Nephrogenous cyclic AMP in primary hepatocellular carcinoma patients with or without hypercalcaemia

To study the relationship between the excretion of nephrogenous cyclic AMP (NcAMP) and other blood and urine parameters as an index of PTH-like activity in patients with primary hepatocellular carcinoma.

After overnight fast, a double voided urine and a blood sample were collected from each subject for determination of various analytes and results compared between various groups.

Fifty-five consecutive untreated patients with primary hepatocellular carcinoma, 14 healthy controls and eight patients with cirrhosis only.

Serum calcium, phosphate, alkaline phosphatase, albumin, creatinine and urinary calcium, creatinine and hydroxyproline were measured by routine methods. cAMP was measured in plasma and urine by a radioimmunoassay (Diagnostic Products Corporation) and PTH measured in serum by an immunoradiometric assay (Nichols Institute). TmP/GFR, NcAMP etc. were calculated according to various published methods.

Four out of 55 patients (7%) with primary hepatocellular carcinoma had hypercalcaemia. These four patients had significantly lower (P less than 0.05) phosphate, PTH and TmP/GFR and elevated NcAMP (P less than 0.001) compared with normocalcaemic hepatocellular carcinoma and cirrhotic patients, and healthy controls. The excretion of hydroxyproline and calcium was significantly elevated (P less than 0.001) in the hypercalcaemic patients. Bone resorption was found to be the major cause of hypercalcaemia in three of the four hypercalcaemic patients. Fifteen hepatocellular carcinoma patients (29%) with normocalcaemia had suppressed PTH.

We conclude that a PTH-like humoral factor such as PTH related peptide is the cause of hypercalcaemia in patients with primary hepatocellular carcinoma, and that in some normocalcaemic patients with this tumour PTH is suppressed.