Thyroid Hormones and its Physiological Significance:
This report depicts the clinical manifestations of a 46 year old primary school teacher with a past medical history of celiac disease as presented before GP. The laboratory data of the suggested tests and all her other vital stats pointed towards Hashimoto thyroiditis as mentioned by her physician. Therefore here in this report a detailed guideline has been given about the disease and prescribed diagnosis procedure along with the available mode of treatment.
Thyroid Hormones and its Physiological Significance:
Thyroid hormones (TH) secreted by thyroid glands are significant for the proper development of the brain in infants, regulates the metabolic activity and has effects upon every organ of the body in adults. The major hormones synthesized by thyroid gland are 3,5,3'-triiodothyronine (T3), thyroxine (T4) and reverse 3,5,3'-triiodothyronine (rT3) which are in turn controlled by thyroid-stimulating hormone (TSH) secreted from the anterior lobe of pituitary gland.Iodine can be considered to have important role for the functioning of thyroid hormone. Thyroid hormone binds to intracellular receptors of mitochondria and results in increased breakdown of nutrients and generation of ATP.Thyroid hormone specifically acts upon beta receptors on the heart, which causes elevated heart beat rate. In gastrointestinal tract, THcauses increase in GI motility. The hormone is necessary for neural development in the brain; it helps in neurogenesis, neuronal migration, neuronal and glial cell differentiation, myelination, and synaptogenesis (Shahid et al, 2019; Yen et al, 2001).
Mechanism of Action:
The thyroid hormone gets transferredin the blood when it is still bound with the serum binding proteins such as transthyretin, thyroid-binding globulin (TBG) or albumin. After reaching the target site, the hormones T4 and T3 dissociates from the binding protein so that they can be transported inside the cells either via diffusion process or by carrier-mediated transport. After transportation they bind to different receptors such as nuclear alpha or beta of respective tissue which activates transcription factors. The whole phenomena activate certain genes of respective cell type, which results in cell-specific response T4and T3 exert (Shahid et al, 2019).
Hypothyroidism and its root causes:
Hypothyroidism, a common thyroid hormone deficiency disorder affects mostly women. The literature survey revealed that the incidence rate of clinical hypothyroidism is 0.5 – 1.9% among women and < 1% among men. Hypothyroidism can be classified based on onset time – congenital and acquired, level of endocrine dysfunction – primary, secondary and central and based on the severity of the disease – clinical and subclinical. The incidence rate of subclinical hypothyroidism is 3 – 13.6% among women and 0.7-5.7% in men (Athanassiou et al, 2010). The disease prognosis can be easily done by measuring the thyroid hormone levels in the blood. The primary causes of hypothyroidism are chronic autoimmune thyroiditis, inadequate intake of iodine, thyroidectomy, treatment with radioactive iodine, radiotherapy, drugs and thyroid gland agenesis or dysgenesis. The secondary or central cause of the disease includes conditions such as pituitary gland adenomas, history of surgery or radiotherapy of the pituitary gland, head trauma history, pituitary apoplexy, Hypothalamic tumors, History of surgery or radiotherapy of the hypothalamus (Athanassiou et al, 2010). Here disorder of thyroid gland causes decreased production and synthesis of thyroid hormones. 50% of the hypothyroidism cases occur due to autoimmune dysfunction resulting in chronic autoimmune thyroiditis. The residual cases are due to drug abnormalities, radiation therapy treatment. Both postpartum and silent thyroiditis resulting in hypothyroidism are considered to be part of chronic autoimmune thyroiditis. The frequency is found to be higher among women both in middle-aged (30 to 50 years) and children (Athanassiou et al, 2010; Mercado et al, 2001).
Hashimoto's thyroiditis (HT):
Chronic autoimmune thyroiditis is also known as Hashimoto thyroiditis occurs due to destruction of thyroid tissues by both cell-mediated and antibody-mediated immune system. Hashimoto's thyroiditis (HT) is a common autoimmune disorder that is found to be related with gastric disorders among 10% to 40% of patients (Mincer et al, 2019). The production of anti-thyroid antibodies which in turn attacks the thyroid cells results in formation of progressive fibrosis.The patients reveal hypochlorhydria-dependent iron-deficient anaemia, which leads to pernicious anaemia followed by severe gastric atrophy(Mincer et al, 2019).
Epidemiology:
It is considered to be one of the most common causes of hypothyroid because after the age of six years in United States and also in certain parts of the world where intake of iodine can be considered to be adequate. The literature revealed the rate of incidence to be 3.5 per 1000 people per year among women and 0.8 per 1000 people per year among men. The incidence rate of thyroid disease generally increases with age.Twin studies have revealed improved concordance of the disease among monozygotic twins in comparison to dizygotic twins. Research study data conducted in Denmark have established concordance rates of about 55% among monozygotic twins when compared with 3% among dizygotic twins. This data suggests that 79% of predisposition is due to genetic factors, allotting 21% for environmental and sex hormone influences (Mincer et al, 2019; Brix et al, 2011; Ruggeri et al, 2017).
