What is the primary cause of hyperthyroid hypokalemic periodic paralysis?

Primary Cause of Hyperthyroid Hypokalemic Periodic Paralysis

Hyperthyroid hypokalemic periodic paralysis (THPP) is primarily caused by a massive shift of potassium into cells triggered by elevated thyroid hormone levels, which leads to acute muscle weakness or paralysis. 1

Pathophysiology

• THPP occurs when excessive thyroid hormone causes an intracellular shift of potassium, resulting in hypokalemia and subsequent muscle weakness or paralysis 1
• This potassium shift is mediated by increased sensitivity to beta-adrenergic stimulation and elevated levels of insulin and catecholamines in the blood 2
• The condition represents a rare complication of hyperthyroidism that is more common in Asian and male patients, but can occur in any population 3

Clinical Presentation

• Acute onset of flaccid muscle weakness or paralysis, typically affecting the extremities 3
• Episodes may be recurrent or isolated 3
• Many patients may have subtle or no obvious symptoms of hyperthyroidism, making diagnosis challenging 1
• Attacks are often triggered by:
  • High carbohydrate meals (which stimulate insulin release) 4
  • Strenuous exercise 1
  • Stress 1

Laboratory Findings

• Hypokalemia (low serum potassium) is the hallmark finding, though normokalemic variants have been reported 5
• Low TSH and elevated free T4/T3 confirming hyperthyroidism 3
• Other possible findings include:
  • Hypophosphatemia with hypophosphaturia 1
  • Hypercalciuria 1
  • Normal acid-base status despite electrolyte abnormalities 1
  • Low urinary potassium excretion (indicating intracellular shift rather than renal loss) 1

Diagnostic Clues

• Presentation in adult males with no family history of periodic paralysis 1
• Cardiovascular signs such as systolic hypertension and tachycardia 1
• ECG findings including high QRS voltage and first-degree atrioventricular block 1
• Low-amplitude electrical compound muscle action potential on electromyography 1

Treatment Approach

Acute Management

• Potassium chloride supplementation to correct hypokalemia and restore muscle strength 1
  • Caution is needed as rebound hyperkalemia may occur when potassium shifts back from intracellular to extracellular compartments 1
• Non-selective beta-blockers (such as propranolol) can be an effective alternative by blocking the adrenergic-mediated potassium shift 1

Long-term Management

• Definitive treatment of the underlying hyperthyroidism is essential and completely abolishes attacks 1, 5
• Anti-thyroid medications such as propylthiouracil or methimazole 4
• Radioactive iodine or surgery may be considered for definitive management of hyperthyroidism 1

Clinical Pitfalls

• THPP may be misdiagnosed as Guillain-Barré syndrome, hysterical paralysis, or other neurological disorders when thyroid function is not evaluated 5
• Some patients present with normokalemic periodic paralysis associated with hyperthyroidism, which can further complicate diagnosis 5
• Failure to recognize THPP may lead to improper management and delay in treating this curable condition 1
• Overly aggressive potassium replacement can lead to dangerous rebound hyperkalemia as the paralysis resolves 1