Progressive escape from parathyroid suppression: a common phenomenon in primary hyperparathyroidism (A calcium clamp study)

Summary OBJECTIVE Induced aggravation of hypercalcaemia In vivo and in vitro causes partial suppression of parathyroid hormone (PTH) secretion in primary hyperparathyroidism (PHP). Furthermore, one in-vitro study also demonstrates progressive escape from such action. The aim of the present in-vivo study was to examine whether escape from suppression is a common feature of PHP. DESIGN A rapid increment in blood ionized calcium (B-Ca2+) to 0.25–0.30 mmol/l above individual baselines was achieved by intravenous calcium infusions. This induced or aggravated hypercalcaemia was kept constant for 2 hours (controls) or 4 hours (patients). PATIENTS AND CONTROLS The study of PHP comprised 19 patients (18 females and one male) aged 39–85 years (geometric mean 66). For comparison we included the results obtained in a control group of 24 healthy subjects (11 women and 13 men) aged 20–68 years (geometric mean 32). MEASUREMENTS The individual levels of B-Ca2+ were controlled by frequent bedside measurements of B-Ca2+. The changes in serum intact parathyroid hormone (S-PTH(1–84)) were registered. RESULTS After 30 minutes of calcium infusion average concentrations of S-PTH(1–84) had decreased from 7.9 (6.7–9.4) pmol/l in PHP and 2.5 (2.1–2.9) pmol/l in controls to their respective nadir values of 2.9 (2.1–4.1) pmol/l and 0.6 (0.5–0.8) pmol/l. While S-PTH(1–84) remained suppressed at a stable level for 120 minutes in controls, in PHP it started to escape progressively after 30 minutes to a level of 4.2 (3.0–5.8) pmol/l (P < 0.001). Linear regression analysis of the individual S-PTH(1–84) observations in PHP, from 30 to 240 minutes of study, revealed that five patients did not escape (group A) while the remainder 14 patients escaped progressively (group B). Within group B, seven patients escaped significantly after 120 minutes, 10 after 180 minutes and 14 after 240 minutes. Although comparable respecting B-Ca2+ before and during calcium infusion, group A and B presented different S-PTH(1–84) curves. Thus, at times zero, 30, 120 and 240 minutes their respective average concentrations of S-PTH(1–84) measured 9 9 (9.1–10.9) vs 7.3 (5.9–9.0) (P < 0.02), 4.6 (3.7–5.7) vs 2.5 (1.6–3.9) (P < 0.01), 5.0 (3.9–6.5) vs 3.0 (1.9–4.8) (P < 0.05) and 5.2 (3.6–7.4) vs 3.9 (2.6–6.0) (NS) pmol/l. CONCLUSIONS We hypothesize that two different mechanisms are involved in the parathyroid response to the calcium clamp, an initial and fast inhibition of PTH release, while the subsequent course depends on the balance between the intra-glandular secretion rate of PTH and the intra-glandular capacity for PTH degradation. The escape from parathyroid suppression during a sustained stable increment in B-Ca2+ suggests that the basal secretion over-rides degradation in a majority of the patients with PHP.