A 46-year-old man comes to the office due to bilateral ankle and facial swelling, especially prominent in the periorbital area. He has no shortness of breath, fever, or changes in urine color. The patient does not use tobacco, alcohol, or illicit drugs. He has no significant medical history and takes no medications. His temperature is 37.1 C (99 F), blood pressure is 130/70 mm Hg, pulse is 78/min, and respirations are 14/min. Examination shows bilateral 1+ pitting ankle edema. Auscultation shows clear lungs, normal heart sounds, and no murmurs. Dipstick urinalysis is positive for protein. A 24-hour urine collection shows proteinuria of 4.6 g/day. Laboratory results are as follows: Which of the following is the most likely cause of this patient's low serum calcium level?

Question

A 46-year-old man comes to the office due to bilateral ankle and facial swelling, especially prominent in the periorbital area.  He has no shortness of breath, fever, or changes in urine color.  The patient does not use tobacco, alcohol, or illicit drugs.  He has no significant medical history and takes no medications.  His temperature is 37.1 C (99 F), blood pressure is 130/70 mm Hg, pulse is 78/min, and respirations are 14/min.  Examination shows bilateral 1+ pitting ankle edema.  Auscultation shows clear lungs, normal heart sounds, and no murmurs.  Dipstick urinalysis is positive for protein.  A 24-hour urine collection shows proteinuria of 4.6 g/day.  Laboratory results are as follows:  Which of the following is the most likely cause of this patient's low serum calcium level?

Quizplus · Accepted Answer

Approximately 40%-45% of total blood calcium is bound to albumin and other plasma proteins, the remainder is transported in the blood as ionized calcium (40%-55%) or complexed with phosphate and other anions (5%-15%). As a result, patients with hypoalbuminemia may have a significant deficit in total blood calcium. However, the ionized plasma calcium (physiologically active form) is hormonally regulated and remains stable. Assessing the clinical significance of hypocalcemia detected in a common serum metabolic panel requires correction for the serum albumin concentration. The serum calcium concentration decreases by 0.8 mg/dL for every 1 g/dL decrease in serum albumin; the corrected calcium level can be calculated using the following formula: Corrected calcium = (measured total calcium) + 0.8 × (4.0 g/dL − serum albumin in g/dL) This patient with nephrotic syndrome (heavy proteinuria, hypoalbuminemia, edema) has a corrected calcium of 8.94 mg/dL ([7.5 mg/dL] + 0.8 × [4 g/dL − 2.2 g/dL]). The hypocalcemia is most likely due to hypoalbuminemia (from nephrotic-range proteinuria) and is not clinically significant. Direct measurement of ionized calcium is performed in many clinical laboratories, but it requires special handling and may not be readily available. (Choices A and B) Vitamin D is formed in the skin or absorbed from the intestine. It is then hydroxylated in the liver (25-hydroxylation) to produce physiologically inert 25-hydroxyvitamin D (25[OH]D). The second step (1-alpha-hydroxylation) occurs in the kidney to form the physiologically active form of vitamin D (1,25[OH]₂D), which plays an active role in calcium and phosphorus absorption from the small intestine. Patients with chronic renal failure are unable to form 1,25(OH)₂D, leading to hypocalcemia secondary to decreased intestinal absorption. However, this patient's normal creatinine level makes this unlikely. (Choice C) Hypoparathyroidism can cause hypocalcemia, and is most commonly due to autoimmune destruction of the parathyroid gland or surgery (parathyroidectomy, thyroid, or radical head/neck surgery for cancer). In addition to hypocalcemia, these patients would be expected to have decreased parathyroid hormone (PTH) levels and elevated serum phosphorus. This patient's normal serum phosphorus makes this unlikely. (Choice E) Pseudohypoparathyroidism is a rare disorder characterized by PTH resistance in target organs (kidney, bone). These patients have hypocalcemia, elevated phosphorus, and high PTH levels. Educational objective: Patients with hypoalbuminemia can have decreased total serum calcium. However, ionized calcium (physiologically active form) is hormonally regulated and remains stable. References: Interpretation of serum calcium in patients with abnormal serum proteins. (http://www.ncbi.nlm.nih.gov/pubmed/4758544)

A 46-Year-Old Man Comes to the Office Due to Bilateral