Hypothyroid Disease A deficiency of the thyroid hormone leads to hypothyroid disease; a disease that may be characterized both in clinical and pathophysiological manifestations throughout the body system. The most prevalent causes of hypothyroid disease include various autoimmune diseases, medication for hyperthyroid disease, and having had surgery on the thyroid. Other not so common causes of hypothyroidism include certain congenital diseases, pituitary disorder, pregnancy, or a deficiency in iodine. Hypothyroid disease may be divided into primary and secondary hypothyroidism. When there is a deficiency in the synthesis of hormones or damage to thyroid tissue, primary hypothyroidism results. Secondary hypothyroid disease, rather, occurs when there is not enough thyroid-stimulating hormone available. This insufficiency of thyroid-stimulating hormone could be a result of a defect in the anterior pituitary gland. Secondary hypothyroidism may also be caused by an insufficient amount of thyrotropin-releasing hormone, which most likely occurs due to impairment of hypothalamus functioning. Most patients tend to have a diagnosis of primary hypothyroidism. Most frequently this disease is found in women over the age of 60. Autoimmune disorders put a patient at an even higher risk for developing hypothyroidism, as does a family history of autoimmune disorders. In order to test for levels of thyroid hormone or thyroid-stimulating hormone within the body a blood test may be done. If a low level of thyroxine and an increased level of thyroid-stimulating hormone were the results of the blood test, this would be indicative of hypothyroid disease. There are various symptoms of hypothyroid disease and the severity of these symptoms often depends on how deficient the patient is in the thyroid hormone. Symptoms include such manifestations as weariness, lethargy, a reduced appetite, dry skin that is extremely sensitive to cold, constipation, a raspy voice, alopecia, soft and brittle nails, unexplained weight gain, and an irregular menstrual period. Serious complications may result if hypothyroid disease remains untreated. These complications may include the development of a goiter, cardiac problems, a reduced mental status, myxedema, fertility problems, and birth defects. To avoid these complications from occurring, a patient with hypothyroidism should be treated with thyroid hormone replacement therapy in order to achieve adequate levels of the thyroid hormone in the body, therefor reversing the symptoms of hypothyroid disease.
The thyroid gland is a butterfly-shaped structure, situated directly below the larynx at the midline of the anterior neck, with the gland’s two lobes on either side of the larynx attached by the isthmus. This gland is made up of a multitude of very small saclike structures referred to as follicles. These follicles are the functional aspect of the thyroid gland; they are made with a solitary coat of epithelial cells and are filled with a secretory material called colloid. This material is comprised mainly of a glycoprotein-tyrosinc compound, specifically thyroglobulin. This substance that functions in filling the thyroid particles is a big glycoprotein molecule that contains 140 tyrosinc amino acids. When the thyroid is synthesized, iodine attaches to these tyrosinc molecules and both thyroglobulin and iodide are secreted into the colloid of the follicle. This secretion is accomplished through the follicular cells. The function of the thyroid gland depends greatly on iodide absorption. The human body would be unable to synthesize the thyroid hormone without this nutrient. A daily absorption of 150 to 200 micrograms of dietary iodine is an adequate amount in order to form sufficient quantities of thyroid hormone. In order to uptake this iodide from the blood to store it for use in the future, it must be pumped into the follicular cells against the concentration gradient. The sodium-iodide symporter (NIS), an intrinsic membrane protein, transports iodide across the basement membrane of the thyroid cells. As it reaches the apical pendrin, another iodide transport protein, sends iodine into the colloid. It is at this stage, with the iodide in the colloid, that iodide becomes involved in the production of hormones. This whole process is driven by the NIS, which acquires its energy from the sodium-potassium ATP-ase (adenosine triohosphatase). This pump is essential in order for correct thyroid functioning, without it there would remain an exceeding amount of iodide in the circulation and the thyroid gland would not be able to exude enough T3 and T4 (which will be discussed shortly). This process results in a concentration of iodide that is 40 times greater in the normal thyroid gland than of that in the plasma. The sodium-iodide symptorer receives its stimulation from thyroid-stimulating hormone, as well as the thyroid-stimulating hormone receptor-stimulating antibody (an antibody found in Graves disease – an autoimmune disorder that leads to an overactive thyroid hormone). Pendrin is a transporter of chloride and iodide and abnormalities in the gene that encodes pendrin, the pendred syndrome gene have been located in individuals with goiter and congenital deafness.
