Introduction

Thyrotoxicosis is a condition featured by excessive thyroid hormones in blood that triggers a wide range of symptoms impacting various body functions. Among all these, thyrotoxic myopathy (also known as hyperthyroid myopathy) stands out as a significant disruption to the neuromuscular system associated with Graves’ Disease. It generates wasting, weakness, fatigue, and heat intolerance. This comprehensive review dives into the intricate mechanism and manifestation of thyrotoxic myopathy to promote awareness for both healthcare professionals and the affected population. To enhance effective diagnosis, thyroid-related complications management, physical well-being prevention, and overall quality of life among individuals with thyrotoxic myopathy.

Causes of thyrotoxic myopathy

Thyrotoxic myopathy occurs due to excessive thyroid hormones. Instead of facilitating metabolic regulation, they damage skeletal muscles in various ways, leading to muscle weakness, atrophy, and fatigue.

Accelerated muscle breakdown

Excessive thyroid hormones increase the body's metabolic rate, oxidative stress, and inflammatory mediators, inducing increased muscle breakdown (degradation) and fibre damage.^1,2,3 These can cause structural changes such as vacuolar degeneration and increased mitochondrial swelling in skeletal muscles.⁴ They break down muscle protein faster than it rebuilds, resulting in muscle wasting, weakness, and fatigue.

Impaired mitochondrial function and muscle energy imbalance 

Thyroid hormones regulate the production and use of energy (ATP). While the activity of mitochondria (energy production power plant inside cells) is disrupted by increased reactive oxygen species (ROS) production and hyperthyroidism-induced apoptosis (neuronal death).⁵ This can provoke inefficient energy and increased muscle fatigue.

Furthermore, excessive thyroid hormones could also raise ATP demand by stimulating sodium and potassium imbalances, which further deplete muscle energy reserves. Thyroid hormones affect glycolysis and lipid oxidation promotion. Excessive metabolic activation increases lactate production, causing early muscle fatigue and cramps.

Changes in the neuromuscular junction

In some cases, excessive thyroid hormones can reduce acetylcholine receptor sensitivity, leading to inefficient neuromuscular transmission, which weakens the muscles.⁶

Clinical manifestations

Skeletal muscle involvement 

Thyrotoxic myopathy commonly occurs before or after hyperthyroidism. Typically initial among the proximal muscle groups in a single limb. Weakness, wasting, and fatigue without paralysis or sensory disturbances slowly progress to the distal and bilateral limbs symmetrically. This causes patients who have difficulty with daily tasks such as climbing stairs, standing up from a seated position due to weakness in the quadriceps, hip flexors, pelvic girdle, and shoulder muscles.

While muscle fatigue is typically progressive, it worsens with exertion. Muscle wasting (atrophy) occurs due to increased protein catabolism that breaks down muscles, leading to reduced muscle mass. Though less common, some cases may also experience muscle pain (myalgia) and cramps.

Distinct from other myopathies, where its deep tendon reflexes (DTR) and sensation remain intact. An EMG could reveal a myopathic pattern with reduced amplitude motor unit potentials.⁷

Bulbar muscle involvement

In some acute cases, thyrotoxic myopathy can weaken the pharyngeal and laryngeal muscles promptly causing general paralysis in a few days. Despite dysphonia (weak and hoarse voice), chewing and swallowing difficulties (dysphagia). Individuals may also experience frequent coughing during meals, choking on food or liquids, slurred or nasal speech, and vocal fatigue.^8,9

Respiratory muscle involvement

In rarer cases, acute thyrotoxic myopathy can progress to weaken or paralyse the respiratory muscles (i.e. diaphragm and intercostal muscles). This can cause shortness of breath or orthopnea, potentially requiring mechanical ventilation. However, with adequate treatment of underlying hyperthyroidism (or hyperthyroid crisis), respiratory weakness is usually reversible, with significant improvement.¹⁰

Thyrotoxic periodic paralysis

Thyrotoxic periodic paralysis (TPP) is an uncommon yet dangerous complication of thyrotoxicosis. It is characterised by hypokalemia (low potassium level) associated with acute proximal symmetrical lower limb weakness that progresses to all four limbs, even bulbar and respiratory muscles. Particularly recorded and described among East Asian males with hyperthyroidism, with increasing incidences in the West, even among children from other parts of the world.

Individuals usually present with a sudden onset of episodic muscle weakness, more in the proximal lower limbs than the upper distals, along with myalgias after hyperthyroid symptoms onset. It may also present with various other symptoms like racing heart, high heart rate, shortness of breath, swallowing difficulties, speech and visual changes, and even rhabdomyolysis. Other hyperthyroid symptoms like heat intolerance, frequent bowel movement, swollen neck, and bulging eyeballs may also appear.

TPP can be promoted through genetic mutation and imbalances in the activity of sodium-potassium ATPase pump in skeletal muscles of any cause of hyperthyroidism. These attacks are more likely during early mornings, after heavy-carbohydrate, salted meals, or rest post-exertion, upon stress, trauma, or drugs (e.g., diuretics, oestrogens, laxatives, corticosteroids, and NSAIDs) consumption. 

Despite a lack of reflexes during attacks, individuals usually regain their strength in between, with weakness persisting recurrently.¹¹

Diagnosis and evaluation

Thyrotoxic myopathy is diagnosed upon a specialised procedure of hyperthyroidism as follows:

Clinical history and physical examination

A detailed clinical history review is the first step taken by a neurologist, asking about the onset of progressive proximal muscle weakness, fatigue, and muscle wasting. Sensation and if there are any other symptoms of thyrotoxicosis, such as tremors, heat intolerance, and racing heartbeat. A neurological checkup on muscle strength, muscle mass, and deep tendon reflex (DTR).

