Adrenal physiology and pathology Flashcards
What hormones are synthesised in the cortex of the adrenal gland?
Mineralocorticoids
Glucocorticoids
Adrenal androgens
What hormones are synthesised in the medulla of the adrenal gland?
Catecholamines - adrenaline and noradrenaline
How is cortisol and androgen production regulated?
Regulated by hormones produced by hypothalamus and anterior pituitary gland
How is aldosterone production regulated?
Renin-angiotensin-aldosterone system
Plasma potassium
What triggers cortisol release?
Stress
Circadian rhythm
Illness
What is the pathway that triggers cortisol release?
Corticotrophin releasing hormone is released from the hypothalamus
CRH stimulates anterior pituitary to release ACTH
This acts on the adrenal cortex to produce cortisol
What are the 6 classes of steroid receptor?
Glucocorticoid Mineralocorticoid Progestin Oestrogen Androgen Vitamin D
What effects does cortisol have on the CNS?
Mood lability
Euphoria/psychosis
Decreased libido
What effects does cortisol have on bone/connective tissue?
Accelerates osteoporosis
Decreased serum calcium
Decreased collagen formation
Decreased wound healing
What immunological effects does cortisol have?
Reduced capillary dilatation/permeability
Reduced leucocyte migration
Reduced macrophage activity
Reduced inflammatory cytokine production
What effects does cortisol have on metabolism?
Carbohydrate: increases blood sugar
Lipid: increased lipolysis, central redistribution
Protein: increased proteolysis
What effects does cortisol have on the circulatory/renal system?
Increased cardiac output
Increased lood pressure
Increased renal blood flow and GFR
What are the 3 main principles in use of corticosteroids as treatment?
Suppress inflammation
Suppress immune system
Replacement treatment
What 3 main areas do corticosteroids have a role in the treatment of?
Allergic disease: asthma/anaphylaxis
Inflammatory disease: rheumatoid arthritis, ulcerative colitis, Crohns disease
Malignant disease
Where can mineralocorticoid receptors be found?
Kidneys
Salivary glands
Gut
Sweat glands
What does aldosterone regulate?
Sodium/potassium balance - K+/H+ excretion, increases Na+ reabsorption
Blood pressure regulation
Regulation of extracellular volume
What can cause primary adrenal insufficiency?
Addison’s disease
Congenital Adrenal Hyperplasia (CAH)
Adrenal TB/malignancy
What can cause secondary adrenal insufficiency?
Due to lack of ACTH stimulation
Iatrogenic (excess exogenous steroid)
Pituitary/hypothalamic disorders
What is the commonest cause of primary adrenal insufficiency?
Addison’s disease
What is Addison’s disease?
Autoimmune destruction of adrenal cortex resulting in insufficient secretion of cortisol and mineralocorticoids
What autoimmune conditions are associated with Addison’s disease?
Type 1 DM
Autoimmune thyroid disease
Pernicious anaemia
What are the features of Addison’s disease?
Anorexia, weight loss Fatigue/lethargy Dizziness and low BP Abdominal pain, vomiting, diarrhoea Skin pigmentation
How can adrenal insufficiency be diagnosed?
'Suspicious biochemistry' - decreased Na+, increased K+ and hypoglycaemia Short synacthen test Increased ACTH Adrenal autoantibodies Increased renin, reduced aldosterone
What causes the skin pigmentation in Addison’s disease?
Increased ACTH
How is a short synacthen test performed?
Measure plasma cortisol before and 30 minutes after iv ACTH injection
Normal: baseline >250nmol/L, post ACTH >480
How should adrenal insufficiency be managed?
Hydrocortisone as cortisol replacement - if unwell, give iv first - usually 15-30mg daily in divided doses
Fludrocortisone as aldosterone replacement
How much of the adrenal gland is destroyed before a patient becomes symptomatic?
> 90%
What key differences are there clinically between Addison’s and secondary adrenal insufficiency?
No increased levels of ACTH so no skin pigmentation
Aldosterone unaffected
What is Cushing’s syndrome?
Excess cortisol production, a disease with high mortality
What are the signs and symptoms of Cushing’s syndrome?
Easy bruising Facial plethora Striae Proximal myopathy Osteoporosis Buffalo hump Hypertension Thinning of skin Euphoria Psychosis Moon face/red cheeks Increased appetite
What are the ACTH dependant causes of Cushing’s syndrome?
Pituitary adenoma
Ectopic ACTH production from carcinoid tumour
Ectopic CRH
What are the ACTH independent causes of Cushing’s syndrome?
Adrenal adenoma
Adrenal carcinoma
Nodular hyperplasia
How is Cushing’s syndrome diagnoses?
Establishment of cortisol excess: Overnight dexamethasone suppression test 24 hour urinary free cortisol Late night salivary cortisol Low dose dexamethasone suppression test Repeat to confirm
What is the commonest cause of cortisol excess?