Most of the iodide, once it has made it into the follicle, is oxidized by the thyroid peroxidase enzyme. It is oxidized by this enzyme in a reaction that helps to combine the iodide with a tyrosinc molecule to form monoiodotyrosinc and then diiodotyrosinc. A monoiodotyrosinc and a diiodotyrosinc are put together to create triiodothyroninc (T3). Two diiodotyrosinc molecules come together to produce thyroxine (T4). Theses are the only particles released into the circulation – 90% T4 and 10% T3. It is believed by some that T3 is the functional type of the hormone and T4 is converted to T3 before it has the chance to act in the body. Thyroid hormones are transported through the circulation by binding to thyroxine-binding globulin as well as other plasma proteins. The only hormone that may regulate the pituitary feedback mechanism by entering the cells is the free hormone. These free thyroid hormones are acquired, as needed, from the protein-bound thyroid hormone reservoir. More than 99% of both T3 and T4 are transported in the bound form. There are three major thyroid-binding proteins that are used; these include thyroxine-binding globulin, transthyretin, and albumin.
Figure 1 (Porth, 2011, p. 783)

The hypothalamic-pituitary-thyroid feedback system is responsible for regulating the secretions of the thyroid hormone. The hypothalamus supplies a hormone named the thyrotropin-releasing hormone, which functions by regulating the discharge of thyroid-stimulating hormone from the anterior pituitary gland. Thyroid stimulating hormone is an important factor in this system as it works to increase the total action of the thyroid gland by mounting thyroglobulin breakdown and the liberation of thyroid hormone from the follicles and into the bloodstream. Through this mechanism, NIS activity is increased thus stimulating the iodide pump, oxidation of iodide and the iodide-tyrosine complex is increased, and the amount and size of follicle cells are increased. The effects of this thyroid-stimulating hormone on the thyroid hormones themselves takes about 30 minutes, while the other effects that may follow may take a few days or weeks to set in. An elevated level of thyroid hormone act in the feedback inhibition of thyrotropin-releasing hormone or thyroid-stimulating hormone. Elevated levels of iodide may result in a short-term decline in thyroid activity, most likely attributable to a direct obstruction of thyroid-stimulating hormone on the thyroid. Exposure to the cold is one of the most influential stimuli responsible for elevated thyroid hormone production and is likely mediated through thyrotropin-releasing hormone from the hypothalamus. Multiple emotional reactions may also indirectly influence the secretion of thyroid hormones by impacting the production of thyrotropin-releasing hormone and thyroid-stimulating hormone.
Thyroid hormones and altered levels of these hormones significantly affect many major organs of the body. The actions of the thyroid hormone are mostly mediated by T3. Within the cell, T3 binds to a nuclear receptor and leads to the transcription of certain thyroid hormone response genes. Thyroid hormone is a necessity for growth, development, and metabolism. It serves to increase metabolism and protein synthesis. By stimulating mitochondrial oxygen consumption, which results in the manufacturing of ATP, the thyroid hormone is able to increase the activity of the sodium-potassium ATP-ase. This stimulation of mitochondrial oxygen consumption is what leads to an increase in metabolism, a result of the increase in ATP. If there is a lacking availability of thyroid hormone the body would be unable to grow and develop normally. The certain effects of thyroid hormones on different tissues depend upon the metabolism of vitamins, minerals, and substrates, as well as the functioning of other endocrine systems. Thyroid hormones create an effect not only on things such as metabolism and protein synthesis, but also heart rate and the temperature of the body. The foremost influences the thyroid hormones have on the body include metabolic changes for example: alterations in consumption of oxygen as well as alterations in the metabolism of proteins, lipids, carbohydrates, and vitamins. Since thyroid hormones are available to stimulate the breakdown of lipids and carbohydrates a resulting enhanced release of fatty acids occur from the adipocytes. Adipocytes are fat cells primarily made up of adipose tissue that mainly works to store energy as fat. So, overall it can be determined that thyroid hormones serve a great purpose as they have the ability to amplify the total metabolic rate resulting in an increase in heart rate, a higher endurance to cold, and assisting in the metabolism of fats.
