Adrenal disorders Flashcards
Causes of primary adrenal insuficiency
Addisn’s disease
Cogenital adrenal hyperplasia
Adrenal TB
Adrenal malignancy
Causes of secondary arenal insufficiency
Lack of ATCH stimulation
Iatrogenic (excess exogenous steroid)
Pituitary/hypothalamic disorders
What is the commonest cause of primary adrenal insufficiency?
Addison’s disease
What is Addison’s disease?
Autoimmune destruction of adrenal cortes
What percentage of the adrenal cortex is usually destroyed before the patient becomes symptomatic?
> 90%
What is Addison’s disease associated with?
Type 1 diabetes
Autoimmune thyroid problems
Pernicious anaemia
Clinical features of Addison’s disease
Anorexia/weight loss Dizziness Low BP Abdo pain Vomiting Diarrhoea Skin pigmentation
What causes skin pigmentation in Addison’s disease?
As when Addison’s destroy the adrenal cortex the brain responds by making more ACTH
ACTH is derived from POMC which is also a precursor for melanocyte stimulating hormone
What can precipitate Addisonian crisis?
Stress
Infection
Trauma
Surgery
Symptoms/signs of Addisonian crisis
Vomiting
Abdo pain
Hypotension
Shock & death
What biochemical findings would make you suspicious of Addison’s disease?
Low sodium
High potassium
Hypoglycaemia
How is Addison’s disease diagnosed?
Short synacthen test
(Addison’s excluded if after half an hour plasma cortisol >550mmol/L
When should treatment of Addison’s be commenced?
Do not delay treatment to confirm diagnosis
Treatment of Addison’s disease
Hydrocortisone (cortisol replacement
Flurocortisone (aldosterone replacement)
What it is important to monitor in fludrocortisone therapy?
K & BP
What is the commonest cause of secondary adrenal insufficiency?
Exogenous steroids
How does exogenous steroid use differ biochemically from Addisons disease?
Normal ACTH
Aldosterone production intact
Adrenocotical carcinoma
Rare
Usually functional
50% dead within 2 years
Adenoma appearance
Well cricumscribed Usually small Yellow/brown cut surface Well differentiated Small nucleus
What is Conn’s syndrome?
Primary hyperaldosteronism
ACTH-dependent causes of hypercortisolism
ATCH secreting pituitary tumour (Cushing's disease) Ectopic ACTH (small cell lung cancer)
ACTH-independent causes of hypercortisolism
Adrenal adenoma or carcinpoma
Non-lesional adrenal gland atrophies
What is primary hyperaldosteronism usually associated with?
Diffuse or nodular hyperplasia of both adrenal glands
Cuaes of secondary hyepraldosternism
Increased renin
Decreased renal perfusion
Hypovolaemia
Pregnancy
When is an adrenal neuroblastoma usually diagnosed?
18 months
What percentage of adrenal neuroblastomas arise in teh medulla?
40%
rest are mainly along sympathetic chain
What are adrenal neuroblastomas composed of?
Primitive appearing cells but can show maturation and differentiation toward ganglion cells
What 2 factors indicate a poor outcome in adrenal neuroblastoma?
Amplification of N-myc
Expression of telomerase
What is phaechromocytoma a feature of?
MEN 1 gene
MEN 2A (Sipple syndrome)
MEN 2B
What are the features of MEN 2A (Sipple syndrome)?
Phaechromocytoma (may be bilateral or occur at extra adrenal sites)
Medullary tyroid carcinoma
Parathyroid hyperplasia
What are the features of MEN 2B?
Phaechromocytoma
mEDULLARY THYROID CARCINMOA
nEUROMAS
MEN 2B & MEN 2A are both linked to which mutation?
Germline mutation in RET oncogene
What is Von Hippel Lindau syndrome?
Mutation in VHL gene causing an accumulation of HIF proteins & stimulation of cellular proliferation
What screening is vital in Von Hippel Lindau syndrome?
Vascular screening
What is a phaeochromocytoma?
A neoplasm derived from chromaffin cells of the adrenal medulla
Secretes catecholamines
Rare cause of secondary hypertension
What are the 10% rules of phaechromocytoma?
10% are extra-adrenal (paragangliomas, carotid body)
10% are bilateral
10% are malignant (defined by mets, more common in extra-adrenal)
10% are NOT associated with hypertension
25% are familial
How do familial phaeo’s tend to present?
Younger
More often bilateral
More often malignant
Treatment of phaeochromocytoma
Alpha blocker then beta blocker
Where is the most common metastatic spread for phaechromocytoma?
Skeleton
Complications of phaechromocytoma
Cardiac failure
Infarction
Arrythmias
CVA
How is phaeochrmocytoma diagnosed?
Detection of urinary excretion of catecholamines + metabolites
MRI
Symptoms/signs of Cushing’s disease
Osteoporosis Buffalo hump Thin skin AVN of femoral head Proximal myopathy Frontal balding in women Moon face Excess androgen (virilism, hirsutism, acne, ammenorrhoea) Conjunctival oedema Hypertension
How is Cushing’s syndrome diagnosed? (second line)
2 day Dexamethasone Supression Test
- 2mg/day
Cortisol
How is Cushing’s syndrome diagnosed? (first line)
Overnight 1mg dexamethasone supression test
cortisol
Causes of cushing’s syndrome?
Pituitary
Adrenal adenoma
Ectopic (thymus, lung, pancreatic)
Steroid medication
Treatment of adrenal caused Cushing’s
Adrenolectomy
Treatmnet of ectopic cause of cushings
Remove ectopic tissue or bilateral adrenalectomy
What would be the level of ACTH in a ectopic cause of cushing’s?
> 300
What is the role of metyrapone in the treatment of Cushing’s?
While waiting for radiotherapy to work
S/E common
