Elevated Serum Creatine Kinase Research Articles

Investigation of the inhibitory potential of phospholipase A2 inhibitor gamma from Sinonatrix annularis to snake envenomation

SaPLIγ is a novel gamma phospholipase A2 inhibitor (PLI) recently isolated from Sinonatrix annularis, a Chinese endemic non-venomous snake. To explore the neutralization effects of saPLIγ in snakebite envenomation, a dose equivalent to LD50 of Deinagkistrodon acutus, Agkistrodon halys and Naja atra venom with/without saPLIγ was inoculated into the gastrocnemius muscle of female Kunming mice. The ability of saPLIγ to inhibit myonecrosis and systemic toxicity were evaluated through investigations of muscle histopathology, and determination of the serum levels of creatine kinase (CK), lactate dehydrogenase isoenzyme1 (LDH1) and aspartate transferase (AST). Edema of the gastrocnemius muscle was evaluated by calculating the width difference between the inoculated limb and the contralateral leg. Desmin loss in the gastrocnemius muscle was determined by Western blot analysis. Co-immunoprecipitation and shotgun LC-MS/MS analyses were performed to identify venom proteins that interact with saPLIγ. All the envenomed mice had significantly elevated serum CK, LDH1 and AST levels, whereas the levels were decreased significantly in the presence of saPLIγ. Histopathological evaluation of gastrocnemius muscle sections showed severe snake venom-induced damage, characterized by leukocyte infiltration and erythrocyte leakage, leading to local edema. Myonecrosis, hemorrhage and desmin loss were significantly attenuated by saPLIγ. SaPLIγ interacted with a wide range of venom proteins, including PLA2s, metalloproteinases and C type lectins, which may contribute to broad anti-venom effects.

A comparative study of care practices for young boys with Duchenne muscular dystrophy between Japan and European countries: Implications of early diagnosis

Early diagnosis of Duchenne muscular dystrophy (DMD) is widely advocated to initiate proactive interventions and genetic counselling. Genetic testing now allows the diagnosis of DMD even prior to the onset of symptoms. However, little is known about care practices and their impact on young DMD boys and families after receiving an early diagnosis. We analysed 64 young boys (Japan, 19; the United Kingdom, 10; Germany, 18; Hungary, 6; Poland, 5; and the Czech Republic, 6) aged <5 years and diagnosed at ≤2 years old among the participants of the cross-sectional study about care practice in DMD. A combination of elevated serum creatine kinase and genetic testing usually led to the diagnosis (n = 31, 48%); 41 boys visited neuromuscular clinics more than once a year. Early diagnosis did not generally result in higher satisfaction among DMD families, and country-specific differences were observed. Psychosocial support following early diagnosis was perceived as insufficient in most countries, and deficits in access and uptake of genetic counselling resulted in lower satisfaction in the Japanese cohort. In conclusion, seamless and comprehensive support for DMD families following early diagnosis at presymptomatic stages should be taken into consideration if early genetic testing or newborn screening is made available more widely.

Familial partial lipodystrophy and proteinuric renal disease due to a missense c.1045C > T LMNA mutation.

