Continuing Education Activity

Hypothyroid myopathy, affecting around 79% of hypothyroid patients, presents with generalized muscle pain and weakness in both congenital and acquired cases. Thyroid hormone deficiency impacts overall metabolism and organ function, notably the musculoskeletal system. Severe or untreated cases can lead to substantial muscle impairment. This activity discusses its presentation, assessment, and management while emphasizing the interprofessional team's crucial role.

Objectives:

• Identify signs and symptoms of hypothyroid myopathy during clinical evaluations.

• Differentiate generalized muscle weakness related to hypothyroid myopathy from other causes.

• Implement evidence-based guidelines for managing hypothyroid myopathy.

• Collaborate with interprofessional team members on treatments and follow-ups for patients with hypothyroid myopathy to improve patient outcomes. 

Introduction

Hypothyroid myopathy, prevalent in approximately 79% of hypothyroid patients, manifests in both congenital and acquired cases with generalized myalgias and muscle weakness. The thyroid hormone is pivotal for metabolism, growth, and organ function, impacting the musculoskeletal system. Severe or untreated hypothyroidism can prompt substantial muscle disease, causing severe functional limitations.[1] 

Symptoms of hypothyroid myopathy encompass generalized muscle weakness, cramps, stiffness, and fatigue. Proximal muscles like thighs, hips, shoulders, and neck may exhibit pronounced weakness, impacting activities like stair climbing, rising from a seated position, and lifting objects.[2]

Etiology

Hypothyroid myopathy is a condition that occurs when the thyroid gland doesn't produce enough thyroid hormones. The low levels of thyroid hormones affect the body's metabolism, including the metabolism of muscles, which can lead to muscle weakness, fatigue, and other symptoms. Here are some common causes of hypothyroid myopathy:

1. Autoimmune disorders: Hashimoto thyroiditis is an autoimmune disorder that causes the body's immune system to attack the thyroid gland, leading to hypothyroidism.

2. Iodine deficiency: Iodine is an essential nutrient that is required for the production of thyroid hormones. Hypothyroidism and hypothyroid myopathy can occur in areas with a lack of iodine in the diet.[3]

3. Thyroid surgery or radiation therapy: Surgery or radiation therapy to the thyroid gland can damage the gland or reduce its function, leading to hypothyroidism and hypothyroid myopathy.[4]

4. Medications: Certain medications, such as lithium, can interfere with the production of thyroid hormones.

5. Congenital hypothyroidism: Underactive thyroid gland at birth

6. Aging: As people age, their thyroid gland may not function as well.[5]

Overall, hypothyroid myopathy is caused by a lack of thyroid hormones in the body, which can be due to a variety of factors such as autoimmune disorders, iodine deficiency, thyroid surgery, medications, congenital hypothyroidism, and aging.

Epidemiology

Hypothyroidism tends to affect women more often than men and can manifest at any age, typically observed between 40 and 70 years. No specific racial predilection has been identified in studies regarding this condition.

Pathophysiology

The pathogenesis of myopathy in hypothyroidism is not well understood. Thyroid hormones significantly influence cellular metabolism, and their deficiency causes impairment of the cell's normal functioning. Thyroxine (T4) deficiency leads to a reduced mitochondrial oxidative capacity, abnormal glycogenolysis, and an insulin-resistant state of the cell. This leads to selective atrophy of type 2 muscle fibers (fast-twitching type) as they depend on glycolysis for energy, causing the slowing of muscle contraction seen clinically in patients with hypothyroidism.

Muscle hypertrophy is believed to be a compensatory response to the accumulation of glycosaminoglycans in the muscle. An increase in connective tissue and muscle fibers also contributed to this hypertrophy. There is also a decrease in muscle carnitine in patients with thyroid dysfunction, causing myopathic symptoms. The muscle involvement in hypothyroidism is caused by alterations in muscle fibers from fast-twitching type 2 to slow-twitching type 1 fibers, deposition of glycosaminoglycans, poor contractility of actin-myosin units, low myosin ATPase activity, and low ATP turnover in skeletal muscle.[6]

It has been noted that the degree of muscle weakness does not always correlate with the severity of thyroid hormone deficiency. This suggests that besides impaired muscle function, structural muscle injury might have a role in the pathogenesis of myopathy in some cases. Muscle cell membrane permeability changes can lead to serum muscle enzyme elevations in the absence of symptoms or structural abnormalities, and reduced clearance of these enzymes can also contribute to muscle injury.

Animal studies have shown the involvement of thyroid hormone in regulating gene expression of skeletal muscle proteins like myosin ATPase, strengthening the role of thyroid hormone deficiency in the pathogenesis of hypothyroid myopathy.

