Respiratory muscle strength in hypothyroidism.

To investigate respiratory muscle strength in patients with hypothyroidism, global respiratory muscle strength was assessed by measuring mouth pressure during PImax and PEmax efforts. Maximum pressures, VC, FEV1, FVC, T3, T4, and TSH were measured in 43 hypothyroid patients. Measurements were made before and three months after replacement therapy with thyroxine. The results showed that the mean value of PImax and PEmax increased after treatment. Significant change was found in the mean value of VC, FEV1, and FVC after treatment but not in the FEV1/FVC ratio. A highly statistically significant linear relationship was found between PImax and TSH and between PEmax and TSH as well as between PImax and T3 and PEmax and T3. We conclude that hypothyroidism affects respiratory muscle strength and that this weakness is linearly related to thyroid hormone levels. Respiratory muscle weakness is present in both inspiratory and expiratory muscles and is reversible with treatment.     

The relationship between sleep apnea syndrome and hypothyroidism.

To evaluate the prevalence of obstructive sleep apnea syndrome (OSAS) in patients with hypothyroidism, the prevalence of hypothyroidism in patients with OSAS, the possible factors predisposing to sleep-related breathing disorder in hypothyroid patients, and the effect of thyroid hormone in treating hypothyroidism associated with OSAS, we studied 65 patients with proven OSAS (apnea index [AI] > 5) and 20 hypothyroid patients. All patients were monitored for one overnight sleep study using polysomnography (Grass 78). We found only two (3.1 percent) of 65 OSAS patients had thyroid hypofunction. Of 20 patients with hypothyroidism, two showed moderate to severe OSAS and three had mild OSAS. Patients with both hypothyroidism and OSAS had impaired respiratory drive, but this was corrected by thyroid hormone therapy. Patients with hypothyroidism without OSAS were younger and had a lower percentage of ideal body weight than those with both hypothyroidism and OSAS. All hypothyroid patients were snorers. Thyroid hormone replacement was effective in correcting snoring only after one year of therapy. We conclude the following: (1) an overnight sleep study is not necessary in every case of hypothyroidism; (2) thyroid function studies need not be done routinely for every OSAS patient; (3) thyroid hormone therapy is effective for OSAS but it takes longer to correct the snore than respiratory drive; and (4) age and body weight are related to the development of OSAS.     

A case of successful coronary artery bypass grafting in a patient with angina pectoris and hypothyroidism

There is a clinical dilemma in the treatment of patients with hypothyroidism and coronary artery disease; excess thyroid hormone administration may exacerbate anginal symptoms, and yet inadequate thyroid replacement may induce congestive heart failure. A case of successful coronary artery bypass grafting in a patient with angina pectoris and hypothyroidism is described in this paper. A 55 year-old woman with this complication initially received thyroid replacement therapy under strict monitoring. Forty days after the start of the thyroid replacement therapy, serum levels of thyroid hormone had reached the normal range, and then coronary artery bypass grafting was successfully performed. She recovered without any complications, and is now free from chest pain in spite of thyroid replacement therapy.     

Abnormal ventilatory chemosensitivity and congenital myopathy

Abnormal ventilatory function is common in patients with neuromuscular disorders. This report describes depressed ventilatory response to both hypoxia and hypercapnia, as well as arterial oxygen desaturation during sleep in a family with congenital myopathy. The index patient also had an abnormal ventilatory response to metabolic acid loading. There was clinical evidence of proximal muscle weakness, and a muscle biopsy specimen was consistent with myopathy. The reduction in ventilatory drive, however, could not be explained solely by ventilatory muscle weakness. This report describes a distinct familial syndrome of congenital myopathy and abnormal ventilatory response to hypercapnia and hypoxia. All affected family members had unique facial features, proximal muscle weakness, and impaired ventilatory responses. The combination of impaired ventilatory drive and reduced ventilatory muscle strength leaves patients particularly vulnerable, and heightened awareness of this association is important in the treatment of these patients.     

