Monday, January 5, 2015

Management of Hashimoto Thyroiditis



In 1912, Harkarum Hashimoto described a specific type of hypothyroidism called chronic lymphocytic thyroiditis, an autoimmune disorder impacting thyroid-specific antigens, now known as Hashimoto thyroiditis (HT) (Thompson, 2014, p. 152). This author found that 5% of the general population suffers with hypothyroidism, the most frequent cause being HT, and the greatest incidence seen with aging and predominantly in women (p. 152). Sahin et al. (2012) went further to suggest that HT is the most common cause of hypothyroidism in iodine-sufficient areas of the globe with numbers exceeding 10% of the population (p. 319).

According to Sweeney, Stewart and Gaitonde (2014), HT is fairly routine to diagnose, usually characterized by a painless goiter, elevated thyroid peroxidase (TPO) antibodies with presenting symptoms of low thyroid such as cold hands, weight gain and hair loss (p. 389). In some hypothyroid cases there is no goiter, considered a atrophic form, and may correlate with extensive fibrosis of the thyroid and increased susceptibility of overt hypothyroidism (p. 390). Occasionally other unusual diagnostic findings may present, such as suppression of the thyroid-stimulating hormone (TSH), a finding more commonly seen in hyperthyroidism (p. 389). An understanding of the management of hypothyroidism offers great insight into clinical presentations, enabling early detection and appropriate symptom monitoring in the rehabilitation setting for improved thyroid health.

The typical mechanism for hypothyroidism is still not fully understood, but appears to be the byproduct of the interplay between susceptibility genes and environmental factors that produce high levels of antithyroid peroxidase (anti-TPO) and antithyroglobulin (anti-Tg) antibodies (Thompson, 2014, p. 152). Although some studies show that 10-15% of HT patients may actually test antibody negative, demonstrating the need for greater clinical surveillance (Caleo et al. 2013). A clinical correlation between high rates of HT with family history, as well as, a personal history of type 1 diabetes mellitus, Addison disease, Turner syndrome or untreated hepatitis C seems to exist (Sweeney et al., 2014, p.391).According to Sweeney et al. (2014), initial clinical complaints present as fatigue, fullness in the neck, intolerance to cold, increases in body weight and diffuse muscle aches (p. 392). A careful examination should not only include serum TSH and TPO antibody levels, but also a thorough history and palpation of the thyroid (p 392). The palpation of the thyroid gland usually reveals a firm, bumpy surface with symmetrical gland enlargement (p.392). If pain is present in the thyroid region, then a diagnosis of subacute thyroiditis (SAT) may be rendered if associated with fever, elevated serum makers for acute inflammation such as C reactive protein (CRP) and decreased radioactive iodine uptake on thyroid scan (Ipekci, Ozturk and Cakir, 2011, p. 125). In some cases a fine needle aspiration may be indicated formulate a differential diagnosis between painful HT and SAT, as lymphocytic infiltration and fibrosis is seen in HT and granulomatous changes in SAT (p. 127). A thyroidectomy may be considered in cases of unrelenting HT pain, as the causal pain mechanism is still unknown (p. 127). Ipekci et al. (2011) further states the incidence for converting to a permanent form of hypothyroidism is quite high in HT but only 5% in SAT (p.127).

SAT is known as a transient thyrotoxic state that may be caused by an upper respiratory virus that disrupts thyroid follicles via an inflammatory reaction (Sweeney et al, 2014, p. 395). SAT tends to be self-limiting and the thyroid gland can spontaneously resume normal functioning within a few months of diagnosis (p. 395). First line treatment for SAT is aimed at the reduction of anterior neck and jaw pain through the use of high dose nonsteroidal anti-inflammatory or acetylsalicylic acid agents, with prednisone being a pharmacologic alternative (p. 395). Interestingly, in a study of twins living in separate geographic locations, diagnosed with SAT years apart, suggests the pathogenesis of SAT may be a genetic predisposition, specifically in those possessing the human leukocyte antigen (HLA)-B35 (Hamaguchi, Nishimura, Kaneko and Takamura, 2005, p. 562).

