Adrenal gland clinical Flashcards
Name 2 hypofunction disorders of the adrenal gland
Addison’s disease (primary adrenal insufficiency)
Congenital adrenal hyperplasia (a deficiency in 21-hydroxylase)
Most common cause of Addison’s disease (primary adrenal insufficiency)
Autoimmune destruction of adrenal cortex
-adrenal autoantibodies to 21-hydroxylase
Biochemical investigations of Addison’s disease (5)
Rapid ACTH stimulation test (synacthen test) – synacthen is synthetic form of ACTH so would expect it to stimulate adrenal glands and cause rise in cortisol, however in Addison’s cortisol and aldosterone levels would still be low after synacthen injected
Plasma ACTH - elevated
Adrenal antibodies (to 21-hydroxylase)
Morning serum cortisol - in normal person is high but if low, raises suspicion of addison’s
U and Es - elevated blood urea, low Na+, high K+
Addison’s may be associated with what other autoimmune conditions
Thyroid disease (hypo/hyperfunction) Type 1 DM
Symptoms (5) /signs (3) of Addison’s disease
Symptoms
- fatigue/lethargy
- anorexia
- muscle weakness
- unexplained nausea/vomiting
- low mood/irritable
Signs
- hyperpigmentation (of buccal mucosa, eyes, skin)
- weight loss
- hypotension
- salt craving
What can Addison’s disease do to BG levels + why
Hypoglycaemia
-because of deficient counter-regulatory release of cortisol to insulin
If suspicion of Addison’s diagnosis is high and patient acutely unwell, what should you do
just treat with steroids straight away
If rapid ACTH stimulation test gives a result of low aldosterone and cortisol levels, raises suspicion of adrenal insufficiency further so what test should be done next
Plasma ACTH
- if elevated –> primary adrenal insufficiency (Addison’s disease)
-if suppressed –> secondary adrenal insufficiency
Treatment of Addison’s disease (2)
Corticosteroid replacement for life
- oral hydrocortisone (to replace cortisol)
- oral fludrocortisone acetate (to replace aldosterone)
+/-extra salt in diet
Why is the hydrocortisone treatment given for Addison’s disease given in divided doses (2 tablets a day; morning dose higher)
To mimic normal diurnal variation
-as cortisol levels are higher in morning
Being on high dose steroids can do what to the adrenal gland
Suppress the hypothalamic pituitary adrenal axis, so stopping adrenal gland from producing hormones so body just relies on synthetic steroids
What patients are most vulnerable in times of physiological stress (2)
Adrenal hypofunction patients (i.e. Addison’s disease or secondary adrenal insufficiency) on replacement steroids
Patients on steroid dose sufficient to suppress hypothalamic pituitary adrenal axis
Guidelines for management of patients on replacement (synthetic) steroids due to adrenal hypofunction
- during acute illness/acute physiological stress
- during major illness/operation
Acute illness/ acute physiological stress
-double glucocorticoid dose (i.e. double hydrocortisone)
Major illness or operation
- IV hydrocortisone 100mg
- as stress decreases, reduce hydrocortisone dose by 50% per day until back on usual replacement dose
3 self care rules for patients on steroids
Never miss medication
Double hydrocortisone dose in event of acute illness (flu, uTI etc)
If severe vomiting or diarrhoea, go to hospital as likely going in adrenal crisis)
Name the 2 hyperfunction syndromes of the adrenal cortex
Cushing’s syndrome,
Conn’s syndrome
Endocrine causes of hypertension (7)
Conn's syndrome Cushing's syndrome Pheochromocytoma Acromegaly Hyperparathyroidism Hypothyroidism Congenital adrenal hyperplasia
Name a cause of hyperfunction of the adrenal medulla
Pheochromocytoma
Causes of Cushing’s syndrome (4)
Benign pituitary adenoma secreting ACTH (cushing’s disease)
Adrenal adenoma/carcinoma/bilateral hyerplasia causing excess cortisol production
Ectopic ACTH secreting tumour
Long term iatrogenic corticosteroid therapy
Clinical features of Cushing’s syndrome (13)
Symptoms
-mood swings - irritable, depressed
Signs
- weight gain - CENTRAL obesity
- facial plethora (round + red - ‘MOON FACE’)
- buffalo hump - fat in back of neck and shoulders)
- proximal muscle weakness
- thin arms/legs compared to trunk
- decreased sex drive
- skin thinning/atrophy
- hirsutism
- osteoporosis