Proteinuric renal disease is prevalent in congenital or acquired forms of generalized lipodystrophy. In contrast, an association between familial partial lipodystrophy (FPLD) and renal disease has been documented in very few cases. A 22-year-old female patient presented with impaired glucose tolerance, hyperinsulinemia, hirsutism and oligomenorrhea. On examination, there was partial loss of subcutaneous adipose tissue in the face, upper and lower limbs, bird-like facies with micrognathia and low set ears and mild acanthosis nigricans. Laboratory investigations revealed hyperandrogenism, hyperlipidemia, elevated serum creatine kinase and mild proteinuria. A clinical diagnosis of FPLD of the non-Dunnigan variety was made; genetic testing revealed a heterozygous c.1045C > T mutation in exon 6 of the LMNA gene, predicted to result in an abnormal LMNA protein (p.R349W). Electromyography and muscle biopsy were suggestive of non-specific myopathy. Treatment with metformin and later with pioglitazone was initiated. Due to worsening proteinuria, a renal biopsy was performed; histological findings were consistent with mild focal glomerular mesangioproliferative changes, and the patient was started on angiotensin-converting enzyme inhibitor therapy. This is the fourth report of FPLD associated with the c.1045C > T missense LMNA mutation and the second with co-existent proteinuric renal disease. Patients carrying this specific mutation may exhibit a phenotype that includes partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.Learning points:Lipodystrophy is a rare disorder characterized by the complete or partial loss of subcutaneous adipose tissue, insulin resistance, diabetes mellitus and hyperlipidemia.Proteinuric renal disease is a prevalent feature of generalized lipodystrophy but rare in familial partial lipodystrophy.Patients carrying the c.1045C > T missense LMNA mutation (p.R349W) may present with familial partial lipodystrophy, proteinuric nephropathy, cardiomyopathy and atypical myopathy.

A novel frameshift mutation in two siblings with merosin-deficient congenital muscular dystrophy

Introduction: Merosin-deficient congenital muscular dystrophy (MDC1A #607855) is an autosomal recessive disorder characterized by muscle weakness and hypotonia at birth that due to mutations in the laminin α2 (LAMA2) gene mapped to the 6q22-23 chromosomal location. Case reports: We present two siblings with elevated serum creatine kinase level, delayed motor milestones, muscle weakness and contractures of the lower limbs. The older sibling was 3 years old. She had proximal muscle weakness power of grade 3/5. Her deep tendon reflexes were absent. She had contractures on her lower limbs. Her intellectual and speech development was normal. The electromyogram showed a myopathic process. We suspected the diagnose of MDC1A and magnetic resonance imaging (MRI) revealed diffuse white matter hyperintensity supporting the diagnose. Immunohistochemical studies on the muscle biopsy showed dystrophic pattern and a completely negative reaction for merosin. The 20 months old patient was the younger sister of the first case. She had similar clinical features like her sister. Sequencing of two siblings revealed a novel homozygous frameshift mutation p.N55Mfs*16 (c.163_163delA) within the LAMA2 gene. Discussion: This mutation is leading to a premature stop codon and no reported in the literatüre. This study emphasize that in individual with congenital hypotonia, muscle weakness, elevated serum creatine kinase level and white matter abnormalities MDC1A should be kept in mind.

Outcome measures in the idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of rare autoimmune disorders that share some similarities, such as proximal predominant symmetric muscle weakness, also known as myopathy pattern 1,1 except for myopathy pattern 4 (distal arm and proximal leg weakness), in inclusion body myositis (IBM).1,2 Common features in IBM, dermatomyositis, polymyositis, and necrotizing autoimmune myopathy, frequently include serum creatine kinase (CK) elevation and myopathy with muscle membrane irritability on EMG. Muscle histopathology findings vary depending on the underlying disease, and may include inflammatory exudates of variable distribution, intact myofiber lymphocytic invasion, widespread necrosis and phagocytosis, or, in the case of IBM, rimmed vacuoles and protein aggregation.2,3

Novel predictors of neurosyphilis among HIV-negative syphilis patients with neurological symptoms: an observational study

