Sulphate conjugation limits fluctuations in free catecholamines in phaeochromocytoma

Sulphate conjugation represents an efficient mechanism for inactivating catecholamines (CA) with more than 80% of total noradrenaline (NA) and adrenaline (A) and nearly 100% of dopamine (DA), circulating as conjugates. Sulphate conjugation responds rapidly to changes in sympathetic activity and may buffer the haemodynamic and metabolic consequences of wide fluctuations in CA release in phaeochromocytoma. This hypothesis was tested in seven patients with phaeochromocytoma by consecutive measurements of plasma free and conjugated NA, under resting conditions, before operation and at least 4 weeks after tumour removal. Free and total (free plus sulphates) NA were markedly elevated before (4.3, s.e.m. = 1.8 and 13.7, s.e.m. = 4.4 ng/ml, respectively) compared with 1-4 months after surgery (0.48, s.e.m. = 0.13 and 1.8, s.e.m. = 0.53 ng/ml). A and DA were similarly elevated before surgery; after surgery, A was undetectable in three patients and DA was undetectable in all patients. Before surgery consecutive measurements of total NA, 5 min apart, were markedly different (18.8, s.e.m. = 4.8 and 12, s.e.m. = 3.1 ng/ml, respectively), whereas only small differences in free NA levels were present (4.0, s.e.m. = 1.5 and 4.4, s.e.m. = 1.8 ng/ml). In three patients, fluctuations in total NA concentration greater than 12 ng/ml were associated with either no change (one patient) or changes of 0.6 and 2.8 ng/ml in levels of free NA, respectively. Mean blood pressure varied less than 8 mmHg in these patients. These findings indicate that sulphate conjugation is a dynamic process which may limit wide fluctuations in free CA concentration during episodic secretory activity in phaeochromocytoma.