- purpura (red/purple patches on skin)
- purple striae
- easy bruisability
What does a cushingoid appearance refer to
when therapeutic corticosteroids have caused a cushing’s syndrome-like symptoms/signs
Biochemical investigations of Cushing’s syndrome
Late night (11pm) salivary cortisol - elevated in cushing’s, low in normal person
Overnight dexamethasone suppression test (+ morning cortisol measured) - +ve for cushing’s if morning cortisol still elevated, should be suppressed in normal person
24hr urinary cortisol test - +ve for cushing’s if high >50micrograms/hr
First investigation to do to screen for hypercortisolism (i.e. Cushing’s syndrome)
+ confirmation investigations of above
Overnight dexamethasone test or 24hr urine free cortisol
if overnight dexamethasone done then confirm with 24hr urine free cortisol and vice versa
Initial imaging test in patients with confirmed adrenocorticotropic hormone (ACTH)-independent Cushing syndrome
Adrenal CT
Initial imaging test in patients with confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome
Pituitary MRI
Once cushing’s has been confirmed biochemically, what investigation is done to differentiate whether Cushing’s syndrome (hypercortisolism) is ACTH dependent or independent
Morning plasma ACTH
-cortisol is high in morning so ACTH should be low but if ACTH is not suppressed, then indicates pituitary adenoma or ectopic ACTH secretion; suppressed ACTH levels indicate ACTH-independent cushing syndrome
Generally, do ectopic ACTH secreting tumours or pituitary adenomas produce more ACTH?
+ would a low dose or high dose dexamethasone suppression test affect cortisol production in these tumours
Ectopic
Only high dose dexamethasone suppresses cortisol production in pituitary adenomas; low dose has no effect
High dose dexamethasone is not strong enough to suppress ACTH in ectopic ACTH tumours so cortisol still high
What is conn’s syndrome + effects (2)
Primary hyperaldosteronism
-resulting in excessive sodium resorption so water retention (thus increased blood volume) and increased urine excretion of K+ –> ultimately hypertension
-renin-angiotensin II pathway suppressed (renin’s function is to increase BP when low)
Causes of conn’s syndrome (3)
Adrenal adenoma
Adrenal carcinoma
Adrenal hyperplasia
-all excessively and autonomously producing aldosterone
In primary hyperaldosteronism, is the ratio of plasma aldosterone: plasma renin activity increased or decreased + why
Increased
-because increased aldosterone causes hypertension which suppresses renin-angiotensin II pathway as that pathway is triggered when there’s low BP
Is plasma aldosterone and plasma renin activity elevated or reduced in the following
- primary hyperaldosteronism (conn’s syndrome)
- secondary hyperaldosteronism
- congenital adrenal hyperplasia
Primary
-elevated PA, decreased PRA
Secondary
-elevated PA, elevated PRA
CAH
-decreased both
Biochemical investigations of conn’s syndrome (primary aldosteronism)
- screening test (1)
- confirmatory test (1)
Screening:
-Plasma aldosterone: plasma renin activity ratio = 20:1
Confirmatory:
-fludrocortisone suppression test (failure of fludorcortisone to suppress aldosterone levels confirms diagnosis)
Na+ and K+ levels in conn’s syndrome
Na+ high
K+ low/normal
Symptoms (4) /signs (1) of conn’s syndrome
+ some patients may only experience what (i.e. get only this one thing)
Symptoms
- nocturia (having to wake up during night to pee)
- polyuria
- maybe muscle spasm (secondary to hypocalcaemia)
- maybe muscle weakness (secondary to hypokalaemia)
Sign
- hypertension (may only get this sign)
- hypokalaemia/hypernatraemia
- alkalosis
MOST KEY SIGN IS HYPERTENSION
Pathophysiology of a phaeochromocytoma
Majority cases are a benign tumour of the ADRENAL MEDULLARY catecholamine-producing chromaffin cells –> hyper secretion of catecholamines (adrenaline, noradrenaline) –> increased stimulation of alpha and beta-adrenergic receptor
Symptoms (4) /signs (3) of a phaechromocytoma
Symptoms
- palpitations,
- headache,
- diaphoresis (abnormal heavy sweating)
- pallor
Signs
- episodic hypertension
- impaired glucose tolerance/ DM
- tachycardia
characterised by paroxysmal hypertension in a young person associated with the triad of headaches, sweating, and palpitation.
