The clinical manifestations of Graves’ disease, although myriad has one point of common; the disease shares the hallmark of ophthalmopathy among the majority of patients. Mrs. Jones is iagnosed with protruding, staring eyes, fine tremor, palpitation, supple skin and warm body. The following discussion looks at the disease’s expected symptoms, pathophysiology, and clinical manifestations to understand the disease better in the context of the particular case study.
Grave’s disease is an autoimmune disease that results from complex interactions between genetic and environmental factors. It is a serious disorder leading to thyroid storm, where body temperature, blood pressure and heart rate escalate. The clinical manifestations of Grave’s disease depend on the age of the patient at the inception, severity and duration of hyperthyroidism. Based on Mrs. Jones’s diagnosis, it is expected that she suffers weight loss and she has an increased appetite. It is likely that younger patients exhibit symptoms of sympathetic activation like anxiety, hyperactivity and tremor. Nair and Peate (2015) noted that with the increase in patients’ body metabolism, they regularly feel hotter than the surrounding people and can lose weight despite they consume a lot more food side by side some patients might gain weight due to increased appetite.
Mrs. Jones would be asked to check her basal body temperature every morning for two specific reasons. First, since the basal metabolism of Mrs. Jones is higher than normal persons, she would exhibit with a higher than normal basal body temperature and secondly, during the menstrual cycle, the temperature would predict when ovulation occurs. Due to increased metabolic rate and O2 consumption, heat production and heat sensitivity in Mrs. Jones’s body increases. Diagnosis of Grave’s disease shows patients suffering from unexplained weight loss, increased heart rate, nervousness and exophthalmos. The clinical features exhibit nervousness, tremors, excessive sweating, heat intolerance, weight loss, and heightened appetite. Anxiety or nervousness is its most common symptom although not all patients feel nervous. Mrs. Jones is restless and cannot sit still that evidences manifestations of Grave’s disease being unable to concentrate along with an apprehension of impending doom. She experiences fine tremors and heart palpitations, symptoms. Moore (2016) identified symptoms of nervousness, irritability, rapid heartbeat, fine tremor of the hands and fingers, increased perspiration, increased temperature, weight loss despite increased appetite, restlessness, emotional lability and emotional disturbances, heart palpitations, warm and velvety skin, youthful appearance among others for Grave’s disease. These symptoms exhibited by Mrs. Jones together with laboratory tests establish that she has Grave’s disease.
Tremor is an important characteristic of hyperthyroidism. There is a delicate, rapid, continuous tremor of the outstretched fingers. On close physical diagnosis, sufferers of Grave’s disease exhibit fine tremors that may not be discernible but is best demonstrated by placing a paper towel on the outstretched fingers. The heightened levels of T4 and T3 together with the increased levels of oxygen consumption with associated generalized vasodilatation contribute to amplified cardiac output visible in palpitation and sinus tachycardia. McDowall (2016) noted that the fine tremors are attributed to disturbances in the parathyroids which share close anatomical and vascular proximity with the thyroid gland. The fine tremors exhibited by Mrs. Jones confirm she is a patient of Graves’s disease. The fine, regular tremor, in certain severe cases of Grave’s disease may spread to legs with intermittent attacks of trembling that gets exacerbated by emotion and exertion “accompanied by exophthalmos, lid-lagging, thyroid enlargement, loss of weight, tachycardia, nervousness, and a raised basal metabolic rate” (Douthwaite, 2014, p. 484). The raised metabolic rate and immediate response to iodine and to methyl thiouracil account for the fine tremors in Grave’s disease.
Patients with Grave’s disease report a sensation of fullness or tightness in the neck. This is a significant local symptomatology reported by Mrs. Jones she notices that her blouses are tight around her neck. Thyroid nodules are asymptomatic. Some large nodules may displace or compress the trachea, esophagus, and neck vessels, occasionally linked with the signs and symptoms of neck tightness, dysphagia, and a choking sensation (Melmed, 2016). Patients with multinodular goiter complain of a vague tightness in the neck, a clinical presentation reported by Mrs. Jones.
Graves’ disease is an autoimmune disorder in which the thyroid gland is abnormally stimulated by thyroid-stimulating immunoglobulins (TSIs). TSIs are antibodies which are directed against the TSH receptor site in the thyroid follicles. It is caused by IgG antibodies that bind to and activate the TSH receptor. The serum concentrations of these antibodies differ across patients while the antibodies could modify the stimulatory effects of thyroid stimulating hormones. The concomitant production of antibodies blocking the thyrotropin receptor reduces the stimulatory action of thyroid-stimulating antibodies in some patients. The mechanism by which IgG antibodies bind to and stimulate the thyrotropin receptor is not known although several studies suggest that thyroid-stimulating antibodies bind to conformational epitopes in the extracellular domain of the thyrotropin receptor TSHR).
The immunologic mechanisms associated with Graves’ disease exhibit the characteristic — the autoantibodies to the TSHR — having both linear and conformational epitopes. Three types of TSHR antibodies are stimulating, blocking, and cleavage that have different functional abilities and signaling effects such as thyroid cell proliferation or thyroid cell death (Morshed & Davies, 2015). Autoimmunity in Graves’ disease is due to the combination of complex genetic and environmental factors where the chief antigen is the TSHR and accounts of extrathyroidal TSHR manifestation in a range of cell types such as fibroblasts, bone cells and immune cells aggravate the complications of the disease.
