Adrenal glands

• Adrenal gland


  Located immediately anterior to the kidneys beneath the peritoneum (6-10 gms)
• Anatomy of the adrenal glands

  • Consist of two distinct regions (different function and embryological origin)
  • Cortex
  • Zona medulla
• Zona glomerulosa


  Produces mineralocorticoids/aldosterone
• Zona fasciculata and reticularis

  Produces glucocorticoids and androgens
• Zona medulla


  Contains chromaphin cells/adrenaline
• Factors stimulating aldosterone secretion

  • Increase in the concentration of K+ in the interstitial fluid (strong effect)
  • Decrease in Na+ concentration (weak effect)
  • ACTH (weak effect)
  • Renin-angiotensin-aldosterone pathway (strong effect)
  • Low blood pressure
• Blood concentrations of cortisol can be more than 1000-fold higher than aldosterone
• Cortisol


  Has a "weak mineralocorticoid activity", which is because it could bind with the same affinity aldosterone and cortisol receptors
• 11-beta-hydroxysteroid dehydrogenase


  Enzyme that "protects" the cell from cortisol and allows aldosterone to act appropriately
• Aldosterone target cells


  • Kidney
  • Salivary gland
  • Intestine
• Non-target cells for aldosterone

  • Aldosterone receptor
  • Liquorice
• Hyperaldosteronism


  • About 1% of hypertension
  • Conn's syndrome if primary hyperaldosteronism (tumour of the adrenal gland mainly)
  • Excess secretion of aldosterone
  • Hypertension, hypernatremia, hypokalemia which can induce metabolic alkalosis (due to excretion of H+) ie raised HCO3- and base excess
  • Water retention
• Secondary hyperaldosteronism


  Various causes, not related to the adrenal gland (eg hyper secretion of renin)
• Adrenal androgens


  • Mainly dehydroepiandrosterone (DHEA) and Androstendione
  • Release is stimulated by ACTH
  • They are weak androgens but can be converted to testosterone in peripheral tissues (possible independent effect of unmetabolized DHEA)
  • Very high levels at puberty (contribute to development of body hairs in both sex)
  • In adult women, they supply 50-60 % of androgenic hormone requirement (may contribute to development of male characters)
  • They can further be converted to estrogens
  • Their levels decline dramatically with age (therefore this cannot really compensate for the loss of estrogens induced by menopause)
• Causes of excess adrenal androgen secretion

  • Tumour of the adrenal gland (rare, can induce hirsutism in females)
  • Congenital adrenal hyperplasia (CAH) results from a deficiency in one of the enzymes of the last steps of cortisol biosynthesis
• Congenital adrenal hyperplasia (CAH)

  • Because of defective cortisol synthesis, ACTH levels increase, resulting in overproduction and accumulation of cortisol precursors, particularly 17-OHP
  • This causes excessive production of androgens, resulting in virilization (severe form is lethal if not treated, the most attenuated form can induce hirsutism in females)
• Glucocorticoids


  • Mainly corticosterone (5%) and cortisol (95%) in human
  • Act on nuclear receptors
• Functions of glucocorticoids


  • Maintain blood pressure and cardiovascular function
  • Essential for regulation of carbohydrate and protein metabolism
  • Stimulate synthesis of glycogen in the liver, breakdown of protein, breakdown of lipid, conversion of protein and fat products into carbohydrates
  • Reduce (at higher dose) the immune system's inflammatory response
• Importance of Cortisol on Metabolism

  • Promotes glucose and glycogen synthesis in muscles, liver and adipose tissue
  • Increases plasmatic free fatty acid and glycerol levels
  • Increases plasmatic amino acid levels
  • Crucial for maintaining normal metabolism, can raise dramatically during stress to promote energy availability
• Effects of Cortisol on the immune system

  • Decreases fibroblast production of collagen
  • Decreases T cell proliferation and function
  • Decreases adhesion properties of macrophages and neutrophils
  • Decreases production of inflammatory and immune mediators (histamine, cytokine)
  • Causes vasoconstriction
• Cushing's syndrome


  • Incidence 2/10,000
  • Occurs when the body's tissues are exposed to excessive levels of cortisol for long periods of time
  • May be due to prolonged intake of corticoids or overproduction of endogenous cortisol
  • Symptoms include moon face, buffalo hump, muscle weakness, weight gain, poor wound healing, hyperglycaemia
• Diagnostic tests for Cushing's syndrome

