Endocrinology 2

Endocrinology 2: Thyroid Notes

Introduction to Thyroid

  • Responsible for production of two hormones:

    • Thyroid hormone: Critical in regulating body metabolism, neurological development, and numerous other body functions.

    • Calcitonin: Secreted by parafollicular C cells and involved in calcium homeostasis.

  • Conditions affecting thyroid hormone levels are more common than those affecting calcitonin.

Thyroid Anatomy and Development

  • Location: Lower anterior neck.

  • Shape: Butterfly-like structure with 2 lobes on either side of the trachea, connected by a band of thyroid tissue.

  • Parathyroid Glands: Four parathyroid glands located posteriorly, responsible for regulating serum calcium and phosphate levels.

  • Development:

    • The thyroid develops within the first 4-8 weeks of fetal development.

    • Begins producing thyroid hormone by week 11 of gestation.

    • Iodine is essential for thyroid hormone production; deficiency can lead to hypothyroidism in both pregnant individuals and infants.

    • Critical for fetal neurological development; thyroid hormone passes through the placenta.

Importance of Iodine in Thyroid Hormone Synthesis

  • Thyroid hormone: Composed primarily of iodine, making iodine metabolism a key determinant of thyroid function.

  • Sources: Found in seafood, dairy, iodine-enriched bread, and certain vitamins.

  • Recommended Intake: 150 µg/day; intake below 50 µg/day causes an inability to produce adequate hormone and results in hypothyroidism.

Types of Thyroid Cells

  • Thyroid cells are organized into spheres (follicles) surrounding a central core of fluid called colloid.

    • Thyroglobulin: Glycoprotein synthesized by follicular cells, serves as a precursor for thyroid hormones.

    • Active Forms: Triiodothyronine (T3) and Thyroxine (T4) are stored in the thyroid follicle.

    • Parafollicular cells (C cells) produce calcitonin, which decreases blood calcium levels.

Thyroid Hormone Synthesis

  • Hormone Storage: T3 and T4 stored in the colloid of thyroid follicles.

  • Mechanism:

    • Thyroid Stimulating Hormone (TSH) signals the follicular cells to ingest colloid droplets.

    • Inside the cells, droplets are processed into T3 and T4, which are secreted into circulation.

    • TSH activity depends on iodine atom location and number.

Conversion and Activity of Thyroid Hormones

  • Approximately 80% of T4 is metabolized in peripheral tissues (mainly liver and kidneys) into T3 (35%) and reverse T3 (45%).

  • T3 is 3-8 times more metabolically active than T4 and is often referred to as the active form of thyroid hormone.

  • T4 is termed the 'pre' hormone, while thyroglobulin acts as a 'prohormone'.

  • Reverse T3: Metabolically inactive form of thyroid hormone.

Protein Binding of Thyroid Hormone

  • Less than 1% of T3 and T4 are unbound and available for hormone activity.

  • Major Binding Proteins (in order of significance):

    1. Thyroxine-binding globulin (TBG)

    2. Thyroxine-binding prealbumin (TBPA)

    3. Albumin

  • Changes in binding protein levels can affect circulating quantities of T3 and T4, e.g., increased estrogen during pregnancy raises TBG, leading to higher levels of T3 and T4.

Diminished Peripheral Conversion of T4 to T3

  • Occurs under conditions when the body conserves energy, including:

    • Caloric restriction

    • Hepatic disease

    • Major systemic illness

    • Certain medications

  • Results in more T4 being converted to metabolically inactive reverse T3, lowering the basal metabolic rate.

Actions of Thyroid Hormone

  • Hormones released into bloodstream undergo conversion in cytoplasm:

    • T4 converts to T3 (active form).

    • T3 binds to nuclear receptor on thyroid hormone-responsive genes, producing mRNA for proteins influencing metabolism and development.

Effects of Thyroid Hormone Include:

  • Tissue growth and development.

  • Brain maturation and central nervous system activity.

  • Increased heat production and oxygen consumption.

  • Regulation of metabolism.

  • Cardiovascular stimulation.

  • Gastrointestinal regulation.

Disorders Related to Thyroid Hormone Levels:

  • Excess Hormone: Known as Thyrotoxicosis; symptoms include increased metabolic activity like tachycardia and tremors.

  • Deficiency Hormone: Known as Hypothyroidism; symptoms include reduced metabolic activity such as edema and constipation.

Regulation of Thyroid Function

  • Hypothalamic-Pituitary-Thyroid Axis: Key in regulating thyroid hormone production.

    • TRH (Thyrotropin-Releasing Hormone): Synthesized in the hypothalamus, stimulates anterior pituitary to release TSH.

    • TSH (Thyroid-Stimulating Hormone): Circulates to the thyroid, promoting hormone production and release.

    • Feedback mechanisms:

    • T3 and T4 levels provide direct feedback to the pituitary and indirect feedback to the hypothalamus.

    • During low hormone levels, TRH and TSH release increase, stimulating thyroid activity.

    • High thyroid hormone levels inhibit TRH and TSH secretion, reducing thyroid hormone production.

Testing for Thyroid Function

Main Testing Methods:

  • Thyroid stimulating hormone (TSH)

  • Serum T3

  • Serum T4

  • Thyroglobulin

Less Common Tests:

  • Thyroid Autoimmunity Tests:

    • TSH receptor stimulating antibodies

    • TSH receptor antibodies (TRAb)

    • Thyroid stimulating immunoglobulin

    • Antithyroglobulin

    • Thyroid peroxidase antibodies

    • Anti-TSH receptor

Purpose of Testing

  • To confirm the nature and extent of hyperthyroidism or hypothyroidism in symptomatic patients.

  • High-risk groups for screening include:

    • Patients with family history

    • Newborns

    • Elderly

    • Postpartum parents

    • Patients with autoimmune or endocrine disorders.

  • Screening guidelines for hypothyroidism recommend testing at age 35 and every 5 years thereafter, or more frequently based on risk factors (e.g., goiter, lithium use, amiodarone use).

Specimens for Thyroid Testing

  • Typically, serum (gold tube) or plasma (light green tube) samples.

    • Whole blood on filter paper for newborn screenings.