Diagnosis:
Primary hyperparathyroidism
• Assays for intact parathyroid hormone (PTH) do not detect all biologically active forms of PTH that may be present in the circulation. On occasion, biologically active variant forms of PTH circulate in patients with parathyroid adenomas. These patients can have clinical symptoms of hyperparathyroidism in the absence of elevated PTH levels as measured by intact PTH assays or second-generation PTH assays.
• Other potential reasons for normal-low intact PTH levels in the presence of hypercalcemia are listed below:
• Failure to keeping the sample on ice during transport or breaking of the “cold chain,”
• Coexistent sarcoidosis and/or vitamin D toxicity,
• Hypomagnesemia,
• The hook effect, and
• Parathyroid hormone–related protein (PTHrP) secretion by a parathyroid carcinoma.
• Magnesium is necessary for the synthesis, secretion, and function of intact PTH.
• PTHrP can be secreted by various tumors, leading to the humoral hypercalcemia syndrome. PTHrP is also present in the circulation during lactation and fetal life.
• PTH is a heat-labile peptide. When PTH is measured in serum, the specimen should be kept on ice or frozen from the time of collection to measurement (cold chain), thereby preventing degradation of the peptide.
• The hook effect or prozone effect, which can be seen with immunoassays, occurs when a false-negative or falsely low result is obtained in the presence of high levels of analyte. Excess analyte saturates antibody binding sites, preventing lattice or sandwich formation and loss of a measurable signal. The hook effect can be observed using various types of assays, and its occurrence is highly assay dependent.