Adrenal Disorders Flashcards
This deck covers the main adrenal disorders:
- Cushing’s Syndrome
- Addison’s Disease
- Conn’s Syndrome
- Pheochromocytoma
2 types of primary adrenocortical insufficiency
Acute and chronic adrenocortical insufficiency
Adrenal enzyme defects (CAH)
What is Addison’s Disease? [2]
Insufficiency adrenal cortex [1] causing insufficient glucocorticoids and mineralocorticoids [1]
What causes Addison’s? Primary vs Secondary
Mainly Autoimmune
Primary causes
* tuberculosis
* metastases (e.g. bronchial carcinoma)
* meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
* HIV
* antiphospholipid syndrome
Secondary causes
* pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
*Primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
How does Addison’s Present?
State 7 clinical feature with the most likely at the top
In decreasing order of likelihood:
- Weakness, fatigue, weight loss & anorexia
- Skin pigmentation or vitiligo (loss of pigment)
- Hypotension
- Unexplained hypoglycaemia
- Salt Craving
- Postural Symptoms
- N&V + Diarrhoea
What tests do you do if you suspect Addison’s? [5]
Early morning cortisol tests- >500 nmol/L makes Addison very unlikely. <100 nmol/L is definitely abnormal. 100-500 nmol/L requires short synacthen test.
Short Synacthen test (ACTH stimulation) 250 micrograms IM - measure plasma cortisol before and 30 min after synacthen.
U&Es
hyponatraemia, hyperkalemia, hypoglycemia, metabolic acidosis
What does a random cortisol test tell you about addison’s and why is it first line investigation?
If they’re cortisol is >700nmol/l then it’s not Addison’s
First line investigation as high negative predictive value
What does a synacthen test tell you about Addison’s?
Give ACTH to see how much their cortisol goes up
In addison’s they should produce very little cortisol
Why test plasma ACTH in Addison’s? [2]
If its elevated it confirms Primary Adrenal Insufficiency (due to negative feedback)
If its suppressed however the source is secondary (cause is pituitary or hypothalamic dysfunction)
Rx Addison’s disease? [2]
State dose
Glucocorticoid replacement e.g. Hydrocortisone 20-30mg
Mineralocorticoid replacement e.g. Fludrocortisone 50-300 mcg daily
Sick day rules for steroid replacement
Why are glucocorticoid replacements given in divided doses? Give an example of what this may mean
During stressful stimuli they need an increased dose, as their own production is suppressed. But as stress abates, reduce by 50% per day until back on usual dose
Double dose on minor or intercurrent illness
Divided doses: eg
HC 20mg at 9h then 10mg at 18h
Why? To mimic diurnal variation, avoid at bedtime as can cause insomnia
What other conditions are associated with Addison’s [3]
Other autoimmune conditions like:
- Type 1 DM
- Thyroid disease
- Premature ovarian failure
How does Cushing’s Disease present?
- Moon face & pendulous breasts/abdomen, edema
- Proximal myopathy
- Thin skin > ulcers
- Spontaneous purpura
- DM
- Cardiac failure due to muscle atrophy
- Hirsutism
Types of Cushing’s? [6]
ACTH dependant
- Pituitary Tumour - 75% (cushings disease)
- Ectopic ACTH - 5% (lung cancer)
ACTH independant:
- Adrenal adenoma or carcinoma -20%
- CCS therapy
Investigations: Cushing’s Disease
What are the 2 tests used for screening Cushing’s Disease?
What screening test is reliable for Cushing’s syndrome?
Screening
Overnight dex suppression test
24 hour urine cortisol
Late night salivary cortisol - Cushing’s syndrome
Paired morning/midnight cortisol/ACTH test to check ACTH dependency
If ACTH dependent do a High dose Dex test to identify source of ACTH
Localise with MRI/CT/CT chest as appropriate
What is Conn’s Syndrome? [2]
Whats the presentation of Conn’s Syndrome?
