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Graves’ Disease

Graves' disease is an autoimmune disorder Autoimmune Disorder Septic Arthritis characterized by the presence of circulating 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 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-stimulating hormone (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, thereby causing the thyroid gland Thyroid gland 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 to hyperfunction. Clinical features include hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism (of which Graves' disease is the most common cause), orbitopathy, 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, and dermopathy/pretibial 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. Manifestations reflect the muti-systemic effects of a hyperactive 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, including heat Heat Inflammation intolerance, sweating, palpitations Palpitations Ebstein’s Anomaly, tremors, pretibial 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, and exophthalmos. Diagnosis is by 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 laboratory tests showing a low TSH, 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 ( thyroxine Thyroxine 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. Thyroid Hormones ( 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) and triiodothyronine Triiodothyronine 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 ( 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 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 (particularly 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-stimulating immunoglobulins Immunoglobulins 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 subtype). If initial tests are nondiagnostic, 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 uptake (increased uptake) and 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 (diffuse 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) provide diagnostic information. Treatment options include thionamides Thionamides Organic compounds containing the radical -CSNH2. Antithyroid Drugs, radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism, and surgery.

Last updated: 17 Feb, 2021

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

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 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-stimulating hormone (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 gland Thyroid gland 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 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 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 eye disease
  • Dermopathy: pretibial 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

Epidemiology

  • 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.

Etiology

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

Risk 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’s syndrome)
  • Environmental and non-genetic 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

  • 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-stimulating immunoglobulins Immunoglobulins 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 ( 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 gland Thyroid gland 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, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow, 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 gland Thyroid gland 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
    • 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/ 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 gland Thyroid gland 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:
      • 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
Classic negative feedback loop hashimoto

Hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus 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 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 axis Axis The second cervical vertebra. Vertebral Column: Anatomy feedback loop:
When 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 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 are low, the hypothalamus Hypothalamus The hypothalamus is a collection of various nuclei within the diencephalon in the center of the brain. The hypothalamus plays a vital role in endocrine regulation as the primary regulator of the pituitary gland, and it is the major point of integration between the central nervous and endocrine systems. Hypothalamus releases thyrotropin-releasing hormone Thyrotropin-releasing hormone A tripeptide that stimulates the release of thyrotropin and prolactin. It is synthesized by the neurons in the paraventricular nucleus of the hypothalamus. After being released into the pituitary portal circulation, TRH stimulates the release of TSH and PRL from the anterior pituitary gland. Hypothalamic and Pituitary Hormones (TRH), which triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) the pituitary gland Pituitary gland The pituitary gland, also known as the hypophysis, is considered the “master endocrine gland” because it releases hormones that regulate the activity of multiple major endocrine organs in the body. The gland sits on the sella turcica, just below the hypothalamus, which is the primary regulator of the pituitary gland. Pituitary Gland: Anatomy to secrete TSH. The effect of this process is that the thyroid gland Thyroid gland 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 produces thyroxine Thyroxine 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. Thyroid Hormones ( 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) and triiodothyronine Triiodothyronine 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 ( 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) (more 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 is produced, as it gets converted to 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). The increase in 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 (free or unbound 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/ 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) creates a negative feedback Negative feedback Hypothalamic and Pituitary Hormones, inhibiting TRH and TSH release Release Release of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane. Virology.

Image: “Classic Negative Feedback Negative feedback Hypothalamic and Pituitary Hormones Loop” by OpenStax College. License: CC BY 3.0, edited by Lecturio.

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

  • 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 Orbit The orbit is the cavity of the skull in which the eye and its appendages are situated. The orbit is composed of 7 bones and has a pyramidal shape, with its apex pointed posteromedially. The orbital contents comprise the eye, extraocular muscles, 5 cranial nerves, blood vessels, fat, the lacrimal apparatus, among others. Orbit and Extraocular Muscles: Anatomy
  • 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 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 (unclear mechanism for this localization)

Clinical Presentation

Factors affecting presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor

  • 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

  • General (increased basal metabolic rate):
  • 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 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 bruit
  • Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR):
    • 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

  • Graves’ orbitopathy: 
    • Scleral injection
    • Periorbital edema Periorbital Edema Nephrotic Syndrome in Children
    • Lid retraction accompanied by lid lag Lid Lag Ion Channel Myopathy (if ≥ 2 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma, graded as moderate to severe)
    • Exophthalmos/ proptosis Proptosis Retinoblastoma (if ≥ 3 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma, 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 Exposure ABCDE Assessment, 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
    • Non- pitting edema Pitting edema Edema caused by excess fluid without excess colloid. Leaves “pits” due to fluid displacement when pressure is applied to the area 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 Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment 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

