The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 5 2205-2210
Copyright © 2001 by The Endocrine Society
Enhanced Activity of the Purine Nucleotide Cycle of the Exercising Muscle in Patients with Hyperthyroidism
Hiroko Fukui,
Shin-ichi Taniguchi,
Yoshihiko Ueta,
Akio Yoshida,
Akira Ohtahara,
Ichiro Hisatome and
Chiaki Shigemasa
First Department of Internal Medicine, Tottori University Faculty
of Medicine, Yonago 683, Japan
Address all correspondence and requests for reprints to; Shin-ichi Taniguchi, M.D., Ph.D., First Department of Internal Medicine, Tottori University Faculty of Medicine, Yonago 683, Japan. E-mail:
stani{at}grape.med.tottori-u.ac.jp
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Abstract
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Myopathy frequently develops in patients with hyperthyroidism, but its
precise mechanism is not clearly understood. In this study we focused
on the purine nucleotide cycle, which contributes to ATP balance in
skeletal muscles. To investigate purine metabolism in muscles, we
measured metabolites related to the purine nucleotide cycle using the
semiischemic forearm test. We examined the following four groups:
patients with untreated thyrotoxic Graves’ disease (untreated group),
patients with Graves’ disease treated with methimazole (treated
group), patients in remission (remission group), and healthy volunteers
(control group). To trace the glycolytic process, we measured
glycolytic metabolites (lactate and pyruvate) as well as purine
metabolites (ammonia and hypoxanthine).
In the untreated group, the levels of lactate, pyruvate, and ammonia
released were remarkably higher than those in the control group.
Hypoxanthine release also increased in the untreated group, but the
difference among the patient groups was not statistically significant.
The accelerated purine catabolism did not improve after 3 months of
treatment with methimazole, but it was completely normalized in the
remission group. This indicated that long-term maintenance of thyroid
function was necessary for purine catabolism to recover.
We presume that an unbalanced ATP supply or conversion of muscle fiber
type may account for the acceleration of the purine nucleotide cycle
under thyrotoxicosis. Such acceleration of the purine nucleotide cycle
is thought to be in part a protective mechanism against a rapid
collapse of the ATP energy balance in exercising muscles of patients
with hyperthyroidism.
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Introduction
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IT IS WELL known that myopathy often
develops as a complication of hyperthyroidism and is present in
33–60% of thyrotoxic cases. Even though no muscular symptom is
observed, muscle hypotonia or fatigue can appear during exercise
(1, 2). Muscular symptoms will subside rapidly in parallel
with the recovery of thyroid function. According to a study that
involved 240 Japanese patients with thyroid myopathy, major symptoms,
such as muscle hypotonia or amyotrophy, were related to the prevalence
period and the age of the patients at the time of thyrotoxicosis
(3). Under thyrotoxic conditions, ATP is promptly
depleted, and myopathy easily develops, as the im glycogen content
decreases due to the suppression of glycogenesis and glycogenolysis.
This appears to be due to the same factors that cause glycogen storage
disease, which is accompanied by a low capacity to perform
exercise.
During vigorous exercise, glycogen is rapidly consumed, and ATP
consumption by the skeletal muscles increases more than the ATP supply.
At that time, the purine nucleotide cycle tries to catch up with the
insufficient ATP supply (Fig. 1
)
(4). The purine nucleotide cycle consists of three
intermediates, namely, AMP, inosine monophosphate (IMP),
and adenylosuccinic acid. Three enzymes, adenylate kinase,
5'-nucleotidase, and AMP deaminase, regulate the purine nucleotide
cycle. The purine nucleotide cycle plays a critical role in removing
AMP from the exercising muscles to keep a high adenylic acid energy
level (ATP+0.5ADP/ATP+ADP+AMP), which reflects ATP balance within the
muscle cell. Skeletal muscles have a high degree of AMP deaminase
activity and a low degree of 5'-nucleotidase activity compared with the
myocardium (5). Therefore, skeletal muscles convert AMP to
IMP, which is a membrane-impermeable nucleotide, keeping IMP within the
myocyte and promptly produce AMP through adenylosuccinate via
activation of adenylosuccinate synthetase and adenylosuccinate lyase.