History and Physical

Hypothyroid myopathy presents with nonspecific symptoms of myalgias, muscle cramps, fatigue, and muscle weakness, particularly exacerbated with exertion and exercise. Typical features are described below:

Myalgia, a common manifestation of hypothyroidism, refers to nonspecific muscle stiffness or diffuse myalgias, often exacerbated after exercise. They may be associated with serum muscle enzyme elevations; more than 40 percent of patients may have neuromuscular complaints at diagnosis.[2]

Proximal myopathy is characterized by a slowly progressive, symmetric proximal muscle weakness.[7] Shoulder and hip girdle muscles are most commonly affected. Occasionally, hypothyroid myopathy is more fulminant, with marked serum muscle enzyme elevations. A single case of camptocormia due to hypothyroid myopathy involving primarily paraspinal muscles has been reported. On examination, deep tendon reflexes are characteristically described as "hung-up" due to delayed muscle relaxation. Other coexisting clinical signs and symptoms of hypothyroidism may be present.

Muscle pseudohypertrophy infrequently occurs in adults. This is known as Hoffmann syndrome when it is accompanied by stiffness, weakness, and painful muscle cramps. Affected patients have generalized muscular hypertrophy and variable degrees of weakness. The skin and subcutaneous tissues have a thickened, doughy appearance. Serum muscle enzymes are usually elevated. Signs of hypothyroidism are usually readily apparent and longstanding in this setting.[8]

Rhabdomyolysis is a potential complication of hypothyroidism and can lead to extremely high elevations of serum CK and rhabdomyolysis.[9] In some cases, rhabdomyolysis appears to have been precipitated by vigorous exercise, trauma, electrolyte abnormalities, alcohol consumption, or concurrent statin therapy. Renal failure may occur as a secondary complication.

Myoedema refers to a small lump rising on the surface of a muscle when it is struck with a percussion hammer. This phenomenon, characteristic of hypothyroid myopathy, lasts for 30 to 60 seconds due to a sustained contracture associated with delayed relaxation because of the slow reaccumulation of calcium by the sarcoplasmic reticulum. Myoedema is not specific to hypothyroidism, as it can also occur in malnutrition.[8]

Acute compartment syndrome may also be seen with delayed tendon reflexes and muscle hypertrophy, especially when precipitated by trauma, thrombosis, animal bites, intravenous (IV) drug abuse, or surgery.

Four subtypes of myopathy are associated with hypothyroidism: myasthenic syndrome, atrophic form, Kocher-Debre-Semelaigne syndrome, and Hoffman syndrome.

1. Myasthenic syndrome is associated with ptosis and severe weakness beginning in childhood that can progress to loss of mobility in later life.
2. Severe muscle atrophy is seen in the atrophic form of hypothyroid myopathy.
3. Kocher-Debre-Semelaigne syndrome is seen in childhood and is associated with generalized muscular hypertrophy, myxoedema, short stature, and cretinism.[10]
4. Hoffmann syndrome is usually seen in adults and is characterized by pseudohypertrophy, painful spasms, proximal muscle weakness, and stiffness. This is generally seen in primary hypothyroidism and very rarely with secondary hypothyroidism. The cause of muscle pseudohypertrophy in Hoffmann's syndrome is complex and largely unclear. It is postulated to be due to the deposition of glycosaminoglycans and increased muscle fiber size. The muscles commonly involved are the tongue, arm, and leg muscles.[11]

Evaluation

Hypothyroidism is a prerequisite for diagnosing hypothyroid myopathy and is diagnosed by measuring thyroid-stimulating hormone (TSH) and T4 levels in the blood. The most common laboratory finding in the patients' hypothyroid myopathy is the serum elevation of creatine kinase (CK). However, this is not specific to myopathy, and patients may have an elevation of CK for many years prior to developing the myopathy.

Physical evaluation can include a 6-minute walking test, hand grip strength test, and timed chair standing test.[12]

Electromyography (EMG) can demonstrate low/small amplitude potentials, which could help with diagnosis. However, it is normal in half of the patients and does not preclude the diagnosis. Myoedema is electrically silent as well and helps distinguish myotonia on an EMG. Compared with myositis, there is a lack of fibrillation potentials on EMG with relatively normal motor units.[13]

Muscle biopsy is not necessary for diagnosis but, if done, will show swollen and pale muscle tissue with loss of striations and increased separation between the muscle fibers due to mucinous depositions. Type I muscle fiber hypertrophy, type 2 muscle fiber atrophy, focal necrosis, and degeneration of muscle fibers may also be noted.[14] Increased numbers of internal nuclei, mitochondrial inclusions, glycogen accumulation, autophagic vacuoles, and myofibrillar disorganization are some other non-specific histopathological features that could be seen on the muscle biopsy.

Treatment / Management

Management of hypothyroidism is the mainstay of treating hypothyroid myopathy.[7] It is reversible with timely diagnosis and prompt treatment. The initial dose is typically 1.6 mcg/kg body weight per day but may be lower for older patients or those with coronary heart disease. The dose timing is essential, and the medication should be taken on an empty stomach with water, ideally 30 to 60 minutes before breakfast. If a patient has persistent symptoms after 2 to 3 weeks, they should be reevaluated, and serum-free T4 and TSH should be measured in 3 weeks. The maintenance dose may vary according to the cause of hypothyroidism, and the patient should be examined. Serum TSH is measured once yearly or more often if there is an abnormal result or a change in the patient's status.

