L20: Adrenal disorders Flashcards
What is the clinical presentation of cortisol deficiency?
Weakness, tiredness, weight loss, hypoglycaemic, nausea
What is the clinical presentation of mineralocorticoid deficiency?
Dizziness, low Na and high K, hypotension
What is the clinical presentation of androgen deficiency?
Mostly testosterone
No symptoms in men as not major testoterone producing organ
Women–> Hair loss, loss of libido
What is the clinical presentation of cortisol excess?
Weight gain
Features of Cushing syndrome
What is the clinical presentation of mineralocorticoid excess?
High BP and low K+
What is the clinical presentation of ACTH excess from pituitary?
Skin pigmentation–> Melanocyte stimulaton
What is the clinical presentation of adrenal medulla disease?
Excess adrenaline and NA Acute episodes Sweating Anxiety Palpitations High or low BP Collapse Can lead to sudden death
What biochemical assessment (tests) would you do for suspected adrenal hormone deficiency?
Electrolytes–> Na+ low, K+ high (low BP)
Basal cortisol (0900)–> low (should be high)
Stimulation test–> Inject synthestic ATCH (synatchen)–> see if cortisol levels increase
What biochemical assessment (tests) would you do for suspected adrenal hormone excess?
Electrolytes–> Na+ high, K+ low (high BP)
Midnight cortisol–> high (should be low)
24hr urine–> cortisol high
Suppression test–> failure to suppress cortisol
Androgens and derivatives high
What biochemical assessment (tests) would you do for the adrenal medualla?
24hr urine catecholamines –> adrenaline, NA, dopamine, 3-Methoxy-Tyramine
24hr urine metanephrines–> metabolites of adrenaline and NA–> metadrenaline and normetadrenaline
Plasma metanephrines–> more sensitive than 24hr urine
Before doing a biochemical assessment of adrenal medulla function what should be avoided?
Coffee, cake, bananas, chocolate and vanilla
What is Cushing’s syndrome?
Excess secretion of cortisol caused by hyperactivity of the adrenal cortex
What causes Cushing’s syndrome?
Adrenal adenoma–> tumour of the adrenal cortex
Pituitary adenoma–> Cushing’s disease–> tumour of the anterior pituitary–> increase ACTH secretion
Ectopic tumours secreting ACTH or CRH
Glucocorticoid treatment
What are the signs and symptoms of excess cortisol?
1) Thin arms and legs and muscle weakness–> muscle proteolysis
2) Abdominal fat, dorso-cervical fat pad, moon shaped face–> increased lipogenesis
3) Purple striae–> lower abdomen, upper arms and thighs–> catabolic effects–> protein breakdown–> easy bruising due to thinning of skin and subcutaneous tissue
4) High blood pressure and diabetes
- -> hyperglycaemia–> increased muscle proteolysis and hepatic gluconeogenesis–> polyuria and polydipsia
- -> mineralocorticoid effect of excess cortisol–> increased sodium and fluid retention
5) Osteoporosis–> thin bones –> disturbance in calcium metabolism
6) Plethoric (flushed) face
How is a suspected Cushing’s syndrome diagnosed?
Low dose dexamethasone test
Slight decrease in ACTH or Cortisol indicates Cushing’s syndrome
How can you differentiate between the causes of Cushing’s syndrome?
ACTH test
- -> Supressed= adrenal adenoma or glucocorticoid treatment
- -> Elevated= Cushing disease (pituitary tumour) or ectopic tumour
Differentiate between ACTH supressed–> Are they on glucocorticoids? –> yes glucocorticoid fault, no then adrenal ademona
High dose Dexamethosome test
- -> ACTH (therefore cortisol) levels decreased –> Pituitary tumour (Cushing’s disease)–> relatively insensitive to cortisol but a huge amount will have an effect
- -> ACTH level remains the same–> Ectopic tumour
How are adrenal adenomas treated?
Adrenalectomy Laproscopic ‘key hole surgery’
What do we call the disease that cause primary hyperaldosteronism?
Conn’s syndrome–> aldosterone-secreting adrenal adenoma
OR
Bilateral (idiopathetic) adrenal hyperplasia–> no discrete adenoma, increase in cell number
What does hyperaldosteronism lead to (signs and symptoms)?
Endocrine hypertension and hypokalaemia (low K+)
Elevated aldosterone despite the renin-angiotensin aldosterone system
Occasional muscular weakness and spasms
Tingling sensations
Excessive urination
(high BP, LV hypertrophy, stroke, hypernatraemia, hypokalaemia)
How is primary hyperaldosteronism diagnosed?
Clinical suspicion
Increase aldosterone with decreased renin
Scan–> confirm adrenal adenoma or bilateral hyperplasia
How does hyperaldosteronism lead to increased blood pressure?
