PROGRESSIVE ESCAPE FROM PARATHYROID SUPPRESSION - A COMMON PHENOMENONIN PRIMARY HYPERPARATHYROIDISM (A CALCIUM CLAMP STUDY)

OBJECTIVE Induced aggravation of hypercalcaemia in vivo and in vitro c auses partial suppression of parathyroid hormone (PTH) secretion in pr imary hyperparathyroidism (PHP). Furthermore, one in-vitro study also demonstrates progressive escape from such action. The aim of the prese nt in-vivo study was to examine whether escape from suppression is a c ommon feature of PHP. DESIGN A rapid increment in blood ionized calciu m (B-Ca2+) to 0.25-0.30 mmol/l above individual baselines was achieved by intravenous calcium infusions. This induced or aggravated hypercal caemia was kept constant for 2 hours (controls) or 4 hours (patients). PATIENTS AND CONTROLS The study of PHP comprised 19 patients (18 fema les and one male) aged 39-85 years (geometric mean 66). For comparison we included the results obtained in a control group of 24 healthy sub jects (11 women and 13 men) aged 20-68 years (geometric mean 32). MEAS UREMENTS The individual levels of B-Ca2+ were controlled by frequent b edside measurements of B-Ca2+. The changes in serum intact parathyroid hormone (S-PTH(1-84)) were registered. RESULTS After 30 minutes of ca lcium infusion average concentrations of S-PTH(1-84) had decreased fro m 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 aft er 30 minutes to a level of 4.2 (3.0-5.8) pmol/l (P<0.001). Linear reg ression analysis of the individual S-PTH(1-84) observations in PHP, fr om 30 to 240 minutes of study, revealed that five patients did not esc ape (group A) while the remainder 14 patients escaped progressively (g roup B). Within group B, seven patients escaped significantly after 12 0 minutes, 10 after 180 minutes and 14 after 240 minutes. Although com parable 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) an d 5.2 (3.6-7.4) vs 3.9 (2.6-6.0) (NS) pmol/l. CONCLUSIONS We hypothesi ze that two different mechanisms are involved in the parathyroid respo nse to the calcium clamp, an initial and fast inhibition of PTH releas e, while the subsequent course depends on the balance between the intr a-glandular secretion rate of PTH and the intra-glandular capacity for PTH degradation. The escape from parathyroid suppression during a sus tained stable increment in B-Ca2+ suggests that the basal secretion ov er-rides degradation in a majority of the patients with PHP.