Graves’ Disease (Clinical)

Overview

Definition

Graves’ disease is an autoimmune disorder Autoimmune Disorder Septic Arthritis in which antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against the thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones (TSH) receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors cause the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland to hyperfunction. The syndrome may have the following features:

• Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism (most common)
• Goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter: thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy enlargement
• Orbitopathy: Graves’ ophthalmopathy/ thyroid eye disease Thyroid eye disease An autoimmune disorder of the eye, occurring in patients with graves disease. Subtypes include congestive (inflammation of the orbital connective tissue), myopathic (swelling and dysfunction of the extraocular muscles), and mixed congestive-myopathic ophthalmopathy. Graves’ Disease
• Dermopathy: pretibial myxedema Pretibial Myxedema Graves’ Disease

Epidemiology^[4,6,8,9]

• Most common cause of hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, making up 60%–80% of all cases
• Annual incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of 20–50 cases per 100,000 persons
• Female-to-male ratio of 8:1
• Onset usually at 20–40 years of age
• In children, the majority of cases occur after 11 years of age.

Risk factors^[4-6,8,9]

Susceptibility to Graves’ disease is considered to be a combination of multiple factors.

• Genetic factors:
  • Family history Family History Adult Health Maintenance of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy disease or other autoimmune disease (e.g., pernicious anemia Pernicious anemia A megaloblastic anemia occurring in children but more commonly in later life, characterized by histamine-fast achlorhydria, in which the laboratory and clinical manifestations are based on malabsorption of vitamin B12 due to a failure of the gastric mucosa to secrete adequate and potent intrinsic factor. Megaloblastic Anemia, type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus mellitus)
  • Polymorphisms identified in immunoregulatory genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure: PTPN22, CTLA-4, IL2RA, gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics encoding the TSH receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (TSHR)
  • Associated with HLA-DR3 and HLA-B8 HLA-B8 A specific hla-b surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the hla-b*08 allele family. Primary Sclerosing Cholangitis
  • Increased risk of Graves’ disease in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with trisomy 21 Trisomy 21 Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down syndrome (Trisomy 21) ( Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down syndrome (Trisomy 21))
• Environmental and nongenetic factors:
  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases
  • Stress
  • Sudden increases in iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones uptake
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Bacterial and viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Pathophysiology

Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism and goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter^[4,6]

• Thyroid-stimulating immunoglobulins Thyroid-stimulating immunoglobulins Autoantibodies that bind to the thyroid-stimulating hormone (TSH) receptor on thyroid epithelial cells. The autoantibodies mimic TSH causing an unregulated production of thyroid hormones characteristic of graves disease. Graves’ Disease ( type II hypersensitivity reaction Type II hypersensitivity reaction Type II hypersensitivity, also known as antibody-mediated cytotoxic hypersensitivity, is caused by immunoglobulin G (IgG) and IgM antibodies directed against antigens on cells or extracellular materials. The reaction leads to cytotoxic processes involving antibodies and the complement system. Type II Hypersensitivity Reaction):
  • Synthesized in the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland, bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis, and lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy
  • Stimulate TSH receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors on thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland
  • Effects:
    • ↑ Autonomous secretion Secretion Coagulation Studies of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types ( T3 T3 A T3 thyroid hormone normally synthesized and secreted by the thyroid gland in much smaller quantities than thyroxine (T4). Most T3 is derived from peripheral monodeiodination of T4 at the 5′ position of the outer ring of the iodothyronine nucleus. The hormone finally delivered and used by the tissues is mainly t3. Thyroid Hormones and T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones): hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism
    • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy follicular hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation and hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation: diffuse toxic goiter Toxic Goiter Goiter
  • Histologic findings in the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland:
    • Crowded tall follicle epithelial cells, which exhibit hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation and hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation
    • Lymphoid infiltrates also noted
• Negative feedback Negative feedback Hypothalamic and Pituitary Hormones: ↑ thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types → compensatory ↓ TSH

Orbitopathy and myxedema Myxedema A condition characterized by a dry, waxy type of swelling (edema) with abnormal deposits of mucopolysaccharides in the skin and other tissues. It is caused by a deficiency of thyroid hormones. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips. Edema^[3,4,6]

