lecture 9: endocrine system

Biomedicine: Human Sciences

Lecture 9:

Endocrine System

Learning Outcomes

In today’s topic you will learn:

⮚ The structure and function of

the endocrine system.

⮚ The clinical presentations,

investigation procedures and

some orthodox treatments of

endocrine pathologies.

Endocrine System

The endocrine system coordinates the activity of organs through hormones — chemical messengers released into the blood from glands which produce them.

• Hormones have specific target cells, some far from where the hormone is produced, others affect cells of the same organ where they were released, or the same cell.

• Hormones can be:

1. Peptides (proteins — water soluble): i.e, insulin.

2. Steroids: sex hormones; e.g. oestrogen.

3. Amino acid derivatives: adrenaline, thyroxine.

Homeostasis

Two control systems ensure our survival by controlling

homeostasis in two different ways.

AUTONOMIC NERVOUS SYSTEM	ENDOCRINE SYSTEM
Rapid change.	Slower change.
Less precise.	More precise.
Shorter duration.	Longer duration.
Neurotransmitters.	Hormones.
Control centre: Central nervous system.	Control centre: Hypothalamus.

Glands

There are two types of glands:

1. EXOCRINE

• Excrete products into ducts leading to

body cavities / organ / skin.

• Examples: Salivary glands (saliva), gastric

glands (digestive enzymes), mammary glands.

2. ENDOCRINE

• Ductless, secreting hormones directly into

the blood.

• Examples: Pituitary, adrenals, thyroid.

Exocrine and Endocrine Glands

Endocrine = hormones

_{secreted into blood}Exocrine = via a duct

Glands

Endocrine glands include:

• Hypothalamus (neuroendocrine gland).

• Pituitary (glandular and neuroendocrine).

• Pineal.

• Thyroid.

• Parathyroid.

• Adrenal.

• Pancreatic: islets of Langerhans.

• Thymus.

• Ovaries.

• Testes.

Endocrine Tissues

Some tissues of the body are not considered glands but have endocrine function (produce hormones):

• Adipose tissue — leptin (suppresses food intake) and resistin (blood glucose).

• Heart — atrial natriuretic peptide (blood pressure).

• GIT — stomach: ghrelin and gastrin (satiety and gastric emptying). • Liver — angiotensinogen, insulin-like growth factor (IGF), thrombopoietin.

• Placenta — human chorionic gonadotropin (hCG) and progesterone. • Kidneys — erythropoietin (RBC production) and calcitriol (vit. D). • Skin — cholecalciferol (vit. D).

Hormone Activity: Receptors

Hormones have specific target cells.

• They influence the activity of the target

cells by binding to specific receptors.

• The receptors for protein-based

hormones are part of the cell

membrane, whilst lipid hormone

receptors are within the cell.

• Receptors can be made up of

a number of different proteins.

• Receptors allow hormones to

have a stimulating or inhibitory

effect on different cell types.

Hormones

The target cells can alter their sensitivity to the hormone:

Down-regulation:	Up-regulation:
• If a hormone is present in excess, the number of target cell receptors may decrease.	• A deficiency in hormone causes an increase in the number of receptors on target cells.
• Example: Hormones increase during puberty.	• Example: Increased number of oxytocin receptors in third trimester of pregnancy.

Hormone Regulation

Hormone secretions are regulated by:

1. Nervous system signals.

2. Chemical changes in the blood.

3. Other hormones.

• Hormones interact to allow maximum

flexibility in response to the

environment.

• They are controlled through positive

and negative feedback loops.

Endocrine System Control

The pituitary gland is often named the

master endocrine gland as it controls

many of the other endocrine glands in

the body. It is itself regulated (signalled)

by the hypothalamus.

• The pituitary gland has an anterior and

posterior region.

• The hypothalamus and pituitary glands represent the major link between nervous and endocrine systems.

• Together they control almost entirely: growth, development, metabolism and homeostasis.

Hypothalamus

Pituitary Gland

thermo = temperature regulatory = regulation

Hypothalamus

Releasing Hormones:

TRH

Thyrotrophin releasing hormone

GHRH

Growth hormone releasing hormone

CRH

Corticotropin releasing hormone

PRH

Prolactin releasing hormone

GnRH

Gonadotropin releasing

hormone

Inhibiting Hormones:

GHIH

Growth hormone inhibiting hormone

PIH

Prolactin inhibiting hormone (Dopamine)

Pituitary gland

Posterior

• Hormones are

synthesised in the

hypothalamus.

• Receives nerve impulses from the hypothalamus. • Releases these hormones: • Oxytocin

• Antidiuretic hormone (ADH)

The hypothalamus and pituitary gland are connected by a stalk of nerve fibres and network of

Anterior

• Receives seven hormones in capillaries from hypothalamus. • Synthesises and releases: 1. Growth hormone (GH).

2. Thyroid stimulating hormone (TSH)

3. Follicle stimulating hormone (FSH).

4. Luteinising hormone (LH). 5. Prolactin (PRL).

6. Adrenocorticotropic hormone (ACTH).

7. Melanocyte stimulating hormone (MSH).

capillaries. ₁₄© CNM: Human Sciences – Endocrine System. BQ/JD

Hypothalamus and

Anterior Pituitary Hormones

TRH

Thyrotrophin releasing hormone

GHRH

Growth hormone releasing

hormone

GHIH

Growth hormone inhibiting

hormone

CRH

Corticotropin releasing hormone

MSH

PRH

Prolactin

releasing hormone

PIH

Prolactin

inhibiting hormone (Dopamine)

GnRH

Gonadotropin releasing

hormone

FSH

_GHTSH ^ACTHPROLACTIN

Table of Hypothalamic and Anterior Pituitary

Hormones:

Hypothalamic Hormone/s	Anterior Pituitary Hormone	Target tissue
GHRH / GHIH	GH	Most body tissues
TRH	TSH	Thyroid Gland
CRH	ACTH MSH	Adrenal Cortex Skin
PRH / PIH	PRL	Breasts
GnRH	FSH	Ovaries and Testes
GnRH	LH	Ovaries and Testes

Growth Hormone (GH)

ACTIVITY:

1. Regulates metabolism in many organs.

2. Stimulates release of insulin-like

growth factors (IGFs) in cells.

3. Promotes growth and division of most

body cells (especially bone and muscle).

4. Breaks down fats and glycogen.

INCREASED PRODUCTION:

• Night-time (sleep — stage three, four).

• Hypoglycaemia.

• Exercise.

• Childhood and adolescence.

hypo = low

glycaemia = blood sugar

Thyroid Stimulating Hormone (TSH) ACTIVITY:

1. Growth and activity of the thyroid gland: Increasing thyroid hormone production — thyroxine (T₄^{) and tri}iodothyronine (T₃).

PRODUCTION:

• Lowest levels in the early evening and highest during the night.

The thyroid gland:

Adrenocorticotropic Hormone (ACTH)

ACTIVITY:

1. Output of steroid hormones:

Glucocorticoids, especially cortisol.

2. Circadian rhythm (sleep / wake cycle).

INCREASED PRODUCTION:

• Hypoglycaemia.

• Exercise.

• Stressors such as emotions, fever. • Interleukin-1 (inflammatory

response to infection).

PRODUCTION:

• Highest in the morning and lowest at midnight.

circadian

rhythms =

biological

processes

that follow a 24-hour cycle

Prolactin (PRL)

ACTIVITY:

1. Stimulates lactation:

Prolactin + oxytocin = lactation.

2. Prevents pregnancy during lactation (inhibits GnRH).

3. Breast maturation after childbirth. Matures mammary glands in pregnancy.

PRODUCTION:

• After birth (delivery of placenta).

pro = produce -lactin = ‘lactation’

• Suckling: the more milk removed, the more produced. • Emotional stress.

• Sleep.

Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)

• FSH:

• Production of gametes (sex cells)

in males and females.

• Increases oestrogen production (F).

• Stimulates testosterone production (M).

• LH

• Triggers ovulation and formation of the

corpus luteum in females.

• Increases secretion of progesterone (F).

• Stimulates secretion of testosterone (M).

corpus luteum = a hormone secreting structure that develops in an ovary following ovulation

FSH and LH are covered further in semester II

Melanocyte Stimulating Hormone (MSH)

Produced by the anterior pituitary in response to UV light.

• Stimulated by corticotropin releasing hormone (CRH) — released from

hypothalamus. So MSH and ACTH

share CRH as their precursor hormone. • Role in skin, hair and eye pigmentation in humans.

• Can be excessively produced as part of some

melanin = skin pigment -cyte = cell

pathologies, such as the hyperpigmentation of skin seen in Addison’s disease.

Oxytocin

oxy = Greek for sharp

POSTERIOR PITUITARY

ACTIVITY:

1. Contracts uterus in childbirth (parturition). 2. Contracts lactating breast.

3. Bonding hormone (mother with baby): Social bonding, trust, skin contact, cuddle hormone.

PRODUCTION:

• Suckling.

