Urinary excretion of 3-methylhistidine and creatinine and plasma concentrations of amino acids in hyperthyroid patients following preoperative treatment with antithyroid drug or β-blocking agent: Results from a prospective, randomized study

Adlerberth, Annika; Angerås, Ulf; Jagenburg, Rudolf; Lindstedt, Göran; Stenström, Gunnar; Hasselgren, Per-Olof

doi:10.1016/0026-0495(87)90146-6

Cited by 15 publications

(11 citation statements)

References 36 publications

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“…This question awaits answers from studies using a combination of tracer dilution and muscle biopsy techniques. Three previous studies (1,30,42) have, however, shown that urinary excretion of 3-methylhistidine, a marker of muscle myofibrillar protein degradation, is increased in hyperthyroidism. This strongly supports the view that myofibrillar degradation is increased in hyperthyroidism.…”

Section: Discussionmentioning

confidence: 97%

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Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

Riis¹,

Jørgensen²,

Gjedde³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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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...

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Section: Discussionmentioning

confidence: 97%

“…Some report normal values (6,7,20) and others report increased values (1,30,42) that were normalized after treatment. In addition, increased net muscle release of certain amino acids has been reported in hyperthyroid subjects.…”

mentioning

confidence: 99%

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

Riis¹,

Jørgensen²,

Gjedde³

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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“…In short-term studies of normal subjects given toxic doses of desiccated thyroid, Moses et al (1964) observed a decrease in serum creatinine concentration that probably occurred before substantial muscle mass was lost. On the other hand, it is known that mean 24-hour urinary creatinine excretion is significantly lower in thyrotoxic patients as compared to the same patients after attaining euthyroidism or to a control group (Beylot et al, 1984;Rodier et al, 1984;Adlerberth et al, 1987). This has been ascribed to a loss of muscle mass in thyrotoxic patients.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we observed significant elevations in the values for albumin: creatinine, NAG: creatinine and RBP: creatinine ratios in hyperthyroid patients compared to the same patients when euthyroid. We were concerned that the lower-than-normal 24h creatinine excretion that has been observed in hyperthyroid patients (Beylot et al, 1984;Rodier et al, 1984;Adlerberth et al, 1987) could have caused the ratios to be elevated rather than an increase in the concentrations of the protein analytes. This seems unlikely as there was no significant difference in the creatinine concentrations of the random urine specimens between hyperthyroidism and euthyroidism.…”

Section: Discussionmentioning

confidence: 99%

Renal Function and Electrolyte Levels in Hyperthyroidism: Urinary Protein Excretion and the Plasma Concentrations of Urea, Creatinine, Uric Acid, Hydrogen Ion and Electrolytes

Ford

Lim

Chisnall

et al. 1989

Clinical Endocrinology

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In order to help clarify the effects of hyperthyroidism on renal function and electrolyte metabolism, we measured the venous plasma concentrations of urea, creatinine, urate, hydrogen ion and electrolytes, and the urinary concentrations of total protein, albumin, retinol-binding protein, N-acetyl-beta-D-glucosaminidase activity, and creatinine in patients when hyperthyroid and again after they had been euthyroid for at least 4 months. Significant (P less than 0.05) decreases in the mean plasma concentrations of urate and chloride and significant increases in creatinine, total CO2 and hydrogen ion mean concentrations were observed when the patients became euthyroid. The mean concentrations of sodium, potassium and urea did not change significantly. The values of the ratios total protein/creatinine, albumin/creatinine, N-acetylglucosaminidase/creatinine and retinol-binding protein/creatinine were all significantly (P less than 0.05) elevated in random urine specimens obtained from hyperthyroid patients as compared to the values when euthyroid. Mild proteinuria occurs in most thyrotoxic patients which does not appear to be due predominantly to either glomerular or tubular renal injury. The changes in plasma analytes that were observed may be attributed to increases in glomerular filtration rate and tissue nucleic acid turnover and a tendency to respiratory alkalosis in the hyperthyroid patients.

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“…In addition, me toprolol treatment also affected growth and food consumption in a way that may indi cate some interference with basal metabolic processes. This apparent increase in energy consumption was somewhat surprising, since p-adrenoceptor-blocking agents are currently used in the treatment of hyperthy roid patients [30], However, recent studies in rats have failed to demonstrate effects of Pi-blockade on some of the metabolic altera- tions induced by triiodothyronine treatment [31,32], It is not possible from the available data to decide neither what the type of dis turbance is underlying the effects of metoprolol on growth and food consumption, nor if the effects were due to the drug itself, or to its metabolite(s) [22,23],…”

Section: Plasma Lipidsmentioning

confidence: 99%

Effects of Diet and Metoprolol on Lípid Levels in the Blood Plasma and Morphology of the Heart and Intramural Branches of Coronary Arteries of Spontaneously Hypertensive Male Rats

Sjöblom

Eklúnd²,

Östlund-Lindqvist³

et al. 1989

Ann Nutr Metab

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Semipurified diets containing 0.5% cholesterol were used in a 9-month study with spontaneously hypertensive male rats to characterize the effects of the protein source (casein vs. soybean protein), and the selective Β₁-adrenoceptor antagonist metoprolol on both lipid levels in blood plasma and the aorta, and on the morphology of intramural branches of coronary arteries. Raised blood lipid levels were observed in these rats. A significant decline in HDL₂ cholesterol took place, while plasma cholesterol belonging to lipoprotein fractions of lower density increased. Metoprolol treatment led to a substantial elevation of the plasma triacylglycerol level and, with time, a reduced cholesterolemic response. The use of soybean protein instead of casein had a persistent plasma lipid-lowering effect. Arteriosclerotic changes in the form of musculo-elastic thickenings, intimal cushions and homogeneous hyalin deposits appeared in the intramural coronary arteries of rats in all groups after 9 months on the diet. However, intimal deposition of lipid was only present in rats belonging to the casein group not treated with metoprolol. Rats of this group also showed more severe myocardial lesions in the form of scar tissue with or without inflammatory cell reaction.

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Urinary excretion of 3-methylhistidine and creatinine and plasma concentrations of amino acids in hyperthyroid patients following preoperative treatment with antithyroid drug or β-blocking agent: Results from a prospective, randomized study

Cited by 15 publications

References 36 publications

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

Renal Function and Electrolyte Levels in Hyperthyroidism: Urinary Protein Excretion and the Plasma Concentrations of Urea, Creatinine, Uric Acid, Hydrogen Ion and Electrolytes

Effects of Diet and Metoprolol on Lípid Levels in the Blood Plasma and Morphology of the Heart and Intramural Branches of Coronary Arteries of Spontaneously Hypertensive Male Rats

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Urinary excretion of 3-methylhistidine and creatinine and plasma concentrations of amino acids in hyperthyroid patients following preoperative treatment with antithyroid drug or β-blocking agent: Results from a prospective, randomized study

Cited by 15 publications

References 36 publications

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

Whole body and forearm substrate metabolism in hyperthyroidism: evidence of increased basal muscle protein breakdown

Renal Function and Electrolyte Levels in Hyperthyroidism: Urinary Protein Excretion and the Plasma Concentrations of Urea, Creatinine, Uric Acid, Hydrogen Ion and Electrolytes

Effects of Diet and Metoprolol on L&iacute;pid Levels in the Blood Plasma and Morphology of the Heart and Intramural Branches of Coronary Arteries of Spontaneously Hypertensive Male Rats

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Effects of Diet and Metoprolol on Lípid Levels in the Blood Plasma and Morphology of the Heart and Intramural Branches of Coronary Arteries of Spontaneously Hypertensive Male Rats