BackgroundKnown predictors of neurosyphilis were mainly drawn from human immunodeficiency virus (HIV)-infected syphilis patients, which may not be applicable to HIV-negative populations as they have different characteristics, particularly those with neurological symptoms. This study aimed to identify novel predictors of HIV-negative symptomatic neurosyphilis (S-NS).MethodsFrom June 2005 to June 2015, 370 HIV-negative syphilis patients with neurological symptoms were recruited, consisting of 191 S-NS patients (including 123 confirmed neurosyphilis and 68 probable neurosyphilis patients) and 179 syphilis/non-neurosyphilis (N-NS) patients. Clinical and laboratory characteristics of S-NS were compared with N-NS to identify factors predictive of S-NS. Serum rapid plasma reagin (RPR), Treponema pallidum particle agglutination (TPPA), and their parallel testing format for screening S-NS were evaluated.ResultsThe likelihood of S-NS was positively associated with the serum RPR and TPPA titers. The serum TPPA titers performed better than the serum RPR titers in screening S-NS. The optimal cut-off points to recognize S-NS were serum RPR titer ≥1:4 and serum TPPA titer ≥1:2560 respectively. A parallel testing format of a serum RPR titer ≥1:2 and serum TPPA titer ≥1:1280 screened out 95.8% of S-NS and all confirmed cases of neurosyphilis. S-NS was independently associated with male sex, serum RPR titer ≥1:4, serum TPPA titer ≥1:2560, and elevated serum creatine kinase. Concurrence of these factors increased the likelihood of S-NS.ConclusionsQuantitation of serum TPPA is worthwhile and performs better than serum RPR in screening S-NS. Serum RPR, serum TPPA, male sex, and serum creatine kinase can predict S-NS. Moreover, patients with both a serum RPR titer <1:2 and a serum TPPA titer <1:1280 have a low probability of S-NS, suggesting that it is reasonable to reduce lumbar punctures in such individuals.

Exercise responses in patients with chronically high creatine kinase levels.

Elevated serum creatine kinase (CK) is often taken to reflect muscle disease, but many individuals have elevated CK without a specific diagnosis. How elevated CK reflects muscle metabolism during exercise is not known. Participants (46 men, 48 women) underwent incremental exercise testing to assess aerobic performance, cardiovascular response, and ventilatory response. Serum lactate, ammonia, and CK were measured at rest, 4 minutes into exercise, and 2 minutes into recovery. High-CK and control subjects demonstrated similar aerobic capacities and cardiovascular responses to incremental exercise. Those with CK ≥ 300 U/L exhibited significantly higher lactate and ammonia levels after maximal exercise, together with increased ventilatory responses, whereas those with CK ≥200 U/L but ≤ 300 U/L did not. We recommend measurement of lactate and ammonia profiles during a maximal incremental exercise protocol to help identify patients who warrant muscle biopsy to rule out myopathy. Muscle Nerve 56: 264-270, 2017.

Malignant hyperthermia susceptibility in patients with exertional rhabdomyolysis: a retrospective cohort study and updated systematic review

Two potentially fatal syndromes, malignant hyperthermia (MH), an adverse reaction to general anesthesia, and exertional rhabdomyolysis (ER) share some clinical features, including hyperthermia, muscle rigidity, tachycardia, and elevated serum creatine kinase. Some patients with ER have experienced an MH event and/or have been diagnosed as MH susceptible (MHS). In order to assess the relationship between ER and MH further, we conducted a retrospective cohort study summarizing clinical and genetic information on Canadian patients with ER who were diagnosed as MHS. In addition, a systematic literature review was performed to compile further evidence on MH susceptibility and RYR1 and CACNA1S variants associated with rhabdomyolysis. Demographic, clinical, and genetic information was collected on Canadian MHS patients who presented with rhabdomyolysis. In addition, we performed a systematic review of the literature published during 1995-2016 on genetic screening of the RYR1 and CACNA1S genes in patients with ER. Retrospective data on Canadian MHS patients with ER showed that ten out of 17 patients carried RYR1 or CACNA1S variants that were either known MH-causative mutations or potentially pathogenic variants. The systematic review revealed 39 different rare RYR1 variants, including 13 MH-causative/associated mutations and five rare potentially deleterious CACNA1S variants in 78% of patients with ER. Findings from the Canadian patient cohort and the systematic review all signal a potential association between MH susceptibility and ER. The presence of MH-causative mutations and putative deleterious RYR1 variants in ER patients without a history of adverse anesthetic reactions suggests their possible increased risk for MH.

A novel recessive TTN founder variant is a common cause of distal myopathy in the Serbian population.