• Childbirth (positive feedback).

• Emotional state: Fear or anxiety may

tocos = Greek for labour

inhibit release of oxytocin or milk let-down. Emotions can trigger oxytocin — just hearing baby’s cry can start lactation.

Oxytocin

POSTERIOR PITUITARY

• Two weeks before birth, the baby descends

to the bottom of the uterus (womb).

• The head engages with the wall of the cervix.

• Sensory neurons act as pressure receptors

and when stretched send signals to the

hypothalamus.

• Oxytocin is released into the bloodstream.

• Oxytocin causes more forceful contraction of

the uterus.

• Baby’s head engages head of cervix /

pressure receptors … positive feed-forward

cycle that builds up momentum.

Lactation:

It takes two–three days for milk

production to begin.

• The first breast fluid produced is

called colostrum, which contains

water, lacto-sugar and antibodies.

• Colostrum acts as a laxative to

encourage a bowel movement. This

is important to remove bilirubin and

wastes that have accumulated in the

foetal intestines.

Antidiuretic Hormone (ADH)

POSTERIOR PITUITARY

Hypothalamus monitors concentration of body fluid.

ACTIVITY:

1. Reduces urine output by stimulating reabsorption of water in the kidneys. 2. Vasoconstriction in skin and abdominal organs to increase blood pressure.

PRODUCTION:

• Increased osmotic pressure, hypovolaemia (reduced fluid intake, thirst, vomiting). INHIBITION:

• Reduced osmotic pressure, increased fluid intake, alcohol.

anti = against

diuresis = urination

hypo = low

volaemia = blood volume

Antidiuretic

Hormone (ADH):

• ADH acts on the kidneys to prevent

the loss of water into urine.

• Ultimately, the actions of ADH will

increase blood pressure.

Exercise:

Fill in the blanks …

________ releasing hormone

_________ inhibiting hormone

CRH:

Corticotropin releasing

hormone

PRH:

Prolactin

releasing

hormone

PIH:

Prolactin inhibiting hormone a.k.a. ___________

GRH:

Gonadotropin releasing

hormone

hGH PROLACTIN

Summary Quiz:

1. How do cells alter their sensitivity to a hormone?

2. Define what is meant by a hormone.

3. Where are the hormones secreted by the posterior pituitary gland produced? What are the names of these TWO hormones? 4. Compare the TWO types of glands found in the body. 5. What hormone stimulates the release of FSH and LH from the anterior pituitary gland?

6. What is the target tissue of the hormone prolactin?

7. Give THREE functions of the hormone oxytocin.

8. How does ADH prevent the loss of fluid in the body?

9. Name the precursor hormone shared by both ACTH and MSH. 10.Where is thyroid stimulating hormone (TSH) released from?

Pituitary Gland Pathologies

Pituitary gland pathologies are

typically associated with tumours

or autoimmune diseases.

• These disease processes can result

in either hyper- or hypo-secretion of

certain pituitary hormones.

• The signs and symptoms expressed

ultimately depend on the hormones

affected.

Acromegaly and Gigantism

• Gigantism: Excess growth hormone while the bones are still developing — results in the person growing to massive heights.

• Acromegaly: Excess growth hormone post puberty (after growth plates closed). Patient grows outwards as opposed to upwards. CAUSE:

acro- = extreme

-megaly = enlargement

• A pituitary tumour hyper-secreting growth hormone. SIGNS AND SYMPTOMS:

• Large, prominent facial features, increased size

hands and feet.

• Tiredness, deep voice, impotence, joint pain,

bone deformities, soft-tissue swellings.

Acromegaly and Gigantism

Observe the following timeline. What do you notice?

Acromegaly and Gigantism

TREATMENT:

• Surgery to remove tumour. Life-long medications may be needed.

ALTERNATIVE APPROACH:

• Treat / support cause. Nutrition, herbs, homeopathy, acupuncture.

COMPLICATIONS:

• Hypertension, cardiomegaly.

• Type 2 diabetes (growth hormone 🡹 blood glucose levels 🡪 insulin resistance). • Osteoarthritis, vertebral collapse (back pain). • Bowel polyps.

GH affects

almost every

organ system of the body…

Hyperprolactinaemia

Excessive prolactin production. CAUSES:

• Pituitary tumour, acromegaly, pharmacologic (antipsychotics). SIGNS AND SYMPTOMS:

• Galactorrhoea.

• Amenorrhoea (absence of menses — because prolactin inhibits GnRH). • Decreased libido / sexual dysfunction. • Subfertility.

ALTERNATIVE SUPPORT:

hyper = elevated

prolactinaemia = prolactin in blood

Galactorrhoea:

Flow of milk from

breast not associated

with childbirth

• Treat / support the cause. Herbs can help balance hormone levels. Nutrition, acupuncture, homeopathy.

Diabetes Insipidus

Deficiency of ADH production or recognition causing the kidneys to over-excrete water. CAUSES:

• Cranial: Brain trauma, tumour, encephalitis. • Renal (kidney): Chronic kidney disease,

diabetes = disease causing excess thirst and urination

Insipid = ‘bland’

hypercalcaemia and hypokalaemia damages kidney. SIGNS AND SYMPTOMS:

• Polydipsia (extreme thirst) — large consumption.

• Polyuria: Excess urine production (dilute). • Weight loss.

• 🡻 BP, syncope (fainting due to hypovolaemia). © CNM: Human Sciences – Endocrine System. BQ/JD

hypo = low

-kalaemia = potassium polyuria = increased urination

Diabetes Insipidus

DIAGNOSIS:

• 24-hr urine collection (quantity of urine

measured over 24 hours).

• Urine-specific gravity — low

(i.e. urine is more diluted than normal).

• Blood biochemistry (🡹Na).

TREATMENT:

• Treat cause.

• ADH replacement.

• Rehydration: Water and electrolytes.

• Alternative: Homeopathy, acupuncture.

Pineal Gland: Melatonin

The pineal gland is a small pea-sized gland in the midline of the brain that produces melatonin.

• Specialised photoreceptors in the retina detect light /

darkness cues.

• Levels are highest in children and decline with age. • Stimulated by: Night, darkness (retinal feedback). • Reduced by: Daylight, irregular sleep patterns (jetlag, night-shifts).

ACTIVITY:

• Setting of the circadian rhythm:

Metabolic, physiological and behavioural alterations that follow a 24-hour rhythm.

• A potent antioxidant, DNA protective.

Made from

‘serotonin’.

Thymus Gland: Thymosin

The thymus is a bi-lobed gland, located

behind the sternum, which plays an

important role in immune development.

• The thymus atrophies after puberty and

is replaced by fibrous tissue.

ACTIVITY:

• Hormones produced by the thymus

promote the maturation of T-Lymphocytes.

•

• Immature T-cells migrate from the red bone

marrow to the cortex of the thymus. Mature

T-lymphocytes then migrate to the lymphatic system.

Thyroid Gland

A butterfly-shaped gland that is inferior to the larynx and located either side of the trachea.

• Influences metabolic rate (catabolic + anabolic) and is an important ‘growth hormone’ in early life. • Follicular cells produce thyroid hormones:

• Thyroxine (T₄) — has four iodine atoms.

• Triiodothyronine (T₃) — has three iodine atoms. • T₄and T₃are synthesised from tyrosine and iodine from a specialised thyroid protein called thyroglobulin (Tg).

• Follicular cells trap and store most of the body’s iodide via active transport from blood to cytosol.

Iodine atoms 39

Thyroid Gland Histology

Thyroid follicular cells trap and

store iodine.

• Parafollicular cells (lie between

follicles) secrete the hormone

calcitonin, which functions to

lower blood calcium levels.

• The follicles are filled with a

fluid known as colloid that

contains thyroglobulin.

Thyroid Hormones

The major form of thyroid hormone in the blood

is thyroxine (ratio of T₄to T₃is approx. 20:1).

• Selenium-containing enzymes are used in the conversion of T₄to T₃. Zinc is also needed for this.

• T₃is the more biologically active form:

Three-four times more potent than T_4.

• This allows the body to maintain a stable

pool of thyroid hormones from which the

active, free hormones can be released as

required.

• Thyroid hormone levels are measured in terms of free T₄and T₃. • Most body cells have receptors for thyroid hormones.

Thyroid Hormones

ACTIVITY:

• Increase metabolic rate and heat production.

• Essential for normal growth and

development and CNS function.

• Work in conjunction with adrenaline and

noradrenaline, insulin and growth hormone.

PRODUCTION:

• Stimulated by: TSH, exercise, stress,

malnutrition, low blood glucose, low T₃to T₄.

• Reduced by: Low TSH, high T₃.

• Highest levels at night.

• Higher levels during adolescence,

pregnancy and female reproductive years.

Low blood glucose,

stress, exercise, sleep,

malnutrition

Thyroid

Hormones:

TSH is usually low in a

regularly

functioning

thyroid

Raised TSH

levels indicate the thyroid is failing

Thyroid Hormones

LAB TESTING:

1. TSH Levels (measure in the morning as

it is the highest and most reliable /

consistent value).

