Autoimmunity PDF

Introduction to Autoimmunity A healthy, functioning immune system is integral to defending the body against threats. In autoimmune conditions, the immune system experiences a breakdown in recognition of “self” versus “non-self” cells, leading to the immune system attacking host cells and causing im...

Introduction to Autoimmunity A healthy, functioning immune system is integral to defending the body against threats. In autoimmune conditions, the immune system experiences a breakdown in recognition of “self” versus “non-self” cells, leading to the immune system attacking host cells and causing immune dysfunction. This learning module focuses on disease processes associated with autoimmunity and enables you to meet the following course outcomes: CO 1: Analyze pathophysiologic mechanisms associated with selected disease states across the lifespan. CO 2: Examine the way in which homeostatic, adaptive, and compensatory physiological mechanisms can be supported and/or altered through specific therapeutic interventions across the lifespan. CO 3: Distinguish risk factors associated with selected disease states across the lifespan. CO 4: Integrate advanced pathophysiological concepts in the diagnosis and treatment of health problems in selected populations. Term Description Rationale B cells Produce autoantibodies B cells produce autoantibodies when activated by T cells that do not recognize “self” cells and instead activate an immune response. T cells Modulate immune activity T cells modulate the immune and may be involved in response. Due to a breakdown in the breakdown of self- “self” versus “non-self” tolerance, leading to recognition, T cells mount an autoimmune reactions immune response to self- antigens, producing cytokines and activating B cells.  Autoantibodies Bind to self-antigens, Autoantibodies, made by B cells, forming complexes that bind to self-antigens, forming precipitate in tissues immune complexes that precipitate in tissues and cause inflammation. Immune Precipitate in tissues, Immune complexes precipitate in complexes leading to inflammation tissues, leading to inflammation and tissue damage and tissue damage. They are made from autoantibodies that bind to self-antigens. Complement A group of proteins that, The complement system is a system when activated, can group of proteins that, when cause cell lysis and activated, can cause cell lysis inflammation and inflammation. Order of Pathophysiological Events 1. Genetic predisposition: While many individuals are exposed to environmental exposure triggers that precipitate autoimmunity, individuals who develop autoimmune disorders are thought to be genetically predisposed prior to the trigger. 2. Environmental exposure trigger: An infectious or environmental trigger in a genetically predisposed individual first causes cell damage, exposing the immune system to self- antigens and initiating the immune response. 3. Autoantibody production: After environmental exposure triggers cause immune cells to engulf apoptotic and damaged cells and present them to T-cells, T-cells (not recognizing “self” versus “non-self”) mount an immune response to self-antigens, producing cytokines and activating B cells, leading to the production of autoantibodies, a hallmark of SLE. 4. Immune complex formation and deposition in tissues: Autoantibodies target “self” cells, forming immune complexes with self-antigens, which are then deposited in tissues throughout the body. 5. Tissue damage and clinical manifestations: The deposition of immune complexes in body tissues activates cytokines and the complement system, leading to cell and tissue damage including inflammation, vasculitis, and rash. While reviewing the chart of a client with SLE and lupus nephritis, a nurse practitioner prioritizes monitoring renal function and confirming serum autoantibodies to assess current disease activity and guide treatment adjustments. The client is diagnosed with lupus nephritis, a disorder in which immune complexes have triggered inflammation in the kidneys. This inflammation may lead to kidney dysfunction, requiring ongoing monitoring of renal function. While SLE may cause inflammation of the liver, the monitoring priority in clients with lupus nephritis is renal function. Pathophysiology of Autoimmune Disorders Self-tolerance is a key feature of the immune system, helping the body to recognize foreign antigens and self-antigens. Typically, during the process of lymphocyte