Based on the initial symptoms, the patient most likely suffers from hypothyroidism or low thyroid hormone disorder. Further clinical tests and an examination of the family’s medical history reveals that the particular disorder could be Hashimoto’s disease; also called Hashimoto thyroiditis. Hashimoto thyroiditis is classified as an autoimmune disease. In autoimmune disease, one's immune system attacks the body’s tissue specifically the thyroid gland (Skugor & Wilder, 2006, p.2). By attacking the thyroid gland, the disease reduces the gland’s ability to produce thyroid hormones of substantial quantity. This condition leads to hypothyroidism. Thyroid hormone deficiency presents with many symptoms such as myalgia, arthralgia, fatigue, and weight gain. Besides, most patients also present with reduced heart rate, sensations of pins and needles especially on the arms, puffiness of the face, cold intolerance, irregular menstrual periods, and dry skin and cold sensation over certain body parts (Baron-Faust & Buyon, 2003, p. 88).
The body mass index of the patient in the case study indicated that she had gained about 4 kilograms since the emergence of her first symptom of head cold, about three months before her initial medical examination. Hypothyroidism has an effect of increasing one’s body weight. Weight gain or loss is strongly related to basal metabolic rate (BMR). BMR is determined by measuring the quantity of oxygen used by the body at rest. Low level of thyroid hormones is related to low basal metabolic rate (Schneider, 2011, p.48). Changes in energy balance are responsible for the differences in BMRs (American Thyroid Association, 2012). Therefore, reduced BMR caused by hypothyroidism leads to a positive energy balance that result in weight gain. This explains the additional 4kg acquired by the patient by the time the assessment was conducted.
The patient was referred to the first panel of tests to check her thyroid function and the general effects of thyroid hormones on her body. This was a genuine attempt to determine the level of activity of the available thyroid hormones on the patient’s body. Thyroid hormones, particularly triiodothyronine (T3) and tetraiodothyronine (T4) are tyrosine hormones produced by the thyroid gland to primarily regulate metabolism in the body. Thyroid hormones act on almost all body cells. They mediate growth, raise the basal metabolic rate, mediate neural maturation, and enhance the sensitivity of the body to catecholamines such as epinephrine and norepinephrine. The hormones also aid in the regulation of carbohydrate, fat, and protein metabolism.
The patient’s total serum cholesterol level and LDL cholesterol were elevated above the normal concentration as revealed by the tests. Hypothyroidism is associated with elevated blood cholesterol and triglycerides levels (Ehnholm, 2009, p. 251). By controlling the genes responsible for the expression of LDL receptors, triiodothyronine can up-regulate the receptors for low-density lipoprotein (LDL) (Jameson, Degroot, & De Kretser, 2010, p. 1428). This is achieved by the T3 binding directly to particular Thyroid Hormone Response Elements (TREs). Moreover, T3 also regulates sterol regulatory element binding protein-2 (SREBP-2). This protein is responsible for the regulation of expression of the gene responsible for LDL receptor. Hypothyroidism has an effect of slowing the ability of the body to degrade or catabolize cholesterol. Due to hypothyroidism, there is down-regulation of LDL receptors and a reduction in their activity. Reduced number of LDL receptors lead to the accumulation of LDL in the blood stream, hence ultimately increasing both the level of LDL cholesterol and total serum cholesterol levels in the body (Smith, n.d., The Reason for Cholesterol Increase in Hypothyroidism, Para. 1). This explains the increase in the patient’s cholesterol level.
In hypothyroid patients, the activity of the enzyme lipoprotein lipase, which helps in the breakdown of lipoproteins rich in triglycerides, is significantly reduced (Rizos, Elisaf, & Liberopoulos, 2011, p. 2). These patients, therefore, present with elevated levels of triglycerides. This explains the patients raised levels of triglycerides. The test results also revealed low concentrations of tetraiodothyronine (T4). This is the hallmark for the diagnosis of hypothyroidism as it shows that the body produces thyroid hormones in small amounts that may be sufficient enough to sustain the metabolic processes in the body. The patient’s thyroid-stimulating hormone (TSH) was, however, substantially elevated. This was due to the body’s attempt to stimulate the production of more thyroid hormones to raise their levels to the normal levels. Through negative reflex, the reduced thyroid hormone count stimulates the production of more TSH by the anterior pituitary gland in an attempt to stimulate the thyroid gland to produce more thyroid hormones. Hypothyroidism, however, does not significantly affect blood glucose control (Wu, 2014, Effect on diabetes control, Para. 5).