2. Free T₃and T₄— unbound form of thyroid

hormones are more bioavailable to

target cells and tissues.

3. Thyroglobulin (‘Tg’) — levels in the

blood can be used as a tumour marker

for certain kinds of thyroid cancer.

4. Anti-thyroglobulin antibodies(TgAb) —

often found in patients with autoimmune

thyroid disease (Hashimoto's or Graves’).

Hypothyroidism

A condition of thyroid hormone deficiency (an underactive thyroid).

SYMPTOMS:

• Tiredness, malaise, weight gain, cold intolerance, constipation, depression.

hypo = low

thyroid = thyroid hormone

• Slow cognition, poor memory, low libido, deep voice, menstrual changes, muscle aches, arthralgia.

SIGNS:

• Goitre, dry, brittle skin, thin hair, loss of eyebrows.

• Myxoedema (swelling) often around the eyes

(deposition of polysaccharides which attract water).

• Physical exam: Slow tendon reflexes, bradycardia. • Blood tests: High TSH, low thyroid hormones.

Hypothyroidism

CAUSES:

• Hashimoto’s thyroiditis (autoimmune).

• Iodine deficiency, thyroid destruction

(radioactive iodine, surgery, medications,

tumour), fluoride.

ALLOPATHIC TREATMENT:

• Levothyroxine — thyroid hormone replacement.

NATURAL TREATMENT:

• Treat the cause.

• Thyroid support: Iodine, selenium, tyrosine, zinc,

glandular thyroid.

• Herbs; e.g. withania; homeopathy and exercise.

Hyperthyroidism (Graves’ Disease)

Hyperthyroidism is characterised by hyper-metabolism and elevated serum levels of free thyroid hormones (also known as thyrotoxicosis). • More common in women (10:1). CAUSES:

• Graves’ disease (85%): Autoimmune. Increased IgG antibodies bind to TSH receptor and stimulate

production of thyroid hormones. • Excessive iodine supplementation. • Tumour (hypothalamic, pituitary).

hyper = elevated

thyroid = thyroid hormone

Hyperthyroidism (Graves’ Disease)

SIGNS AND SYMPTOMS:

• Nervousness, irritability, hyperactivity, unexplained

weight loss.

• Insomnia, palpitations, muscle weakness, frequent bowel and bladder movements, diarrhoea, fatigue. • Heat sensitivity, increased sweating.

• Signs: Goitre, exophthalmos, tachycardia, tremor, brisk tendon reflexes, lid lag (von Gräfe’s sign). TREATMENT:

• Allopathic: Carbimazole, radioactive iodine,

Exophthalmos:

β-blockers, surgery.

• Alternative: Treat cause. In Graves’ disease

exo- = external opthalmos = eye

herbs and nutritional supplements to restore immune system balance (antioxidants); homeopathy.

Thyroid Gland: Calcitonin

Produced by the parafollicular cells of the

thyroid gland.

• Important during childhood for bone growth.

• Lowers blood calcium by:

1. Inhibiting calcium reabsorption from the

bone and kidneys.

2. Inhibiting osteoclast activity

(opposes parathyroid).

PRODUCTION:

• Stimulated by: Increased blood calcium

levels.

• Inhibited by: Reduced blood calcium levels.

Parathyroid Glands

The parathyroid glands

consist of four small glands.

• They are partially embedded

in the posterior surface of the

lateral lobes of the thyroid.

• Produce parathyroid

hormones.

Parathyroid Hormone (PTH)

Parathyroid hormone increases

blood calcium by:

1. Increasing osteoclast activity.

2. Increasing kidney reabsorption of

calcium and magnesium.

3. Increasing production of calcitriol

which increases calcium absorption

in the GIT.

• PTH release is stimulated by reduced

blood calcium levels and inhibited by

increased blood calcium levels.

• Calcium is essential for muscle contraction,

nerve transmission, blood clotting.

Hyperparathyroidism

Hyperparathyroidism is characterised by elevated blood levels of parathyroid hormone and improper calcium regulation. CAUSES:

• Usually a tumour of the parathyroid gland. SIGNS AND SYMPTOMS:

• Often no / few symptoms.

• Hypercalcaemia 🡪 increased risk of kidney stones, osteoporosis (or osteopenia), low energy, depression.

• In some cases: Nausea, vomiting, constipation, anorexia, muscle paralysis.

hyper = elevated

parathyroid =

parathyroid hormone 52

Hypoparathyroidism

Hypoparathyroidism is characterised by hypo-metabolism and reduced serum levels of parathyroid hormone (PTH).

CAUSES:

• Usually surgery or radiation (treating thyroid).

SIGNS AND SYMPTOMS:

• Hypocalcaemia 🡪 muscle cramps and spasms (tetany), tingling lips, fingers and toes, dry hair, brittle nails, dry scaly skin, cataracts, weakened tooth enamel (in children).

hypo = low

parathyroid =

parathyroid hormone 53

Summary Quiz:

1. Name the hormone that is deficient in diabetes insipidus. 2. What does the number next to the T₄and T₃reflect?

3. Name the thyroid hormone that is the more active form. 4. What do parafollicular cells produce?

5. List FOUR symptoms of hypothyroidism.

6. State TWO signs of hyperthyroidism.

7. Name TWO ways in which parathyroid hormone increases blood calcium

8. State TWO causes of hypoparathyroidism.

9. What is the effect of hypoparathyroidism on muscles? 10.What effect might hyperparathyroidism have on bone?

Adrenal Glands

The adrenals are paired glands superior

to the kidneys. Divided into the:

1. Medulla (inner): Part of the autonomic NS,

producing:

• Adrenaline (epinephrine).

• Noradrenaline (norepinephrine).

• Dopamine.

2. Cortex (outer): Produces three groups

of steroid hormones:

• Glucocorticoids (mostly cortisol).

• Mineralocorticoids (mostly aldosterone).

• Sex hormones (mostly androgens).

Adrenaline and Noradrenaline

Adrenaline (80%) and noradrenaline (20%)

are produced by the adrenal medulla.

• They both intensify the sympathetic response.

• Released by chromaffin cells (quick release

because innervated directly by sympathetic NS).

• Adrenaline has greater influence on the heart.

Noradrenaline affects blood vessels.

• Stimulated by: Exercise, fasting, shock,

elevated temperature, infection, disease,

emotional stress, caffeine.

• Inhibited by: Eating, sleeping, calmness,

diaphragmatic breathing.

Adrenaline and Noradrenaline

Adrenaline binds to receptors on the:

1. Heart: Increases heart rate and

contraction causing an increase in

blood pressure.

2. Vessels: Vasodilation in heart,

brain, skeletal muscles.

Vasoconstriction in digestive tract.

3. Thyroid: Increases metabolism.

4. Skeletal muscle / liver: Increases

blood glucose and triglycerides

(for metabolism)

5. Nervous system: Dilate pupils.

Glucocorticoids

Steroid hormones produced in the adrenal cortex which regulate metabolism and resistance to stress.

• This is mostly cortisol.

ACTIVITY:

1. Stimulating gluconeogenesis. 2. Proteolysis (amino acids from protein). 3. Lipolysis.

4. Production of glucose by the liver.

gluco- = glucose cortico- = cortex -oid = steroid

5. Reduces immune response (and tissue repair).

6. Anti-inflammatory — hence therapeutic use of steroids. 7. Weak reabsorption of sodium and water from kidney tubules.

Mineralocorticoids

Primarily aldosterone — maintains water and electrolyte balance.

ACTIVITY:

1. Reabsorption of sodium in kidneys. 2. Causes retention of water in the kidneys to increase blood volume and blood pressure. 3. Excretion of potassium in urine.

• Stimulated by: 🡻 BP or blood volume (dehydration, haemorrhage) and high blood potassium stimulates the renin-angiotensin aldosterone pathway (RAAS).

• Inhibited by: Low blood potassium. © CNM: Human Sciences – Endocrine System. BQ/JD

mineral = i.e.

Sodium/potassium cortico- = cortex -oid = steroid

Sex Hormones

Primarily androgens in the form of dehydroepiandrosterone (DHEA).

ACTIVITY:

1. Production of pubic and axillary hair. 2. Growth: Increases muscle mass.

3. Converted to testosterone then oestrogen (in females 🡪 promotes libido).

PRODUCTION:

• Stimulated by CRH 🡪 ACTH

• Cortical androgens are insignificant compared to amount produced in the ovaries and testes during puberty and adulthood.

androgens = male sex hormones

Cushing Syndrome

A rare disorder characterised by prolonged

exposure to abnormally high levels of cortisol

(hypercortisolaemia).

• Most commonly affects adults between 25 and 40

• Ex

years old, although can affect children.

CAUSES:

1. Corticosteroid medication: e.g., prednisolone

2. Adrenal Adenoma: Benign or malignant tumours

3. Pituitary Tumour: Excess production of ACTH

causing excess glucocorticoid production from the

adrenal cortex.

