Adrenal Pathology Flashcards
Common causes of hyper active adrenals?
Hyperplasia
Adenoma
Carcinoma
Common causes of hypo active adrenals?
Acute - Waterhouse friderichsen
Chronic - Addisons
What are the two types of adrenocortical hyperplasia?
Acquired
Congenital
What are the two causes of acquired adrenocortical hyperplasia ?
Endogenous ACTH (Cushings disease) Ectopic ACTH ( From small cell lung cancer)
If the hyperplasia is diffuse how is the growth driven?
ACTH driven
If the hyperplasia is nodular how is the growth driven?
ATCH independant (tumour sarcoid etc)
Why does an increase in ACTH cause hyperplasia?
ACTH is a stimulant and bind to receptors within the adrenal gland, increase in stimuli increases the drive for growth to keep up with demand.
What is the main cause of congenital adrenocortical hyperplasia?
Autosomal recessive metabolic disorder
-deficiency in enzyme required for steroid biosynthesis
What is likely to be seen in an autosomal recessive metabolic disorder resulting in adrenocortical hyperplasia?
Deficiency in target hormone
Increased ACTH and another hormone
If a child presents with an adrenal tumour what should be screened for?
Genetic syndrome p53 inhibition
How can adrenal tumours be found?
Hormonal affects
Mass lesion, incidental finding
Carcinomas can undergo necrosis resulting in a fever
Adrenal adenoma
Well circumscribed
Yellow cut surface
Well differentiated
N/C ratio is normal
Are most adrenal adenomas functional?
Most aren’t but some can be
Why are the cut surfaces of adrenal adenomas yellow?
Adrenal glands are the centre of lipid metabolism into steroids
Carcinomas are less likely to be functional that adenomas?
False - more likely to be
If a carcinoma is virilising what does this usually signify?
Malignant potential
Adrenal Carcinoma
Closely resembles and adenoma
Local invasion - retroperitoneal and kidney
Metastasis - Liver Lung Bone
What is the 5 year survival with an adrenal carcinoma?
20-35%
What is the main differentiating feature between a carcinoma and an adenoma?
Carcinomas undergoes metastasis
How else are carcinomas different to adenomas?
Can weigh over 50g or >20cm
Haemorrhage and Necrosis
Atypical frequent mitosis
Capsular invasions
Primary hyperaldosteronism
Conns
Primary Hypercortsisolism
Cushings
Causes of acute adrenal failure?
Rapid withdrawal of steroids
Massive adrenal haemorrhage
Causes of adrenal haemorrhage?
Newborn
Anticoagulation therapy
Septicaemic infection
What is Waterhouse- Friderichsen syndrome?
Acute adrenal failure due to severe adrenal haemorrhage as a result of a septicaemic infection
In ectopic ACTH production what else is notable ?
Hypokalaemia, due to high levels of ACTH and mineralocorticoids causing water retention.
What is the main chronic adrenal insufficiency?
Addisons disease
What is Addisons disease?
Inadequate adrenocorticoid levels due to bilateral autoimmune destruction of the adrenal glands.
Symptoms of Addison’s
Anorexia Weight loss Dizziness and feinting Non specific abdominal pain D+V Hyperpigmentation
In Addisons where is hyperpigmentation first noticed?
Palmar creases
Dentists may notice in Buccal cavity
Why does hyperpigmentation occur in addison’s?
ACTH can stimulate melanocytes to produce melanin
What is used to diagnose Addisons?
Low Na+ High K+ Hypoglycaemia ACTH levels High Renin and Low Aldosterone Adrenal autoantibodies CT MRI
What variation of the SynACTHen test is used and why?
Short synACTHen
-plasma cortisol levels 30 mins after IV ACTH
As this is a medical emergency patients die quickly
What results should be looked for in a short synACTHen test?
Normal - >250 pre and post ACTH of >550
What is the key point in treating suspected Addison’s disease?
Don’t wait for lab results
What is the treatment of Addisons and any acutely presenting adrenal failure?
IV 100mg Cortison and 1000ml of saline
What is the treatment for Addisons?
Oral 15-30 mg divided 3x daily
10mg morning 5mg lunch and 5mg at dinner
In regards to Addisons what should also be considered?
Aldosterone replacement- Fludrocortisones
-monitor BP and K+
Much like diabetics what is important to tell the patient?
Don’t stop treatment if ill, in fact increase dose
If unable to digest orally due to D+V then admission for IV
What is secondary adrenal insufficiency ?
Lack of CRH or ACTH
What is the commonest cause of secondary adrenal insufficiency?
Exogenous long term steroid use
Why does exogenous steroid use result in insufficiency ?
Negative feedback inhibits ACTH production, which is main stimulant for adrenal growth, as a result adrenal glands are atrophied - don’t react to ACTH anymore
What test can still be used in secondary insufficiency?
SynACTHen test
What are the key features that can distinguish secondary from primary adrenal insufficiency?
Pale skin as no ACTH
Aldosterone production is intact
What is the management of secondary adrenal failure
Hydrocortisone but no mineralcorticoids
As well as autoimmune list some other common causes of adrenal failure
TB
HIV
How can an iatrogenic Cushing’s lead to Addisons?
Chronic ACTH suppression leads to adrenal Hypotrophy so unable to produce steroids endogenously
If a patient with iatrogenic cushings falls ill what must be given?
Extra steroids whilst ill
What should be done if withdrawing a patient of long term steroids?
Done slowly over 4/6 weeks,
If patient unable to tolerate continue with treatment.
What is the physiology behind primary aldosteronism?
