Thyroid Disorder: An Overview

 

S. Anandkumar*, Jessly Chacko, Theertha C. K, M. Usha

Department of Pharmacy Practice, Swamy Vivekanandha College of Pharmacy, Tiruchengode, Tamilnadu, India.

*Corresponding Author E-mail: sakumar0307@gmail.com

 

ABSTRACT:

The focus of this review article is on thyroid disorders which can be hypothyroidism or hyperthyroidism, along with the treatment options. Thyroid disorder is a medical condition which affects the function of the thyroid gland. A thyroid disorder is one of the most common endocrine diseases across the world and affects an estimated 42 million people in India. Thyroid gland is one of the largest endocrine gland in the body which plays a major role in the metabolism, growth and development of the human body. It also helps to regulate many body functions by constantly releasing a steady a mount of thyroid hormones into the bloodstream. The persistence increasing or decreasing abnormalities in these hormone levels may cause various complications. Imbalance of thyroid hormones can leads to either hypo or hyperthyroidism. The major complication of hyperthyroidism are Graves’ disease, toxic multinodular goiter, and toxic adenoma. The diagnosis is based on abnormal values ofTSH, T4, T3 and Free T4 tests. Thyroid hormones play an important role in stimulating erythripoiesis and increase erythrocyte 2, 3-diphosphoglycerate concentrations. One of the major complications of thyroid dysfunction is anemia. Based on the thyroid disease the treatment may vary. Management of thyroid disorders includes levothyroxine, Thyroid hormone replacement and thyrectomy.

 

KEYWORDS: Thyroid Disorder, Hypothyroidism, Hyperthyroidism, Thyroid hormone, Thyroxine.

 

 


INTRODUCTION:

A thyroid disorder is one of the most common endocrine diseases across the globe and affects an estimated 42 million people in India1. Thyroid is one of the largest endocrine gland in the body which is positioned in the neck in front of trachea and larynx at the level of 5th, 6th, 7th, cervical and 1st thoracic vertebrae2. This highly vascularised gland weighs about 25g and surrounded by fibrous capsule.

 

Function of butterfly shaped gland is to synthesize, store and release thyroid hormones into our body3. The thyroid hormones (TH) secreted by thyroid gland control a wide range of physiological functions in the body which may include growth, metabolism and energy homeostasis4. The population aging largely contributes to this trend, and makes it rather unlikely to be reversed. Thyroid hormones generally stimulate erythropoiesis and also increase erythrocyte 2, 3-diphosphoglycerate concentrations, which serve to enhance the delivery of oxygen to tissues. In the absence of thyroid hormones, anemia frequently develops and may be normocytic, hypochromic-microcytic, or macrocytic5.

 

The two main type of thyroid disorder are hypothyroidism and hyperthyroidisms. Primary hypothyroidism, which is one of the most common endocrine diseases, which is caused by thyroid hormone deficiency due to alterations in the thyroid gland. The prevalence of hypothyroidism in general population ranges from 3.8% to 4.6%6. Elevated secretion of thyroid hormone leads to a condition of hyperthyroidism (thyrotoxicosis), which further results in increased metabolism. It is accompanied by suppressed TSH (to undetectable levels)4.

 

Hypothyroidism can be further divided into primary hypothyroidism and secondary hyperthyroidism. Primary hypothyroidism is a disorder of the thyroid gland causing decreased synthesis and secretion of thyroid hormones. Secondary hypothyroidism is caused by a disorder of the pituitary or the hypothalamus, leading to decreased TSH secretion and consequently to decreased synthesis and secretion of thyroid hormones7.

 

Hyperthyroidism is an excessive concentration of thyroid hormones in tissues caused by increased synthesis of thyroid hormones, excessive release of preformed thyroid hormones, or an endogenous or exogenous extra thyroidal source. The most common causes of an excessive production of thyroid hormones are Graves’s disease, toxic multinodular goiter, and toxic adenoma8.

 

Symptoms:

Hypothyroidism:

Fatique, dry coarse skin, cold intolerance, voice hoarseness, dry skin, facial periorbital oedema, voice hoarseness, slowed movements, decreased hearing, mental impairment, sleepiness, bradycardia, weight gain, paresthesia, constipation, and hair loss7.

Hyperthyroidism:

Adrenergic: Palpitations, tachycardia, anxiety, tremor, heat intolerance, stare, lid lag, hyperdefecation (not diarrhea). Cardiovascular: Tachycardia, irregular pulse (in atrial fibrillation), peripheral edema (in heart failure), dyspnea and orthopnea Cutaneous: Onycholysis (Plummer nails), patchy or generalized hyperpigmentation (especially of the face and neck), clubbing of fingers and toes accompanied by soft-tissue swelling of the feet and hands (thyroid acropachy). Hypermetabolism: Fever (in thyroid storm), Weight loss in spite of increased appetite. Neuropsychiatric: Rapid and pressured speech, anxiety, insomnia, psychosis (if hyperthyroidism is severe). Ocular: Discomfort or pain to the eyes due to light exposure (Photophobia), incomplete closure of the eyes when sleeping reported by the patient’s partner, increased lacrimation, increased eye sensitivity to wind or smoke, sensation of a foreign body or sand in the eyes8.