Cushing Syndrome

SIGNS AND SYMPTOMS:

• Central weight gain, moon face, buffalo hump, insulin resistance.

• Depression, insomnia, psychosis, poor libido, hirsutism, amenorrhoea (also releases some androgens).

• Easy bruising, thin skin, abdominal stretch marks (due to protein taken

from collagen and lowered immunity). • Reduced immunity.

• Muscular weakness, back pain.

• Bone fractures, osteoporosis.

• Hypertension.

hirsutism = excessive ‘male pattern’ hair growth

Cushing Syndrome

TREATMENT:

• Drugs inhibiting cortisol

production, surgery (for tumours).

NATURAL SUPPORT:

• Treat cause with herbs,

homeopathy and nutritional

supplements if indicated.

COMPLICATIONS:

• Lowered immunity, fragile skin,

bone fractures, diabetes mellitus.

Addison’s Disease

Adrenal insufficiency: Hypo-functioning of

the adrenal cortex causing a deficiency of

mineralocorticoids and glucocorticoids.

CAUSES:

• Atrophy of the adrenal gland (often autoimmune) (85%). • Secondary to a disease or abrupt cessation of steroids.

SIGNS AND SYMPTOMS:

• Weakness, fatigue and hypotension.

• Hyperpigmentation of skin and mucous membranes.

• Diarrhoea, weight loss, anorexia, malaise, muscle

weakness, depression, increased thirst.

• Impotence / amenorrhoea, nausea / vomiting.

Addison’s Disease

• Adrenal failure leads to lack of adrenal hormone production and a failure of the normal negative feedback mechanism. • The hypothalamus produces an excess of corticotrophin releasing hormone (CRH), which causes the pituitary to

erroneously produce melanocyte stimulating hormone.

• This causes the skin colour to darken, hence hyperpigmentation.

Addisonian Crisis:

• A complication of Addison's disease when the individual has no capacity to cope with stress (e.g. psychological, infection etc.) SIGNS AND SYMPTOMS:

• Severe lethargy and low blood pressure (low sodium). • Hypoglycaemic, syncope (fainting).

• Severe pain, renal failure, fever.

Pancreas

The pancreas has both an

endocrine and exocrine function.

• Endocrine function is via the cells

called the islets of Langerhans.

The pancreas contains different types of

endocrine cells including:

1. Alpha cells: Produce glucagon.

2. Beta cells: Produce insulin.

• Main endocrine function of the pancreas is to regulate blood glucose levels and maintain within normal range (4-7 mmol/L).

Islet = an ‘island’ of tissue structurally

distinct from

surrounding tissues 66

Pancreas: Insulin

Lowers blood glucose levels, amino acids and

fatty acids by:

1. Stimulating cells to uptake glucose from blood.

2. Promoting synthesis of proteins, glycogen

(glycogenesis) and fats (lipogenesis).

Stimulated by:

• Directly: High blood glucose, elevated blood amino acids, eating, sweet taste (including artificial

sweeteners). Indirectly: GH and ACTH

acting to elevate blood sugar levels. Reduced by:

• Low blood glucose, starvation, glucagon.

glycogen = a polysaccharide -lysis = breakdown

lipo- = fat

genesis = creation

Pancreas: Glucagon

Acts on the liver to elevate blood

glucose levels.

• Converts glycogen to glucose in liver

and skeletal muscle (glycogenolysis).

• Gluconeogenesis from lactic acid and

amino acids.

• Lipolysis to break down stored fat for

use for metabolism.

PRODUCTION:

• Stimulated by: Low blood sugar,

exercise, stress (fight-or-flight).

• Reduced by: Insulin, hyperglycaemia.

Diabetes Mellitus

mellitus = honey-like gestation = pregnancy

A metabolic disorder associated with hyperglycaemia, characterised by a deficiency of insulin due to impaired production or insulin resistance.

• Causes a disruption of carbohydrate and fat metabolism and elevated blood glucose levels 🡪 hyperglycaemia.

TYPES:

1. Type I: Autoimmune.

2. Type II: Insulin resistance.

3. Secondary (1-2% of cases): Due to certain

medications (cortisone), pancreatitis.

4. Gestational: During pregnancy as a result of placental hormones (i.e. human placental lactogen). There is a sevenfold increased risk of developing Type II diabetes later in life

Type I Diabetes

• Previously called juvenile-onset or insulin-dependent (IDDM).

• Type 1 diabetes refers to an absolute deficiency of insulin causing persistent hyperglycaemia

CAUSES:

• An auto-immune condition causing destruction of pancreatic ß-cells.

• Likely due to the environment in genetically susceptible people. • Viruses (e.g. polio, rotavirus)

• Dietary factors — infant exposure to dairy products (cow's milk and the milk protein β casein), vitamin D deficiency, omega-3 deficiency, early exposure to gluten.

Type I Diabetes

SIGNS AND SYMPTOMS:

• Polydipsia (excessive thirst).

• Polyuria (excess urination).

• Polyphagia (excessive appetite).

• Glycosuria (glucose in urine)

• Unexplained weight loss

• Weakness, extreme fatigue and mental

status changes.

• Blurred vision

^{• Slow healing of cuts / infections.}• Ketoacidosis: Fruity smelling breath

(exhaled acetone), shortness of breath.

Type I Diabetes

TREATMENT:

• Insulin.

ALTERNATIVE SUPPORT:

• Herbs (support pancreas, insulin sensitivity).

• Nutrition — low GI and GL, antioxidants / alpha

lipoic acid. Reduce saturated and trans fats,

whilst increasing essential fatty acids

(increase membrane fluidity).

• Chromium (increases insulin binding to cells —

increases number of insulin receptors) and cinnamon.

• Vit. D, magnesium-rich foods, zinc, alkalising the body. Homeopathy and acupuncture.

Type II Diabetes

• Previously called adult-onset or non-insulin-dependent diabetes. • Cells developed insulin resistance: Glucose cannot enter cells. • Hyperglycaemia develops when pancreatic beta cells can no

longer secrete insulin to compensate for insulin resistance. • A third of adults over 65 and increasing numbers of children have impaired glucose tolerance.

CAUSES:

• Genetic: Strong hereditary link, 🡹 in Native Americans, Hispanics, African-Americans and Asians.

• Lifestyle: Obesity and weight gain, low fibre, high glycaemic index (GI) diet (sugar, white rice, white bread)

lack of exercise.

• Other risk factors include: History of gestational diabetes. © CNM: Human Sciences – Endocrine System. BQ/JD

Type II Diabetes

SIGNS AND SYMPTOMS:

• Polydipsia (excessive thirst).

• Polyuria (excess urination).

• Polyphagia (excessive appetite).

• Acanthosis nigricans (image below).

• Often asymptomatic because of mild

hyperglycaemia (unlike in Type I diabetes).

• Initial symptoms are often complications,

indicating the disease has been present

for some time.

• Ketoacidosis in rare, severe cases (same

complications as Type I).

Type II Diabetes

DIAGNOSIS:

• Fasting / random blood glucose test.

• Oral glucose tolerance test.

• Glycated haemoglobin (HbA1c)

> 48 mmol / mol = diabetes.

• Urine test (assists diagnosis only).

ALLOPATHIC TREATMENT:

• Diet (low GI and GL), exercise, oral

anti-hyperglycaemics (e.g. metformin), insulin or both.

• Statins and anti-hypertensives to prevent complications.

NATURAL APPROACH:

• Diet, exercise, weight loss, chromium: Herbs — gymnema. Cinnamon, vitamin D, berberine, homeopathy.

Diabetic Complications

Chronic hyperglycaemia

causes complications: Micro

and macro-vascular disease:

• Heart disease,

hypercholesterolaemia,

hypertension.

• Retinopathy.

• Nephropathy (diabetic kidney

disease).

• Peripheral neuropathy.

Ketoacidosis

When glucose supply is low or when cells cannot utilise glucose, the mitochondria can use ketones to make energy.

• Ketones are derived from the breakdown of fatty acids.

• Ketones (or keto-acids) are acidic and can be toxic if they accumulate to excessive levels. • May result in coma or death.

• Ketones can be tested using a urine dipstick. • Breath smelling fruity (acetone) and increased thirst are key signs.

Acetone: 77

Hypoglycaemia

Hypoglycaemia can affect diabetics in

response to treatment (e.g. insulin or

other glucose lowering drugs).

SIGNS AND SYMPTOMS:

• Shaking and trembling.

• Sweating.

• Pins and needles in the lips and tongue.

• Extreme hunger and irritability.

• Headache.

• Slurred speech, confusion, tiredness.

• Ketoacidosis and coma.

