Name
HYPOKALEMIC PERIODIC PARALYSIS
DESCRIPTION
DETAIL
CAUSES • Exact pathogenesis unknown • Abnormality is in the muscle membrane • Hypokalemia due to intracellular shift of potassium • Total body potassium is normal (i.e., hypokalemia is not due to potassium loss) • Muscle fi bers chronically depolarized by 10-15 mV, but membrane conductance normal between attacks • Several mutations in either calcium (type 1 FHPP) or sodium (type 2 FHPP) channel have been identified (alpha-1 subunit of ion channel protein) • Both calcium and sodium channel mutations show incomplete phenotypic penetrance in females • Very rare form of FHPP due to potassium channel mutation recently reported • Cation channel mutations may induce FHPP by changing behavior or expression of other ion channels in muscle • Contractile apparatus normal • Pathogenesis of FHPP and THPP may be different since thyroid hormone doesn’t worsen FHPP and patients with THPP lack the ion channel gene mutations seen in FHPP • Acetazolamide may precipitate attacks in patients with type 2 FHPP caused by sodium channel mutation -------------------------------------------------------------------------- DIFFERENTIAL DIAGNOSIS • Akinetic epilepsy • Andersen’s syndrome (episodic paralysis, ventricular dysthymias, and dysmorphic features) • Barium poisoning • Cataplexy • Drop attacks • Episodic ataxia • Guillain-Barré syndrome • Hyperkalemic periodic paralysis (adynamia episodica) • Hyperventilation • Myasthenia gravis • Myotonia congenita • Normokalemic periodic paralysis • Paramyotonia congenita • Presyncope • Secondary hypokalemia (laxative or diuretic use, diarrhea, vomiting, renal or adrenal disease, clay ingestion) • Sleep paralysis • Tick paralysisLABORATORY • Hallmark is low serum K+ (as low as 1.3 mEq/L [1.3 mmol/L]) • Low serum phosphorous and low serum magnesium also found • Urine K+ normal or low • Elevated T3, T4, free thyroid index, and decreased TSH (THPP only) • Serum CK level normal or slightly increased • Acid-base balance normal • Urine potassium/creatinine ratio low (<2) • Increased urinary calcium (THPP only) SPECIAL TESTS • With mild hypokalemia electrocardiogram (ECG) may show S-T depression, fl attened T waves, presence of U waves • With severe hypokalemia ECG may show peaked P waves, prolonged P-R interval, widened QRS • With hyperthyroidism (THPP), ECG may show sinus tachycardia, 1st degree AV block, or left ventricular hypertrophy (LVH) • Electromyography rarely helpful unless done during or immediately after an attack (usually normal between attacks) • Genetic testing (DNA sequencing) to differentiate type 1 FHPP from type 2 FHPP (calcium vs sodium channel mutations) IMAGING Thyroid scans using radioiodine (THPP only) DIAGNOSTIC PROCEDURES Provocative testing (50 to 100 g oral glucose with 2 to 4 g oral sodium followed by exercise, or 50 to 100 g oral glucose with 10-20 IU subcutaneous insulin) may be required. Patient should have cardiac monitoring during testing.
TYPENOTES
RISK FACTORS: Male, Age under 35, Family history (FHPP), Asian (THPP), Genetic counseling (FHPP) as there is a 50% risk of transmitting abnormal gene to offspring and a .50% chance of affected siblingsAPPROPRIATE HEALTH CARE • Severe hypokalemia or weakness - inpatient with cardiac monitoring • Mild hypokalemia or weakness - outpatient with close follow up GENERAL MEASURES May rarely need respiratory support ACTIVITY As tolerated DIET • Avoid high carbohydrate, high sodium foods • K+ rich fruit of dubious benefit DRUG(S) OF CHOICE . Acute attack . Oral potassium chloride, 0.2 to 0.4 mEq/kg (0.2-0.4 mmol/kg), repeated every 15 to 30 min depending on response of ECG, serum K+, muscle strength (usual dose: 40 mEq [40 mmol]) . In life-threatening situation or if vomiting give intravenous KCl in mannitol. 5% glucose or normal saline IV may worsen situation. Bolus 0.1 mEq/kg (0.1 mmol/kg) every 5 to 10 min; monitor ECG, serum K+. (Usual dose: 15 mEq [15 mmol] over 15 minutes then 10 mEq/hr [10 mmol/hr] if peripheral IV, up to 60 mEq/hr [60 mmol/hr] if central IV and cardiac monitoring.) . IV propranolol (THPP only) . Prevention of attacks in FHPP . Oral KCl . Acetazolamide (Diamox), 125 to 1,000 mg/d divided qd to bid (type 1 FHPP only) . Prevention of attacks in THPP . Treat underlying thyrotoxicosis with beta-adrenergic blocking agents [propranolol (Inderal) and others] . Acetazolamide contraindicated Precautions: • Infusion of IV KCl must be monitored to avoid inadvertent infusion of large and potentially fatal doses • Peripheral intravenous KCl infusion rates greater than 10 mEq/h (10 mmol/h) may be painful and increase the risk of rebound hyperkalemia • Rebound hyperkalemia may occur in patients who receive more than 90 mEq KCl in 24 hours and in patients with THPP who receive KCl and propranolol • Acetazolamide - drowsiness or paresthesias at high doses. May precipitate or worsen paralysis in patients with type 2 FHPP. • Propranolol - impaired hepatic or renal function ALTERNATIVE DRUGS . Acute attack . None . Prevention of attacks in FHPP . Triamterene (Dyrenium) 25 to 100 mg/d . Spironolactone (Aldactone) 25 to 100 mg/d . Prevention of attacks in THPP . Propylthiouracil, radioactive ablation of the thyroid PATIENT MONITORING • Follow serum K+, electrolytes (if on acetazolamide) • Follow thyroid function tests (if on propranolol or propylthiouracil) POSSIBLE COMPLICATIONS Cardiac arrhythmias, respiratory collapse EXPECTED COURSE/PROGNOSIS • Frequency of attacks usually lessens with age • After years of prolonged, frequent attacks patient may develop persistent proximal weakness
RELATED DISEASE
Not Available Disease
DISEASE
INVESTIGATION
SERUM POTASSIUM, SERUM MAGNESIUM, COMPLETE BLOOD COUNT, ECG, SERUM PHOSPHORUS, THYROID SCAN, THYROID PROFILE