12-23 Endocrine System

Define hormone

Hormones are chemical messengers produced by glands in the endocrine system and are released into the bloodstream to target organs and tissues, influencing various physiological functions.

3 Key Principles of Hormonal Regulation

• Specificity: Hormones exert their effects on specific target cells that possess the appropriate receptors. This ensures that hormonal signals are directed and effective.

• Feedback Mechanisms: Many hormonal systems operate on feedback loops, primarily negative feedback, which helps maintain balance. For example, increased levels of a hormone may inhibit further secretion from the gland that produces it.

• Concentration and Timing: The effects of hormones depend on their concentration in the bloodstream and the timing of their release. Pulsatile release can enhance or diminish the response of target cells.

Define Autocrine Signalling

• In this type of signalling, a cell releases hormones or signalling molecules that bind to receptors on its own surface, affecting its own activity.

• This mechanism allows for self-regulation and fine-tuning of cellular functions.

• e.g., Interleukin-1 (IL-1): When pathogens activate macrophages, they secrete IL-1. This cytokine can bind to receptors on the same macrophage that released it, enhancing its own activity, such as increasing the production of other inflammatory mediators and promoting cell proliferation.

Define Paracrine Signalling

• Paracrine signaling involves the release of hormones or signaling molecules that act on nearby cells rather than on the originating cell itself.

• This type of signaling is essential for local communication between cells.

• For instance, in pancreatic islets, glucagon-like peptide-1 (GLP-1) released from alpha-cells can enhance insulin secretion from adjacent beta-cells, demonstrating how paracrine signaling can coordinate activities among different cell types within a tissue

Classification of Hormones based on their Chemical Structure

• Peptide Hormones: These are composed of amino acids and include insulin and glucagon. They are synthesized in ribosomes and processed in the endoplasmic reticulum and stored in vesicles before being secreted.

• Steroid Hormones: Derived from cholesterol, these hormones (e.g., cortisol, testosterone) are synthesized in the adrenal cortex and gonads. They are released immediately after synthesizing because they can easily pass through cell membranes due to their lipophilic nature.

• Amine Hormones: These are derived from amino acids and can have properties similar to either peptide or steroid hormones:

  • Catecholamines e.g. epinephrine and norepinephrine are synthesized from the amino acid tyrosine

  • Thyroid hormones e.g. thyroxine [T4] and triiodothyronine [T3] are synthesized from the amino acid tyrosine in the thyroid gland.

  • Serotonin is synthesized from the amino acid tryptophan in the enterochromaffin cells of the gastrointestinal tract and in serotonergic neurons in the brain.

  • Melatonin is synthesized from serotonin in the pineal gland

The mechanism of action for hormones typically involves binding to what types specific receptors on target cells?

• Membrane-bound Receptors: Peptide hormones usually bind to receptors on the cell membrane, triggering a cascade of intracellular events via second messengers (e.g., cAMP).

• Intracellular Receptors: Steroid hormones typically pass through the cell membrane and bind to receptors inside the cell, directly influencing gene expression by acting on DNA.

Mechanisms of the Regulation of Hormonal Activity

• Feedback Control: Negative feedback loops are crucial for maintaining hormone levels within a specific range. For example, high levels of thyroid hormones inhibit further release from the thyroid gland.

• Hormonal Interactions: Hormones can influence each other's activity through synergistic or antagonistic effects. For instance, insulin and glucagon have opposing actions on blood glucose levels.

• Environmental Factors: External stimuli such as stress, light exposure, and nutritional status can influence hormone secretion patterns. For example, stress can increase cortisol levels, affecting metabolism.

Structure and Function of the Hypothalamic-Neurohypophysial System

• Hypothalamus: Located at the base of the brain, the hypothalamus serves as a control center for many autonomic functions. It synthesizes hormones that are transported to the posterior pituitary.

• Posterior Pituitary Gland: Unlike the anterior pituitary, which produces its own hormones, the posterior pituitary stores and releases hormones produced in the hypothalamus. The connection between these two structures is primarily neural, hence the term "neurohypophysial."

Define and Explain Neurosecretion

Neurosecretion refers to the process by which nerve cells (neurons) secrete hormones into the bloodstream. In the case of the hypothalamic-neurohypophysial system:

• Hormone Synthesis: Hormones are synthesized in neurosecretory cells located in specific nuclei of the hypothalamus, particularly the supraoptic and paraventricular nuclei.

• Transport: These hormones are transported down axons to the posterior pituitary gland, where they are stored in nerve terminals until needed.

• Release: When stimulated by appropriate signals (e.g., nerve impulses), these hormones are released into the bloodstream.

Hormones of the Posterior Pituitary Gland - Function and Role

• Oxytocin

• Vasopressin (Antidiuretic Hormone, ADH)

Function, Physiological Effects and Regulation of Secretion of Oxytocin

• Function: Oxytocin is involved in several physiological functions, including stimulating uterine contractions during childbirth and promoting milk ejection during breastfeeding.

• Role in Behavior: It also plays a role in social bonding and emotional responses.

• Regulation:

  • Released in response to cervical stretching during labor or nipple stimulation during breastfeeding.

  • Positive feedback mechanism: The more oxytocin released, the stronger uterine contractions become, further stimulating its release.

• Physiological Effects:

  • Stimulates uterine contractions during labor, facilitating childbirth.

  • Promotes milk ejection from mammary glands during lactation.

  • Enhances emotional bonding between individuals, particularly between mothers and infants.

Function, Physiological Effects and Regulation of Secretion of Vasopressin

• Function: Vasopressin regulates water balance in the body by promoting water reabsorption in the kidneys, thus concentrating urine and reducing urine volume.

• Role in Blood Pressure Regulation: It also has vasoconstrictive properties that can help increase blood pressure during times of low blood volume or dehydration.

• Regulation:

  • Triggered by increased plasma osmolality (concentration of solutes) or decreased blood volume/pressure.