Local Hormones

Hormone	Secreted by	Action
Histamine	• Basophils, mast cells	• Inflammation — vasodilatation and increased blood vessel permeability.
Prostaglandins, leukotrienes, thromboxanes	• Most tissues	• Chemical messengers involved in many different body processes.
Serotonin	• Intestines, brain	• Blood clotting, temperature regulation, appetite, sleep.
Dopamine	• Brain mostly	• Muscle tone and some movements.
Erythropoietin	• Kidneys	• Red blood cell production.
CCK	• GI tract	• Stimulates bile and pancreatic juice secretion.

lecture 9: endocrine system

Biomedicine: Human Sciences

Lecture 9:

Endocrine System

Learning Outcomes

In today’s topic you will learn:

⮚ The structure and function of

the endocrine system.

⮚ The clinical presentations,

investigation procedures and

some orthodox treatments of

endocrine pathologies.

Endocrine System

The endocrine system coordinates the activity of organs through hormones — chemical messengers released into the blood from glands which produce them.

• Hormones have specific target cells, some far from where the hormone is produced, others affect cells of the same organ where they were released, or the same cell.

• Hormones can be:

1. Peptides (proteins — water soluble): i.e, insulin.

2. Steroids: sex hormones; e.g. oestrogen.

3. Amino acid derivatives: adrenaline, thyroxine.

Homeostasis

Two control systems ensure our survival by controlling

homeostasis in two different ways.

AUTONOMIC NERVOUS SYSTEM	ENDOCRINE SYSTEM
Rapid change.	Slower change.
Less precise.	More precise.
Shorter duration.	Longer duration.
Neurotransmitters.	Hormones.
Control centre: Central nervous system.	Control centre: Hypothalamus.

Glands

There are two types of glands:

1. EXOCRINE

• Excrete products into ducts leading to

body cavities / organ / skin.

• Examples: Salivary glands (saliva), gastric

glands (digestive enzymes), mammary glands.

2. ENDOCRINE

• Ductless, secreting hormones directly into

the blood.

• Examples: Pituitary, adrenals, thyroid.

Exocrine and Endocrine Glands

Endocrine = hormones

_{secreted into blood}Exocrine = via a duct

Glands

Endocrine glands include:

• Hypothalamus (neuroendocrine gland).

• Pituitary (glandular and neuroendocrine).

• Pineal.

• Thyroid.

• Parathyroid.

• Adrenal.

• Pancreatic: islets of Langerhans.

• Thymus.

• Ovaries.

• Testes.

Endocrine Tissues

Some tissues of the body are not considered glands but have endocrine function (produce hormones):

• Adipose tissue — leptin (suppresses food intake) and resistin (blood glucose).

• Heart — atrial natriuretic peptide (blood pressure).

• GIT — stomach: ghrelin and gastrin (satiety and gastric emptying). • Liver — angiotensinogen, insulin-like growth factor (IGF), thrombopoietin.

• Placenta — human chorionic gonadotropin (hCG) and progesterone. • Kidneys — erythropoietin (RBC production) and calcitriol (vit. D). • Skin — cholecalciferol (vit. D).

Hormone Activity: Receptors

Hormones have specific target cells.

• They influence the activity of the target

cells by binding to specific receptors.

• The receptors for protein-based

hormones are part of the cell

membrane, whilst lipid hormone

receptors are within the cell.

• Receptors can be made up of

a number of different proteins.

• Receptors allow hormones to

have a stimulating or inhibitory

effect on different cell types.

Hormones

The target cells can alter their sensitivity to the hormone:

Down-regulation:	Up-regulation:
• If a hormone is present in excess, the number of target cell receptors may decrease.	• A deficiency in hormone causes an increase in the number of receptors on target cells.
• Example: Hormones increase during puberty.	• Example: Increased number of oxytocin receptors in third trimester of pregnancy.

Hormone Regulation

Hormone secretions are regulated by:

1. Nervous system signals.

2. Chemical changes in the blood.

3. Other hormones.

• Hormones interact to allow maximum

flexibility in response to the

environment.

• They are controlled through positive

and negative feedback loops.

Endocrine System Control

The pituitary gland is often named the

master endocrine gland as it controls

many of the other endocrine glands in

the body. It is itself regulated (signalled)

by the hypothalamus.

• The pituitary gland has an anterior and

posterior region.

• The hypothalamus and pituitary glands represent the major link between nervous and endocrine systems.

• Together they control almost entirely: growth, development, metabolism and homeostasis.

Hypothalamus

Pituitary Gland

thermo = temperature regulatory = regulation

Hypothalamus

Releasing Hormones:

TRH

Thyrotrophin releasing hormone

GHRH

Growth hormone releasing hormone

CRH

Corticotropin releasing hormone

PRH

Prolactin releasing hormone

GnRH

Gonadotropin releasing

hormone

Inhibiting Hormones:

GHIH

Growth hormone inhibiting hormone

PIH

Prolactin inhibiting hormone (Dopamine)

Pituitary gland

Posterior

• Hormones are

synthesised in the

hypothalamus.

• Receives nerve impulses from the hypothalamus. • Releases these hormones: • Oxytocin

• Antidiuretic hormone (ADH)

The hypothalamus and pituitary gland are connected by a stalk of nerve fibres and network of

Anterior

• Receives seven hormones in capillaries from hypothalamus. • Synthesises and releases: 1. Growth hormone (GH).

2. Thyroid stimulating hormone (TSH)

3. Follicle stimulating hormone (FSH).

4. Luteinising hormone (LH). 5. Prolactin (PRL).

6. Adrenocorticotropic hormone (ACTH).

7. Melanocyte stimulating hormone (MSH).

capillaries. ₁₄© CNM: Human Sciences – Endocrine System. BQ/JD

Hypothalamus and

Anterior Pituitary Hormones

TRH

Thyrotrophin releasing hormone

GHRH

Growth hormone releasing

hormone

GHIH

Growth hormone inhibiting

hormone

CRH

Corticotropin releasing hormone

MSH

PRH

Prolactin

releasing hormone

PIH

Prolactin

inhibiting hormone (Dopamine)

GnRH

Gonadotropin releasing

hormone

FSH

_GHTSH ^ACTHPROLACTIN

Table of Hypothalamic and Anterior Pituitary

Hormones:

Hypothalamic Hormone/s	Anterior Pituitary Hormone	Target tissue
GHRH / GHIH	GH	Most body tissues
TRH	TSH	Thyroid Gland
CRH	ACTH MSH	Adrenal Cortex Skin
PRH / PIH	PRL	Breasts
GnRH	FSH	Ovaries and Testes
GnRH	LH	Ovaries and Testes

Growth Hormone (GH)

ACTIVITY:

1. Regulates metabolism in many organs.

2. Stimulates release of insulin-like

growth factors (IGFs) in cells.

3. Promotes growth and division of most

body cells (especially bone and muscle).

4. Breaks down fats and glycogen.

INCREASED PRODUCTION:

• Night-time (sleep — stage three, four).

• Hypoglycaemia.

• Exercise.

• Childhood and adolescence.

hypo = low

glycaemia = blood sugar

Thyroid Stimulating Hormone (TSH) ACTIVITY:

1. Growth and activity of the thyroid gland: Increasing thyroid hormone production — thyroxine (T₄^{) and tri}iodothyronine (T₃).

PRODUCTION:

• Lowest levels in the early evening and highest during the night.

The thyroid gland:

Adrenocorticotropic Hormone (ACTH)

ACTIVITY:

1. Output of steroid hormones:

Glucocorticoids, especially cortisol.

2. Circadian rhythm (sleep / wake cycle).

INCREASED PRODUCTION:

• Hypoglycaemia.

• Exercise.

• Stressors such as emotions, fever. • Interleukin-1 (inflammatory

response to infection).

PRODUCTION:

• Highest in the morning and lowest at midnight.

circadian

rhythms =

biological

processes

that follow a 24-hour cycle

Prolactin (PRL)

ACTIVITY:

1. Stimulates lactation:

Prolactin + oxytocin = lactation.

2. Prevents pregnancy during lactation (inhibits GnRH).

3. Breast maturation after childbirth. Matures mammary glands in pregnancy.

PRODUCTION:

• After birth (delivery of placenta).

pro = produce -lactin = ‘lactation’

• Suckling: the more milk removed, the more produced. • Emotional stress.

• Sleep.

Follicle Stimulating Hormone (FSH) and Luteinising Hormone (LH)

• FSH:

• Production of gametes (sex cells)

in males and females.

• Increases oestrogen production (F).

• Stimulates testosterone production (M).

• LH

• Triggers ovulation and formation of the

corpus luteum in females.

• Increases secretion of progesterone (F).

• Stimulates secretion of testosterone (M).

corpus luteum = a hormone secreting structure that develops in an ovary following ovulation

FSH and LH are covered further in semester II

Melanocyte Stimulating Hormone (MSH)

Produced by the anterior pituitary in response to UV light.

• Stimulated by corticotropin releasing hormone (CRH) — released from

hypothalamus. So MSH and ACTH

share CRH as their precursor hormone. • Role in skin, hair and eye pigmentation in humans.