maturation, the body eliminates any lymphocytes that are autoreactive, or primed to act against “self” tissues. In autoimmune disorders, autoreactive B and T lymphocytes are not eliminated or neutralized. When the immune system is unable to distinguish between “self” and “non-self,” the body produces an immunologic reaction mediated by the production of autoantibodies against host tissues. Autoimmune diseases can impact almost all cell types, tissues, and organ systems in the body. Types of Autoimmune Diseases Autoimmune diseases can be broadly categorized based on the primary tissues or organ systems they affect. Click each section below to learn how common autoimmune disorders are classified. Systemic Autoimmune Diseases Systemic Lupus Erythematosus (SLE) Rheumatoid Arthritis Scleroderma Sjogren Syndrome Mixed Connective Tissue Disease (MCTD) Tissue-Specific Autoimmune Diseases Endocrine Autoimmune Diseases ○ Type 1 Diabetes Mellitus: Pancreas ○ Hashimoto’s Thyroiditis: Thyroid ○ Graves’ Disease: Thyroid Gastrointestinal (GI) Autoimmune Diseases  ○ Celiac Disease: Small Intestine ○ Crohn’s Disease and Ulcerative Colitis: GI Tract Neurological Autoimmune Diseases ○ Multiple Sclerosis: Central Nervous System ○ Myasthenia Gravis: Neuromuscular Junction ○ Guillain-Barré Syndrome: Peripheral Nervous System Dermatological Autoimmune Diseases ○ Psoriasis Hematological Autoimmune Diseases ○ Immune Thrombocytopenic Purpura (ITP) ○ Autoimmune Hemolytic Anemia, Lymphopenia, and Neutropenia Musculoskeletal Autoimmune Diseases ○ Ankylosing Spondylitis Pathophysiology of Systemic Lupus Erythematosus Systemic lupus erythematosus (SLE) is a complex autoimmune condition that can impact various organ systems within the body, manifesting in a wide range of signs and symptoms that vary greatly among individuals. Typically, an infectious or environmental trigger in a genetically predisposed individual first causes cell damage, exposing the immune system to self-antigens. Immune cells engulf apoptotic and damaged cells and present them to T-cells. Due to a breakdown in “self” versus “non-self” recognition, T-cells mount an immune response to self-antigens, producing cytokines and activating B-cells, leading to the production of autoantibodies, a hallmark of SLE. Autoantibodies target “self” cells, forming immune complexes with self-antigens, which are then deposited in tissues throughout the body. The deposition of immune complexes in body tissues activates cytokines and the complement system, leading to cell and tissue damage including inflammation, vasculitis, and rash. Antinuclear antibodies (ANA) are one type of autoantibody produced in SLE, with lab tests able to demonstrate the presence of ANA in the blood as one potential diagnostic indicator for SLE (Justiz et al., 2023). Antinuclear Antibodies in Lupus The precise cause of lupus is not completely understood. Lupus is likely triggered by a combination of factors such as infection, stress, and hormones that somehow results in the immune system attacking its own organs and tissues. A family history of lupus increases the risk of developing the disease, which affects women at much higher rates than men. In North America and Europe, lupus is most common among Black, Asian, and Hispanic women. Patients with lupus have high levels of antinuclear antibodies (ANAs) circulating in the bloodstream, which results in the immune system targeting the body’s own tissues. This autoimmune attack eventually leads to chronic inflammation and damage throughout the body. Clinical Application: Systemic Lupus Erythematosus Amelia Barksdale (pronouns: she/her/hers) is a 30-year-old female. Last week, she had a telemedicine appointment with her primary care provider to discuss her concerns about a rash on her arms, legs, and face after sun exposure and increased fatigue. After sending Amelia for lab testing and receiving the results, the primary care provider called Amelia back to the office for an exam. The data within the electronic health record that indicates clinical manifestations potentially related to SLE includes the following: rash after sun exposure, described as a malar rash in a butterfly shape on face muscle and joint pain fatigue elevated temperature anemia and positive ANA These clinical manifestations could all be potentially related to SLE. The client’s WBC and platelet counts are normal and the lack of enlarged lymph nodes is also normal. The NP should order the complete metabolic panel (CMP), a tissue biopsy, and urinalysis to confirm an SLE diagnosis. A complete metabolic panel (CMP) would provide information on kidney function, fluid and electrolyte balance, liver function, and albumin levels. Since the client had a positive ANA and SLE is suspected, the information from these diagnostic labs can be helpful in assessing the involvement of other organ systems. SLE can cause malar rashes, similar to the one Amelia presents with; therefore, histopathology from a biopsy can be helpful in determining immune activity in the tissue from the rash, potentially contributing to SLE diagnosis. SLE can frequently involve the kidneys; therefore, it is important to gather information about kidney function, including a CMP and urinalysis. The client is not suspected to have an infection at this time; therefore, blood cultures are not indicated. The client is not displaying neurologic symptoms at this time; therefore, a CT scan of the brain is not indicated. Systemic Lupus Erythematosus Risk Factors Several genetic, hormonal, environmental, and ethnicity-related risk factors are associated with an increased likelihood of developing systemic lupus erythematosus (SLE). The presence of risk factors does not guarantee disease onset. Conversely, SLE can also occur in individuals without any known risk factors (Justiz et al., 2023). Ethnicity While SLE prevalence varies by ethnicity, rates are highest in African-American populations, followed by Asian and Hispanic populations. SLE prevalence is lowest in Caucasian populations. Sex SLE is significantly more common in females, with hormonal influences thought to play a role in the activation of immune responses. Environment Environmental triggers can initiate an immune response in genetically predisposed individuals. These include ultraviolet (UV) exposure, viral infections, smoking, and exposure to other dietary components. Genetics Several links to genetics are thought to be associated with increased SLE prevalence. Individuals with SLE usually have family members with an autoimmune disorder. Genetic links have been found with the major histocompatibility complex (MHC) locus and those with Klinefelter syndrome. Additionally, the significantly higher incidence in females suggests a link with X chromosome genes. Systemic Lupus Erythematosus Clinical Manifestations The clinical manifestations of systemic lupus erythematosus (SLE) vary widely among individuals, depending on the organs and symptoms impacted by immune complexes. The nature of SLE means that signs and symptoms can range from mild to severe and can also fluctuate, with clients with SLE experiencing flares and remissions. Most individuals with SLE will experience disease onset between the ages of 15 and 45 (Justiz et al., 2023). Due to the diversity of presentation, SLE can be difficult to diagnose. Most commonly, clients will initially experience nonspecific clinical manifestations (fatigue, fever, weight loss). Other body systems commonly affected include the musculoskeletal system (joint pain, swelling, muscle weakness), integumentary system (rash, photosensitivity, lesions), renal system (lupus nephritis and proteinuria), hematologic system (pancytopenia), neurologic system (headache, seizure, inflammation), and cardiovascular system (inflammation, atherosclerosis) (Centers for Disease Control and Prevention [CDC], 2022b; Justiz et al., 2023). Lupus Symptoms Systemic lupus erythematosus (SLE), or lupus, is an autoimmune disease characterized by chronic inflammation with widespread effects throughout the body. Many patients with lupus develop a distinctive, butterfly-shaped rash on the face called a malar rash. Lupus is difficult to diagnose due to its extensive influence on multiple body systems. Many symptoms are also associated with other health conditions. Different patients often experience unique combinations of symptoms, at varying levels of severity. Signs and symptoms of lupus include: a malar rash on the cheeks and nose, extreme fatigue, fever, headaches, dizziness, confusion, memory problems, chronic muscle and joint pain, difficulty breathing, and kidney problems. Cardiovascular problems may include heart damage, anemia, or blood clots. Due to the impaired blood supply, some patients develop Raynaud’s phenomenon, a condition in which the extremities (hands and feet) become cold and numb with skin color changes. Systemic Lupus Erythematosus Diagnosis Diagnosing systemic lupus erythematosus (SLE) presents a significant challenge for healthcare providers, largely due to the potential for symptoms to overlap with a variety of other medical conditions. It is crucial to consider SLE in the differential diagnosis when presented with persistent or unexplained symptoms that span multiple organ systems. Recognizing these patterns is key to ensuring that SLE is identified early, allowing for timely and appropriate management. The complexity of SLE diagnosis lies in the necessity of a thorough evaluation that encompasses the client’s full clinical picture and a series of targeted laboratory tests, as no one symptom or lab result can conclusively establish the presence of the disease (Centers for Disease Control and Prevention [CDC], 2022; Justiz et al., 2023). Evaluation of Initial Symptoms Providers should gather a thorough medical history, including the duration, frequency, and patterns of symptoms. An inquiry into family history is also important as many individuals with SLE have family members with an autoimmune disorder.  Providers should perform a full physical exam as multiple organ systems may be involved in SLE. Providers suspecting SLE should order an antinuclear antibody (ANA) lab test, as that is considered the gold standard for screening for SLE. A positive ANA is not conclusive for SLE but would indicate that further testing is needed to differentiate SLE from conditions with similar presentations. Further Testing If ANA is positive, ○ additional, more specific antibody tests should be conducted, ○ biopsies should be considered from the skin or kidneys to assess for signs of autoimmune activity, and ○ imaging studies can be used to assess organ involvement and complications. Diagnosis Confirmation Diagnosis is confirmed by considering the holistic clinical picture, including specific antibody tests, histopathology, and imaging findings. Providers should also ensure they have ruled out other disease processes with similar presentations to ensure accurate diagnosis. Systemic Lupus Erythematosus Treatment The management of systemic lupus erythematosus (SLE) is tailored to mitigate organ damage and induce remission. Treatment strategies are determined by the specific organ systems affected and the severity of the disease. The overall goals of treatment are to prevent flare-ups, address symptoms as they occur, and minimize or prevent damage to tissues. With current treatments, most individuals with SLE can lead healthy lives (Centers for Disease Control and Prevention [CDC], 2022; Justiz et al., 2023). Medications: Nonsteroidal anti-inflammatory drugs (NSAIDs) can reduce joint pain and swelling. Corticosteroids can decrease inflammation and suppress the immune response. Antimalarial drugs such as hydroxychloroquine and chloroquine can manage joint pain, skin rashes, and fatigue. BLyS-specific inhibitors can reduce the number of abnormal B-cells in the immune system. Immunosuppressive and chemotherapeutic agents can be used in severe cases where major organs are affected and other treatments have failed. Lifestyle Adjustments  Avoid triggers (sun exposure, infection) and avoid certain foods (including alfalfa sprouts and echinacea). Maintain a healthy diet rich in vitamin D, practice stress reduction, engage in regular exercise, practice good sleep hygiene, and avoid smoking. Education and Support Living with SLE requires adherence to medication and lifestyle regimens. Clients will need education on disease monitoring, medication adherence, and lifestyle changes. They may benefit from medical support services, including case management or care navigation. Specific Symptom Management Since SLE can impact almost all organ systems and manifests differently in every individual, symptom management must be tailored to specific client concerns. Imaging studies can be used to assess for suspected organ involvement. Medication therapy can be customized to specific client needs. Pathophysiology of Graves' Disease Graves’ disease is a complex autoimmune disease primarily targeting the thyroid gland. Graves’ disease occurs when T lymphocytes become sensitized to self-antigens within the thyroid gland. Those sensitized T lymphocytes then stimulate B lymphocytes to produce thyroid-stimulating immunoglobulin (TSI), also known as thyroid-stimulating antibody (TSAb). TSI binds to the thyroid-stimulating hormone (TSH) receptors on thyroid cell membranes, mimicking TSH and leading to increased thyroid hormone synthesis and