After the initial diagnosis, the patient was placed on a small dose of thyroxine and the same tests were performed three months later. The tests revealed that not only had the level of serum total cholesterol decreased by 0.2mmol/l, but the LDL cholesterol level had also decreased by 0.4mmol/l. This can be explained by the effects of the thyroxine dose on the patient's metabolism of cholesterol. The thyroxin up-regulated and activated the LDL receptor by binding directly to thyroid hormone responsive elements (TREs).Besides, the thyroxin also raises sterol regulatory element binding protein-2 (SREBP-2) which in turn up-regulates LDL receptors. The increase in LDL receptors led to an increase in catabolism of cholesterol. The increase in cholesterol catabolism, in turn, led to the lowering of the level of serum total cholesterol and LDL cholesterol.
The tests also showed that the patient's blood triglyceride level reduced by 0.2mmol/l. The increased thyroxin level led to an increase in the activity of the enzyme lipoprotein lipase. This enzyme then catalyzed the breakdown of lipoproteins rich in triglycerides eventually leading to their decline in the body. The extra dose of thyroxin resulted in the increase in body T4 by 5.2pmol/l. The test results also showed that the level of TSH in the body reduced by about 12.2mU/l. This is due to the negative reflex action of the increased thyroxin on the anterior pituitary gland to decrease the production of more TSH in an attempt to lower the level of thyroxin.
Patients with hypothyroidism have higher mean 24-hours systolic pressure and pulse pressure compared to normal individuals (Wynn, n.d., para. 1). The previous assessment revealed a systolic pressure of 138mmHg. Hypothyroidism leads to the production of excess noradrenaline from adrenal medulla which causes constriction of blood vessels in the body (Stop the thyroid madness, n.d). This tends to increase blood pressure within the body. After three months of thyroxin therapy, the systolic pressure reduced to 134mmHg. This is due to the action of thyroxin to lower the production of catecholamines, hence inhibiting blood vessel constriction. This contributed to the decrease in the systolic pressure.
The presence of TPO antibodies in one’s blood indicates that the thyroid disorder in question is an autoimmune disorder. Therefore, it helps distinguish them from other thyroid disorders (Mayo Clinic, 2015). In Hashimoto thyroiditis, the body makes thyroid peroxides antibody (TPOAb) that attacks healthy thyroid cells leading to their damage. The level of thyroid peroxidase antibody (TPOAb) can, therefore, be used to diagnose Hashimoto’s disease. Therefore, the fact that the patient’s thyroid peroxidase antibody (TPOAb) test turned positive indicates that the patient’s hypothyroidism is attributed to Hashimoto thyroiditis.
After another three months, a decision to begin statin therapy was made following the patients prevailing dyslipidemia. Statins are lipid-lowering medications that inhibit the activity of the enzyme HMG-CoA reductase. This enzyme is essential in cholesterol synthesis. The drugs are competitive inhibitors that act at the rate limiting step of hepatic cholesterol synthesis that involves enzyme HMG-CoA reductase. Among these drugs are rosuvastatin, fluvastatin, and simvastatin. Before commencing statin treatments, it is important to conduct baseline biochemical tests to monitor treatment and adverse effects of the drugs. The most significant adverse effects are muscle and tendon pain, weakness, stiffness, and cramping. Other important adverse effects include liver damage leading to the rise in liver enzyme levels in the blood, and hepatic and sexual dysfunction.
Elevation of creatine kinase level is a reliable indication of statin-induced myopathy in patients on statins (Ferri, 2015, p. 1081). The activity of serum creatine kinase rises significantly in myopathies caused by statin therapy. It is, therefore, important to determine the level of serum creatine kinase before the beginning statin treatment to monitor the drugs side effects. It is also important to exclude the secondary causes of hypercholesteremia such as hypothyroidism. This is done by adequately treating the cause of the elevated cholesterol before beginning statin treatment. This was monitored by determining the level of T4 and TSH in the patient’s blood. The high T4 level of 14.4pmol/l indicated that the patient was no longer having thyroid hormone deficiencies by the time the statin treatment began.
