Case Presentation: A 54-year-old man with a history of alcoholic cirrhosis presented to the emergency department for evaluation of a new facial rash and was found to be hypercalcemic to 15.6 mg/dL. A subsequent ionized calcium and cystatin C were also found to be elevated at 1.90 mMol/L and 2.55 mg/L (eGFR 23), respectively. His review of systems was negative with no nausea, vomiting, muscle weakness, or increased urinary frequency. The rash was non-pruritic and not painful. His only complaint was the cosmetic appearance of the rash on his face and neck. He noted 2-3 months of over-the-counter vitamin A replacement at three times the previously prescribed dose. He was prescribed 10,000 units/day but was taking 9,000 mcg/day as he thought this was the equivalent dose; 10,000 units of vitamin A is comparable to 3,000 mcg. The workup for hypercalcemia was notable for appropriately low PTH at 10 pg/mL. normal vitamin D 25-Hydroxy at 36 ng/mL, low vitamin D 1,2-dihydroxy at 17.8 pg/mL and elevated PTHrP at 5.3 pmol/L. Vitamin A level of retinyl palmitate was elevated at 0.38 mg/L (normal is 0-0.10 mg/L) and retinol was normal at 0.83 mg/L. TSH, SPEP and immunofixation results were normal. CT of the chest, abdomen and pelvis was obtained to evaluate for malignancy given the elevated PTHrP and did not reveal focal findings. He was otherwise up-to-date with age-appropriate cancer screening. The patient was started on 200 mL/hr of normal saline and diuretics were held. He received one dose of calcitonin on day 2; bisphosphonates were avoided given renal dysfunction. Dermatology clinically diagnosed the rash as seborrheic dermatitis and commented on increased skin sensitivity due to vitamin A toxicity. His hypercalcemia improved with IV fluids, and he was discharged after nine days once his calcium had normalized.
Discussion: Though hypercalcemia is a common finding, vitamin A toxicity is a rare cause. The mechanism is due to its role in bone metabolism via osteoclast activation and decreased osteoblast formation. Vitamin A deficiency is frequently seen in patients with chronic liver disease; this patient was inadvertently taking three times the usual dose. Nutraceutical preparations can include two forms, retinyl palmitate and retinol. The latter is more potent, while retinyl palmitate is more commonly available over the counter. In this case, the patient’s retinyl palmitate level was likely elevated secondary to vitamin A supplementation with retinyl palmitate. He had hypercalcemia with appropriately low PTH and a negative workup for other causes, including malignancy. His elevated PTHrP was likely due to decreased clearance from acute renal injury. Hypercalcemia of malignancy does not typically improve with supportive care alone. These findings, along with an elevated retinyl palmitate and improvement with conservative management, favors a diagnosis of vitamin A-mediated hypercalcemia.
Conclusions: Hypercalcemia is a common finding but can have an uncommon etiology. Considering a broad differential is important in high risk patients such as those with cirrhosis who are typically advised to take supplemental vitamin A.