A 29-year-old woman comes to the office for evaluation of hypercalcemia. Her serum calcium was 12.1 mg/dL on routine laboratory investigations performed for a life insurance application. The patient feels well and has had no excessive urination, bone pain, abdominal pain, headache, or constipation. Medical history is significant for upper gastrointestinal hemorrhage a year ago; the bleed was due to a large gastric ulcer, for which she is currently taking an oral proton pump inhibitor. She has a 10-pack-year smoking history but does not use alcohol or illicit drugs. The patient's menstrual cycles are regular; she has never been pregnant, is sexually active with one partner, and uses barrier contraception to prevent pregnancy. The patient's mother underwent parathyroid surgery for symptomatic hypercalcemia and takes a pill twice a week for an unspecified pituitary tumor. Blood pressure is 128/80 mm Hg and pulse is 78/min. BMI is 27 kg/m². Neck examination is unremarkable. A few small subcutaneous lipomas are present on the patient's back. The rest of her physical examination is unremarkable. Laboratory results are as follows: Bone mineral density by DXA is normal. Which of the following is the best next step in management of this patient?

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Explanation: 11ec2b69_bed4_5748_8f63_07fe740fabff_MD0005_00 This patient has significant hypercalcemia with an elevated parathyroid hormone level consistent with primary hyperparathyroidism. In light of her young age, history of gastric ulcer, and family history of parathyroid and pituitary disease, this constellation of clinical features is highly suggestive of multiple endocrine neoplasia type 1 (MEN1). MEN1 is characterized by the "3 Ps": parathyroid adenomas or hyperplasia, pancreatic and gastrointestinal neuroendocrine tumors (eg, gastrinoma/Zollinger-Ellison syndrome), and pituitary adenomas (eg, prolactinoma). Additional findings (eg, multiple cutaneous lipomas) may also occur. Indications for parathyroidectomy in patients with MEN1, similar to those for sporadic primary hyperparathyroidism, include symptomatic hypercalcemia (or calcium >1 mg/dL above normal), end-organ complications (eg, osteoporosis, chronic kidney disease, nephrolithiasis), and increased risk for complications (eg, urinary calcium excretion >400 mg/day). Patients age <50 are likely to develop complications later in life and should also undergo parathyroidectomy; as patients with MEN1 typically present at a relatively young age, most should be offered surgery. Patients with MEN1 usually have multiple parathyroid adenomas and, therefore, require subtotal (>3½ glands) or total parathyroidectomy with autotransplant into a muscle pocket. (Choices B, C, and D) Calcitonin and metanephrine assays are used to screen for medullary thyroid cancer and pheochromocytoma, respectively. However, these tumors are components of MEN2, not MEN1, so testing is not required. MEN2 (Choice E) Zollinger-Ellison syndrome is characterized by an elevated serum gastrin level. However, gastrin can also be elevated due to hypercalcemia or use of proton pump inhibitors. Measurement of gastrin levels should be deferred until the patient is normocalcemic and has discontinued acid-reducing therapy for at least 2 weeks. Educational objective: Multiple endocrine neoplasia type 1 is composed of parathyroid adenomas or hyperplasia (primary hyperparathyroidism), pancreatic and gastrointestinal neuroendocrine tumors, and pituitary adenomas: the 3 Ps. Multiple parathyroid glands are usually involved; parathyroidectomy with autotransplant is necessary. References: Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). (http://www.ncbi.nlm.nih.gov/pubmed/22723327)

A 29-Year-Old Woman Comes to the Office for Evaluation of Hypercalcemia