A 33-year-old woman presents to the emergency department with muscle spasms. She has noticed "twitching" in both her upper and lower extremities over the past 3 days that have interfered with her training for a marathon. She has felt more fatigued over the past month. She has no significant medical history. She takes no medication other than whey protein supplements, a multivitamin, and fish oil. Her temperature is 98.5°F (36.9°C), blood pressure is 103/71 mmHg, pulse is 105/min, respirations are 11/min, and oxygen saturation is 100% on room air. Physical exam reveals a thin woman with thinning hair. She appears pale and her mucous membranes are dry. Her neurological and cardiac exams are unremarkable. Laboratory studies are ordered as seen below. Hemoglobin: 10 g/dL Hematocrit: 30% Leukocyte count: 6,100/mm^3 with normal differential Platelet count: 187,500/mm^3 Serum: Na+: 130 mEq/L Cl-: 100 mEq/L K+: 2.3 mEq/L HCO3-: 28 mEq/L BUN: 40 mg/dL Glucose: 79 mg/dL Creatinine: 0.9 mg/dL Ca2+: 8.2 mg/dL Mg2+: 1.8 mg/dL Thyroid stimulating hormone (TSH): 4.0 mIU/L Free T4: 0.4 ng/dL (normal: 0.7-1.53 ng/dL) The patient is given 4 liters of lactated ringer solution and 40 mEq of potassium. Her repeat whole blood potassium 3 hours later is 2.4 mEq/L, and her repeat BUN is 20 mEq/L. Another 40 mEq of potassium is administered. Another repeat whole blood potassium is 2.5 mEq/L. The patient’s muscle spasms persist. Which of the following is the most likely underlying etiology for this patient’s chief concern?
Hypocalcemia
Hypothyroidism
Hyponatremia
Hypomagnesemia
Hypomagnesemia
This patient is presenting with what appears to be anorexia nervosa (thin habitus, possible excessive exercise in the setting of marathon running, thinning hair, dry mucous membranes, decreased free T4 level, and multiple electrolyte derangements). The lack of improvement in either her muscle spasms with fluid repletion or her hypokalemia with adequate repletion, even in the setting of normal serum magnesium, suggests depleted magnesium stores are the underlying etiology of her symptoms.

Hypomagnesemia typically occurs in alcoholics, malnourished patients, and patients with eating disorders such as anorexia or bulimia nervosa. Patients may present with a wide array of symptoms including weakness, confusion, dysrhythmias, hypotension, and overall malaise. Hypomagnesemia can cause hypocalcemia as magnesium is needed for proper parathyroid hormone secretion. Another pathognomonic finding associated with hypomagnesemia is hypokalemia which is refractory to repletion. The pathophysiology is thought to be due to increased potassium wasting in the kidney due to increased activity of renal outer medullary potassium (ROMK) channels. The serum magnesium level should be checked and repletion should occur accordingly. Serum magnesium levels represent 1% or less of total body magnesium stores and do not reflect if a patient truly has hypomagnesemia, particularly if there is intracellular depletion (such as in chronically malnourished patients). Thus, any patient with findings consistent with hypomagnesemia with normal serum magnesium should have their other electrolytes repleted and be given magnesium. Magnesium repletion is a safe intervention with a wide therapeutic index, and the serum level often does not correlate with total body stores.

Razzaque discusses the relationship between serum magnesium levels and total body magnesium status. The author finds that inadequate magnesium balance is associated with myriad disorders including skeletal deformities, cardiovascular diseases, and metabolic syndrome. The author recommends the use of the magnesium loading test to provide more accurate reflections of total body magnesium status.

Incorrect Answers:
Answer A: Hypocalcemia may present with perioral numbness, paresthesias, and muscle spasms. It can occur secondary to poor nutrition, vitamin D deficiency, and hypoparathyroidism. Low serum calcium may also be seen in patients with low albumin and in states of hyperventilation (which lowers the free calcium but not the total calcium due to a respiratory alkalosis that causes albumin to bind free calcium and release protons). Hypomagnesemia can also cause hypocalcemia as magnesium is needed for proper parathyroid hormone release.

Answer C: Hyponatremia may present with malaise, nausea, vomiting, headache, and confusion. Patients may also be asymptomatic in mild cases. Asymptomatic patients with hyponatremia and functioning kidneys require only fluid restriction. On the other hand, severe hyponatremia presents with very low sodium (often < 120 mEq/L) and neurological symptoms such as profound confusion or seizures. Treatment with hypertonic saline would be indicated in this situation.

Answer D: Hypothyroidism presents with fatigue, malaise, weight gain, bradycardia, scarce lanugo, and depression. This patient’s TSH is on the high end of normal and her T4 is lower than the cutoff value. However, this is likely a compensatory response to her low BMI and excessive exercise in order to slow down her metabolism to conserve energy.

Answer E: Hypovolemia was certainly present in this patient given her dry mucous membranes and prerenal pattern of labs (BUN:Cr ratio > 20:1). After receiving 4L of fluids, it is clear that dehydration is not the cause of her symptoms as her BUN corrects and her symptoms persist. In general, hypovolemia should be treated with oral rehydration, if possible.

Bullet Summary:
Hypomagnesemia can cause hypocalcemia and hypokalemia refractory to repletion (a normal serum level does not indicate normal intracellular levels of magnesium).