Case Discussion A 35 year-old man who had been diagnosed as chronic hepatitis C with mild abnormal liver function patient and was treated with interferon at out-patient clinic. He complained of intermittent muscle weakness that was more severe in the proximal parts of the extremities one month prior to admission. The muscle weakness was heralded by muscle aches and cramping that usually occurred in the early morning, and was not precipitated by large meals or strenuous exercise; but it did resolve spontaneously. However, the attacks occurred with increased frequency in the following two weeks, with three to four episodes a day. Finally, he could not even get out of the bed and therefore he was brought to the emergency room for further treatment. On arrival, the consciousness was clear. His body height was 161 cm, body weight was 57kg. The body temperature was 37.2 oC, the blood pressure was 142/76 mmHg, and the pulse rate was 120 bpm. A complete loss of the muscle power over both thighs was found, while the arms could not resist the gravity. The muscle power distal to the thighs and the arms was intact. Fine tremors of both hands were also noted. Neither muscle wasting, goiter, ophthalmopathy, nor respiratory distress was found. There was no sensory defect or focal neurological sign. Electrocardiogram showed sinus tachycardia without flattened T wave or U wave. <Laboratory and Image Study> 1. CBC/DC & coagulation profiles: Date WBC K/£gL RBC M/£gL Hgb g/dL Hct % MCV fL Plt K/£gL During attack 8.95 4.55 12 36 92.3 489 Free of attack 8.54 4.71 12.3 36.7 92.2 423 2. Biochemistry Date BUN mg/dl Cre mg/dl Na mmol/l K mmol/l Cl mmol/l Ca mmol/l P mmol/l GOT U/l T-Bil mg/dl LDH U/l CPK mg/dl During attack 20 1.2 142 2.5 106 2.3 0.9 105 0.6 250 115 Free of attack 19 1.1 138 3.8 102 2.3 1.2 87 0.5 190 85 3. Urine analysis: Date Appearance Sp. gr pH Protein mg/dL Glu g/dL Ketones O.B Urobil EU/dL Bil During attack Y;C 1.020 6.0 ¡Ð ¡Ð ¡Ð ¡Ð 0.1 ¡Ð Free of attack Y;C 1.026 6.0 ¡Ð ¡Ð ¡Ð ¡Ð 0.1 ¡Ð Date Nitrite WBC RBC /HPF WBC /HPF EpithCell /HPF Cast /LPF Crystal Bact During attack ¡Ð ¡Ð 3-5 0-1 3-5 ¡Ð ¡Ð ¡Ð Free of attack ¡Ð ¡Ð 0-1 0 3-5 ¡Ð ¡Ð ¡Ð During attack: Arterial blood gas: PH:7.36, PaCO2: 42.3, PO2: 95, HCO3-: 22.6 Spot urinary potassium to creatinine ratio [UK/UCre (nmol/nmol)]: 3.3 Transtubular potassium concentration gradient (TTKG): 2.6 Thyroid function test: TSH < 0.1 £gIU/mL, free T4: 20.84 ng/dl <Course and Treatment> At Emergency department, serum and spot urine potassium, creatinine and osmolality were all checked as well as thyroid function test. Intravenous KCL supplement, oral propanolol 10 mg 1# tid and carbimazole 10 mg bid were prescribed since the blood tests revealed hypokalemia and hyperthyroidism. He was transferred to general ward under the impression of thyrotoxic periodic paralysis later. However, symptoms of persistent tachycardia and frequent episodes of muscle weakness persisted even after potassium supplement and oral ƒÒ-blockers administration. Muscle power recovered gradually hours later. Both anti-microsomal antibody (AMA) and TSH receptor antibody (TSHr Ab) were significantly elevated. The thyroid ultrasonography showed a hypoechoic heterogeneous pattern, which suggested autoimmune thyroid disease and a 99mTc-pertechnetate thyroid scan also revealed the diffuse enlargement of the thyroid gland with an increased rate of tracer uptake (5.28%; normal range 0.4-2.4 %). These findings were all compatible with typical Graves¡¦ disease. The patient was treated with carbimazole 10 mg bid and higher dose of propranolol (40 mg tid). The frequency of the attacks declined gradually, and he was discharged with a diagnosis of interferon-induced TPP. The post-treatment course was smooth without recurrence. <Analysis> The Patient was diagnosed as hypokalemia and hyperthyroidism. He denied history of binge drinking or heavy meal prior to these attacks. There were also no gastrointestinal symptoms such as vomiting and diarrhea. Besides, he also denied the use of diuretics or laxatives. The spot urinary UK/UCre was 3.3 and the TTKG was 2.6, which rendered renal or gastrointestinal potassium wasting less likely. Thyrotoxic periodic paralysis was the final diagnosis that was proved by thyroid function test, immunological exams and imaging studies. Thyrotoxic periodic paralysis (TPP) is manifested as recurrent episodes of hypokalemia and muscle weakness which lasts from hours to days. It is most common in adults aged 20-40 years. The incidence of the disorder is relatively higher among Asians, especially in male. Hyperinsulinemia, a carbohydrate or salt load, and exercise are important in precipitating paralytic attacks. It is one of clinical periodic paralysis diseases. Periodic paralysis is a group of genetic diseases including hypokalemic or hyperkalemic type. Both forms may be inherited or occur without a family history. If inherited, they often occur in an autosomal dominant fashion. The periodic paralysis has been associated with thyrotoxicosis from various etiologies. The pathogenesis of