Parathyroid hormone and cirrhosis of the liver. Fifty patients with liver cirrhosis (36 alcoholic, 1 drug-induced, 7 posthepatitic, and 6 cryptogenic) and normal renal function were investigated to determine whether PTH levels in serum, measured using the common midregion human PTH-(44-68) RIA, are elevated in such patients and whether this is related to impaired liver function rather than to the effect of secondary hyperparathyroidism. Their data were compared with those from 25 control subjects. The median PTH level of 462 +/- 18 ng/L (+/- SEM) was significantly increased (P less than 0.01) in cirrhotics compared with that of 236 +/- 13 ng/L in the control group. Significant correlations were found between PTH levels and parameters of liver function such as prothrombin time (r = -0.40; P less than 0.01), albumin as a percentage of total protein (r = -0.48; P less than 0.01), bilirubin (r = 0.35; P less than 0.05), albumin (r = -0.34; p less than 0.05), and cholesterol (r = -0.32; P less than 0.05), but not for antipyrine clearance, suggesting increasing PTH with decreasing liver function. The median calcium level (2.26 +/- 0.03 mmol/L), corrected for changes in albumin, was near the lower limit of the normal range (2.25-2.60), but corrected calcium and PTH were positively correlated (r = 0.33; P less than 0.05), indicating that the elevation is not reactive to calcium depletion. A negative correlation existed between PTH and 25-hydroxy-cholecalciferol (r = -0.49; P less than 0.05), the main circulating metabolite of vitamin D. Normal values in an immunoradiometric assay that detects the whole sequence of human PTH-(1-84) suggest that fragments rather than the intact hormone are responsible for PTH elevations in cirrhosis. The positive correlation between midregion PTH and corrected calcium is probably an artifact of the correction formula. In conclusion, midregion PTH fragments are increased in patients with liver cirrhosis. The reason for this elevation may well be the impaired liver function rather than secondary hyperparathyroidism. 