Initial evaluation

  • Clinical findings from history and examination
  • Laboratory tests:
    • 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 tests: 
      • ↓ TSH
      • 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/ 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
    • 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 (TRAb), particularly 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-stimulating immunoglobulins Immunoglobulins 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:
      • 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
      • 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-stimulating immunoglobulins Immunoglobulins 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 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:

Imaging

  • 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 Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor is ambiguous
    • 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 uptake ( RAIU RAIU Thyrotoxicosis and Hyperthyroidism):
      • Uptake is increased.
      • Uptake is diffusely distributed throughout the thyroid gland Thyroid gland 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.
    • 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 Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. 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)

Management

Principles of treatment

  • Goals: 
  • 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:
  • Multiple options can be utilized with the same patient to reach goals.
  • Choice of treatment(s) 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 rate Mortality rate Calculated as the ratio of the total number of people who die due to all causes over a specific time period to the total number of people in the selected population. Measures of Health Status of up to 30%.

Thionamides Thionamides Organic compounds containing the radical -CSNH2. Antithyroid Drugs

  • 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
  • May be used initially to achieve euthyroid Euthyroid Thyroiditis state
  • Intake for up to 2 years may help reach remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches (rate of remission Remission A spontaneous diminution or abatement of a disease over time, without formal treatment. Cluster Headaches: 40%).
  • May be followed by radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism or surgery
  • Risks:
    • 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 > 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)
    • Hepatotoxicity Hepatotoxicity Acetaminophen ( 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 > 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 (check WBC count with any sign of infection!)
  • 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
    • 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:
      • 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 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 storm
      • Short acting

Radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism and surgery

  • Radioiodine ablation Radioiodine Ablation Thyrotoxicosis and Hyperthyroidism:
    • 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 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-131 (I-131) 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 and 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 follows.
    • 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.
    • 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 for up to a week should be avoided).
    • 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:
      • 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
      • Those with moderate-to-severe orbitopathy
  • Surgery ( thyroidectomy Thyroidectomy Surgical removal of the thyroid gland. Goiter):
    • 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
      • Pregnant women with antithyroid drug allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction
      • 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

Other therapies

  • 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 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–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
    • 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 gland Thyroid gland 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
  • 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 edema Periorbital Edema Nephrotic Syndrome in Children 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.
    • Moderate-to-severe orbitopathy:
      • Pulse therapy with intravenous 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
  • For dermopathy:
    • Pretibial 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 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

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’s syndrome): 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 Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor 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 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 uptake. 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 gland Thyroid gland 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. 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 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 uptake. 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 gland Thyroid gland 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, 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 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-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 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 uptake 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 gland Thyroid gland 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 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 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 uptake 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.

References

  1. Davies, T., Burch, H. (2020). Treatment of Graves’ orbitopathy (ophthalmopathy). UpToDate. Retrieved February 11, 2021, from https://www.uptodate.com/contents/treatment-of-graves-orbitopathy-ophthalmopathy
  2. Davies, T., Burch, H. (2020). Clinical features and diagnosis of Graves’ orbitopathy (ophthalmopathy). UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-graves-orbitopathy-ophthalmopathy
  3. Davies, T. (2019). Pretibial myxedema (thyroid dermopathy) in autoimmune thyroid disease. UpToDate. Retrieved February 10, 2021, from https://www.uptodate.com/contents/pretibial-myxedema-thyroid-dermopathy-in-autoimmune-thyroid-disease
  4. Fitzgerald P.A. (2021). Hyperthyroidism (thyrotoxicosis). Papadakis M.A., & McPhee S.J., & Rabow M.W. (Eds.). Current Medical Diagnosis & Treatment 2021. McGraw-Hill. 
  5. Jameson J, & Mandel S.J., & Weetman A.P. (2018). Hyperthyroidism. Jameson J, & Fauci A.S., & Kasper D.L., & Hauser S.L., & Longo D.L., & Loscalzo J(Eds.). Harrison’s Principles of Internal Medicine, 20e. McGraw-Hill.
  6. Maitra, A. (2021). The Endocrine System. Kumar V., Abbas, A., Aster, J. , Robbins & Cotran Pathologic Basis of Disease, 10e. Elsevier.
  7. Smith M.A. (2019). Graves disease and goiter. Usatine R.P., & Smith M.A., & Mayeaux, Jr. E.J., & Chumley H.S. (Eds.). The Color Atlas and Synopsis of Family Medicine, 3e. McGraw-Hill.
  8. Ross, D. (2020). Graves’ hyperthyroidism in nonpregnant adults: Overview of treatment. UpToDate. Retieved February 10, 2021, from https://www.uptodate.com/contents/graves-hyperthyroidism-in-nonpregnant-adults-overview-of-treatment
  9. Yeung, S., Habra, M. (2020). Graves Disease. Medscape. Retrieved January 24, 2021, from https://emedicine.medscape.com/article/120619-overview

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