According to a study, using T4 requirements is more accurate when correlated with lean body mass rather than total body weight. The study also found that the average full replacement dose after thyroidectomy varied depending on the patient's body mass index (BMI). Patients with a BMI of less than 25 kg/m² had an average dose of 1.76 mcg/kg body weight, while patients with a BMI between 25 and 29 kg/m² had an average dose of 1.47 mcg/kg. Patients with a BMI between 30 and 34 kg/m² had an average dose of 1.42 mcg/kg, while those with a BMI between 35 and 39 kg/m² had an average dose of 1.27 mcg/kg. Patients with a BMI over 40 kg/m² had an average dosage of 1.28 mcg/kg.[15]

With adequate thyroid hormone replacement and restoration of normal thyroid function, gradual resolution of most neuromuscular symptoms is noted in most of the patients. CK levels fall quickly with thyroxine replacement within a few weeks and could resolve even before TSH comes to a normal range. Hence, this can be used as a surrogate to monitor response to treatment in the initial stages, as the myopathic symptoms can take up to 6 months to resolve. Most of the symptoms resolve within a year of adequate hormone replacement.[7]

Physical therapy can also be a part of the treatment plan while thyroid levels are reported.

Differential Diagnosis

Differential diagnosis includes the following:

• Acid maltase deficiency
• Acute poliomyelitis
• Amyotrophic lateral sclerosis
• Becker muscular dystrophy
• Inclusion body myositis
• Polymyositis
• Peripheral neuropathy

Prognosis

In general, the prognosis for hypothyroid myopathy is good with appropriate treatment.[7] Most patients experience muscle strength and function improvement with thyroid hormone replacement therapy. However, the recovery process may take some time, and patients may need to continue treatment for an extended period.

The prognosis may be poor in severe cases, where the diagnosis is delayed or the patient has other underlying medical issues. In such cases, patients may experience permanent muscle damage, leading to muscle strength and function loss.

Complications

Hypothyroid myopathy may progress and cause symptoms and complications listed below. 

• Muscle cramps: Hypothyroid myopathy can cause muscle cramps due to prolonged contraction of already weak muscles.
• Reduced mobility: Muscle weakness and fatigue caused by hypothyroid myopathy can reduce mobility, making it difficult to perform daily activities such as walking, climbing stairs, and standing up from a seated position.
• Increased risk of falls: Reduced mobility can lead to an increased risk of falls, especially in older adults. Falls can cause injuries such as fractures, further reducing mobility and quality of life.
• Respiratory complications: Severe hypothyroid myopathy can weaken the breathing muscles, leading to respiratory complications such as shortness of breath and difficulty breathing.
• Cardiovascular complications: Hypothyroid myopathy can also affect the heart muscles, leading to cardiovascular complications such as an increased risk of heart failure and arrhythmias.

Deterrence and Patient Education

Patients should be advised to promptly inform their healthcare provider about any emergence or aggravation of muscle weakness, cramping, or myalgias as part of monitoring for hypothyroid myopathy. Regular follow-up appointments are crucial to evaluate thyroid function changes and make appropriate medication dosage adjustments as needed.

Pearls and Other Issues

Key facts regarding hypothyroid myopathy are listed below. 

• In patients with severe hypothyroid myopathy, it may be necessary to delay thyroid hormone replacement therapy until other comorbidities are managed and the patient is stable.
• Hypothyroid myopathy can present with a wide range of symptoms, including muscle weakness, cramps, stiffness, and pain.
• In some cases, hypothyroid myopathy can be the first sign of underlying hypothyroidism, and patients with unexplained muscle weakness should be screened for thyroid dysfunction.
• In patients with hypothyroid myopathy who are being treated with thyroid hormone replacement therapy, it is important to monitor thyroid function regularly to ensure they receive an adequate dose.
• Hypothyroid myopathy can affect patients of all ages, but it is more common in older adults.

Enhancing Healthcare Team Outcomes

Hypothyroid myopathy is fairly common but often missed because clinicians fail to ask patients about muscle-related symptoms. It is often mistaken for fatigue. The condition is best managed by an interprofessional team that includes clinicians, orthopedic nurses, pharmacists, and therapists. The key is to replace the thyroid hormone, encourage physical activity, and enroll in a physical therapy program.

All interprofessional team members should be empowered to bring up the possibility of hypothyroid myopathy in these patients and not rely only on the clinician to consider the condition. Nurses can also counsel patients on their condition and monitor their progress, communicating with the physical therapist if that is part of the treatment regimen. The therapist should repeat various evaluation tests (eg, 6-minute walking test, grip strength, and timed chair standing test) and report any deterioration or improvement to the rest of the interprofessional team.

The recovery is not immediate and may take months or even several years. The patient should be monitored by taking serial CK levels at regular intervals. Even after treatment, residual muscle pain and fatigue may persist in some patients. Nursing staff should assist with monitoring, follow-up, and educating the patient and family.

Collaboration, shared decision-making, and communication are critical elements for a good outcome.