Serum N-Terminal Pro-Atrial Natriuretic Factor 1-98 Before and During Thyroxine Replacement Therapy in Severe Hypothyroidism

Decreased plasma concentrations of atrial natriuretic factor (ANF) and of its N-terminal prohormones have been demonstrated in severely hypothyroid patients compared with control subjects, and shown to normalize with thyroxine (T₄) replacement therapy. Whether this depends on thyroid hormone deficiency exclusively or is secondary to hemodynamic changes that result from it remains a matter of debate. In a recent investigation dose-related increases in both ANF and N-terminal prohormones of ANF by T₄ replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid hormones may enhance synthesis rather than release of atrial peptide hormones. The aim of the present study was to confirm this assumption in hypothyroid patients with normal cardiac performance. Serum N-terminal amino acids 1-98 (ie, pro-ANF 1-98) of pro-ANF was determined in 11 severely hypothyroid patients without pericardi al effusion and with normal cardiac left ventricular function. Mean pro-ANF 1-98 concentration before T₄ replacement therapy remained unchanged after 10 days on T₄ (p =.12). After 2 months of therapy, mean pro-ANF 1-98 was significantly increased compared with pretreatment values (p <.003). A significant correlation to the increase in free T₄ (r = 0.48, p <.01) but not to the decrease in thyrotropin (TSH) (r = –0.32, p =.09) was found. The present results indicate that thyroid hormones directly increase pro-ANF 1-98 independently of cardiac hemodynamics in the hypothyroid state.