Authors: Hannah Howse, MD (EM Resident Physician, Mizzou – Columbia, MO); Jessica Pelletier, DO, MHPE (Assistant Professor of EM/Assistant Residency Director, Mizzou – Columbia, MO) // Reviewed by: Sophia Görgens, MD (EM Physician, BIDMC, MA); Cassandra Mackey, MD (Assistant Professor of Emergency Medicine, UMass Chan Medical School); Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)
A 28-year-old otherwise healthy male presents for an acute episode of bilateral lower extremity weakness causing him to fall in the bathroom. The episode started approximately 30 minutes prior to arrival. He had a similar episode three months prior which resolved quickly during his ED visit.
Initial vital signs:
HR: 107
BP: 165/91
O2: 97% on room air
Temp: 37.1 C
Physical exam:
General: sitting comfortably in a wheelchair
HEENT: normocephalic, mild proptosis bilaterally, pupils equal and reactive bilaterally, EOMI intact
Cardiac: Tachycardia, no murmurs/rubs/gallops, adequate peripheral perfusion, no edema, 2+ pulses in all extremities
Pulmonary: normal inspiratory effort, lungs clear bilaterally to auscultation, no wheezes
Abdomen: soft, nontender to palpation in all 4 quadrants
Neuro: sensation intact in all distributions to light touch. Hip flexion ⅖ bilaterally, knee extension ⅗ bilaterally, plantar and dorsiflexion ⅘. Bilateral upper extremities shoulder flexion, elbow flexion, and extension 5/5.
MSK: no rashes or lesions appreciated.
Lab results:
CBC: unremarkable
CMP:
Potassium: 2.0 mEq/L
Magnesium: 1.33 mg/dL
Phosphorus: 0.9 mg/dL
TSH: <0.008 mIU/L
Free Thyroxine: 5.1 ng/dL
Question: What is the diagnosis?
Answer: Thyrotoxic periodic paralysis
Background:
- Periodic paralysis encompasses a group of disorders most commonly manifested in teenagers and young adults.
- This group of disorders includes: hypokalemic paralysis with associated thyrotoxicosis, hyperkalemic paralysis, and normokalemic paralysis.1
- Hypokalemic paralysis can further be divided into primary and secondary causes:
- Primary cause: genetic calcium channelopathy.
- Secondary cause:
- Renal tubular acidosis.
- Hyperthyroid periodic paralysis.
- Hypokalemia secondary to GI losses (diarrhea).
- Hyperkalemic Paralysis:
- Autosomal dominant sodium channel mutation.
- Normokalemic paralysis
- Both sporadic and inherited cases
- Incidence of 0.001%2
- Episodes are characterized by periodic, rapidly resolving, paralysis lasting between 15 minutes and 1 hour.
- Number of attacks vary significantly between patients.
- Proximal muscle groups are most commonly involved.3
- Hypokalemic paralysis can further be divided into primary and secondary causes:
Etiology:
- Primary hypokalemic periodic paralysis: autosomal dominant mutation in voltage-gated calcium channel (CACNA1S gene).4
- Episodes often triggered by rest after intensive exercise, stress, and high carbohydrate meals.
- Secondary hypokalemic periodic paralysis:4
- Thyrotoxic periodic paralysis: Loss of function mutation of the skeletal muscle-specific inward rectifying K channel (KIR2.6).
- Renal tubular acidosis and GI losses: secondarily cause hypokalemia and resultant periodic paralysis.
- Hyperkalemic Periodic Paralysis: autosomal dominant mutation in sodium channel (SCN4A gene).5
Epidemiology:
Hypokalemic Paralysis:1
- Prevalence: 1 in 100,000 individuals worldwide.
- Men are most commonly affected (3:1 male-to-female ratio).
- More prevalent in Asian populations.
Thyrotoxic Periodic Paralysis:5
- Prevalence is estimated to be < 1 in 100,000 individuals worldwide.
- May have a higher prevalence among populations with higher rates of hyperthyroidism.
- Most commonly affects young men between the ages of 20-40.
- Male to female ratio is estimated to be 7:1.
Hyperkalemic Paralysis:6
- Prevalence of 1 in 100,000 individuals.
- First episode typically occurs between ages 10-20.
- Male-to-female ratio is estimated to be 2:1.
Clinical Presentation:
All variants:6
- Young patients, typically in 2nd or 3rd decade of life, with acute onset, episodic paralysis.
- Most commonly affects proximal muscles greater than distal.
- Quickly resolves with normalization of electrolyte abnormalities.
- May present with symptoms related to thyroid abnormalities.
- Hypothyroidism:
- Cold intolerance.
- Fatigue.
- Weakness.
- Hyperthyroidism:
- Heat intolerance.
- Anxiety.
- Palpitations.
- Hypothyroidism:
Evaluation:
- Detailed neurologic exam and family history including reflexes, detailed spine exam to evaluate for spinal tenderness, nuchal rigidity, sensation, and muscle strength in proximal and distal muscles.
- Reflexes may or may not be impacted, literature shows cases with hyperreflexia related to hyperthyroidism, normal reflexes, or hyporeflexia.
- ECG, and telemetry to monitor cardiac changes in the setting of electrolyte abnormalities and possible fatal cardiac arrhythmias.
- CBC, CMP, TSH, phosphorus, and magnesium to help evaluate for other causes of weakness including additional electrolyte abnormalities, concomitant thyroid disease, leukocytosis in the setting of possible infection, anemia causing weakness.
- Potassium levels can further aid in the treatment and diagnosis.
Diagnosis:
- Consider diagnosis in young patients presenting with episodic, bilateral acute paralysis without other obvious cause.
