Hyperparathyroidism in Emergency Medicine Workup

Updated: Oct 18, 2016
  • Author: Philip N Salen, MD; Chief Editor: Erik D Schraga, MD  more...
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Workup

Approach Considerations

Patients with mild pHPT are often identified during routine laboratory evaluation or when undergoing workup for bone loss. As such, they tend to be postmenopausal women who are at risk for osteoporosis that undergo BMD studies and calciotropic hormone measurements for evaluation. [19]  With the advent of multichannel autoanalyzer testing of PTH, increasing neck imaging studies, and calcium measurements taken for screening and bone health evaluation, patients with biochemically mild profiles are frequently identified. Among the increasing numbers of patients diagnosed with PHPT, subsets of patients are now more frequently identified with biochemically mild PHPT, who are either normocalcemic with elevated PTH or hypercalcemic with an inappropriately normal or high-normal PTH. [19]

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Laboratory Studies

The biochemical hallmarks of PHPT include elevated serum calcium levels in the presence of elevated or inappropriately normal levels of PTH. All nonparathyroid causes of hypercalcemia are associated with PTH levels that are suppressed. Malignancy-associated hypercalcemia is a disorder to consider primarily in the differential diagnosis of PHPT, and will be excluded with a low PTH level. [7]

  • Elevated PTH levels in the setting of hypercalcemia establish the diagnosis of hyperparathyroidism. The normal range for the PTH-intact assay is 10-65 pg/mL. The introduction of an immunoradiometric assay for PTH that detects only the fully intact PTH molecule has improved diagnostic accuracy of PTH determination. [20]
  • The threshold value for serum calcium, above which parathyroidectomy is indicated, is persistent elevation more than 1 mg/dL (0.25 mM/liter) above the upper limits of normal. [21]
  • The most common alternative 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, which makes this correction of particular importance for that population.
  • Levels of 25-hydroxyvitamin D should be assessed in all patients suspected of having PHPT, and vitamin D deficiency should be cautiously corrected at the time it is detected. [21]
  • It is important to monitor renal function, both at the time of diagnosis and during follow-up of hyperparathyroid patients. [21] Urinary calcium excretion may be elevated in patients with symptomatic PHPT and predisposes to ureteral colic.
  • Increased bone turnover may be reflected in elevated levels of markers of bone formation, alkaline phosphatase, and bone resorption, urinary pyridinoline, though these tests do not aid in diagnosis of PHPT.
  • Lithium and thiazide diuretics induce changes in parathyroid function that can potentially mimic PHPT. To evaluate whether these medications are causing hypercalcemia, they can be withdrawn for 3 months, if medically safe, and the patient’s calcium and PTH can be retested. Usually, drug withdrawal does not alter biochemical results and the medications, excluded as causal, can be reinstituted. [7]
  • 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. [22] Intraoperative use of the PTH assay provides quantitative confirmation 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% [23] and has decreased the need for performing frozen sections. [24]
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Imaging Studies

Positive imaging studies are not necessary for the confirmation of a diagnosis of PHPT. Moreover, negative imaging study results do not exclude the diagnosis of primary hyperthyroidism. Parathyroid imaging studies have the potential for false-positive or false-negative findings that can be misleading. Therefore, biochemical confirmation of the diagnosis of PHPT should always precede parathyroid imaging studies. [8]

Preoperative imaging in the setting of PHPT 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 PHPT include technetium-99m (99m Tc) sestamibi imaging, ultrasonography, CT scanning, and MRI. [8]

  • 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 is99m 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. [25]
    • In sestamibi scanning, the dual isotope technique in which an I-123NaI or99m Tc sestamibi image of the thyroid is subtracted from a99m Tc sestamibi image is commonly used. [26]
    • 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 most helpful ultrasonography results reveal parathyroid tissue in one of the normal cervical locations adjacent to the thyroid gland. [26]
    • Ultrasonography may be useful but is operator-dependent. [25]
  • 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 routine 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 PHPT, regardless of age. [1] 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. [27]
  • Cystic bone lesions called brown tumors are seen only in severely symptomatic patients with long standing disease. 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.
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Procedures

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

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