  • Osmoreceptors in the hypothalamus detect changes in osmolality and stimulate ADH release when necessary.

  • Baroreceptors located in blood vessels sense changes in blood pressure and can also influence ADH secretion.

• Physiological Effects:

  • Increases water reabsorption in kidney tubules, leading to reduced urine output and increased blood volume.

  • Constricts blood vessels, which can raise blood pressure during stress or dehydration.

Structure and Function of the Hypothalamic-Adenohypophysial System

• Hypothalamus: Located at the base of the brain, the hypothalamus serves as a master regulator of endocrine function. It produces several releasing and inhibiting hormones that control the secretion of hormones from the anterior pituitary.

• Anterior Pituitary Gland: This gland produces its own hormones in response to signals from the hypothalamus. It is connected to the hypothalamus via a specialized blood vessel system known as the hypothalamic-pituitary portal system, which allows for efficient transport of hormones.

Hormones of the Anterior Pituitary Gland

• Growth Hormone (GH)

• Thyroid-Stimulating Hormone (TSH)

• Adrenocorticotropic Hormone (ACTH)

• Luteinizing Hormone (LH)

• Follicle-Stimulating Hormone (FSH)

• Prolactin (PRL)

Function, Physiological Effects and Regulation of Secretion of Growth Hormone (GH)

• Function: Stimulates growth and cell reproduction. It promotes protein synthesis and fat breakdown while inhibiting glucose uptake in some tissues.

• Regulation: Secretion is stimulated by Growth Hormone-Releasing Hormone (GHRH) from the hypothalamus and inhibited by Somatostatin (growth hormone-inhibiting hormone) based on feedback from blood glucose levels and other factors.

• Physiological Effects: Stimulates growth of bones and muscles. Increases protein synthesis and mobilizes fats for energy.

Function, Physiological Effects and Regulation of Secretion of Thyroid-Stimulating Hormone (TSH)

• Function: Stimulates the thyroid gland to produce thyroid hormones (T3 and T4), which regulate metabolism, energy levels, and growth.

• Regulation: Released in response to Thyrotropin-Releasing Hormone (TRH) from the hypothalamus. TRH stimulates TSH release; high levels of thyroid hormones provide negative feedback to reduce TRH secretion.

• Physiological Effects:

  • Increase BMR (basal metabolic rate) by stimulating the metabolism of carbohydrates, fats, and proteins

  • Stimulate the growth of bones and tissues

  • By increasing metabolic activity, thyroid hormones contribute to thermogenesis (heat production) in the body

  • T3 increases heart rate and enhances cardiac muscle contractility, leading to increased cardiac output.

  • T3 and T4 play a role in lipid metabolism by promoting the breakdown of cholesterol and increasing the clearance of low-density lipoprotein (LDL) from the bloodstream

  • They stimulate glycogenolysis (the breakdown of glycogen to glucose) in the liver, increasing blood glucose levels when needed

  • They promote gluconeogenesis (the production of glucose from non-carbohydrate sources).

  • Adequate levels of thyroid hormones are important for regular menstrual cycles in women. Hypothyroidism can lead to irregularities in menstrual function.

Function, Physiological Effects and Regulation of Secretion of Adrenocorticotropic Hormone (ACTH)

• Function: Stimulates the adrenal cortex to produce cortisol, a hormone involved in stress response, metabolism, and immune function.

• Regulation: Triggered by Corticotropin-Releasing Hormone (CRH) from the hypothalamus. CRH stimulates ACTH release; cortisol levels provide negative feedback to inhibit further ACTH secretion.

• Physiological Effects: Stimulates cortisol release from the adrenal glands, which helps manage stress responses and affects metabolism.

Function, Physiological Effects and Regulation of Secretion of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH)

• Function: Both are gonadotropins that regulate reproductive processes. LH stimulates ovulation and testosterone production, while FSH promotes follicle development in ovaries and sperm production in testes.

• Regulation: Controlled by Gonadotropin-Releasing Hormone (GnRH) from the hypothalamus. GnRH stimulates their release; sex steroid hormones (estrogen/testosterone) provide feedback inhibition on GnRH secretion.

• Physiological Effects: Regulate menstrual cycles in females and spermatogenesis in males. Influence secondary sexual characteristics.

Function, Physiological Effects and Regulation of Secretion of Prolactin (PRL)

• Function: Promotes milk production in lactating women and has roles in reproductive health.

• Regulation: Its secretion is primarily inhibited by Dopamine from the hypothalamus. Stress or suckling can stimulate its release despite this inhibition.

• Physiological Effects: Essential for milk production after childbirth. Plays a role in reproductive health and behaviour.

Functional Anatomy of the Thyroid Gland

The thyroid gland is a butterfly-shaped endocrine gland located in the anterior neck, just below the larynx and in front of the trachea. It consists of two lobes connected by a narrow isthmus. The functional anatomy includes:

• Follicles: The thyroid is composed of numerous spherical structures called follicles, which are filled with colloid, a protein-rich substance containing thyroglobulin. Follicles are the functional units responsible for hormone production.

• Follicular Cells: These epithelial cells line the follicles and are responsible for synthesizing thyroid hormones (thyroxine [T4] and triiodothyronine [T3]).

• Parafollicular Cells (C Cells): Located between the follicles, these cells produce calcitonin, a hormone involved in calcium homeostasis.

The thyroid gland requires iodine to synthesize its hormones, making iodine an essential nutrient for proper thyroid function.

Iodine-Containing Hormones produced by the thyroid gland

Thyroxine (T4):

• Composed of four iodine atoms.

• It is the primary hormone secreted by the thyroid gland and is converted into T3 in peripheral tissues.

Triiodothyronine (T3):

• Contains three iodine atoms.

• Although produced in smaller quantities than T4, T3 is more biologically active and has a more potent effect on metabolism.