thyroid gland growth, resulting in hyperthyroidism, thyromegaly, and other associated signs and symptoms (Pokhrel & Bhusal, 2023). Clinical Application: Graves' Disease Elena Cortez (pronouns she/her/hers) is a 32-year-old female, 4 months postpartum following an uncomplicated, full-term, vaginal birth. She presents with complaints of periodic palpitations, unexplained weight loss, and increased anxiety over the past 2 weeks. She also states she has been feeling hot and sweating and has an increased appetite. Elena denies pain but states there is a feeling of “fullness” in her throat. The data within the electronic health record that indicates clinical manifestations potentially related to Graves’ disease include the following: weight loss despite increased appetite, anxiety, and insomnia palpitations, tremor, and sinus tachycardia feeling hot, sweating, warm and moist skin enlarged thyroid gland with a feeling of “fullness” in the throat postpartum period These clinical manifestations may be related to Graves’ disease and associated hyperthyroidism. The client having a normal respiratory rate, an uncomplicated, full-term, vaginal birth, with completed OB follow-up, no past medical history, and lungs that are clear to auscultation are all normal findings. Which of the following diagnostics should the nurse practitioner (NP) order to confirm a Graves’ disease diagnosis based on the information provided? Thyroid-stimulating hormone (TSH) receptor antibody blood levels Thyroid-stimulating hormone (TSH) blood level Thyroid hormone blood levels Thyroid ultrasonogram with Doppler The initial assessment of suspected thyroid disorders includes obtaining a TSH blood level. If TSH is decreased, measurement of thyroid hormones (T3 and T4) is performed. A diagnosis of hyperthyroidism is confirmed with decreased TSH and high levels of T3 and T4. Then, providers must determine the cause of hyperthyroidism. If TSH is decreased, measurement of thyroid hormones (T3 and T4) is performed. A diagnosis of hyperthyroidism is confirmed with decreased TSH and high levels of T3 and T4. Then, providers must determine the cause of hyperthyroidism. To differentiate Graves’ disease from other causes of hyperthyroidism, the provider can assess TSH receptor antibody (TRAb) assays, including thyroid-stimulating immunoglobulin (TSI) and thyrotropin-binding inhibitory immunoglobulin (TBII). A thyroid ultrasonogram with Doppler can assess for a thyroid gland hypervascularization. While radioactive iodine uptake scans are used to diagnose Graves’ disease, they use I-123 as it emits less radiation than I-131. Radioactive iodine I-131 is only used for treatment. Graves' Disease Risk Factors Graves’ disease has several risk factors that increase the likelihood of developing the condition (National Institute of Diabetes and Digestive and Kidney Diseases, 2021). Gender: Graves’ disease predominantly affects women. Age: Graves’ disease is more common in people under 40. Family history: Having a family member with Graves’ disease or another autoimmune disorder significantly raises the risk of developing Graves’ disease. Autoimmune disorders: Individuals with other autoimmune conditions, such as type 1 diabetes or rheumatoid arthritis, are at increased risk. Pregnancy: Women who are pregnant or newly postpartum are at an increased risk of developing Graves’ disease. Smoking: Tobacco use elevates the risk and can worsen symptoms associated with Graves’ disease. Grave's Disease Clinical Manifestations The clinical manifestations of Graves’ disease vary depending on factors, including age, severity, and duration of the condition. Many clients present with classic signs of hyperthyroidism, while some show atypical or non-specific symptoms. Common general symptoms include heat intolerance, excessive sweating, anxiety, insomnia, weight loss, and palpitations. Clients may experience diverse symptom presentations, underscoring the need for a comprehensive approach to diagnosis and management (Pokhrel & Bhusal, 2023). Multiple body systems may be impacted by Graves’ disease, including the cardiovascular system (tachycardia, systolic hypertension), neurologic system (tremors, nervousness), reproductive system (irregular menstrual cycles), musculoskeletal system (muscle weakness, osteopathy), integumentary system (warm, moist skin, hair loss, thyroid dermopathy), as well as changes to the thyroid gland and eyes (Pokhrel & Bhusal, 2023). Graves’ Disease Signs and Symptoms