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