• Believed to be an autoimmune response directed at an antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (TSH receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors) shared by the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy and the orbit
• The process in dermal tissues is considered to be similar, with TSH receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors protein expression noted in normal dermal fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis.
  • Activation of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions within the retro-orbital space and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions → ↑ cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response → tissue activation and remodeling
  • Activated fibroblasts Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Sarcoidosis increase glycosaminoglycans (which trap water), leading to:
    • ↑ Fluid retention
    • Swelling Swelling Inflammation and fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans of the muscles involved
    • Fatty infiltration (↑ adipocytes Adipocytes Cells in the body that store fats, usually in the form of triglycerides. White adipocytes are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. Brown adipocytes are thermogenic cells that can be found in newborns of some species and hibernating mammals. Adipose Tissue: Histology)
  • Effects:
    • Protrusion, and possible displacement Displacement The process by which an emotional or behavioral response that is appropriate for one situation appears in another situation for which it is inappropriate. Defense Mechanisms, of the eyeball (Graves’ orbitopathy) 
    • Infiltration in the shin Shin Erythema Nodosum area or pretibial myxedema Pretibial Myxedema Graves’ Disease (unclear mechanism for this localization)

Clinical Presentation

Factors affecting presentation^[4–6]

• Severity and duration of disease
• Susceptibility to excess thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone
• Patient’s age: In the elderly, features are subtle.

Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism and goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter^[4,6]

Elevated thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone levels have effects throughout the body, including:

• General (increased basal metabolic rate):
  • Heat Heat Inflammation intolerance, sweating
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
• Dermatologic:
  • Warm, moist skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions (due to vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs)
  • Fine hair and onycholysis Onycholysis Separation of nail plate from the underlying nail bed. It can be a sign of skin disease, infection (such as onychomycosis) or tissue injury. Psoriasis
• Goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter:
  • Diffuse and painless thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy enlargement (2–3x normal)
  • +/- Thyroid bruit Thyroid Bruit Graves’ Disease
• Cardiac:
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, palpitations Palpitations Ebstein’s Anomaly, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, tachyarrhythmias
  • Increased blood pressure, widened pulse pressure
  • Aortic systolic murmur
  • Congestive heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
• GI:
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea due to increased GI motility GI Motility The primary functions of the GI tract are digestion and absorption, which require coordinated contractions of the smooth muscles present in the GI tract. Peristaltic waves, segmentation contractions, and the migrating motor complex are all important contraction patterns that help to mix contents, get them in contact with the intestinal walls, and propel material down the tract at appropriate times and in appropriate amounts. Gastrointestinal Motility
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics
• Musculoskeletal:
  • Thyrotoxic (proximal) myopathy Myopathy Dermatomyositis
  • Osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis, higher fracture Fracture A fracture is a disruption of the cortex of any bone and periosteum and is commonly due to mechanical stress after an injury or accident. Open fractures due to trauma can be a medical emergency. Fractures are frequently associated with automobile accidents, workplace injuries, and trauma. Overview of Bone Fractures rate 
• Reproductive:
  • Oligomenorrhea Oligomenorrhea Polycystic Ovarian Syndrome or amenorrhea Amenorrhea Absence of menstruation. Congenital Malformations of the Female Reproductive System
  • Gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia (in males)
  • Reduced libido, and infertility Infertility Infertility is the inability to conceive in the context of regular intercourse. The most common causes of infertility in women are related to ovulatory dysfunction or tubal obstruction, whereas, in men, abnormal sperm is a common cause. Infertility
• Neuropsychiatric:
  • Hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder, restlessness, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
  • Fine tremors, overactive reflexes
• Elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship:
  • Commonly lack most signs and symptoms
  • Often present with fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, depression, or weight loss Weight loss Decrease in existing body weight. Bariatric Surgery (“apathetic hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism”)

Orbitopathy and myxedema Myxedema A condition characterized by a dry, waxy type of swelling (edema) with abnormal deposits of mucopolysaccharides in the skin and other tissues. It is caused by a deficiency of thyroid hormones. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips. Edema^[2-4,6]

