Article by Dr. Nuovo

Polymyositis is an idiopathic inflammatory myopathy presenting with subacute-chronic symmetric proximal limb weakness. Increased creatine kinase (CK) levels, myositis-specific or -associated serum autoantibodies, EMG and imaging techniques can provide additional diagnostic clues. Nevertheless, the gold standard for the diagnosis of polymyositis is muscle biopsy, typically showing endomysial inflammatory infiltrates that invade healthy muscle fibers expressing the MHC-I antigen [1].

 

“Polymyositis-like syndrome” in hypothyroid patients

Polymyositis can be mimicked by a broad range of diseases, including thyroid disorders. In particular, proximal muscle weakness and elevation of muscle enzymes may be a clinical manifestation of hypothyroidism. Clinical and pathologic features of “polymyositis-like syndrome” among hypothyroid patients have been systematically reviewed by Madariaga and collegues [2]. In all cases laboratory analyses showed low thyroid hormone (T4) values and increased thyroid-stimulating hormone (TSH) levels. Furthermore, abnormal titers of antiperoxidase, antithyroglobulin, or anti-TSH receptor antibodies were reported in patients with autoimmune thyreopathy. Significantly, no patients showed the presence of myositis-specific or -associated autoantibodies, such as anti-Jo-1, anti-SRP, and anti-Mi2. Complaints of weakness primarily affecting proximal muscles were constantly present in the investigated cohort of patients, whereas objective weakness was detected in only half of the cases. Other common manifestations included muscle tenderness, muscle induration (in the absence of generalized muscular hypertrophy and stiffness), muscular wasting, and delayed relaxation of deep tendon reflexes. Increased serum CK were common, with levels up to 40-fold of normal values. Other muscle enzymes including lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine transaminase (ALT), and aldolase (ALD) were also reported to be elevated in some cases. Abnormal EMG patterns were identified in nearly half of investigated patients, showing polyphasic, short-duration or low-amplitude motor-unit potentials, as well as insertional activity. Muscle biopsy often revealed abnormal findings, including type II fiber atrophy, type I fiber hypertrophy and increased number of central nuclei. The most significant difference between conventional polymyositis and polymyositis-like syndrome is the clinical recovery and resolution of the laboratory abnormalities after thyroid hormone replacement in patients with the latter disorder. In particular, hormonal therapy would be able to restore serum muscle enzyme concentrations after an average of 9 weeks of treatment. Furthermore, clinical resolution of muscle weakness usually occurs after an average of 10 weeks.

 

Coexistence of polymyositis and thyroid diseases

Idiopathic inflammatory myopathies including polymyositis are commonly associated with autoimmune hypothyroidism (Hashimoto’s thyroiditis) or hyperthyroidism (Graves’ disease) [3; 4]. In particular, polymyositis diagnosis usually precedes or parallels hypothyroidism and often occurs following the diagnosis of hyperthyroidism. In order to explain this coexistence, a common etiopathogenesis has been suggested. The proposed mechanisms include: (1) shared environmental factors (e.g. virus, drugs, chemicals) triggering both polymyositis and autoimmune thyroid diseases in genetically predisposed individuals; (2) cross-reactivity of anti-thyroid autoantibodies or autoreactive T cells with other tissues and organs; (3) cytokine imbalance; (4) genetic risk factors associated with both the diseases [5]. Although most of thyroid dysfunctions coexistent with polymyositis arise from an abnormal immune response, some patients with non-autoimmune hyperthyroidism/hypothyroidism have been reported. In these cases, hypothyroidism might represent a physiologic adaptive response to systemic illness; on the other hand, polymyositis could be related to the use of anti-thyroid drugs such as propylthiouracil. Nevertheless, we cannot exclude the possibility of seronegative autoimmune thyroiditis for these patients and more studies will be necessary in order to conclude a causal association.

 

In the end, thyroid assessment is strongly recommended in patients with musculoskeletal symptoms, as both muscle weakness and elevation of creatine kinase could be caused by thyroid diseases. At the same time, a comprehensive thyroid evaluation is mandatory in patients diagnosed with polymyositis, as thyroid dysfunction, whether autoimmune or not, is clearly related with onset or relapse of disease activity.