Synthesis of Thyroid Hormones

1. Iodide Uptake: Follicular cells actively transport iodide from the bloodstream into the thyroid gland.

2. Thyroglobulin Synthesis: Thyroglobulin is synthesized in the follicular cells and secreted into the colloid.

3. Iodination: Iodide is oxidized and attached to tyrosine residues on thyroglobulin, forming monoiodotyrosine (MIT) and diiodotyrosine (DIT).

4. Coupling: MIT and DIT combine to form T3 and T4 within the colloid.

5. Release: When stimulated by thyroid-stimulating hormone (TSH), thyroglobulin is taken back into follicular cells, where it is broken down to release T3 and T4 into circulation.

Physiological Effects of the Thyroid Hormones

• Metabolism: They increase basal metabolic rate (BMR), enhancing oxygen consumption and heat production.

• Growth and Development: Essential for normal growth, development, and maturation of tissues, particularly in children.

• Cardiovascular Effects: Increase heart rate and cardiac output, enhancing blood flow to tissues.

• Nervous System: Influence cognitive functions, mood, and overall brain health.

Regulation of Secretion of the Thyroid Hormones

• Thyroid-Stimulating Hormone (TSH): Released from the anterior pituitary gland in response to Thyrotropin-Releasing Hormone (TRH) from the hypothalamus. Increased levels of TSH stimulate the synthesis and release of T3 and T4.

• Negative Feedback Mechanism: Elevated levels of T3 and T4 inhibit TRH and TSH secretion, maintaining hormone levels within a normal range.

Disorders of the Thyroid Gland

Hyperthyroidism

• An overproduction of thyroid hormones leads to an accelerated metabolism.

• Causes:

  • Graves' disease (an autoimmune disorder).

  • Toxic nodular goiter or thyroiditis.

• Symptoms: Weight loss, increased heart rate, anxiety, heat intolerance, sweating, tremors, and goiter (enlarged thyroid).

Hypothyroidism

• Insufficient production of thyroid hormones results in a slowed metabolism.

• Causes:

  • Hashimoto's thyroiditis (an autoimmune disorder).

  • Iodine deficiency or surgical removal of the thyroid.

• Symptoms: Weight gain, fatigue, cold intolerance, depression, dry skin, hair loss, and goiter.

Other Disorders

• Goiter: Enlargement of the thyroid gland due to insufficient iodine intake or other factors affecting hormone production.

• Thyroid Nodules: Abnormal growths within the thyroid that can be benign or malignant; some may produce excess hormones leading to hyperthyroidism.

Thyroid Function Tests

Thyroid function tests are essential diagnostic tools used to assess the health and functionality of the thyroid gland. These tests help determine whether the thyroid is producing appropriate levels of hormones, which are critical for regulating metabolism, growth, and development. The primary tests include:

• Serum Thyroid Hormone Levels

• Thyroid Antibodies

• Radioactive Iodine Uptake Test (RAIU)

Thyroid Function Tests - Serum Thyroid Hormone Levels

• Thyroxine (T4): This test measures the total or free levels of T4 in the blood. Elevated levels may indicate hyperthyroidism, while low levels suggest hypothyroidism.

• Triiodothyronine (T3): Similar to T4, this test assesses T3 levels. It is particularly useful in diagnosing hyperthyroidism, especially when T4 levels are normal.

• Thyroid-Stimulating Hormone (TSH): Produced by the anterior pituitary gland, TSH regulates thyroid hormone production. High TSH levels often indicate hypothyroidism (as the pituitary tries to stimulate the underactive thyroid), while low levels suggest hyperthyroidism.

Thyroid Function Tests - Thyroid Antibodies

• Thyroid Peroxidase Antibodies (TPOAb): Elevated levels can indicate autoimmune thyroid diseases such as Hashimoto's thyroiditis.

• Thyroglobulin Antibodies (TgAb): These antibodies can also be present in autoimmune conditions affecting the thyroid.

Radioactive Iodine Uptake Test (RAIU)/ Werner's test

Procedure

1. Preparation: Patients may need to avoid certain medications and foods that contain iodine before the test.

2. Administration: A small amount of radioactive iodine (I-123 or I-131) is administered orally.

3. Measurement: After a specified period (usually 6 hours and again at 24 hours), a gamma camera measures how much of the radioactive iodine has been absorbed by the thyroid gland.

Interpretation of Results

• Increased Uptake:

  • Indicates hyperthyroidism or conditions like Graves' disease, where the thyroid is overactive and absorbs more iodine.

• Decreased Uptake:

  • Suggests hypothyroidism or conditions such as thyroiditis, where the gland is less active and absorbs less iodine.

Clinical Significance

The RAIU test helps differentiate between various types of thyroid dysfunction:

• Hyperthyroidism: High uptake suggests conditions like Graves' disease or toxic nodular goiter.

• Hypothyroidism: Low uptake may indicate Hashimoto's thyroiditis or other forms of thyroid failure.

• Thyroid Nodules: If a nodule is present, RAIU can help determine if it is "hot" (functioning) or "cold" (non-functioning), which has implications for cancer risk.

Functional Anatomy of the Adrenal Glands

The adrenal glands are small, triangular-shaped glands located on top of each kidney. They are composed of two distinct regions, each responsible for producing different types of hormones:

• Adrenal Cortex: The outer layer of the adrenal gland, which is further divided into three zones:

  • Zona Glomerulosa: Produces mineralocorticoids (e.g., aldosterone).

  • Zona Fasciculata: Produces glucocorticoids (e.g., cortisol).

  • Zona Reticularis: Produces androgens (e.g., dehydroepiandrosterone [DHEA]).

• Adrenal Medulla: The inner part of the adrenal gland that functions as an endocrine organ and is primarily responsible for producing catecholamines (epinephrine and norepinephrine).

Hormones Released by the Adrenal Medulla

Epinephrine (Adrenaline):

• A major hormone involved in the body's "fight or flight" response.

• It is released in larger quantities than norepinephrine.