Graves’ disease is an autoimmune condition resulting in hyperthyroidism. Hyperthyroidism is the overproduction of thyroid hormones. In response to thyroid stimulating hormone (TSH), the thyroid gland produces the hormones triiodothyronine (T3) and thyroxine (T4). T3 and T4 influence the function of many of the body’s organs, including those of the heart, brain, liver, and skin. In Graves' disease, immune cells make abnormal antibodies that act like thyroid stimulating hormone (TSH). This causes the thyroid to produce too much T3 and T4, leading to hyperthyroidism. As thyroid hormones have a wide range of effects on the body, symptoms of Graves’ disease can include an enlarged thyroid, known as goiter, bulging eyes known as exophthalmos, and skin changes on the shins, known as pretibial myxedema. Graves' Disease Diagnosis The diagnosis of Graves’ disease requires a comprehensive approach, starting with a detailed health history and physical examination. Providers should inquire about a family history of Graves’ disease or other autoimmune diseases during their conversation with the client. The evaluation process also includes several diagnostic tests to confirm hyperthyroidism and distinguish Graves’ disease from other thyroid conditions (Pokhrel & Bhusal, 2023). Thyroid Function Tests Initial assessment includes a thyroid-stimulating hormone (TSH) test. If TSH is decreased, measurement of thyroid hormones (T3 and T4) is performed. A diagnosis of hyperthyroidism is confirmed with decreased TSH and high levels of T3 and T4. Tests to Differentiate Graves’ Disease The following diagnostics may be used to differentiate Graves’ disease from other causes of hyperthyroidism: TSH receptor antibody (TRAb) assays, including thyroid stimulating immunoglobulin (TSI) and thyrotropin-binding inhibitory immunoglobulin (TBII)  radioactive iodine uptake scan with I-123 (less radiation than the I-131 used for treatment) to show increased uptake in Graves’ disease thyroid ultrasonogram with Doppler to assess for a hypervascular thyroid gland Additional Tests labs to assess for associated conditions such as microcytic anemia, thrombocytopenia, bilirubinemia, elevated transaminases, hypercalcemia, high alkaline phosphatase, and altered LDL and HDL cholesterol levels imaging (CT or MRI) for assessing Graves’ orbitopathy Graves' Disease Treatment Treatment for Graves’ disease aims to rapidly control symptoms and reduce thyroid hormone secretion, with the approach varying based on the disease’s presentation. Treatments for Graves’ disease (such as radioactive iodine therapy and thyroidectomy) can cause hypothyroidism, resulting in changes to the treatment approach after intervention. Symptom Control Beta adrenergic blockers can control symptoms such as tachycardia in clients with heart rates over 90 beats per minute, those with cardiovascular disease, or the elderly. Cardioselective beta blockers like atenolol are preferred. Non-selective alternatives like propranolol or calcium channel blockers can also be used for heart rate control. Antithyroid Medications Different antithyroid medications are available depending on the needs of the client. Methimazole is preferred for clients who are not pregnant. Propylthiouracil (PTU) is preferred during the first trimester of pregnancy. Monitor for medication side effects, including allergic reactions, neutropenia, and hepatotoxicity. Treatment duration varies. Consider discontinuing medications after 12-18 months if thyroid function normalizes. Radioactive Iodine Therapy Radioactive iodine therapy (RAI) is indicated for non-pregnant adult clients over age 21 who are not planning to be pregnant in the near future and those with contraindications for antithyroid medications or surgery. Treated with I-131 to destroy thyroid cells after preparation with beta-adrenergic blockers and methimazole. Post-treatment monitoring with repeat thyroid function testing for up to six months. Thyroidectomy  Indicated for large goiters, neck compression symptoms, co-existing thyroid cancer, or severe orbitopathy. Pre-surgery: Achieve euthyroid state with medications and use beta blockers and potassium iodide to reduce vascularity. Post-surgery: Levothyroxine required with dosage adjustments based on thyroid- stimulating hormone (TSH) levels. Action Diagnostic Treatment Rationale Assessing a X The initial assessment of thyroid-stimulating suspected thyroid disorders hormone (TSH) includes obtaining a TSH blood