An aldosterone secreting tumour [1] in the adrenal cortex [1]
Hypertension
- Overactivation of RAAS > hypertension
Hypokalemia
- Excess aldosterone, overwork of Na/K pump
What are 3 causes of primary hyperaldosteronism?
State levels of renin and aldosterone in:
- Primary hyperaldosteronism
- Secondary hyperaldoesteronism
Bilateral idiopathic hyperaldosteronism
Conn’s syndrome (adenoma)
Familial hyperaldosteronism
- Primary hyperaldosteronism - Ald high, renin low so PRA: PAC ratio high
- Secondary hyperaldosteronism
Ald high, renin high
Tests for Conn’s Syndrome? [3]
Explain the upright posture test [3]
If you see hypertension & hypokalemia:
- Plasma aldosterone (PAC) /renin ratio (PRA)
- > 20 & a raised aldosterone indicates Conn’s syndrome
Following this a high-resolution CT abdomen and adrenal vein sampling is used to differentiate between unilateral and bilateral sources of aldosterone excess
Aldosterone is affected by upright posture and therefore samples are taken lying down and then repeated after being upright for a few hours [1]
Plasma aldosterone increases with bilateral hyperplasia [1] but not affected in adrenal adenoma [1]
What is a pheochromocytoma?
A tumour of the adrenal medulla that secretes excess catecholamines
How does pheochromocytoma present?
Hypertension along with paroxysmal attacks of:
- Headaches
- Sweat
- Palpitations
- Tremor
- Pallor
- Anxiety/fear
How do you investigate a pheochromocytoma?
patient with High BP & paroxysmal adrenaline attacks
24 hr urinary collection of metanephrines
Followed by adrenal MRI/CT
How do you manage pheochromocytoma? [3]
• Surgical excision:
o Pre-op: use alpha blocker (PHENOXYBENZAMINE) to avoid unopposed alpha adrenergic stimulation (use beta blocker too if heart disease or tachycardia)
o Post-op: 24h urine metadrenalines 2w postop and monitor BP due to hypotension risk
• Malignant: adjuvant chemo, RT or therapeutic radio labelled MIBG
Familial hyperaldosteronism
Describe the mutation [2]
Describe the pattern of inheritance [1]
Overactivity of the aldosterone synthase gene [1] CYP11B2 [1]
AD inheritance
Conn syndrome Mx
Medical management [1] - give an example [1]
Surgical management [1]
Aldosterone antagonist - K sparing diuretics eg spironolactone
Surgical removal - adrenalectomy (laparoscopic)
What are the side effects [3] of spironolactone and explain why these are the side effects [1]
Not only blocks aldosterone receptors but also testosterone receptors
SE: gynecomastia, menstrual problems, erectile dysfunction
Management of Cushing’s syndrome
What NOT to do and why [2]
Dont suddenly withdraw steroids as can cause adrenal crisis
Surgical excision of pituitary adenoma
Adrenal steroid inhibitors eg ketoconazole, metyrapone (especially useful for ectopic ACTH)
Summary of difference between Conns and Addisons
Addisons: High K, Low Na, hypotension
Conns: Low K, High Na, hypertension, alkalosis
Addisonian crisis
Name 4 causes
- auses
- sepsis or surgery causing an acute exacerbation of chronic insufficiency (Addison’s, Hypopituitarism)
- adrenal haemorrhage eg Waterhouse-Friderichsen syndrome (fulminant meningococcemia)
- steroid withdrawal
Addisonian crisis
Management [4]
Management
* hydrocortisone 100 mg im or iv
* 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
* continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
* oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Addisonian crisis
Management [4]
Management
* hydrocortisone 100 mg im or iv
* 1 litre normal saline infused over 30-60 mins or with dextrose if hypoglycaemic
* continue hydrocortisone 6 hourly until the patient is stable. No fludrocortisone is required because high cortisol exerts weak mineralocorticoid action
* oral replacement may begin after 24 hours and be reduced to maintenance over 3-4 days
Management of Conns syndrome
- Unilateral adenoma & found to be functioning > surgical removal
- bilateral adrenal hyperplasia, surgery not possible but medical management - spironolactone.
