What are the two distinct parts of the adrenal glands?
Adrenal cortex - outer
Adrenal medulla - inner
What is the hormone responsible for controlling the activity of the adrenal cortex?
Adrenocorticotrophic hormone (ACTH)
Where is adrenocorticotrophic hormone (ACTH) produced?
Anterior pituitary gland
What are the groups of hormones produced by the adrenal cortex?
Glucocorticoids
Mineralocorticoids
Androgens
What is the function of the adrenal medulla?
To secrete adrenaline and noradrenaline
What is the most important glucocorticoid?
Cortisol
What is the most important mineralocorticoid?
Aldosterone
Which adrenal gland is bigger?
The left
What shape is the right adrenal gland?
Pyramid
What shape is the left adrenal gland?
Crescent
What arteries supply the adrenal glands?
Superior suprarenal artery
Middle suprarenal artery
Inferior suprarenal artery
Where does the right adrenal vein empty into?
Straight into the inferior vena cava
Where does the left adrenal vein empty into?
The left renal vein
What are the three zones of the adrenal cortex and what does each zone secrete?
Outer zona glomerulosa - mineralocorcicoids
Middle zona fasciculata- glucocorticoids
Inner zona reticularis - androgens and glucocorticoids
What stimulates the release of aldosterone from the zona glomerulosa?
Angiotensin II
High plasma potassium
ACTH
What is the action of aldosterone?
Acts on the distal convoluted tubule and collecting ducts of the kidney. Causes reabsorption of sodium ions in exchange for potassium ions and hydrogen ions. Water is resorbed with the sodium and hence blood volume is increased.
What percentage of plasma aldosterone is free and in what form is the rest?
40% is free
60% bound to albumin
What is the half life of aldosterone and where is it degraded?
15 minutes
In the liver
What stimulates the release of cortisol from the zona fasciculata?
ACTH in response to a stressful stimulus
What might increase the release of ACTH and therefore cortisol?
Trauma
Haemorrhage
Fever
Prolonged stress (eg exhaustion)
What are the actions of cortisol?
Carbohydrate metabolism:
Stimulates gluconeogenesis
Stimulates glycogenesis
Counteracts insulin
Protein metabolism:
Increases breakdown of proteins
Fat metabolism:
Stimulates lipolysis
Immune system:
Prevents the release of some cytokines to stop or reduce inflammation
Prevents proliferation of T cells
Endocrine system:
Suppresses secretion of anterior pituitary hormones - ACTH, LH, FSH, TSH and GH
Nervous system:
Neuron development and cognitive function
Water metabolism:
Weak mineralocorticoid effect
Calcium metabolism:
Increases calcium resorption from bone
Downregulates production of collagen
Prolongs wound healing
What is the normal range of cortisol in the blood?
This is time dependent. Levels in the morning are much higher and decrease throughout the day.
09:00 - normal levels are between 140-700 nmol/dL
Midnight - normal levels are between 80-350 nmol/dL
How is cortisol transported in the blood?
80% bound to cortisol binding protein
15% bound to albumin
5% free and active
Where is cortisol metabolised?
Liver
What are the main androgens made in the adrenal cortex?
Dehydroepiandrosterone (DHEA)
Androstenedione
What are the clinical features of hyperaldosteronism?
Hypertension Hypokalaemia Alkalosis Polyuria Polydipsia (thirst) Muscle weakness and spasm
Is hypernatraemia a feature of hyperaldosteronism?
Rarely because of other mechanisms regulating fluid volume
What blood tests would you do in someone with whom you suspected hyperaldosteronism?
U&Es
Aldosterone level
Renin level
ABG
In someone with high levels of aldosterone but low levels of renin, what is the likely diagnosis?
Primary hyperaldosteronism - Conn’s syndrome (adenoma of the zona glomerulosa)
What is the most common cause of secondary hyperaldosteronism?
Excessive diuretic therapy
What are the causes of secondary hyperaldosteronism?
Excessive diuretic therapy
Anything that results in reduced renal perfusion: Renal artery stenosis Congestive heart failure Nephritic syndrome Cirrhosis with ascites
How are people with hyperaldosteronism treated?
Spironolactone (potassium sparing)
Surgical removal of adenoma if Conn’s
Treat hypertension
What are the causes of hypoaldosteronism?
Primary:
Primary adrenal insufficiency
Congenital adrenal hyperplasia
Aldosterone synthase deficiency
Secondary (hyporeninemic): Renal dysfunction - Diabetic nephropathy ACE inhibitors NSAIDs Cyclosporin
What are the clinical features of hypoaldosteronism?
Hyperkalaemia
Mild metabolic acidosis
Volume depletion and postural hypotension
Why is alkalosis a complication of hyperaldosteronism and acidosis a complication of hypoaldosteronism?
Aldosterone increases re-uptake of sodium through the proton exchange. The urine becomes more acidic as the serum becomes more alkaline.
How is hypoaldosteronism treated?
Fludrocortisone
Loop diuretic for potassium removal (furosemide)
How would you treat someone with high levels of aldosterone who presented with postural hypotension and hyperkalaemia?
This is most likely pseudoaldosteronism. Treatment is with NaCl and treatment for hyperkalaemia.
What do we call excess glucocorticoid?
Cushing’s syndrome
What are the causes of Cushing’s syndrome?