Besides these major aforementioned effects, the thyroid hormone also effects other systems, including but not limited to: sympathetic system, the formation of new red blood cells, cardiac functioning, skeletal muscles, the maturation of the liver’s bilirubin, GI tract, cholesterol levels, and the nervous system. The thyroid hormones increase the amount of beta-adrenergic receptors in the heart, liver, muscle, and fat cells, contributing to their effects on the sympathetic adrenergic system. With an increase in these beta-adrenergic receptors, the heart’s contractility increases and enhances the effects of the calcium ATP-ase within the sarcoplasm. Red blood cell formation, also known as erythropoiesis, is effected by the thyroid hormones as they serve to produce more red blood cells using the erythropoietin mechanism. These hormones increase the catabolism and the glycogenolysis of protein within the skeletal muscles. Thyroid hormone also is able to increase the absorption of glucose and helps to maintain normal gut functioning. Cholesterol levels are lowered by thyroid hormones because they introduce low-density lipoprotein receptors in the liver to aid in elimination of low-density lipoprotein cholesterol. Thyroid hormones indirectly stimulate IGF-1, which promotes bone growth along with preserving the normal growth hormone gene expression. The thyroid hormone helps in the developmental stages of the nervous system and allows the continuance of normal mental and emotional functioning. Other ways the hormone affects the nervous system is that it maintains the hypoxic and hypercapnic drives that may occur with respiration and maintains the normal reflexes of the body, especially in the perceived reflex arches.
Hypothyroid disease is the most prevalent malady of the thyroid gland’s functioning. This disease is distinguished by a decreased production of thyroid hormones. Extensive brain injury, hemorrhages in the subarachnoid space, pituitary adenomas or tumors, and lymphocyte hypophysitis could be the cause of decreased secretions of hormones of the pituitary and thus lead to hypothyroidism. Lymphocyte hypophysitis is defined as inflammation to the pituitary gland most likely due to autoimmunity. The most frequent source of hypothyroidism is an insufficient availability of iodide, except in the US. This is not the major cause of hypothyroid disease in America because there is a fairly large amount of iodide in our diet. Most often this disease is found in women over the age of 60. However, it may occur in younger adults and this may lead to the development of a goiter. A goiter is defined as a significant growth of the thyroid gland. This disease may be a result of an attack on the thyroid gland itself or an adverse effect of taking hyperthyroid medications. Hypothyroidism presents with many characteristic features including weariness, lethargy, a reduced appetite, dry skin that is extremely sensitive to cold, constipation, a raspy voice, alopecia, soft and brittle nails, unexplained weight gain, and an irregular menstrual period. There are two types, primary and secondary hypothyroid disease. Primary is the most common, while secondary only makes up less than 1% of hypothyroidism cases. Autoimmune disorders are a major contributor to the primary hypothyroid condition occurring in older aged adults. What happen are thyroid cells and tissues are progressively eradicated causing a drop in the levels of thyroid stimulating hormone. In addition, the disorder creates abnormal amounts of antibodies that attack the thyroid, specifically known as anti-TPO antibodies. The most common way to test for hypothyroidism is to test for serum thyroid-stimulating hormone, which is secreted from the thyrotropin -releasing hormone. (Yamada & Mori, 2008)
