Learning Outcome

• To understand the basics of the endocrine system

• To outline some endocrine disorders, their diagnosis & treatments

Endocrine System

• Hormone system found in all mammals

• Composed of glands, hormones & receptors

• A network of glands that secrete hormones

  • to maintain physiological & biochemical homeostasis

  • to respond to changes in physiological status, e.g., pregnancy, puberty & trauma

Endocrine glands

• tissues/organs that produce and secrete/release chemical substances (hormones) directly into the blood circulation or intercellular space

• located throughout our body

• hypothalamus, pineal, pituitary, thyroid, parathyroid and adrenal glands, thymus, pancreas and the gonads

Hormones

• chemical messengers that are formed in endocrine glands and released into bloodstream to regulate the distant target cells and organs

• endocrine gland receives chemical signals

  • synthesises and releases hormone

• act on target cells and organs with hormone-specific receptors

• hormone-receptor complex initiates a cascade of signal transduction events that modulate genes expression

  • regulate physiological and cellular processes

• can also be synthesised and secreted in response to internal or external stress, e.g., fight or flight response during an emergency

Types of hormones

• Protein/polypeptide hormones (e.g., insulin, growth hormone)

  • mostly synthesised by anterior pituitary, placenta, pancreas, & parathyroid glands

  • water-soluble; attach to cell membrane receptors

• steroid hormones (e.g., oestrogens, testosterone)

  • synthesised by gonads, placenta & adrenal glands

  • lipid-soluble; require carrier proteins

• amine hormones (e.g., epinephrine, thyroid hormones)

  • synthesised by thyroid gland & adrenal medulla

Hormone Receptors

• large protein molecules located:

  • in/on the cell membrane

  • in the cytoplasm

  • in the nucleus

• highly-specific for a single hormone

Hypothalamus

• located at the base of the brain

• major function → maintain homeostasis

• integral component in CNS & endocrine system

Hypothalamus Obesity

• obesity caused by physical injury or inborn damage to the hypothalamus

• characterised by rapid, excessive and intractable weight gain

• disrupted balance between energy intake and expenditure

  • increased calorie intake and/or decreased calorie burning

    • rapid weight gain

• symptoms: uncontrollable hunger, rapid & excessive weight gain, low metabolic rate

• common cause of injury: tumour, haemmorhage, brain surgery, trauma, infection, inflammation

• diagnosis: personal history, physical examination, blood & urine tests, imaging tests

• treatment: dietary & physical activity planning, medications, surgery

Pituitary Gland

• anterior pituitary (adenohypophysis) & posterior pituitary (neurohypophysis)

• attached to hypothalamus via infundibulum

• master gland → controls several other endocrine (e.g., thyroid, adrenals, ovaries & testicles)

Anterior pituitary

• active, hormone-synthesising lobe

• made up of different cell types that produce and secrete different types of hormones → controlled by hypothalamus

Posterior pituitary

• does not synthesise hormone

• store the hormone synthesised by hypothalamus

  • antidiuretic hormone (ADH)

  • oxytocin

Disorder of Pituitary Gland

Hypopituitarism

• diminished one or more hormones secretion by pituitary gland

• decreased growth hormone secretion

  • early feature of pituitary failure

  • growth retardation or dwarfism in children

• growth hormone & gonadotropins secretion are affected first

• possible causes: pituitary tumours, head trauma, brain surgery, radiation therapy, poor blood supply to pituitary gland, infections or inflammatory diseases, hypothalamic disorders

Panhypopituitarism

• concentrations of all pituitary hormones are low or zero

• complete loss of pituitary function

• congenital or neonatal onset → stillbirth or death soon after birth

• as a result of pituitary tumour or injury

• symptoms:

  • growth hormone deficiency

    • growth retardation (children)

    • decreased muscle bulk & strength, increased body fat, fatigue, social withdrawal, loss of motivation (adults)

  • gonadotropins (LH & FSH) deficiency

    • decreased body hair & libido, irregular or no menstruation, infertility (women)

    • erectile dysfunction, infertility, decreased facial & body hair

  • TSH deficiency

    • symptoms may take 4-8 weeks to appear

    • inability to tolerate cold temperature, mild myxedema, dry skin, fatigue, weight gain, constipation

  • ACTH deficiency

    • rare, but can be life threatening

    • nausea, vomiting, low blood pressure, hypoglycaemia, decreased glycogen reserves, fatigue

• diagnosis:

  • laboratory evaluation

    • measurement of pituitary hormones & hormones from the target endocrine glands by using immunoassays

  • CT scan or MRI

• treatment:

  • hormone replacement therapy, surgery, radiation therapy

Adrenal Glands

• paired glands located on top of the kidneys

• composed of:

  • inner adrenal medulla

    • secretes catecholamines, i.e., epinephrine & norepinephrine

    • “fight-or-flight” response

  • outer adrenal cortex

    • produces different classes of steroid hormones in each different classes of steroid hormones in each different zones

    • necessary for fluid & electrolyte balance, regulation of metabolism & immune system

Disorder of Adrenal Glands

Cushing’s syndrome

• obesity of the trunk particularly upper back & abdomen

• loss of muscle in the limbs

• round & red face

• thin & fragile skin with purple stretch marks

• easily bruised skin

• (men) reduced libido & erectile dysfunction

• (women) hirsutism with menstrual disturbance

• characterised by excess glucocorticoids (cortisol) or very high cortisol levels in the body

causes:

• cortisol-secreting adrenal adenoma or carcinoma (~10% each)

• ACTH-secreting pituitary adenoma (~70%) or non-pituitary tumours that secrete excess plasma ACTH (10%)

• prolonged consumption of synthetic corticosteroids (e.g., prednisone, dexamethasone) in autoimmune and inflammatory diseases

Laboratory testing via immunoassays

• 24-hour urine free cortisol measurement

• serum ACTH level

  • pituitary-dependent Cushing’s syndrome: 40-260 pg/ml

  • ectopic ACTH production by non-pituitary tumour: >300 pg/ml

  • adrenal tumour: <10 pg/ml

• overnight dexamethasone suppression test

  • normally dexamethasone suppresses the secretion of ACTH (cortisol level <50 nmol/L)

  • patients take 1 mg of dexamethasone at 11pm-12am and blood specimen is taken at 8-9am the following day

  • exclude cushing’s syndrome: cortisol level <50 nmol/L

  • failure to suppress: further investigation is required

• differential diagnosis via 48-hour dexamethasone suppression test

  • low (0.5-6 hourly) and high (2mg-6 hourly) doses, each given for 48 hours starting from 9am on the first day

  • low dose test: confirm the presence of Cushing’s syndrome

  • Cushing’s syndrome: 50% suppression of plasma cortisol

  • Cushing’s syndrome due to adrenal tumour or ectopic ACTH secretion: no suppression

  • need to combine with serum ACTH measurement

• Other tests: saliva test, imaging test

• Treatment:

  • surgery

  • radiation therapy

  • medications

  • reduce the dosage of corticosteroid medications