³¹Phosphor-Kernspinspektroskopie: Gestörter Energiestoffwechsel bei latenter Hyperthyreose^[*]

Zusammenfassung

Die ³¹Phosphor-Kernspinspektroskopie erlaubt die Untersuchung des Energiestoffwechsels menschlichen Gewebes in vivo. In der vorliegenden Studie sollte geprüft werden, ob auch bei latenter Hyperthyreose Abweichungen des muskulären Energiestoffwechsels auftreten, wie sie bei manifester Hyperthyreose bereits nachgewiesen wurden. Bei 10 Patienten mit unbehandelter manifester und 20 mit unbehandelter latenter Hyperthyreose sowie 24 schilddrüsengesunden Probanden wurde eine spektroskopische Untersuchung an der Wadenmuskulatur in einem 1,5-Tesla-Magneten durchgeführt. Die Muskelkonzentrationen von Phosphokreatin, anorganischem Phosphat und ATP wurden quantifiziert im Vergleich mit einer K₂HPO₄-Lösung als externem Standard. Dabei fand sich bei Patienten mit manifester und mit latenter Hyperthyreose eine signifikant verringerte Phosphorkreatin-Konzentration und eine tendentiell erniedrigte ATP-Konzentration. Zwischen den beiden Patientengruppen fanden sich keine signifikanten Konzentrationsunterschiede der Metaboliten. Die vorliegende Arbeit zeigte damit erstmals, daß Stoffwechselstörungen bei unbehandelter latenter Hyperthyreose gemessen werden können. Der Energiestoffwechsel des Skelettmuskels bei latenter Hyperthyreose wies dabei Veränderungen wie bei manifester Hyperthyreose auf.

Summary

³¹ Phosphorous magnetic resonance spectroscopy allows an in vivo examination of energy metabolism. The present study was designed to evaluate whether in patients with latent hyperthyroidism alterations of muscle energy metabolism could be found similar to those observed in patients with overt hyperthyroidism. In 10 patients with overt hyperthyroidism before therapy and 20 with latent hyperthyroidism (also without therapy) and in 24 healthy volunteers magnetic resonance spectroscopy of the calf muscle was performed within a 1.5-Tesla magnet. Muscle concentrations of phosphocreatine, inorganic phosphate, and ATP were quantified compared to an external standard solution of K₂HPO₄. In the patients with overt hyperthyroidism and with latent hyperthyroidism a significant decrease of phosphocreatine was found. Further, the ATP concentration in patients with latent and manifest hyperthyroidism tended towards lower values. There were no significant differences in the decrease of phosphocreatine and ATP between both patient groups. Therefore, this study for the first time shows that alterations of energy metabolism in latent hyperthyroidism can be measured and that they are similar to those observed in overt hyperthyroidism.