Some cases of hypothyroidism are caused by chronic autoimmune thyroiditis, referred to as Hashimoto’s thyroiditis. Hashimoto’s disease is an inflammatory attack on the thyroid gland and often is characterized by a goiter. This disease process causes secretion of the formerly mentioned anti-thyroid antibodies. These antibodies attach the thyroid gland leading to deterioration and a lessened amount of thyroid hormones being produced. Usually this disease occurs because of an antigen being presented within the body by an antigen-presenting cell. This cell is taken up in the body and gets made into peptide epitopes. These epitopes bind to MCH type II molecules located on the diseased cells. MCH-2 are melanin-concentrating hormone receptors that are G-protein coupled receptors. This binding to the MCH-2 receptors on the diseased cells results in the formation of complexes called bimolecular complexes. These then attach to T-cell antigen receptors resulting in the activation of T cells to secrete cytokines. This whole process of Hashimoto’s can lead to a diagnosis of hypothyroidism. (Barbesino & Chiovato, 2000)
Another cause of hypothyroidism is genetic abnormalities such as those seen in congenital hypothyroid disease. This is often caused by a defect in the thyroid gland development at birth. Congenital hypothyroidism is often a result of an inherited autosomal recessive or autosomal dominant gene; this is called congenital hypothyroidism of central origin. This hypothyroid disease that is present at birth may manifest itself in findings of decreased T4, thyroid-stimulating hormone, thyroglobulin, and an abnormally small thyroid gland. Also, if abnormal secretions or activity of thyroid stimulating hormones, T4, thyrotropin -releasing hormones exist this could cause hypothyroidism. In addition, abnormal activity of T3 could also lead to the development of this disease. As mentioned, the best detection of hypothyroidism is through testing for abnormal levels of thyroid hormones. Gene defects may result in the development of hypothyroidism. For example, mutations in the gene PAX8, a gene involved in the production and regulation of thyroid peroxidase and thyroglobulin, may lead to congenital hypothyroidism. Similarly, thyroid transcription factor1 is involved in the regulation of thyroid peroxidase, thyroglobulin, and thyroid-stimulating hormone receptor genes and a mutation in this could be associated with impaired thyroid functioning. Many of the genetic abnormalities lead to irregular breakdown of thyrotropin, a hormone secreted from the pituitary gland stimulating the thyroid gland’s activity. (Kopp, 2002)
There are many other mutations in genes that may lead to abnormal thyroid development, which can be seen in the following table:

Figure 2 (Kopp, 2002, table 1)

In hypothyroidism, decreased thyroid stimulating hormones are found and this decrease is likely related to abnormal functioning of the pituitary gland. There may be many reasons for this impaired functioning such as a tumor, traumatic injury, lesion, an absence of cell growth, or slow cell growth. These different explanations may cause a decrease in thyroid stimulating hormone as a result of a defect in thyrotropin-releasing hormone function, inadequate secretion of thyroid stimulating hormone, or even a defect in the breakdown of thyroid-stimulating hormone. A defect in thyrotropin-releasing hormone could be, for example, the receptor being unable to translate the message from the hypothalamus to the pituitary gland to secrete more hormones. Drugs and dietary substances may lead to goiters or even to hypothyroidism, often referred to as drug induced hypothyroidism (Vagenakis & Braverman, 1976). For example, decreased secretion of thyroid stimulating hormone may be caused by taking medications such as glucocorticoids, dopamine, or human growth hormones. Complications such as a major surgery, bone marrow transplants, severe injury, AIDS, major depressive disorder, eating disorders, and old age may also lead to decrease secretion of this hormone. A defect in the breakdown of thyroid-stimulating hormone may result in the secretion of inactive thyroid stimulating hormone, which is unable to stimulate thyroid hormone release in this inactive state. This thyroid stimulating hormone synthesis problem is often seen in individuals diagnosed with central hypothyroid disease. Hormone supplementation is ineffective in these patients, as they cannot even correctly produce thyroid-stimulating hormone from thyrotropin-releasing hormones in the first place. Instead these patients must be treated by undergoing glycosylation, a process in which a carbohydrate is bonded to a hydroxyl or a glycosol group of a separate molecule.