  • Cushing's disease if pituitary tumour ACTH dependent
  • Cushing's syndrome (any other clinical cases)
  • ACTH dependent (pituitary tumour or ectopic tumour), ACTH levels extremely high
  • Non-ACTH dependent (iatrogenic cause, adrenal tumour), ACTH level extremely low
  • Dexamethazone (cortisol agonist) suppression test: Normal condition is suppressible, Cushing's syndrome patients are non suppressible (excluding iatrogenic), Cushing's disease (pituitary tumour) are responsive to very high dose (partial decrease)
• Addison's disease


  • Incidence: 1/10,000
  • Severe or total deficiency of the adrenal cortex, usually caused by a destruction of the gland
  • Classical Addison's disease: total or near total destruction of both adrenal glands (primary insufficiency; cause: autoimmune disease, can also be related to tuberculosis)
  • Secondary adrenal insufficiency: Pituitary alteration of secretion of ACTH, aldosterone secretion may remain adequate
  • Symptoms include fatigue, loss of appetite, nausea, weight loss, low blood pressure, muscle weakness, craving for salty foods, inappropriate tan, hyperpigmentation (ACTH/MSH oversecreted)
• Adrenal medulla


  • 80% Adrenaline, 20% Noradrenaline
  • Stored in granules of the chromaphin cells, arranged in clusters usually around medullary veins
  • Chromaphin cells are embryologically related to catecholamine neurones
  • Preganglionic cholinergic neurones (from splanchnic nerve) trigger the release (stored catecholamines released in response to sympathetic stimulation) only source of epinephrine that enters the blood stream
• Catecholamine synthesis


  1. Hydroxylation of tyrosine (tyrosine hydroxylase)

  2. Decarboxylation of DOPA to dopamine

  3. Hydroxylation to Norepinephrine (in dense granules)

  4. Methylation of Norepinephrine to Epinephrine (Phenyethanolamine-N-Methyl Transferase, cytosol, induced by cortisol)
• Factors stimulating sympathetic activation

  • Stress (wound, shock, anxiety, fear, apprehension, psychic distress, panic reactions)
  • Emotional excitement, sexual activity, increased metabolic demand, physical activity, hypoglycaemia
  • Caffeine, nicotine, fever, hypoxia
• Effects of catecholamines


  • Increase glycogenolysis (levels of CA rise during exercise so that blood glucose levels meet the needs of the increased metabolic rate)
  • Increase in gluconeogenesis in the liver, skeletal muscle
  • Increase inotropic effect (affecting force of muscular contraction in the heart)
  • Increase amylase secretion by the salivary gland
  • Decrease insulin secretion
  • Relaxation of the uterine musculature
  • Conversion of triglycerides to free fatty acids, and glycerol in adipose tissue (fat mobilisation)
  • Elevations in blood pressure (E>NE), heart rate, cardiac output (depending on amount of catecholamine)
  • Dilation of bronchial musculature
• Phaechromocytoma


  • Rare disease (2/100,000)
  • Catecholamine-secreting tumours causing an overproduction of catecholamine
  • Symptoms include headaches, excess sweating, racing heart, anxiety, nervous shaking, nausea, weight loss, heat intolerance, hyperglycaemia
• Stress response


  1. Stress activates nervous and endocrine responses that prepare the body for physical activity

  2. Increased CRH release from the hypothalamus and increased sympathetic stimulation of the adrenal medulla

  3. CRH stimulates ACTH secretion from the anterior pituitary, which in turn stimulates cortisol from the adrenal cortex

  4. Increased sympathetic stimulation of the adrenal medulla increases epinephrine secretion

  5. Increased sympathetic stimulation increases norepinephrine secretion from sympathetic (postganglionic) nerve endings
• Effects of catecholamines and cortisol during stress

  • Increase blood glucose levels and the release of fatty acids from adipose tissue and the liver
  • Sympathetic innervation of the pancreas decreases insulin secretion
  • Glucose becomes more available to the nervous system; and fatty acids (in addition to glucose) can be used by skeletal muscle, cardiac muscle, and other tissues
  • Epinephrine and sympathetic stimulation also increase cardiac output, blood pressure, and act on the CNS to increase alertness and aggressiveness
  • Cortisol decreases the initial inflammatory response
• Treatment of anaphylaxis


  • Adrenaline has physiological benefits: Stimulation of α adrenoceptors increases peripheral vascular resistance improving blood pressure and coronary perfusion, reducing peripheral vasodilation, and angioedema
  • Stimulation of β1 adrenoceptors has both positive inotropic and chronotropic cardiac effects
  • Stimulation of β2 receptors causes bronchodilation as well as increasing intracellular cyclic AMP production in mast cells and basophils, reducing release of inflammatory mediators