84例成人甲状腺机能减退性肌病临床荟萃分析

目的了解成人甲状腺机能减退性肌病的临床特点,提高对该病的认识。方法回顾分析1994年至2007年国内相关文献报道及中山大学附属第二医院收治的共84例甲状腺机能减退性肌病患者的临床资料。结果本组84例患者中多发性肌炎样综合征占64．3％,Hoffmann综合征占26．2％,不伴肌强直的肥大性肌病、不伴肌肥大的肌强直及肌萎缩3者共占9．5％。多发性肌炎样综合征患者都有四肢近端肌无力,57．7％有肌痛,33．3％肌电图显示肌源性损害,30％的患者肌活检见肌纤维肿胀断裂,40％有炎性细胞浸润。Hoffmann综合征患者都有肌肥大,68．4％有肌僵硬,36．8％的患者活动后有局部肌球形成,肌电图显66．7％示肌源性损害,16．7％出现肌强直（样）电位。所有患者甲状腺素替代治疗后症状消失,肌酶及甲状腺功能指标恢复正常。结论甲状腺机能减退性肌病分为不同临床类型,表现多样,预后好,甲状腺素替代治疗可治愈。临床对有肌病表现的患者应注意甲状腺机能减退性肌病。     

MYOPATHIES ASSOCIATED WITH HYPOTHYROIDISM: A REVIEW BASED UPON 13 CASES

The clinical and myopathological features of 13 patients with a myopathy occurring in association with hypothyroidism are presented. Seven patients had hypothyroid myopathy, including two with the Hoffmann syndrome and one with the Kocher-Debre-Semelaigne syndrome. Five patients had an inflammatory myopathy and one had polymyalgia rheumatica. Serum CK activity was elevated up to 12-fold in the patients with hypothyroid myopathy and returned to normal after treatment with thyroxine. Pathological changes in these cases included type 1 or type 2 fibre atrophy or hypertrophy, myofibre necrosis and regeneration in four cases and, in one case, prominent core-like areas containing amorphous granulo-filamentous material. The findings in this series of cases illustrate the clinical and histopathological heterogeneity of patients with hypothyroid myopathy and the need to consider other myopathies in hypothyroid patients who present with muscular symptoms.     

Hypothyroidism presenting as muscle stiffness and pseudohypertrophy: Hoffmann's syndrome

There is a spectrum of muscular abnormalities that occurs in patients with hypothyroidism. Alterations in deep tendon reflexes are commonly observed although more extensive muscle disease is less frequently seen. Two patients who demonstrated increased muscle mass, muscle stiffness with variable degrees of muscle weakness and low levels of serum thyroxine (Hoffmann's syndrome) are described. At the time of presentation, the serum creatinine phosphokinase level was more than 10 times greater than normal, and electromyography revealed repetitive positive waves. After therapy with thyroid hormone, there was complete resolution of the muscle abnormalities, and laboratory studies were performed. In this report, we review the clinical syndrome of muscle dysfunction that can be seen with the more severe forms of hypothyroid myopathy.     

A young lady with swelling and stiffness of calf muscles

Hypothyroidism causes a variety of changes in the body. Though uncommon, hypothyroidism can present as myopathy. Hoffman's syndrome is a specific, rare form of hypothyroid myopathy, which causes proximal weakness and pseudohypertrophy of muscles.     

Use of intravenous immunoglobulin and intravenous methylprednisolone in hyperhaemolysis syndrome in sickle cell disease

Hyperhaemolysis syndrome (HS), a syndrome in which there is destruction of both donor and recipient red cells after transfusion, is well recognised in patients with sickle cell disease and beta-thalassaemia. It has also been reported in a patient with myelofibrosis. In acute forms of HS, evidence of red cell antibody-mediated haemolysis is lacking, and it has been proposed that the transfused and the patient's own red blood cells were destroyed by hyperactive macrophages. Continuation of transfusion may be lethal as this can further exacerbate haemolysis. We report two cases of HS successfully treated with IVIg and IV methylprednisolone. The cessation of haemolysis following administration of IVIg and IV methylprednisolone supports the view that hyperactive macrophages contribute to the RBC destruction. IVIg and methylprednisolone appear to have a synergistic effect on suppressing the activity of macrophages.     