The deficit of thyroid hormones in the circulation may have both direct and indirect effects on pulmonary functioning. Direct effects of hypothyroidism include an enhanced oxygen gradient, a lower diffusion ability of carbon monoxide, depressed drives for ventilation, sleeping problems such as sleep apnea, decreased vital capacity as well as total lung capacity, decrease in expiratory reserve volume, and upper airway blockages. Indirect effects of this deficit of thyroid hormones may encompass symptoms and signs such as a weakened neuromuscular system, phrenic nerve paralysis (phrenic nerves carry sensory messages from sections of the lung’s pleura, from the pericardium of the heart, and carries motor information to the muscle of the diaphragm), atelectasis often as a result of excessive weight gain, pulmonary edema as a result of congestive heart failure (CHF), and an increased risk of theophylline intoxication. Of all the effects of hypothyroidism on the pulmonary system, the decreased expiratory reserve volume is the most prevalent in these patients. It was identified that many of these pulmonary complications returned to normal after patient’s dropped a large amount of excess weight, making the case that it may be debated whether many of the complications are related to thyroid hormone deficiency itself or just as a result of obesity. However, some findings of lung defects were found in patients that were not obese. These findings included decreased vital capacity and a decreased arterial oxygen supply, which are both likely due to the weakened respiratory muscles.
Thyroid dysfunction can affect the cardiovascular system greatly. Thyroid hormone deficits cause a depression of sympathetic activity leading to a lowered heart rate. In addition, hypothyroidism leads to increased systemic vascular resistance and a decreased cardiac out, preload, and contractility. A decrease in T3 leads to vasodilation of the smooth muscles in the vasculature, which is the cause of the increased systemic vascular resistance. This increased resistance also leads to another problem present in some hypothyroid patients – increased diastolic blood pressure. Contractility decreases within the heart are a result of abnormalities in cardiac myocyte, muscle cells of the heart, proteins that are responsible for the regulation of preload and afterload. Since T3 is often found in ventricular cardiac myoctes and is responsible for the transcription and translation of many cardiac genes, a decrease in T3 – as seen in hypothyroid disease – leads to a decreased stability of these cardiac muscle cells as well as a decreased rate of protein synthesis. Another issue that arises is that with a inadequate afterload, blood is sufficiently transported to the lungs to become oxygenated which will cause decreased oxygen delivery to the rest of the body resulting in the exhaustion hypothyroid patients may feel, this may be exacerbated by exercise. Contractility is also affected because thyroid hormones are involved in the regulation of enzymes that regulate calcium levels in the heart. It is known that calcium is needed in order for the heart muscle to contract because cardiac contractions rely on the ability of the sarcomeres to contract, which is directly related to the amount of calcium in the cell. Therefore a decrease in thyroid hormones leads to a decrease in the actions of those particular enzymes that are responsible for the calcium levels in the heart furthermore resulting in decreased intracellular calcium, decreased contractility of sarcomeres, and thus decreased contractility of the whole heart muscle. (Cini et al., 2009)
An EKG of a patient with hypothyroidism will likely show evidence of bradycardia, decreased voltage QRS complexes, as well as decreased voltage of P waves and T waves. Bradycardia is a decrease in the heart rate less than 60 beats a minute. The diffuse infiltration and myxedema of the heart’s tissue associated with hypothyroidism as well as problems related to obesity results in the decreased QRS complex voltage. Myxedema is a term to refer to severe hypothyroidism that is manifested by signs such as edema, dry skin, dry hair, and a decreased mental and physical energy availability. A myxedema coma is a life-threatening emergency characterized by a decreased heart rate, decreased temperature, hypoglycemia, decreased ventilation, hypoxia and hypercapnia. Individuals experiencing myxedema coma usually develop severe and long-lasting hypothyroidism that is often left untreated. These patients have an increased risk of cardiorespiratory failure leading to death. Also, hypothyroidism usually occurs with increased cholesterol levels, which leads to a high risk for the development for coronary artery disease and atherosclerosis.
