Hyperparathyroidism, Primary

HYPERPARATHYROIDISM, PRIMARY 71A

A 56-year-old woman presents to her primary care clinician complaining of progressive fatigue, weakness, and diffuse bony pain. She says that her symptoms have been getting worse over the past 2 months. Her medical history is notable for well-controlled hypertension and recurrent renal stones. Physical examination is unremarkable. A serum calcium level is elevated.

What are the salient features of this patient’s problem? How do you think through her problem?

Salient features: Female sex; fatigue; weakness; bone pain; renal stones; elevated serum calcium

How to think through: The diagnosis of hypercalcemia requires recognition of a constellation of common symptoms. In addition to her fatigue, weakness, diffuse bony pain, and nephrolithiasis, what other symptoms should be elicited? (Other neuromuscular or psychiatric symptoms, including depression; other renal symptoms, including polyuria; gastrointestinal symptoms, including anorexia.) Because the differential diagnosis of hypercalcemia is complex, it is useful to remember that two causes account for 90% of cases. What are these two causes? (Primary hyperparathyroidism and malignancy.) How should an elevated serum calcium level be confirmed? (Obtain a serum albumin level and correct the serum calcium value for a low albumin, if present, or obtain an ionized calcium level.) Often a serum phosphate level is available with the initial calcium value; how can this guide the differential diagnosis? (Primary hyperparathyroidism and malignancy with an elevated parathyroid hormone–related protein [PTHrP] both increase renal excretion of phosphate, leading to a low serum phosphate. Other causes of hypercalcemia generally lead to an elevated serum phosphate.) If the serum PTH level is found to be elevated in this case, what is the likelihood of malignant hypercalcemia? (Very low. Cancer leads to hypercalcemia by secretion of PTHrP or by bony metastasis; the serum PTH level is suppressed in almost all such cases. A PTH-secreting tumor is the rare exception.) What is the most likely diagnosis here, and how should this be confirmed? (Primary hyperparathyroidism is most likely. A 24-hour urinary calcium collection is needed. Low urine calcium indicates familial hypocalciuric hypercalcemia, a benign entity.) How should she be treated? (Symptomatic patients with primary hyperparathyroidism are best managed with parathyroidectomy.)