Norepinephrine (Noradrenaline):

• Functions similarly to epinephrine but has a slightly different role in the stress response.

Physiological Effects of Epinephrine and Norepinephrine

• Increased Heart Rate: Both hormones stimulate the heart, increasing cardiac output.

• Bronchodilation: They relax bronchial muscles, improving airflow to the lungs.

• Increased Blood Glucose Levels: They promote glycogenolysis (the breakdown of glycogen to glucose) in the liver, providing quick energy.

• Increased Blood Flow to Muscles: Blood vessels in skeletal muscles dilate, enhancing blood flow during physical activity.

• Decreased Blood Flow to Non-Essential Organs: Blood vessels in the digestive system constrict, redirecting blood flow to areas that need it more during stress.

Regulation of Secretion of Epinephrine and Norepinephrine

• Sympathetic Nervous System Activation: Stressful stimuli activate the sympathetic nervous system, leading to stimulation of the adrenal medulla.

• Hypothalamic Control: The hypothalamus releases corticotropin-releasing hormone (CRH), which indirectly influences adrenal medulla activity through its effects on the adrenal cortex.

Physiological Effects of Glucocorticoids - Cortisol

• Metabolic Effects:

  • Increases blood glucose levels by promoting gluconeogenesis (the formation of glucose from non-carbohydrate sources) in the liver.

  • Enhances protein catabolism and fat metabolism, providing energy during stress.

• Anti-inflammatory Effects:

  • Inhibits immune responses and reduces inflammation by suppressing the activity of immune cells.

• Stress Response:

  • Prepares the body to respond to stressors by mobilizing energy resources and modulating immune function.

Regulation of Secretion of Cortisol

• Adrenocorticotropic Hormone (ACTH): Released from the anterior pituitary gland in response to corticotropin-releasing hormone (CRH) from the hypothalamus. ACTH stimulates cortisol production in the adrenal cortex.

• Negative Feedback Mechanism: Elevated cortisol levels inhibit both CRH and ACTH secretion, maintaining hormone levels within a normal range.

Pharmacological Effects of Glucocorticoids

Glucocorticoids are commonly used in medicine for their anti-inflammatory and immunosuppressive properties. Some pharmacological effects include:

• Treatment of Inflammatory Conditions: Glucocorticoids are used to manage conditions such as asthma, arthritis, and allergic reactions due to their ability to reduce inflammation.

• Immunosuppression: They are used in organ transplantation to prevent rejection by suppressing immune responses.

• Hormonal Replacement Therapy: In cases of adrenal insufficiency (e.g., Addison's disease), glucocorticoids are administered to replace deficient hormones.

Physiological Effects of Mineralocorticoids - Aldosterone

Aldosterone plays a crucial role in regulating electrolyte balance and blood pressure:

• Sodium Retention: Aldosterone promotes sodium reabsorption in the kidneys, leading to increased blood volume and blood pressure.

• Potassium Excretion: It enhances potassium excretion into urine, helping maintain proper potassium levels in the body.

Regulation of Secretion of Aldosterone

• Renin-Angiotensin-Aldosterone System (RAAS): Low blood pressure or low sodium levels stimulate renin release from the kidneys, leading to a cascade that ultimately increases aldosterone secretion.

  • Renin = An enzyme secreted by the juxtaglomerular cells of the kidneys

  • Renin converts angiotensinogen (produced by the liver) into angiotensin I.

  • Angiotensin I = An inactive precursor that is converted to angiotensin II by the action of angiotensin-converting enzyme (ACE), primarily in the lungs.

  • Angiotensin II = A potent vasoconstrictor that increases blood pressure by constricting blood vessels. Stimulates the release of aldosterone from the adrenal cortex.

  • Aldosterone = A mineralocorticoid hormone produced by the adrenal glands

• Plasma Potassium Levels: Elevated potassium levels directly stimulate aldosterone release.

Functional Effects of Adrenal Sex Hormones

Adrenal sex hormones are produced mainly in the zona reticularis of the adrenal cortex and include androgens such as dehydroepiandrosterone (DHEA) and androstenedione.

• Development of Secondary Sexual Characteristics:

  • Androgens contribute to the development of male secondary sexual characteristics, such as increased muscle mass and body hair growth.

  • In females, they play a role in libido and can influence hair growth patterns.

• Precursor for Sex Steroids:

  • Adrenal androgens serve as precursors for sex hormones such as testosterone and estrogen, which are produced primarily in the testes and ovaries, respectively.

• Influence on Metabolism:

  • Adrenal sex hormones can affect fat distribution and muscle mass, contributing to overall metabolic health.

Regulation of Adrenal Sex Hormone Secretion

• Adrenocorticotropic Hormone (ACTH):

  • ACTH stimulates the zona reticularis to produce adrenal androgens. This regulation is less precise than that for glucocorticoids or mineralocorticoids but still plays a significant role.

• Feedback Mechanisms:

  • Levels of circulating sex hormones can influence ACTH secretion through negative feedback loops, although this feedback mechanism is more pronounced for gonadal hormones than for adrenal androgens.

Pathological Effects of Adrenal Cortex Disorders

Cushing's Syndrome

• caused by excessive cortisol production, which can result from adrenal tumors, pituitary adenomas (Cushing's disease), or ectopic ACTH production.

• Pathological Effects:

  • Obesity: Central obesity with a characteristic "moon face" and "buffalo hump."

  • Skin Changes: Thinning skin, easy bruising, and purple striae (stretch marks).

  • Metabolic Effects: Hyperglycemia (high blood sugar), insulin resistance, and increased risk of diabetes.

  • Muscle Weakness: Proximal muscle weakness due to protein catabolism.

  • Psychological Effects: Mood swings, depression, and cognitive difficulties.

Addison's Disease

• insufficient production of adrenal hormones, particularly cortisol and aldosterone, usually due to autoimmune destruction of the adrenal cortex.

• Pathological Effects:

  • Fatigue and Weakness: Chronic fatigue and muscle weakness due to low cortisol levels.