Figure 3: Hypothyroidism is characterized on an EKG by low voltages, ST deviation or T wave inversions across most or all leads, and sinus bradycardia ("ECG Tutorial," n.d.).

As mentioned previously, hypothyroid disease causes a decrease in the metabolic rate. This is significant because a decrease in metabolism leads to a decrease in ventilation. Ventilation perfusion depends upon the amount of carbon dioxide in the blood; plasma carbon dioxide concentration is controlled by metabolism. A decreased metabolism leads to less authority over the levels of oxygen and carbon dioxide levels. As a result, these patients have a decreased response to worsening hypercapnia, a condition characterized by abnormally high levels of carbon dioxide in the blood related to hypoventilation, and isocapneic hypoxia. The decreased metabolic rate also has other effects within the body. Thyroid hormones play a large role in stimulating the synthesis and degradation of protein. Because of this, protein production as well as amino acid oxidation is greatly reduced in cases of hypothyroidism. The decreased production of proteins may further lead to a negative nitrogen balance. Lipid metabolism is also regulated by thyroid hormones; in the case of hypothyroidism lipogenesis, the formation of fat or lipid, and lipolysis, the breakdown of fat or lipid, are decreased which increase low-density lipoprotein cholesterol concentrations. This decrease in lipogenesis and lipolysis is due to the fact that there is a decrease in the production of beta-adrenergic receptors on adipocytes, which also leads to heightened amounts of fatty acids and triglycerides. This effect on lipid metabolism contributes to the symptom of weight gain that affects the majority of individuals with hypothyroidism. The metabolism of carbohydrates is also lowered in patients with hypothyroidism. Thyroid hormones increase glycogen synthesis and glycogen breakdown, so with a decrease in thyroid hormones glycogen storage is increased because glycogen breakdown is decreased. This is directly related to the decrease in beta and alpha-adrenergic receptor stimulation. The decrease in cholesterol synthesis in this disease process is attributed to the decrease of HMG-CoA reductase in these patients, which is an important factor in the synthesis of cholesterol. This often leads to hypercholesteremia.
Kidney development and electrolyte metabolism depends greatly on the thyroid hormones. With hypothyroid disease, glomerular filtration rate is decreased leading to sodium levels being decreased and thus decrease in water excretion. Since patients with hypothyroidism cannot excrete enough water from their body, excess amounts build up leading to the non-pitting edema often found in these patients most often seen in the hands, feet, face and eyelids. This retention of water within the body is attributed to kidney dysfunction in which the glomerular filtration rate is lowered significantly. This occurs because of a decrease in the sodium-potassium ATP-ase pump stimulation leading to decreased transporter proteins. So overall, kidney dysfunction’s inability to properly filter blood is a major proponent of the edema noted in individuals with hypothyroidism.
Hypothyroid disease causes dilation of the gastrointestinal tract leading to the symptom of decreased peristalsis or gastrointestinal motility. Peristalsis is the wave of contractions to push the contents of the gastrointestinal tract down in order for it to eventually pass out of the body. This occurs because thyrotropin-releasing hormone plays a major role in gastric emptying as it increases the motor activity of the stomach. So in patients with hypothyroidism, there is a decreased amount of thyrotropin-releasing hormone leading to delayed gastric emptying and decreased motor functioning or peristalsis of the gastrointestinal tract. The finding of an atrophied mucosa of the colon may also result in this inability to move gastric contents along in a timely fashion. In addition, it is noted that a decrease in the electrical or motor activity of the esophagus, stomach, small intestines, and colon. Because of the effects hypothyroid disease has on the gastrointestinal tract, many of these patients will complain of symptoms of constipation.