TPP is uncertain, but there is evidence for a decrease in the activity of the calcium pump, whereas hyperkalemic periodic paralysis is related to sodium channel. It involves attacks of muscle weakness or paralysis alternating with periods of normal muscle function. Attacks usually begin after symptoms of hyperthyroidism have developed. The frequency of attacks varies from daily to yearly. Episodes of muscle weakness may last for a few hours or may persist for several days. Serum potassium level decreases, but not necessarily below normal, during attacks. Patients experience urinary retention with elevated urine levels of sodium, potassium, and chloride. A concomitant decrease in serum phosphorous level also occurs. Creatine phosphokinase (CPK) level rises during attacks.Potassium will remain normal between attacks and the total body potassium is not decreased. Weakness most commonly affects the proximal muscle group of the arms and legs. The muscles associated with respiration can sometimes be affected and this can be fatal. Arrhythmias can also occur. Although muscle strength is initially normal between attacks, repeated attacks may eventually cause progressive and persistent muscle weakness. Risk factors include a family history of periodic paralysis and hyperthyroidism. The best treatment is a rapid reduction in thyroid hormone levels and £]-blocker. Potassium should also be given during the attack. Oral potassium supplement is preferred, but if the weakness persisted, intravenous potassium may be necessary with caution. For patients with hypokalemic periodic paralysis, administering potassium may stop an attack. However, taking regular doses of potassium will not prevent future attacks. Diet with low carbohydrates and salt may be recommended to prevent attacks. Acetazolamide, a medication that is effective in attack prevention with familial periodic paralysis, is usually not effective with thyrotoxic periodic paralysis. <Reference> 1. J Emerg Med. 2005 Feb;28(2):201-9 2. J Emerg Med. 2004 Feb;26(2):157-61 3. Thyroid. 2002 Jan;12(1):77-80. 4. Arch Intern Med 2004, 164, (14), 1561-6 5. Mayo Clin Proc. 2005 Jan;80(1):99-105. 6. Harrison¡¦s principles of internal medicine 15 edition Ä~Äò±Ð¨|¦ÒÃD 1. (D) ·|³y¦¨periodic paralysisªº±¡§Î¦p¤U¡A¦óªÌ¬°¥¿½T¡H A Hyperkalemia B Hypokalemia C Hyperthyroidism D All of above 2. (B) ¦b¿ò¶Ç©Êªºperiodic paralysis¯f±w¤¤¡A³Ì±`¨£ªº¿ò¶Ç¤è¦¡¬°¦ó¡H A Autosomal recessive B Autosomal dominant C X-linked dominant D X-linked recessive 3. (E) ¤Þ°_hypokalemic periodic paralysisªº­ì¦]¥]¬A¡H A High-carbohydrate meal B High-salt meal C Vigorous exercise D Thyrotoxicosis E All of above 4. (A) Thyrotoxic (hypokalemic) periodic paralysis³Q»{¬°¬O¨º¤@ºØÂ÷¤l³q¹D²§±`¡H A Ca (calcium) channel B Na (sodium) channel C K (potassium) channel D Cl (chloride) channel 5. (B) Hyperkalemic periodic paralysis³Q»{¬°¬O¨º¤@ºØÂ÷¤l³q¹D²§±`¡H A Ca (calcium) channel B Na (sodium) channel C K (potassium) channel D Cl (chloride) channel 6. (A) ¦óªÌ¤£¬Othyrotoxic periodic paralysisªºÁ{§Éªí²{¡H A Weakness in muscle of both hands and feet B Hypokalemia during attack C Tachycardia D Potential arrhythmia 7. (E) Thyrotoxic periodic paralysis®É¥i¯à¨£¨ìªº¹êÅç«Çªí²{¡H A Hypokalemia B Mild elevated CPK C Low TTKG D Hypophosphatemia E All of above 8. (D) ¦óªÌ¬Othyrotoxic periodic paralysisªºªvÀø¡H A Anti-thyroid agent B £]-blocker C Potassium supplement D All of above 9. (B) ¦óªÌ¤£¬Oµo¥Íthyrotoxic periodic paralysisªº°ª¦MÀI¸s? A Asian male B Asian female C Family history of hyperthyroidism D All of above 10. (A) ¹w¨¾thyrotoxic (hypokalemic) periodic paralysisªº¤èªk¤£¥]¬A¡H A Oral potassium B £]-blocker C Low carbohydrate diet D Anti-thyroid agent µª®×¸Ñ»¡ (D ) Periodic paralysis is a group of diseases including hypokalemic or hyperkalemic periodic paralysis. TPP is one of the hypokalemic periodic paralysis. (B ) Hypokalemic or hyperkalemic periodic paralysis may be inherited or occur without a family history. If inherited, they often occur in an autosomal dominant fashion. (E ) Hyperinsulinemia, a carbohydrate or salt load, and exercise are important in precipitating paralytic attacks. (A ) The pathogenesis of TPP is uncertain, but there is evidence for a decrease in the activity of the calcium pump, whereas hyperkalemic periodic paralysis is related to sodium channel. (B ) ¦P¤W (A ) Weakness most commonly affects the proximal muscle group of the arms and legs. Arrhythmias can also occur. (E ) Serum potassium level decreases during attacks. A concomitant decrease in serum phosphorous level also occurs. Creatine phosphokinase (CPK) level rises during attacks. Since potassium shifts into cell, so TTKG is low. (D ) Anti-thyroid agent, oral or IV £]-blocker and even potassium supplement are important in treatment of TPP (B ) The incidence of the disorder is relatively higher among Asians, especially in male. Risk factors include a family history of periodic paralysis and hyperthyroidism. (A ) Regular doses of potassium will not prevent future attacks. Diet with low carbohydrates and salt may be recommended to prevent attacks.