The purine nucleotide cycle is known to work only after vigorous
long-term exercises. When the im ATP content decreases after hard
exercise, the AMP degradation (IMP
inosinehypoxanthine) progresses
to maintain a high constant intracellular energy level, and
simultaneously ammonia production increases due to AMP deamination
(AMPIMP+NH4). Accordingly, increases in
hypoxanthine and ammonia, which are membrane-permeable metabolites, are
supposed to be important parameters of purine catabolic reactions.
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Figure 1. The glycogenolysis/glycolysis and purine
catabolism pathway in muscle. 1) Adenylate kinase; 2) AMP deaminase; 3)
5'-nucleotidase.
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In glycogen storage disease types III, V, and VII, which are due to a
disorder of glycogenolysis, AMP deamination is greatly accelerated
because of an insufficient ATP supply from glycogenolysis. As a
consequence, large amounts of ammonia and hypoxanthine are released
into the blood. In addition to glycogen storage diseases, an enhanced
degradation of purine nucleotides is often observed in muscles of
patients with hypoparathyroidism or myopathy associated with
electrolyte disorders such as hypokalemia and hypophosphatemia
(6), so enhanced production of purine metabolites could be
associated with the impairment of ATP balance within skeletal
muscles.
We presume that myopathy in hyperthyroidism may also belong to the
group of skeletal muscle catabolic disorders caused by an impairment of
ATP balance. Based on this assumption, we used a semiischemic forearm
exercise test to investigate purine nucleotide cycle activity in the
skeletal muscles of patients with hyperthyroidism.
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Subjects and Methods
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Semiischemic forearm exercise test
As hard exercise is not an appropriate way to evaluate the
purine nucleotide cycle activity in patients with myogenic symptoms, we
employed the semiischemic forearm exercise test. This test induces a
rapid decrease in the ATP content of the muscle and stimulates the
purine nucleotide cycle. After resting in the supine position for 30
min, a manschette tourniquet was placed around the patient’s forearm,
and a pressure equivalent to the mean of the systolic/diastolic
pressure was applied. The patient was then asked to repeat a handgrip
exercise at 70% of maximum using a dynamometers at a rate of one
handgrip per s for 2 min. Blood was sampled from the forearm vein to
measure lactate, pyruvate, ammonia, and hypoxanthine, at rest,
immediately after exercise, and 10 min thereafter. The samples were
kept at -80 C, except for those used to determine ammonia, which were
collected in a frozen heparinized test tube and measured within a few
hours. Serum lactate, pyruvate, and ammonia were analyzed using an
enzymatic method (COBAS-FARA, Roche, Basel, Switzerland).
The procedure used to measure hypoxanthine was similar to those
described previously (7, 8). In brief, samples were
centrifuged at 2600 x g at 4 C for 15 min. Methanol
(1.6 mL) was added to 0.4-mL plasma samples, which were then
centrifuged at 29,000 x g for 5 min. Supernatants (1.0
mL) were decanted at 40 C, and 0.2 mL 0.3% ammonia was added. The
plasma hypoxanthine concentration was then measured by high pressure
liquid chromatography (model 510, Waters Corp., Milford,
MA).