Schlüsselwörter

Latente/manifeste Hyperthyreose - ³¹ Phosphorspektroskopie - Skelettmuskel

Key words

Latent/overt hyperthyroidism - phosphorous-31-spectroscopy - skeletal muscle

^* Herrn Prof. Dr. Dr. h. c. H. Hundeshagen zum 65. Geburtstag

• LITERATUR

• 1 Argov Z, Bank WJ, Maris J, Peterson P, Chance B. Bioenergetic heterogeneity of human mitochondrial myopathies: Phosphorus magnetic resonance spectroscopy study. Neurol 1987; 37: 257-62.
• 2 Argov Z, Renshaw PF, Boden B, Winokur A, Bank WJ. Effects of thyroid hormones on skeletal muscle bioenergetics. J Clin Invest 1988; 81: 1695-701.
• 3 Arnold DL, Taylor DJ, Radda GK. Investigation of human mitochondrial myopathies by phosphorus magnetic resonance spectroscopy. Ann Neurol 1985; 18: 189-96.
• 4 Barany M, Glonek T. In: Phosphorus-31 NMR. Gorenstein D. ed. New York: Academic Press; 1984: 511-45.
• 5 Barany M, Siegel IM, Venkatasubramanbian PM, Mok E, Wilbur AC. Human leg neuromuscular diseases: P-31 spectroscopy. Radiology 1989; 172: 503-8.
• 6 Bessman SP, Geiger PJ. Transport of energy in muscle: phosphorylcreatine shuttle. Science 1981; 211: 448-52.
• 7 Bottomley PA. Human in vivo NMR spectroscopy in diagnostic medicine: clinical tool or research probe?. Radiology 1989; 170: 1-15.
• 8 Burt CT, Glonek T, Barany M. Analysis of phosphate metabolites, the intracellular pH, and the state of adenosine triphosphate in intact muscle by phosphorus nuclear magnetic resonance. J Biol Chem 1976; 251/9: 2584-91.
• 9 Chalovich JM, Burt CT, Danon MJ, Glonek T, Barany M. Phosphodiesters in muscular biopsies. Ann NY Acad Sei 1979; 317: 649-68.
• 10 Dawson MJ. Quantitative analysis of metabolite levels in normal human subjects by 31P topical magnetic resonance. Biosci Rep 1982; 02: 727-33.
• 11 Dillmann WH. Schilddriisenhormone. In: Endokrinologie. Hesch RD. Hrsg. München: Urban & Schwarzenberg; 1989. Kapitel 9.7: 320-35.
• 12 Edwards RHT, Dawon MJ, Wilkie DR, Gordon RE, Shaw D. Clinical use of nuclear magnetic resonance in the investigation of myopathy. Lancet 1982; 27: 725-30.
• 13 Gorbmann A, Dickhoff WW, Vigna SR, Clark NB, Ralph CL. The thyroid gland. In: Comparative endocrinology. Chichester: John Wiley & Sons; 1983
• 14 Guernsey DL, Edelmann LS. Regulation of thermogenesis by thyroid hormones. In: Molecular basis of thyroid hormone action. Oppenheimer JH, Samuels HH. eds. London, New York: Academic Press; 1983
• 15 Gyulai L, Zygmund R, Leigh JS, Chance B. Bioenergetic studies of mitochondrial oxidative phosphorylation using 31-phosphorus NMR. J Biol Chem 1985; 260: 3947-54.
• 16 Harris RC, Hultman E, Nordesjoe LO. Glycogen, glycolic intermediates and high- energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest 1974; 33: 109-20.
• 17 Harris RC, Edwards RHT, Hultman E. et al. The time course of phosphorycreatinc resynthesis during recovery of the quadriceps muscle in man. Pflügers Arch 1976; 367: 137-42.
• 18 Hoch FL. Thyrotoxicosis as a disease of mitochondria. N Engl J Med 1962; 266: 446-98.
• 19 lanuzzo D, Patel P, Chen V, O’Brien P, Williams C. Thyroidal trophic influence on skeletal muscle myosin. Nature 1977; 270: 74-6.
• 20 Ingwall JS. Phosphorus nuclear magnetic resonance spectroscopy of cardiac and skeletal muscles. Am J Physiol 1982; 242: H729-H744.
• 21 Kuhlback B. Creatine and creatinine metabolism in thyrotoxicosis and hypothyroidism. Acta Med Scand (Suppl) 1957; 01: 331.
• 22 Lenkinski RE, Holland GA, Allman T. et al. Integrated MR imaging and spectroscopy with chemical shift imaging of P-31 at 1.5 T: initial clinical experience. Radiology 1988; 169: 201-6.
• 23 Luyten PR, Groen JP, Vermeulen JWAH, Den Hollander JA. Experimental approaches to image localized human 31P NMR spectroscopy. Magn Reson Med 1989; 11: 1-21.