blood level level. If TSH is decreased, measurement of thyroid hormones (T3 and T4) is performed. A diagnosis of hyperthyroidism is confirmed with decreased TSH and high levels of T3 and T4. Then, providers must determine the cause of hyperthyroidism. Administering anti- X Different antithyroid medications thyroid medications are available for the treatment of Graves’ disease, depending on the needs of the client. Administering beta X Beta adrenergic blockers can adrenergic blocking treat symptoms such as medications tachycardia in clients with heart rates over 90 beats per minute, those with cardiovascular disease, or the elderly. Thyroidectomy X A thyroidectomy surgery is indicated to treat large goiters, neck compression symptoms, co-existing thyroid cancer, or severe orbitopathy.  Radioactive iodine X Radioactive iodine uptake scan uptake scan with I- with I-123 is used to diagnose 123 Graves’ disease. I-131 is the radioactive iodine used for treatment. Case Study: Autoimmunity Chandra Rimes (pronouns: she/her/hers) is a 25-year-old female. She is a full-time graduate student who also works full-time and is presenting to her primary care provider today for stress, insomnia, and anxiety. Chandra is experiencing potential clinical manifestations of hyperthyroidism, including irregular menstrual cycles and insomnia. Multiple body systems can be impacted by hyperthyroidism caused by Graves’ disease, including the menstrual cycle. Clients with hyperthyroidism may also experience insomnia. While these symptoms can also be unrelated to Graves’ disease, providers should take care to obtain all information that can help piece together the entire clinical picture as autoimmune disorders cause symptoms that may overlap with other medical conditions. The client is not experiencing weight gain, but rather unexplained weight loss despite an increased appetite. The client is also not experiencing bradycardia but rather tachycardia. Tachycardia can be a symptom of hyperthyroidism. The nurse practitioner (NP) orders labs for Chandra. Which lab results indicate the client is experiencing primary hyperthyroidism? Decreased thyroid-stimulating hormone (TSH) with increased thyroid hormone levels Clients with primary hyperthyroidism experience decreased TSH levels caused by increased thyroid hormone levels. The pathophysiological alteration in Graves’ disease is Increased thyroid hormone production, which is Autoimmune in nature. Graves’ disease is an autoimmune (not infectious) disorder characterized by the production of thyroid antibodies that cause increased (not decreased) production of thyroid hormones. Purpose Test Rationale Assess for Thyroid-stimulating Assessing the TSH receptor antibodies lab autoimmune hormone (TSH) tests [such as TSH receptor antibody etiology receptor antibodies (TRAb) assays, including thyroid stimulating lab tests immunoglobulin (TSI) and thyrotropin- binding inhibitory immunoglobulin (TBII)] helps assess for an autoimmune etiology to hyperthyroidism. These tests are not used for assessing for the accumulation of iodine in the thyroid gland or assessing for thyroid gland hypervascularization.  Assess for the Radioactive iodine A radioactive iodine uptake scan assesses accumulation of uptake scan for the accumulation of iodine in the thyroid iodine in the gland. In Graves’ disease, the thyroid will thyroid gland have increased iodine uptake. This test is not used for assessing for autoimmune etiology directly or for assessing for thyroid gland hypervascularization. Assess for a Thyroid A thyroid ultrasonogram with Doppler can hypervascular ultrasonogram with help visualize the thyroid structure, thyroid gland Doppler including assessing for thyroid gland hypervascularization. This test does not directly assess for autoimmune etiology or the accumulation of iodine in the thyroid gland. Which of the following treatments may be appropriate for Graves’ disease? Thyroidectomy Beta blocker medications Radioactive iodine therapy (RAI) Radioactive iodine therapy (RAI) I-131 can be used to destroy thyroid cells in radioactive iodine therapy. Beta adrenergic blocking medications can be used to control symptoms of Graves’ disease in clients experiencing tachycardia with heart rates over 90 beats per minute, those with cardiovascular disease, or older adults. Thyroidectomy is indicated for large goiters, neck compression symptoms, co-existing thyroid cancer, or severe orbitopathy. Methimazole is preferred in the