Use of Intravenous Immunoglobulin and Intravenous Methylprednisolone in Hyperhaemolysis Syndrome in Sickle Cell Disease

Hyperhaemolysis syndrome (HS), a syndrome in which there is destruction of both donor and recipient red cells after transfusion, is well recognised in patients with sickle cell disease and β-thalassaemia. It has also been reported in a patient with myelofibrosis. In acute forms of HS, evidence of red cell antibody-mediated haemolysis is lacking, and it has been proposed that the transfused and the patient's own red blood cells were destroyed by hyperactive macrophages. Continuation of transfusion may be lethal as this can further exacerbate haemolysis. We report two cases of HS successfully treated with IVIg and IV methylprednisolone. The cessation of haemolysis following administration of IVIg and IV methylprednisolone supports the view that hyperactive macrophages contribute to the RBC destruction. IVIg and methylprednisolone appear to have a synergistic effect on suppressing the activity of macrophages.     

Haemophagocytic syndromes in adults: current concepts and challenges ahead

Haemophagocytic syndrome (HS), also referred to as haemophagocytic lymphohistiocytosis or macrophage activation syndrome, comprises a heterogeneous group of disorders featuring sepsislike characteristics typically combined with haemophagocytosis, hyperferritinemia, hypercytokinemia and variable cytopenias, often resulting in fatal multiple organ failure. The availability of widely accepted diagnostic and therapeutic guidelines for the hereditary, paediatric forms of HS has improved outcome and lead to a better pathophysiological understanding. Although similar, reactive (secondary) HS in adults are distinct from childhood forms. Limited awareness of this type of disorder and the absence of clinical guidelines are to blame for delayed diagnosis and dire prognosis in many cases of HS in adults. Moreover, the underlying mechanisms of adult HS remain to be unravelled yet. We summarise general features of HS and discuss particular characteristics of this disorder inadults. Furthermore, we describe a simple screening and diagnostic algorithm based on serum markers of macrophage activation (ferritin, soluble CD163 and soluble CD25) and morphological evidence of haemophagocytosis. Application of this strategy might be instrumental for recruiting patients for clinical studies, early diagnosis and hence improved prognosis. Indeed, there is evidence that a subgroup of patients with systemic inflammatory response syndrome presenting with signs of macrophage activation benefit from early administration of intravenous immunoglobulins. Clinical studies are needed to validate our diagnostic approach and to establish well defined prognostic and therapeutic algorithms. Finally, we will discuss whether similar processes contribute to HS in adults compared to childhood forms.     

甲状腺功能减退性肌病误诊3例并文献复习

目的提高风湿免疫科临床医师对甲状腺功能减退性肌病的认识及诊断水平。方法分析3例误诊为结缔组织病的甲状腺功能减退性肌病病例,参考国内外文献探讨误诊的原因,并对甲状腺功能减退性肌病进行复习。结果山西医科大学第二医院风湿免疫科近半年收治了3例以"肌无力、肌酶谱升高"为主要表现的患者,初步诊断均为结缔组织病,其中2例给予糖皮质激素治疗,行甲状腺功能检查后均诊断为甲状腺功能减退症,结合患者病史、症状、体征及肌酶谱、肌电图等结果确诊为甲状腺功能减退性肌病,给予左旋甲状腺素钠片治疗,2例患者症状、体征及心肌酶谱、甲状腺功能均恢复正常。第3例患者在治疗中,临床表现及心肌酶谱也明显恢复。结论对临床出现肌无力、肌酶谱升高,但查体肌力、肌张力正常的患者,应考虑甲状腺功能减退性肌病的可能,对此类患者应该常规行甲状腺功能检查,以减少误诊误治。     

