FUNCTIONAL EVIDENCE FOR 2 TYPES OF PARATHYROID ADENOMA

OBJECTIVE The carboxyterminal parathyroid hormone (C-PTH)/intact (I-) PTH ratio is influenced by serum calcium concentrations in man, increa sing to a maximum value in hypercalcaemia and decreasing to a minimum value in hypocalcaemia. We decided to use this ratio to screen for par athyroid tumour with a normal sensitivity to calcium, symptomatic main ly through a mass effect. DESIGN AND SUBJECTS Nineteen patients with h ypercalcaemia and elevated or inappropriate PTH, were studied in the b asal state and during CaCl2 and Na(2)EDTA infusion and compared with 2 6 normal individuals. They all had one parathyroid adenoma removed sur gically, and two remained hypercalcaemic. RESULTS In the basal state, the patients were hypercalcaemic (ionized calcium 1.44 +/- 0.12 vs. 1. 23 +/- 0.03 mmol/l, P<0.001) and had elevated PTH levels (I-PTH: 10.8 +/- 8.0 vs. 2.3 +/- 0.6 pmol/l, P<0.001; C-PTH: 31.6 +/- 38.9 vs. 5.25 +/- 1.11 pmol/l, P<0.001) when compared with normals. Their mean C-PT H/I-PTH ratio was similar to normals (2.7 +/- 1.3 vs. 2.4 +/- 0.6, NS) but, when individual values were considered, three patients had eleva ted values at 4.9, 5.3 and 5.8 (normal=1.2-3.6). The regression line b etween basal C-and I-PTH revealed a significantly higher slope in thes e patients (P<0.0001). The 16 patients with a normal basal C-PTH/I-PTH ratio had, as a group, an increased set point of I-or C-PTH stimulati on by calcium and increased values of stimulated and non-suppressible I-and C-PTH, but these abnormalities were not all present in the small er tumours (less than or equal to 200 mg). Only three tumours in that group were larger than 1000mg. Serum calcium concentration was related to the increased set point and non-suppressible fraction of I-PTH in these patients (r(2) = 0.797). The three patients with a high basal C- PTH/I-PTH ratio had large tumours (2346, 4364 and 17300 mg) and were m ore difficult to study, requiring a larger decrease in calcium concent ration to achieve maximal stimulation. In the basal state, they were a lready expressing a non-suppressible level of I-or C-PTH and already h ad a maximal C-PTH/I-PTH ratio. Our data further suggest a normal set point of I-and C-PTH stimulation in the two patients who achieved suff icient hypocalcaemia and a normal set point of C-PTH/I-PTH ratio modul ation in these three patients. Their hypercalcaemia was essentially re lated to the non-suppressible fraction of PTH. Furthermore, larger tum ours were less active than smaller ones and produced less stimulated I -PTH/100 mg of tissue. CONCLUSIONS These data indicate two types of pa rathyroid tumours when calcium sensitivity is considered: (1) a majori ty of small tumours with abnormal sensitivity to calcium, symptomatic through an abnormal set point and an increased non-suppressible fracti on and (2) a smaller number of larger tumours, with normal sensitivity to calcium and an increased non-suppressible fraction, of PTH.