  • Weight Loss and Anorexia: Unintentional weight loss and decreased appetite.

  • Hypotension: Low blood pressure due to decreased aldosterone leading to sodium loss.

  • Hyperpigmentation: Darkening of the skin, particularly in areas exposed to sunlight, due to increased ACTH levels stimulating melanocyte activity.

  • Electrolyte Imbalance: Hyponatremia (low sodium) and hyperkalemia (high potassium) due to aldosterone deficiency.

Hyperaldosteronism (Conn's Syndrome)

• excessive secretion of aldosterone, often due to an adrenal adenoma or hyperplasia.

• Pathological Effects:

  • Hypertension: Elevated blood pressure due to increased sodium reabsorption and water retention.

  • Hypokalemia: Low potassium levels leading to muscle weakness, cramps, and arrhythmias.

  • Metabolic Alkalosis: Increased bicarbonate levels due to hydrogen ion loss.

Adrenal Insufficiency Can be primary (Addison's disease) or secondary (due to pituitary failure). Symptoms include fatigue, weakness, weight loss, low blood pressure, and electrolyte imbalances.

Adrenal Gland Tests

Thorn's Test

• Purpose: Thorn's test is used to evaluate the adrenal cortex's ability to respond to ACTH stimulation.

• Procedure:

  • A baseline cortisol level is measured.

  • ACTH is administered intravenously or intramuscularly.

  • Cortisol levels are measured again after a specified time (usually within one hour).

• Interpretation:

  • Normal response shows a significant increase in cortisol levels following ACTH administration.

  • In cases of adrenal insufficiency (e.g., Addison's disease), there will be little or no increase in cortisol levels.

Dexamethasone Suppression Test

• Purpose: This test assesses the feedback mechanism of cortisol regulation and helps diagnose Cushing's syndrome.

• Procedure:

  • Patients are given dexamethasone (a synthetic glucocorticoid) orally at night.

  • Serum cortisol levels are measured the following morning.

• Interpretation:

  • In healthy individuals, dexamethasone suppresses cortisol production, resulting in low morning cortisol levels.

  • In Cushing's syndrome, cortisol levels remain elevated despite dexamethasone administration.

Saline Suppression Test

• Purpose: This test evaluates the response of aldosterone secretion in patients suspected of having hyperaldosteronism.

• Procedure:

  • Patients receive intravenous saline infusion over a specified period (e.g., several hours).

  • Plasma aldosterone levels are measured before and after saline administration.

• Interpretation:

  • In normal individuals, saline infusion should suppress aldosterone secretion due to increased blood volume and sodium levels.

  • In primary hyperaldosteronism (Conn’s syndrome), aldosterone levels remain elevated despite saline infusion.

Endocrine Pancreas

• The endocrine pancreas is a critical component of the body's metabolic regulation, primarily through the secretion of hormones that control blood glucose levels.

• The pancreas has both exocrine (digestive enzymes) and endocrine functions.

• The endocrine part consists of clusters of cells known as islets of Langerhans, which contain several types of hormone-producing cells.

Hormones of the Endocrine Pancreas

• Insulin

• Glucagon

• Somatostatin

• Pancreatic Polypeptide

Source, Physiological Effects and Regulation of Secretion of Insulin

Source: Produced by beta cells in the islets of Langerhans.

Physiological Effects:

• Lowers blood glucose levels by promoting glucose uptake in cells, especially muscle and adipose tissue.

• Stimulates glycogenesis (conversion of glucose to glycogen) in the liver.

• Enhances fat storage by promoting lipogenesis and inhibiting lipolysis.

Regulation of Secretion:

• Secretion is stimulated by elevated blood glucose levels, certain amino acids, and gastrointestinal hormones (e.g., GLP-1).

• Inhibited by low blood glucose levels.

Source, Physiological Effects and Regulation of Secretion of Glucagon

• Source: Produced by alpha cells in the islets of Langerhans.

• Physiological Effects:

  • Increases blood glucose levels by promoting glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (production of glucose from non-carbohydrate sources) in the liver.

• Regulation of Secretion:

  • Secreted when blood glucose levels are low.

  • Stimulated by certain amino acids

  • Inhibited by insulin

Source, Physiological Effects and Regulation of Secretion of Somatostatin

• Source: Produced by delta cells in the islets of Langerhans.

• Physiological Effects: Inhibits the release of both insulin and glucagon, helping to regulate the overall balance between these hormones.

• Regulation of Secretion: Released in response to elevated blood glucose and amino acid levels.

Source, Physiological Effects and Regulation of Secretion of Pancreatic Polypeptide

• Source: Produced by PP cells in the islets of Langerhans.

• Physiological Effects: Regulates pancreatic secretions and gastrointestinal motility.

• Regulation of Secretion: Stimulated by protein-rich meals and fasting.

Disorders of the Endocrine Pancreas

• Diabetes Mellitus:

  • Type 1 Diabetes: An autoimmune disorder resulting in the destruction of beta cells, leading to little or no insulin production. Patients require insulin therapy.

  • Type 2 Diabetes: Characterized by insulin resistance and relative insulin deficiency. Management includes lifestyle changes, oral medications, and sometimes insulin.

• Hypoglycemia: Abnormally low blood glucose levels, which can occur due to excessive insulin production or administration, leading to symptoms like sweating, confusion, and fainting.

• Insulinomas: Rare tumors of the pancreas that secrete excess insulin, causing recurrent hypoglycemia.

Pancreas Function Tests

• Fasting Blood Glucose Test:

  • Measures blood sugar levels after fasting for at least 8 hours.

  • Normal range: 2.8-6.1 mol/L.

  • Levels of 100-125 mg/dL indicate prediabetes, while levels of 126 mg/dL or higher suggest diabetes.

• Hemoglobin A1c Test:

  • Reflects average blood glucose levels over the past 2-3 months.

  • Normal range: Below 5.7%.

