A 56-year-old man complains of increased thirst and increased urinary volume and frequency. He has also noticed new symptoms of constipation and generalized aches and pains. He has no significant past medical problems and his physical examination is normal. Initial investigations consist of a normal complete blood count (CBC) fasting blood glucose and urinalysis. His sodium, urea, and creatinine are normal, but calcium is 12.4 mg/dL (8.4-10.2 mg/dL). Further testing reveals an elevated PTH level. Which of the following is the most likely mechanism for the polyuria in this condition?
This man has primary hyperparathyroidism. Hypercalcemia induces a tubular concentrating defect by interfering with ADH-mediated water pore function (aquaporin-2 channel) on distal tubular cells. This results in the polyuria and polydipsia symptoms of diabetes insipidus. Chronic hypercalcemia can also cause renal stones, type 1 (distal) RTA and chronic renal failure but these effects are not directly responsible for the polyuria. PTH has no direct effect on the concentrating ability of the distal tubule.
direct effect of PTH on the kidney
hypercalcemia-induced renal tubular acidosis (RTA)
hypercalcemia-induced chronic renal failure
hypercalcemia-induced defect in renal concentrating ability (nephrogenic diabetes insipidus)
Endocrinology