To determine the maximum increase (
) in each metabolite during
exercise, lactate, pyruvate, and ammonia (immediately after
exercise - at rest) and hypoxanthine (10 min after - at
rest) were calculated. Although it is reasonable to measure the
difference between arterial and venous (A-V) concentrations of the
metabolites to examine muscle metabolism, we measured the changes in
the metabolites in the venous samples instead. In a preliminary study
we compared the changes in A-V concentration difference of
hypoxanthine, ammonia and lactate in the semiischemic forearm
with the changes in venous blood samples taken from the antecubital
vein (n = 5). As shown in Fig. 2, there were no significant differences between the increases in the A-V
difference in hypoxanthine, ammonia, or lactate and their
increases in the antecubital vein. This means the increases in
metabolites in blood from the antecubital vein after exercise were
almost equivalent to those in the A-V concentration difference in the
metabolites after exercise, indicating that the changes in the level of
metabolites in the venous sample reflected the metabolism of the
skeletal muscles instead of the A-V concentration difference of the
metabolites.
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Figure 2. Comparison of the changes in A-V
concentration difference in hypoxanthine, ammonia, and lactate with
their changes in the venous sample of control subjects (n = 5). V,
Concentration in the venous sample; V-A, A-V concentration difference.
Note that there were no significant differences between them.
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Subjects
Subjects were divided into four groups as follows: the untreated
group (untreated patients with Graves’ disease), the
methimazole (MMI)-treated group (patients with Graves’ disease
treated with methimazole), the remission group (patients with Graves’
disease in remission), and the control group (healthy volunteers)
(Table 1). We explained the purpose of
the study to all subjects and obtained their informed consent. The 20
patients in the untreated group consisted of 3 men and 17 women with a
mean age of 44.4 yr who were complaining of finger tremors,
palpitation, weight loss, and squatting and/or arm-up limitation in
daily life.
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Table 1. Serum free T3, free T4, and
TSH concentrations in untreated Graves’ disease, MMI-treated Graves’
disease, remission, and control groups
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Diagnosis of Graves’ disease was confirmed by the elevated free
T3 level (24.88 ± 9.22 pmol/L), the
undetectable TSH level, and the positive TSH binding inhibitory Ig
and/or thyroid-stimulating antibody. Their CPK, lactate
dehydrogenase, and GOT levels were within normal range (data not
shown). Patients with periodic paralysis were not included.
MMI-treated subjects, basically drawn from the untreated group, were
treated with MMI and performed the semiischemic forearm test again.
Free T4 (17.25 ± 5.41 pmol/L) normalized at
3 months after daily administration of 30 mg MMI. Patients who were in
a hypothyroid state during MMI treatment were not included in the
second trial. Eleven of the 20 patients in the MMI-treated group who
performed the second exercise test still complained of muscle symptoms.
The remission group included treated patients in whom normalized
thyroid function and absence of thyroid-stimulating antibody and TSH
binding inhibitory Ig lasted for at least 1 yr.
Statistical analysis
The values of lactate, pyruvate, ammonia, and
hypoxanthine in each group were determined and compared by ANOVA.
Differences with P < 0.05 were considered
statistically significant. The correlation between lactate and ammonia
was also estimated, and the regression line was calculated.
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Results
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Release of glycolytic metabolites after exercise in the untreated
group
As expected, handgrip forearm exercise under semiischemic
conditions resulted in poor ATP supply from aerobic glycolysis and
induced anaerobic glycolysis, which produces lactate and pyruvate.
After performing the handgrip exercise for 2 min, lactate (3.58 ±
2.62 vs. 1.94 ± 1.20 mmol/L; P <
0.05) and pyruvate (90.0 ± 57.4 vs. 32.1 ± 20.7
µmol/L; P < 0.05) were significantly higher in the
untreated group than in the control group (Fig. 3, A and B).
Purine metabolic products after exercise in the untreated
group
Then we estimated purine metabolic products. After performing the
handgrip exercise for 2 min, the level of ammonia released was
significantly higher in the untreated group (80.6 ± 81.3
vs. 18.3 ± 18.9 µmol/L; P < 0.05)
than in the control group. The level of hypoxanthine released was also
increased in the untreated group, but there was no significant
difference between the untreated group and the control group (5.85
± 5.25 vs. 3.45 ± 3.08 µmol/L; P =
0.184; Fig. 4, A and B).
