Persistent alterations of vasopressin and N-terminal proatrial natriuretic peptide plasma levels in long-term abstinent alcoholics

Background: During alcohol withdrawal and early abstinence, severe alterations of electrolyte and water homeostasis and their regulating hormones are well recognized. Almost nothing is known about regeneration of these functions with long-term abstinence. This cohort study was designed to monitor determinants of electrolyte and water balance over 280 days of abstinence in alcohol-dependent men compared with healthy controls. Methods: Vasopressin (AVP), N-terminal proatrial natriuretic peptide, aldosterone, angiotensin II, and electrolytes, together with major parameters of kidney and liver function, were monitored in 35 male alcoholics aged 44+/-8 years. Of these, 21 could be followed up to 280 days of strictly controlled abstinence due to their participation in the Outpatient Long-Term Intensive Therapy for Alcoholics. The control group comprised 20 healthy male volunteers aged 39+/-7 years. Results: Basal AVP levels were found to be suppressed over the whole study period. In contrast, N-terminal proatrial natriuretic peptide remained increased over all 280 days. No persistent alterations were found for aldosterone or angiotensin II. Sodium and potassium in plasma and urine returned to normal within a few weeks. Creatinine clearance, urea nitrogen in plasma and urine, urinary osmolality, hematocrit, and hemoglobin remained low as compared with controls over the entire study. Conclusions: Chronic alcohol abuse causes severe and persistent alterations in the hormonal regulatory systems of electrolyte and water balance. The suppressed basal secretion of AVP may reflect a dysregulation in the brain that influences the hypothalamic-pituitary-adrenal axis function, mood, memory, addiction behavior, and craving during alcohol abstinence. These findings may provide a ground for future therapeutic approaches to stable abstinence.