Medical Pharmacology: Thyroid Pharmacology and Physiology

Table of Contents
Thyroid Localization and Anatomy Histological Section Thyroid Physiology Overview Thyroid System Overview Thyroid Hormone Synthesis Receptors TSH receptors (TSH-R) TSH-R: localization and properties Iodide Metabolism Iodide Intake Non-Physiological Thyroid Stimulation Thyroid Hormones Pharmacokinetics Factors altering clearance Mechanisms of Action Metabolic Effects Thyroid Hormonal Effects Thyroid Preparations Preparation of Choice-Synthetic levothyroxine Anti-Thyroid Drugs Overview Classes Thioamides: Major drugs for thyrotoxicosis Propylthiouracil Methimazole Anion Inhibitors Iodides Iodinated Radiographic Contrast Agents Radioactive Iodine Adrenoceptor Antagonists	Hypothyroidism Overview Cretinism Myxedema Classification Pathogenesis Causes Clinical Presentation Neonates Young Children Older Child Adult Advanced Disease Laboratory Tests Pharmacological Treatment Synthetic Hormones Neonatal, infantile, and juvenile hypothyroidism Adults Thyrotoxicosis Definition Most important causes Causes Clinical Presentation Common Manifestations Ocular Cardiovascular Graves' disease Major Presentations Thyroid Pathology Other organ involvement Opthalmopathy Dermopathy Clinical Presentations Thyroid Storm Thyroid Cancer Overview (Video)

**Thyroid and Parathyroid Gland Anatomical Localization**

Fuelbottle: "Thyroid and parathyroid gland" source: http://training.seer.cancer.gov/anatomy/endocrine/glands/thyroid.html http://en.wikipedia.org/wiki/File:Illu_thyroid_parathyroid.jpg

**Section through the Thyroid Gland (Equine)**

Thyroid: Histological section Legend: 1. Follicles 2. Follicular Epithelial Cells 3. Endothelial Cells Gille U "Histological section through the thyroid of a horse" http://en.wikipedia.org/wiki/File:Thyoid-histology.jpg

Thyroid: Histological section
- Legend:
  - 1. Follicles
  - 2. Follicular Epithelial Cells
  - 3. Endothelial Cells
Gille U "Histological section through the thyroid of a horse" http://en.wikipedia.org/wiki/File:Thyoid-histology.jpg

**"Overview of the Thyroid System"**

Haggstrom M Overview of the thyroid system. http://en.wikipedia.org/wiki/File:Thyroid_system.svg

**"Thyroid Hormone Synthesis"**

Haggstrom M "Thyroid Hormone Synthesis" http://en.wikipedia.org/wiki/File:Thyroid_hormone_synthesis.png "Synthesis of the thyroid hormones, as seen on an individual thyroid follicular cell: Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis. Meanwhile, a sodium-iodide (Na/I) synporter pumps iodide (I^-) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms. This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner. In the colloid, iodide (I^-) is oxidized to iodine (I^o) by an enzyme called thyroid peroxidase. Iodine (I^o) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total contain approximately 120 tyrosyl residues). In conjugation, adjacent tyrosyl residues are paired together. The entire complex re-enters the follicular cell by endocytosis. Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules, which enters the blood by largely unknown mechanisms" Boron WF Boulpaep E (2003) Chapter 48; "Synthesis of thyroid hormones" Medical Physiology: A Cellular and Molecular Approach. Elseview/Saunders. p 1300. Thyroid: http://en.wikipedia.org/wiki/Thyroid

"Thyroid Hormone Synthesis"

Haggstrom M "Thyroid Hormone Synthesis" http://en.wikipedia.org/wiki/File:Thyroid_hormone_synthesis.png
"Synthesis of the thyroid hormones, as seen on an individual thyroid follicular cell:
- Thyroglobulin is synthesized in the rough endoplasmic reticulum and follows the secretory pathway to enter the colloid in the lumen of the thyroid follicle by exocytosis.
- Meanwhile, a sodium-iodide (Na/I) synporter pumps iodide (I^-) actively into the cell, which previously has crossed the endothelium by largely unknown mechanisms.
- This iodide enters the follicular lumen from the cytoplasm by the transporter pendrin, in a purportedly passive manner.
- In the colloid, iodide (I^-) is oxidized to iodine (I^o) by an enzyme called thyroid peroxidase.
- Iodine (I^o) is very reactive and iodinates the thyroglobulin at tyrosyl residues in its protein chain (in total contain approximately 120 tyrosyl residues).
- In conjugation, adjacent tyrosyl residues are paired together.
- The entire complex re-enters the follicular cell by endocytosis.
- Proteolysis by various proteases liberates thyroxine and triiodothyronine molecules, which enters the blood by largely unknown mechanisms"
  - Boron WF Boulpaep E (2003) Chapter 48; "Synthesis of thyroid hormones" Medical Physiology: A Cellular and Molecular Approach. Elseview/Saunders. p 1300.
  - Thyroid: http://en.wikipedia.org/wiki/Thyroid