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Figure 4. Purine metabolite production in the
untreated group during exercise. Ammonia and hypoxanthine in the
control (n = 15) and untreated groups (n = 20) were estimated
(ammonia, immediately after exercise - at rest;
hypoxanthine, 10 min after exercise - at rest). The raw values
of ammonia were as follows: control group: at rest, 28.87 ± 13.61
µmol/L; after exercise, 69.55 ± 59.30 µmol/L; and untreated
group: at rest, 22.76 ± 7.13 µmol/L; after exercise, 87.67
± 79.28 µmol/L. The raw values of hypoxanthine were as follows:
control group: at rest, 1.43 ± 1.64 mmol/L; after exercise,
4.66 ± 3.57 mmol/L; and untreated group: at rest, 2.69 ±
3.08 mmol/L; after exercise, 7.36 ± 5.21 mmol/L.
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Changes in muscle metabolic products in association with
the recovery of thyroid function
To study the direct effect of thyrotoxicosis on purine nucleotide
catabolism, the semiischemic forearm exercise test was carried out in
both the MMI-treated and remission groups. Figure 5 shows the responses of glycolytic and
purine metabolites in the untreated, MMI-treated, and the remission
groups. Lactate release did not decrease significantly in the
MMI-treated group. In the remission group, the release of lactate
markedly decreased, but the reduction was not significant either (Fig. 5A). The release of pyruvate and ammonia decreased in the MMI-treated
group, but the reduction was not significant. However, in the remission
group, the levels of pyruvate and ammonia normalized (Fig. 5, B and C).
We also measured the level of hypoxanthine in the remission group
(3.87 ± 2.99 µmol/L), and it was almost identical to that in
the control group (data not shown).
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Figure 5. Change in glycolytic and purine metabolite
production by treatment of thyrotoxicosis. Lactate, pyruvate, and
ammonia in the untreated (n = 20), MMI-treated (n = 11),
and remission (n = 13) groups. The raw values of lactate (A)were
as follows: untreated group: at rest, 1.00 ± 0.19 mmol/L; after
exercise, 4.59 ± 2.67 mmol/L; MMI-treated group: at rest,
1.08 ± 0.21 mmol/L; after exercise, 4.36 ± 1.59 mmol/L; and
remission group: at rest, 0.98 ± 0.30 mmol/L; after exercise,
4.36 ± 1.59 mmol/L. The raw values of pyruvate (B)were as
follows: untreated group: at rest, 1.00 ± 0.19 mmol/L; after
exercise, 4.59 ± 2.67 mmol/L; MMI-treated group: at rest,
1.08 ± 0.21 mmol/L; after exercise, 4.36 ± 1.59 mmol/L; and
remission group: at rest, 0.98 ± 0.30 mmol/L; after exercise,
4.36 ± 1.59 mmol/L. The raw values of hypoxanthine (C) were as
follows: untreated group: at rest, 1.00 ± 0.19 mmol/L; after
exercise, 4.59 ± 2.67 mmol/L; MMI-treated group: at rest,
1.08 ± 0.21 mmol/L; after exercise, 4.36 ± 1.59 mmol/L; and
remission group: at rest, 0.98 ± 0.30 mmol/L; after exercise,
4.36 ± 1.59 mmol/L.
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Correlation between lactate and ammonia
To estimate the relationship between glycolysis and the purine
nucleotide cycle, we compared lactate and ammonia in these
groups. A significant positive correlation between lactate and
ammonia was found in all groups (Fig. 6). Therefore, ammonia production is
supposed to be closely related to lactate production. When regression
lines were calculated and compared among all groups, the slopes of the
regression line in the untreated, MMI-treated, remission and
control groups were 28.04, 34.5, 14.3, and 9.9, respectively. Based on
these results, as the slope value of the regression line in the
untreated group was much higher than that in the control group, ammonia
production seemed to be much more accelerated than that of lactate in
hyperthyroidism. Therefore, purine catabolism through the activation of
the purine nucleotide cycle appeared to be more accelerated than
glycolysis in hyperthyroidism. Such an enhancement of purine catabolism
persisted for at least 3 months during MMI treatment, and it normalized
after long-term maintenance of thyroid function. Simultaneously, we
also estimated the correlation between lactate and hypoxanthine
in each of the four groups, but there was no significant correlation
between them (data not shown). This discrepancy between ammonia and
hypoxanthine seemed to be a feature peculiar to patients with
Graves’ disease.
