The effect of thyroid hormones on the renin-angiotensin-aldosterone sy
stem has not been fully resolved. Highly specific immunoassays for mea
surement of renin, aldosterone, free T4 (fT4), free T3 (fT3) and ultra
sensitive TSH enables a direct and more accurate measurement of these
hormones. We investigated the relationship between plasma renin, aldos
terone and thyroid hormones in the basal state and after intravenous f
rusemide. This is a cross-sectional study involving 37 patients with t
hyrotoxicosis, 42 rendered euthyroid with normal fT4, fT3 and TSH leve
ls, 17 with euthyroid levels of fT4 and fT3 but suppressed TSH, and 11
with hypothyroidism. Basal plasma renin was significantly higher in t
hyrotoxicosis (63.4 +/- 9.8 mu U/ml, mean +/- SEM) compared to euthyro
id (32.7 +/- 4.4 mu U/ml) and hypothyroid (26.7 +/- 9.8 mu U/ml). Basa
l plasma renin for euthyroid with suppressed TSH (41.0 +/- 7.4 mu U/ml
) was significantly higher than hypothyroid (p = 0.02). Basal plasma a
ldosterones were not significantly different except for suppressed TSH
(157.7 +/- 13 pg/ml), which was higher than normal (109.9 +/- 10.4 pg
/ml; p = 0.04). Following frusemide, plasma renin and aldosterone were
significantly increased in all groups. Plasma renin was highly correl
ated to fT3 (r = 0.405, p < 0.001), total T3 (r = 0.359, p < 0.001), f
T4 (r = 0.331, p < 0.001) and TSH (r = 0.300, p < 0.001) in the basal
state, but less to total T4 (r = 0.248, p < 0.01). Plasma renin correl
ated poorly to serum aldosterone (r = 0.212, p < 0.03). This study cle
arly showed that regulation of renin was mainly influenced by fT3, and
that aldosterone response to frusemide was blunted in thyrotoxicosis
despite normal electrolytes.