Chromogranin 'A' in normal subjects, essential hypertensives and adrenalectomized patients.

OBJECTIVE: Chromogranin A (CgA) is an acidic glycoprotein co-stored in vesicles and co-released with catecholamines. Although currently used as a humoral marker of endocrine tumours, several aspects of CgA secretion still need to be clarified in humans. PATIENTS: Fifty-four controls, 83 essential hypertensive and six adrenalectomized patients were studied. DESIGN: In the controls and hypertensive patients, CgA and catecholamines were measured before (supine position) and after changes in posture (2' upright position), insulin-induced hypoglycaemia (0.15 IU/kg i.v.) and glucagon injection (1 mg i.v.). In addition, blood samples were taken in the morning (0800 h) and in the afternoon (1800 h), and every 5 h for 24 h. In the adrenalectomized patients, blood samples were obtained in the morning and in the afternoon. MEASUREMENTS: CgA was measured by an immunoradiometric assay, and noradrenaline and adrenaline by high-performance liquid chromatography. RESULTS: In controls, posture slightly increased plasma catecholamines without affecting CgA levels. Hypoglycaemia evoked a rise in noradrenaline (P < 0.04), adrenaline (P < 0.01) and CgA (79.6 +/- 11.8 vs. 46.1 +/- 10.1 microg/l, P < 0.03). Glucagon injection increased plasma adrenaline (P < 0.01) but not noradrenaline or CgA levels. At variance with blood pressure and catecholamines, CgA increased significantly in the afternoon (51.1 +/- 4.0 vs. 45.0 +/- 3.9 microg/l, P < 0.05); it also had a circadian rhythm, with peak values during the night (at 2300 h, 65.4 +/- 9.0 microg/l) and a nadir in the morning (at 0800 h, 43.1 +/- 6.6 microg/l). In hypertensives, basal and stimulated CgA levels as well as diurnal/circadian variations of this peptide were similar to those in normal subjects. In adrenalectomized patients plasma CgA in the morning (34.3 +/- 6.5 microg/l) was lower (P < 0.03) than in all controls and hypertensives studied, but also showed an afternoon increment (46.4 +/- 6.6 microg/l, P < 0.003). No correlation was found between CgA and catecholamines or blood pressure in all subjects or in the subgroups. CONCLUSIONS: In normal humans, chromogranin A and catecholamines are not always co-secreted, and co-secretion occurs only for marked exocytotic adrenergic stimuli, such as hypoglycaemic stress. In addition, chromogranin A has a circadian rhythm unrelated to plasma catecholamines. Basal plasma concentrations and the secretory pattern of chromogranin A in hypertensives do not differ from the findings in controls. Finally, the adrenal glands contribute partially to circulating chromogranin A and are not involved in the circadian rhythm of this peptide in humans.