 

Thyroid test:

Thyroid is a butterfly shaped gland located in the neck in front of trachea and larynx. The main function of this gland is to synthesize, store and release thyroid hormones into our body3. Thyroid function tests (TFTs) are routine to interpret and confirm euthyroidism, hypothyroidism or hyperthyroidism9


 

Table 1-A Thyroid Function Test Result in Different Thyroid Conditions

 

Total T4

Free T4

Total T3

T3 Resin Uptake

Free Thyroxine Index

TSH

Normal

4.5-10.9mcg/dL

0.8ng/dL

60-181ng/dL

22-34%

1.0-4.3units

0.5-4.7milli-international units per liter

Hyperthyroid

↑↑

↑↑

↑↑↑

↑↑↑

↓↓

Hypothyroid

↓↓

↓↓

↓↓

↓↓↓

↑↑

Increased TBG

Normal

Normal

Normal

 


Thyroxine:

Thyroxine also known as T4 is a hormone produced by the thyroid gland on the influence of thyroid‐stimulating hormone (TSH). Thyroxine plays a key role in every process in the body, including oxygen consumption, growth, and heart rate10. It is the inactive form, which is converted into active form with the help of liver and kidney called triiodothyronine.

 

TSH test:

The release of TSH from the pituitary gland is stimulated by Thyrotropin releasing hormone (TRH) from the hypothalamus which, sequentially, regulates a variety of steps in the production of thyroid hormones. TSH gives significantly minute changes in free T3 and free T4. Thyroid tests involve series of blood tests used to measure function of thyroid gland. TSH secretion follows a circadian rhythm, with maximum levels observed in the early morning and a lowest in the late afternoon to mid-evening11.

 

Table 1-B : Other Test of Thyroid Function/Status

Thyroid Test

Clinical Utility

Free T3

To determine the degree of hyperthyroidism when TSH is suppressed ( sometimes use in conjunction with free T4)

Reverse T3

No clinical utility (elevate in non-thyroidism during pregnancy)

Thyroid stimulating immunoglobin &TSH receptor antibodies

Evaluation of the cause of hyperthyroidism(used in conjunction with thyroid uptake and scan and/or at time when radioiodine scanning cannot be performed (i.e.pregnancy)

Thyroglobulin

Follow-up of differentiated thyroid cancer

Ant-thyroglobulin antibodies

Only useful in conjunction with thyroglobulin (to assure reliability to thyroglobulin result)

Calcitonin

Diagnosis and follow –up of medullary thyroid cancer

24 hours urine iodine

To assure excess iodine from amiodarone or I.V. contrast has dissipated from the body

Total T3 and T4

No clinical utility with the availability of assays for free hormone levels

Free T4 by equilibrium dialysis

Considered the goal standard for free T4 measurement (seldom ordered as the test is costly and not widely available)

 

Causes of Thyroid Disorders:

Iodine Deficiency:

Iodine is a vital element of thyroid hormones; a low or high intake may head to thyroid disease12. Inadequate intakes of iodine reduce thyroid function and upshot in a group of disorders-goiter, cognitive impairment, and congenital abnormalities-cumulatively called as the iodine deficiency disorders (IDDs)13.

 

TSH levels:

Hypothalamus releases a substance called thyrotropin-releasing hormone (TRH) which stimulates the production of TSH by pituitary gland. A thyroid-stimulating hormone (TSH) blood test is performed to check for thyroid gland related problems. TSH causes the thyroid gland to produce two hormones namely triiodothyronine (T3) and thyroxine (T4).

 

Parathyroid Hormone:

PTH controls the levels calcium and phosphorus in the blood. Behind the thyroid gland there is four pea-sized glands is there that is PTH.A parathyroid hormone (PTH) blood test identifies the level of parathyroid hormone in the blood. This test is used to detect hyperparathyroidism, to check the status of chronic kidney disease, to find the cause of abnormal calcium levels.

 

Thyroid Cancer:

Thyroid cancer is the major endocrine cancer. Follicular epithelial cell-derived papillary thyroid cancer (PTC), follicular thyroid cancer (FTC), anaplastic thyroid cancer (ATC), and para-follicular C-cell-derived medullary thyroid cancer (MTC), are types of thyroid cancer. Even though, thyroid cancer is generally curable with the present standard treatments of surgery and adjuvant radioiodine therapy. Still there remain many patients whose conditions are incurable, disabling, and even fatal14.

 

Thyroid Treatment:

The standard treatment of hypothyroidism is Levothyroxine (L-T4). It is effective when administered orally, has a long serum half-life which allows daily administration15. Hyperthyroidism is treated by reducing the excess hormone levels by administering ant thyroid drugs or by radioactive iodine (radioiodine ablation) treatment or by surgical treatment (complete or partial removal of thyroid) termed as thyroidectomy.