Article by Dr. SARA NUOVO, MD

Footnotes

[1] Vattemi G et al. Muscle biopsy features of idiopathic inflammatory myopathies and differential diagnosis. Auto Immun Highlights. 2014 Sep 10;5(3):77-85. eCollection 2014 Dec. Review. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4386579/

[2] Madariaga MG et al. Polymyositis-like syndrome in hypothyroidism: review of cases reported over the past twenty-five years. Thyroid. 2002 Apr;12(4):331-6. Review. http://online.liebertpub.com/doi/pdf/10.1089/10507250252949478

[3] Selva-O'Callaghan A et al. Clinical significance of thyroid disease in patients with inflammatory myopathy. Medicine (Baltimore). 2007 Sep;86(5):293-8. http://www.ncbi.nlm.nih.gov/pubmed/17873759

[4] Ng KP et al. Concomitant diseases in a cohort of patients with idiopathic myositis during long-term follow-up. Clin Rheumatol. 2009 Aug;28(8):947-53. Epub 2009 Apr 23. http://www.ncbi.nlm.nih.gov/pubmed/19387765

[5] Wang H et al. Polymyositis associated with hypothyroidism or hyperthyroidism: two cases and review of the literature. Clin Rheumatol. 2011 Apr;30(4):449-58. Epub 2010 Sep 21. Review. http://www.ncbi.nlm.nih.gov/pubmed/20857158

 

Additional notes on Thyroid and thyroid testing

There is a type of Polymyositis that is related to the thyroid. It is usually called a "polymyositis like syndrome", and differs from polymyositis is some features, but largely by the fact that when the thyroid is regulated to proper TSH levels the symptoms of polymyositis disappear. There are also differences on biopsy.

However the very fact that thyroid deficiency can cause polymyositis like symptoms does lead one to suspect that an endocrine disorder may be linked to polymyositis. "Thyroid disorders are clinically relevant in patients with inflammatory myopathies" (Selva-O'Callaghan 2007).[1]

The thyroid gland is a critical part of the endocrine system, and controls or influences many of the bodies functions and processes. Of particular interest to us, "Neuromuscular disorders are common in hypothyroidism.", and in fact "Proximal muscle weakness in hypothyroidism may mimic polymyositis". (Smit, Staniland 2003) [2]

So if you are hypothyroid, or even think you might be, a full thyroid panel will give you a much better indication if your thyroid may be influencing your muscular disease.

"A TFT panel typically includes thyroid hormones such as (TSH, thyrotropin) and thyroxine (T4), and triiodothyronine (T3) depending on local laboratory policy.

Other tests include thyroid hormone binding ratio, thyroxine binding index or uptake analysis. A complete thyroid panel may be useful in determining the thyroid interaction in the case of complex disorders.

TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive thyroid) or hypothyroidism (underactive thyroid), or to monitor the effectiveness of either thyroid-suppression or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease, such as atrial fibrillation and anxiety disorder." (Wikipedia)

 

T4-to-T3 Conversion and Hypothyroidism page: Read why in-range TSH and T4 levels may be present without adequate T3 levels.

 

"Thyroid insufficiency. Is TSH the only diagnostic tool?" The explanation is that TSH is grossly in feedback with serum T4 only, not so much with serum T3, while the patient's wellbeing depends on the free T3 that is disposable inside the cells. As hypothyroid patients are usually unable to convert inactive T4 into active T3, owing to a lack of 5' -deiodinase in the liver and kidneys, the administration of T4 can eventually correct the serum TSH level, but rarely provides the patient with the T3 needed to be relieved of his symptoms. (Baiser, Hertoghe et all 2000) [3]

These findings indicate that in hypothyroid patients L-T4-replacement...that is sufficient to maintain a normal serum TSH, is accompanied by a serum free T4 that is higher than that in untreated euthyroid patients or normal individuals and may not result in an appropriately normal serum free T3 concentration. (Woeber 2002) [4]

THYROID TESTS

A pretty excellent sheet of overviewing tests available for thyroid panel, and what is being tested, can be found at the Navy's Bureau of Medicine and Surgery. It also gives a brief explanation of the tests.[5]

Routinely three hormones are often measured namely Thyroxine, tri-iodothyronine and Thyroid Stimulating Hormone (TSH).