Anemia, a disease process in which the body lacks the adequate amount of red blood cells, occurs in about half of the patients diagnosed with hypothyroidism. Often this presents as iron deficiency anemia. Thyroid hormones play a part in the production of red blood cells from erythropoietin. A decrease in thyroid hormones, such as in hypothyroidism, leads to a decrease in red blood cell formation resulting in decreased oxygen carrying capacity. This is because hemoglobin, the oxygen-carrying component of red blood cells, is lessened as the amount of red blood cells is lessened. Coagulation factors also rely on thyroid hormones so with a decrease in hormone, these patients have inadequate coagulation resulting in symptoms of easy bruising and bleeding.
Hypothyroid disease affects the menstrual cycle of females. It may cause polymenorrhea which is when the menstrual cycle occurs more frequently, happening in 21-day intervals. It may also result in menorrhagia, which is the term to describe a heavy blood flow during the menstrual cycle. These changes may be attributed to different factors associated with hypothyroidism. The decreased coagulation factors may be the cause of the more frequent periods of bleeding and/or the heavy flow. Also women with increased thyroid stimulating hormone levels in the blood are more prone to experiencing menstrual cycle issues. Hypothyroidism may also lead to infertility, if the disease process is severe enough, although the exact pathophysiology for this occurrence has not yet been determined. Male’s reproductive systems are not as susceptible to problems developing from hypothyroidism, but it is known that it may result in a decrease in testosterone levels in some patients.
The skin of a patient with hypothyroidism often is dry. This symptom is due to the affects hypothyroidism has on the sweat glands. The exact mechanism of how the sweat glands secretions decrease is unknown, but it has been verified that the sweat glands of these patients are atrophied due to the degeneration of cells. A decrease in skin perfusion, as a result of balancing out the cold intolerance that presents with hypothyroidism, occurs leading to the cool and pale characteristics of the skin of these patients. Hair growth is also affected because hypothyroidism causes a decrease in the S phase, when DNA replication occurs, the G2 phase, the gap following DNA synthesis before mitosis begins, and the M phase, when the cell is divided into two daughter cells. The reduction in these phases all leads to an abnormal functioning of hair growth that the thyroid hormones usually keep under control.
Thyroid hormones have certain effects on the neuromuscular function and tone. The brain in individuals with hypothyroidism that goes untreated becomes slowly atrophied. This leads to clinical manifestations of depression, lethargy, and disorientation or confusion. A lack of thyroid hormones leads to decreased nerve firing in the frontal cortex of the brain, which leads to the symptom of depression. Degeneration of the neurons in the brain is what leads to the feelings of lethargy. Lastly, the inflammation that occurs in the brain leads to the symptom of confusion. Cognitive deficits such as a decreased ability to make decisions or plan, is often seen in patients with hypothyroidism. This occurs because the maturation of axons is impaired leading to the prevention of myelination of small axons. Myelination is imperative in cognitive development and is very important in the rate by which delivery of signals throughout the body are carried by the nerves.
Thyroid-stimulating hormone lab values are essential in diagnosing a patient with hypothyroidism. An fT4 assay should also be included when evaluating a patient, especially if a goiter is present, if central hypothyroidism is suspected, or if thyroid-stimulating levels are elevated. As the disease worsens, or if left untreated, the serum fT4 decreases and serum thyroid-stimulating hormone concentration increases. Abnormal T3 concentrations in the serum occur once the disease process has progressed to the most severe stage. This is because the thyroid tissue is dysfunctional and cannot regulate the secretion and synthesis of T3 as it does under normal circumstances. To differentiate between central and primary hypothyroidism, serum thyroid-stimulating hormone levels should be evaluated. Transient thyroid-stimulating hormone, which is able to cause tumors in patients with primary hypothyroid disease, manifests itself in findings of absent thyroid peroxidase antibodies.
