Prepare for your USMLE Step 2 CK with a question focusing on hypokalemia in adults. Can you formulate and prioritize a differential diagnosis for a patient presenting with hypokalemia, and identify the additional tests needed to confirm your diagnoses? Enhance your clinical reasoning skills with this important assessment.
A 26-year-old man presents to the emergency department for evaluation of sudden-onset weakness that started two hours ago. The patient has experienced two similar episodes that each resolved within one hour. However, today, the patient was unable to get out of bed and continued to be weak for 2 1/2 hours, prompting the patient to call an ambulance. The patient has experienced about six months of heat intolerance, palpitations, anxiety, and weight loss. On physical examination, the patient is noted to be thin and diaphoretic. The patient is alert and oriented and appears anxious. The patient’s skin is warm to the touch, and the patient has thinning hair. There is flaccid paralysis of the lower extremities as well as decreased strength in the proximal arms. Distal arm strength is normal without fatigability. Reflexes are diminished throughout. Laboratory studies are notable for a serum potassium of 2.1 mEq/L. Which of the following laboratory results would be consistent with the underlying diagnosis?
A. Low TSH and high T4
B. Low magnesium
C. Elevated urine potassium-to-creatinine ratio
D. Positive acetylcholine receptor antibodies
E. Elevated creatine kinase
Scroll down for the correct answer!
The correct answer to today’s USMLE® Step 2 CK Question is…
A. Low TSH and high T4
Before we get to the Main Explanation, let’s see why the answer wasn’t B, C, D, or E. Skip to the bottom if you want to see the correct answer right away!
Incorrect answer explanations
Today’s incorrect answers are…
B. Low magnesium
Incorrect: Hypomagnesemia can cause hypokalemia. However, severe hypomagnesemia is typically associated with seizures, tetany, and hyperreflexia. This patient is not exhibiting these but has evidence of thyrotoxicosis.
C. Elevated urine potassium-to-creatinine ratio
Incorrect: An elevated urine potassium-to-creatinine ratio would be seen in renal potassium wasting syndromes. This patient’s signs and symptoms are more concerning for thyrotoxic periodic paralysis.
D. Positive acetylcholine receptor antibodies
Incorrect: Anti-acetylcholine receptor antibodies are seen with myasthenia gravis, which can also cause proximal limb weakness. However, this patient did not demonstrate typical muscle fatigability during the examination.
E. Elevated creatine kinase
Incorrect: Rhabdomyolysis can result in muscle weakness but more commonly results in muscle pain. Additionally, it is more often associated with hyperkalemia rather than hypokalemia.
Main Explanation
This patient is experiencing leg paralysis and proximal arm weakness in association with severe hypokalemia. Additionally, the patient has had several months of symptoms consistent with hyperthyroidism (e.g. heat intolerance, palpitations, weight loss). The patient has evidence of muscle weakness and thyrotoxicosis on examination. Thus, thyrotoxic periodic paralysis is the most likely diagnosis. This would be associated with a low TSH and elevated T4.
There are many potential causes of hypokalemia. Often, this can be elicited from the history and presentation (e.g., decreased potassium intake, recent GI illness, diuretic use). If the cause is not obvious, additional workup can be obtained. This should start with obtaining a serum magnesium level to rule out hypomagnesemia. From there, patients should be evaluated for potential causes of transcellular potassium shifts. This should include reviewing medications (e.g., theophylline, beta-agonists, insulin) and evaluating for conditions like hyperthyroidism, which may be accompanied by symptoms (e.g., heat intolerance, palpitations) and a low TSH.
Periodic paralysis (PP) is a muscle disease where patients experience episodes of muscle weakness that can last from hours to days. When patients are also hypokalemic during these episodes of muscle weakness and are found to have symptoms and evidence of thyrotoxicosis, then thyrotoxic periodic paralysis can be diagnosed.
If these causes are ruled out, the next step is to obtain urine studies in order to calculate a urine potassium-to-creatinine ratio. If this ratio is ≤ 1.5, extrarenal potassium wasting is most etiology, which can be caused by laxative overuse, other causes of severe diarrhea, or excessive sweating. If the ratio is > 1.5, then a condition causing renal potassium wasting is likely. In patients with hypertension or evidence of hypervolemia, consider diseases affecting mineralocorticoid activity, such as Cushing syndrome, hyperaldosteronism, and congenital adrenal hyperplasia. If no cause is found, the next step is to check the patient’s acid-base status. Metabolic acidosis is associated with renal tubular acidosis and acetazolamide use. Metabolic alkalosis is associated with Bartter and Gitelman syndrome as well as diuretics.
Major takeaway
When evaluating a patient with hypokalemia, consider additional workup based on the history and physical examination. Thyroid studies should be performed in patients where no cause can be identified and in patients with symptoms suggestive of hyperthyroidism (e.g. heat intolerance, palpitations, weight loss).
References
- Lulsegged, A., Wlodek, C., and Rossi, M. (2011). Thyrotoxic periodic paralysis: Case reports and an up-to-date review of the literature. Case Reports in Endocrinology. https://www.hindawi.com/journals/crie/2011/867475/
- Idham, M., and Prajitno, J.H. (2022). Management of hypokalemia in patients with thyrotoxicosis periodic paralysis in Soetomo general hospital: A case report. Annals of Medicine and Surgery, 84. https://www.sciencedirect.com/science/article/pii/S2049080122016855
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