Parathyroid Hormone (PTH), Intact, Serum

Intact PTH is an exceptionally labile analyte with a plasma half-life of approximately 2–4 minutes in vivo — in vitro degradation in unsealed or improperly handled specimens is rapid and significant. While PTH is more stable in separated serum than in whole blood (proteolytic degradation is slowed after clot removal and refrigeration), delayed centrifugation, prolonged room temperature exposure of whole blood before separation, and delayed refrigeration of separated serum all produce artifactually reduced PTH concentrations. Specimens must be centrifuged and serum separated promptly — ideally within 30–60 minutes of collection — and refrigerated immediately. This is the most common pre-analytical cause of spuriously low PTH results.

PTH exhibits modest diurnal variation — with higher values in the early morning and late afternoon and a nocturnal peak — and is influenced by meal timing, as postprandial calcium absorption acutely suppresses PTH through the calcium-sensing receptor. Variation is approximately 10–20% across the day. For serial monitoring and most clinical interpretive purposes, this variation is clinically minor; however, standardised fasting morning collection is recommended when precise baseline comparison is required, particularly for primary hyperparathyroidism monitoring or research contexts.

Vitamin D deficiency reduces intestinal calcium absorption and lowers serum ionised calcium, stimulating compensatory parathyroid secretion — producing secondary hyperparathyroidism characterised by elevated PTH with normal or low-normal serum calcium. This is the most common cause of elevated PTH in the general population and is clinically important to distinguish from primary hyperparathyroidism (where calcium is elevated, not normal or low). Concurrent 25-OH vitamin D must always be measured alongside PTH — isolated elevated PTH without concurrent calcium and vitamin D is a clinically incomplete evaluation.

CKD impairs renal phosphate excretion (phosphate retention suppresses ionised calcium via precipitation, stimulating PTH), reduces renal 1α-hydroxylase activity (reducing calcitriol production and intestinal calcium absorption, further lowering ionised calcium), and reduces FGF-23-mediated vitamin D regulation — collectively producing progressive secondary hyperparathyroidism proportional to the degree of renal function impairment. Additionally, CKD reduces PTH clearance — PTH C-terminal fragments accumulate in renal failure, causing second-generation 'intact PTH' assays to overestimate true PTH 1-84 levels in CKD patients; third-generation 'whole PTH' assays are more specific in this context. eGFR must always be documented when interpreting PTH in the context of elevated values.

Lithium raises the calcium set-point of the calcium-sensing receptor — increasing the ionised calcium concentration required to suppress PTH secretion — producing a functional primary hyperparathyroid-like picture with elevated PTH and mildly elevated calcium that can mimic primary hyperparathyroidism on standard biochemistry. Lithium-associated hyperparathyroidism may be reversible on discontinuation (where clinically feasible) or may reflect unmasking of a co-existing parathyroid adenoma. Current and prior lithium therapy must be documented on the requisition form.

Thiazide diuretics increase renal calcium reabsorption in the distal tubule, raising serum calcium and potentially lowering PTH through negative feedback — a useful clinical distinction from primary hyperparathyroidism, where PTH remains elevated despite hypercalcaemia. However, thiazides can also unmask underlying primary hyperparathyroidism by revealing calcium elevations previously masked by normal renal calcium excretion. Thiazide use should be documented alongside the PTH request.