  • Levels of 5.7% to 6.4% indicate prediabetes, while 6.5% or higher indicates diabetes.

• C-Peptide Test:

  • Measures the level of C-peptide, a byproduct of insulin production, to assess endogenous insulin secretion.

  • Useful in distinguishing between type 1 and type 2 diabetes.

• Oral Glucose Tolerance Test (OGTT):

  • A more comprehensive test for assessing glucose metabolism and insulin response.

Oral Glucose Tolerance Test (OGTT)

Procedure

1. Preparation:

   • Patients should fast overnight (at least 8 hours) before the test.

   • They should also avoid strenuous exercise and certain medications that can affect glucose metabolism prior to the test.

2. Initial Blood Sample:

   • A fasting blood sample is taken to measure baseline glucose levels.

3. Glucose Administration:

   • The patient is then given a standard glucose solution (usually containing 75 grams of glucose dissolved in water) to drink.

4. Subsequent Blood Samples:

   • Blood samples are taken at regular intervals, typically at 30 minutes, 1 hour, 2 hours, and sometimes up to 3 hours after consuming the glucose solution to measure blood glucose levels.

Interpretation of Results

• Normal Response:

  • Fasting glucose: Less than 100 mg/dL.

  • 2-hour post-glucose level: Less than 140 mg/dL.

• Prediabetes:

  • Fasting glucose: Between 100-125 mg/dL.

  • 2-hour post-glucose level: Between 140-199 mg/dL.

• Diabetes:

  • Fasting glucose: Greater than or equal to 126 mg/dL.

  • 2-hour post-glucose level: Greater than or equal to 200 mg/dL.

Clinical Significance

• Diagnosing gestational diabetes in pregnant women.

• Identifying insulin resistance and impaired glucose tolerance in individuals at risk for developing type 2 diabetes.

• Monitoring the effectiveness of dietary changes and medications in managing blood sugar levels in diabetic patients.

Blood Sugar Concentration - Capillary Blood - OGTT

Normal

• Fasting < 7 mmol/L

• 1 hr after intake < 11 mmol/L

• 2 hr after intake < 8 mmol/L

Lowered Glucose Tolerance

• Fasting < 7 mmol/L

• 2 hr after intake ≥ 8-11 mmol/L

Diabetes

• Fasting > 7 mmol/L

• 2 hr after intake ≥ 11 mmol/L

Key Hormones Involved in Calcium-Phosphorus Homeostasis

• Parathyroid Hormone (PTH)

• Calcitonin

• Calcitriol (Active Vitamin D)

Source, Physiological Effects and Regulation of Secretion of Parathyroid Hormone (PTH)

• Source: Secreted by the parathyroid glands.

• Physiological Effects:

  • Increases blood calcium levels by stimulating osteoclast activity (bone resorption), increasing renal tubular reabsorption of calcium, and promoting conversion of vitamin D to its active form (calcitriol).

  • Decreases phosphate reabsorption in the kidneys, leading to increased phosphate excretion.

• Regulation of Secretion: Secreted in response to low blood calcium levels; secretion decreases when calcium levels rise.

Source, Physiological Effects and Regulation of Secretion of Calcitonin

• Source: Produced by parafollicular cells (C cells) in the thyroid gland.

• Physiological Effects:

  • Lowers blood calcium levels by inhibiting osteoclast activity and promoting calcium deposition in bones.

  • Increases renal excretion of calcium and phosphate.

• Regulation of Secretion: Released in response to high blood calcium levels; its role is less critical compared to PTH.

Source, Physiological Effects and Regulation of Secretion of Calcitriol (Active Vitamin D)

• Source: Formed from vitamin D3 (cholecalciferol) through a series of conversions in the liver and kidneys.

• Physiological Effects:

  • Increases intestinal absorption of calcium and phosphate from food.

  • Works synergistically with PTH to mobilize calcium from bones.

• Regulation of Secretion: Stimulated by PTH and low serum calcium levels; inhibited when calcium levels are adequate.

Disorders of Calcium-Phosphorus Homeostasis

• Hyperparathyroidism: Excessive secretion of PTH leads to elevated blood calcium levels (hypercalcemia), which can cause bone loss, kidney stones, and neurological symptoms.

• Hypoparathyroidism: Insufficient PTH secretion results in low blood calcium levels (hypocalcemia), causing muscle cramps, spasms (tetany), and potentially life-threatening cardiac issues.

• Vitamin D Deficiency/Rickets/Osteomalacia: Insufficient vitamin D leads to impaired calcium absorption, resulting in weak bones in children (rickets) or adults (osteomalacia).

• Paget's Disease: A disorder characterized by abnormal bone remodeling due to excessive osteoclast activity often associated with increased PTH activity.

• Osteoporosis: A condition where decreased bone density occurs due to an imbalance between bone resorption and formation, often influenced by hormonal changes including PTH.

Male Reproductive System Functions

• primarily responsible for the production of sperm and the secretion of male hormones (androgens).

Spermatogenesis - Definition and Phases

Spermatogenesis is the process by which sperm cells are produced in the testes.

1. Spermatogonial Phase:

   • Begins with spermatogonia (germ cells) undergoing mitosis to produce primary spermatocytes.

2. Meiotic Phase:

   • Primary spermatocytes undergo meiosis to form secondary spermatocytes, which further divide to produce spermatids.

3. Spermiogenesis:

   • Spermatids undergo morphological changes to become mature spermatozoa. This includes the development of a flagellum and condensation of nuclear material.

The entire process takes approximately 74 days and occurs within the seminiferous tubules of the testes.

Hormonal Function of the Testicles

• Types of Androgens:

  • Testosterone is the primary androgen, but other androgens include dihydrotestosterone (DHT) and androstenedione.

• Physiological Functions:

  • Development of male secondary sexual characteristics (e.g., facial hair, deep voice).

  • Regulation of libido (sexual drive).

  • Promotion of spermatogenesis.

