In healthy humans, parathyroid hormone (PTH) is secreted via basal mode with superimposed oscillatory bursts every 8 to 12 min. Amplitude and frequency changes mediate the instantaneous response of the parathyroids to changes in ambient Ca(2+) concentrations. The parathyroid gland tetrad may be synchronized by autonomic innervation. This study investigated the effect of total parathyroidectomy and heterotopic autotransplantation of parathyroid tissue (PTX) on PTH secretion patterns in nine patients with end-stage renal disease. Intact-PTH versus time concentration profiles were obtained early (1 to 8 wk, n = 4) or late (15 to 33 mo, n = 5) after PTX. In four patients late after PTX, Ca(2+) responsiveness of PTH secretion was additionally investigated by citrate and calcium clamp studies. The nonrandomness of plasma PTH fluctuations was assessed by the approximate entropy (ApEn) statistic, and secretion characteristics by multiparametric deconvolution analysis. Results were compared with those of matched normal subjects and chronic renal failure (CRF) patients without PTX. PTH burst frequency was 2.9 +/- 0.1 h(-1) early and 7 +/- 0.4 h(-1) late after PTX as compared with 8.1 +/- 0.4 h(-1) in CRF and 7 +/- 0.3 h(-1) in healthy controls. Fractional pulsatile PTH secretion was diminished after PTX (18 +/- 2%) compared with healthy controls (32 +/- 5%, P < 0.05) and CRF patients (25 +/- 4%, P = 0.05). The orderliness of PTH release was significantly reduced after PTX (ApEn: 1.59 +/- 0.03 versus 1.41 +/- 0.09 in healthy and 1.46 +/- 0.03 in CRF controls, P < 0.01). Acute hypocalcemia elicited a lesser increase in pulsatile PTH secretion in PTX patients (147 +/- 134%) than in the CRF (500 +/- 92%, P = 0.05) and healthy controls (1410 +/- 290%, P < 0.05), mainly due to a diminished mass of PTH secreted per burst. Pulsatile PTH secretion was also resistant to hypercalcemia, wherein the suppression of burst mass was significantly reduced compared with that in healthy controls. In conclusion, pulsatile PTH secretion is partially restored within 2 yr of PTX. However, the capacity of the autotransplanted tissue to adapt to changes in ionized calcium remains profoundly disturbed.