Endocrine: Thyroid Hormones Overview

Endocrine: Thyroid and Growth Axes and Integration across Axes

• The thyroid is a lobed gland located below the larynx that regulates metabolism.
• The thyroid gland produces the hormones T3 and T4, which are derived from tyrosine and contain iodine.
• Learning Objectives for the Thyroid include identifying the biosynthesis, storage, and secretion of T3 and T4, and their regulation; describing the absorption, uptake, distribution, and excretion of iodide; explaining the importance of thyroid hormone binding in blood on free and total thyroid hormone levels.
• The significance of converting T4 to T3 and reverse T3 (rT3) in extra-thyroidal tissues needs to be understood; as well as the physiologic effects and mechanisms of action of thyroid hormones.
• The causes and consequences of over-secretion and under-secretion of thyroid hormones need to be understood, along with what conditions can cause an enlargement of the thyroid gland.

Learning Objectives – Thyroid

• Identify the processes of triiodothyronine (T3) and thyroxine (T4) biosynthesis, storage, and secretion, and their regulation.
• Describe the absorption, uptake, distribution, and excretion of iodide.
• Explain the importance of thyroid hormone binding in the blood, concerning free and total thyroid hormone levels.
• Understand the significance of the conversion of T4 to T3 and reverse T3 (rT3) in extra-thyroidal tissues.
• Describe the physiological effects and mechanisms of action of thyroid hormones.
• Understand the causes and consequences of thyroid hormone over-secretion and under-secretion.
• Explain conditions that cause thyroid gland enlargement.

The Thyroid is a Lobed Gland Below the Larynx that Regulates Metabolism

• The hypothalamus releases TRH (Thyrotropin-releasing hormone).
• The anterior pituitary releases TSH (Thyroid-stimulating hormone) in response to TRH.
• The thyroid produces thyroid hormones (T3 and T4).
• Thyroid hormones increase metabolic rate and heat production, enhance growth and CNS development, and increase sympathetic activity.

Signal Transduction Pathways Used by Major Hormones

• Cyclic AMP/PKA pathway: Alters preexisting proteins.
• IP3/Ca2+ and DAG/PKC pathway: Alters preexisting proteins.
• Tyrosine kinase pathway: Alters preexisting proteins, turns on gene transcription, leading to synthesis of designated protein.
• JAK/STAT pathway: Turns on gene transcription, leading to synthesis of designated protein.
• Hormone-response elements on DNA: Turns genes on, leading to synthesis of designated proteins.

Synthesis, Storage, and Secretion of Thyroid Hormone into Circulation

• Tyrosine-containing thyroglobulin (Tg) is produced in follicular cells and transported to the colloid.
• Iodide is actively transported into the colloid.
• Iodide is oxidised to an active form by thyroperoxidase (TPO) at the luminal membrane.
• Active iodide exits the cell at the lumina channels.
• Iodination of tyrosine produces monoiodotyrosine (MIT) and diiodotyrosine (DIT).
• Coupling MIT with DIT produces T3.
• Coupling DIT with DIT produces T4.
• Thyroid follicular cells engulf the Tg-containing colloid by phagocytosis.
• Lysosomes in the follicular cells break down the Tg, releasing T3 and T4 into the blood.

Learning Objectives – Thyroid

• Identify the steps in the biosynthesis, storage, and secretion of triiodothyronine (T3) and thyroxine (T4) and their regulation.
• Describe the absorption, uptake, distribution, and excretion of iodide.
• Explain the importance of thyroid hormone binding in blood on free and total thyroid hormone levels.
• Understand the significance of the conversion of T4 to T3 and reverse T3 (rT3) in extra-thyroid tissues.
• Describe the physiologic effects and mechanisms of action of thyroid hormones.
• Understand the causes and consequences of a) over-secretion and b) under-secretion of thyroid hormones.
• Explain conditions that cause thyroid gland enlargement.

Factors Regulating Growth

• Genetics
• Maternal/fetal/placental factors (not including GH).
• Appropriate levels of growth-influencing hormones (GHRH).
• Adequate diet with sufficient protein and essential amino acids.
• Avoid chronic diseases and environmental stress.

Growth Hormones Regulation

• Growth hormone secretion is regulated by hypothalamic hormones (GH releasing hormone and somatostatin), glucose levels, and insulin-like growth factor 1 (IGF-1).
• The target organs or cells affected by insulin-like growth factors in longitudinal growth are detailed.
• The metabolic and growth-promoting actions of growth hormone are described, including its impact on cell division, protein synthesis, and bone growth.
• The role of somatostatin in inhibiting growth hormone and thyroid-stimulating hormone (TSH) to control growth and metabolism is explained.
• Cell signaling defects that cause specific endocrine diseases in the thyroid and growth axes are detailed.

Causes of Goiter Formation

• Iodine deficiency
• Autoimmune diseases (e.g., Graves' disease)
• Eating large amounts of soy, brassica vegetables, and peanuts (which contain antithyroid factors).
• Smoking (compounds in cigarettes can decrease the uptake of iodine).

HPT Axis Dysfunction

• Causes and symptoms of hyperthyroidism and hypothyroidism are described in a table.
• Different hormone levels are discussed, including T3, T4, and TSH.

Thyroid Storm

• A massive release of T4 and increased sensitivity to catecholamines can elevate cardiac muscle's metabolic demand, potentially causing myocardial ischemia.
• Symptoms include high fever, agitation, delirium, congestive heart failure, and loss of consciousness.

Hashimoto's Disease

• Hashimoto's disease is a type of hypothyroidism.
• Autoimmune factors damage the thyroid gland.
• Common symptoms include weight gain, cold intolerance, fatigue, slow pulse, slow reflexes, depression, and memory problems.

Euthyroid Sick

• Patients may exhibit hypothyroid symptoms but have underlying illnesses affecting thyroid hormone conversion and rT3 levels.
• Diagnosis depends on the ratio of T3 to rT3.

T3 and T4 are Important Regulators of Basal Metabolic Rate

• Their actions increase the basal metabolic rate, which influences oxygen consumption and energy expenditure.
• They play a key role in calorigenic reactions and the synthesis and degradation of carbohydrates, fats, and proteins.
• Thyroid hormones affect the body by stimulating metabolic processes.

Sympathomimetic Effects of Thyroid Hormone

• Thyroid hormones affect the body in a manner similar to the sympathetic nervous system (SNS).
• Target cells become more responsive to epinephrine and norepinephrine.
• Thyroid hormones increase the number of catecholamine receptors on target cells.
• The thyroid hormones enable the body to handle stress.

Growth Spurts During Childhood

• Postnatal growth spurts are not gender-dependent.
• Pubertal growth spurts are influenced by sex hormones (androgens and estrogens).
• Timing of these growth spurts varies between genders.

Important Note about the Growth Hormone Axis

• The Hypothalamic-Pituitary-Growth hormone (HPG) axis, regulates growth hormone secretion by receiving inputs from the hypothalamus and anterior pituitary.

Growth Hormone Functions

• The growth hormone has direct and indirect effects on metabolism and stimulates growth, through cell division and protein synthesis and bone growth.

IGF Signaling

• Insulin-like growth factors (IGFs) signal via Receptor Tyrosine Kinases, altering preexisting protein, activating protein kinase receptors.
• The pathway leads to increased and controlled cell growth and proliferation, crucial for various functions.