• Graves’ orbitopathy:
  • Scleral injection
  • Periorbital Periorbital Orbital and Preseptal Cellulitis edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Lid retraction accompanied by lid lag Lid Lag Ion Channel Myopathy (if ≥ 2 mm, graded as moderate to severe)
  • Exophthalmos/ proptosis Proptosis Retinoblastoma (if ≥ 3 mm, graded as moderate to severe)
  • Diplopia Diplopia A visual symptom in which a single object is perceived by the visual cortex as two objects rather than one. Disorders associated with this condition include refractive errors; strabismus; oculomotor nerve diseases; trochlear nerve diseases; abducens nerve diseases; and diseases of the brain stem and occipital lobe. Myasthenia Gravis (noted in moderate-to-severe orbitopathy)
  • Severe corneal exposure, optic nerve compression Nerve Compression Brachial Plexus Injuries (sight threatening)
• Myxedema Myxedema A condition characterized by a dry, waxy type of swelling (edema) with abnormal deposits of mucopolysaccharides in the skin and other tissues. It is caused by a deficiency of thyroid hormones. The skin becomes puffy around the eyes and on the cheeks. The face is dull and expressionless with thickened nose and lips. Edema:
  • Nonpitting edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Well-demarcated papules and nodules in affected area (may be pigmented)
  • Most common in lower legs/ shins Shins Erythema Nodosum (pretibial area)
  • Can affect feet, arms, elbows, face
• Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy acropachy: soft-tissue swelling Swelling Inflammation of the hands and clubbing Clubbing Cardiovascular Examination of the fingers

Diagnosis

The diagnosis of Graves’ disease Graves’ disease A common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy). Thyrotoxicosis and Hyperthyroidism is primarily made with lab testing combined with characteristic features on clinical presentation, though a radioactive iodine uptake Radioactive Iodine Uptake Thyrotoxicosis and Hyperthyroidism scan may be helpful in cases of diagnostic uncertainty.

Initial evaluation^[4,6,10,11]

• Clinical findings from history and examination
• Thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy:
  • ↓ TSH
  • ↑ T₃ and T₄
• Thyrotropin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (TRAbs):
  • Types of assays:^[11]
    • Thyroid-stimulating immunoglobulin ( TSI TSI Shigella) assays: measure immunoglobulin-stimulated increases in cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors production
    • TSH receptor-binding inhibitor immunoglobulin (TBII) assays (3rd generation): measure how binding to a recombinant TSH receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors is competitively inhibited by labeled TSH or a TRAb 
  • Indications for TRAb testing: when there is clinical evidence of hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism without orbitopathy or a nodular goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter
    • Note: If orbitopathy is present, testing is not indicated because the diagnosis of Graves’ disease Graves’ disease A common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy). Thyrotoxicosis and Hyperthyroidism can be made on the basis of clinical presentation and with routine thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy.
  • Found in 90% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • TSIs are rarely observed in other autoimmune thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy diseases.
• Antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions against thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy peroxidase and thyroglobulin Thyroglobulin Thyroid Hormones:
  • Usually present 
  • Also found in other autoimmune thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy diseases (e.g., Hashimoto’s thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis)
• Nonspecific laboratory findings:
  • CBC: normocytic anemia Normocytic Anemia Anemia: Overview and Types (the red cell mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast actually increases, but the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast increases more)
  • Lipid: ↓ cholesterol Cholesterol The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. Cholesterol Metabolism, ↓ triglycerides Triglycerides Fatty Acids and Lipids

Imaging^[4,6,11]

• Additional diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests performed if presentation is ambiguous:
  • Radioactive iodine uptake Radioactive Iodine Uptake Thyrotoxicosis and Hyperthyroidism ( RAIU RAIU Thyrotoxicosis and Hyperthyroidism):
    • Typically the 1st imaging test recommended^[10,11]
    • Absolutely contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
    • A nuclear medicine Nuclear medicine A specialty field of radiology concerned with diagnostic, therapeutic, and investigative use of radioactive compounds. Nuclear Imaging scan that tracks the uptake of radioactively labeled iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones molecules into cells, identifying “active” areas of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone production 
    • Uptake is increased. 
    • Uptake is diffusely distributed throughout the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland.
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy ultrasound with Doppler Doppler Ultrasonography applying the doppler effect, with frequency-shifted ultrasound reflections produced by moving targets (usually red blood cells) in the bloodstream along the ultrasound axis in direct proportion to the velocity of movement of the targets, to determine both direction and velocity of blood flow. Ultrasound (Sonography):
    • Utilized if RAIU RAIU Thyrotoxicosis and Hyperthyroidism is contraindicated (e.g., pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care)
    • High thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure in Graves’ disease
• CT or MRI of the orbits obtained in the following situations:
  • In orbitopathy with nondiagnostic thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy tests 
  • In unilateral orbitopathy (to rule out space-occupying lesions) 
  • In moderate-to-severe orbital changes (to determine complications or risks thereof)
  • If pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types disease suspected

