Familial periodic paralysis

CASE PRESENTATIONS OF THE BROWN UNIVERSITY DEPARTMENT OF MEDICINE

Case 1

CHIEF COMPLAINT: Leg weakness

HISTORY OF PRESENT ILLNESS:

A 20-year-old Laotian man with no significant medical history presented after awaking in the middle of the night with profound weakness of his lower extremities. He was unable to bear weight and also noted a milder degree of upper extremity weakness. He had no back pain or sensory changes, nor had he noted any change in bowel or bladder function. On the night prior to admission he reported having a mild frontal headache and an episode of vomiting. He had played soccer the day prior to admission without any difficulty. On further review of his history, the patient recalled a similar episode that occurred approximately one month prior, during which he experienced similar transient lower extremity weakness that resolved spontaneously after 12 hours. He sought evaluation in the Rhode Island Hospital emergency department.

REVIEW OF SYMPTOMS:

The patient reported having episodic palpitations, frequent sweats, and tremulousness for many years. He denied diarrhea, fevers, chills, seizures, arthralgias, and myalgias.

PAST MEDICAL HISTORY: Negative.

MEDICATIONS: No prescription or over-the-counter medications, no supplements or herbal remedies.

ALLERGIES: No known drug allergies.

SOCIAL HISTORY: Lives with his family. Student, part-time maintenance worker. No smoking, alcohol consumption, or drug use.

FAMILY HISTORY: Father with a heart murmur.

PHYSICAI, EXAM IN THE ED

Vital Signs: Temp: 98.1F HR: 111 BP: 137/65 RR: 16 SaO2 98% RA

General: Asian male, thin, no apparent distress.

HEENT: PERRE, EOMl, sclerae anicteric, oropharynx clear.

Neck: Supple. Thyroid diffusely enlarged, nontender.

Cardiovascular: Tachycardie with a regular rhythm. II/VI blowing systolic ejection murmur loudest at left upper sternal border.

Lungs: Clear to auscultation bilaterally.

Abdomen: Normal bowel sounds, soft, nontender, nondistended.

Extremities: No edema or cyanosis. Muscles nontender to palpation.

Neurologic: Alert and oriented. Speech clear, coherent, and fluent. Cranial nerves II-XII intact. Upper extremities displayed a fine tremor with proximal 3/5 strength and distal 4/5 strength. Lower extremities with proximal and distal 2/5 strength with inability to lift legs off the bed. Sensory exam intact. Unable to elicit patellar or Achilles reflexes, biceps and brachioradialis reflexes were 1 +. Toes down-going bilaterally.

LABS:

CBC: WBC count: 10,000 per mL

Hemoglobin: 1 5.4 g/dL

Hematocrit: 46.4%

Platelet cont: 282,000 per mL

WBC Differential: 85% segmented neutrophils, 13% lymphocytes, 1% monocytes, 1% eosinophils

Chem 7:

Sodium: 141 mmol/L

Potassium: 1.6 mmol/L

Chloride: 109 mmol/L

Bicarbonate: 24 mmol/L

BUN: 15mg/dL

Creatinine: 0.7 mg/dL

Glucose: 138 mg/dL

Chemistry:

Calcium: 9.4 mg/dL

Magnesium: 1.3 mg/dL

Phosphorus: 1.7 mg/dL CPK 675 IU/L

Troponin I:

Chest radiography: Negative

Computed tomography of the brain: Negative

Electrocardiogram: Sinus tachycardia, possible left ventricular hypertrophy with associated ST-T changes, also a question of anterolateral T wave abnormalities.

EMERGENCY DEPARTMENT COURSE: Potassium repletion was begun in the emergency department with a 60 mEq PO dose and a 10 mEq IV dose.

HOSPITAL COURSE:

The patient was admitted to the medical step-down unit secondary to his severe electrolyte abnormalities. Potassium repletion was continued, and magnesium was also repleted. Immediate laboratory evaluation for thyroid disease revealed a thyroidstimulating hormone (TSH)

The thyroid uptake and scan revealed 87% uptake in a homogenous pattern consistent with Graves disease. Methimazole therapy was instituted and propranolol was continued. An echocardiogram was performed to evaluate for left ventricular hypertrophy. The study was normal with the exception of mild RV dilation. The patients weakness quicldy resolved with normalization of his potassium level and he was discharged on hospital day 3.

