Diurnal hormone-metabolite profiles in hypothyroidism

To investigate the influence of thyroid hormones on intermediary metabolism in man, hormone and metabolite profiles were obtained over a 12-h period of normal meals and activity in eight hypothyroid subjects before and during thyroxine replacement therapy, and in sixteen matched controls. The fasting blood glucose concentration and the mean 12-h blood glucose concentration were normal in hypothyroid subjects but the blood glucose response to breakfast was exaggerated. Fasting blood lactate and pyruvate levels were normal but post-prandial hyperlactataemia and hyperpyruvicaemia were found and mean 12 h values for lactate (hypothyroid 1.80 +/- 0.06 v. control 0.77 +/- 0.03 mmol/l, P less than 0.01) and pyruvate (0.10 +/- 0.01 v. 0.08 +/- 0.003 mmol/l, P less than 0.01) were elevated. Blood alanine concentrations were elevated only in the evening. Although plasma non-esterified fatty acid levels were normal, fasting blood glycerol levels were decreased (0.06 +/- 0.01 v 0.08 +/- 0.01 mmol/l, P less than 0.001) and this decrease persisted throughout the 12-h period. Blood total ketone body concentrations did not differ from controls, but, as for plasma NEFA and blood glycerol, the normal preprandial rise in concentration was absent. Serum insulin, glucagon and growth hormone concentrations did not differ from control values at any time. Six months of thyroxine (T4) treatment produced a rise in blood glycerol concentration (mean 12 h value during T4 therapy, 0.06 +/- 0.01; before T4 therapy, 0.04 +/- 0.005 mmol/l; P less than 0.01) but not to control values (0.08 +/- 0.01 mmol/l). Concentrations of glucose and other gluconeogenic precursors were unaltered by therapy but the insulin response to meals and the mean 12 h serum insulin concentration were increased.