Management

Principles of treatment^[4,6,7]

• Goals:
  • Reach euthyroid Euthyroid Thyroiditis state by reducing thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone synthesis Synthesis Polymerase Chain Reaction (PCR).
  • Control symptoms and complications
• Options to decrease thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
  • Antithyroid drugs 
  • Radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism (results in permanent hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism)
  • Surgery ( thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter, results in permanent hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism)
• No consensus on optimal treatment:
  • All 3 may be considered per the American Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy Association (ATA) guidelines, though certain methods are preferred in certain clinical situations (see table).^[11]
  • Multiple options can be utilized with the same patient to reach goals.
  • Choice of treatment(s) is dependent on individual clinical factors and preference.
• Untreated hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism carries a mortality Mortality All deaths reported in a given population. Measures of Health Status rate of up to 30%

Antithyroid drugs^{[4–7,10,11]}

Mechanism and use:

• Mechanism:
  • Reduce oxidation and organification of iodide Iodide Inorganic binary compounds of iodine or the i- ion. Thyroid Hormones by inhibiting thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy peroxidase
  • Inhibit extrathyroidal conversion of T₄ → T₃
• May be used initially to achieve euthyroid Euthyroid Thyroiditis state:
  • Starting dose can be gradually reduced as thyrotoxicosis Thyrotoxicosis A hypermetabolic syndrome caused by excess thyroid hormones which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid hyperplasia; thyroid neoplasms; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by nervousness; tachycardia; fatigue; weight loss; heat intolerance; and excessive sweating. Thyrotoxicosis and Hyperthyroidism improves. 
  • Titrate dose based on free T₃ and T₄ levels.
  • Review thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy 3–4 weeks after starting treatment.
  • A majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship reach euthyroidism within 3–4 weeks after starting treatment. 
• May be followed by radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism or surgery
• Baseline CBC count and hepatic panel required

Options:

• Methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs:
  • Typical starting dose: 10‒30 mg once daily (based on initial free T₄ levels)
  • ATA rough guideline for starting doses:
    • Free T₄ 1‒1.5x upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal: 5‒10 mg
    • Free T₄ 1.5‒2x upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal: 10‒20 mg
    • Free T₄ 2‒3x upper limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation of normal: 20‒40 mg
  • Typical maintenance dose Maintenance Dose Dosage Calculation: 2.5‒10 mg once daily
  • Usual 1st choice
  • Longer acting
  • Fewer side effects
  • Associated with congenital aplasia Aplasia Cranial Nerve Palsies cutis if used during the 1st trimester of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Propylthiouracil Propylthiouracil A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of thyroxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs ( PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs):
  • Starting dose: 100 mg (range, 50‒150) 3 times daily
  • Typical maintenance dose Maintenance Dose Dosage Calculation: 50‒100 mg once daily
  • Used in the 1st trimester of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care and in thyroid storm Thyroid Storm Thyrotoxicosis and Hyperthyroidism
  • Short acting
• Carbimazole (not available in the US)
  • Rapidly converted to methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs in vivo
  • 10 mg of carbimazole = 6 mg of methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs

Remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches:^[10,11] 

• Maximum remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches rates are typically achieved within 12–18 months. 
• Measurement of TRAb titers is recommended prior to stopping antithyroid medication.
  • Normal levels indicate greater chance of remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches 
  • High levels warrant continuation of therapy and reevaluation in 12 months or consideration of radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism/surgery.

