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

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.

Fifty-four controls, 83 essential hypertensive and six adrenalectomized patients were studied.

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.

CgA was measured by an immunoradiometric assay, and noradrenaline and adrenaline by high-performance liquid chromatography.

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.

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.