A 62-year-old woman presents to the emergency department with a 3-week history of worsening fatigue, constipation, frequent urination, and increased thirst. Past medical history is unremarkable, and she does not take any medications. She does not drink alcohol, smoke cigarettes, or use illicit drugs. Vital signs show that she is afebrile with a pulse rate of 114 beats/minute and a blood pressure reading of 146/82 mmHg. Physical examination reveals that she appears lethargic and has dry mucous membranes. Cardiac examination reveals tachycardia with a regular rhythm. Laboratory tests indicate a normal blood glucose, serum calcium level of 14.6 mg/dL, a phosphorus level of 2.5 mg/dL, and a parathyroid hormone level of 784 pg/mL.
Which of the following conditions most likely accounts for this patient’s polyuria and dehydration?
E) Nephrogenic diabetes insipidus
Nephrogenic diabetes insipidus (DI) can be caused by primary hyperparathyroidism. Primary hyperparathyroidism causes hypercalcemia and low phosphate levels due to abnormal, increased secretion of parathyroid hormone (PTH). The most common cause of primary hyperparathyroidism is parathyroid adenoma, though parathyroid hyperplasia and carcinoma are also possible causes. Common symptoms of primary hyperparathyroidism arise from the resulting hypercalcemia and may include recurrent kidney stones, bone pain from bone resorption, frequent urination, dehydration, constipation, and mood changes. Excessive urination and fluid loss are secondary to the direct effects of elevated calcium levels on the kidneys, leading to renal resistance and a lack of response to antidiuretic hormone (ADH), which is called nephrogenic diabetes insipidus. The lack of response to ADH leads to insufficient aquaporin expression in the renal collecting tubules, resulting in an increased urine output, presenting clinically as frequent urination and dehydration.
Answer choice A: Allergic interstitial nephritis, is incorrect. Allergic interstitial nephritis leads to pyuria (mainly eosinophils) and azotemia, often associated with the use of certain classes of drugs like diuretics, penicillins, proton pump inhibitors, nonsteroidal anti-inflammatory drugs, and sulfonamides.
Answer choice B: Central diabetes insipidus, is incorrect. Central diabetes insipidus causes increased urination and dehydration due to inadequate production of ADH from a brain injury or lesion.
Answer choice C: Chronic pyelonephritis, is incorrect. Chronic pyelonephritis can be seen in patients with a history of acute pyelonephritis, particularly those with risk factors like kidney stones or vesicoureteral reflux.
Answer choice D: Glycosuria, is incorrect. Glycosuria involves glucose in the urine, typically in patients with high blood sugar levels due to diabetes mellitus. This patient has a normal blood glucose.
Key Learning Point
Nephrogenic diabetes insipidus can result from hypercalcemia, commonly due to primary hyperparathyroidism, where elevated calcium impairs the kidney's response to antidiuretic hormone (ADH), leading to polyuria and dehydration despite adequate ADH levels.