Rhabdomyolysis, renal failure, pericardial effusion, and acquired von Willebrand disease resulting from hypothyroidism in a 10-year-old girl.

A 10-year-old girl manifested unexplained muscle aches and high creatine phosphokinase (CPK) concentrations attributed to rhabdomyolysis in association with severe hypothyroidism due to autoimmune thyroiditis. The response to therapy strongly suggested that hypothyroidism was the cause of rhabdomyolysis. Hypothyroidism is a rare cause of rhabdomyolysis. It should always be considered in a patient with muscular symptoms and elevated CPK concentrations. In addition, the patient developed other uncommon manifestations of hypothyroidism such as pericardial effusion, acute renal failure, and acquired von Willebrand disease. After thyroxine replacement, the symptoms and abnormal findings disappeared. The patient was also diagnosed as having celiac disease, which is often associated with autoimmune thyroiditis. Conditions accompanying autoimmune thyroid disease may result from altered thyroid function and from the presence of other autoimmune diseases. The butterfly-shaped thyroid gland has a tremendous impact on metabolism, which may be compared to a phenomenon termed the "Butterfly Effect".     

Severe respiratory failure secondary to Cushing's myopathy.

We report a 55-year-old woman with typical clinical, biochemical and radiological features of Cushing's disease, who developed a severe respiratory insufficiency as the main symptom. She also complained of proximal muscle weakness over the last year and progressive dyspnea over the last four months. Bronchospasm, respiratory infection or cardiologic dysfunction were excluded. Arterial blood gas analysis showed severe respiratory insufficiency with hypoxemia and hypercapnia, respiratory acidosis and a normal alveolar-arterial oxygen gradient. Spirometry and plethysmography showed a restrictive ventilatory failure and maximum inspiratory and expiratory pressures were reduced. These findings were strongly suggestive of neuromuscular disease. Serum creatine kinase, aldolase, sodium, potassium and thyroid function tests were normal. An electromyogram and a muscle biopsy confirmed myopathic disease. Ketoconazole therapy improved her symptoms and respiratory function tests. In conclusion although proximal myopathy is a frequent presenting symptom of Cushing's syndrome, involvement of respiratory muscles with severe restrictive ventilatory dysfunction has not been previously reported as the main initial feature of Cushing's disease. Medical treatment of hypercortisolism improves muscle strength and resolves the respiratory insufficiency.     

Type III hyperlipidaemia with primary hypothyroidism: a unique clinical course of hyperlipidaemia during replacement therapy of thyroid hormone

A patient is described with type III hyperlipidaemia and primary hypothyroidism who had a unique clinical course of hyperlipidaemia. The patient was a 65-year-old man with primary hypothyroidism. His plasma total cholesterol, triglyceride and high density lipoprotein-cholesterol concentrations 1 year after starting thyroid hormone replacement therapy were 7.98, 4.04 and 0.72 mmol/l, respectively. His plasma apolipoprotein (apo) E level was 0.29 g/l and its phenotype was E2/2. Remarkably, this patient had no hyperlipidaemia before starting thyroid hormone replacement therapy but it became overt only after the hypothyroidism had been treated. Although we have not confirmed the mechanism for this, we speculate that a decrease in enzyme activities responsible for cholesterol production may have been sufficient to surpass the effect of apolipoprotein E2/2 and the decrease in enzyme activities involved in degrading and excreting plasma cholesterol, resulting in normolipidaemia.     

原发性甲状腺功能减退致类多肌炎样综合征四例报道并文献复习

目的 提高甲状腺功能减退致类多肌炎样综合征的认识.方法 报道4例确诊为原发性甲状腺功能减退致类多肌炎样综合征的临床特点.结果 4例患者均为男性,开始均出现双下肢乏力和肌酸激酶明显增高等类多肌炎样表现,后检查确诊为原发性甲状腺功能减退,经过甲状腺激素补充治疗后类多肌炎样表现明显好转.结论 甲状腺功能减退可合并类多肌炎样综合征,临床上肌酸激酶增高时应注意筛杳甲状腺功能.     

