Most cases of CTS are of unknown cause. Carpal tunnel syndrome can be associated with any condition that causes pressure on the median nerve at the wrist. Some common conditions that can lead to CTS include obesity, oral contraceptives, hypothyroidism, arthritis, diabetes, prediabetes (impaired glucose tolerance), and trauma. Carpal tunnel is also a feature of a form of Charcot-Marie-Tooth syndrome type 1 called hereditary neuropathy with liability to pressure palsies.
Other causes of this condition include intrinsic factors that exert pressure within the tunnel, and extrinsic factors (pressure exerted from outside the tunnel), which include benign tumors such as lipomas, ganglion, and vascular malformation. Carpal tunnel syndrome often is a symptom of transthyretin amyloidosis-associated polyneuropathy and prior carpal tunnel syndrome surgery is very common in individuals who later present with transthyretin amyloid-associated cardiomyopathy, suggesting that transthyretin amyloid deposition may cause carpal tunnel syndrome.
The median nerve can usually move up to 9.6 mm to allow the wrist to flex, and to a lesser extent during extension. Long-term compression of the median nerve can inhibit nerve gliding, which may lead to injury and scarring. When scarring occurs, the nerve will adhere to the tissue around it and become locked into a fixed position, so that less movement is apparent.
Normal pressure of the carpal tunnel has been defined as a range of 2–10 mm, and wrist flexion increases this pressure 8-fold, while extension increases it 10-fold. Repetitive flexion and extension in the wrist significantly increase the fluid pressure in the tunnel through thickening of the synovial tissue that lines the tendons within the carpal tunnel.
The international debate regarding the relationship between CTS and repetitive motion in work is ongoing. The Occupational Safety and Health Administration (OSHA) has adopted rules and regulations regarding cumulative trauma disorders. Occupational risk factors of repetitive tasks, force, posture, and vibration have been cited. The relationship between work and CTS is controversial; in many locations, workers diagnosed with carpal tunnel syndrome are entitled to time off and compensation.
Some speculate that carpal tunnel syndrome is provoked by repetitive movement and manipulating activities and that the exposure can be cumulative. It has also been stated that symptoms are commonly exacerbated by forceful and repetitive use of the hand and wrists in industrial occupations, but it is unclear as to whether this refers to pain (which may not be due to carpal tunnel syndrome) or the more typical numbness symptoms.
A review of available scientific data by the National Institute for Occupational Safety and Health (NIOSH) indicated that job tasks that involve highly repetitive manual acts or specific wrist postures were associated with incidents of CTS, but causation was not established, and the distinction from work-related arm pains that are not carpal tunnel syndrome was not clear. It has been proposed that repetitive use of the arm can affect the biomechanics of the upper limb or cause damage to tissues. It has also been proposed that postural and spinal assessment along with ergonomic assessments should be included in the overall determination of the condition. Addressing these factors has been found to improve comfort in some studies. A 2010 survey by NIOSH showed that 2/3 of the 5 million carpal tunnel cases in the US that year were related to work. Women have more work-related carpal tunnel syndrome than men.
Speculation that CTS is work-related is based on claims such as CTS being found mostly in the working adult population, though evidence is lacking for this. For instance, in one recent representative series of a consecutive experience, most patients were older and not working. Based on the claimed increased incidence in the workplace, arm use is implicated, but the weight of evidence suggests that this is an inherent, genetic, slowly but inevitably progressive idiopathic peripheral mononeuropathy.