Sweeney et al. (2014) found patients with overt hypothyroidism showed elevated TSH and low free T4 levels, with typical treatment consisting of T4 or levothyroxine (Synthroid) to achieve a goal of TSH levels of 1 to 3 mlU per L (p.392). Thompson (2014) went further to state that laboratory findings for hypothyroidism may include decreased T4, possibly decreased T3 and the presence of antibodies for an array of thyroid antigens (p. 152). HT is considered an autoimmune disorder that is part of an organ-specific autoimmune subgroup, best known as autoimmune thyroid disease (AITD) (Nada and Hammouda, 2014, p. 575). Findings show that T lymphocytes and regulatory T cells get down regulated in AITD, compromising the body’s ability to control autoimmune processes (p. 579). Apoptosis or cellular death of thyroid cells was first observed in 1995, a probable result of the dysfunctional immune response (Asik et al., 2013, p. 54). Of significance, it is suspected that apoptosis could take many years to occur, suggesting that early diagnosis and appropriate treatment is a necessary step in preserving overall thyroid health (p. 54).

Pharmacologic treatment of HT typically consists of a T4 hormone called levothyroxine (Synthroid), starting at a low initial dose of 1.6 mcg per kg daily, with incremental changes made every three months, as needed (Sweeney et al., 2014, p. 392). Levothyroxine’s action replaces endogenous thyroid hormones, causing an increased metabolic rate in body tissues (Ciccone, 2013, p. 618). It promotes gluconeogenesis, mobilizes glycogen stores, stimulates protein synthesis, promotes cellular growth and aids in brain and central nervous system (CNS) development (p. 618-619). However, excessive T4 dosing may result in iatrogenic hyperthyroidism and other side effects include insomnia, headache, cardiac arrhythmias, angina, abdominal cramping, vomiting, diarrhea, menstrual issues, sweating, weight loss and heat intolerance (p. 619).

Levothyroxine has variable absorption in the gastrointestinal (GI) tract and is distributed to most tissues with the exception of the placenta and breast milk (Ciccone, 2013, p. 619). Levothyroxine is best taken on an empty stomach, 30 minutes to one hour before breakfast and four hours before or after taking an antacid to obtain the best absorption (NIH, 2013). Ciccone (2013) reports that levothyroxine gets metabolized into active T3 by the liver and other body tissues, with excretion occurring in the feces through the bile (p. 619). It is contraindicated in patients with a history of a recent myocardial infarction, hypersensitivity or hyperthyroidism, and should be used cautiously in the presence of severe renal or adrenal insufficiency and during use with infants or the geriatric population (p. 619).

Drug to drug interactions that reduce effectiveness of levothyroxine include bile acid sequestrants used for high cholesterol or concurrent estrogen therapy (Ciccone, 2013, p. 619). It may minimize the anti-clotting efforts with warfarin, reduce effectiveness of insulin or other oral hypoglycemic agents but may potentiate cardiovascular effects when combined with adrenergic agents such as bronchodilators or vasopressors (p. 619). Drug to food interactions occur with items containing high levels of calcium, iron, magnesium or zinc as it may bind to levothyroxine thus limiting overall absorption (p. 619). Drug formulations for levothyroxine are available in tablet, soft gels and powder form for injections, with dosing routes being oral, intramuscular or through an intravenous application (p. 620).

Thyroid (Armour thyroid) is a desiccated thyroid hormone preparation used for treatment of hypothyroidism through a T3/T4 combination therapy of levothyroxine and liothyronine (Cytomel) that compensates for hormone deficiencies and helps restore hormonal balance (Gaitonde, Rowley, and Sweeney, 2012, p. 249). Ciccone (2013) not only indicates its use in thyroid supplementation and treatment of euthyroid goiters, but also as suppression testing to differentiate mild hypothyroidism from thyroid gland autonomy (p. 1072). According to Vigneri et al. (1993), autonomous thyroid nodules may develop as a result of iodine deficiency, independent of TSH, with a clinical diagnosis determined by the presence of negative suppression of nodular iodine uptake and scan imaging upon T3 administration.

The drug action of thyroid (Armour thyroid) increases the metabolic rate of body tissues, a similar mechanism to those mentioned for levothyroxine, although it also possesses T3 in addition to T4 activity (Ciccone, 2013, p. 1072). The adverse reactions, drug to drug and drug to food interactions are similar to those mentioned for levothyroxine, however, there is an additional contraindication listed with hypersensitivity to beef (p. 1073). These thyroid formulations are limited to oral tablet use, with each 1gr being equivalent to 100 mcg of T4 or 25 mcg of T3 ; T3 being well absorbed and T4 having variable absorption (p. 1073).

