005
English Aldosteronism, Hyperaldosteronism, Hyperaldosteronism, unspecified, aldosteronism, aldosteronism (diagnosis), hyperaldosteronism, Aldosteronism NOS, Hyperaldosteronism NOS, Hyperaldosteronism [Disease/Finding], Hyperaldosteronism NOS (disorder), Aldosteronism (disorder), Aldosteronism, NOS, Hyperaldosteronism, NOS
Dutch aldosteronisme NAO, aldosteronisme, Hyperaldosteronisme, niet gespecificeerd, hyperaldosteronisme, Aldosteronisme, Aldosteronisme, hyper-, Hyperaldosteronisme
French Aldostéronisme SAI, Aldostéronisme, Hyperaldostéronisme, Hyperaldostéronisme primitif
German Aldosteronismus NNB, Hyperaldosteronismus, nicht naeher bezeichnet, Aldosteronismus, Hyperaldosteronismus
Italian Aldosteronismo NAS, Aldosteronismo, Iperaldosteronismo
Portuguese Aldosteronismo NE, Hiperaldosteronismo, Aldosteronismo
Spanish Aldosteronismo NEOM, hiperaldosteronismo, SAI (trastorno), hiperaldosteronismo, SAI, aldosteronismo con hiperplasia de la corteza suprarrenal, hiperaldosteronismo (trastorno), hiperaldosteronismo, Hiperaldosteronismo, Aldosteronismo
Japanese アルドステロン症NOS, アルドステロンショウ, アルドステロンショウNOS, コウアルドステロンショウ, コン症候群, アルドステロン過剰症, アルドステロン過剰, アルドステロン症, 高アルドステロン症, Conn症候群
Swedish Hyperaldosteronism
Czech aldosteronismus, hyperaldosteronismus, Aldosteronismus, Aldosteronismus NOS, Hyperaldosteronismus
Finnish Hyperaldosteronismi
Korean 고알도스테론증, 상세불명의 고알도스테론증
Polish Aldosteronizm, Zespół Conna, Hiperaldosteronizm pierwotny, Hiperaldosteronizm
Hungarian Hyperaldosteronismus k.m.n., Hyperaldosteronismus, Hyperaldosteronizmus
Norwegian Hyperaldosteronisme, Aldosteronisme

Ontology: Conn Syndrome (C1384514)

Definition (NCI) An endocrine disorder characterized by excessive production of aldosterone by the adrenal glands. Causes include adrenal gland adenoma and adrenal gland hyperplasia. The overproduction of aldosterone results in sodium and water retention and hypokalemia. Patients present with high blood pressure, muscle weakness, and headache.
Definition (MSH) Primary hyperaldosteronism caused by the excess production of ALDOSTERONE by an ADENOMA of the ZONA GLOMERULOSA or CONN ADENOMA.
Definition (CSP) overproduction of aldosterone by an adrenal cortical adenoma, characterized typically by low potassium levels, underacidity of the body, muscular weakness, excess urination, excess thirst, and high blood pressure.
Concepts Disease or Syndrome (T047)
MSH D006929
ICD9 255.12
ICD10 E26.0 , E26.01
SnomedCT 258117004, 13536004, 154709005, 267484005, 190506003, 190507007
English Aldosteronism Primary, Conn Syndrome, primary hyperaldosteronism, primary aldosteronism (diagnosis), primary aldosteronism, Conn's syndrome (diagnosis), Idiopathic aldosteronism, Idiopathic hyperaldosteronism, Conns Syndrome, Conn's Syndrome, Syndrome, Conn's, conn syndrome, conn's syndrome, conns syndrome, Primary aldosteronism (disorder), Conn's syndrome, Conn syndrome, Primary aldosteronism, Primary hyperaldosteronism, Idiopathic aldosteronism (disorder), Primary hyperaldosteronism (disorder), hyperaldosteronism; primary, primary; hyperaldosteronism, Conn, Primary aldosteronism (disorder) [Ambiguous], Syndrome, Conn, Primary Hyperaldosteronism, Hyperaldosteronism, Primary
Italian Iperaldosteronismo primitivo, Sindrome di Conn
Dutch Conn-syndroom, hyperaldosteronisme; primair, primair; hyperaldosteronisme, Primair hyperaldosteronisme, primair hyperaldosteronisme
French Syndrome de conn, Syndrome de Conn, Hyperaldostéronisme primaire, Hyperaldostéronisme primaire à rénine basse
German Conn-Syndrom, Primaerer Hyperaldosteronismus, primaerer Hyperaldosteronismus
Portuguese Síndrome de Conn, Hiperaldesteronismo primário
Spanish Síndrome de Conn, aldosteronismo idiopático, aldosteronismo primario, hiperaldosteronismo idiopático (trastorno), hiperaldosteronismo idiopático, hiperaldosteronismo primario (concepto no activo), hiperaldosteronismo primario (trastorno), hiperaldosteronismo primario, síndrome de Conn, Hiperaldosteronismo primario
Japanese 原発性アルドステロン症, コーン症候群, コーンショウコウグン, ゲンパツセイアルドステロンショウ
Czech Primární hyperaldosteronismus, primární hyperaldosteronismus, Connův syndrom
Korean 원발성 고알도스테론증
Hungarian Conn-syndroma, Primaer hyperaldosteronismus