Adverse effects:

• Teratogenicity ( methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs > PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs)
• Hepatotoxicity Hepatotoxicity Acetaminophen ( PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs > methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs)
• Agranulocytosis Agranulocytosis A decrease in the number of granulocytes; (basophils; eosinophils; and neutrophils). Lincosamides ( PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs > methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs. Check WBC count with any sign of infection!)
• Perinuclear antineutrophil cytoplasmic antibody (pANCA)–positive small-vessel vasculitis Small-Vessel Vasculitis Henoch-Schönlein Purpura

Follow-up:^[10]

• All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be monitored closely for relapse Relapse Relapsing Fever during the 1st year of treatment. 
• Thereafter, annual monitoring is recommended.
• Evidence is insufficient to recommend for or against routine monitoring of CBC or liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests.

Patient information:^[10]

• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship should be informed about the potential side effects of antithyroid drug therapy.
• They should be reminded to seek help promptly if they develop:
  • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice 
  • Light-colored stools 
  • Dark urine 
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever 
  • Pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis 
  • Cystitis Cystitis Inflammation of the urinary bladder, either from bacterial or non-bacterial causes. Cystitis is usually associated with painful urination (dysuria), increased frequency, urgency, and suprapubic pain. Urinary Tract Infections (UTIs) 

Radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism^{[4,6,7,10,11]}

• Method:
  • Capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides or solution of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia iodine-131 (I-131, radioactive iodine Radioactive iodine Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes. Antithyroid Drugs (RAI)) taken orally 
  • I-131 concentrates in the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy → progressive thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy cell destruction
  • Ablation is reached at about 6–18 weeks.
  • Some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may require a second dose.
  • Antithyroid drugs should be paused 1 week prior to ablation in order to achieve maximal ablation.
• Cautions:
  • I-131 emits radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma (prolonged, close contact with other people, especially pregnant women and small children, should be avoided for up to a week).
  • May trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation a thyroid storm Thyroid Storm Thyrotoxicosis and Hyperthyroidism (rare); those at high risk for thyroid storm Thyroid Storm Thyrotoxicosis and Hyperthyroidism should be pretreated with methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs (paused 2‒3 days prior to RAI administration and resumed 3‒7 days after RAI administration)
• Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:^[10]
  • Pregnant or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding:
    • Conception should be postponed until at least 6 months after therapy for both men and women.
    • A pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test should be obtained 48 hours prior to RAI administration.^[11]
  • Active/severe orbitopathy (since the TRAbs persist despite thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy destruction, which may worsen orbitopathy)
• Adverse effects:
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways 
  • Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess swelling Swelling Inflammation 
  • Sialadenitis Sialadenitis Inflammation of salivary tissue (salivary glands), usually due to infection or injuries. Diseases of the Salivary Glands ( inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of salivary glands Salivary glands The salivary glands are exocrine glands positioned in and around the oral cavity. These glands are responsible for secreting saliva into the mouth, which aids in digestion. There are 3 major paired salivary glands: the sublingual, submandibular, and parotid glands. Salivary Glands: Anatomy)
• Follow-up:
  • Check TSH, free T₄, and total T₃ every 4‒6 weeks for 6 months (or until the patient becomes hypothyroid and is stabilized on thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone replacement).
  • Consider retreatment with RAI if hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism persists > 6 months.

Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy surgery ( thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter)^[4,6,7,10]