Excess aldosterone
Increased Na+ reabsorption and K+ secretion
Increased blood volume and pressure
↑ BP–> increased renal perfusion–> ↓ renin
Normal ↓ renin–> ↓ aldosterone
However Conn’s syndrome–> ↑ aldosterone despite renin↓
What is congenital adrenal hyperplasia (CAH)?
Inherited disorder–> autosomal recessive
Deficiency in enzyme needed to synthesis corticosteroids from cholesterol
Lack of cortisol–> no negative feedback so ↑ACTH secretion–> enlargement of adrenal cortex (hyperplasia)
What is the most common enzyme deficiency in CAD? What does this deficiency result in?
Deficiency in 21-hydroxylase
Position means inhibits production of glucocorticoids and mineralocorticoid
No affect on adrogen synthesis
Therefore 17α hydroxylase precursor–> diverted to produce more androgens
What does increased androgen production result in in CAH?
Genital ambiguity in female infants–> look like boys–> clitoromegaly
Salt wasting crises–> high rate of Na+ loss in urine
Hypotension, hyponatraemia, hyperkalaemia, hypoglycaemia and virilisation (male characterisitcs)
How is CAH treated?
Long term glucocorticoids and mineralocorticoids
Determine sex of baby
Corrective surgery
Treat adrenal crisis
What is Addison’s disease?
Chronic adrenal insufficiency
Decreased activity of the adrenal cortex
Leading to decrease glucocorticoids (cortisol), mineralocorticoids (aldosterone)
What can cause Addison’s disease?
Auto immune destruction of adrenal cortex
Disorders of pituitary or hypothalamus–> decreased secretion of ACTH and CRF–> glucocorticoid secretion reduced
Infection
Infiltration
Malignancy
Genetic
Vascular
Iatrogenic –> caused by medical treatment
What are the symptoms of Addison’s disease?
Fatigue Weakness Anorexia Weight loss Nausea Abdominal pain Dizziness and pigmentation
(postural hypotension, lethargy, weight loss, anorexia, increased skin pigmentation, hypoglycaemia)
What are the signs of Addison’s disease?
Underweight Signs of weight loss General Malaise Other autoimmune disease --> Vitiligo --> Thyroid Postural hypotension Pigmentation
What causes increased skin pigmentation?
Increase in ACTH from POMC and α-MSH and γ-MSH
Melanocyte stimulating hormone
Stimulate meloncytes to produce more melanin
What is Addisonian crisis?
Clinical emergency of Addison’s disease
Caused by trauma, severe infections, abrupt withdrawal of steroids, salt deprevation, cold exposure, severe stress, over exertion
Leads to collapse, hypotension, dehydration, pigmentation and coma
How is Addisonian crisis treated?
Rapid rehydration–> fluid replacement dextrose in normal saline
Intraventous hydrocortisone–> replace cortisol
Fludrocortisone –> aldosterone replacement
What other adrenal insufficencies are there?
Secondary adrenal failure–> ACTH deficiency from hypopituitrism
Steroid-induced hypoadrenalism–> ACTH suppression
How can steroid cause mineralocorticoid effects?
Steroid receptor–> nuclear DNA binding proteins
Three main domain–> DNA binding region rich in cysteine and basic AA, hydrophobic hormone-binding region and variable region
Hormone binding region sequence homology with mineralocorticoid receptor and androgens meaning excess cortisol will bind–> Na+ retention and water retention etc…
What does excessive secretion of male androgens in females do?
Stimulate growth and development of male genital tract and male secondary characteristics (heigh, body shape, facial and body hair, muscle protein etc)
Over production in female–> male characteristics
What does the female androgen oestrogen do?
Stimulate growth and development of female genital tract, breasts and female secondary characteristics
Fat in breast and buttocks, broad hips, body hair distribution
Weakly anabolic and decrease circulating cholesterol levels
What is phaeochromocytoma?
Tumour of the adrenal medulla
Dusty, coloured, cell tumour
What is paraganglioma?
Extra-adrenal tumour
Chromaffin tissue origin
What are the symptoms associated with phaeochromocytoma and paraganglioma? What happens in acute crisis?
Acute episode Sweating Panic attacks Palpitations High or low BP Collapse
(severe hypertension. headaches, palpitation, diaphoresis (excessive sweating), anxiety, weight loss, elevated blood glucose)
Acute crisis--> hypertensive crisis Encephalopathy Hyperglycaemia Cardiac arrythmias Sudden death
How is phaeochromocytoma and paraganglioma managed?
Alpha blockade (phenoxybenzamine) and beta blockade (bisoprolol) and surgical incision Important to alpha blockade before beta blockade--> unapposed alpha stimulation--> hypertensive crisis
What are the causes of phaeochromocytoma and paraganglioma?
Genetic causes
Especially if malignant, extra-adrenal and bilateral