In cases of persistent hypothyroidism, combination T3/T4 therapy with dessicated hormone preparations of Amour thyroid or levothyroxine (Synthroid) plus Liothyronine (Cytomel) may be the treatment of choice, although the use of dessicated preparations made from domesticated animals is not recommended by the American Association of Clinical Endocrinologists (Gaitonde et al., 2012, p. 249). According to Antonio Bianco, MD in an interview with Gustafson (2014), he suggested genetic testing of type 2 deiodinase polymorphism known as a disruption in the enzymatic conversion of T4 into T3 and necessary for the appropriate management of persistent hypothyroidism associated with unsuccessful T4 replacement therapy. Gaitonde et al. (2012) states although T3 is a biologically active form, its short half-life and dependency upon the peripheral conversion of T4 into T3 by deiodinase enzymes may result in impaired serum concentration levels, creating a hormone imbalance.

Liothyronine (Cytomel) is a T3 supplement used for treatment of hypothyroidism and in suppression testing to differentiate hyperthyroid from thyroid gland autonomy, and as an intravenous formulation for treatment of myxedema coma (Ciccone, 2013, p. 624). As with the other thyroid hormones, it has an action that increases the metabolic rate of body tissues and aims to restore hormonal balance (p. 624). It is contraindicated in patients with a history of a recent myocardial infarction, hypersensitivity or hyperthyroidism, and should be used cautiously in the presence of severe renal and adrenal insufficiency or during use with infants or the geriatric population (p. 625). The pharmokinetics demonstrate good absorption that gets distributed to most body tissues, although it does not tend to cross the placenta and may sparingly enter into breast milk (p. 625). It is metabolized by the liver and other tissues, getting excreted in the feces through the bile (p. 625).

Drug to drug interactions that reduce effectiveness of liothyronine include bile acid sequestrants used to control high cholesterol or concurrent estrogen therapy (Ciccone, 2013, p. 625). Liothyronine may limit the anti-clotting effect of warfarin, reduce effectiveness of insulin or other oral hypoglycemic agents, but may potentiate cardiovascular effects when combined with adrenergic agents such as bronchodilators or vasopressors (p. 625). Drug to food interactions were not common although care should be taken with iodine containing products such as seaweed.

When reviewing studies on HT, Nada et al. (2014) found patients with HT had variability in presentation, either high or suppressed TSH along with positive tests for anti-TPO and anti-Tg (p.575). A study by Sahin et al. (2012) revealed TSH seemed closely associated with vitamin D levels with their findings showing TSH levels of 3.88 mlU/l when vitamin D levels were above 30ng/ml with 25(OH)D testing (p. 318). Their animal studies revealed that low dose vitamin D and cyclosporine A, a powerful immunosuppressant, correlated with a reduction in experimental autoimmune thyroiditis (p. 317). Their conclusion was that vitamin D deficiency may be involved in the primary pathogenesis of HT and not simply an adverse result of HT (p. 319).

A review of studies concerning complications related to HT revealed evidence of Hashimoto’s encephalopathy first documented in 1966 following a patient presentation of aphasia, seizures, disorientation and hemiparesis (Yong, Soule and Hunt, 2014). They felt it was a rare diagnosis of exclusion, factoring in the seizures and neurologic symptoms, positive thyroid autoantibodies and responsiveness to steroids. Myeloneuropathy, a complication of HT, is also a rare diagnosis of exclusion, looking carefully at the autoimmune factors including anti-thyroid antibodies in order to not mistake it for a B12 deficiency (Kayal, Basumatary, Dutta, Mahanta, Islam and Mahanta, 2013, pp. 427-428). The myeloneuropahty presentation is characterized by scattered weakness and spasticity along with peripheral neuropathy, and it also is highly responsive to steroid therapy (p. 427).

Studies revealing risks from HT included a report by Thompson (2014), stating HT has an increased risk for developing lymphoma, making careful monitoring of long term laboratory levels a necessity (p. 152). Dhanwal (2011) found that thyroid hormones play a role in balancing bone mineral and bone density, noting increased fracture risk in both clinical presentations with hypothyroidism or hyperthyroidism (p. S111). Hypothyroidism, to a lesser extent, did reveal some reduction in bone mineral density (BMD) in qualitative ultrasound studies, and showed poor bone quality that directly correlated with increased TSH (p. S111).

Issues necessary to consider in physical therapy (PT) that are associated with hypothyroidism, specifically HT, include aiding in the diagnosis of an occult thyroid disorder or monitoring for medication trends or tolerances. Caution needs to be used during the performance of aerobics and conditioning exercises due to the increased risk of angina or cardiac arrhythmias. The incidence of increased sweating may heighten the risk of skin issues such as rashes, infections and blisters, making certain heat generating activities less tolerable. It is important to stay aware of the patient’s mental clarity, motor coordination, pain complaints and fatigue level as a way to assist in monitoring their medication response or effectiveness of their thyroid dose. Querying the patient about the timing of their thyroid medication and foods ingested may reveal absorption issues or possible interactions with concurrent drugs such as lithium or amiodarone.