• Rarely done
• Choice of treatment in:
  • Severe active orbitopathy
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with goiters causing obstructive symptoms
  • Cases with a concomitant suspicious thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy nodule Nodule Chalazion
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship wishing to avoid antithyroid drugs or radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism
• Advantages:^[10]
  • No recurrent hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism 
  • No radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma risk 
  • Rapid control 
  • No detrimental effect on orbitopathy 
• Disadvantages:^[10]
  • Risk of postoperative hypoparathyroidism Hypoparathyroidism Hypoparathyroidism is defined as reduced parathyroid hormone (PTH) levels due to poor function of the parathyroid glands. The cause of hypoparathyroidism is most commonly iatrogenic following neck surgery, but it can also be associated with genetic or autoimmune disorders as well as infiltrative diseases causing destruction of the normal parathyroid tissue. Hypoparathyroidism 
  • Risk of recurrent nerve palsy Palsy paralysis of an area of the body, thus incapable of voluntary movement Cranial Nerve Palsies 
  • Permanent hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism 
  • Risks related to surgery and anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts 
  • Cost 
  • Scarring Scarring Inflammation 
• Presurgery considerations:^[10]
  • Antithyroid drugs should be used to achieve euthyroidism to reduce the risk of perioperative or postoperative thyrotoxicosis Thyrotoxicosis A hypermetabolic syndrome caused by excess thyroid hormones which may come from endogenous or exogenous sources. The endogenous source of hormone may be thyroid hyperplasia; thyroid neoplasms; or hormone-producing extrathyroidal tissue. Thyrotoxicosis is characterized by nervousness; tachycardia; fatigue; weight loss; heat intolerance; and excessive sweating. Thyrotoxicosis and Hyperthyroidism.
  • Vitamin D deficiency Vitamin D Deficiency A nutritional condition produced by a deficiency of vitamin D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as rickets in children and osteomalacia in adults. Fat-soluble Vitamins and their Deficiencies should be corrected to reduce the risk of postoperative hypocalcemia Hypocalcemia Hypocalcemia, a serum calcium < 8.5 mg/dL, can result from various conditions. The causes may include hypoparathyroidism, drugs, disorders leading to vitamin D deficiency, and more. Calcium levels are regulated and affected by different elements such as dietary intake, parathyroid hormone (PTH), vitamin D, pH, and albumin. Presentation can range from an asymptomatic (mild deficiency) to a life-threatening condition (acute, significant deficiency). Hypocalcemia.
• Postoperative considerations:^[11]
  • Thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types:
    • L-thyroxine L-Thyroxine Thyroid Replacement Therapy should be started immediately at a dose appropriate for weight (1.6 µg/kg).
    • Check TSH 6‒8 weeks postoperatively.
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes:
    • Monitor serum calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and intact parathyroid Parathyroid The parathyroid glands are 2 pairs of small endocrine glands found in close proximity to the thyroid gland. The superior parathyroid glands are lodged within the parenchyma of the upper poles of the right and left thyroid lobes; the inferior parathyroid glands are close to the inferior tips or poles of the lobes. Parathyroid Glands: Anatomy hormone levels.
    • Supplement with oral calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes +/– calcitriol Calcitriol The physiologically active form of vitamin d. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (calcifediol). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption. Parathyroid Glands: Anatomy as needed.

Other therapies^{[4–7,10,11]}

For hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism and goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter:

• β-blockers:
  • Antagonizes β-receptor–mediated actions of catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones
  • Improve palpitations Palpitations Ebstein’s Anomaly, tremors, tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children, anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder, heat Heat Inflammation intolerance
  • Recommended by the ATA in all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with symptomatic hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, but especially:
    • Elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • Those with heart rates > 90/min
    • Those with cardiovascular disease^[11]
  • β₁-Selectivity preferred
  • Oral options and dosing per ATA guidelines:
    • Atenolol Atenolol A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. Class 2 Antiarrhythmic Drugs (Beta Blockers) 25‒100 mg once or twice daily
    • Metoprolol Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat angina pectoris; hypertension; and cardiac arrhythmias. Antiadrenergic Drugs 25‒50 mg 2–3 times daily
    • Propranolol Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for myocardial infarction; arrhythmia; angina pectoris; hypertension; hyperthyroidism; migraine; pheochromocytoma; and anxiety but adverse effects instigate replacement by newer drugs. Antiadrenergic Drugs 10‒40 mg 3–4 times daily
  • IV option for ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus settings: esmolol Esmolol Antiadrenergic Drugs IV 50‒100 µg/kg/min
• Iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones elixirs (saturated solution of potassium iodide Potassium iodide An inorganic compound that is used as a source of iodine in thyrotoxic crisis and in the preparation of thyrotoxic patients for thyroidectomy. Antithyroid Drugs):
  • Used before surgery
  • Reduces vascularity of the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland

For orbitopathy:

