GLUCOSE-TURNOVER, FUEL OXIDATION AND FOREARM SUBSTRATE EXCHANGE IN PATIENTS WITH THYROTOXICOSIS BEFORE AND AFTER MEDICAL-TREATMENT

OBJECTIVE Accelerated metabolism is a hallmark of thyrotoxicosis, but the underlying biochemical mechanisms are incompletely understood and the majority of studies have investigated normal subjects rendered onl y modestly hyperthyroid for a brief period of time. We have therefore studied a group of thyrotoxic patients using several different techniq ues. DESIGN Twelve patients with newly diagnosed diffuse (10 patients) or nodular (2 patients) toxic goitre (10 women, 2 men; age 42.8 +/- 3 .2 years; BMI 21.6 +/- 0.7 kg/m(2)) before ('pretreatment') and after ('treated') 11.2 +/- 1.0 weeks treatment with methimazole and compared these patients to a control group ('control') of 11 subjects (9 women , 2 men; age 40.5 +/- 3.9 years; BMI 22.5 +/- 1.0 kg/m(2)). All were s tudied for 3 hours in the basal state, using indirect calorimetry, iso tope dilution for the measurement of glucose turnover and the forearm technique for assessment of muscle metabolism. RESULTS Prior to treatm ent patients with thyrotoxicosis were characterized by increased (P < 0.05) levels of T3 (3.75 +/- 0.23 nmol/l (pretreatment), 1.89 +/- 0.08 (treated) and 1.75 +/- 0.11 (control)), resting energy expenditure (1 30.5 +/- 3.5 (pretreatment), 107.7 +/- 2.7 (treated) and 106.3 +/- 3.1 (control), % of predicted), protein oxidation (0.67 +/- 0.03 (pretrea tment), 0.54 +/- 0.06 (treated) and 0.46 +/- 0.05 (control), mg/kg/min ), lipid oxidation (1.34 +/- 0.08 (pretreatment), 1.00 +/- 0.06 (treat ed) and 1.02 +/- 0.04 (control), mg/kg/min), endogenous glucose produc tion (2.51 +/- 0.13 (pretreatment), 1.86 +/- 0.12 (treated) and 1.85 /- 0.12 (control), mg/kg/min), non-oxidative glucose turnover (1.28 +/ - 0.16 (pretreatment), 0.75 +/- 0.18 (treated) and 0.71 +/- 0.11 (cont rol), mg/kg/min) and a 50% increase in total forearm blood flow. Gluco se oxidation (1.23 +/- 0.09 (pretreatment), 1.13 +/- 0.10 (treated) an d 1.21 +/- 0.11 (control) mg/kg/min), exchange of substrates in the mu scles of the forearm and circulating levels of insulin, C-peptide, gro wth hormone or glucagon were not influenced by hyperthyroidism. Propra nolol (20 mg thrice daily) given to 7 of the patients for 2 days did n ot affect circulating levels of thyroid hormones, energy expenditure o r glucose turnover rates. CONCLUSIONS These results suggest that all m ajor fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non-oxidative glucose metabolism may further aggrav ate the condition. All abnormalities diminish with medical treatment o f the disease.