  • Maintenance of muscle mass and bone density.

• Regulation of Secretion:

  • Testosterone secretion is regulated by luteinizing hormone (LH) from the anterior pituitary, which stimulates Leydig cells in the testes.

  • Follicle-stimulating hormone (FSH) also plays a role by supporting spermatogenesis in conjunction with testosterone.

Erection

• Triggered by sexual arousal, leading to increased blood flow into the penis due to vasodilation.

• The release of nitric oxide (NO) in response to stimulation causes smooth muscle relaxation in penile arteries.

Ejaculation

• Involves two phases:

  • emission (movement of sperm into the urethra)

  • expulsion (forceful release through rhythmic contractions)

• This process is coordinated by both sympathetic and parasympathetic nervous systems.

• Number of sperm cells in an ejaculate > 60-106 ml/L

Female Reproductive System - Function

• responsible for producing ova (eggs)

• facilitating fertilization

• supporting foetal development during pregnancy

Oogenesis

Oogenesis is the process by which oocytes (egg cells) are produced in the ovaries:

1. Oocyte Development:

   • Begins before birth with oogonia developing into primary oocytes, which enter meiosis but pause until puberty.

   • At puberty, primary oocytes resume meiosis during each menstrual cycle, leading to secondary oocyte formation.

2. Ovulation:

   • The release of a mature secondary oocyte from the ovary occurs approximately every 28 days during the menstrual cycle.

Hormonal Function of the Ovaries

• Estrogens:

  • Types: Estradiol is the most potent form.

  • Physiological Functions:

    • Promote development of female secondary sexual characteristics.

    • Regulate menstrual cycle and prepare the endometrium for potential implantation.

  • Regulation of Secretion:

    • Stimulated by follicle-stimulating hormone (FSH) from the anterior pituitary.

• Progesterone:

  • Physiological Functions:

    • Prepares the endometrium for implantation after ovulation.

    • Maintains pregnancy by inhibiting uterine contractions.

  • Regulation of Secretion:

    • Secreted by the corpus luteum after ovulation; its levels drop if pregnancy does not occur, leading to menstruation.

Menstrual Cycle

The menstrual cycle typically lasts about 28 days (21-31) and consists of several phases:

1. Follicular Phase:

   • FSH stimulates follicle growth; estrogen levels rise as follicles mature.

2. Ovulatory Phase:

   • A surge in LH triggers ovulation, releasing a secondary oocyte.

3. Luteal Phase:

   • The corpus luteum forms from the ruptured follicle, secreting progesterone and estrogen. If fertilization does not occur, hormone levels drop, leading to menstruation.

   • Duration = 14 days

Menstrual bleeding 3-8 days (usually 4-5 days)

Pregnancy, Birth, and Lactation

• Pregnancy:

  • Begins with fertilization when a sperm cell successfully penetrates an ovum. The resulting zygote implants in the uterine wall.

• Birth:

  • Triggered by hormonal changes that initiate labor contractions; oxytocin plays a key role in stimulating uterine contractions during labor.

• Lactation:

  • Prolactin stimulates milk production in response to suckling, while oxytocin facilitates milk ejection from mammary glands.

Tests for Early Pregnancy

• Urine Tests: Detect human chorionic gonadotropin (hCG), a hormone produced shortly after implantation.

• Blood Tests: Measure hCG levels more accurately; can detect pregnancy earlier than urine tests.

Galli-Mainini Test

The Galli-Mainini test is a historical immunological test used for the early detection of pregnancy by identifying the presence of human chorionic gonadotropin (hCG) in a woman's urine or serum.

• The Galli-Mainini test is designed to detect hCG, a hormone produced by the placenta shortly after implantation of a fertilized egg in the uterus.

• A urine or blood sample is collected from the woman suspected of being pregnant.

• The test involves mixing the sample with specific reagents that react with hCG.

• Historically, this test utilized animal models (such as rabbits) where the urine was injected into the animal, and then the animal's physiological response was observed. If pregnancy was present, it would cause changes in the animal's ovaries (e.g., ovarian enlargement).

• A positive result indicates the presence of hCG and suggests that the woman is pregnant.

• A negative result indicates that hCG is not detectable, suggesting that the woman is not pregnant.

Immunological Tests - Pregnancy

Immunological tests are critical tools in diagnosing various diseases by detecting specific antibodies or antigens in biological samples.

• Urine Pregnancy Tests (Home Tests)

  • When urine is applied to the test strip, it interacts with these antibodies.

  • The woman collects a urine sample, typically using the first-morning urine for a higher concentration of hCG.

  • The sample is applied to a test strip or device.

  • If hCG is present, it binds to the antibodies on the strip, leading to a visible change (such as a color change or line appearing).

  • A positive result indicates pregnancy, while a negative result suggests that hCG is not detectable.

• Blood Pregnancy Tests:

  • Qualitative Blood Test: Similar to urine tests, this test determines whether hCG is present in the blood but does not measure its quantity.

  • Quantitative Blood Test (Beta hCG Test): This test measures the exact level of hCG in the blood and can provide more information about the pregnancy's status (e.g., confirming early pregnancy or monitoring for potential complications).

Clinical Significance of Immunological tests

• Diagnosing infectious diseases (e.g., viral, bacterial, parasitic).

• Identifying autoimmune disorders (e.g., lupus, rheumatoid arthritis).

• Evaluating immune deficiencies.

• Monitoring vaccine responses and immune status.

• Early Detection: These tests can detect pregnancy as early as a few days after a missed period for urine tests and even earlier with blood tests.

• Convenience: Home pregnancy tests are widely available and easy to use, providing quick results without needing medical supervision.

• Clinical Use: Blood tests are more sensitive and can be used in clinical settings to monitor pregnancies or diagnose potential issues such as ectopic pregnancies or miscarriages.

