phosphocreatine and Hypothyroidism

Subclinical hypothyroidism (sHT) is considered to be a milder form of thyroid dysfunction. Few earlier studies have reported neuromuscular symptoms as well as impaired muscle metabolism in sHT patients.. In this study we report our findings on muscle bioenergetics in sHT patients using phosphorous magnetic resonance spectroscopy (31P MRS) and look upon the possibility to use 31P MRS technique as a clinical marker for monitoring muscle function in subclinical thyroid dysfunction.. Seventeen normal subjects, 15 patients with sHT, and 9 patients with hypothyroidism performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MR Spectroscopy measurements of inorganic phosphate (Pi), phosphocreatine (PCr), and ATP of the calf muscle were taken during rest, at the end of exercise and in the recovery phase. PCr recovery rate constant (kPCr) and oxidative capacity were calculated by monoexponential fit of PCr vs time (t) at the beginning of recovery.. We observed that changes in some of the phosphometabolites (increased phosphodiester levels and Pi concentration) in sHT patients which were similar to those detected in patients with hypothyroidism. However, our results do not demonstrate impaired muscle oxidative metabolism in sHT patients based upon PCr dynamics as observed in hypothyroid patients.. 31P MRS-based PCr recovery rate could be used as a marker for monitoring muscle oxidative metabolism in sub clinical thyroid dysfunction.

Topics: Adult; Asymptomatic Diseases; Energy Metabolism; Exercise; Female; Humans; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphorus; Recovery of Function; Rest; Young Adult

Topics: Female; Humans; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Muscle, Skeletal; Phosphocreatine

Mitochondrial metabolism particularly oxidative phosphorylation is greatly influenced by thyroid hormones. Earlier studies have described neuromuscular symptoms as well as impaired muscle metabolism in hypothyroid and hyperthyroid patients. In this study, we intend to look in to the muscle bioenergetics including phosphocreatine recovery kinetics based oxidative metabolism in thyroid dysfunction using in vivo (31)P nuclear magnetic resonance spectroscopy (MRS). (31)P MRS was carried out at resting state on 32 hypothyroid, 10 hyperthyroid patients and 25 control subjects. Nine out of 32 hypothyroid patients and 17 out of 25 control subjects under went exercise protocol for oxidative metabolism study and performed plantar flexion exercise while lying supine in 1.5 T magnetic resonance scanner using custom built exercise device. MRS measurements of inorganic phosphate (Pi), phosphocreatine (PCr), phosphodiesters (PDE) and adenosine triphosphate (ATP) of the calf muscle were acquired during rest, exercise and recovery phase. PCr recovery rate constant (k(PCr)) and oxidative capacity were calculated by monoexponential fit of PCr versus time (t) at the beginning of recovery. During resting condition in hypothyroid patients, PCr/Pi ratio was reduced whereas PDE/ATP and Pi/ATP were increased. However, in case of hyperthyroidism, an increased PCr/Pi ratio and reduced PDE/ATP and Pi/ATP were observed. The results confirmed differential energy status of the muscle due to increased or decreased levels of thyroid hormone. Our results also demonstrate reduced oxidative metabolism in hypothyroid patients based on PCr recovery kinetics. PCr recovery kinetics study after exercise revealed decreased PCr recovery rate constant (k(PCr)) in hypothyroid patients compared to controls that resulted in decrease in oxidative capacity of muscle by 50% in hypothyroids. These findings are consistent with a defect of high energy phosphate mitochondrial metabolism in thyroid dysfunction.