Iatrogenic Cushing’s syndrome
What usually causes iatrogenic Cushing’s syndrome?
Prolonged high dose steroid treatment
eg. treatment for asthma, rheumatoid arthritis, inflammatory bowel disease, transplants
This causes chronic suppression of pituitary ACTH production and adrenal atrophy
What should happen to the dose of steroid a patient takes when undergoing surgery or if ill, when they have ACTH suppression?
Increased doses of steroid as they are unable to respond normally to illness or stress
What is primary aldosteronism?
Autonomous production of aldosterone independent of its regulators
When should you suspect a secondary cause of hypertension?
Young patient
Resistant hypertension
What clinical signs would make you consider primary aldosteronism in a patient with hypertension?
Resistant hypertension
Hypokalaemia
Alkalosis
What cardiovascular actions does aldosterone have?
Increased sympathetic outflow Increased cardiac collagen Increased blood pressure Increased left ventricular hypertrophy Increased atheroma development Sodium retention
What is Conn’s syndrome?
An adrenal adenoma causing primary aldosteronism
What is the most common cause of primary aldosteronism?
Bilateral adrenal hyperplasia
What are some of the rarer causes of primary aldosteronism?
Genetic mutation
Unilateral hyperplasia
How is primary aldosteronism diagnosed?
Step 1: confirm aldosterone excess
Measure plasma aldosterone and renin and express as ratio (ARR-aldosterone to renin ratio)
If ratio > 750 then investigate further with saline suppression test
Failure of plasma aldosterone to suppress by > 50% with 2 litres of normal saline confirms PA
Step 2: confirm subtype
Adrenal CT to demonstrate adenoma
Sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess
What are surgical management options for primary aldosteronism?
Unilateral laparoscopic adrenalectomy - only if adrenal adenoma (and excess confirmed in adrenal vein sampling)
Cure of hypokalaemia
Cures hypertension in 30-70% cases
What therapy can be given for treatment of bilateral adrenal hyperplasia causing primary aldosteronism?
Mineralocorticoid receptor antagonists (spironolactone or eplerenone)
What is the most common cause of congenital adrenal hyperplasia?
21α hydroxylase deficiency
What is congenital adrenal hyperplasia?
Any of several autosomal recessive diseases associated with enzyme defects in the steroid pathway
What is the classical presentation of congenital adrenal hyperplasia in males?
Adrenal insufficiency at around 2-3 weeks
Poor weight gain
What is the classical presentation of congenital adrenal hyperplasia in females?
Genital ambiguity
What are some of the non-classical features of congenital adrenal hyperplasia?
Hirsutes Acne Oligomenorrhoea Precocious puberty Infertility or sub-fertility
What three areas does the adrenal cortex consist of?
Zona glomerulosa
Zona fasciculate
Zona reticularis
What is a phaeochromocytoma?
A rare tumour of adrenal gland tissue, found either in the adrenal gland or in the sympathetic chain
What are the symptoms of phaeochromocytoma?
Hypertension - 50% paroxysmal Headache Sweating Palpitations Breathlessness Constipation Anxiety/Fear Weight loss Flushing – uncommon Incidental finding on imaging Family tracing
What is the name given to an extra-adrenal phaeochromocytoma?
Paraganglioma
What are the signs of phaeochromocytoma?
Hypertension Postural hypotension in 50% cases Pallor Bradycardia and Tachycardia Pyrexia
What are the signs of complications from phaeochromocytoma?
Left ventricular failure Myocardial necrosis Stroke Shock Paralytic ileus of bowel
What is the classical triad presentation of phaeochromocytoma?
Hypertension
Headache
Sweating
What are the biochemical abnormalities seen in phaeochromocytoma?
Hyperglycaemia – adrenaline secreting tumours
May have low potassium level
High haematocrit – i.e. raised Hb concentration
Mild hypercalcaemia
Lactic acidosis – in absence of shock
Why is phaeochromocytoma known as the 10% tumour?
10% malignant 10% extra-adrenal [probably 20-30%] 10% bilateral 10% associated with hyperglycaemia 10% in children 10% familial (but probably 25%)
How is phaeochromocytoma diagnosed?
Catecholamine excess confirmed - plasma & urine
Source of catecholamine excess found - MRI Scan
Abdomen
Whole body
MIBG – meta-iodobenzylguanidine
PET Scan
How should phaeochromocytoma be treated?
Full α and β- blockade: phenoxybenzamine and atenolol or metoprolol Fluid and/or blood replacement Careful anaesthetic assessment Surgical - laparoscopic Total excision wherever possible Tumour de-bulking Chemotherapy if malignant Radio-labelled MIBG Long-term follow-up Genetic testing Family tracing and investigation
What syndromes is phaeochromocytoma associated with?
Multiple Endocrine Neoplasia II Von-Hippel-Lindau syndrome Succinate dehydrogenase mutations Neurofibromatosis Tuberose sclerosis