Autonomous production of aldosterone independent of the Renin-Angiotensin system.
Reabsorption on Na+ and excretion of K+
What are some of the effects aldosterone has?
Increased Cardiac collagen, sympathetic outflow, altered endothelial pressor response, sodium retention.
What are some clinical signs and symptoms in Primary aldosteronism?
Significant resistant hypertension
Increased Left Ventricular hypertrophy
Increased atheromas
Hypokalaemia
What is Conns?
Aldosterone production from an Adrenal Adenoma
What is the commonest cause of primary hyperaldosteronism?
Bilateral Adrenal Hyperplasia
List a rare cause of Primary hyperaldosteronism
K+ Channel mutation
What is main stay of diagnosis in hyperaldosteronism?
Aldosterone excess - Aldosterone higher than renin
Give 2L of saline - normal would lead to aldosterone suppression.
What else can be used after aldosterone excess test in hyperaldosteronism?
Imaging CT and PET scan
Adrenal Vein sampling
What is the medical treatment of hyperaldosteronism and when is it used?
Spironolactone
In bilateral adrenal hyperplasia
What is spironolactone?
A Potassium sparing diuretic
Steriod which blocks the effect of aldosterone
What is the surgical treatment of hyperaldosteronism and when is it used?
Unilateral laparoscopic adrenalectomy
Designed as curative treatment for adrenal adenoma
- 30-70% curative
- older is less curative
Congenital adrenal hyperplasia
Rare conditions linked to defect enzyme in steroid synthesis
What is the most common cause of congenital adrenal hyperplasia?
21α hydroxylase deficiency
- autosomal recessive
In 21α hydroxylase deficiency what occurs?
No aldosterone or cortisol and excess androgens
What happens as a result of excess aldosterone?
Salt Wasting
What happens as a result of excess androgens?
Virilisation
What is the diagnostic test of a 21α hydrolase deficiency?
17-OH progesterone levels will be high when tested
In a Neonatal adrenal crisis what signs indicate a 21α hydroxylase deficiency ?
Male - excess testosterone
Female - Ambiguous genitalia
What is a classic presentation of 21α hydroxylase deficiency ?
Presents 2/3 weeks old with biochemical Addisons
-hypoglycaemia and poor weight gain
What is the non classical presentation of 21α hydroxylase deficiency ?
Presents generally in older female
-Hirsutism, Acne, Precocious puberty, infertility, oligomenorrhoea
What is the treatment for a classic presentation of a 21α hydroxylase deficiency ?
Glucocorticoid and mineralocorticoid replacement
Surgical correction - to achieve maximum growth
Why does excess androgens reduce maximum height?
As triggers early onset puberty so growth plates fuse early.
What is the treatment aims for a non classic presentation of a 21α hydroxylase deficiency ?
Restore fertility
Suppress excess androgens
What are some clues that could hint towards a Phaechromyocytoma
Labile hypertension - rapidly fluctuating BP
High Diastolic
Postural hypotension
What is a Phaechromyocytoma?
Rare adrenal medullary tumour
1 in 100,000
Insidious onset
Why is a Phaechromyocytoma called a tumour of 10’s?
10% malignant
10% Bilateral
10% Extra adrenal
10% children
If the a Phaechromyocytoma occurs in the sympathetic chain what is it called?
Paraganglioma
Why can the same tumour occur in the medula and sympathetic chain?
Because the medulla is made up of sympathetic splanchnic nerves.
What is Phaechromyocytoma linked to?
MEN2
- Think Phaechromyocytoma and Neurofibromatosis
What is Phaechromyocytoma often confused with?
Angina Anxiety Menopause Pregnancy Hypoglycaemia
What is the classic triad of a Phaechromyocytoma symptoms?
Hypertension
Headache
Sweating
What others presenting complaints do people with a Phaechromyocytoma come in with?
Palpitations Panic attacks Anxiety Weight loss Flushing Constipation
List some complications of a Phaechromyocytoma
LVF
Myocardial necrosis
Stroke
Paralytic ileum
What are the biochemical signs of a Phaechromyocytoma?
Hyperglycaemia
Slightly low K+
High haematocrit
Mild hypercalcaemia
When should investigations be under taken?
Phaechromomycytoma
Over 50 with marked resistant hypertension
Family members diagnosed with MEN2
Which is more useful in the diagnosis of a Phaechromyocytoma?
Catelcolamines or Metanephrines
Metanephrines as they are more stable, so give a more accurate measurement.
What is the diagnostic test for a Phaechromyocytoma?
24 hr metanephrine urine collection
MRI
Plasma at time of symptoms
Why if possible should an MRI be done from pelvis to head?
As Phaechromyocytoma can occur anywhere in the sympathetic chain as preganglioma
What is the first step in the treatment of a Phaechromyocytoma?
Alpha blocker followed by a Beta blocker
Give an example of an alpha blocker used
Phenoxybenzamine
What is the beta blockers used in Phaechromyocytoma’s?
Propanolol
What should follow the Alpha and beta blockade in the treatment of Phaechromyocytoma?
Fluid and Blood replacement to control the hypotension as a result of vasodilation due to the blockade
What are the final steps in the treatment of a Phaechromyocytoma?
Surgical excision is posible
Chemotherapy or radiotherapy if surgery isn’t an option
If surgery is successful what will happen in the case of a Phaechromyocytoma?
Reversal of the hypertension to normal requiring no other treatment.
Following treatment what should a patient who suffered with a Phaechromyocytoma undergo?
Long term follow up
Genetic testing
- if +ve check immediate family members
