Thyroid Hormones

The 2 primary 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 triiodothyronine (T3) and thyroxine (T4). These 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 synthesized and secreted 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 they are responsible for stimulating metabolism in most cells of the body. Their secretion Secretion Coagulation Studies is regulated primarily by thyroid-stimulating hormone (TSH), which is produced by 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. Thyroid-stimulating hormone is regulated by thyroid-releasing hormone (TRH; which is stimulatory) and somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions (which is inhibitory). Both of these 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 produced by 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. T3 is far more active than T4, so most T4 is converted to T3 in the periphery (e.g., liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy). T3 helps to maintain normal cellular metabolism, oxygen consumption, energy levels, heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology, thermoregulation Thermoregulation Body temperature can be divided into external temperature, which involves the skin, and core temperature, which involves the CNS and viscera. While external temperature can be variable, the core temperature is maintained within a narrow range of 36.5-37.5ºC (97.7-99.5ºF). Body Temperature Regulation, bowel movements, mental health, and neurologic function. Abnormalities 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 hormone levels can lead to hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism and 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.

Last updated: Aug 3, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

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 released 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 gland

The primary 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 released from 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 include:

  • 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, triiodothyronine (T3) and thyroxine (T4):
    • Produced by follicular cells
    • Act on most cells/tissues in the body
    • Stimulate metabolism and oxygen consumption → primary regulators of body metabolism
    • Increase circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
    • Promote nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification and skeletal development
  • Calcitonin Calcitonin A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. Other Antiresorptive Drugs
    • Produced by parafollicular cells (also known as C cells C cells Calcium Hemostasis and Bone Metabolism) 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
    • Works to ↓ Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+ serum levels, opposing the action of parathyroid hormone Parathyroid hormone A polypeptide hormone (84 amino acid residues) secreted by the parathyroid glands which performs the essential role of maintaining intracellular calcium levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of calcium from bone, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates. Parathyroid Glands: Anatomy (PTH)
    • In 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:
      • Inhibits osteoclasts Osteoclasts A large multinuclear cell associated with the bone resorption. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. Bones: Development and Ossification → inhibits 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 breakdown
      • Stimulates osteoblasts Osteoblasts Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. Bones: Development and Ossification (mild effect) → promotes 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 deposition and ossification Ossification The process of bone formation. Histogenesis of bone including ossification. Bones: Development and Ossification
    • In kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy:
      • Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+ reabsorption → ↓ serum Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)2+ level
      • Phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes reabsorption → ↓ serum phosphate Phosphate Inorganic salts of phosphoric acid. Electrolytes
    • Although produced 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 gland, not generally included in the term “ 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

The hypothalamic-pituitary-thyroid (HPT) axis Axis The second cervical vertebra. Vertebral Column: Anatomy

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 of T3 and T4 is regulated by 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 secreted by 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 and 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. This complex interaction is known as the HPT axis Axis The second cervical vertebra. Vertebral Column: Anatomy:

  • 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 secretes:
    • 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; stimulatory) 
    • Somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions (inhibitory)
  • TRH stimulates thyrotropes in the anterior 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 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 thyroid-stimulating hormone (TSH).
  • TSH stimulates 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 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 T3 and T4
  • T3 and T4:
    • Stimulate metabolism throughout the body (their primary physiologic effect)
    • Feedback within the HPT axis Axis The second cervical vertebra. Vertebral Column: Anatomy:
      • Inhibit the 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 of TSH and TRH 
      • Stimulate the 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 of somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions 
  • Physiologic relationship Relationship A connection, association, or involvement between 2 or more parties. Clinician–Patient Relationship between the 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 in the HPT axis Axis The second cervical vertebra. Vertebral Column: Anatomy:
    • As T3 or T4 ↑ → TSH ↓
    • As T3 or T4 ↓ → TSH ↑
Hypothalamic-pituitary-thyroid axis

Hypothalamic-pituitary-thyroid axis Axis The second cervical vertebra. Vertebral Column: Anatomy and the negative feedback Negative feedback Hypothalamic and Pituitary Hormones loops

Image by Lecturio.