The general view of Graves’ disease is that TSHR-Abs trigger the disease through accelerating thyroid antigen expression that directly interact with and affect the immune system including stimulation of growing thermocytes. However, direct autoantibody induced mechanisms alone are not responsible for T cell activation and resultant thyroid infiltration. In fact, studies “supporting the induction of apoptosis by cleavage TSHR-Abs suggests that such antibodies may be active very early in the disease” (Morshed & Davies, 2015). The role of thyroid cells in Graves’ disease is established being the source of thyroid antigens and the target of thyroid-stimulating antibodies. The thyroid cells also represent several molecules that modify intrathyroidal autoimmunity.
The thyroid cells express HLA class II molecules in reciprocation to interferon-γ produced by infiltrating T cells in a manner that cells present antigens like the TSHR to stimulated T cells. HLA class II expression is a late phenomenon that occurs after the appearance of the infiltrate. This indicates that HLA class II antigen expression is not the major contributor of Graves’ disease but perpetuates and the autoimmune reaction. Naïve cells receiving co-stimulatory signal from antigen-presenting cells do not react with thyroid cells presenting antigen (Marelli-Berg et al. 1997). This is because they lack the crucial co-stimulatory molecules, CD80 and CD86 which activate T cells with the agency CD28. Accordingly, the onset of Grave’s disease takes place in dendritic cells and B cells representing CD80 and CD86 that eventually intensify the autoimmune mechanism due to the presentation of thyroid cells presenting antigen as may the expression of other molecules by thyroid cells including CD40, CD54 and inteleukin-1 and interleukin-6 (Weetman, 2000). Potential antigen-presenting cells express on their surface an assortment of co-stimulatory proteins known as B7 that reacts with molecules CD28 and CTLA-4. The co-stimulatory process is instrumental in orienting the direction of the immune response. Jameson and Groot (2015) noted that in the absence of co-stimulatory signals in the case of B7 cells, HLA class II expression by thyroid cells would result in activation of T cells. On the other hand, it will induce peripheral tolerance of naïve, not earlier stimulated T cells.
Clinical manifestations. Graves’ ophthalmopathy is the clinical manifestation of an inflammatory disorder of the orbit. Manifestations of Graves’ ophthalmopathy are mostly connected with its central pathophysiologic event, the increase in the volume of retro-orbital tissue due to inflammation that accounts for the protruding of the eye bulb and causing proptosis or exophthalmos. Inflammatory changes can also cause diplopia. Lid retraction is also seen that can be worsened by the simultaneous thyrotoxicosis. Jameson and Groot (2015) explained that “Lagophthalmos (incomplete palpebral closure) and lacrimal gland dysfunction may combine to cause drying of the mucosal and corneal surfaces and consequently irritation and (less often) corneal ulceration” with photophobia, burning sensation, tearing and a sandy sensation as the common symptoms (p. e1980). Thyroid acropachy is yet another rare clinical manifestation of Graves’ disease that is characterized by clubbing and soft tissue swelling of the last phalanx of the fingers and toes. Localized dermopathy is very much common over the anterolateral aspects of the shin but may be present at other locations. Other clinical features that appear in more than half of the patients with Graves’ disease include nervousness, fatigue, a rapid heartbeat or palpitations, heat intolerance and weight loss.
Reasons of Protruding Eyes
The telltale sign of Graves’ disease is the eye inflammation and the development of protruding eyes called Graves’ ophthalmopathy. Graves’ ophthalmopathy is distinctive of endema and inflammation of the extraocular muscles and an increase in orbital connective tissue and fat. The endema is caused by the hydrophyllic action of glycosaminoglycans as a result of the secretion of fibroblasts. The enlargement of the volume of the retrobulbar tissue is accountable for the frequent manifestation of ophthalmopathy. During the last stages of ophthalmopathy, the muscles turn atrophic or fibrotic. In the initial stages, the muscle cells are normal and patients have red, painful, watering eyes and swollen and retracted eyelids. Their eyes begin to protrude and eye movements become painful and restricted and vision starts to diminish. Bahn (2015) pointed that the disease manifestations of ophthalmopathy variably cover redness and bulging of the eyelids and the conjunctivae, forward protrusion of the globes (proptosis), ocular pain, along with double vision and sight loss. He added that mechanically these features gain dimensions with the gradual growth of the orbital adipose tissues and extra-ocular muscles within the confines of the bony orbit. With the rise in orbital pressure, proptosis may develop.
Grave's disease different from Hashimoto's Thyroiditis
Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) are said to be two autoimmune thyroid diseases but at different ends of the spectrum, explained by the prevalence of HT in one and GD in the second of monozygotic twins (Schaffer, Puthenpura & Marshall, 2016). Alternatively, on a theoretical basis, as Schaffer et al. suggested, HT and GD are two isolated disease processes, partly described by the whole-genome scanning studies in humans. Occurrence of shift between the two diseases adds to more complexities in differentiation and classification. Although the ultrasonographic records of both HT and GD are similar in respect of hypoechoic and heterogeneous echotexture, GD exhibits noticeable hypervascularity with power Doppler analysis, HT’s vascularity is unpredictable, ranging from avascular to hypervascular (Schiefer & Dean, 2008). It has been found that many people with HT later develop GD. Patients showing features of both HT and GD develops a condition called Hashitoxcosis. While Graves’ disease is caused by autoantibodies to TSHR, in HT, autoantibodies to thyroid peroxidase and occasionally to thyroglobulin are related to the destruction of thyroid follicular cells and hypothyroidism.
The above discussion elaborates on the diagnosis, clinical manifestations, and basic pathophysiology of Graves’ disease which is an autoimmune disorder, the hallmark feature of which is protruding eyes. Mrs. Jones is diagnosed with Graves’ disease as per the diagnosis and clinical manifestations. The pathophysiologic events of GD detail the autoantibodies to TSHR, mimicking the stimulatory effects of TSH.
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