23274 PTH, Intact, Without Calcium

Diagnosis and differential diagnosis of hypercalcemia. Diagnosis of primary, secondary, and tertiary hyperparathyroidism. Diagnosis of hypoparathyroidism. Monitoring end-stage renal failure patients for possible renal osteodystrophy.

Separate plasma from the blood within 2 hours of venipuncture. Specimen must be free of particulate matter including fibrin which can interfere with the assay. After centrifugation and removal from cells, locally collected plasma specimens for PTH must be kept on ice or maintained at refrigerated temperature until testing is ready to be performed, as PTH is not stable at room temperature and disintegrates at room temperature. Marshfield Labs cannot guarantee all refrigerated outreach PTH samples will be tested within 48 hours of collection therefore it is recommended that outreach specimens for PTH testing be frozen immediately after collection and sent to MFLD center lab frozen. One freeze and thaw cycle is acceptable.

PTH exhibits diurnal variation and healthy subjects have basal values from 9 to 12pm are considered optimal for differentiating normal and abnormal results. Early draws in the 5 to 7 am should be avoided. Higher values are seen during 2pm to 6 am period.

PTH on fluids other than serum such as Fine needle Aspirates must be ordered as a PTH-O (PTH, Intact - Other Fluids) test with the fluid source noted.

Ingestion of milk before test may cause falsely low values. Radioisotope testing within 7 days may alter the results. For patients receiving high dose (>5 mg/day) biotin therapy, the specimen should be collected at least 8 hours after the last biotin administration.

Heterophilic antibodies in human serum can react with the immunoglobulins included in the assay components causing interference with immunoassay.

For Tosoh AIA immunoassay method performed at Diagnostic and Treatment Center lab, the drug asfotase alfa (Strensiq®), used for the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP), may cause falsely increased or decreased test results. Test results from patients treated with asfotase alfa should be interpreted with respect to the clinical picture of the patient. Recommend sending test to Marshfield Center lab for analysis by an alternate method.

Intact PTH (1-84) is a biologically active hormone produced by parathyroid hormones and secreted into systemic circulation. It exerts its effects through the interaction of its first 34 amino acids with the type 1 PTH/PTHrP receptor (PTHR1). PTH fragments, containing carboxyl-(C) or amino-terminal (N-terminal) portions of the molecule arise from either intra-glandular or peripheral degradation of the hormone, are also present in the circulation. As a result, circulating immune-reactive PTH in normocalcemic subjects comprises: PTH 1-84, C-terminal fragments and N-terminal fragments. An increasing body of evidence suggests that some of these fragments, particularly the N-terminally truncated fragment PTH 7-84 (also referred to as non-PTH 1-84), interact with distinct receptors (C-PTH receptor, C-PTHR) and thereby may have important roles in the regulation of bone resorption and serum calcium concentration.

The intact (1-84) PTH has a short half-life of about 5 minutes, whereas the carboxy and midmolecule fragments, which are biologically inactive, have half-lives 10- to 20-fold higher make up >90% of the total circulating PTH and are primarily cleared by the kidneys. In patients with renal failure, PTH-C fragments can accumulate to high levels. PTH 1-84 is also elevated in these patients.

Intact PTH assays measures not only PTH (1-84) but other fragments including PTH (7-84) which may accumulate in patients with renal insufficiency.

The serum calcium level regulates PTH secretion via negative feedback through the parathyroid calcium sensing receptor (CASR). Decreased calcium levels stimulate PTH release. Secreted PTH causes rapid increase in renal tubular reabsorption of calcium and decrease in phosphorus reabsorption. PTH also functions by enhancing mobilization of calcium from bone and increasing renal synthesis of 1,25-dihydroxy vitamin D, which, in turn, increases intestinal calcium absorption. In rare inherited syndromes of parathyroid hormone resistance or unresponsiveness and in renal failure, PTH release may not increase serum calcium levels.

Parathyroid hormone (PTH) values should be interpreted in conjunction with serum calcium and phosphorus levels, and the overall clinical presentation and history of the patient.

An elevated PTH value with normal serum calcium are not always necessarily indicative of primary hyperparathyroidism. It is possible that the elevation in PTH is due to secondary causes, the most likely cause is due vitamin D deficiency.

CALCIUM	INTACT PTH	INTERPRETATION
Normal	Normal	Calcium regulation functioning OK.
Low	High	PTH responding correctly, run other tests to check hypocalcaemia.
Low	Normal/Low	PTH not responding correctly, possibility of hypoparathyroidism.
High	High	Hyperparathyroidism
High	Low	PTH responding correctly, run other tests to check for non-parathyroid –related reasons for high calcium.