Case 2

CHIEF COMPLAINT: "My strength is gone."

HISTORY OF PRESENT ILLNESS:

A 30-year-old African American male reported a 2-year history of hyperthyroidism. He was in his usual state of health until approximately 10 days prior to admission. At that time, he noted increasing anxiety, irritability, heat intolerance, palpitations, diarrhea, and intermittent blurry vision. He presented to an outside hospital with an episode of severe generalized weakness and was found to have a serum potassium level of 1.8 mmol/L. The weakness resolved with potassium repletion and he was discharged after a brief stay.

A week after discharge, the patient was seen by his primary care physician. The patient complained of persistent mild weakness and intermittent leg cramps. Serum potassium level was 4.7 mmol/L. That night, he awoke with the urge to urinate, but had extreme difficulty lifting his arms and legs. He could not get out of bed without assistance, and subsequently sought evaluation in the Miriam Hospital emergency department.

REVIEW OF SYMPTOMS: The patient reported a 30-pound weight loss over a 2-year period. No chest pain or shortness of breath. No melena or bright red blood per rectum.

PAST MEDICAL HISTORY: Graves disease confirmed by 24-hour thyroid uptake and scan 1 month prior to admission (58.5%, which may have been an underestimate given recent use of propylthiouracil). Had been scheduled for thyroid ablation treatment, but did not keep appointment. Hypertension.

MEDICATIONS: Atenolol 50 mg daily. Erratic use of propylthiouracil.

ALLERGIES: No known drug allergies.

SOCIAL HISTORY: Quit smoking 1 month prior. Denies alcohol, occasional marijuana. Lives with mother, receives disability benefits.

FAMILY HISTORY: Parents alive, father with diabetes. Siblings healthy, no thyroid disease.

PHYSICAL EXAM IN THE ED

Vital Signs: Temp: 36.8 C HR: 121 BP: 167/90 RR: 18 SaO2:99%RA

General: Anxious-appearing, diaphoretic young adult male in mild distress.

HEENT: Mild exophthalmos

Neck: Thyroid symmetrically enlarged, nontender, positive bruit.

CVS: Tachycardie, no murmur, rub, or gallop.

Lungs: Clear to auscultation bilaterally.

Abdomen: Positive bowel sounds, soft, nontender, nondistended. Occult blood negative.

Extremities: No cyanosis, clubbing, or edema.

Neurologic: Strength 4/5 upper and lower extremities bilaterally, deep tendon reflexes 3+ with swift relaxation phase, otherwise nonfocal.

LABS:

CBC: WBC count: 4,500 per mL

Hematocrit: 39.4%

Platelet count: 273,000 per mL

WBC differential: 63% segmented neutrophils, 1% bands, 30% lymphocytes, 6% monocytes

Chem 7:

Sodium: 139 mmol/L

Potassium: 2.4 mmol/L

Chloride: 104 mmol/L

Bicarbonate: 26 mmol/L

BUN: 15 mg/dL

Creatinine: 0.6 mg/dL

Glucose: 225 mg/dL

Chemistry:

Calcium: 9.2 mg/dL

Magnesium: 1.4 mg/dL

CPK: 110 IU/L

Thyroid function studies:

3rd generation TSH: 0.084 uU/mL

Free T^sub 3^: >2000 pg/dL

Free T^sub 4^: 7.63 ng/dL

Hemoglobin A^sub 1^C: 6.3%

Electrocardiogram: Sinus tachycardia, rate 125.

Abdominal computed tomography: No adrenal masses.

EMERGENCY DEPARTMENT COURSE: Potassium repletion was begun in the emergency department, with 40 mEq PO and 40 mEq IV.

He also received labetalol 10 mg IV and 1 liter normal saline IV.