• Can be excessively produced as part of some

melanin = skin pigment -cyte = cell

pathologies, such as the hyperpigmentation of skin seen in Addison’s disease.

Oxytocin

oxy = Greek for sharp

POSTERIOR PITUITARY

ACTIVITY:

1. Contracts uterus in childbirth (parturition). 2. Contracts lactating breast.

3. Bonding hormone (mother with baby): Social bonding, trust, skin contact, cuddle hormone.

PRODUCTION:

• Suckling.

• Childbirth (positive feedback).

• Emotional state: Fear or anxiety may

tocos = Greek for labour

inhibit release of oxytocin or milk let-down. Emotions can trigger oxytocin — just hearing baby’s cry can start lactation.

Oxytocin

POSTERIOR PITUITARY

• Two weeks before birth, the baby descends

to the bottom of the uterus (womb).

• The head engages with the wall of the cervix.

• Sensory neurons act as pressure receptors

and when stretched send signals to the

hypothalamus.

• Oxytocin is released into the bloodstream.

• Oxytocin causes more forceful contraction of

the uterus.

• Baby’s head engages head of cervix /

pressure receptors … positive feed-forward

cycle that builds up momentum.

Lactation:

It takes two–three days for milk

production to begin.

• The first breast fluid produced is

called colostrum, which contains

water, lacto-sugar and antibodies.

• Colostrum acts as a laxative to

encourage a bowel movement. This

is important to remove bilirubin and

wastes that have accumulated in the

foetal intestines.

Antidiuretic Hormone (ADH)

POSTERIOR PITUITARY

Hypothalamus monitors concentration of body fluid.

ACTIVITY:

1. Reduces urine output by stimulating reabsorption of water in the kidneys. 2. Vasoconstriction in skin and abdominal organs to increase blood pressure.

PRODUCTION:

• Increased osmotic pressure, hypovolaemia (reduced fluid intake, thirst, vomiting). INHIBITION:

• Reduced osmotic pressure, increased fluid intake, alcohol.

anti = against

diuresis = urination

hypo = low

volaemia = blood volume

Antidiuretic

Hormone (ADH):

• ADH acts on the kidneys to prevent

the loss of water into urine.

• Ultimately, the actions of ADH will

increase blood pressure.

Exercise:

Fill in the blanks …

________ releasing hormone

_________ inhibiting hormone

CRH:

Corticotropin releasing

hormone

PRH:

Prolactin

releasing

hormone

PIH:

Prolactin inhibiting hormone a.k.a. ___________

GRH:

Gonadotropin releasing

hormone

hGH PROLACTIN

Summary Quiz:

1. How do cells alter their sensitivity to a hormone?

2. Define what is meant by a hormone.

6. What is the target tissue of the hormone prolactin?

7. Give THREE functions of the hormone oxytocin.

8. How does ADH prevent the loss of fluid in the body?

9. Name the precursor hormone shared by both ACTH and MSH. 10.Where is thyroid stimulating hormone (TSH) released from?

Pituitary Gland Pathologies

Pituitary gland pathologies are

typically associated with tumours

or autoimmune diseases.

• These disease processes can result

in either hyper- or hypo-secretion of

certain pituitary hormones.

• The signs and symptoms expressed

ultimately depend on the hormones

affected.

Acromegaly and Gigantism

• Gigantism: Excess growth hormone while the bones are still developing — results in the person growing to massive heights.

• Acromegaly: Excess growth hormone post puberty (after growth plates closed). Patient grows outwards as opposed to upwards. CAUSE:

acro- = extreme

-megaly = enlargement

• A pituitary tumour hyper-secreting growth hormone. SIGNS AND SYMPTOMS:

• Large, prominent facial features, increased size

hands and feet.

• Tiredness, deep voice, impotence, joint pain,

bone deformities, soft-tissue swellings.

Acromegaly and Gigantism

Observe the following timeline. What do you notice?

Acromegaly and Gigantism

TREATMENT:

• Surgery to remove tumour. Life-long medications may be needed.

ALTERNATIVE APPROACH:

• Treat / support cause. Nutrition, herbs, homeopathy, acupuncture.

COMPLICATIONS:

• Hypertension, cardiomegaly.

• Type 2 diabetes (growth hormone 🡹 blood glucose levels 🡪 insulin resistance). • Osteoarthritis, vertebral collapse (back pain). • Bowel polyps.

GH affects

almost every

organ system of the body…

Hyperprolactinaemia

Excessive prolactin production. CAUSES:

• Pituitary tumour, acromegaly, pharmacologic (antipsychotics). SIGNS AND SYMPTOMS:

• Galactorrhoea.

• Amenorrhoea (absence of menses — because prolactin inhibits GnRH). • Decreased libido / sexual dysfunction. • Subfertility.

ALTERNATIVE SUPPORT:

hyper = elevated

prolactinaemia = prolactin in blood

Galactorrhoea:

Flow of milk from

breast not associated

with childbirth

• Treat / support the cause. Herbs can help balance hormone levels. Nutrition, acupuncture, homeopathy.

Diabetes Insipidus

Deficiency of ADH production or recognition causing the kidneys to over-excrete water. CAUSES:

• Cranial: Brain trauma, tumour, encephalitis. • Renal (kidney): Chronic kidney disease,

diabetes = disease causing excess thirst and urination

Insipid = ‘bland’

hypercalcaemia and hypokalaemia damages kidney. SIGNS AND SYMPTOMS:

• Polydipsia (extreme thirst) — large consumption.

• Polyuria: Excess urine production (dilute). • Weight loss.

hypo = low

-kalaemia = potassium polyuria = increased urination

Diabetes Insipidus

DIAGNOSIS:

• 24-hr urine collection (quantity of urine

measured over 24 hours).

• Urine-specific gravity — low

(i.e. urine is more diluted than normal).

• Blood biochemistry (🡹Na).

TREATMENT:

• Treat cause.

• ADH replacement.

• Rehydration: Water and electrolytes.

• Alternative: Homeopathy, acupuncture.

Pineal Gland: Melatonin

The pineal gland is a small pea-sized gland in the midline of the brain that produces melatonin.

• Specialised photoreceptors in the retina detect light /

darkness cues.

• Levels are highest in children and decline with age. • Stimulated by: Night, darkness (retinal feedback). • Reduced by: Daylight, irregular sleep patterns (jetlag, night-shifts).

ACTIVITY:

• Setting of the circadian rhythm:

Metabolic, physiological and behavioural alterations that follow a 24-hour rhythm.

• A potent antioxidant, DNA protective.

Made from

‘serotonin’.

Thymus Gland: Thymosin

The thymus is a bi-lobed gland, located

behind the sternum, which plays an

important role in immune development.

• The thymus atrophies after puberty and

is replaced by fibrous tissue.

ACTIVITY:

• Hormones produced by the thymus

promote the maturation of T-Lymphocytes.

•

• Immature T-cells migrate from the red bone

marrow to the cortex of the thymus. Mature

T-lymphocytes then migrate to the lymphatic system.

Thyroid Gland

A butterfly-shaped gland that is inferior to the larynx and located either side of the trachea.

• Influences metabolic rate (catabolic + anabolic) and is an important ‘growth hormone’ in early life. • Follicular cells produce thyroid hormones:

• Thyroxine (T₄) — has four iodine atoms.

• Triiodothyronine (T₃) — has three iodine atoms. • T₄and T₃are synthesised from tyrosine and iodine from a specialised thyroid protein called thyroglobulin (Tg).

• Follicular cells trap and store most of the body’s iodide via active transport from blood to cytosol.

Iodine atoms 39

Thyroid Gland Histology

Thyroid follicular cells trap and

store iodine.

• Parafollicular cells (lie between

follicles) secrete the hormone

calcitonin, which functions to

lower blood calcium levels.

• The follicles are filled with a

fluid known as colloid that

contains thyroglobulin.

Thyroid Hormones

The major form of thyroid hormone in the blood

is thyroxine (ratio of T₄to T₃is approx. 20:1).

• Selenium-containing enzymes are used in the conversion of T₄to T₃. Zinc is also needed for this.

• T₃is the more biologically active form:

Three-four times more potent than T_4.

• This allows the body to maintain a stable

pool of thyroid hormones from which the

active, free hormones can be released as

required.

• Thyroid hormone levels are measured in terms of free T₄and T₃. • Most body cells have receptors for thyroid hormones.

Thyroid Hormones

ACTIVITY:

• Increase metabolic rate and heat production.

• Essential for normal growth and

development and CNS function.

• Work in conjunction with adrenaline and

noradrenaline, insulin and growth hormone.

PRODUCTION:

• Stimulated by: TSH, exercise, stress,

malnutrition, low blood glucose, low T₃to T₄.

• Reduced by: Low TSH, high T₃.

• Highest levels at night.

• Higher levels during adolescence,

pregnancy and female reproductive years.