A difficult case of inflammatory myositis

A 79-year-old lady presented with subclinical autoimmune hypothyroidism and proximal muscle weakness, which failed to respond to thyroxine. Subsequent electromyography and muscle biopsy confirmed polymyositis, which responded well to immunosuppressive therapy. She presented 4 months later with a thyroid carcinoma, most likely anaplastic, and died shortly afterwards. Although the association between malignancy and polymyositis remains controversial, to our knowledge this is the first report of thyroid carcinoma occuring in association with polymyositis and autoimmune hypothyroidism.     

Successful outcome of pregnancy in a thyroidectomized-parathyroidectomized young woman affected by severe hypothyroidism.

Severe hypothyroidism was discovered in a young woman in her 29th week of pregnancy. Previously, at the age of 12 years, she had undergone thyroid surgery for Graves' disease that resulted in persistent hypothyroidism and hypoparathyroidism. After surgical excision, the patient started levothyroxine replacement therapy and had regular control of thyroid function with normal findings throughout the years. The dose of levothyroxine had not been adjusted when the pregnancy started, and at the 29th week of gestation the patient had a thyrotropin (TSH) of 72.4 microU/mL. Ultrasound studies were performed in order to monitor fetal development. The fetal parameters analyzed before the adjustment of levothyroxine therapy showed growth retardation of various degrees. All analyzed fetal parameters (biparietal diameter, cranial and abdominal circumference, humerus and femur length) improved during the last 6 weeks of gestation, showing a good correlation with the newly achieved euthyroid state of the mother. The infant was clinically euthyroid at birth and was found normal at all evaluations of the neonatal hypothyroidism screening program (1, 5, 30 days).     

Severe hypothyroidism induced by thyroid metastasis of colon adenocarcinoma: a case report and review of the literature

An 85-year-old man who had undergone a right hemicolectomy for colon cancer presented with severe hypothyroidism and hoarseness 21 months after the operation. The serum thyrotropin (TSH) was markedly elevated to 118.14 microIU/mL and serum free thyroxine (fT4) level was markedly suppressed to 0.34 ng/dL. Symptoms of hoarseness and neck swelling were already evident 4 months prior at which time tests for normal thyroid function were performed. The patient was referred due to aggravated pain on his diffusely enlarged hard goiter. An enlarged thyroid with some calcification was noticed in the neck ultrasonography with multiple cervical lymphadenopathies. Core biopsy of the thyroid gland showed invasion of poorly differentiated adenocarcinoma cells. Immunohistochemical studies showed positive staining only for carcinoembryonic antigen (CEA). There were multiple lung parenchymal nodules and adrenal masses at the time of evaluation. The patient was started on palliative chemotherapy with thyroid hormone replacement and gradually became euthyroid. From these findings and the clinical observations, thyroid metastasis with hypothyroidism developing acutely from metastatic colon adenocarcinoma was diagnosed.     

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.     

Atrioventricular block complicating amiodarone-induced hypothyroidism in a patient with pre-excitation and rate-dependent bilateral bundle branch block

As a clinical entity atrioventricular (AV) block due to hypothyroidism is rare. Such a case induced by hypothyroidism complicating long-term therapy with amiodarone in a 45 year old woman with pre-excitation is presented. Electrophysiologic data obtained before and during thyroxine replacement therapy showed that hypothyroidism lengthens the effective refractory period of the atria, AV node, bypass tract and His-Purkinje system (that in the ventricle not being measured); this lengthening resembles the effects of long-term administration of amiodarone. These observations suggest that depressed thyroid function may be protective against arrhythmias but a patient with preexisting conduction system disease may develop AV block. The tendency to develop AV block in a patient who is euthyroid was reduced by bypass tract conduction. These findings are significant not only in monitoring amiodarone effects during chronic prophylactic drug therapy but also in providing further insight into the complex interrelation between the action of the drug and the thyroid hormones on cardiac muscle.     

