Ghrelin stimulates GH secretion as well as appetite and food intake. To explore whether ghrelin is involved in the regulation of appetite and body weight in hyperthyroidism, circulating ghrelin levels were measured in nine hyperthyroid patients before and after medical treatment and compared with those in eight healthy control subjects. All participants were studied in the postabsorptive state and during a 3-h euglycemic hyperinsulinemic clamp. Before treatment the patients had 3- to 5-fold elevations of T(3), and during treatment the patients gained 5 kg of body weight. Ghrelin levels were decreased in hyperthyroidism both in the fasting state (hyperthyroid, 1080 +/- 195 pg/ml; euthyroid, 1480 +/- 215 pg/ml; P = 0.03) and during clamp (hyperthyroid, 833 +/- 150 pg/ml; euthyroid, 1210 +/- 180 pg/m; P = 0.02). After treatment, ghrelin levels did not differ from those in control subjects. In all three study groups the clamp significantly reduced ghrelin levels compared with fasting levels. In conclusion, ghrelin levels are reduced in hyperthyroidism and become normalized by medical antithyroid treatment. Hyperinsulinemia suppresses ghrelin regardless of thyroid status. Ghrelin is not a primary stimulator of appetite and food intake in hyperthyroidism, and the mechanisms underlying the suppressive effect of hyperthyroidism on ghrelin secretion remain unclear.

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...

Hyperthyroidism is characterized by increased levels of circulating free fatty acids (FFA) and increased lipid oxidation, but it is uncertain which regional fat depots contribute. The present study was designed to define the participation of femoral and abdominal fat stores in the overall stimulation of lipolysis in hyperthyroidism in the basal state and during insulin stimulation. We studied nine women with newly diagnosed hyperthyroidism (HT) and after (euthyroidism, ET) medical treatment with methimazol and compared with eight control subjects (CTR). All subjects were studied in the postabsorptive state and during a 3-h hyperinsulinemic euglycemic clamp with microdialysis catheters sc in the abdominal and femoral adipose tissue. Before treatment, patients had elevated circulating concentrations of triiodthyronine, FFA, and glycerol. Levels of interstitial glycerol ( micro mol/liter) in abdominal adipose tissue [485 +/- 24 (HT), 226 +/- 20 (ET) (P < 0.001), 265 +/- 34 (CTR) (P < 0.001)] and in femoral adipose tissue [468 +/- 41(HT), 245 +/- 29 (ET) (P < 0.01), 278 +/- 31(CTR) (P < 0.005)] were elevated in the basal hyperthyroid state, and these differences prevailed during the glucose clamp [230 +/- 23 (HT), 113 +/- 13 (ET) (P < 0.01), 132 +/- 22(CTR) (P < 0.01) and 303 +/- 39 (HT), 122 +/- 15 (ET) (P < 0.01), 166 +/- 21(CTR) (P < 0.01)]. These results suggest that femoral and abdominal adipose tissue contribute equally to the excessive rate of lipolysis in hyperthyroidism and that both tissues are resistant to the actions of insulin.

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.

Background: Recent studies have indicated the existence of causal links between the endocrine and immune systems and cardiovascular disease. Mannan-binding lectin (MBL), a protein of the innate immune system, may constitute a connection between these fields. Methods: To test whether thyroid hormone regulates MBL levels, we studied eight patients with Graves' hyperthyroidism before and after methimazole therapy, eight healthy subjects before and after short-term experimental hyperthyroidism, and eight hypothyroid patients with chronic autoimmune thyroiditis before and after L-thyroxine substitution. Results: In all hyperthyroid patients, MBL levels were increased -median (range), 1886 ng/ml (1478 -7344) -before treatment and decreased to 954 ng/ml (312 -3222) after treatment (P ¼ 0.01, paired comparison: Wilcoxon's signed ranks test). The healthy subjects had MBL levels of 1081 ng/ml (312 -1578). Administration of thyroid hormones to these persons induced mild hyperthyroidism and increased MBL levels significantly to 1714 ng/ml (356-2488) (P ¼ 0.01). Two of the eight hypothyroid patients had undetectably low levels of MBL both before and after L-thyroxine substitution. The other six hypothyroid patients had decreased levels of MBL of 145 ng/ml (20-457) compared with 979 ng/ml (214 -1533) after L-thyroxine substitution (P ¼ 0.03, paired comparison: Wilcoxon's signed ranks test). Conclusion: Our data show that thyroid hormone increases levels of MBL. MBL is part of the inflammatory complement system, and this modulation of complement activation may play a role in the pathogenesis of a number of key components of thyroid diseases.