Thyroid Hormone Synthesis and Transportation

Synthesis Synthesis Polymerase Chain Reaction (PCR)

  • 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 consists 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 follicular cells wrapped around colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids.
  • Components required to make 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:
    • Iodine (I2): must be obtained from the diet
    • Thyroglobulin (Tg): produced 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 follicular cells 
  • Iodide (I) is taken into 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 follicular cells by the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia iodide symporter Symporter Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is ‘powered’ by the movement of another ion or molecule with its electrochemical gradient. The Cell: Cell Membrane (NIS).
  • I and Tg are moved into the colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids:
  • I is oxidized to form I2 (the form that can be bound to Tg).
  • 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 (TPO): combines I2 and Tg via iodination to form 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 intermediates
    • Mono-iodotyrosine (MIT; “T1”)
    • Di-iodotyrosine (DIT; “T2”) 
  • TPO then further combines these intermediates via a process called conjugation Conjugation A parasexual process in bacteria; algae; fungi; and ciliate eukaryota for achieving exchange of chromosome material during fusion of two cells. In bacteria, this is a unidirectional transfer of genetic material; in protozoa it is a bi-directional exchange. In algae and fungi, it is a form of sexual reproduction, with the union of male and female gametes. Bacteriology to make T3 and T4:
    • MIT + DITT3 
    • DIT + DIT → T4 
  • T3 and T4 are endocytosed into the follicular cells, cleaved by lysosomes Lysosomes A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured or undergoes membrane fusion. The Cell: Organelles, and secreted into the blood.
  • T4 activation:
    • Active (free) T3 is 10× stronger than active (free) T4.
    • Most T4 is converted to T3 by the peripheral enzyme 5’-mono-deiodinase.
    • Some T4 is converted to reverse T3 (rT3) (an inactive metabolite).
Steps for synthesis of thyroid hormones

Steps for synthesis Synthesis Polymerase Chain Reaction (PCR) 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:
Through the sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia iodide symporter Symporter Membrane transporters that co-transport two or more dissimilar molecules in the same direction across a membrane. Usually the transport of one ion or molecule is against its electrochemical gradient and is ‘powered’ by the movement of another ion or molecule with its electrochemical gradient. The Cell: Cell Membrane (NIS), odide (I) is brought into 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 follicular cells where the I is oxidized into iodine (I2) and then secreted into colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids through pendrin channels Channels The Cell: Cell Membrane. The follicular cells produce Tg, which is exocytosed into the colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids. 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 (TPO) then combines the I2 and Tg molecules to form mono-iodotyrosine (MIT), or T1, and di-iodotyrosine (DIT), or T2. The TPO then uses the MIT and DIT to form triiodothyronine (T3), thyroxine (T4), and reverse triiodothyronine (rT3), an inactive metabolite. 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 endocytosed back into the follicular cells, processed in the lysosome, and then excreted into the blood.

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Transportation

  • T3 and T4 are hydrophobic/lipophilic (can cross cell membranes → 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 are intracellular). 
  • More than 99% of T3 and T4 are protein-bound for transport within the blood by:
    • Thyroid-binding globulin (TBG) (primary binder)
    • Transthyretin Transthyretin Amyloidosis
    • Albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests
    • Lipoproteins Lipoproteins Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of triglycerides and cholesterol esters surrounded by a layer of hydrophilic free cholesterol; phospholipids; and apolipoproteins. Lipoproteins are classified by their varying buoyant density and sizes. Lipid Metabolism
  • Protein-bound 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 inactive, serving as a reservoir Reservoir Animate or inanimate sources which normally harbor disease-causing organisms and thus serve as potential sources of disease outbreaks. Reservoirs are distinguished from vectors (disease vectors) and carriers, which are agents of disease transmission rather than continuing sources of potential disease outbreaks. Humans may serve both as disease reservoirs and carriers. Escherichia coli.
  • Free and bound forms are in an equilibrium Equilibrium Occurs when tumor cells survive the initial elimination attempt These cells are not able to progress, being maintained in a state of dormancy by the adaptive immune system. In this phase, tumor immunogenicity is edited, where T cells keep selectively attacking highly immunogenic tumor cells.This attack leaves other cells with less immunogenicity to potentially develop resistance to the immune response. Cancer Immunotherapy → levels of free hormone remain fairly constant