Severe ascites with hypothyroidism and elevated CA125 concentration: a case report

Ascites caused by hypothyroidism is rare and the pathogenesis is unclear. Several reports have presented cases of progressive ascites with hypothyroidism and elevated tumor markers. We report a 31-year-old female case with massive ascites and elevated serum CA 125 concentrations. The patient had no typical feature of hypothyroidism except an accumulation of ascitic fluid which showed elevated total protein concentration and a high serum-ascites albumin gradient (SAAG). There was no finding of malignancy. Following thyroid hormone replacement, the ascites was completely resolved accompanied by reduced concentrations of serum CA125. In general, primary hypothyroidism with ascites presents with coexisting massive pericardial or pleural effusion. The massive ascites and increased serum CA125 concentrations may have led us to make the incorrect diagnosis of ovarian malignancy. The evaluation of thyroid function is useful to determine the pathology of high-protein ascites or elevated tumor markers, and ascites may be treatable by thyroid replacement therapy.     

A case of Kearns-Sayre syndrome with impaired respiratory regulation]

We reported a case of Kearns-Sayre syndrome with impaired respiratory regulation. A 55-year-old male was admitted to our hospital complaining of chronic progressive external ophthalmoplegia, limb muscle weakness and dyspnea. On admission, because arterial blood gas analysis showed marked alveolar hypoventilation, ventilatory response was measured and diminished chemosensitivity to both hypoxia and hypercapnia was found. His vital capacity and forced expiratory volume in 1 second were slightly decreased, and a chest X-ray film revealed a moderate degree of elevation of the bilateral diaphragm. Therefore, we considered that the diminished response to hypoxia and hypercapnia in this case was caused by an impairment of the respiratory center, as well as chemoreceptors and also the presence of respiratory muscular weakness.     

Endocrine myopathies: clinical and histopathological features of the major forms

Endocrinopathies, such as thyroid and parathyroid diseases, disorders of the adrenal axis, and acromegaly are included among the many causes of myopathy. Muscle disturbances caused by endocrine disorders are mainly due to alterations in the protein and carbohydrate metabolisms. Either a deficiency or excess of hormones produced by the glands can cause muscle dysfunction that can be reversed by starting hormone replacement therapy or acting on hormone dysfunction. The diagnosis is usually easy if a muscle disorder occurs in an overt endocrinopathy; however, in few patients, myopathy could be the first manifestation of the underlying endocrinopathy. In this article we discuss pathophysiology, clinical features and management of muscle involvement related to the major endocrine diseases.Key words: endocrine myopathies, muscle weakness, creatine kinase, hypothyroidism, myalgia, rhabdomyolysis     

Does Treating Subclinical Hypothyroidism Improve Markers of Cardiovascular Risk?

Subclinical hypothyroidism is defined as an elevated serum thyroid-stimulating hormone (TSH) level in the face of normal free thyroid hormone values. The overall prevalence of subclinical hypothyroidism is 4-10% in the general population and up to 20% in women aged >60 years. The potential benefits and risks of therapy for subclinical hypothyroidism have been debated for 2 decades, and a consensus is still lacking. Besides avoiding the progression to overt hypothyroidism, the decision to treat patients with subclinical hypothyroidism relies mainly on the risk of metabolic and cardiovascular alterations. Subclinical hypothyroidism causes changes in cardiovascular function similar to, but less marked than, those occurring in patients with overt hypothyroidism. Diastolic dysfunction both at rest and upon effort is the most consistent cardiac abnormality in patients with subclinical hypothyroidism, and also in those with slightly elevated TSH levels (>6 mIU/L). Moreover, mild thyroid failure may increase diastolic blood pressure as a result of increased systemic vascular resistance. Restoration of euthyroidism by levothyroxine replacement is generally able to improve all these abnormalities. Early clinical and autopsy studies had suggested an association between subclinical hypothyroidism and coronary heart disease, which has been subsequently confirmed by some, but not all, large cross-sectional and prospective studies. Altered coagulation parameters, elevated lipoprotein (a) levels, and low-grade chronic inflammation are regarded to coalesce with the hypercholesterolemia of untreated patients with subclinical hypothyroidism to enhance the ischemic cardiovascular risk. Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism. However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. On the other hand, levothyroxine replacement therapy can always be discontinued if there is no apparent benefit. Levothyroxine replacement therapy is usually safe providing that excessive administration is avoided by monitoring serum TSH levels. However, the possibility that restoring euthyroidism may be harmful in the oldest of the elderly population of hypothyroid patients has been recently raised, and should be taken into account in making the decision to treat patients with subclinical hypothyroidism who are aged >85 years.     

