Phosphorus is involved in multiple biologic processes, including cellular energy metabolism, bone formation, and acid-base homeostasis.  Although biologically active phosphorus is largely found intracellularly, serum phosphorus levels are often reflective of available body stores and are maintained through the action of hormones (eg, parathyroid hormone, calcitriol, FGF-23) on the small intestines, bones, and kidneys.

Malnourishment (eg, due to chronic alcohol use disorder) results in the depletion of phosphate, although serum levels may remain normal due to transcellular shifts.  Reintroduction of carbohydrates (ie, dextrose-containing intravenous fluids) increases insulin secretion, which stimulates the redistribution of phosphate from the serum into muscle and hepatic cells for use during glycolysis (eg, formation of ATP, 2-3 diphosphoglycerate).  This leads to profound hypophosphatemia; lack of adequate intracellular phosphate can result in failure of cellular energy metabolism, producing the clinical features of refeeding syndrome (eg, muscular weakness, arrhythmias, congestive heart failure).

(Choice A)  Increased parathyroid hormone reduces the proximal tubular reabsorption of phosphorus.  Although hyperparathyroidism results in hypophosphatemia, this occurs over a prolonged period and would not occur acutely after infusion of dextrose-containing fluids.

(Choice B)  Although chronic diarrhea can cause hypophosphatemia, it predominantly occurs from reduced intestinal absorption of phosphorus, not increased excretion (only a small fraction of total body phosphorus is excreted into the intestines and lost in the feces).  Furthermore, this patient is not having diarrhea.

(Choice C)  Phosphorus can combine with calcium to form salts, which can be deposited in the skin or other organs (ie, dystrophic calcification).  However, this typically occurs in the setting of hyperphosphatemia (not hypophosphatemia) in end-stage renal disease.

(Choice D)  Hungry bone syndrome causes hypophosphatemia and hypocalcemia due to the rapid formation of bone after parathyroidectomy in a patient with chronic hyperparathyroidism.  However, significant hypocalcemia typically results in tetany, not diffuse weakness, and this disorder usually occurs in the early postoperative period (2-4 days).

Educational objective:
Refeeding syndrome occurs after the reintroduction of carbohydrates in patients with chronic malnourishment, which stimulates insulin secretion and drives phosphorus intracellularly in an effort to maintain cellular energy metabolism (eg, ATP production); this redistribution of phosphorus can result in severe hypophosphatemia.