Variants in the TTN gene have been associated with distal myopathies and other distinctive phenotypes involving skeletal and cardiac muscle. Through whole-exome sequencing we identified a novel stop-gain variant (c.107635C>T, p.(Gln35879Ter)) in the TTN gene, coding a part of the M-line of titin, in 14 patients with autosomal recessive distal myopathy and Serbian ancestry. All patients share a common 1 Mb core haplotype associated with c.107635C>T, suggesting a founder variant. In compound heterozygotes, nine other TTN variants were identified: four stop-gain, three frameshift, one missense and one splice donor variant. Patients homozygous for the common variant did not show significant clinical differences to the compound heterozygous patients. The clinical presentation of all patients was an adult onset distal myopathy with predominant lower limb involvement. In addition, most patients had normal to mildly elevated serum creatine kinase levels, myopathic electromyograms, normal cardiologic and respiratory tests and muscle pathology consistent with a dystrophic process. In this study, we describe a distinct phenotype for patients with distal myopathy associated with novel recessive TTN variants including a Serbian founder variant. Our results expand the phenotypic and genetic spectrum of titinopathies and will facilitate the diagnosis of this condition in patients of Serbian origin.

Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies.

Evolocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin/kexin type 9), markedly reduces low-density lipoprotein cholesterol across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group. This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and, of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in 2 OLE trials. AEs were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs, laboratory assessments, and AEs of interest were evaluated. Overall AE rates were similar between evolocumab and control in the parent trials (51.1% versus 49.6%) and in year 1 of OLE trials (70.0% versus 66.0%), as were those for serious AEs. Elevations of serum transaminases, bilirubin, and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive AEs were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups versus 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing antievolocumab antibodies were detected. Overall, this integrated safety analysis of 6026 patients pooled across phase 2/3 trials and 4465 patients who continued in OLE trials for 1 year supports a favorable benefit-risk profile for evolocumab.

Modified Calcium Homeostasis in Aged Mouse Skeletal Muscle

In aging decreased physical activity and reduced muscle mass (sarcopenia) leads to impaired muscle force and increased fatigability accompanied by a decline in sarcoplasmic reticulum (SR) calcium release. As an essential trace element selenium plays a significant role in muscle functions, as in selenium deficiency skeletal muscle disorders manifesting in muscle pain, fatigue, proximal weakness, and serum creatine kinase elevation could develop. Here in vivo physical activity of control and myostatin deficient (Cmpt) mice during 22 months were examined. Their performance in grip and voluntary wheel tests reached its maximum 3 month after birth and declined after 10 month. This decrease was faster in Cmpt mice as the average daily running distance decreased to 37% in control and to 25% in Cmpt mice in old age. In vitro force was measured on soleus and extensor digitorum longus (EDL) muscles from 20-month-old control, Cmpt, and selenium supplemented mice. Albeit the absolute force was higher in Cmpt than in control mice, after normalization to cross section EDL was significantly stronger in the latter (4.70±0.88 vs 7.61±0.96 mN/mm2, respectively). Selenium supplementation significantly increased the maximal force of EDL (10.89±0.60 mN/mm2). Changes in intracellular calcium concentration were measured on enzymatically isolated intact flexor digitorum brevis muscle fibers using Fura-2. The rate of KCl depolarization-evoked SR calcium release was greater in selenium supplemented than in control animals (691±100 vs 481±33 µM/s, respectively). Western-blot analysis revealed no change in the expression of the dihydropyridine receptor in the three animal groups while that of the ryanodine receptor declined with aging which was reversed by long-term training. Our results support the positive effects of selenium and training on SR calcium release in old age associated muscle weakness. On the other hand, the increased muscle mass of Cmpt mice during their lifespan doesn’t improve their physical performance in old age. Supported by: NKFIH-K-115461