Low blood glucose,

stress, exercise, sleep,

malnutrition

Thyroid

Hormones:

TSH is usually low in a

regularly

functioning

thyroid

Raised TSH

levels indicate the thyroid is failing

Thyroid Hormones

LAB TESTING:

1. TSH Levels (measure in the morning as

it is the highest and most reliable /

consistent value).

2. Free T₃and T₄— unbound form of thyroid

hormones are more bioavailable to

target cells and tissues.

3. Thyroglobulin (‘Tg’) — levels in the

blood can be used as a tumour marker

for certain kinds of thyroid cancer.

4. Anti-thyroglobulin antibodies(TgAb) —

often found in patients with autoimmune

thyroid disease (Hashimoto's or Graves’).

Hypothyroidism

A condition of thyroid hormone deficiency (an underactive thyroid).

SYMPTOMS:

• Tiredness, malaise, weight gain, cold intolerance, constipation, depression.

hypo = low

thyroid = thyroid hormone

• Slow cognition, poor memory, low libido, deep voice, menstrual changes, muscle aches, arthralgia.

SIGNS:

• Goitre, dry, brittle skin, thin hair, loss of eyebrows.

• Myxoedema (swelling) often around the eyes

(deposition of polysaccharides which attract water).

• Physical exam: Slow tendon reflexes, bradycardia. • Blood tests: High TSH, low thyroid hormones.

Hypothyroidism

CAUSES:

• Hashimoto’s thyroiditis (autoimmune).

• Iodine deficiency, thyroid destruction

(radioactive iodine, surgery, medications,

tumour), fluoride.

ALLOPATHIC TREATMENT:

• Levothyroxine — thyroid hormone replacement.

NATURAL TREATMENT:

• Treat the cause.

• Thyroid support: Iodine, selenium, tyrosine, zinc,

glandular thyroid.

• Herbs; e.g. withania; homeopathy and exercise.

Hyperthyroidism (Graves’ Disease)

Hyperthyroidism is characterised by hyper-metabolism and elevated serum levels of free thyroid hormones (also known as thyrotoxicosis). • More common in women (10:1). CAUSES:

• Graves’ disease (85%): Autoimmune. Increased IgG antibodies bind to TSH receptor and stimulate

production of thyroid hormones. • Excessive iodine supplementation. • Tumour (hypothalamic, pituitary).

hyper = elevated

thyroid = thyroid hormone

Hyperthyroidism (Graves’ Disease)

SIGNS AND SYMPTOMS:

• Nervousness, irritability, hyperactivity, unexplained

weight loss.

• Insomnia, palpitations, muscle weakness, frequent bowel and bladder movements, diarrhoea, fatigue. • Heat sensitivity, increased sweating.

• Signs: Goitre, exophthalmos, tachycardia, tremor, brisk tendon reflexes, lid lag (von Gräfe’s sign). TREATMENT:

• Allopathic: Carbimazole, radioactive iodine,

Exophthalmos:

β-blockers, surgery.

• Alternative: Treat cause. In Graves’ disease

exo- = external opthalmos = eye

herbs and nutritional supplements to restore immune system balance (antioxidants); homeopathy.

Thyroid Gland: Calcitonin

Produced by the parafollicular cells of the

thyroid gland.

• Important during childhood for bone growth.

• Lowers blood calcium by:

1. Inhibiting calcium reabsorption from the

bone and kidneys.

2. Inhibiting osteoclast activity

(opposes parathyroid).

PRODUCTION:

• Stimulated by: Increased blood calcium

levels.

• Inhibited by: Reduced blood calcium levels.

Parathyroid Glands

The parathyroid glands

consist of four small glands.

• They are partially embedded

in the posterior surface of the

lateral lobes of the thyroid.

• Produce parathyroid

hormones.

Parathyroid Hormone (PTH)

Parathyroid hormone increases

blood calcium by:

1. Increasing osteoclast activity.

2. Increasing kidney reabsorption of

calcium and magnesium.

3. Increasing production of calcitriol

which increases calcium absorption

in the GIT.

• PTH release is stimulated by reduced

blood calcium levels and inhibited by

increased blood calcium levels.

• Calcium is essential for muscle contraction,

nerve transmission, blood clotting.

Hyperparathyroidism

Hyperparathyroidism is characterised by elevated blood levels of parathyroid hormone and improper calcium regulation. CAUSES:

• Usually a tumour of the parathyroid gland. SIGNS AND SYMPTOMS:

• Often no / few symptoms.

• Hypercalcaemia 🡪 increased risk of kidney stones, osteoporosis (or osteopenia), low energy, depression.

• In some cases: Nausea, vomiting, constipation, anorexia, muscle paralysis.

hyper = elevated

parathyroid =

parathyroid hormone 52

Hypoparathyroidism

Hypoparathyroidism is characterised by hypo-metabolism and reduced serum levels of parathyroid hormone (PTH).

CAUSES:

• Usually surgery or radiation (treating thyroid).

SIGNS AND SYMPTOMS:

• Hypocalcaemia 🡪 muscle cramps and spasms (tetany), tingling lips, fingers and toes, dry hair, brittle nails, dry scaly skin, cataracts, weakened tooth enamel (in children).

hypo = low

parathyroid =

parathyroid hormone 53

Summary Quiz:

1. Name the hormone that is deficient in diabetes insipidus. 2. What does the number next to the T₄and T₃reflect?

3. Name the thyroid hormone that is the more active form. 4. What do parafollicular cells produce?

5. List FOUR symptoms of hypothyroidism.

6. State TWO signs of hyperthyroidism.

7. Name TWO ways in which parathyroid hormone increases blood calcium

8. State TWO causes of hypoparathyroidism.

9. What is the effect of hypoparathyroidism on muscles? 10.What effect might hyperparathyroidism have on bone?

Adrenal Glands

The adrenals are paired glands superior

to the kidneys. Divided into the:

1. Medulla (inner): Part of the autonomic NS,

producing:

• Adrenaline (epinephrine).

• Noradrenaline (norepinephrine).

• Dopamine.

2. Cortex (outer): Produces three groups

of steroid hormones:

• Glucocorticoids (mostly cortisol).

• Mineralocorticoids (mostly aldosterone).

• Sex hormones (mostly androgens).

Adrenaline and Noradrenaline

Adrenaline (80%) and noradrenaline (20%)

are produced by the adrenal medulla.

• They both intensify the sympathetic response.

• Released by chromaffin cells (quick release

because innervated directly by sympathetic NS).

• Adrenaline has greater influence on the heart.

Noradrenaline affects blood vessels.

• Stimulated by: Exercise, fasting, shock,

elevated temperature, infection, disease,

emotional stress, caffeine.

• Inhibited by: Eating, sleeping, calmness,

diaphragmatic breathing.

Adrenaline and Noradrenaline

Adrenaline binds to receptors on the:

1. Heart: Increases heart rate and

contraction causing an increase in

blood pressure.

2. Vessels: Vasodilation in heart,

brain, skeletal muscles.

Vasoconstriction in digestive tract.

3. Thyroid: Increases metabolism.

4. Skeletal muscle / liver: Increases

blood glucose and triglycerides

(for metabolism)

5. Nervous system: Dilate pupils.

Glucocorticoids

Steroid hormones produced in the adrenal cortex which regulate metabolism and resistance to stress.

• This is mostly cortisol.

ACTIVITY:

1. Stimulating gluconeogenesis. 2. Proteolysis (amino acids from protein). 3. Lipolysis.

4. Production of glucose by the liver.

gluco- = glucose cortico- = cortex -oid = steroid

5. Reduces immune response (and tissue repair).

6. Anti-inflammatory — hence therapeutic use of steroids. 7. Weak reabsorption of sodium and water from kidney tubules.

Mineralocorticoids

Primarily aldosterone — maintains water and electrolyte balance.

ACTIVITY:

1. Reabsorption of sodium in kidneys. 2. Causes retention of water in the kidneys to increase blood volume and blood pressure. 3. Excretion of potassium in urine.

• Stimulated by: 🡻 BP or blood volume (dehydration, haemorrhage) and high blood potassium stimulates the renin-angiotensin aldosterone pathway (RAAS).

mineral = i.e.

Sodium/potassium cortico- = cortex -oid = steroid

Sex Hormones

Primarily androgens in the form of dehydroepiandrosterone (DHEA).

ACTIVITY:

1. Production of pubic and axillary hair. 2. Growth: Increases muscle mass.

3. Converted to testosterone then oestrogen (in females 🡪 promotes libido).

PRODUCTION:

• Stimulated by CRH 🡪 ACTH

• Cortical androgens are insignificant compared to amount produced in the ovaries and testes during puberty and adulthood.

androgens = male sex hormones

Cushing Syndrome

A rare disorder characterised by prolonged

exposure to abnormally high levels of cortisol

(hypercortisolaemia).

• Most commonly affects adults between 25 and 40

• Ex

years old, although can affect children.

CAUSES:

1. Corticosteroid medication: e.g., prednisolone

2. Adrenal Adenoma: Benign or malignant tumours

3. Pituitary Tumour: Excess production of ACTH

causing excess glucocorticoid production from the

adrenal cortex.