Physiologic Effects of the Thyroid Hormones

  • Within the cell, T3 binds to 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 hormone 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 (THR).
  • T3–THR complex binds to 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 response elements (TREs) within DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure →  stimulates transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription/ translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation of a number of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis including:
    • Na+/K+ ATPase
    • Gluconeogenic enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Respiratory enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
    • Myosin Myosin A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind actins and hydrolyze mgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and mgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain. Skeletal Muscle Contraction heavy chains Heavy chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kda. Immunoglobulins: Types and Functions
    • β-adrenergic 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
  • These proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis generally:
    • ↑ Cellular metabolism
    • ↑ Cellular oxygen consumption
    • ↑ Cellular glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance
    • Circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment and respiration Respiration The act of breathing with the lungs, consisting of inhalation, or the taking into the lungs of the ambient air, and of exhalation, or the expelling of the modified air which contains more carbon dioxide than the air taken in. Nose and Nasal Cavity: Anatomy
    • Promote nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification and skeletal development
  • Clinically, these 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 help maintain normal:
    • Energy levels
    • Weight
    • Thermoregulation Thermoregulation Body temperature can be divided into external temperature, which involves the skin, and core temperature, which involves the CNS and viscera. While external temperature can be variable, the core temperature is maintained within a narrow range of 36.5-37.5ºC (97.7-99.5ºF). Body Temperature Regulation
    • Heart rates
    • Bowel movements
    • Mood
Peripheral conversion of t4 and t3

Peripheral conversion of T4 and T3:
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 exert their greatest influence over transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription as T3. Triiodothyronine moves into the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles where it binds to the THR. The T3-THR complex acts as a transcription factor Transcription factor Generic term for proteins necessary for transcription Regulation of Transcription and is able to bind BIND Hyperbilirubinemia of the Newborn directly to the DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure at sequences known as TREs. With the help of additional transcription-regulating proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis, transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of messenger RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure ( mRNA mRNA RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3′ end, referred to as the poly(a) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. RNA Types and Structure) occurs with mRNAs encoding a number of proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis involved in metabolism.
T4: thyroxine
T3: triiodothyronine

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Clinical Relevance

When 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 produced at abnormal levels, symptoms can develop.

Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism

Hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism is the inappropriate secretion Secretion Coagulation Studies 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 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 and T4), leading to an abnormal increase in the basal metabolic rate. 

  • Etiology:
    • 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 (autoimmune disease caused by TSH-receptor 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)
    • Multinodular 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
    • Toxic 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 adenoma
    • TSH-secreting pituitary adenomas Pituitary adenomas Pituitary adenomas are tumors that develop within the anterior lobe of the pituitary gland. Non-functioning or non-secretory adenomas do not secrete hormones but can compress surrounding pituitary tissue, leading to hypopituitarism. Secretory adenomas secrete various hormones depending on the cell type from which they evolved, leading to hyperpituitarism. Pituitary Adenomas
  • Clinical presentation: 
    • Unintentional weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
    • Feeling hot
    • 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
    • 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
    • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder/irritability and 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
    • Pretibial myxedema Pretibial Myxedema Graves’ Disease
    • Lid lag Lid Lag Ion Channel Myopathy of the eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis during vertical eye movements
  • Diagnosis: by laboratory assessment
  • Management: 
    • Medications
    • Surgery
    • 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

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

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 is the inadequate 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 hormone, leading to an abnormal decrease in the metabolic rate. 

  • Etiology:
    • 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
    • Iodine deficiency
    • 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 infiltration
    • Congenital Congenital Chorioretinitis agenesis Agenesis Teratogenic Birth Defects/dysgenesis
  • Clinical presentation: 
    • Difficulty losing weight
    • Feeling cold
    • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
    • 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
    • Hyporeflexia Hyporeflexia Duchenne Muscular Dystrophy
  • Diagnosis: by laboratory assessment
    • Primary 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: ↑ TSH + ↓ free T4
    • Secondary 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 (adenomas, hypopituitarism Hypopituitarism Hypopituitarism is a condition characterized by pituitary hormone deficiency. This condition primarily results from a disease of the pituitary gland, but it may arise from hypothalamic dysfunction. Pituitary tumors are one of the most common causes. The majority of cases affect the anterior pituitary lobe (adenohypophysis), which accounts for 80% of the gland. Hypopituitarism): ↓ TSH + ↓ free T4
  • Management: 

References

  1. Brent, G.A. (2020). Thyroid hormone action. UpToDate. Retrieved July 30, 2021, from https://www.uptodate.com/contents/thyroid-hormone-action 
  2. Ross, D.S. (2020). Overview of the clinical manifestations of hyperthyroidism in adults. UpToDate. Retrieved July 30, 2021, from https://www.uptodate.com/contents/overview-of-the-clinical-manifestations-of-hyperthyroidism-in-adults 
  3. Saladin, K.S., Miller, L. (2004). Anatomy and physiology, 3rd ed., pp. 647–648. 
  4. Ross, D.S. (2022). Thyroid hormone synthesis and physiology. UpToDate. Retrieved Feb 15, 2022 from https://www.uptodate.com/contents/thyroid-hormone-synthesis-and-physiology

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