Serum creatine kinase elevations in ultramarathon runners at high altitude

ABSTRACTObjectives: Creatine kinase (CK) is a sensitive enzyme marker for muscle damage in athletes. Elevated CK levels have been reported in many endurance physical activities. The consequence and possible long-term sequela of the CK elevation in athletes is unknown. There is a paucity of literature stating actual numerical values of CK associated with competing in an ultramarathon with extreme environmental conditions. Our hypothesis was that the serum CK levels increase significantly as a result of running a 161 km ultramarathon at high altitude.Methods: This was a prospective observational study of participants of the Leadville 100 ultramarathon race in Leadville, Colorado at high altitude (2800–3840 m) in August 2014. We collected blood samples from sixty-four volunteer runners before and eighty-three runners immediately after the race.Results: Out of 669 athletes who started the race, 352 successfully completed the race in less than the 30-hour cut-off time (52%). The majority of runners were male (84%). We were able to collect both pre- and post-race blood samples from 36 runners. Out of these 36 runners, the mean pre-race CK was increased from 126 ± 64 U/L to 14,569 ± 14,729 U/L (p < 0.001). There was a weak linear correlation between lower sodium levels and higher CK levels post-race (p = 0.003; R2 = 0.10). Using a multiple regression model, other than a negative correlation between sodium and CK levels (p = 0.001), there were no statistically significant correlations between post-race CK levels and athletes’ age, BMI, or finishing time.Conclusions: Significant elevation of CK level occurs as a result of running ultramarathons. The majority of athletes with significantly elevated CK levels were asymptomatic and required no major medical attention.

The swinging pendulum of biomarkers in mitochondrial disease

Mitochondrial diseases are clinically and genetically heterogeneous metabolic disorders that often present a substantial diagnostic challenge even for experienced clinicians.1 Although diagnostic clues are sought using widely available clinical chemistry tests (e.g., elevated serum lactate, pyruvate, or creatine kinase levels), patients are frequently subjected to invasive investigations including a muscle biopsy. Even then, a definitive diagnosis may not be forthcoming and consequently the identification of noninvasive diagnostic biomarkers has the potential to streamline the diagnostic process for both clinicians and patients.

Clinicopathological Features of Telbivudine-Associated Myopathy.

Telbivudine, a thymidine nucleoside analog, is a common therapeutic option for chronic hepatitis B infection. While raised serum creatine kinase is common, myopathy associated with telbivudine is rare. Reports on its myopathological features are few and immunohistochemical analyses of inflammatory cell infiltrates have not been previously described. We describe the clinical, myopathological and immunohistochemical features of four patients who developed myopathy after telbivudine therapy for chronic hepatitis B infection. All four patients presented with progressive proximal muscle weakness, elevation of serum creatine kinase and myopathic changes on electromyography. Muscle biopsies showed myofiber degeneration/necrosis, regeneration, and fibers with cytoplasmic bodies and cytochrome c oxidase deficiency. There was minimal inflammation associated with strong sarcolemmal overexpression of class I major histocompatibility complex (MHC class I). Upon withdrawal of telbivudine, muscle weakness improved in all patients and eventually completely resolved in three. In our series, telbivudine-associated myopathy is characterized by necrotizing myopathy which improved on drug withdrawal. Although the occasional loss of cytochrome c oxidase is consistent with mitochondrial toxicity, the overexpression of MHC class I in all patients could suggest an underlying immune-mediated mechanism which may warrant further investigation.

Exertional rhabdomyolysis: physiological response or manifestation of an underlying myopathy?

Exertional rhabdomyolysis is characterised by muscle breakdown associated with strenuous exercise or normal exercise under extreme circumstances. Key features are severe muscle pain and sudden transient elevation of serum creatine...

Current and emerging treatment strategies for Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families.

A case of malignant hyperthermia that was difficult to be differentiated from oral antipsychotic polypharmacy-associated neuroleptic malignant syndrome.