In conclusion, it is clear that HT has a multifactorial origin, with causation ranging from increased stress, infection and pregnancy to limited iodine absorption, genetic issues, radiation exposure and abnormal hormone levels (Sahin et al., 2012, p. 319). Time is crucial, as minimizing the duration of symptoms is necessary to limit the permanent, long term thyroid damage that may occur from persistent abnormal thyroid hormone levels that enables autoimmune thyroid destruction. The rehabilitation setting is a perfect venue for closely monitoring the physical, emotional and spiritual issues associated with disease states, with time provided for patient education regarding stress management and physical therapy treatment for the associated risks and comorbidities of HT.

References


Asik, M., Sahin, M., Anaforoglu, I, Ankan S., Haydardedeoglu, F. I., Ertugrul T. D., & Tutuncu,
N. B. (2013). The antibody response to endoplasmic reticulum stress in Hashimoto’s thyroiditis. Turk Jen, 17, 53-56. Doi: 10.4274/Tjem.2151

Caleo, A., Vigliar, E., Vitale, M., Di Crescenzo, V., Cinelli, M., Carlomagno, C.,…Zeppa, P. (2013). Cytological diagnosis of thyroid nodules in Hashimoto thyroiditis in elderly patients. BMC Surgery, 13(Suppl 2), S41. Retrieved from http://www.biomedcentral.com/1471-2482/13/S2/S41

Ciccone, C. D. (2013). Drug guide for rehabilitation professionals. Philadelphia, PA: F. A. Davis Company.

Dhanwal, D. K. (2011). Thyroid disorders and bone mineral metabolism. Indian J Endocrinol
Metab, 15(Suppl2), S107-S112. Doi: 10.4103/2230-8210.83339

Gaitonde, D. Y., Rowley, K. D. & Sweeney, L. B. (2012). Hypothyroidism: An Update. Am
Fam Physician, 86(3):244-251. Retrieved from http://www.aafp.org/afp/2012/0801/p244.html

Hamaguchi, E., Nishimura, Y., Kaneko, S.& Takamura, T. (2005). Subacute Thyroiditis
Developed in Identical Twins Two Years Apart. Endocrine Journal, 52(5), 559–562.
Retrieved from https://www.jstage.jst.go.jp/article/endocrj/52/5/52_5_559/_pdf

Ipekci, S., Ozturk, K. & Cakir, M. (2011). A difficult decision—Hashimoto’s thyroiditis or
subactue thyroiditis? Turk Jem, 15, 125-127. Retrieved from www.researchgate.net

Kayal, A. K., Basumatary, L. J., Dutta, S., Mahanta, N., Islam, S. & Mahanta, A. (2013).
Myeloneuropathy in a case of Hashimoto’s disease. Neurology India, 61(4), 426-428.
DOI: 10.4103/0028-3886.117591

National Institutes of Health (NIH) (2013). Levothyroxine. Medline Plus. Retrieved from
http://www.nlm.nih.gov/medlineplus/druginfo/meds/a682461.html

Nada, A. & Hammoda, M. (2014). Immunoregulatory T cells, LFA-3 and HLA-DR in
autoimmune thyroid diseases. Indian Journal of Endocrinology and Metabolism, 18(4),
574-581. Doi: 10.4103/2230-8210.137524

Sahin, M., Taslipinar, A., Keapcilar, L., Yilmaz, H., Akgul, E. O., Beyhan, Z.,….Delibasi, T.
(2012). Low vitamin D3 levels in euthyroid Hashimoto thyroiditis. International Medical
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Sweeney, L. B., Stewart, C. & Gaitonde, D. Y. (2014). Thyroiditis: An integrated approach.
American Family Physician, 90(6), 389-396. Retrieved from http://www.aafp.org/afp/2014/0915/p389.html

Thompson, L. D. R. (2014). Chronic lymphocytic thyroiditis (Hashimoto thyroiditis). Ear, Nose
& Throat Journal, 93(4-5), 152-153. Retrieved from www.entjournal.com/article/chronic-lymphocytic-thyroiditis-hashimoto-thyroiditis

Vigneri, R., Catalfamo, R., Freni, V., Giuffrida, D., Gullo, D., Ippolito, A.,… Regalbuto C.
(1993). Physiopathology of the autonomous thyroid nodule. Minerva Endocrinol, 18(4),
143-145. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8190053

Yong, K. W., Soule, S. & Hunt, P. (2014). Endocrine encephalopathy. NZMJ, 127(1394).
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