Clinical Manifestations:
Initial symptoms depict constipation, fatigueness and weight gain. With the advancement of the disease manifestations of symptoms such as intolerance to cold, decreased sweating, nerve deafness, peripheral neuropathy, goiter enlargement, voice hoarseness, decreased energy, muscle cramps, joint pain, hair loss, sleep apnea, and menorrhagia, mental health disorders such as depression, dementia, memory loss are evident. Physical findings includes cold, dry skin, facial edema particularly nonpitting edema in the hands, relaxation of tendon reflexes which got delayed, high blood pressure, ataxia, macroglossia and slow speech. The patient also complained about the celiac disease in the past. The data that are available in the literature also states certain symptoms of celiac disease (CD) are associated with hypothyroidism. The prevalence rate of CD was found to be 2 to 5 percent in patients suffering from autoimmune thyroid disorders (Ch’ng, et al, 2007).The pathophysiology of the disease shows infiltration of lymphocytes and fibrosis as notable features of the disease. The diagnosis depends upon clinical manifestations of the disease in correlation with laboratory data such as enhanced TSH and normal or low thyroxine levels (Takamatsu et al, 1998). The case report presented similar facts such as serum TSH level was 15 mU/L (Ref.range:0.4 – 4.5 mU/L), free thyroxine (FT4): 5 pmol/L (10 - 20 pmol/L) and total triiodothyronine (T3): 0.9 nmol/L (0.9 - 2.5 nmol/L) which supported the diagnosis as the level of the TSH is higher than the normal range and the free thyroxine level was lower than the normal range mentioned. Physical examinations of the patient revealed that both the thyroid lobes are diffusely enlarged with firm consistency which matches with the pathophysiology of the disease. Significantly higher levels of anti-thyroid peroxidase (TPO) antibodies can be observed among patients suffering from Hashimoto thyroiditis. In vitro conditions demonstrated that anti-TPO antibodies fixes complement and kill erythyrocytes.The report data about the anti-thyroglobulin (anti-Tg) antibody and anti-thyroid-peroxidase (anti-TPO) levels were significantly elevated justified by the above statement. The patient belongs to the middle-aged group which also matches with the prevalence data. Myxedema can be considered as the classic skin characteristic in relation to hypothyroidism, caused primarily due to increased glycosaminoglycan deposition. Though uncommon but found amongst the many cases, skin is mostly dry and scaly. Reduced hair growth, dull and brittle hair and diffused or partial alopecia are also very common. Epidermal thinning is evident via histopathological examination. Water retention is caused due to increased dermal mucopolysaccharides. The patient here also reported that hair felt drier, cold dry rough skin and slight non-pitting oedema around the ankles. Bradycardia, fatigues, exercise intolerance, decreased muscle strength are among the other symptomatic features observed among patients suffering from Hashimoto thyroiditis. Experimentally it is proved that rats (animal models) with hypothyroid condition have decreased survival rates. Biochemical changes have resulted in lowered oxidation rate of pyruvate and palmitate in muscle cells and enhanced utilization of glycogen, followed by diminishing of fatty acid mobilization. Among significant features muscle weakness and myopathy are noteworthy.The female patient also reported overall muscle aches and stiffness around her neck. Among the vital signs: blood pressure 140/95 mmHg, pulse rate 98 per minute, respiration rate 16 per minute, and body temperature 36.5℃, BMI: 26.1 matches with the symptomatic features of the disease. Anaemia can be observed among 30% to 40% of the patients. Creatine kinase, prolactin hormone, total cholesterol, LDL, and triglyceride levels can also become elevated among patients (Liu et al, 2016) (Yoo et al. 2016.) Other tests report data such as total cholesterol 7mmol/L (3- 5.5 mmol/L), complete blood count showed decreased RBC count and low Hb level. It was observed that individuals suffering with subclinical hypothyroidism may show high level of LDL cholesterol level. Higher level of TSH hormone contributes to high cholesterol level. The condition of anaemia is frequently observed to be associated with thyroid problems. Different forms of anaemia may develop during thyroid dysfunction such as normocytic anaemia (most commonly associated) and macrocytic or microcytic anaemia (less frequently associated). The patient report on complete blood count showed lowered count of RBC and low Hb level which matches with the literature reports about the disease (Ruggeri et al, 2017; Fein, et al, 1975). Women suffering from thyroid problems show problems in the menstrual cycle. Both the conditions of hypothyroidism and hyperthyroidism can result in heavy, light or even irregular periods. The thyroid hormone problems can stop the menstrual cycle for several months, a condition known as amenorrhea. It was evidenced based on a study conducted with 171 female patients with premenopausal hypothyroid conditions and normal group containing 214 people revealed that out of the total 214 normal controls, 196 had normal menstruation, 19 had irregularities in their period cycle (oligomenorrhoea). The patient also reported about the menstrual irregularities in her case history (Krassas, et al, 1999).
Available Treatment:
The preferred treatment for hypothyroidism is replacement of thyroid hormone. Patients suffering from cardiovascular disease and elderly patients should be given lower doses of drugs. On the contrary, during pregnancy the dosage of thyroxine can be elevated by 30%. The disease is a lifetime disorder and the key management is to follow up the levels of the particular hormone. Also the drug dose may cause lymphoma therefore follow upcheck up of the neck region is highly suggested. The autoimmune diet heals the gut and in turn diminishes the harshness of the disease response. Much deeper research work is needed before it becomes a mainstream topic (Mincer et al, 2019). Another treatment option for hypothyroidism is surgery based treatment also known as thyroidectomy (the partial or total removal of thyroid gland) though this method is rarely applied in comparison to thyroid hormone medications (Vaidya, et al, 2008).
Hashimoto thyroiditis or chronic autoimmune thyroiditis is an autoimmune disease. The diagnosis depends upon clinical manifestations of the patient correlating with laboratory data. The suggested test skilfully confirmed the presence of the disease and the available mode of treatment has also been discussed along with the diagnosis procedure.
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