• With hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism treatment, irritation and periorbital Periorbital Orbital and Preseptal Cellulitis edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema usually subside; proptosis Proptosis Retinoblastoma and extraocular muscle Extraocular Muscle Strabismus disorders persist.
• Artificial tears to improve eye symptoms
• Selenium Selenium An element with the atomic symbol se, atomic number 34, and atomic weight 78. 97. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. Trace Elements may help.
• Sight-threatening orbitopathy:
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids:
    • Pulse therapy with IV methylprednisolone Methylprednisolone A prednisolone derivative with similar anti-inflammatory action. Immunosuppressants 500 mg once weekly for 6 weeks and then 250 mg once weekly for another 6 weeks
    • Oral prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants 60‒100 mg/day if unable to have IV methylprednisolone Methylprednisolone A prednisolone derivative with similar anti-inflammatory action. Immunosuppressants
  • Surgical decompression or external orbital radiation Radiation Emission or propagation of acoustic waves (sound), electromagnetic energy waves (such as light; radio waves; gamma rays; or x-rays), or a stream of subatomic particles (such as electrons; neutrons; protons; or alpha particles). Osteosarcoma 
  • Teprotumumab (insulin-like growth factor I receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors inhibitor, licensed in US)

For dermopathy:

• Pretibial myxedema Pretibial Myxedema Graves’ Disease may persist even when normal thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function is achieved.
• Use of compression Compression Blunt Chest Trauma stockings
• Lymphedema Lymphedema Edema due to obstruction of lymph vessels or disorders of the lymph nodes. Lymphatic Filariasis (Elephantiasis) physiotherapy Physiotherapy Spinal Stenosis

Additional recommendations:

• Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes supplementation due to risk of osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis

Management of Graves’ disease Graves’ disease A common form of hyperthyroidism with a diffuse hyperplastic goiter. It is an autoimmune disorder that produces antibodies against the thyroid stimulating hormone receptor. These autoantibodies activate the TSH receptor, thereby stimulating the thyroid gland and hypersecretion of thyroid hormones. These autoantibodies can also affect the eyes (Graves ophthalmopathy) and the skin (Graves dermopathy). Thyrotoxicosis and Hyperthyroidism during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care^[11]

• Testing TRAbs:
  • In most cases, measure TRAbs at:
    • Initial prenatal visit
    • 18‒22 weeks (if elevated at initial visit)
    • 30‒34 weeks (if elevated at initial visit)
  • TRAb testing is not needed if the patient is in remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches and is not taking antithyroid medications.
• Diagnosed and treated prior to pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
  • If currently taking methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs → switch to PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs prior to conception 
  • If in remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches and no longer taking antithyroid medications → check thyroid function tests Thyroid Function Tests Blood tests used to evaluate the functioning of the thyroid gland. Ion Channel Myopathy at initial prenatal visit
• Diagnosed during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care:
  • In the 1st trimester → begin PTU PTU A thiourea antithyroid agent. Propylthiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to triiodothyronine. It is used in the treatment of hyperthyroidism. Antithyroid Drugs
  • In the 2nd or 3rd trimester → begin methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs
  • If thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter is needed, it is best performed during the 2nd trimester.