Cushing’s disease (anterior pituitary tumour leading to excess production of ACTH)
Treatment with corticosteroids
Adrenal tumours
What are the clinical features of Cushing’s syndrome?
Hyperglycaemia and diabetes Muscle weakness and wasting Fat redistribution - to face (moon face), neck (buffalo hump) and abdomen Infection (often of the skin), poor healing Acne Hirsutism Male-pattern baldness Cataracts Suppression of growth in children Depression and insomnia Hypertension and heart failure Osteoporosis and vertebral collapse Renal stones Peptic ulcers Amenorrhoea
Why is diagnosing Cushing’s syndrome harder than just a simple blood test?
Because of the circadian rhythm of cortisol release
What screening tests are used to suggest likelihood of a diagnosis of Cushing’s syndrome?
Overnight dexamethasone suppression test
Twenty-four hour urinary free cortisol - 1% of free cortisol is excreted unmetabolized so can measure this to get indicator of cortisol levels throughout the day.
How is the overnight dexamethasone suppression test carried out?
Plasma cortisol is measured before oral dexamethasone dose is given in the evening. Endogenous cortisol would be suppressed in a normal person when re-measured at 8 the next morning.
What are the second line investigations used to diagnose Cushing’s syndrome?
Forty-eight hour dexamethasone suppression test - dexamethasone given every 6 hours
Midnight cortisol - usually lowest at this point
What is the most common cause of Cushing’s syndrome?
Treatment with steroids
What is the additional sign seen specifically in Cushing’s disease?
Pigmented skin
Why do people with Cushing’s disease develop pigmented skin?
ACTH is made from the same gene as melanocyte-stimulating hormone. The gene is called POMC
Which group is most likely to develop Cushing’s disease?
Young adult women
How do you treat someone with Cushing’s syndrome?
Cortisol inhibiting medication - metyrapone
Cushing’s disease - Surgical removal of the tumour
Radiotherapy
Stop steroids if iatrogenic cause
What disease is most commonly associated with ectopic adrenocorticotrophic hormone (ACTH) production?
Small cell carcinoma of the lung
Is benign adenoma of the adrenal cortex a common cause of Cushing’s syndrome?
Benign tumours of the adrenal cortex are relatively common but only a small proportion of them will actually produce any hormone (representing only 10% of adult Cushing’s syndrome cases). They are however the most common cause of Cushing’s syndrome in children.
How can you localise the cause of Cushing’s syndrome?
See how levels of ACTH react to dexamethasone suppression test.
What are the clinical features of congenital adrenal hyperplasia?
Excess androgen release
Precocious puberty in males (sometimes as early as 6 months) - this can cause early bone epiphyseal fusion and therefore short adult height.
Masculinisation in females (similar to polycystic ovarian syndrome) - masculine body shape, balding of temporal skull, increased bulk, deepening of voice, enlargening of clitoris.
What is the most common deficiency as a result of a genetic mutation that leads to congenital adrenal hyperplasia?
Deficiency of 21-hydroxylase
What is the underlying mechanism of congenital adrenal hyperplasia as a result of 21-hydroxylase deficiency?
Deficiency in 21-hydroxylase leads to deficiency of cortisol and aldosterone. No cortisol therefore to suppress release of ACTH. ACTH continues to stimulate adrenal gland leading to hyperplasia and excessive release of androgens.
How are those with congenital adrenal hyperplasia treated?
Replacement therapy of the deficient steroids. Hydrocortisone (cortisol) and fludrocortisone (mineralocorticoid)
What is the term used to describe primary insufficiency of the adrenal cortex?
Addison’s disease
What are the clinical features of Addison’s disease?
Postural hypotension Hyponatraemia Hyperkalaemia Hypoglycaemia Lethargy Nausea Depression Muscle weakness Weight loss Pigmentation of skin (due to increased ACTH)
How would you investigate suspected adrenal cortex insufficiency?
Initial 9am cortisol level
ACTH stimulation test - if cortisol levels do not rise sufficiently with injection of ACTH
ECG - peaked T waves in chest leads indicates hyperkalaemia
What might exacerbate an adrenal crisis?
Infection (Waterhouse-Friderichsen syndrome)
Haemorrhagic necrosis following DIC
Stressful event
Stopping steroid treatment suddenly
What are the characteristics of adrenal crisis?
Severe vomiting Confusion Convulsions Fever Hypotensive shock Hypovolaemic shock Hypoglycaemia Hypothryoid Syncope
What is Waterhouse-Friderichsen syndrome?
Adrenal gland failure due to bleeding into the adrenal glands, caused by severe bacterial (or rarely viral) infection.
What organism is most commonly associated with Waterhouse-Friderichsen syndrome?
Neisseria meningitidis
What is the name of the rare tumour of the catecholamine producing cells in the adrenal medulla?
Phaeochromocytoma
What are the clinical features of a phaeochromocytoma?
Paroxysmal severe hypertension Headaches Anxiety - panic attack Elevated glucose Weight loss
What tests you order for someone with a suspected phaeochromocytoma?
Look for plasma free metanephrines
Look for catecholamine products in the urine (eg VMA)
What is the condition that causes inheritable phaeochromocytoma?
Multiple endocrine neoplasia syndromes (MENS)
What imaging techniques are used to further investigate masses of the adrenal gland?
Ultrasound
CT
What test might you use to differentiate between Cushing’s disease and ectopic ACTH production?
Corticotrophin release hormone test - CRH has no effect on an ectopic secreting tumour.