It is also important to determine the level of lipid such as triglycerides before the onset of treatment (Patient, n.d.). This would be used to determine the efficacy of the therapy by comparing this level with values obtained in later tests. The levels of aspartate transaminase and alanine aminotransferase usually rise in hepatotoxicity caused by the statins. It is, therefore, important to determine alanine aminotransferase activity before the onset of treatment to aid in monitoring the course of treatment with time.
Damage to the liver by statins causes an increase in the levels of alkaline phosphatase and gamma-glutamyl transferase (Bouyet, 1992, p. 202).It was, therefore, important to determine their levels before beginning the treatment to monitor the course of therapy. In some instances, statin therapy may act to raise the quantity of serum bilirubin in the body by activating haem oxygenase-1.It was, therefore, important to determine the serum levels of bilirubin in the patient as was done to monitor the efficacy of statin therapy.
After eight years of statin and thyroxin therapy, the patient suffered immune-mediated necrotizing myopathy induced by statins. This particular myopathy is strongly linked to inflammatory reactions that lead to myogenic changes including muscle-fiber fibrosis as shown by the patient’s quadriceps muscle biopsy. Further diagnostic confirmation is done by analysis of antibodies to 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR).The high levels of anti-HMGCR of 70U/l in patients’ blood revealed that the patient was suffering from immune-mediated necrotizing myopathy.
The patient had been exposed to statin for years before developing autoimmune myopathy during which there were no anti-HMGCR antibodies. The level of creatine kinase rose markedly to 7540U/l with the development of myopathy. Anti-HMGCR antibodies were also expressed in the patient’s blood as shown by the tests. The activity of creatine kinase reduces to normal levels after treatment. The level of anti-HMGCR antibodies also normalized with continued treatment.
The patient was placed on methylprednisolone, and the statin therapy was replaced by other cholesterol and lipid therapy after developing immune-mediated necrotizing myopathy caused by statins leading to muscle weakness. Methylprednisolone is synthetic corticosteroid that resembles the glucocorticoids produced by the human adrenal glands. Methylprednisolone is used to replace the natural glucocorticoids in patients who do not produce them in their adrenal glands. The drug is also anti-inflammatory and aids in relieving inflammation (MedicineNet.com, 2015, Drug Class and Mechanism, para. 1). It is, therefore, important in the treatment of conditions such as arthritis, severe allergies, and even asthma. By putting the patient on Methylprednisolone therapy, the inflammation causing fibrosis of the patient's muscles was relieved. The patient was also placed on other lipid and cholesterol treatment drugs since the statin therapy was causing autoimmune necrotizing myopathy. For this reason, the patient was able to improve in her muscle activity with time.
The medical history of the patient’s mother and sister of rheumatoid arthritis and type 1 diabetes mellitus respectively are also of significance in the diagnosis of the patient’s initial condition. One of the best examples of familial clustering of autoimmune diseases involves rheumatoid arthritis, Hashimoto's disease and type 1 diabetes mellitus (Genet, 2005).These diseases are usually present on a particular family’s line of genealogy. The presence of one of the diseases can be a hallmark for the presence of any of the other in other family members. In the study conducted by Thomas et al. (1983, p. 2), about 13% of patients with rheumatoid arthritis were found to have had a first degree or second degree relative with type 1 diabetes mellitus while 13% had a similarly close relative with an autoimmune thyroid disease. The clustering is attributed to shared genes, environment, and interaction of both.
The father’s medical condition was also important especially after determining dyslipidaemia as another metabolic disorder in the patient. This reveals that cause of myocardial infarction that resulted in the death of the patient's father is likely due to familial dyslipidaemia. There is a chance that the patient inherited dyslipidaemia from her father. It, therefore, helps in diagnosis of the patient’s additional metabolic derangement due to dyslipidaemia.