Topics: Adolescent; Adult; Child; Energy Metabolism; Female; Humans; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Metabolic Clearance Rate; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphorus Isotopes; Thigh; Young Adult

Whether cyclical changes in energy-related phosphate metabolites arise during a cardiac cycle in isolated rat hearts and are affected by differences in myosin isozyme composition was determined. Myocardial adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH in normal, hypothyroid and hyperthyroid rat hearts were measured using the pacing-gated 31P nuclear magnetic resonance technique. Maximal decrease in ATP and PCr, and maximal increase in Pi at the peak-systole in normal rat hearts were observed. In hypothyroid and hyperthyroid rats, similar cyclical changes in phosphate metabolites were observed during the cycle. However, the magnitude of fluctuations was smaller in hypothyroid rats and larger in hyperthyroid rats compared with that observed in normal rats. Cardiac myosin isozyme patterns were also different amongst the experimental groups. The results suggest that cyclical changes and the magnitude of fluctuations in energy-related phosphate metabolites during a cardiac cycle may depend on the cardiac workload and the intrinsic properties in the enzyme kinetics of myosin.

Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Heart; Heart Rate; Hydrogen-Ion Concentration; Hyperthyroidism; Hypothyroidism; In Vitro Techniques; Isoenzymes; Magnetic Resonance Spectroscopy; Male; Myocardium; Myosins; Phosphates; Phosphocreatine; Phosphorus; Rats; Rats, Wistar; Reference Values; Systole; Time Factors

Metabolic consequences of hypothyroidism in adult human brain, despite neuropsychological symptoms, have not been reported. We used 31P nuclear magnetic-resonance spectroscopy of the frontal lobe to examine the effect of acute hypothyroidism on cerebral metabolism. Paired analysis showed that the phosphocreatine/inorganic-phosphate (PCr/Pi) ratio increased from a median of 2.04 (interquartile range 0.15) to 2.22 (0.25) after treatment with levothyroxine (p = 0.01). These reversible alterations in adult cerebral phosphate metabolism during acute hypothyroidism parallel PCr/Pi ratio changes described in skeletal muscle. This is the first direct evidence of cerebral metabolic effects of hypothyroidism on adult brain.

Topics: Acute Disease; Adult; Brain; Carcinoma; Energy Metabolism; Humans; Hypothyroidism; Magnetic Resonance Spectroscopy; Middle Aged; Phosphates; Phosphocreatine; Thyroid Neoplasms; Thyroidectomy; Thyroxine

Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre-exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle.

Topics: Adult; Aged; Aged, 80 and over; Exercise; Female; Humans; Hydrogen-Ion Concentration; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria, Muscle; Muscles; Phosphates; Phosphocreatine

Phosphorus nuclear magnetic resonance spectroscopy was used to investigate the muscle bioenergetics in different hypothyroid states. Using the thenar muscle group as reference, 2 patients with chronic and severe hormonal deficiency, 3 patients with subacute hypothyroidism, and 8 patients with moderate thyroid insufficiency with isolated high blood TSH levels were studied at rest, during exercise, and during subsequent recovery. The patients were compared with 15 control subjects. Only 1 patient presented a clinical myopathy. The intracellular pH and the relative measurements of inorganic phosphate, phosphocreatine, phosphodiesters, and ATP were directly calculated from phosphorus spectra. Resting muscle showed a significant rise in the inorganic phosphate to ATP ratio. In working hypothyroid muscle, a more important decrease in phosphocreatine levels was noted in patients with chronic and subacute thyroid deficiency, while the intracellular pH fall was greater in all hypothyroid patients than in control subjects. The phosphocreatine recovery rate was lower in all deficient patients, reflecting a probable mitochondrial metabolism impairment. These results are consistent with a defect of the high energy phosphate metabolism in hypothyroidism, even in moderate or recent hormonal deficiency.