Most phaechromocytomas are sporadic but some are hereditary, name some genetic conditions that predispose you tot his tumour (2)
multiple endocrine neoplasia (MEN) type 2,
Von Hippel-Lindau syndrome,
Investigations of phaeochromocytoma (3)
24hr urine for catecholamines, metanephrines, normetanephrines and creatinine - elevated
Serum metaneprhines and normetanephrines - elevated
Genetic testing - to test for hereditary conditions like MEN type 2 that predispose you
Complications of phaeochromocytoma
Complications include hypertensive crisis, myocardial infarction, and hypotension.
When doing biochemical investigations for a phaeochromocytoma, why is it not enough to base the diagnosis on purely raised plasma catecholamines + what plasma test is more accurate
Disadvantage to testing for plasma catecholamines is that they are released episodically, unlike plasma metanephrines, which are released continually.
What are metanephrines and normetanephrines
by products of adrenaline and noradrenaline breakdown
Imaging investigations of a phaeochromocytoma once biochemical diagnosis confirmed (2)
Abdomen and pelvis CT
Abdomen and pelvis MRI
Mutation of what gene is associated with phaeochromocytomas
succinate dehydrogenase (SDH) B/C/D
Treatment of phaeochromocytoma
- pre-surgery (2)
- surgical (1)
1st line - medical treatment before surgery
=ANTIHYPERTENSIVES for a week to lower risk of dangerously high BP during surgery:
—> alpha blockers (doxasozin)
—> then beta blockers (atenolol) - only give after alpha blockers have had adequate effect on BP
HIGH SALT DIET (draws more fluid into blood, preventing development of low BP as alpha and beta blockers can cause orthostatic hypotension)
Then ADRENALECTOMY if suitable candidate
Clinical features of classical (simple virilising or salt-wasting types) congenital adrenal hyperplasia (7)
Ambiguous genitalia/virilisation of females Weight loss Failure to thrive Vomiting Hypotension Short stature Precocious (early) puberty
2 types of congenital adrenal hyperplasia
Classical (simple virilising or salt-wasting types)
-detected at birth/infancy
Non-classical
-detected childhood/early adulthood
Treatment of Cushing’s DISEASE (i.e. an ACTH secreting pituitary tumour) (3)
Medical therapy before surgery
-mifepristone (antagonist of glucocorticoid and progesterone receptors)
Transpehnoidal pituitary adenomectomy
Corticosteroid replacement therapy (hydrocortisone)
Treatment of Cushing’s syndrome due to an ACTH-independent
- both
- adrenal adenoma
- adrenal carcinoma
Both:
- Medical therapy before surgery
- –> mifepristone (antagonist of glucocorticoid and progesterone receptors)
Adenoma:
-Adrenalectomy or tumour resection
Carcinoma:
- adrenalectomy or tumour resection
- chemotherapy/radiotherapy
If only unilateral adrenalectomy then don’t need permanent post-surgical corticosteroid replacement but if bilateral then do need
Treatment of conn’s syndrome due to unilateral adrenal adenoma/carcinoma/hyperplasia (2)
Prep-op aldosterone antagonist (spironolactone)
then
Adrenalectomy
What therapeutic drug antagonises action of aldosterone
Spironolactone (K+ sparing diuretic)
Secondary hyperaldosteronism is usually due to what
*not pituitary adenoma
is a physiological response to decreased renal perfusion (i.e. decreased blood flow to kidneys) –> over-production of aldosterone from adrenals
Name an acute cause of adrenal insufficiency (Addison’s is chronic; not acute)
meningococcal septicaemia