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Discussion
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It is well known that patients with hyperthyroidism present muscle
hypotonia, fatigue, and myopathy. Several studies pointed out that
hyperthyroidism alters the ATP energy balance of skeletal muscle by
increasing glycolysis or glycogenolysis (9, 10, 11). In the
present study we focused on purine nucleotide metabolism of muscles,
which is regulated by the purine nucleotide cycle in hyperthyroidism
and also contributes to ATP energy balance.
In this study an elevation of serum lactate and pyruvate was observed
after forearm exercise in patients with hyperthyroidism. Lactate and
pyruvate are the metabolic products of glycolysis/glycogenolysis, and
the glycolysis/glycogenolysis process is supposed to be accelerated in
hyperthyroidism. This was not surprising, as the consumption of ATP in
hyperthyroidism is known to be much greater than that in the normal
state. Under semiischemic conditions, aerobic glycolysis tends to be
suppressed, and instead, anaerobic glycolysis starts to work to catch
up with the reduction of aerobic ATP supply. Then lactate, an anaerobic
glycolytic metabolite, should be produced and released into the
blood flow. The enhancement of muscle glycolysis in hyperthyroidism has
been demonstrated by Kruk et al. (12). They
observed that the lactate level was higher in hyperthyroidism than in
healthy controls. These results indicated that in hyperthyroidism
the muscle ATP content decreased, and this decrease was followed by
enhanced glycolysis/glycogenolysis.
Furthermore, an elevation of hypoxanthine and ammonia after forearm
exercise was observed in thyrotoxic patients. This indicated that the
activity of the purine nucleotide cycle was clearly accelerated in
hyperthyroidism. In general, an acceleration of purine catabolism
occurs due to the disturbances of the glycolytic systems similar to
that in muscle phosphorylase deficiency (glycogen storage disease type
V) (7). This is because ADP is rapidly converted to
AMP by adenylate kinase when the ATP supply is disturbed by
impairment of the glycolytic system. Additionally, once the
purine nucleotide cycle is activated (IMPinosinehypoxanthine),
hypoxanthine and ammonia production is augmented by AMP
deamination.
We observed a significant increase in ammonia after exercise in
patients with hyperthyroidism. However, the difference in hypoxanthine
release between hyperthyroidism and healthy controls was not
significant, although the average value appeared to be higher in
thyrotoxic patients. This result was puzzling, because accelerated
purine catabolism should produce hypoxanthine in parallel with ammonia
as metabolites. In glycogen storage disease type V, which accompanies
the acceleration of the purine nucleotide cycle, hypoxanthine
production strongly correlates with ammonia production
(7). We propose the following possibilities to explain
this discrepancy. When IMP is converted to hypoxanthine, the salvage
process (IMP to AMP) also works, which influences the release of
hypoxanthine independently of the release of ammonia (13).
Although the conversion of IMP to inosine is regulated by
5'-nucleotidase (Fig. 1
), this enzyme is controlled by the
intracellular pH. In hyperthyroidism, semiischemic exercise rapidly
increases im lactate, and accumulated lactate reduces the im pH level.
Such a pH reduction may suppress 5'-nucleotidase activity, and the
conversion of IMP to inosine would be suppressed; therefore, the
subsequent hypoxanthine production may also be decreased. Another
explanation is that thyrotoxicosis directly suppresses 5'-nucleotidase
activity, and then hypoxanthine production is suppressed. To elucidate
the hypoxanthine result, it will be necessary to measure
5'-nucleotidase activity and IMP and inosine production in the
exercising muscle in patients with hyperthyroidism.
