Glucose turnover, fuel oxidation and forearm substrate exchange in patients with thyrotoxicosis before and after medical treatment

Abstract

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 only modestly hyperthyroid for a brief period of time. We have therefore studied a group of thyrotoxic patients using several different techniques. 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/m2) 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/m2). All were studied for 3 hours in the basal state, using indirect calorimetry, isotope dilution for the measurement of glucose turnover and the forearm technique for assessment of muscle metabolism. Prior to treatment 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 (130.5 +/- 3.5 (pretreatment), 107.7 +/- 2.7 (treated) and 106.3 +/- 3.1 (control), % of predicted), protein oxidation (0.67 +/- 0.03 (pretreatment), 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 (treated) and 1.02 +/- 0.04 (control), mg/kg/min), endogenous glucose production (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 (control), mg/kg/min) and a 50% increase in total forearm blood flow. Glucose oxidation (1.23 +/- 0.09 (pretreatment), 1.13 +/- 0.10 (treated) and 1.21 +/- 0.11 (control) mg/kg/min), exchange of substrates in the muscles of the forearm and circulating levels of insulin, C-peptide, growth hormone or glucagon were not influenced by hyperthyroidism. Propranolol (20 mg thrice daily) given to 7 of the patients for 2 days did not affect circulating levels of thyroid hormones, energy expenditure or glucose turnover rates. These results suggest that all major fuel sources contribute to the hypermetabolism of thyrotoxicosis and that augmented non-oxidative glucose metabolism may further aggravate the condition. All abnormalities diminish with medical treatment of the disease.