Hyperparathyroidism in Emergency Medicine Workup

• Elevated parathyroid hormone (PTH) levels in the setting of hypercalcemia establish the diagnosis of hyperparathyroidism. The most common other cause of hypercalcemia in older individuals, hypercalcemia of malignancy, is associated with suppressed PTH levels.
• Although measuring the concentration of ionized calcium rather than the total calcium concentration provides added accuracy, one may alternatively use the total serum calcium concentration corrected for the patient's albumin concentration. This can be achieved by adding 0.8 per dL to the total serum calcium value for every 1 g/dL below a serum albumin concentration of 4 g/dL. Those with secondary hyperparathyroidism and associated chronic renal failure are especially prone to hypoalbuminemia, thus, this correction is of particular importance.
• The normal range for the PTH-intact assay is generally 10-65 pg/mL.
• A decreased serum phosphate level of less than 2.5 mg/dL (0.81 mmol/L) may be seen.
• Increased bone turnover may be reflected in elevated levels of markers of bone formation (alkaline phosphatase) and bone resorption (urinary pyridinoline), though these tests are not likely of diagnostic value.
• Urinary calcium excretion may be elevated.
• A newly introduced immunoradiometric assay for PTH detects only the fully intact molecule and, as such, may be more accurate than the most commonly used assay that measures truncated, nonfunctional molecules along with the full-length molecule. This may be of benefit in cases of diagnostic uncertainty.^[14]
• Expedited determination of PTH levels in the intraoperative setting with rapid laboratory assays has been used during parathyroid excisions. Because of the short half-life of PTH (< 5 min), intraoperative measurement is recommended by the National Academy of Clinical Biochemistry Guidelines.^[15] The commercially available rapid PTH assay provides an accurate PTH level that can be used intraoperatively to determine quantitatively when all hyperfunctioning parathyroid tissue has been excised. A decrease in the PTH concentration of more than 50% from the baseline level 5-10 minutes after excision of all suspected hyperfunctioning parathyroid tissue suggests the absence of any residual hyperfunctioning tissue.
• The advent of intraoperative PTH testing has reduced the postoperative failure rate of initial parathyroidectomy surgery from 6% to 1.5%^[16] and has decreased the need for performing frozen sections.^[17]

Positive imaging studies are not useful for the confirmation of a diagnosis of primary hyperparathyroidism. Moreover, negative imaging study results do not exclude the diagnosis of primary hyperthyroidism. All imaging parathyroid imaging studies demonstrate both false-positive and false-negative findings that can be misleading. Therefore, all patients being evaluated for preoperative parathyroid imaging studies should have a biochemically confirmed diagnosis of primary hyperparathyroidism.^[6]

Preoperative imaging in the setting of primary hyperparathyroidism is designed to assist the surgeon in identifying the anatomic localization of abnormally functioning or enlarged parathyroid glands. The noninvasive imaging modalities commonly used in patients with primary hyperparathyroidism include technetium-99m (^99m Tc) sestamibi imaging, ultrasonography, CT scanning, and MRI.^[6]

• Ultrasonography and^99m Tc sestamibi scanning have the advantages of being widely available and relatively inexpensive compared with other noninvasive modalities.

  • The most sensitive and reliable technique is^99m Tc sestamibi tomographic reprojection nuclear scanning because of its ability to produce a 3-dimensional image that can be used for visual reference by the surgeon intraoperatively.^[18]
  • In sestamibi scanning, the dual isotope technique in which an I-123NaI or^99m Tc sestamibi image of the thyroid is subtracted from a^99m Tc sestamibi image is commonly used.^[19]
  • Sestamibi scintigraphy has the advantage of being able to screen the entire mediastinal and cervical regions.
  • High-resolution real-time cervical ultrasonography using a 10-MHz transducer results in true positive findings in 50-60% of patients who undergo evaluation for persistent or recurrent primary hyperparathyroidism.
  • Using ultrasonography, hyperfunctioning parathyroid tissue has a characteristic sonolucent signal that is distinct from thyroid.
  • The best ultrasonography results reveal parathyroid tissue in one of the normal cervical locations adjacent to the thyroid gland.^[19]
  • Ultrasonography may be useful but is also operator-dependent.^[18]
• Plain-film radiography has limited diagnostic value, especially in the early stages of the disease. Normal findings do not rule out hyperparathyroidism. Distinct radiographic abnormalities are uncommon and typically are only found with overt, symptomatic disease. The findings include subperiosteal resorption that is best seen at the radial sides of the phalanges, distal phalangeal tufts, and distal clavicles. However, in most older patients, no specific radiologic manifestations are observed, and skeletal radiography is not recommended.
• Bone-density measurements based on dual energy x-ray absorptiometry (DXA) at the hip and spine should be obtained in individuals with primary hyperthyroidism, regardless of age.^[3] Recommended management of primary hyperparathyroidism includes surgical intervention be undertaken if the bone mineral density T-score at any of 3 sites (lumbar spine, proximal femur, or forearm) is less than - 2.5 standard deviation.^[20]
• Cystic bone lesions called brown tumors are seen only in patients who are severely affected. Soft tissue calcification may be apparent in the joints, kidneys, and lungs using conventional radiography and may be more readily evident on bone scans.
• CT scanning of the spine provides reproducible quantitative estimates of spinal bone density. Serial measurements can provide an early indication of whether or not progressive osteopenia is present.

• If malignancy is suspected, percutaneous needle biopsy may be performed for aspiration cytology and tissue PTH determination.