treatment of non-pregnant clients. PTU is preferred in the treatment of pregnant clients in the first trimester. After confirming the diagnosis of Graves’ disease with labs, ultrasound, and a radioactive iodine uptake scan, the nurse practitioner (NP) confirms that Chandra has a negative pregnancy test and initiates medication therapy using methimazole. The client returns for a follow-up appointment and reports an improvement in her symptoms but complains of feeling fatigued and has a heart rate of 55. Which of the following should the NP assess to evaluate the outcome of therapy? Thyroid-stimulating hormone (TSH) Monitoring the TSH will help determine if methimazole has helped the client become euthyroid. The client’s symptoms of fatigue and bradycardia indicate that her hyperthyroid has potentially been overtreated and that medication might need to be adjusted to bring TSH within the normal range (as opposed to having a low TSH in hyperthyroidism and a high TSH in hypothyroidism). It would not be helpful to assess thyroid antibodies, thyroid ultrasound, or sleep habits to determine the outcome of therapy as those were all part of the initial diagnosis. Assessing TSH levels is helpful to evaluate the outcome of therapy. Application: Systemic Lupus Erythematosus A nurse practitioner (NP) is evaluating a 40-year-old female named Irina Lebedev (pronouns: she/her/hers). Irina has no medical history but has been struggling with joint pain, fatigue, and a malar rash for the past few months. She is concerned because her mother had rheumatoid arthritis. Irina is in the United States on a work visa, and her pain is making it hard for her to work. The NP suspects the client may have an autoimmune disorder, such as systemic lupus erythematosus (SLE). Arrange the following steps in the correct order to diagnose and manage the client’s condition. Perform a complete physical examination and interview. ○ The NP should first perform a complete physical exam and interview. Diagnosing autoimmune diseases can be challenging due to overlap with other medical conditions. The provider must fully assess the client and recognize that persistent or unexplained symptoms involving multiple systems and organs may point to an autoimmune disorder. Order an ANA antibody test.  ○ Providers suspecting SLE should order an antinuclear antibody (ANA) lab test, the gold standard for screening for SLE. A positive ANA is not conclusive for SLE but would indicate that further testing is needed to differentiate SLE from conditions with similar presentations. If ANA is positive, order more specific antibody tests and skin biopsy. ○ If ANA is positive, additional, more specific antibody tests should be conducted to confirm a SLE diagnosis. Skin or kidney biopsies should also be considered to assess for signs of autoimmune activity. Once diagnosis is confirmed, educate the client about systemic lupus erythematosus (SLE). ○ Once diagnosis is confirmed, the client will require extensive education about managing the disease process. Prescribe NSAIDs for joint pain. ○ The client is concerned about her pain. NSAIDs are preferred medications to treat pain associated with SLE. ○ Not Associated With Clinical Diagnosti Graves’ Item Manifestation c Test Disease Rationale Enlarged X An enlarged thyroid thyroid gland (goiter) can be a clinical  manifestation of Graves’ disease. Serum thyroid- X Assessing the stimulating serum TSH can hormone provide (TSH) information about whether a client has hyperthyroidism. If TSH is decreased, more studies should be done to confirm elevated thyroid hormone levels and elevated thyroid antibody levels. Thyroid X A thyroid ultrasonogram ultrasound is a with Doppler diagnostic test that can help providers visualize the thyroid and assess for hypervascularity,  as seen in Graves’ disease. Radioactive X A radioactive iodine uptake iodine uptake test scan is a diagnostic test to assess for the accumulation of iodine in the thyroid gland. In Graves’ disease, the thyroid will have increased iodine uptake. Unintentional X Unintentional weight loss weight loss can be a clinical manifestation of hyperthyroidism and Graves’ disease. Increased X Increased appetite appetite can be a clinical manifestation of hyperthyroidism and Graves’ disease. Racing heart X Racing heart (also known as tachycardia or palpitations) can be a clinical manifestation of hyperthyroidism and Graves’ disease. Rash X A rash is not typically associated with Graves’ disease.