Corticosteroid myopathy: a clinical and pathological study

In six patients with Cushing's syndrome and three with steroid myopathy, the clinical, functional, biochemical and structural characteristics of myopathy are described. Proximal muscle weakness occurred in all the patients, preferentially affected the lower limbs and was accompanied by muscle wasting in all but one patient. Force measurements confirmed quadriceps weakness in every patient. Vastus lateralis muscle biopsies showed light microscopic abnormalities in two of three patients with steroid myopathy and one of five patients with Cushing's syndrome. Type II fibre atrophy was the commonest abnormality. Reduced type II mean fibre areas occurred in all the patients with steroid myopathy and were common in Cushing's syndrome patients. Type I mean fibre areas were also reduced in two of the former group and one of the latter group and two further patients in this group had areas at the lower end of the normal range. Abnormalities in electron microscopy, mitochondrial function tests and chemical content of skeletal muscle were frequent and are described and discussed. A plasma creatine kinase activity (CK) at the lower end of the normal range, a myopathic electromyogram (EMG) and a raised 24-h urinary 3-methylhistidine/creatinine ratio on a creatine free diet were other characteristic findings in both groups of patients.     

Vitamin-D-resistant osteomalacia in hemodialysis patients lacking secondary hyperparathyroidism

We describe a sporadic, vitamin-D-resistant osteomalacic syndrome in 19 patients undergoing hemodialysis. The syndrome was found in less than 1.5% of patients from referring dialysis centers. All 19 patients had multiple fractures, severe myopathy, and many developed spontaneous hypercalcemia. Severe osteomalacia without evidence of secondary hyperparathyroidism distinguished this syndrome from other forms of renal osteodystrophy. Bone aluminum, measured in six patients, was greatly elevated. Therapy with calcitriol (1 alpha, 25-dihydroxycholecalciferol) lad to clinical improvement in seven patients with reduced pain and myopathy, decreased serum alkaline phosphatase, or both, but no improvement in bone histology. Patients who did not respond clinically to calcitriol developed marked hypercalcemia. The cause of this severe osteomalacia, which occurs despite normal or slightly elevated levels of serum calcium and phosphorus and fails to mineralize with calcitriol, is unclear.     

Hypothyroid myopathy-pathological and ultrastructural study

Seventeen patients with hypothyroid myopathy were studied before and after thyroxine (T4) treatment. The severity of clinical myopathy was assessed with the aid of a modified rating scale. Laboratory findings including thyroid function, serum creatine kinase (CK), and electromyography were assessed at regular time intervals until a final muscle biopsy was performed. The average period of follow-up was 1.8 years. The authors emphasize: 1) in skeletal muscle pathology of hypothyroidism, the fiber atrophy and increased central nuclear counts are evidence of clinical myopathy during thyroxine treatment; 2) in ultrastructural pathology, the abnormal glycogen accumulation accounts largely for clinical severity and its ongoing resolution is parallel to steady amelioration following T4 therapy, while mitochondrial abnormalities are insignificant in clinical correlation and probably become permanent in some cases with prolonged hypothyroidism; and 3) serial needle biopsies of skeletal muscle are impractical for long-term study of hypothyroid myopathy, but they may be reserved for those patients with a sustained myopathic complaints on T4 therapy.     

Carbohydrate metabolism in hypothyroid myopathy

The carbohydrate metabolism in hypothyroid patients was investigated. After an overnight fast, the blood glucose level was 24% lower and the blood lactate level was 35% lower in the untreated hypothyroid patients than that observed in the treated hypothyroid patients or in the normal subjects. There was no difference in the blood alanine or plasma free fatty acid values between the subject groups. Skeletal muscle biopsied from two hypothyroid patients with marked myopathy showed normal glycogen content, 0.83%–0.86% (normal 1.06%), but reduced activity of acid maltase, 32–50 nmoles/min/g (normal 97). Forearm ischemic stimulation applied to hypothyroid patients failed to elevate the level of lactate. The results are compatible with impaired glycogenolysis from the skeletal muscle, which may be a contributory factor in the myopathy in hypothyroidism.     