It is now clear that both glycolysis and purine nucleotide catabolism
are remarkably accelerated in hyperthyroidism. There are several
explanations for the mechanisms involved in the acceleration of purine
metabolism. In hyperthyroidism, a large amount of ATP is supposed to be
consumed during exercise compared with that in healthy controls, and
the ATP supply from the glycolytic system is rapidly depleted, which
automatically advances to purine catabolism (14). Other
studies pointed out changes in the composition of muscle fiber type
induced by hyperthyroidism. Fitts et al. reported that type
II fibers (anaerobic glycolytic muscle) in rat muscles were increased
by the administration of T3 and
T4 (15). The content of type I
fibers in hypothyroidism is higher than that in healthy subjects, and
it is decreased by T4 administration
(16). Moreover, Celsing et al. found that type
I fibers could be converted to type II fibers in skeletal muscles of
patients with hyperthyroidism (17). It is well known that
AMP deaminase activity of type II fibers is higher than that of type I
fibers. Therefore, the whole AMP deaminase activity in muscle could be
enhanced by the conversion of type I to type II fibers in
hyperthyroidism. Moreover, it was reported that the im glycogen content
in hyperthyroidism was remarkably lower than that in healthy controls.
Celsing et al. demonstrated that the glycogen content was
markedly lower in type I fibers in hyperthyroidism using biopsy
specimens of muscles (17). Taken together, we presume the
following possibilities for enhanced purine catabolism in
hyperthyroidism: 1) an increase in ATP consumption due to the augmented
basal metabolic rate; 2) the acceleration of AMP deaminase activity by
the conversion of muscle fiber type; and 3) a poor supplementation of
ATP due to the low im glycogen content. As mentioned above, purine
catabolism contributes to the ATP energy balance in skeletal muscle.
The acceleration of purine catabolism results in the rapid conversion
of AMP to IMP, which maintains the im energy charge. Thus, acceleration
of purine catabolism may be a protective adjustment of skeletal muscles
of patients with hyperthyroidism to avoid a rapid collapse of ATP
energy balance.
It seemed important to determine whether the improvement of
hyperthyroidism was associated with the normalization of glycolysis and
purine nucleotide catabolism. As shown in Fig. 5, purine catabolism
normalized in parallel with the recovery of thyroid function. All
responses of metabolites, except lactate, completely improved in the
remission group. This result again confirms that purine metabolism of
skeletal muscles is directly affected by thyrotoxicosis. In this
respect it is noteworthy that a positive correlation between lactate
and ammonia was observed and that the regression line did not improve
after 3 months of treatment with MMI (Fig. 5, untreated vs.
MMI-treated group). This result suggests that purine catabolism
(AMPIMP + NH4) is more accelerated in
hyperthyroidism than in anaerobic glycolysis (glycogenlactate). The
maintenance of thyroid function for 2 months was not enough to improve
the accelerated purine catabolism in skeletal muscles. However, the
values of the regression line in the remission group were almost
identical to those in healthy controls, indicating that long-term
maintenance of thyroid function is necessary to improve the purine
metabolic change in muscles in hyperthyroidism. Complete recovery of
fiber type change or glycolysis in hyperthyroidism may require a
long-term maintenance of thyroid function. This observation is
compatible with clinical findings, as muscular symptoms in patients
with Graves’ disease tend to continue even after the complete recovery
of thyroid function by MMI treatment.
In conclusion, our study revealed that glycolysis and purine catabolism
were remarkably accelerated in hyperthyroidism, purine catabolism would
normalize in association with a long-term maintenance of thyroid
function, and thyrotoxic myopathy could be closely related to the
acceleration of purine catabolism.
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Acknowledgments
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We thank Prof. Kazumitsu Hirai for his continuous
encouragement.
