Endocrine System Part II: Thyroid, Parathyroid, and Adrenal Glands

Thyroid Gland

Overview and Anatomy

The thyroid gland is the largest endocrine-only gland in the human body. It consists of two lateral lobes connected by an isthmus and is located anterior to the trachea.

• Follicles: Spherical structures that store thyroid hormones.

• Parafollicular cells: Secrete calcitonin, involved in calcium regulation.

• Epithelial follicular cells: Produce thyroglobulin and secrete it into the colloid-filled follicle.

Synthesis of Thyroid Hormones (T3 & T4)

Thyroid hormone synthesis is a multi-step process:

1. Iodine is absorbed by follicular epithelial cells from the bloodstream and transported to the follicle.

2. Follicular cells secrete thyroglobulin into the follicle.

3. Iodine molecules are added to thyroglobulin.

4. Iodine-thyroglobulin complexes combine.

5. Iodine-thyroglobulin is taken up into follicular epithelial cells.

6. Lysosomal enzymes release T3 and T4 from thyroglobulin.

7. T3 and T4 are secreted into the extracellular fluid.

8. At target tissues, T4 is converted to T3 (the more active form).

• T3 (triiodothyronine) and T4 (tetraiodothyronine or thyroxine) are the main thyroid hormones.

General Properties and Functions of T3 and T4

• Amino acid-based but lipid-soluble; travel in blood bound to carriers.

• Enter cells and bind nuclear receptors to trigger gene transcription.

• Increase metabolic rate and heat production (calorigenic effect).

• Regulate tissue growth and development, especially skeletal, nervous, and reproductive systems.

• Permissive for catecholamines (maintain adrenergic receptors in blood vessels).

• T4 is converted to T3 at target tissues; T3 is about 10 times more active.

Regulation: Thyroid Negative Feedback Loop

• Low T3/T4 stimulates the hypothalamus to release thyrotropin-releasing hormone (TRH).

• TRH stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH, thyrotropin).

• TSH stimulates the thyroid gland to secrete T3/T4.

• Rising T3/T4 levels inhibit TRH and TSH release (negative feedback).

Parafollicular Cells and Calcitonin

• Secrete calcitonin, which is an antagonist to parathyroid hormone (PTH).

• Inhibits osteoclasts, reducing blood calcium levels.

• Produced in response to high blood calcium; helps restore homeostasis.

Thyroid Disorders

• Hyperthyroidism: Excess T3/T4; symptoms include weight loss, sweating, nervousness, rapid heartbeat.

• Hypothyroidism: Deficient T3/T4; symptoms include fatigue, weight gain, cold intolerance, dry skin, hair loss, constipation, muscle aches, decreased heart rate.

Causes of Thyroid Dysfunction

• Increased activity: Tumors, Graves' disease, failure of feedback inhibition, increased TRH/TSH secretion, can lead to goiter.

• Decreased activity: Gland damage, decreased TRH/TSH, insufficient iodine (can also cause goiter).

Diagnosis of Thyroid Issues

Blood tests measure TSH and T4 levels to distinguish between normal, hyperthyroid, and hypothyroid states.

Condition	TSH	T4
Normal	Normal	Normal
Hyperthyroidism	Low	High
Hypothyroidism (Primary)	High	Low
Hypothyroidism (Secondary)	Low	Low

Parathyroid Gland

Overview and Function

The parathyroid glands are located on the posterior surface of the thyroid. The number and location can vary.

• Secrete parathyroid hormone (PTH).

• PTH release is stimulated by low blood calcium and inhibited by high calcium levels.

Actions of PTH

• Bones: Stimulates osteoclast activity to release calcium.

• Kidneys: Increases calcium reabsorption and promotes activation of vitamin D.

• Small intestine: Increased vitamin D activity leads to greater calcium absorption from the diet (indirect effect).

Adrenal Glands

Overview and Anatomy

The adrenal glands are located superior to each kidney and consist of two regions: the cortex and the medulla.

• Adrenal cortex: Outer, glandular region producing steroid hormones.

• Adrenal medulla: Inner, nervous tissue region producing amino acid-based hormones.

Anatomy of Adrenal Cortex

• Zona glomerulosa: Produces mineralocorticoids (salt).

• Zona fasciculata: Produces glucocorticoids (sugar).

