This issue highlights Pediatric Endocrine Self-Assessment Program. Test your clinical knowledge and prepare for your exam. Available on the online store.
You are asked to evaluate an 18-year-old girl because of concerns about hypocalcemia. At her recent precollege physical she described a several month history of fatigue and intermittent right upper-quadrant pain.
Laboratory test results:
- Calcium = 7.8 mg/dL (8.5-10.5 mg/dL) (SI: 2.0 mmol/L [2.1-2.6 mmol/L])
- AST = 1480 U/L (10-40 U/L) (SI: 24.7 µkat/L [0.2-0.7 µkat/L])
- Albumin = 2.5 g/L (3.5-5.5 g/L) (SI: 25 g/L [35-55 g/L])
- PTH = 20 pg/mL (16-87 pg/mL) (SI: 20 ng/L [16-87 ng/L])
- Total 25-hydroxyvitamin D = 16 ng/mL (20-80 ng/mL) (SI: 39.9 nmol/L [49.9-199.7 nmol/L])
Her medical history is notable for systemic lupus erythematosus, which has been well controlled with methotrexate.
On physical examination, she is a fatigued-appearing teenager with mild scleral icterus.
Which of the following medications is most likely to correct this patient’s laboratory abnormalities?
- Immunosuppressant therapy
- Calcium and calcitriol
This patient’s presentation with liver failure in the setting of known autoimmune disease is most likely consistent with autoimmune hepatitis. Impaired liver function results in decreased production of albumin, which is the major protein bound to calcium in the circulation. Serum calcium exists in 3 primary forms: 40% bound to albumin, 15% bound to organic and inorganic anions, and 45% circulating as metabolically active, free ionized calcium. Because calcium has a key role in multiple biologic processes, levels of ionized calcium are tightly regulated within a narrow range. When protein levels fluctuate, the percentage of unbound calcium is therefore adjusted to maintain normal ionized calcium levels in the circulation.
Serum calcium levels measured by most laboratories reflect both bound and ionized calcium levels. In patients with hypoalbuminemia, this results in a phenomenon called “pseudohypocalcemia,” in which total serum calcium levels are low while ionized calcium levels are normal. In patients with abnormal albumin levels, measurement of ionized calcium levels is a more accurate method of assessing calcium metabolism. Additionally, the following equation may be used to correct calcium in cases of hypoalbuminemia or hyperalbuminemia:
Corrected (calcium) = Measured total (calcium) + (0.8 x [4 – (albumin)])
Because this patient’s low calcium levels reflect her hypoalbuminemia, giving additional calcium with or without calcitriol (Answers A and E) is unlikely to substantially increase her total calcium levels. Her 25-hydroxyvitamin D levels are mildly low, which is common in patients with cholestatic disorders due to chronic malabsorption of fat-soluble vitamins. In addition, and similar to the phenomenon of “pseudohypocalcemia,” decreased production of albumin and other carrier proteins leads to a reduction in serum vitamin D levels, while bioavailable vitamin D remains unaffected. Thus, prescribing cholecalciferol (Answer B) is incorrect. This patient’s PTH levels are appropriate given her normal levels of biologically active serum calcium; therefore, administration of additional PTH (Answer D) is not indicated. Treating her underlying autoimmune disease with steroids (Answer C) or other immunosuppressant medications is the best strategy to improve her liver function and restore her albumin levels.
Explain why the total serum calcium concentration is often low in the setting of hypoalbuminemia despite a normal ionized calcium level.
Peacock M. Calcium metabolism in health and disease. Clin J Am Soc Nephrol. 2010;5(Suppl 1):S23-S30. PMID: 20089499