Hypothalamic hypothyroidism due to isolated thyrotropin-releasing hormone (TRH) deficiency

Cold intolerance and secondary amenorrhea developed in a patient who had meningoencephalitis 4 yr prior to study. A clinical diagnosis of hypothalamic hypothyroidism was made on the basis of low serum thyroxine and triiodothyronine levels, and low plasma thyrotropin concentrations, which were responsive to thyrotropin-releasing hormone (TRH). The secretion of the remaining pituitary hormones (growth hormone, prolactin, adrenocorticotropin and gonadotropins) was intact. Not only was thyroid function normalized by oral administration of TRH, but also menses resumed after adequate replacement therapy with thyroid hormone. These results imply that hypothyroidism in this patient was due to isolated dysfunction of hypothalamic TRH release.     

Ventilatory and P0.1 response to hypercapnia in quadriplegia.

Unlike individuals with comparable degrees of respiratory muscle weakness from other causes, quadriplegic patients have a blunted ventilatory and P0.1 response to hypercapnia. This suggests that the diminished response in quadriplegia is due, in part, to an alteration in respiratory drive. We measured the hypercapnic response in 9 subjects with chronic quadriplegia (Q) and 8 normal controls (N). Ventilatory muscle strength, maximum voluntary ventilation (MVV), and lung volumes were measured in all subjects. The ventilatory response (HCVR) in Q was significantly less than in N (0.73 +/- 0.37 vs 2.95 +/- 0.4 L.min-1.mmHg-1; P less than 0.001), even when normalized for indices of respiratory muscle performance (e.g., vital capacity, MVV). There was no significant change in the HCVR in Q after the administration of naloxone. We also serially studied 2 subjects with acute quadriplegia, and found that despite progressive improvement in respiratory muscle performance, there was no accompanying increase in the response to hypercapnia. These data suggest that muscle weakness alone cannot explain the blunted hypercapnic response in quadriplegia, and are consistent with the hypothesis that these subjects have a reduced ventilatory drive.     

Symptomatic ascites in a patient with hypothyroidism of short duration

Symptomatic ascites as a presenting symptom of hypothyroidism is quite rare. In most of the case reports, patients with ascites requiring therapeutic abdominal paracentesis have long-standing hypothyroidism. We present a case of symptomatic ascites in a subject with hypothyroidism following radioiodine therapy for Graves disease. A 70-year-old African-American man presented with increasing weakness, shortness of breath, weight gain, constipation, and abdominal distention. Past history was significant for coronary artery disease, diabetes, hypertension and history of radioiodine therapy for Graves disease 9 months prior to the presentation. He was taking levothyroxine at 50 microg per day for 3 months prior to the presentation. Physical examination findings were significant for puffiness around the eyes, decreased breath sounds at the lung bases, and distended abdomen with free fluid, hung-up reflexes, and cold extremities. The thyroid-stimulating hormone level at the time was 64 with a free T4 less than 0.4 ng/dL. Analysis of the ascitic fluid revealed an exudative effusion with a serum to ascitic fluid albumin gradient of 1.2. The patient required therapeutic abdominal paracentesis twice, with 4 L each time, to relieve the symptoms. Work-up to rule out other causes did not reveal any other relevant abnormality. After initiation of thyroid hormone replacement, the patient responded very well and the ascites resolved within 2 months. We conclude that ascites associated with hypothyroidism is rare but must be recognized early, since thyroid replacement is the definitive therapy.