Differential Diagnosis

• Granulomatous thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis ( de Quervain syndrome De Quervain syndrome Spontaneously remitting inflammatory condition of the thyroid gland, characterized by fever; muscle weakness; sore throat; severe thyroid pain; and an enlarged damaged gland containing giant cells. The disease frequently follows a viral infection. Thyroiditis): thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation usually associated with a previous viral infection and the most common cause of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways. Presentation includes neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess tenderness with goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter. Work-up shows low TSH, elevated free T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones, increased sedimentation rate, and a low or absent radioactive iodine uptake Radioactive Iodine Uptake Thyrotoxicosis and Hyperthyroidism. Often a self-limited course that can go through a hyperthyroid state and then a euthyroid Euthyroid Thyroiditis state followed by hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism. Recovery to normal thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function takes months.
• Subacute lymphocytic thyroiditis Subacute lymphocytic thyroiditis Thyroiditis ( painless thyroiditis Painless Thyroiditis Thyroiditis): an autoimmune disease with diffuse enlargement of the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland. The same process occurs in postpartum thyroiditis Postpartum thyroiditis Transient autoimmune thyroiditis occurring in the postpartum period. It is characterized by the presence of high titers of autoantibodies against thyroid peroxidase and thyroglobulin. Clinical signs include the triphasic thyroid hormone pattern: beginning with thyrotoxicosis, followed with hypothyroidism, then return to euthyroid state by 1 year postpartum. Postpartum Complications. Laboratory tests depend on the phase of the disease but the initial hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism shows low TSH and elevated T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones. The condition is associated with a low radioactive iodine uptake Radioactive Iodine Uptake Thyrotoxicosis and Hyperthyroidism. The disease pattern is a transient hyperthyroid state and then hypothyroid followed by recovery. Some cases do not become euthyroid Euthyroid Thyroiditis, however.
• Multinodular toxic goiter Toxic Goiter Goiter: multiple nodules in an enlarged thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland, producing excess thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types. Commonly found in elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship in iodine-deficient areas. Work-up demonstrates elevated thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types with high radioactive iodine uptake Radioactive Iodine Uptake Thyrotoxicosis and Hyperthyroidism showing multiple spots of iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones concentration.
• Toxic adenoma Toxic Adenoma Thyrotoxicosis and Hyperthyroidism: a condition in which the thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland contains a solitary nodule Nodule Chalazion that actively secretes thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormones Hormones Hormones are messenger molecules that are synthesized in one part of the body and move through the bloodstream to exert specific regulatory effects on another part of the body. Hormones play critical roles in coordinating cellular activities throughout the body in response to the constant changes in both the internal and external environments. Hormones: Overview and Types. Tests are consistent with hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, with radioactive iodine uptake Radioactive Iodine Uptake Thyrotoxicosis and Hyperthyroidism showing 1 spot of iodine Iodine A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126. 90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. Thyroid Hormones concentration.
• Factitious thyrotoxicosis Factitious Thyrotoxicosis Thyrotoxicosis and Hyperthyroidism: occurs with the intake of excessive amounts of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone (most common preparation is levothyroxine Levothyroxine Thyroid Replacement Therapy). Separate outbreaks Outbreaks Sudden increase in the incidence of a disease. The concept includes epidemics and pandemics. Influenza Viruses/Influenza of so-called hamburger thyroiditis Thyroiditis Thyroiditis is a catchall term used to describe a variety of conditions that have inflammation of the thyroid gland in common. It includes pathologies that cause an acute illness with severe thyroid pain (e.g., subacute thyroiditis and infectious thyroiditis) as well as conditions in which there is no clinically evident inflammation and the manifestations primarily reflect thyroid dysfunction or a goiter (e.g., painless thyroiditis and fibrous Riedel’s thyroiditis). Thyroiditis, which was caused by the ingestion of bovine thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy tissue (i.e., ground-up neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess muscle), occurred in 1984–85 in Minnesota, South Dakota, and Nebraska. Manifestations show hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism with no exophthalmos or goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter. Features include low TSH, normal/elevated T4 T4 The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form triiodothyronine which exerts a broad spectrum of stimulatory effects on cell metabolism. Thyroid Hormones, low thyroglobulin Thyroglobulin Thyroid Hormones level, and low radioiodine uptake.

Billing and Coding

Diagnosis Codes:

This code is used to diagnose Graves’ disease, an autoimmune disorder Autoimmune Disorder Septic Arthritis that is the most common cause of hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, characterized by a diffusely enlarged thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy gland ( goiter Goiter A goiter is a chronic enlargement of the thyroid gland due to nonneoplastic growth occurring in the setting of hypothyroidism, hyperthyroidism, or euthyroidism. Morphologically, thyroid enlargement can be diffuse (smooth consistency) or nodular (uninodular or multinodular). Goiter).

Evaluation & Workup:

This code is for the Thyroid-Stimulating Immunoglobulin ( TSI TSI Shigella) or TSH-Receptor Antibody (TRAb) test, which is a specific blood test that confirms the autoimmune basis of the hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism in Graves’ disease.

Medications:

This code is for methimazole Methimazole A thioureylene antithyroid agent that inhibits the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin. This is done by interfering with the oxidation of iodide ion and iodotyrosyl groups through inhibition of the peroxidase enzyme. Antithyroid Drugs, an antithyroid drug that blocks the production of thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy hormone and is the primary medical treatment for Graves’ disease.