Pathology of the Adrenal Glands Flashcards
Briefly describe how congenital problems can cause adrenocortical hyperplasia?
Group of autosomal recessive disorders
Deficiency/ lack of enzyme required for biosynthesis
Altered biosynthesis leads to increased androgen production
Reduced cortisol stimulates ACTH release and cortical hyperplasia
What are the 2 causes of endogenous ACTH production in acquired adrenocortical hyperplasia?
Pituitary adenoma (Cushing's disease) Ectopic ACTH (paraneoplastic syndrome - SCLC)
With adrenocortical hyperplasia, is the adrenal gland enlargement diffuse or nodular?
Could be either
Diffuse - ACTH driven
Nodular - usually ACTH independent
What is the most common presentation of adrenocortical tumours?
Adults M=F Incidental finding Hormonal effects Mass lesion Carcinoma with necrosis can cause fever
What do adrenocortical adenomas look like?
Well circumscribed and differentiated encapsulated lesions 2-3 cm Yellow/ yellow brown surface Small nuclei, rare mitoses
Are most adrenocortical adenomas functional or non-functional?
Most commonly non-functional but can be functional
Are most adrenocortical carcinomas more likely to be functional?
Yes
Are adrenocortical carcinomas common?
No - rare
Where do adrenocortical carcinomas spread?
Local invasion - retroperitoneum, kidney
Mets - usually vascular (liver, lung and bone)
Peritoneum and pleura
regional lymph nodes
Adrenocortical carcinomas and adenomas can be hard to tell apart. What features are suggestive of malignancy?
Large size (>50g, often >20cm) Haemorrhage and necrosis Frequent mitoses, atypical mitoses lack of clear cells capsular or vascular invasion
What is the only definite criteria for an adrenocortical carcinoma?
Metastatic spread
Define primary aldosteronism.
Autonomous production of aldosterone independent of it’s regulators (ATII and K+)
How does primary aldosteronism present?
Significant hyperthyriodism
Hypokalaemia (~30% cases)
Alkalosis
What are the 4 subtypes of 1y aldosteronism?
Adrenal adenoma – Conn’s syndrome
Bilateral adrenal hyperplasia
Rare – genetic mutations and unilateral hyperplasia
How do you confirm aldosterone excess?
Measure Plasma aldosterone & renin (aldo:renin ratio)
Ratio >750 then Ix with saline suppression test
Failure of plasma aldosterone to suppress by >50% with 2L normal saline confirms 1y aldosteronism
How do you decide what the cause of the 1y aldosteronism is?
Confirm sub-type:
Adrenal CT – adenoma
Sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess
How is bilateral adrenal hyperplasia managed?
Spironolactone or Epelerone (MR anatgonists)
How is 1y aldosteronism caused by an adrenal adenoma managed?
Unilateral laproscopic adrenalectomy - cures hypokalaemia and HTN in 30-70% cases
What is congenital adrenal hyperplasia?
Rare conditions associated with enzyme defects in the steroid pathway.
What is the most common enzyme defect associated with congenital adrenal hyperplasia?
21a-hydroxylase deficiency
Why is congenital adrenal hyperplasia a problem?
Altered biosynthesis leads to androgen excess. Decreased cortisol production stimulates ACTH release and cortical hyperplasia
What investigations are required for CAH?
Basal (or stimulated) 17-hydroxylase progesterone (key enzyme that helps us make cortisol and aldosterone)
What is the classical presentation of CAH?
males: poor weight gain
Adrenal insufficiency
Decreased Na+ but high potassium
Females: genital ambiguity
What S&S are seen in non-classical presentation of CAH?
hirsutes, acne, oligomenorrhoea, precocious puberty, infertility
What are the prinicples of treatment of CAH in a child?
Timely recognition required Glucocorticoid replacement Mineralocorticoid replacement (in some) Surgical correction of ambiguous genitalia Achieve maximal growth
If CAH is realised in an adult, what treatment principles are required?
Control androgen excess
Restore fertility
Avoid steroid over-replacement
What are acquired forms of adrenocortical hyperplasia?
Endogenous ACTH production (ituitary adenoma or ectopic ACTH from other tumour: paraneoplastic syndrome)
Bilateral adrena enlargement
The 2 forms of adrenocrotical hyperplasia are diffuse and nodular. What differentiates them?
Diffuse: ACTH driven
Nodular: ACTH independent
What can cause secondary adrenalcortical hypofunction?
Failure to stimulate adrenal cortex (hypothamalic disorder)
Suppression of adrenal cortex
What can cause acute primary adrenalcortical hypofunction?
Rapid withdrawl of steroid treatment
Adrenal crisis in pts with chronic adrenocortical insufficiecy
Massive adrenal haemorrhage
How is adrenalcortical insufficiency treated?
Hydrocortisone
Fludrocortisone
Education
What test is used to diagnose adrenalcortical insufficiency?
Short Synacthen test
What colour are phaeochromocytomas typically described as?
Tan
Which cells are phaeochormocytomas derived from?
Chromaffin cells of adrenal medulla
What do phaeochromocytomas secrete?
Cathecholamines
What scan can detect phaeochromocytomas and neuroblastomas?
MIBG scan
How are phaeochromocytomas treated?
Surgical excision
HTN treatment
Full alpha and beta-blockade - Phenoxybenzamine and Atenolol
Fluid and/or blood replacement
Describe both normal and results showing adrenal insufficiency from a short synacthen test.
Measure plasma cortisol before and 30 mins after IV ACTH injection
Normal: baseline >250nol/L Post-ACTH >480nmol/L
Addisons – baseline is very low Post-ACTH rise is very high
What are the biochemical abnormalities associated with phaeochormocytoma?
Hyperglycaemia Decreased K+ (maybe) High haemotocrit Mild hypercalcaemia lactic acidosis - in absence of shock
In the case of phaeochromocytoma, who should be investigated?
Family members with syndromes resistant HTN <50yo with HTN Classical symptoms Consider Ix if HTN and hyperglycaemia
What are the classical symtpoms of phaeochromocytoma?
“dreadful” “feeling of impending doom” Pallor Anxiety constipation Weight loss abdominal pain Pyrexia and sweating Hypertension postural hypotension Headache palpitations
Why are phaeochromocytomas known as the 10% tumour?
10% exra-adrenal 10% bilateral 10% malignant 10% not associated with HTN 10-25% familial
How is MEN inherited?
Autosomal doinant genetic condition
Briefly , what is Von-Hippel-Lindau syndrome?
Mutation in HIF 1-alpha
Autosomal dominant
Range of ascular tumours
Family screening vital