Received October 23, 2000.
Revised January 18, 2001.
Accepted February 8, 2001.
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References
|
|---|
-
Hofmann WW, Smith RA. 1970 Hypokalemic
periodic paralysis studies in vitro. Brain. 93:445–474.[Free Full Text]
-
Edelman IS, Ismali-Beigi F. 1970 Mechanism of
thyroid calorogenesis: role of active sodium transport. Proc Natl Acad
Sci USA. 67:1071–1078.[Abstract/Free Full Text]
-
Ruff RT. 1986 Endocrine myopathies. Myology.
1881–1887.
-
Aragon JJ, Tornheim K, Goodman MN, et al. 1981 Replenishment of citric acid cycle intermediates by the purine
nucleotide cycle in rat skeletel muscle. Curr Top Cell Regul. 18:131.[Medline]
-
Zoref-Shani E, Shainberg A, Kessler-Icekson G. 1986 Production and degradation of AMP in cultured rat skeletal and
heart muscle: a comparative study. Adv Exp Med Biol. 195:485–491.
-
Hara N, Mineo I, Kono N, Shimizu T, et al. 1987 Enhanced release of ammonia and hypoxanthine from exercising muscles in
patients with idiopathic hypoparathyroidism. Muscle Nerve. 10:599–602.[CrossRef][Medline]
-
Mineo I, Kono N, Shimizu T, et al. 1985 Excess
purine degradation in exercising muscles of patients with glycogen
storage disease types V and VII. J Clin Invest. 76:556–560.
-
Kono N, Mineo I, Sumi S, et al. 1984 Metabolic
basis of improved exercise tolerance: muscle phosphorylase deficiency
after glucagon administration. Neurology. 34:1471–1476.[Abstract/Free Full Text]
-
Gustafsson R, Tara JR, Lindberg O, et al. 1965 The
relationship between the structure and activity of rat skeletal muscle
mitochondria after thyroidectomy and thyroid hormone treatment. J
Cell Biol. 26:555–570.[Abstract/Free Full Text]
-
Kubista V, Kubista J, Petle D. 1971 Thyroid hormone
induced changes in the enzyme activity pattern of energy supplying
metabolism of fast (white), slow (red), and heart muscle of the rat. Eur J Biochem. 18:553–560.[Medline]
-
Tara JR, Ernster L, Lindberg O, et al. 1963 The
action of thyroid hormone at the cell level. Biochem J. 86:408–428.[Medline]
-
Kruk B, Brzezinska Z, Kaciuba-Uscilko H, and Nazar
K. 1988 Thyroid hormones and muscle metabolism in dogs. Horm Metab
Res. 20:620–623.[Medline]
-
Hisatome I, Kitamura H, Saitoh M, et al. 1991 Excess release of hypoxanthine from exercising muscle in two Gout
patients with partial HGPRTase deficiency: lack of ammonia release. Am J Med. 90:533–535.[Medline]
-
Hisatome I, Ishiko R, Mashiba H, et al. 1990 Excess
purine degradation in skeletal muscle with hyperthyroidism. Musle
Nerve. 13:558–559.
-
Fitts RH, Winder WW, Brooke MH, et al. 1980 Contractile, biochemical and histochemical properties of thyrotoxic rat
soleus muscle. Am J Physiol. 238:C15–C20.
-
McKeran O, Slaving G, Andrews TM, et al. 1975 Muscle fiber type changes in hypothyroid myopathy. J Clin Pathol. 28:659–663.[Abstract/Free Full Text]
-
Celsing F, Blomstrand F, Melichna J, et al. 1986 Effect of hyperthyroidism on fibre-type composition, fibre area,
glycogen content and enzyme activity in human skeletal muscle. Clin
Physiol. 6:171–181.[Medline]
Top
Abstract
Introduction
), MMI-treated
(
), remission (•), and control (
) groups were calculated, and
each regression formula is shown.