- Long-term: will need follow-up with endocrinology and neurology for EMG to rule out any other causes of paralysis.7
Treatment:
- Hypokalemia is not due to total body potassium depletion, but rather due to an intracellular shift of potassium
- Consider endocrinology consultation in the ED for hyperthyroidism treatment recommendations including propranolol, methimazole, and propylthiouracil (PTU).9
- Consider ICU if related to thyrotoxicosis as these patients require monitoring for cardiac arrhythmias.
Prognosis:
- Acute episodes of paralysis typically resolve with electrolyte correction; however, long term, patients are very likely to have recurrent attacks that decrease with increasing age
- Recommend avoiding triggers10
- Triggers for periodic episodes include:11
- Alcohol
- Carbohydrate heavy meals
- Emotional stress
- Extreme weather
- Fasting
- Heavy exercise
- High salt intake
- Medications causing hypokalemia
- Pregnancy
- Steroids
- Patients often experience:12
- Fatigue
- Myalgias
- Generalized Weakness
Pearls and Pitfalls:
- Periodic paralyses are a rare set of disorders related to genetic mutations, thyroid derangements, or potassium derangements that cause temporary paralysis (proximal > distal).
- Classically presents in young patients.
- Episodes triggered by stressors.
- Treatment involves thoughtful correction of potassium and thyroid hormone abnormalities – therefore most patients will require admission.
A 32-year-old man presents to the ED with an acute onset of profound lower extremity weakness that began this morning after a high-carbohydrate meal the previous night. He reports no trauma, back pain, or sensory deficits. His vital signs show an HR of 110 bpm, BP of 135/80 mm Hg, RR of 16/min, and T of 37.2°C. Physical exam reveals symmetric flaccid paralysis of the lower extremities with hyporeflexia, and an ECG shows U waves and a prolonged QT interval. What is the most appropriate next step in care?
A) Administer calcium gluconate for presumed hypocalcemia
B) Administer potassium gluconate and obtain thyroid function tests
C) Initiate high-dose corticosteroids for suspected myasthenia gravis
D) Perform a lumbar puncture to evaluate for Guillain-Barré syndrome
E) Perform urgent MRI of the spine to rule out cord compression
Correct answer: B
This patient presents with classic features of thyrotoxic periodic paralysis (TPP), a rare but serious complication of hyperthyroidismcharacterized by acute, reversible episodes of muscle weakness due to hypokalemia. The history of a high-carbohydrate meal, which can precipitate TPP by driving potassium intracellularly via insulin release, combined with symmetric flaccid paralysis, hyporeflexia, and ECG findings (U waves, prolonged QT interval) suggestive of hypokalemia, strongly supports this diagnosis. Administration of potassium gluconate will reverse the paralysis and prevent life-threatening dysrhythmias, while thyroid function tests (e.g., TSH, free T4) are essential to confirm underlying hyperthyroidism, most commonly due to Graves disease in TPP.
TPP predominantly affects young male patients (20–40 years) and seems to be most prevalent in East Asian populations. Risk factors include male sex (20:1 male-to-female ratio), hyperthyroidism (often undiagnosed), and triggers such as high-carbohydrate intake, exercise, or stress, which shift potassium into cells. Signs and symptoms include sudden-onset muscle weakness (typically proximal and lower extremity), hyporeflexia, and sparing of sensory and cranial nerve function. Hypokalemia (serum potassium often < 3.0 mEq/L) is a hallmark, though total body potassium is normal, reflecting intracellular redistribution rather than actual depletion. Diagnosis relies on clinical presentation, hypokalemia, and evidence of hyperthyroidism (suppressed TSH, elevated free T4).
In the ED, TPP is treated by focusing on correcting hypokalemia and stabilizing the patient while addressing the underlying hyperthyroidism. Intravenous potassium chloride (e.g., 10–20 mEq/hour with cardiac monitoring) rapidly reverses paralysis, but caution is needed to avoid rebound hyperkalemia as potassium shifts back extracellularly during recovery. Instead, a recommended treatment approach is slow, incremental potassium repletion if possible (unless the potassium is severely low). Nonselective beta-blockers (e.g., propranolol) can stabilize cardiac effects and reduce thyroid hormone effects acutely, while definitive treatment of hyperthyroidism (antithyroid drugs, e.g., methimazole) can be initiated after consultation with endocrinology. Patients require close monitoring for dysrhythmias or respiratory failure, though respiratory involvement is rare. Education on avoiding triggers (e.g., high-carbohydrate meals) is also key during discharge planning.
Calcium gluconate (A) is used for hypocalcemia, which may cause tetany, seizures, or ECG changes (prolonged QT due to ST segment lengthening), but not U waves or flaccid paralysis. This patient’s presentation and ECG findings align with hypokalemia, not hypocalcemia, making calcium administration inappropriate and potentially harmful.
Myasthenia gravis (C) typically causes fatigable weakness, often involving ocular or bulbar muscles, and is not associated with hypokalemia or ECG changes like U waves. This patient’s symmetric flaccid paralysis and metabolic trigger (carbohydrate meal) are inconsistent with myasthenia. Corticosteroids are not indicated for TPP and could worsen hyperthyroid effects.
Guillain-Barré syndrome (GBS) (D) presents with ascending weakness, often postinfection, with areflexia and potential sensory deficits or albuminocytologic dissociation on cerebrospinal fluid analysis. However, this patient’s acute onset after a carbohydrate load, lack of sensory symptoms, and ECG findings consistent with hypokalemia point to TPP rather than GBS. Lumbar puncture is unnecessary and delays critical potassium repletion.
Spinal cord compression (E) typically causes sensory deficits, hyperreflexia below the lesion, and bowel and bladder dysfunction, none of which are present here. The metabolic trigger, hyporeflexia, and ECG abnormalities suggest TPP, not a structural lesion. Imaging would delay treatment and is not indicated based on this clinical picture.
