SERUM N-TERMINAL PROATRIAL 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 hypo thyroid patients compared with control subjects, and shown to normaliz e with thyroxine (T-4) replacement therapy. Whether this depends on th yroid hormone deficiency exclusively or is secondary to hemodynamic ch anges that result from it remains a matter of debate. In a recent inve stigation dose-related increases in both ANF and N-terminal prohormone s of ANF by T-4 replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid horm ones may enhance synthesis rather than release of atrial peptide hormo nes. The aim of the present study was to confirm this assumption in hy pothyroid patients with normal cardiac performance. Serum N-terminal a mino acids 1-98 tie, pro-ANF 1-98) of pro-ANF was determined in 11 sev erely hypothyroid patients without pericardial effusion and with norma l cardiac left ventricular function. Mean pro-ANF 1-98 concentration b efore T-4 replacement therapy remained unchanged after 10 days on T-4 (p=.12). After 2 months of therapy, mean pro-ANF 1-98 was significantl y increased compared with pretreatment values (p<.003). A significant correlation to the increase in free T-4 (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.