SH

Clinical Chem Endocrinology

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