Treatment of hypothyroid disease includes a couple of options. Normally the body can convert T4 hormones into T3 hormones as needed, but if these hormones are not being produced naturally medication may be needed to increase amounts of these hormones. This is done through replacement therapy. Synthetic hormone replacement, using thyroxine, work to enhance the metabolism of cells and tissues throughout the body. When it comes to dosing, every patient is different and will require different amounts of supplements to have an effect. Dosages are usually started at about 12.5 micrograms per day, and increases or decreases depending on the unique needs of the patient. Factors that contribute to dosing include age, weight, and the presence or absence of cardiovascular disease. Once the right dose is achieved, these replacement hormone medications may result in maintaining optimal cognitive function, utilization of food, and a steady body temperature. Natural thyroid hormone replacement supplements may be used instead of the synthetic hormone replacement medications. The natural replacements both hormone types – levothyroxine T3 and T4. It is suggested that this medicine is taken by mouth an hour before breakfast. Each of these modes of treatment work differently in different patients and the patient should see which option best suits them in terms of relieving symptoms of hypothyroid disease.
The most prevalent treatment for extended control of both primary and secondary hypothyroidism is Levothyroxine (LT4) with a medication referred to as L-24. A healthy thyroid gland usually secretes about 90 mcg of T4, but the average dosage of L-24, an oral thyroxine medication, is between 100-200 mcg. This dosage is higher than the normal production in the body because a major 80% of the drug is absorbed when given by mouth. Elderly patients, over 70 years old, require a lower dosage of the medication because they have a 10% drop in the amount absorbed. This medication should be given on an empty stomach to aid in absorption. The dosage depends on body weight and is given as 1.6 mcg per kg of the ideal body weight, but the starting doses still tend to vary a lot (Roos, Linn-Rasker, Van Domburg, Tijssen, & Berghout, 2005). The initial dose of the medication should be fairly low and then should be increased as needed. The half-life of this drug is around six days, but it takes five or more half-lives of L-24 for the effect to take place and thyroid hormone concentrations to reach a normal amount. The medication amount should remain steady unless weight gains, loss, or age increases significantly. If a patient seems to have an abnormally high dose of L-24, they should be monitored for signs of non-compliance with their medication regimen. In order for this medication to be as effective as possible, it should be taken at the same time every day. Since thyroid-stimulating hormones decrease slowly throughout the day and begin to increase as bedtime approaches, many researchers believe the medication should be taken before bedtime as opposed to in the morning. However, taking the medication at night has shown no increase in the concentration of thyroid-stimulating hormone levels during the day. This medication is given to lessen the symptoms of hypothyroid disease and to bring the thyroid hormone concentrations back to normal. L-24 is able to do this by acting to increase the creation of new glucose by increasing metabolism of the body’s tissues, enhances the ability to utilize stored glycogen, promotes the synthesis of proteins, stimulates cell growth and division, and contributes to the brain and CNS development. It is imperative to monitor levels of this drug given because too much L-24 could result in dangerously high levels of thyroid hormones leading to complications such as insomnia, anxiety, increased heart rate, high blood pressure, diarrhea, alopecia, and osteoporosis (especially in elderly or post-menopausal women). This medication is contraindicated in patients who have a recent history of heart attack and in individuals with hyperthyroid disease, which is defined as an overactive thyroid gland resulting in overproduction of thyroid hormones. Adverse effects of this medication include trouble sleeping, angina, irregular rate or rhythm of the heart beat (also known as an arrhythmia), increased heart rate, stomach cramps, diarrhea, vomiting, increased sweat gland secretions, and menstrual cycle abnormalities. An excessive amount of the drug may result in weight loss and heat intolerance. The patient should immediately discontinue the use of the medication if increased heart rate or angina is present and should be prescribed a lessened dose of L-24. Apical pulse and blood pressure should be monitored throughout any individual on this medication. (Bolk, Visser, Kalsbeek, Van Domburg, & Berghout, 2007)