Malignant hyperthermia (MH) occurred during anesthesia with volatile inhalation anesthetics in a patient under treatment with multiple oral antipsychotic drugs and with a history of multi-acting receptor-targeted antipsychotic drug (MARTA)-induced elevation of serum creatine kinase (CK). Since the patient was considered to be at high risk for neuroleptic malignant syndrome (NMS) based on this history, differential diagnosis between MH and NMS was difficult at the time of onset. Later, the patient was found to be predisposed to MH based on abnormal high rate of the Ca2+-induced Ca2+ release (CICR). We concluded that MH was induced by the volatile inhalation anesthetics.

Effect of fraction iv portion of &lt;i&gt;Ximenia americana&lt;/i&gt; stem bark on &lt;i&gt;Trypanosoma congolense&lt;/i&gt; - induced serum enzymes changes in rats

The current study investigates the effect of fraction IV portion of Ximenia americana stem bark on Trypanosoma congolense induced serum enzymes changes in rats. Following infection with trypanosomes, the rats were monitored for levels of some serum enzymes. The results revealed that there was significant (P<0.05) elevation of serum enzymes Aspartate AminoTransferase (AST), Alanine AminoTransferase (ALT), Alkaline Phosphatase (AP), Gamma GlutamylTransferase (GGT) and Creatine Kinase (CK) in the infected animals. Treatment with 25 mg/Kg body weight fraction IV portion of Ximenia americana led to significant (P<0.05) reduction in levels of the enzymes. It is concluded that treatment with fraction IV portion of Ximenia americana was able to modulate the effect of trypanosomosis induced serum enzyme levels of the infected rats. Key words : Fraction IV, serum enzymes, Trypanosoma congolense, Ximenia americana

Absence of anti-HMG-CoA reductase autoantibodies in severe self-limited statin-related myopathy.

Patients with self-limited statin-related myopathy improve spontaneously when statins are stopped. In contrast, patients with statin-associated autoimmune myopathy have autoantibodies recognizing 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) and usually require immunosuppressive therapy to control their disease. On initial presentation, it can sometimes be difficult to distinguish between these 2 diseases, as both present with muscle pain, weakness, and elevated serum creatine kinase (CK) levels. The goal of this study was to determine whether patients with severe self-limited statin-related myopathy also make anti-HMGCR autoantibodies. We screened 101 subjects with severe self-limited cerivastatin-related myopathy for anti-HMGCR autoantibodies. No patient with severe self-limited cerivastatin-related myopathy had anti-HMGCR autoantibodies. Anti-HMGCR autoantibody testing can be used to help differentiate whether a patient has self-limited myopathy due to cerivastatin or autoimmune statin-associated myopathy; these findings may apply to other statins as well. Muscle Nerve 54: 142-144, 2016.

Hypothyroid myopathy: A peculiar clinical presentation of thyroid failure. Review of the literature.

Abnormalities in thyroid function are common endocrine disorders that affect 5-10% of the general population, with hypothyroidism occurring more frequently than hyperthyroidism. Clinical symptoms and signs are often nonspecific, particularly in hypothyroidism. Muscular symptoms (stiffness, myalgias, cramps, easy fatigability) are mentioned by the majority of patients with frank hypothyroidism. Often underestimated is the fact that muscle symptoms may represent the predominant or the only clinical manifestation of hypothyroidism, raising the issue of a differential diagnosis with other causes of myopathy, which sometimes can be difficult. Elevated serum creatine kinase, which not necessarily correlates with the severity of the myopathic symptoms, is certainly suggestive of muscle impairment, though it does not explain the cause. Rare muscular manifestations, associated with hypothyroidism, are rhabdomyolysis, acute compartment syndrome, Hoffman's syndrome and Kocher-Debré-Sémélaigne syndrome. Though the pathogenesis of hypothyroid myopathy is not entirely known, proposed mechanisms include altered glycogenolytic and oxidative metabolism, altered expression of contractile proteins, and neuro-mediated damage. Correlation studies of haplotype, muscle gene expression and protein characterization, could help understanding the pathophysiological mechanisms of this myopathic presentation of hypothyroidism.