THYROXINE (T4)

Thyroxine is found in the blood in two forms i.e. bound to proteins and free of protein binding.The free component is the active form of the hormone and comprises only 0.03% of the circulating total T4. Some laboratories still measure total thyroxine which comprises both the bound and free forms. The trouble with this is that the level of total thyroxine very much depends on the amount bound to proteins and therefore the level of binding proteins in the blood. The major protein binding thyroxine is called Thyroid Binding Protein (TBG). TBG can be low in some patients due to an inherited but seemingly harmless deficiency. In these patients total thyroxine is low but the free and active component is normal. Medicines such as the contraceptive pill and life events such as pregnancy can also alter binding proteins giving spuriously high levels of total thyroxine.

For these reasons most laboratories have now introduced the measurement of free thyroxine and this is what we measure.

TRI-IODOTHYRONINE (T3)

There are two assays available, one measures total T3 and the other free T3. The total T3 comprises of both protein bound and free T3. The free component is the active form and comprises 0.3% of total circulating T3. Gradually laboratories are moving over to free T3 measurements as more reliable free T3 assays become available.T3 is the biologically active thyroid hormone, possessing 5 times the metabolic power of T4. In man some 80% of T3 is produced from T4 by conversion in liver and kidney. Therefore little is produced in the thyroid itself. The conversion of T4 to T3 can depend on a number of situations such as chronic illness or surgical stress which cause a fall in T4 to T3 conversion (called low T3 syndrome). Starvation also alters T4 to T3 conversion with a fall in T3 as the body tries to reduce its metabolism to conserve energy.

What does T3 do?

T3 alters the metabolism of the body. It alters protein manufacture, cellular activity and is essential for growth and well being. Without T3 the patient develops hypothyroidism. Too much and the patient develops an overactive thyroid called thyrotoxicosis.

TSH

TSH is released by the pituitary gland and circulates in the blood stream to the thyroid where it controls release of the thyroid hormones T4 and T3. TSH release is very sensitive to alterations in the blood thyroid hormones, with small decreases augmenting TSH secretion and small increases reducing release. Therefore in hypothyroidism, TSH is raised above normal reference ranges whereas in thyotoxicosis TSH is suppressed into the undetectable range. In thyrotoxicosis the thyroid automatically manufactures too much T4 and T3 without the need for TSH to switch on. As TSH is so sensitive to changes in thyroid hormone levels it is used as the number one test for screening for thyroid disease. If the laboratories notice a raised TSH then automatically T4 is measured. If the laboratories notice a suppressed TSH then T4 and T3 are measured. Why both? Because there are some patients whose thyroid oversecrete only T3 called T3 Toxicosis and both hormones need to be measured to detect this form of thyrotoxicosis; it is usually seen in those who have had previously a thyroidectomy or radioactive iodine for thyrotoxicosis in the past.

TRH Testing

When the level of TSH is borderline low or high sometimes the specialist will request a TRH test. This a hormone released by the brain (hypothalamus) which controls the pituitary release of TSH. By using this simple test the specialist can tell whether a patient has in reality an overactive, normal or underactive thyroid. It is interesting to note that a large study of TRH tests showed a significant number of cases of hypothyroidism being missed by using too high a reference range, and suggested a normal range should not be above 3.5 mIU/l. (Moncayo 2006) [6]

Footnotes:

1. Selva-O'Callaghan A, Redondo-Benito A,Trallero-Araguás E,Martínez-Gómez X,Palou E, Vilardell-Tarres M. Clinical significance of thyroid disease in patients with inflammatory myopathy. Medicine (Baltimore), 2007 Sep;86(5):293-8., 2007 as found at VIEW

2. Smith, Craig J, Staniland J. A Difficult Case of Inflammatory Myositis. Age and Ageing, Vol 32 #3, 351-352, 2003 as found at VIEW

3. Baisier, W.V., Hertoghe J,Eeckhaut W. Thyroid Insufficiency. Is TSH Measurement the Only Diagnostic Tool?. Journal of Nutritional and Environmental Medicine, 10,105-113, 2000 as found at VIEW

4. Woeber KA, . Levothyroxine therapy and serum free thyroxine and free triiodothyronine concentrations. Endocrinol Invest, 25(2):106-9, 2002 as found at VIEW

5. NAVMED P-5139, . Health Care in Military Settings. Operational Medicine, P-5139, 0 as found at VIEW

6. Moncaya H, Dapunt O. Diagnostic accuracy of basal TSH determinations based on the intravenous TRH stimulation test. BMC Endocrine Disorders, 7:5, 2007 as found at VIEW