Abstract
Chronic back or limb pain is often debilitating and disabling resulting in loss of efficiency, depression, and low self-esteem. Diagnosis usually suggests arthritis or nerve root pathology and patients receive long-term oral analgesics and invasive procedures with little or no relief. Hypothyroidism may present as peripheral neuropathy which may be clinically indistinguishable from entrapment neuropathy as occurs with neural canal stenosis. Muscle cramps, aches, proximal symmetrical muscle weakness, stiffness, polymyositis, and exercise intolerance may be the only presenting symptom indicating hypothyroidism. We present five cases of acute on chronic pain that improved significantly on treatment with thyroxine. Neuromuscular pain may be the only presenting symptom of hypothyroidism. Thyroid profile (TSH, FT3, FT4) and anti-thyroid peroxidase (anti-TPO) antibodies should be screened before subjecting the patient to multiple analgesics and procedures.
Keywords: Acute pain, hypothyroidism, TSH
Introduction
Fifty percent of the patients presenting to the pain clinic complain of low backache. Seventy to eighty percent of adults visit the pain clinic for the same at least once in their lifetime. Most episodes of backache are usually self-limiting but become chronic with episodes of acute exacerbation, which is a leading cause of long-term work disability, depression, and low self-esteem. Diagnosis usually suggests arthritis or disc and nerve root pathology for which the patient is usually prescribed analgesics and pain modulators, or in severe cases, invasive therapies like facet joint blocks or epidural/intraarticular steroids and alternative therapies such as transcutaneous electrical stimulation (TENS) and even acupuncture with at times little or no relief. We present five cases of acute on chronic pain which did not respond to the conventional treatment. Written informed consent was obtained from all patients to include their data for publication. The institutional ethics committee exempted this case series from ethics committee review (XXXX/IEC/03/97 dated: 14/09/2021).
Case Series
The first case was a 21-year-old young male with severe low backache radiating to both legs and constipation. Magnetic resonant imaging (MRI) of the spine was unremarkable. Oral analgesics and TENS were ineffective.
The other three cases were elderly males with acute on chronic low backache with radiation and muscle cramps in their legs. All three suffered from either diabetes mellitus and/or hypothyroidism on treatment and were well controlled on medication. MRI spine was suggestive of disc/facet or canal stenosis. The pain was severe enough to limit even the routine activities. A combination of oral medications and invasive procedures such as facet joint block, epidural steroids, and even acupuncture had not offered any relief.
The fifth case was an elderly male who was diagnosed with a frozen shoulder. Oral analgesics and physiotherapy failed to resolve the pain. Detailed presentation and treatment modalities used are presented in Table 1.
Table 1.
Patient characteristics
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | |
|---|---|---|---|---|---|
| Age/Sex | 21 y/M | 60 y/M | 68 y/M | 60 y/M | 54 y/M |
| Comorbidities | ASA I | Diabetes mellitus | Hypertension, Diabetes mellitus, Hypothyroidism | Hypertension hypothyroid | Diabetes mellitus |
| Chief complaints | Pain L4-5 radiating to legs | Severe low backache, leg cramps | Severe low backache, pain in the gluteal region, leg cramps | Severe low backache Leg cramps | Pain Rt shoulder ? Frozen shoulder |
| Other complaints | Constipation Hair loss | Limiting daily activities | Limiting daily activities | Limiting daily activities | Severe limitation of movement at shoulders |
| MRI | No abnormality | L1-5 degenerative changes | Facetopathy, herniated disc, and canal stenosis L2-5 | Herniated disc and canal stenosis L3-L4 | No abnormality |
| Treatment | Oral analgesics | Oral analgesics | Oral analgesics | Oral analgesics | Oral analgesics |
| Procedures | TENS | Epidural steroids | B/l Facet joint Block + Epidural steroid | Epidural steroid, acupuncture | Physiotherapy |
| TSH (mIU/L) | 9.6 | 8.5 | 7.6 | 8.3 | 10.2 |
All five cases had some points in common. Proximal girdle muscles were involved. There was an acute exacerbation of symptoms and the pain was severe enough so as to limit daily activities with no response to conventional therapies. Thinking out of the box, the endocrinology profile of these patients was repeated.
The diabetic profile was normal, however, serum vitamin D3 was found to be on the lower side. The most surprising finding was high thyroid stimulating hormone (TSH) levels (7–10 mIU/L) and low normal free triiodothyonine (FT3) and free thyroxine (FT4) levels. In two of the patients who were already on thyroxine, the dose was increased, whereas it was started for the other three patients. Symptoms were relieved within 2 weeks and the previous state was achieved with 4–6 weeks of therapy. TSH returned to normal range with therapy when repeated after 4 weeks.
