Sampling and storage conditions influencing the measurement of parathyroid hormone in blood samples: a systematic review

Abstract

Parathyroid hormone (PTH) is relatively unstable: optimisation of pre-analytical conditions, including specimen type, sampling time and storage conditions, is essential. We have undertaken a systematic review of these pre-analytical conditions. An electronic search of the PubMed, Embase, Cochrane, Centre for Research and Dissemination and Bandolier databases was undertaken. Of 5511 papers identified, 96 underwent full text review, of which 83 were finally included. At room temperature PTH was stable in ethylenediaminetetraacetic acid (EDTA) preserved whole blood for at least 24 h and in EDTA plasma for at least 48 h after venepuncture. Losses were observed in clotted blood samples after 3 h and in serum after 2 h. At 4°C PTH was more stable in EDTA plasma (at least 72 h) than serum (at least 24 h). Central venous PTH concentrations were higher than peripheral venous concentrations. In the northern hemisphere, PTH concentrations were higher in winter than summer. PTH has a circadian rhythm characterised by a nocturnal acrophase and mid-morning nadir. Data related to frozen storage of PTH (−20°C and −80°C) were limited and contradictory. We recommend that blood samples for PTH measurement should be taken into tubes containing EDTA, ideally between 10:00 and 16:00, and plasma separated within 24 h of venepuncture. Plasma samples should be stored at 4°C and analysed within 72 h of venepuncture. Particular regard must be paid to the venepuncture site when interpreting PTH concentration. Further research is required to clarify the suitability of freezing samples prior to PTH measurement.

Considerations in parathyroid hormone testing

“…Two of the authors (EC and JCS) participate to the IFCC Scientific Division Working Group on PTH, but totally disagree with the conclusions published by other experts that signed on behalf of this group [23]. For us, and in contrast with these colleagues, serum seems the most appropriate to measure PTH, mainly because it allows the simultaneous determination of calcium.…”

“…PTH stability in EDTA or serum should be the paramount of our concerns. As previously stated, many papers have been published on the topic and a recent systematic review on the subject has been published in this journal [23]. As the authors of this review, we have to complain about the tremendous variability -due to both pre-and intra-analytical variables -between the studies, which does not help to decide whether EDTA should be preferred over serum or not.…”

“…Hanon et al have recently reviewed the circadian variation of PTH [23]. Briefly, PTH follows a bimodal rhythm, with a nocturnal acrophase a mid-morning nadir and a smaller afternoon peak, even if all the studies do not totally agree on peak times.…”

“…Briefly, PTH follows a bimodal rhythm, with a nocturnal acrophase a mid-morning nadir and a smaller afternoon peak, even if all the studies do not totally agree on peak times. Sensu stricto, it may thus be logical to collect samples for PTH determination during the nadir phase, i.e., between 10:00 and 16:00 [23,41]. To correctly interpret PTH levels, we have however to consider calcium (and phosphate) concentrations.…”

Laboratory approaches for the diagnosis and assessment of hypercalcemia

“…Caution should be paid to specimen collection to minimize the variability. PTH is reported to be more stable when collected in ethylenediamine tetraacetic acid (EDTA) plasma [100][101][102] . PTH has been reported to be stable in serum for only 4 h when stored as unseparated whole blood 103 .…”