Fenofibrate--induced myopathy in a patient with undiagnosed hypothyroidism--case report and a review of the literature

Hypothyroidism is one of the common causes of the secondary hypercholesterolemia. The prevalence of hypothyroidism in the general population is estimated to be as high as about 1.5%. Frequency of the hypothyroidism in patients with hyperlipidemia is high, and can be observed in 4.2-10% in different populations. Most commonly, there is no need to treat the hypothyroid patients with the hypolipidemic drugs. Substitution treatment with the thyroid hormones usually results in either normalization or significant decreasing of the lipid levels. Hypothyroidism with symptoms of involvement of skeletal muscles is referred as to hypothyroid myopathy in English literature, and can be present in 30-80% patients with deficiency of the thyroid hormones. Hypothyroidism is a risk factor of developing of toxic injury of muscles, what is thought to be related to hypolipidemic drug intake. We report a case of a patient with undiagnosed hypothyroidism with muscle involvement manifestation, who was treated with fenofibrate due to accidentally diagnosed hypercholesterolemia. Hypolipidemic management resulted in rapid exacerbation of previously moderate myopathy. High concentrations of muscle enzymes and moderate increasing of creatinine concentration were detected. Improvement was observed after discontinuation of fenofibrate administration, but muscle symptoms and elevation of muscle enzymes and creatinine persisted. After administration of levothyroxin, muscle weakness and laboratory abnormalities were observed no longer. After several months of follow-up we believe that treatment with fenofibrate in our patient was complicated with muscle tissue damage and exacerbated symptoms of myopathy originally related to decompensated hypothyroidism.     

Sleep apnea and hypothyroidism: mechanisms and management

PURPOSE: There is a high incidence of sleep apnea in patients with untreated hypothyroidism. Thyroxine treatment is said to significantly reduce the apnea index and length and sleep apnea symptoms. We undertook a review of 10 consecutive hypothyroid patients with sleep apnea to investigate mechanisms and management of these two disorders. PATIENTS AND METHODS: Polysomnograms were obtained in 10 consecutive hypothyroid patients referred to our sleep disorders unit. All patients were studied while hypothyroid. Eight patients were restudied later when euthyroid. Lung function, blood gas values, and awake supraglottic resistance were also assessed in each patient. RESULTS: All 10 patients had sleep apnea and were treated with thyroxine. In one patient, hypothyroid myopathy involving the upper airway was demonstrated to be a potential mechanism of sleep apnea in hypothyroidism. Nocturnal angina and ventricular arrhythmias developed in two patients, despite the use of low thyroxine doses. Nasal continuous positive airways pressure (CPAP) was begun in eight patients. Initiation of CPAP prevented further angina or arrythmia in the patients with these cardiac complications. Six of the eight patients who were available for follow-up studies had persistent sleep apnea despite an euthyroid status (apnea index before thyroxine, 51 +/- 6; apnea index after thyroxine, 45 +/- 8), and CPAP therapy was continued in these patients. CONCLUSION: Our experience suggests that the apnea index does not decrease significantly in all patients with hypothyroidism and sleep apnea when euthyroidism is achieved. Treatment of hypothyroidism in the presence of sleep apnea is potentially hazardous and may lead to cardiovascular complications. Management by a combination of CPAP and low-dose thyroxine is helpful in this situation.     

A case of myopathy associated with hypothyroidism and hyperprolactinaemia

We report a case of a serious myopathy related to hypothyroidism with pituitary enlargement and hyperprolactinemia. CASE REPORT: Mr D.L 33 years old man suffering from myalgia, muscular weakness and cramps for six months. The laboratory check-up revealed a high serum creatin phosphokinase level, an autoimmune hypothyroidism, hyperprolactinemia and pituitary enlargement. The electromyogram was normal and the muscle biopsy showed no obvious inflammation. The outcome was favourable under L. thyroxin. DISCUSSION: The frequency of myopathy during hypothyroidism ranges from 30 to 80%. The main symptoms related are weakness, muscular cramps and myalgia. However, hyperprolactinemia and pituitary enlargement described in this case are due to reactional mechanism. These several hypothyroid manifestations improve remarkably under L.thyroxin. CONCLUSION: Proximal myopathy may rarely be displayed as the sole manifestation of hypothyroidism. Therefore, it is recommended that hypothyroid myopathy should be taken into account during differential diagnosis of proximal muscle weakness.     

Rhabdomyolyse sévère révélant une myopathie hypothyroïdienne d’origine auto-immune: À propos de deux cas

While muscular manifestations are common of hypothyroidism, hypothyroid myopathy is most often limited to myalgia, muscular stiffness and cramps with, in some patients, elevated levels of muscle enzymes. We report two cases of rhabdomyolysis related to hypothyroid myopathy. One of the patients developed acute renal failure. Thyroid hormone replacement therapy improved thyroid and renal function with involution of rhabdomyolysis. Hypothyroidism appears to be an authentic cause of rhabdomyolysis and should be carefully ruled out in all patients with elevated serum levels of muscle enzymes.     

Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia

A number of disorders have been described to cause protein losing enteropathy (PLE) in children. Primary intestinal lymphangiectasia (PIL) is one mechanism leading to PLE. Few syndromes are associated with PIL; Hennekam syndrome (HS) is one of them. The principal treatment for PIL is a high protein, low fat diet with medium chain triglycerides supplementation. Supportive therapy includes albumin infusion. Few publications have supported the use of octreotide to diminish protein loss and minimize hypoalbuminemia seen in PIL. There are no publications on the treatment of PIL with octreotide in patients with HS. We report two children with HS and PLE in which we used octreotide to decrease intestinal protein loss. In one patient, octreotide increased serum albumin to an acceptable level without further need for albumin infusions. The other patient responded more dramatically with near normal serum albumin levels and cessation of albumin infusions. In achieving a good response to octreotide in both patients, we add to the publications supporting the use of octreotide in PIL and suggest that octreotide should be tried in patients with PIL secondary to HS. To the best of our knowledge, this is the first case report on the use of octreotide in HS-associated PIL.     

Calcitriol-Mediated Hypercalcaemia and Increased Interleukins in a Patient with Sarcoid Myopathy

In this report we describe a patient with Sjo¨gren’s syndrome (SS) and calcitriol-mediated hypercalcaemia. Initially, there was no clinical evidence of sarcoidosis. The patient had hypercalcaemia associated with increased calcitriol serum levels; circulating interleukin-6 and tumour necrosis factor alpha levels were also elevated. At the beginning, therapy with clodronate was effective in decreasing the serum calcium levels. However, the serum calcitriol decreased only after chloroquine treatment was added. After 2 years of therapy, the patient developed progressive and extensive muscle weakness. A muscle biopsy revealed a very prominent non-caseating granulomatous myopathy. Corticosteroid therapy was then instituted. Although both chloroquine and corticosteroid therapy were associated with decreased serum interleukin and calcitriol levels, only corticosteroid therapy was effective in treating the sarcoid myopathy. The role of cytokines in calcitriol mediated hypercalcaemia is discussed. Received: 1 February 1999 / Accepted: 2 June 1999     

Thyroid hormone regulates heparan sulfate proteoglycan expression in the growth plate

Thyroid hormone is essential for normal skeletal development. Hypothyroidism is associated with growth arrest, failure of chondrocyte differentiation, and abnormal matrix synthesis. Thyroid hormone modulates the Indian hedgehog/PTHrP feedback loop and regulates fibroblast growth factor (FGF)/FGF receptor signaling. Because heparan sulfate (HS) proteoglycans (Prgs) (HSPGs) are absolutely required by these signaling pathways, we have investigated whether thyroid status affects HSPG expression within the growth plate. Tibial growth plate sections were obtained from 12-wk-old rats rendered euthyroid, thyrotoxic, or hypothyroid at 6 wk of age, 14-d-old congenitally hypothyroid Pax8-null mice, and TRalpha/TRbeta double-null mice lacking all thyroid hormone receptors. HS and chondroitin sulfate Prg expression was determined by immunohistochemistry using three monoclonal antibodies. There was increased HS staining in growth plates from hypothyroid animals predominantly within the extracellular matrix of reserve and proliferative zones. Cellular HS staining was also increased particularly in prehypertrophic chondrocytes. T3 regulation of HSPG core protein and HS synthetic and modification enzyme expression was studied in ATDC5 cells using semiquantitative RT-PCR. Thyroid hormone negatively regulated expression of the core protein Gpc6, the polymerase Ext1, and the modification enzyme Hs6st2. These studies demonstrate that the expression and distribution of growth plate Prgs are regulated by thyroid hormone, and the regulation of HSPG expression provides an important additional link between FGF and Indian hedgehog signaling and T3. These novel observations suggest that the cartilage matrix and especially HSPGs are critical mediators of the skeletal response to thyroid hormone.