HOSPITAL COURSE:

The patient was admitted to the medical service for monitoring, repletion of electrolytes, and management of hyperthyroidism. Endocrine and Renal consultation were obtained. He was started on propranolol, propylthiouracil, and intravenous hydrocortisone for his hyperthyroidism. His weakness improved significantly with postassium repletion, but waxed and waned, possibly in association with administration of a sliding-scale insulin regimen.

He was discharged to home on hospital day 8 with weakness resolved and symptoms of hyperthyroidism controlled.

DIAGNOSIS: Thyrotoxic hypokalemic periodic paralysis

DISCUSSION

What is the association between thyrotoxicosis and hypokalemic periodic paralysis?

Hypokalemic periodic paralysis is an uncommon disorder characterized by sudden shifts of potassium into the intracellular compartment. It is most commonly described in young Asian or Hispanic males, as in case 1, but is not exclusive to those groups. Physicians in Asia and Latin America are well-acquainted with the diagnosis, but physicians in the United States frequently miss it.

Clinically, it is characterized by episodic weakness affecting proximal muscles more so than distal ones; bulbar and respiratory muscles are much less commonly involved, although respiratory failure has been described. Cardiac arrhythmias can occur and may be fatal. Some patients experience a prodrome of muscle pain or cramping. Not surprisingly, creatine phosphokinase levels may be elevated.

Episodes are likely triggered by increased secretion of epinephrine or insulin. They frequently occur after a period of rest after exercise or at night - hence the names "night paralysis" and "night palsy" - and can also be elicited by carbohydrate or sodium loading. Serum potassium levels return to normal between episodes.

The disorder has both inherited and acquired forms. The familial form is inherited in an autosomal dominant pattern, although with incomplete penetrance. A mutation in voltage-sensitive calcium channels in skeletal muscle appears to be involved but is not well understood.

Thyrotoxic periodic paralysis is clinically indistinguishable from the familial form. The hypokalemia appears to be related to the hyperadrenergic state and an exaggerated insulin response, with increased activity of Na-K-ATPase at skeletal muscle ion channels. Asian males with hyperthyroidism appear to be at particular risk, with as many as 10% exhibiting symptoms of periodic paralysis. Hyperthyroidism may not be clinically apparent, consequently thyroid function studies should be considered in any patient presenting with episodic weakness.

What is the management ofthyrotoxic periodic paralysis?

Oral potassium repletion has long been the mainstay of treatment for acute episodes of both forms of hypokalemic periodic paralysis. Weakness typically resolves quickly. Potassium should be given cautiously, especially in patients with impaired renal function, as rebound hyperkalemia may occur as potassium shifts extracellularly. It is important to remember that patients with periodic paralysis are not total body potassium depleted.

Phosphate and magnesium levels may also be low, but typically return to normal with normalization of potassium levels. Nonselective beta-adrenergic blockers can help prevent further attacks by attenuating potassium shifts; they are also effective in acute episodes and avoid the risk of rebound hyperkalemia. Correction of the underlying thyroid disorder and reestablishment of the euthyroid state is the definitive treatment.

REFERENCES

Brown RH, Mendell JR. Muscular dystrophies and other muscle diseases. In: Braunwald G, et al. Harrison's Principles of Internal Medicine 15th ed. New York, NY: McGraw-Hill; 2001:2540.

Lin SH, Lin YF. Propranolol rapidly reverses paralysis, hypokalemia, and hypophosphatemia in thyrotoxic periodic paralysis. Am J Kidney Dis 2001;37:620.

Manoukian MA, Foote JA, Crapo LM. Clinical and metabolic features of thyrotoxic periodic paralysis in 24 episodes. Arch Intern Medl 999; 159:601.

ACKNOWLEDGEMENT: Papa Kaku Badoe, MD; Elisa Freeman, MD; Olga Lurye, MD; Michael Maher, MD; Ian Wu, MD

MARY H. HOHENHAUS, MD, AND RANDALL S. PELLISH, MD

CORRESPONDENCE:

Mary Hohenhaus, MD

Phone: (401) 444-4000

e-mail: MHohenhaus@litespan.org

Copyright Rhode Island Medical Society Jan 2005
Provided by ProQuest Information and Learning Company. All rights Reserved