A 40-year-old African American man arrived at the emergency room experiencing profound muscle weakness. Past medical history revealed sporadic muscle tightness occurring 1-3 times per week, alleviated by consuming bananas. He was not using any medications, and his family history was noteworthy for hyperthyroidism and episodes of hypokalemia in his brother and mother.
Upon presentation, vital signs were temperature 98.4°F, blood pressure 127/83 mmHg, heart rate 111 beats/minute, respiratory rate 11 breaths/ minute, and oxygen saturation 96% on room air. Physical examination revealed pronounced weakness in both upper and lower extremities (strength assessed at 0/5) with areflexia.
Laboratory results are shown in Table 1. The electrocardiogram demonstrated sinus tachycardia with prolonged QTc interval of 606 ms. Swift replacement of hypokalemia effectively alleviated his symptoms, albeit leading to transient hyperkalemia that spontaneously resolved.
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Tests |
Results |
Normal range |
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Sodium |
139 mmol/L |
132-148 mmol/L |
|
Potassium |
<1.5 mmol/L |
3.5-5 mmol/L |
|
Chloride |
105 mmol/L |
98-111 mmol/L |
|
Bicarbonate |
21 mmol/L |
23-32 mmol/L |
|
Blood Urea Nitrogen |
18 mg/dL |
10-25 mg/dL |
|
Creatinine |
0.91 mg/dL |
0.7-1.4 mg/dL |
|
Calcium |
9.3 mg/dL |
8.4-10.5 mg/dL |
|
Albumin |
3.9 g/dL |
3.5-5.0 g/dL |
|
Total protein |
7.2 g/dL |
6.6-8.7 g/dL |
|
Glucose |
90 mg/dL |
65-100 mg/dL |
|
Magnesium |
1.9 mg/dL |
1.6-2.6 mg/dL |
|
Phosphorus |
2.1 mg/dL |
2.5-4.5 mg/dL |
|
AST |
64 U/L |
5-40 U/L |
|
ALT |
153 U/L |
5-41 |
|
Bilirubin- total |
0.3 mg/dL |
0.2-1.2 mg/dL |
|
Alkaline phosphatase |
79 U/L |
40-129 U/L |
|
Random urine K/Cr ratio |
10.7 mmol/g Cr |
17-121 mmol/g Cr |
|
TSH |
< 0.006 mcIU/mL |
0.270-4.200 mcIU/mL |
|
Free T3 |
13.0 pg/mL |
2.1-4.4 pg/mL |
|
Free T4 |
3.04 ng/dL |
0.9-1.70 ng/dL |
|
Thyroid Stimulating Ig (TSI) |
3.43 IU/L |
<=0.54 IU/L |
|
Thyroid Peroxidase Ab |
62.6 IU/mL |
0.0-9.0 IU/mL |
The correct answer, link to published case and explanation will be provided in the comment section.
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The correct answer is explained below:
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The correct answer is: hypokalemic periodic paralysis.
Periodic paralysis (PP) is a rare channelopathy marked by recurrent episodes of flaccid skeletal muscle paralysis. Hypokalemic periodic paralysis (HypoPP) is categorized into familial or acquired forms. Triggers for episodes of HypoPP are primarily associated with intense exercise and high carbohydrate intake, and less frequently related to viral infections, stress, cold, salt consumption, and medications (such as glucocorticoids and insulin).
Familial HypoPP is associated with variants in the skeletal muscle sodium channel gene SCN4A in 20% of patients or the L-type calcium channel gene CACNA1S in 60% of patients. The majority of reported pathogenic variants involve arginine residues in S4 transmembrane segments, with notable hotspots at codons R528 and R1239. Generally, the existence of hyperthyroidism is more strongly associated with a diagnosis of acquired thyrotoxic periodic paralysis (TPP), with most cases occurring in Asian males without a family history of the condition. Pathogenic variants in KCNJ2 and KCNJ18 are associated with susceptibility to TPP. KCNJ2 and KCNJ18 encode Kir 2.1 and Kir2.6 respectively, inwardly rectifying potassium channels expressed in skeletal muscle and transcriptionally regulated by thyroid hormone.
Genetic testing in the discussed patient revealed a heterozygous pathogenic variant in CACNA1S [c.1583 G>A (p. R528H)] and normal sequencing of SCN4A, KCNJ2 and KCNJ18. The patient received a diagnosis of familial hypokalemic periodic paralysis and concurrent hyperthyroidism due to Graves’ disease. The likelihood of TPP in this case is reduced, given the patient is not of Asian descent, has a family history of HypoPP, and lacks identifiable variants in KCNJ2 and KCNJ18. The pathogenic variant observed in this case has been documented previously. This variant leads to a substantial reduction in the whole-cell calcium channel current and induces depolarization of the resting cell potential in response to hypokalemia.
Management of acute paralytic episodes involves maintaining proper control of serum potassium levels, necessitating vigilant monitoring for post-treatment hyperkalemia. Lifestyle and dietary modifications to avoid triggering factors are integral to treatment. Although the precise mechanism is not fully elucidated, carbonic anhydrase inhibitors have demonstrated efficacy in reducing the frequency of familiar HypoPP episodes. There is variability in the response to carbonic anhydrase inhibitors based on genotype; individuals with CACNA1S variants tend to exhibit a more favorable response compared to SCN4A variants. Additionally, the incorporation of a potassium-sparing diuretic, either in conjunction with carbonic anhydrase inhibitors or as a standalone treatment, may offer advantages for specific patients.
Read more in the published article: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03749-x
Read more in the published article: https://bmcnephrol.biomedcentral.com/articles/10.1186/s12882-024-03749-x