• 24 Moka D, Theissen P, Linden A, Waters W, Schicha H. Einfluß von Hyper- und Hypothyreose auf den Energiestoffwechsel der Skelettmiiskulatur - Eine Untersuchung mit ^3lP-Kernspinspektroskopie. Nucl-Med 1991; 30: 77-83.
• 25 Monreal M, Lafoz E, Foz M. Occult thyrotoxicosis in patients with atrial fibrillation and an acute atrial embolism. Angiology 1988; 39: 981-5.
• 26 Nowotny B, an Wder Heiden, Teuber J, Schmidt R, Usadel KH. Behandlungsbedürftigkeit der latenten Hyperthyreose. In: Schilddrüse. 1991 (im Druck).
• 27 Olbricht T, Reiners C, Benker G. Andere Erkrankungen und Autonomie. In: Schilddrüse 1989. Börner W, Weinheimer B. Hrsg. New York, Berlin: Walter de Gruyter; 1991: 216.
• 28 Ordidge RJ, Connelly A, Lohman JAB. Image-selected in vivo spectroscopy (ISIS). A new technique for spatially selective NMR spectroscop. J Magn Rcson 1986; 66: 283-94.
• 29 Pearce J, Aziz H. The neuromyopathy of hypothyroidism; some new observations. J Neurol Sei 1969; 09: 243-53.
• 30 Rockel M, Teuber J, Schmidt R. et al. Korrelation einer »latenten Hyperthyreose« mit psychischen und somatischen Veränderungen. Klin Wschr 1987; 65: 264-73.
• 31 Ross DS, Neer MR, Ridgway EC, Daniels GH. Subclinical hyperthyroidism and reduced bone density as a possible result of prolonged suppression of the pituitary-thyroid axis with L-thyroxine. Am J Med 1987; 82: 1167-70.
• 32 Sahlin K, Palmskog G, Hultman E. Adenine nucleotide amd IMP contents of the quadriceps muscle in man after excercise. Pflügers Arch 1978; 3747: 193-8.
• 33 Satoyoshi E, Murakami K, Kowa II. Myopathy in thyrotoxicosis: Neurology (Minneap). 1963; 13: 645.
• 34 Schicha H. Radiojodtherapie - neuester Stand: Nichtimmunogene Hyperthyreose. Akt Endokr Stoffw 1992; 13: 71-9.
• 35 Studcr Ramelli F. Simple goiter and its variants: euthyroid and hyperthyroid multinodular goiters. Endocr Rev 1982; 03: 40-61.
• 36 Sterling K, Lazarus JH, Milch PO, Sakurada T, Brenner MA. Mitochondrial thyroid hormone receptor: localization and physiological significance. Science 1978; 201: 1126-9.
• 37 Taylor DJ, Bore PJ, Styles P, Gadian DG, Radda GK. Bioenergetics of intact human muscle, a 31-P nuclear magnetic resonance study. Mol Biol Med 1983; 01: 77-94.
• 38 Tenerz A, Forberg F, Jaansson R. Is a more active attitude warranted in patients with subclinical thyrotoxicosis?. J Intern Med 1990; 228: 229-33.
• 39 Tofts PS. The noninvasive measurement of absolute metabolite concentration in vivo using surface-coil NMR spectroscopy. J Magn Reson 1988; 80: 84-95.
• 40 Van der Veen JWC, De Beer R, Luyten PR, Van Ormondt D. Accurate quantification of in vivo 31-P NMR signals using the variable projection method and prior knowledge. Magn Reson Med 1988; 06: 92-8.
• 41 van Hardeveld C, Kassenaar AAH. Thyroid hormone uptake and T₄ derived T₃ formation in different skeletal muscle types of normal and hyperthyroid rats. Acta Endocrinol 1978; 88: 306-20.
• 42 Vardarh I, Vardarh I, Schmidt R. et al. Significance of latent hyperthyroidism. Klin Wschr 1989; 67: 543-50.
• 43 Venkatasubramanian PN, Mafee MF, Barrany M. Quantitation of phosphate metabolites in human leg in vivo. Magn Reson Med 1988; 06: 359-63.
• 44 Wiles CM, Young A, Jones DA, Edwards RHT. Muscle relaxation rate, fibre-type composition and energy turnover in hyperand hypothyroid patients. Clin Sei 1979; 57: 375-84.
• 45 Wilkie DR, Dawson MJ, Edwards RHT, Gordon RE, Shaw D. 31P NMR studies of resting muscle in normal human subjects. In: Cross-bridge mechanisms in muscle contraction. Proc 2nd internat symp, Poliak G, Sugi H. eds. Seattle: 1983: 333-46.
• 46 Zohar A, Renshaw PF, Boden B, Winokur A, Bank WJ. Effects of thyroid hormones on skeletal muscle bioenergetics. J Clin Invest 1988; 81: 1695-701.
• 47 Zuercher RM, Horber FF, Gruenig BE, Frey FJ. Effect of thyroid dysfunction on thigh muscle efficiency. J Clin Endocrin Metab 1989; 69/5: 1082-6.