The Case

A 24-year-old man with no past medical or surgical history presented to the emergency department with 5 days of progressively worsening bilateral leg cramping, paresthesias, and multiple falls. The following ECG is obtained:

EKG

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EKG Characteristics

  • Rate

    88

  • Rhythm

    Sinus Rhythm with PAC's

  • Intervals

    Normal PR and QRS interval, Prolonged QTc interval (619 ms)

  • Axis

    Normal

  • ST Segments

    Normal

  • Additional Features

    Diffuse, prominent, prolonged T-waves

Diagnosis

Diagnosis: Hypokalemia secondary to Thyrotoxicosis/Thyrotoxic Periodic Paralysis

Background on Thyrotoxic Periodic Paralysis:

  • This entity is relatively uncommon in the U.S. and tends to occur in men of Asian descent.
  • Clinically presents with episodic muscle weakness (generally more pronounced proximally and in the lower extremities), tachycardia, SVT, or atrial fibrillation.
  • Hypokalemia is the cause of muscle weakness and is thought to be caused by the Na+/K+-ATPase shifting K+ intracellularly in the hyperthyroid, hyperadrenergic state.
    • Thyroid hormone itself can increase the amount of Na+/K+-ATPase genes transcribed, leading to an increase in number of pumps on the surface of skeletal muscle cells.
    • Thyroid hormone also increases the Na+/K+-ATPase’s intrinsic activity while also stimulating beta-2 receptors leading to increased sensitivity to catecholamines.
    • Additionally, some TPP patients have underlying gene mutations preventing outward flow of potassium out of skeletal muscle cells.
  • Hypokalemia is secondary to an underlying hyperthyroid pathology and thus treatment is driven by treating the underlying hyperthyroid state. Potassium should be replenished aggressively, particularly when EKG abnormalities are present.  However, patients are at risk for rebound hyperkalemia as you simultaneously treat the underlying hyperthyroid state and should be monitored closely.
  • EKG findings can be an early clue to hypokalemia in someone presenting with weakness.  Findings include:
    • PR prolongation
    • QTc prolongation
    • Presence of U waves
    • Non-specific ST-depression

Questions

  1. What is your differential diagnosis for this EKG?

    Hypokalemia, hypocalcemia, hypomagnesemia, hypothermia, increased ICP, congenital Long QT syndrome, QT prolonging medications

Discussion

Case Discussion:

A 24-year-old man with no past medical or surgical history presented to the emergency department with 5 days of progressively worsening bilateral leg cramping, paresthesias, and multiple falls. He also noted palpitations with walking and a feeling of twitching in his thighs while at rest. The remainder of his review of systems was negative.

Initial vitals were obtained: T 36.8 C HR 147 BP 124/76 RR 16 SpO2 98% on RA

His physical exam was notable for 4/5 weakness in his bilateral upper extremities, 3/5 weakness in his bilateral lower extremities, and sluggish reflexes in all extremities. He was not able to ambulate without two-person assistance. The remainder of his exam was normal.

The patient was noted to have a K+ of 2.3, an undetectable TSH, a T3 of 4.59, and a T4 of 2.56. His hyperthyroidism was managed aggressively with the following:

  1. Aggressive intravenous fluid resuscitation and potassium replenishment.
  2. Methimazole (a thionamide) which blocks thyroid hormone synthesis.
  3. Lugol’s Solution (Iodine and Potassium Iodide in Water) which blocks the release of prestored thyroid hormone and iodine transport. This must be given at least 1 hour after thionamide as it may lead to a paradoxical increase in thyroid hormone synthesis (the Jod-Basedow phenomenon).
  4. Propranolol (a beta-adrenergic blocker) which decreases adrenergic tone and treats tachycardia but also prevents peripheral conversion of T4 to T3.
  5. Hydrocortisone (a glucocorticoid) which decreases peripheral conversion of T4 to T3.
    • The patient was admitted to the Medical ICU for aggressive electrolyte replacement, q2h BMPs, and due to concern for decompensation as signaled by his elevated troponin.
    • After anti-thyroid therapy was initiated and his potassium was replenished safely, he was diagnosed with Grave’s Disease.
    • The patient’s weakness quickly resolved after potassium normalization.

Pearls

  • When encountering interval abnormalities on EKG, always consider acute electrolyte abnormalities.
  • Classically, hypokalemia can be identified with PR prolongation, QTc prolongation, non-specific ST-segment depressions, and large U waves.
  • Consider hyperthyroidism as an etiology of severe hypokalemia.

Sources

  1. Chan A, Shinde R, Chow CC, Cockram CS, Swaminathan R. In vivo and in vitro sodium pump activity in subjects with thyrotoxic periodic paralysis. BMJ. 1991 Nov 02;303(6810):1096-9.
  2. Chaudhury S, Ismail-Beigi F, Gick GG, Levenson R, Edelman IS. Effect of thyroid hormone on the abundance of Na,K-adenosine triphosphatase alpha-subunit messenger ribonucleic acid. Mol Endocrinol. 1987 Jan;1(1):83-9.
  3. Farkas, Josh. The Internet Book of Critical Care. https://emcrit.org/ibcc/tstorm/
  4. Goldberger, Zachary. An Electrocardiogram Triad in Thyrotoxic Hypokalemic Periodic Paralysis. Circulation. 2007.  https://www.ahajournals.org/doi/full/10.1161/CIRCULATIONAHA.106.652396#FIG1181225
  5. Idrose AM. Acute and emergency care for thyrotoxicosis and thyroid storm. Acute Med Surg. 2015 May 12;2(3):147-157. doi: 10.1002/ams2.104. PMID: 29123713; PMCID: PMC5667251.
  6. Kung AW. Thyrotoxic periodic paralysis: a diagnostic challenge. Journal of Clinical Endocrinology and Metabolism. 2006; 91: 2490–2495.
  7. Lin SH. Thyrotoxic periodic paralysis. Mayo Clinic Proceedings. 2005; 80: 99–105.
  8. Siddamreddy S, Dandu VH. Thyrotoxic Periodic Paralysis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.  https://www.ncbi.nlm.nih.gov/books/NBK560670/