To assess the underlying mechanisms, we examined seven hyperthyroid women with Graves' disease before (Ht) and after (Eut) medical treatment and seven control subjects (Ctr). All subjects underwent a 3-h study in the postabsorptive state. After regional catheterization, protein dynamics of the whole body and of the forearm muscles were measured by amino acid tracer dilution technique using [15 N]phenylalanine and [ 2 H4]tyrosine. Before treatment, triiodothyronine was elevated (6.6 nmol/l) and whole body protein breakdown was icreased 40%. The net forearm release of phenylalanine was increased in hyperthyroidism (g ⅐ 100 ml Ϫ1 ⅐ min Ϫ1 ): Ϫ7.0 Ϯ 1.2 Ht vs. Ϫ3.8 Ϯ 0.8 Eut (P ϭ 0.04), Ϫ4.2 Ϯ 0.3 Ctr (P ϭ 0.048). Muscle protein breakdown, assessed by phenylalanine rate of appearance, was increased (g ⅐ 100 ml Ϫ1 ⅐ min Ϫ1 ): 15.5 Ϯ 2.0 Ht vs. 9.6 Ϯ 1.4 Eut (P ϭ 0.03), 9.9 Ϯ 0.6 Ctr (P ϭ 0.02). Muscle protein synthesis rate did not differ significantly. Muscle mass and muscle function were decreased 10 -20% before treatment. All abnormalities were normalized after therapy. In conclusion, our results show that hyperthyroidism is associated with increased muscle amino acid release resulting from increased muscle protein breakdown. These abnormalities can explain the clinical manifestations of sarcopenia and myopathy. hyperthyroidism; skeletal muscle; amino acids; stable isotopes; tracers; protein synthesis; protein breakdown; energy metabolism THYROID HORMONES HAVE PROFOUND metabolic effects, and chronic hyperthyroidism is characterized by increased energy expenditure (EE) with increased oxidation of protein, glucose, and lipids (19,28). Loss of muscle mass and subsequent sarcopenia are prominent clinical features of hyperthyroidism (27), and recovery of muscle mass and function is prolonged, lasting several months (24). Accelerated whole body protein catabolism has been demonstrated in experimental hyperthyroidism (16), but studies of whole body leucine kinetics in clinical and experimental hyperthyroidism have yielded inconsistent results. Studies of protein metabolism in hyperthyroid patients before and after treatment have suggested that the net protein catabolism is mainly because of depressed rates of whole body protein synthesis (7, 20) with low or normal rates of proteolysis. In experimental hyperthyroidism, increased rates of proteolysis with no change in protein synthesis rates have been reported (6, 16), whereas Tauveron et al. (35) found both increased proteolysis and synthesis. Thyroid hormones have both anabolic and catabolic effects; therefore, the net effect on protein metabolism may vary, and the above inconsistencies may relate to heterogeneity both of the hyperthyroid subjects, in terms of severity and duration of hyperthyroidism, and of the methods employed.The metabolism of muscle protein in hyperthyroid subjects has previously been described measuring urinary excretion or arteriovenous differences of 3-methylhistidine to estimate myofibrillar degradation, giving conflicting results. Some report no...

In the presence of comparable levels of all major metabolic hormones, insulin sensitivity peaks at physiological levels of FFAs with a gradual decrease at elevated as well as suppressed FFA concentrations. These data constitute comprehensive dose-response curves for FFAs in the full physiological range from close to zero to above 2000 micromol/liter.

Objective: Concentrations of the orexigenic peptide ghrelin is affected by a number of hormones, which also affect circulating levels of free fatty acids (FFAs). The present study was therefore designed to determine the direct effect of FFAs on circulating ghrelin. Design: Eight lean, healthy men were examined for 8 h on four occasions using variable infusion rates (0, 3, 6 and 12 ml/kg per min) of intralipid to create different plasma FFA concentrations. Constant levels of insulin and GH were obtained by administration of acipimox (250 mg) and somatostatin (300 mg/h). At the end of each study day a hyperinsulinaemic-euglycaemic clamp was performed.

Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. It lowers hepatic glucose production and peripheral insulin resistance. Hypoglycaemia is seen only after intake of toxic doses or in combination with other antidiabetic drugs or after prolonged fasting. As metformin is excreted by the kidneys, care must be taken in renal insufficiency or liver disease because of risk of lactic acidosis. Large overdoses of metformin can lead to lactic acidosis as well. Suicide with metformin is rare. Intake of 35 g of metformin has been shown to be lethal (Teale et al. 1998). In the present paper we report on the treatment and outcome of a 70 year old man after ingestion of 63 g of metformin. Previously, survival after intake of up to 50 g has been described. Case reportA 70 year old man with type 2 diabetes mellitus who was being treated with metformin 850 mg twice daily and glimepiride 2 mg once daily was admitted in intensive care after deliberately taking an overdose of metformin of 63 g. The table shows laboratory results taken during admission. The patient had no known micro-or macrovascular complications and no other concomitant diseases than mild hypertension, which was treated with thiazides and ramipril. There was no history of recent alcohol abuse. Upon recovery the patient confirmed that no other toxic substances or overdoses of other drugs had been taken.On admission he was unconcious and hyperventilating. His blood pressure was 160/70, pulse rate110. He was hypoglycaemic; glucose 0.4 mmol/l, serum lactate was 17.7 mmol/l, pH 7.08, pCO 2 3.6, pO 2 12.0, bicarbonate 9.2 mmol/l and creatinin was 206 mmol/l. The metformin concentration was not measured.

Serum ghrelin levels are reversibly increased in hypothyroid patients. It remains to be investigated whether this represents a direct effect of iodothyronines on ghrelin secretion or clearance or a compensatory response to the abnormal energy metabolism in hypothyroid patients.