 


 


Figure 1: Hypothyroidism Treatment with Levothyroxine

 


Thyroid Hormone Replacement:

Thyroid hormone replacement Although the thyroid gland produces T4 and T3, LT4 monotherapy has been the mainstay of thyroid hormone replacement since the 1970s replacing desiccated thyroid extract (DTE) which had been used for many years prior. This is because it is easily administered, well absorbed by the oral route and its long half-life allows for once daily dosing with very stable serum levels. It was also shown to be converted to T3 within the body alleviating the need to add LT3 which does not have the same stable pharmacological profile. Moreover, it has also been shown that the majority of circulating T3 comes from peripheral conversion of T4 to T3 and not secretion of T3 from the thyroid, hence T4:T3 secretion ratio of approximately 14:1 appears average in humans, suggesting only a small role for secreted T3. However, there is a small group of patients who do not feel back to their euthyroid wellbeing despite having thyroid function tests suggestive of adequate replacement on LT4. Several studies showing that on LT4 monotherapy serum T3 levels are significantly lower for the same TSH in euthyroid patients, although the clinical significance of this is unknown. Another study showes it is impossible to normalise serum TSH, T3 and T4 levels or tissue T3 levels in laboratory animals giving them LT4 monotherapy.

 

Role of the T and B Lymphocytes in Pathogenesis of Autoimmune Thyroid Diseases:

Auto-immune thyroid disorders broadly include Graves disease and Hashimotos thyroiditis, which are the most common causes of thyroid gland dysfunctions. In these disorders develop due to complex interactions between environmental and genetic factors and are characterized by reactivity to self thyroid antigens due to autoreactive lymphocytes escaping tolerance. Both cell mediated and humoral response lead to tissue injury in auto-immune thyroid disease. The differentiation of CD4+ cells in the specific setting of immune mediators (for ex: cytokines, chemokines) results in differentiation of various T cell subsets. T cell description has shown a mixed pattern of cytokine production indicating that both subtypes of T helper, Th1 and Th2, responses are involved in all types of AITD. Moreover, recent studies described T cell subtypes Th17 and Treg that also play an essential role in pathogenesis of AITD. These review will focused on role of the T regulatory Treg and T helper (especially Th17) lymphocytes, and also of B lymphocytes in AITD pathogenesis.

 

Graves disease and Hashimotos thyroiditis are classified as autoimmune thyroid disorders characterized by the breakdown of self-tolerance to thyroid antigens resulting in circulation of antibodies and lymphocyte infiltration. There is a developing trend for the prevalence of Hashimotos disease and it is estimated at approximately 5-10%. Women are diagnosed with it five to ten times more often than men and its frequency increases with the age (the highest number of cases is observed between 45 and 65). In paediatric population, the most common age at presentation is adolescence yet, HT may develop at any time, rarely even in infants. In case of Graves disease, meta analyses of different studies have estimated the general frequency of the disease to be about 1%. However, Graves disease is 4-5 times more common in women than in men.15

 

CONCLUSION:

Thyroid disease without proper diagnosis may put patients at risk for certain serious conditions, such as cardiovascular diseases, osteoporosis and infertility. The cause of thyroid disease worldwide is iodine deficiency, which causes goitre and hypothyroidism in some. However, autoimmune thyroid disease is the predominant form of thyroid dysfunction in the developed world. Although considerable advances have been made in our understanding of the immune system, we still do not understand thyroid autoimmunity completely. Inorder to overcome the hormonal imbalances associated with hypothyroidism, thyroid replacement medication are generally used. Hyperthyroidism (overactive thyroid) occurs when the thyroid gland produces too much of the hormone thyroxine and is usually treated with medications, surgery, or oral radioactive iodine. However, these treatments are indefinite and may cause the thyroid to secrete inadequate amounts of T3 and T4 and function insufficiently after treatment.

 

Although thyroid cancer accounts for only 1% of all malignancies, it is the commonest endocrine tumour. There is evidence that maternal thyroid hormone deficiency results in impaired neurodevelopment of the foetus. Appropriate screening, monitoring and counselling helps in early detection and overcoming the negative impact of the disease. Thyroid physiology can be better understood by molecular biology (action of thyroid hormones at a cellular level) and has resulted in the production of hormone analogues that may be useful in obesity and other conditions. These represent good examples of scientific excellence in collaboration with the pharmaceutical industry. Advances in thyroidology resulting in improved clinical care to patients will help in clear understanding of these diseases and their rational therapy.

 

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Received on 01.11.2019         Modified on 21.12.2019

Accepted on 18.01.2020       ©A&V Publications All right reserved

Res.  J. Pharmacology and Pharmacodynamics.2020; 12(1):01-04.

DOI: 10.5958/2321-5836.2020.00001.4