Topics: Adenosine Triphosphate; Adult; Aged; Energy Metabolism; Esters; Exercise; Female; Humans; Hypothyroidism; Magnetic Resonance Spectroscopy; Middle Aged; Muscles; Phosphates; Phosphocreatine; Phosphorus

31P magnetic resonance spectroscopy allows non-invasive evaluation of phosphorus metabolism in man. The purpose of the present study was to assess the influence of hyper- and hypothyroidism on the metabolism of resting human skeletal muscle. The present data show that quantitative measurement of phosphate metabolism by NMR is possible as also demonstrated by other studies. Using a quantitative evaluation method with an external standard, significant differences in the levels of phosphocreatine, adenosine triphosphate, and phosphodiesters were found. In hypothyroid patients a TSH-dependent increase in phosphodiesters and a decrease in adenosine triphosphate and phosphocreatine was observed. In hyperthyroidism a similar decrease in adenosine triphosphate but a considerably higher decrease in phosphocreatine occurred. In the light of the results of other studies of muscle metabolism, these changes appear to be non-specific so that further studies are required to assess the clinical value of such measurements.

Topics: Adenosine Triphosphate; Adult; Aged; Aged, 80 and over; Energy Metabolism; Female; Humans; Hyperthyroidism; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscles; Phosphocreatine

31P NMR spectroscopy was used to monitor the cardiac energy metabolism in hypothyroid rat hearts. Differential alterations in phosphocreatine and inorganic phosphate levels were observed upon treatment of hypothyroid animals with DT4 and LT4, while both agents were equipotent in reducing cholesterol. These results show potential for NMR spectroscopy as a technique to determine therapeutic selectivity.

Topics: Adenosine Triphosphate; Animals; Anticholesteremic Agents; Cholesterol; Dextrothyroxine; Energy Metabolism; Heart; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Myocardium; Phosphates; Phosphocreatine; Rats; Rats, Inbred Strains; Thyroxine

We have used 31P nuclear magnetic resonance (NMR) techniques to characterize bioenergetic changes in the Langendorff-perfused rat heart accompanying alterations in thyroid state. Cytosolic phosphocreatine and inorganic phosphate concentrations changed significantly in both the hypo- and hyperthyroid groups compared to controls; the calculated phosphorylation potential [( ATP]/[ADP][Pi]) increased by 60% in hypothyroidism and decreased by 60% in hyperthyroidism relative to the euthyroid value of 47 X 10(3) M-1. Creatine phosphokinase (CPK) and mitochondrial ATP synthase rates were measured in the intact tissue using a saturation-transfer NMR method. There were no significant differences in the measured fluxes through the CPK reaction among the three groups (4.24 +/- 1.00 mM X sec-1 for the euthyroid group). Although O2 consumption increased by 46% in hearts from hyperthyroid animals, no change in the measured mitochondrial ATP synthase flux was observed compared to the euthyroid flux of 1.05 +/- 0.11 mM X sec-1. These results suggest that the apparent in situ P/O ratio of mitochondria in hearts from hyperthyroid animals is reduced relative to that in euthyroid controls.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; ATP Synthetase Complexes; Cardiomegaly; Creatine Kinase; Energy Metabolism; Hyperthyroidism; Hypothyroidism; Magnetic Resonance Spectroscopy; Male; Multienzyme Complexes; Myocardium; Oxygen Consumption; Perfusion; Phosphates; Phosphocreatine; Phosphorus Isotopes; Phosphotransferases; Rats; Rats, Inbred Strains

Topics: Adenosine Triphosphate; Animals; Creatine; Creatine Kinase; Glycogen; Hyperthyroidism; Hypothyroidism; Muscles; Phosphocreatine; Rats

Topics: Adenosine Triphosphate; Amino Acids; Animals; Body Weight; Brain; Brain Chemistry; Carbon Dioxide; Carbon Radioisotopes; Glucose; Glycogen; Hyperthyroidism; Hypothyroidism; Leucine; Lipids; Liver; Organ Size; Phosphocreatine; Rats; Time Factors

Topics: Adenine Nucleotides; Animals; Citrates; Citric Acid Cycle; Fluorometry; Glycolysis; Heart Arrest; Hyperthyroidism; Hypothyroidism; Isocitrates; Male; Myocardium; NAD; Phosphocreatine; Phosphofructokinase-1; Rats; Time Factors