Thyroid function tests

Thyroid function tests are critical for a thyrotoxic myopathy diagnosis. Hyperthyroidism, typically low levels of thyroid-stimulating hormone (TSH), accompanied by elevated triiodothyronine (T3) and thyroxine (T4) levels. These laboratory findings help differentiate thyrotoxic myopathy from other muscle disorders, as the muscle weakness is reversible after proper management of underlying thyroid dysfunction.

Serum creatine kinase (CK)

In thyrotoxic myopathy, serum creatine kinase (CK) levels are usually normal or mildly elevated, unlike other inflammatory or metabolic myopathies where CK is significantly increased. While mild elevation may occur due to muscle catabolism, but normal CK levels typically help to distinguish thyrotoxic myopathy from other conditions like polymyositis or muscular dystrophies.

Electromyography (EMG) findings

Upon thyrotoxic myopathy, the electromyography (EMG) typically shows a myopathic pattern, characterised by low amplitude, short-duration motor unit potentials without significant fibrillation or denervation. Nerve conduction studies remain normal, unlike neurogenic disorders. Hence, helps to differentiate thyrotoxic myopathy from neuropathy and motor neuron disease (MND).

Potassium levels in suspected periodic paralysis cases

Among thyrotoxic periodic paralysis (TPP), serum potassium levels are low during a paralysis attack due to excessive sodium-potassium ATPase activity that increases the intracellular potassium shift. While potassium levels are typically normal between attacks, having a measurement during an episode is crucial for differentiating TPP from other periodic paralysis.¹¹

Management and treatment

General treatment

Effective thyrotoxic myopathy management typically focuses on treating the underlying thyrotoxicosis to stop muscle deterioration and restore strength.

Antithyroid medications

Antithyroid drugs, such as methimazole (Tapazole®) and propylthiouracil (PTU) are commonly used to block thyroid hormone synthesis and restore normal T3 and T4 levels in treating hyperthyroidism. These medications are also the first-line treatment for Graves’ disease, the most common cause of thyrotoxicosis.

Beta-blockers

Beta-blockers, such as propranolol or atenolol inhibit high thyroid hormone induced excessive adrenergic stimulation, can help to alleviate symptoms such as muscle tremors, palpitations, and heat intolerance.

Radioactive iodine therapy (RAI)

Radioactive iodine therapy (RAI) is a definite treatment for Graves’ disease. It involves oral capsule or liquid consumption of thyroid cells-targeting radioactive iodine that specifically destroys them. As it cures hyperthyroidism permanently, most people will have to take thyroid hormone medication (levothyroxine) for the rest of their lives to maintain normal thyroid hormone levels.

Surgery 

In cases of severe hyperthyroidism with large goitres or medication failure, a surgeon may remove partial or all of the thyroid gland through thyroidectomy. Despite promising therapeutic effects, the hypothyroidism afterwards would require lifelong thyroid hormone medication.¹²

Supportive therapy

Physical therapy

Physical therapy is crucial in rehabilitating muscle strength and endurance among individuals with thyrotoxic myopathy. While progressive resistance training helps rebuild proximal muscle strength, aerobic exercises, such as low-impact walking or cycling improve cardiorespiratory endurance and reduce fatigue. Stretching could help to maintain muscle flexibility and prevent stiffness whilst regaining functional mobility, through balance and coordination training.

Given the risk of excessive muscle breakdown, a gradual, supervised exercise program should be tailored to ensure safe muscle recovery. A gradual improvement upon muscle function is usually seen over weeks to months.

Nutritional support

Proper nutrition helps prevent excessive muscle wasting in thyrotoxic myopathy. A high-protein, calorie-rich diet supports muscle repair and recovery. Electrolyte balance, especially potassium and magnesium, is crucial, particularly in thyrotoxic periodic paralysis cases. Adequate vitamin D and calcium intake support overall muscle health.

Management of thyrotoxic periodic paralysis

Acute paralytic episodes would require immediate oral or intravenous supplementation while avoiding hyperkalemia. Beta-blockers (e.g., propranolol) to reduce the intracellular shift of phosphate and potassium. Long-term management, such as antithyroid drugs, radioactive iodine, or surgery. Triggers, such as high-carbohydrate meals and excessive strenuous exercises should be avoided to prevent recurrent paralysis episodes.¹¹

Prognosis and recovery

While early diagnosis and appropriate treatment are critical to reverse thyrotoxic myopathy and gradually improve muscle strength once thyroid functions are normalised. Recovery time varies, with mild cases improving within weeks, whereas, severe and prolonged ones take months to regain full muscle function.

Individuals with thyrotoxic periodic paralysis (TPP) could also recover once hyperthyroidism is controlled, preventing recurrent attacks. However, prolonged untreated thyrotoxicosis could result in persistent muscle wasting and weakness. Hence, delaying recovery.

With regular follow-ups, thyroid status and recurrence can be prevented with early thyroid management, nutritional support, and physical therapy to enhance muscle regeneration.

Summary

Thyrotoxic myopathy is a neuromuscular complication of thyrotoxicosis, caused by excessive thyroid hormones. It results in muscle wasting, weakness, and fatigue, primarily affecting proximal muscles. Despite limbs, bulbar and respiratory muscles can also impair swallowing and breathing. Thyrotoxic periodic paralysis (TPP) presents with sudden muscle paralysis due to hypokalemia. Accurately diagnosis through thyroid function tests, electromyography, and potassium levels. Appropriate treatments such as antithyroid medications, beta-blockers, and radioactive iodine or surgery when necessary. With timely treatment, nutritional and physical therapy to aid muscle recovery. It could gradually improve back to normal.