• Zona reticularis: Produces gonadocorticoids (sex).

Mineralocorticoids (Salt)

• Regulate blood salt concentrations, mainly Na+ and K+.

• Na+ levels affect blood volume and pressure; K+ affects cell membrane potentials.

• Aldosterone is the primary mineralocorticoid.

Actions of Aldosterone

• Stimulates synthesis of Na+/K+ pumps in the kidney.

• Increases Na+ reabsorption (raises blood pressure/volume).

• Increases K+ secretion (K+ loss via urine).

Regulation of Aldosterone

1. Renin-angiotensin-aldosterone system (RAAS): Decreased blood pressure triggers renin release, leading to angiotensin II formation, which stimulates aldosterone secretion.

2. Plasma K+ levels: High K+ stimulates, low K+ inhibits aldosterone release.

3. ACTH: Usually minor effect, but can increase aldosterone under intense stress.

4. Atrial natriuretic peptide (ANP): Released by the heart in response to high blood pressure; inhibits aldosterone and renin secretion.

Disorders of Aldosterone

• Aldosteronism (hypersecretion): Usually due to adrenal tumors; causes hypertension, edema, and excessive K+ loss (can lead to paralysis).

• Addison's disease (hyposecretion): Autoimmune destruction of adrenal gland; symptoms include low blood pressure, dehydration, muscle weakness, and salt cravings.

Glucocorticoids (Sugar)

• Regulate metabolism and stress response.

• Main glucocorticoid: cortisol.

Regulation of Cortisol

1. Corticotropin-releasing hormone (CRH) from hypothalamus stimulates

2. Release of ACTH from anterior pituitary, which stimulates

3. Release of cortisol from adrenal cortex (zona fasciculata).

4. High cortisol inhibits CRH (negative feedback).

• Cortisol secretion follows a 24-hour cycle; stress can override feedback and increase secretion.

Actions of Cortisol

• Stimulates protein breakdown and fat release in adipose tissue.

• Raises blood glucose by stimulating gluconeogenesis in the liver.

• Enhances sympathetic nervous system effects (vasoconstriction).

• Excess cortisol can depress cartilage/bone formation, immune function, and disrupt other systems.

Disorders of Cortisol

• Cushing's disease/syndrome (hypersecretion): Caused by ACTH-secreting tumors or glucocorticoid drugs; symptoms include high blood glucose, muscle/bone loss, edema, immune suppression.

• Addison's disease (hyposecretion): Early sign is skin bronzing/hyperpigmentation due to increased ACTH.

Gonadocorticoids (Sex)

• Minor role compared to gonads after puberty.

• Examples: androstenedione, dehydroepiandrosterone (DHEA).

• Converted to testosterone or estrogen at target organs.

• Contribute to secondary sex characteristics and sex drive in women; main estrogen source in post-menopausal women.

• Release triggered by ACTH; feedback mechanisms are unclear.

Disorders of Gonadocorticoids

• Andrenogenital syndrome (hypersecretion): May cause masculinization, especially in females or prepubertal males.

Adrenal Medulla

• Part of the sympathetic nervous system; derived from nervous tissue.

• Releases catecholamines: epinephrine (80%) and norepinephrine (20%).

• Stimulated by preganglionic neurons of the autonomic nervous system.

Actions of Catecholamines

• Increase heart rate and blood pressure (vasoconstriction).

• Divert blood to essential organs (heart, skeletal muscle).

• Increase blood glucose levels.

• Decrease gut motility (not increase).

Stress Response and the Adrenal Gland

• Short-term stress (fight or flight): mediated by catecholamines.

• Long-term stress (resistance reaction): mediated by glucocorticoids and mineralocorticoids.

Disorders of Catecholamines

• Hyposecretion is usually not clinically significant due to compensation by the nervous system.

• Hypersecretion (e.g., adrenal tumors) can cause symptoms of sympathetic nervous system overactivity.

Summary Table: Adrenal Cortex Hormones

Zone	Hormone Class	Main Hormone(s)	Main Function
Zona glomerulosa	Mineralocorticoids	Aldosterone	Regulate Na+/K+, blood pressure
Zona fasciculata	Glucocorticoids	Cortisol	Regulate metabolism, stress response
Zona reticularis	Gonadocorticoids	Androgens (DHEA, androstenedione)	Sex characteristics, libido

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