Following muscle weakness experienced by the patient, a muscle biopsy was essential to reveal muscle fibrosis and inflammatory infiltration. This was very significant in diagnosing the necrotizing myopathy. The level of creatine kinase analysis showed markedly high levels of creatine kinase that marked the onset of immune-mediated necrotizing myopathy. Analysis of antibodies to 3-hydroxy-3-methylglutaryl-coenzymeA reductase (HMGCR) also proved particularly important in the diagnosis of the myopathy. The high levels of anti-HMGCR of 70U/l in patients’ blood revealed that the patient was suffering from immune-mediated necrotizing myopathy.
Cholesterol levels in serum are measured in laboratories enzymatically in a series of coupled chemical reactions (Centers for Disease Control and Prevention, n.d., p. 3). Cholesteryl esters are hydrolyzed while the 3-hydroxyl group of the cholesterol is oxidized. Hydrogen peroxide is a byproduct of the reactions and is quantitatively measured by reacting with aminophenazone and chlorophenol in a reaction that leads to color changes catalyzed by a peroxidase enzyme. Absorbance is then measured at 500nm.The color intensity observed and measured by spectrophotometry is directly proportional to the concentration of cholesterol.
In the determination of triglycerides, it is measured enzymatically in a series of coupled reactions in which triglycerides are initially hydrolyzed to form glycerol. Glycerol oxidase is then used to oxidize glycerol leading to the formation of hydrogen peroxide as one of the by-products. The hydrogen peroxide is then reacted with aminophenazone and chlorophenol in a reaction that leads to color changes. The absorbance of the product solutions is then taken at 500nm and plotted on a graph to determine the concentration of triglycerides.
High-density lipoproteins are measured directly in blood. In the procedure, a blocking reagent is used to apoB containing lipoproteins un-reactive. In this way, lipoproteins containing apoB are excluded from the experimental assay and therefore the test only detects HDL-cholesterol.
Creatine kinase activity is measured directly by a coupled enzymatic reaction that results in the production of NADH. In the reaction, phosphocreatine is reacted with ADP to form creatine and ATP (CDC, n.d). The ATP is used to phosphorylate glucose in a reaction catalyzed by hexokinase leading to the formation of glucose-6-phosphate.The glucose-6-phosphate is oxidized in the presence of glucose-6-phosphate dehydrogenase by NADP to form 6-phosphogluconate and NADPH (Rodak et al., 2016, p. 115). The amount of enzyme that transfers one micromole of phosphate to ADP in one minute from phosphocreatine at pH of 6 makes one unit of creatine kinase.
Determination of the level of serum alanine aminotransferase is based on pyruvate hydrazone absorbance in alkaline medium (“Aminotransferase”, n.d). An amino group is transferred from alanine to 2-oxoglutarate leading to the formation of glutamate and pyruvate catalyzed by the enzyme alanine aminotransferase. The increase in pyruvate reflects an increase in ALT. Spectrophotometrically, the level of pyruvate is determined in the form of hydrazone by reacting with 2, 4-dinitrophenylhydrazine in an alkaline medium.
Muscle biopsy is usually done to diagnose diseases of the muscle or myopathy. There are two types of muscle biopsy namely needle muscle biopsy and open muscle biopsy. In both, tissue or cells from the muscle with myopathy are removed, studied under a microscope and other laboratory tests are performed on it to determine the cause of the myopathy by a specialist. The choice for the muscle for biopsy is usually based on the site of symptoms such as weakness and pain in the muscle. In needle muscle biopsy, a needle is inserted into the affected muscle to obtain a muscle tissue sample.
Open muscle biopsy is done in cases when a large specimen of the affected muscle is required for analysis. A local anesthetic such as lidocaine is used to suppress pain just before an incision is made to gain access to the muscle tissue. Intact pieces of the sample muscle tissue are obtained from the belly of the muscle and wrapped in gauze slightly dampened in saline. The samples are then sent to the laboratory for analysis. Electromyography is a related procedure for determining neuromuscular abnormalities. The procedure is done to measure muscle’s electrical activity at rest, forceful muscle contraction and under a slight contraction of the muscle.
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