Cushing Syndrome

SIGNS AND SYMPTOMS:

• Central weight gain, moon face, buffalo hump, insulin resistance.

• Depression, insomnia, psychosis, poor libido, hirsutism, amenorrhoea (also releases some androgens).

• Easy bruising, thin skin, abdominal stretch marks (due to protein taken

from collagen and lowered immunity). • Reduced immunity.

• Muscular weakness, back pain.

• Bone fractures, osteoporosis.

• Hypertension.

hirsutism = excessive ‘male pattern’ hair growth

Cushing Syndrome

TREATMENT:

• Drugs inhibiting cortisol

production, surgery (for tumours).

NATURAL SUPPORT:

• Treat cause with herbs,

homeopathy and nutritional

supplements if indicated.

COMPLICATIONS:

• Lowered immunity, fragile skin,

bone fractures, diabetes mellitus.

Addison’s Disease

Adrenal insufficiency: Hypo-functioning of

the adrenal cortex causing a deficiency of

mineralocorticoids and glucocorticoids.

CAUSES:

• Atrophy of the adrenal gland (often autoimmune) (85%). • Secondary to a disease or abrupt cessation of steroids.

SIGNS AND SYMPTOMS:

• Weakness, fatigue and hypotension.

• Hyperpigmentation of skin and mucous membranes.

• Diarrhoea, weight loss, anorexia, malaise, muscle

weakness, depression, increased thirst.

• Impotence / amenorrhoea, nausea / vomiting.

Addison’s Disease

erroneously produce melanocyte stimulating hormone.

• This causes the skin colour to darken, hence hyperpigmentation.

Addisonian Crisis:

• A complication of Addison's disease when the individual has no capacity to cope with stress (e.g. psychological, infection etc.) SIGNS AND SYMPTOMS:

• Severe lethargy and low blood pressure (low sodium). • Hypoglycaemic, syncope (fainting).

• Severe pain, renal failure, fever.

Pancreas

The pancreas has both an

endocrine and exocrine function.

• Endocrine function is via the cells

called the islets of Langerhans.

The pancreas contains different types of

endocrine cells including:

1. Alpha cells: Produce glucagon.

2. Beta cells: Produce insulin.

• Main endocrine function of the pancreas is to regulate blood glucose levels and maintain within normal range (4-7 mmol/L).

Islet = an ‘island’ of tissue structurally

distinct from

surrounding tissues 66

Pancreas: Insulin

Lowers blood glucose levels, amino acids and

fatty acids by:

1. Stimulating cells to uptake glucose from blood.

2. Promoting synthesis of proteins, glycogen

(glycogenesis) and fats (lipogenesis).

Stimulated by:

• Directly: High blood glucose, elevated blood amino acids, eating, sweet taste (including artificial

sweeteners). Indirectly: GH and ACTH

acting to elevate blood sugar levels. Reduced by:

• Low blood glucose, starvation, glucagon.

glycogen = a polysaccharide -lysis = breakdown

lipo- = fat

genesis = creation

Pancreas: Glucagon

Acts on the liver to elevate blood

glucose levels.

• Converts glycogen to glucose in liver

and skeletal muscle (glycogenolysis).

• Gluconeogenesis from lactic acid and

amino acids.

• Lipolysis to break down stored fat for

use for metabolism.

PRODUCTION:

• Stimulated by: Low blood sugar,

exercise, stress (fight-or-flight).

• Reduced by: Insulin, hyperglycaemia.

Diabetes Mellitus

mellitus = honey-like gestation = pregnancy

A metabolic disorder associated with hyperglycaemia, characterised by a deficiency of insulin due to impaired production or insulin resistance.

• Causes a disruption of carbohydrate and fat metabolism and elevated blood glucose levels 🡪 hyperglycaemia.

TYPES:

1. Type I: Autoimmune.

2. Type II: Insulin resistance.

3. Secondary (1-2% of cases): Due to certain

medications (cortisone), pancreatitis.

4. Gestational: During pregnancy as a result of placental hormones (i.e. human placental lactogen). There is a sevenfold increased risk of developing Type II diabetes later in life

Type I Diabetes

• Previously called juvenile-onset or insulin-dependent (IDDM).

• Type 1 diabetes refers to an absolute deficiency of insulin causing persistent hyperglycaemia

CAUSES:

• An auto-immune condition causing destruction of pancreatic ß-cells.

• Likely due to the environment in genetically susceptible people. • Viruses (e.g. polio, rotavirus)

• Dietary factors — infant exposure to dairy products (cow's milk and the milk protein β casein), vitamin D deficiency, omega-3 deficiency, early exposure to gluten.

Type I Diabetes

SIGNS AND SYMPTOMS:

• Polydipsia (excessive thirst).

• Polyuria (excess urination).

• Polyphagia (excessive appetite).

• Glycosuria (glucose in urine)

• Unexplained weight loss

• Weakness, extreme fatigue and mental

status changes.

• Blurred vision

^{• Slow healing of cuts / infections.}• Ketoacidosis: Fruity smelling breath

(exhaled acetone), shortness of breath.

Type I Diabetes

TREATMENT:

• Insulin.

ALTERNATIVE SUPPORT:

• Herbs (support pancreas, insulin sensitivity).

• Nutrition — low GI and GL, antioxidants / alpha

lipoic acid. Reduce saturated and trans fats,

whilst increasing essential fatty acids

(increase membrane fluidity).

• Chromium (increases insulin binding to cells —

increases number of insulin receptors) and cinnamon.

• Vit. D, magnesium-rich foods, zinc, alkalising the body. Homeopathy and acupuncture.

Type II Diabetes

• Previously called adult-onset or non-insulin-dependent diabetes. • Cells developed insulin resistance: Glucose cannot enter cells. • Hyperglycaemia develops when pancreatic beta cells can no

longer secrete insulin to compensate for insulin resistance. • A third of adults over 65 and increasing numbers of children have impaired glucose tolerance.

CAUSES:

• Genetic: Strong hereditary link, 🡹 in Native Americans, Hispanics, African-Americans and Asians.

• Lifestyle: Obesity and weight gain, low fibre, high glycaemic index (GI) diet (sugar, white rice, white bread)

lack of exercise.

Type II Diabetes

SIGNS AND SYMPTOMS:

• Polydipsia (excessive thirst).

• Polyuria (excess urination).

• Polyphagia (excessive appetite).

• Acanthosis nigricans (image below).

• Often asymptomatic because of mild

hyperglycaemia (unlike in Type I diabetes).

• Initial symptoms are often complications,

indicating the disease has been present

for some time.

• Ketoacidosis in rare, severe cases (same

complications as Type I).

Type II Diabetes

DIAGNOSIS:

• Fasting / random blood glucose test.

• Oral glucose tolerance test.

• Glycated haemoglobin (HbA1c)

> 48 mmol / mol = diabetes.

• Urine test (assists diagnosis only).

ALLOPATHIC TREATMENT:

• Diet (low GI and GL), exercise, oral

anti-hyperglycaemics (e.g. metformin), insulin or both.

• Statins and anti-hypertensives to prevent complications.

NATURAL APPROACH:

• Diet, exercise, weight loss, chromium: Herbs — gymnema. Cinnamon, vitamin D, berberine, homeopathy.

Diabetic Complications

Chronic hyperglycaemia

causes complications: Micro

and macro-vascular disease:

• Heart disease,

hypercholesterolaemia,

hypertension.

• Retinopathy.

• Nephropathy (diabetic kidney

disease).

• Peripheral neuropathy.

Ketoacidosis

When glucose supply is low or when cells cannot utilise glucose, the mitochondria can use ketones to make energy.

• Ketones are derived from the breakdown of fatty acids.

• Ketones (or keto-acids) are acidic and can be toxic if they accumulate to excessive levels. • May result in coma or death.

• Ketones can be tested using a urine dipstick. • Breath smelling fruity (acetone) and increased thirst are key signs.

Acetone: 77

Hypoglycaemia

Hypoglycaemia can affect diabetics in

response to treatment (e.g. insulin or

other glucose lowering drugs).

SIGNS AND SYMPTOMS:

• Shaking and trembling.

• Sweating.

• Pins and needles in the lips and tongue.

• Extreme hunger and irritability.

• Headache.

• Slurred speech, confusion, tiredness.

• Ketoacidosis and coma.

Local Hormones

Hormone	Secreted by	Action
Histamine	• Basophils, mast cells	• Inflammation — vasodilatation and increased blood vessel permeability.
Prostaglandins, leukotrienes, thromboxanes	• Most tissues	• Chemical messengers involved in many different body processes.
Serotonin	• Intestines, brain	• Blood clotting, temperature regulation, appetite, sleep.
Dopamine	• Brain mostly	• Muscle tone and some movements.
Erythropoietin	• Kidneys	• Red blood cell production.
CCK	• GI tract	• Stimulates bile and pancreatic juice secretion.