Discussion
Thyroid hormone is known to affect neural development and function. Hypothyroidism results in peripheral neuropathy,[1,2] which may be clinically indistinguishable from entrapment neuropathy as occurs with neural canal stenosis.
Nerve compression and axonal degeneration both may occur as a consequence of hypothyroidism. Accumulation of mucopolysaccharides, chondroitin sulfate, and hyaluronic acid in the interstitial space leads to water retention and consequent entrapment neuropathy, while energy deficit due to decreased oxidation of nutrients may reduce the function initially, followed by structural changes in the form of primary axonal degeneration in the form of axon shrinkage, disintegration of neurofilaments and neurotubules, and active axonal breakdown.[1]
It affects type 1 skeletal muscle fibers and there is a shift of fast twitch fibers to slow twitch fibers. This is due to low activity of enzymes affecting the aerobic and anaerobic glucose metabolism resulting in reduced mitochondrial function,[1,2,3] leading to muscle weakness, fatigue, and exertional pain. Deposition of mucopolysaccharide in connective tissue leads to joint effusion and laxity of ligaments,[4,5] thus further aggravating pain.
Mild to moderate hypothyroidism may result in neuromuscular symptoms in up to 50–80% of cases. These include muscle cramps and aches, proximal symmetrical muscle weakness, stiffness, polymyositis, and exercise intolerance, which may be the only presenting symptom indicating hypothyroidism.[5] Severe deficiency may result in Hoffman or Stiff-man syndrome characterized by muscle stiffness, increased muscle mass, and elevated creatine kinase.
In various studies describing musculoskeletal symptoms in hypothyroidism, approximately 50% of the patients show objective signs of muscle weakness [Table 2].
Table 2.
Hypothyroidism and neuromusculoskeletal symptoms
| Nickel et al.[2] (1961) | Duyff et al.[3] (2000)8 | Madariaga et al.[4] (2002) | Cakir et al.[5] (2003) | Singh et al.[6] (2018)11 | |
|---|---|---|---|---|---|
| n | 25 | 24 | 32 | 33 | 200 |
| Symptoms (%) | Muscle cramps in legs and lower back (56%) | Proximal weakness; deltoids and iliopsoas (54%) | Proximal weakness and CK elevation (100%) | Contracture Limited joint mobility Carpal tunnel syndrome Trigger finger | Myalgia (71.5%) Stiffness and cramps (80%) Arthralgia (60%) Adhesive capsulitis (25%) CTS (8%) Back pain (30%) |
| Objective signs | 28% | (38%) | Weakness (47%) |
Incidence of hypothyroidism in patients with only musculoskeletal symptoms however hasn’t been studied much. There are a few isolated case reports dating to the 1960s and 1970s in which the main presentation was severe acute debilitating muscle pain that responded to thyroxine treatment [Table 3].
Table 3.
Neuromusculoskeletal symptoms and hypothyroidism
| Wilson & Walton*[7] (1959)12 | Golding et al.[8] (1970) | Kung et al.*[9] (1987) | Singh et al.[10] (2015) | |
|---|---|---|---|---|
| n | 3 | 9 | 2 | 1 |
| Symptoms | Generalized aches Stiff muscles Cramps Provoked by exercise | Generalized aches Mainly neck, back, wrists & arms, and lower limbs | Proximal cramps, deltoids, and iliopsoas | Presented with features of L4-5 radiculopathy No response to invasive procedures |
| TSH---↑ | TSH: 25 mIU/L | |||
*Presented with symptoms post-treatment for hyperthyroidism
Therefore, it may not be wrong to state that while musculoskeletal symptoms are evident in diagnosed hypothyroidism, a high degree of suspicion may identify hypothyroidism as the cause of musculoskeletal symptoms. TSH should therefore be routinely checked in patients with acute on chronic pain along with FT3 and FT4 and anti-TPO (Anti-thyroid peroxidase) antibodies if TSH >2.5 mIU/L, as TSH alone may not be reliable in patients who are elderly, have stress, obesity, depression, or diabetes mellitus.
To conclude, neuromuscular pain may be the only presenting symptom of hypothyroidism. Thyroid profile (TSH, FT3, FT4) and anti-TPO antibodies should be screened before subjecting the patient to multiple analgesics and procedures.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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