Epiphysis (Pineal Gland) with Glandular Effects

The epiphysis, commonly known as the pineal gland, is a small endocrine gland located in the brain. It plays a crucial role in regulating circadian rhythms and reproductive hormones.

• Hormone Produced:

  • Melatonin: The primary hormone secreted by the pineal gland, melatonin is synthesized from serotonin during the night.

• Physiological Effects:

  • Regulates sleep-wake cycles by promoting sleepiness in response to darkness.

  • Influences seasonal reproductive functions in some animals by modulating gonadal activity.

Thymus with Glandular Effects

The thymus is an organ located in the upper chest, playing a vital role in the immune system, particularly during childhood.

• Hormones Produced:

  • Thymosin, Thymopoietin, and other thymic hormones.

• Physiological Effects:

  • Stimulate the development and differentiation of T lymphocytes (T cells), which are crucial for adaptive immunity.

  • Promote immune responses and help establish self-tolerance to prevent autoimmune diseases.

Non-Endocrine Organs with Glandular Effects

Several non-endocrine organs also produce hormones or hormone-like substances that exert regulatory effects on various physiological processes:

1. Adipose Tissue:

   • Produces hormones such as leptin (regulates energy balance and appetite) and adiponectin (enhances insulin sensitivity).

2. Muscle Tissue:

   • Produces myokines like irisin, which promotes energy expenditure and glucose metabolism.

3. Gastrointestinal Tract:

   • Produces various hormones (e.g., gastrin, secretin, cholecystokinin) that regulate digestion, appetite, and metabolism.

Types of Tissue Hormones and their Effects

• Cytokines:

  • Small proteins released by cells that affect the behavior of other cells.

  • Effects: Involved in immune responses, inflammation, and cell signaling. Examples include interleukins and tumor necrosis factor (TNF).

• Eicosanoids:

  • Lipid-derived signaling molecules produced from arachidonic acid.

  • Effects: Regulate inflammation, pain response, blood pressure, and reproductive functions. Prostaglandins and leukotrienes are key examples.

• Growth Factors:

  • Proteins that stimulate cell growth, proliferation, and differentiation.

  • Effects: Play critical roles in wound healing and tissue repair. Examples include epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF).

• Myokines:

  • Hormones produced by muscle cells during contraction.

  • Effects: Influence metabolism and insulin sensitivity; examples include irisin.

• Adipokines:

  • Hormones secreted by adipose tissue.

  • Effects: Regulate energy metabolism and inflammation; examples include leptin and adiponectin.

Summary of Effects of Tissue Hormones

• They can influence local cellular activities (autocrine signaling) or affect nearby cells (paracrine signaling).

• They play essential roles in regulating metabolism, immune responses, inflammation, tissue repair, and overall homeostasis.

• Dysregulation of these hormones can contribute to various diseases, including obesity, diabetes, cardiovascular diseases, and autoimmune disorders.

Define Normoglycemia

A state of normal blood glucose levels, typically defined as fasting plasma glucose levels between 2.8-6.1mmol/L.

Define Hyperglycemia

Elevated blood glucose levels, defined as fasting plasma glucose levels greater than 11 mmol/L

Define Hypoglycemia

Abnormally low blood glucose levels, generally recognized as blood glucose levels below 2.3mmol/L

Define Glucosuria

The presence of glucose in the urine, often occurring when blood glucose levels exceed the renal threshold for glucose reabsorption.

Define Hyperpituitarism

An overproduction of hormones from the pituitary gland, often due to a pituitary adenoma.

Define Acromegaly

A disorder resulting from excess growth hormone in adulthood, characterized by enlarged bones and tissues, particularly in the hands, feet, and face.

Define Pituitary Gigantism

Excess growth hormone secretion during childhood or adolescence, leading to excessive growth and height.

Define Hypopituitarism

A condition where the pituitary gland fails to produce one or more of its hormones or does not produce enough of them.

Define Pituitary Nanism (Dwarfism)

A form of dwarfism caused by insufficient growth hormone production during childhood.

Define Hyperglucocorticism

An excess of glucocorticoids (such as cortisol) in the body, often due to Cushing’s syndrome.

Define Hypocortisism

A deficiency of cortisol production, commonly associated with Addison’s disease.

Define Hyperthyroidism

An overactive thyroid condition resulting in excessive production of thyroid hormones, leading to increased metabolism.

Define Thyrotoxicosis

A clinical syndrome resulting from elevated levels of thyroid hormones in the body, which can occur in hyperthyroidism or from other causes.

Define Hypothyroidism

A condition characterized by insufficient production of thyroid hormones, leading to a reduced metabolic rate.

Define Myxoedema

A severe form of hypothyroidism in adults characterized by swelling of the skin and underlying tissues due to accumulation of mucopolysaccharides.

Define Goiter

An enlargement of the thyroid gland that can occur with both hyperthyroidism and hypothyroidism due to various causes, including iodine deficiency.

Define Hyperinsulinism

An excessive secretion of insulin, often leading to hypoglycemia and associated with conditions such as insulinomas or reactive hypoglycemia.

Define Diabetes Mellitus

A group of metabolic disorders characterized by chronic hyperglycemia due to defects in insulin secretion, insulin action, or both.

Define Diabetes Insipidus

A condition characterized by excessive thirst and excretion of large amounts of dilute urine due to insufficient production of antidiuretic hormone (ADH).

Define Normospermia

A condition where sperm count is within normal limits; typically defined as having more than 15 million sperm per milliliter of semen.

Define Oligospermia

A condition characterized by a lower than normal sperm count in semen; defined as fewer than 15 million sperm per milliliter.

Define Menstruation

The monthly shedding of the uterine lining (endometrium) when pregnancy does not occur; typically lasts 3 to 7 days.

Define Ovulation

The release of a mature ovum (egg) from the ovary, occurring approximately midway through the menstrual cycle.

Define Dysmenorrhea

Painful menstruation that can interfere with daily activities; may be primary (without underlying conditions) or secondary (due to conditions like endometriosis).