Adrenal Disorders Flashcards
What hormones does the medulla produce?
Norepinephrine and epinephrine
What is the common approach for endocrine symptoms?
Clinical suspicion - test for assessing functional status - aetiology - if tumour - endocrine deficiency correction
Describe the hypathalmo- hypopituitary axis
If under stress the hypothalamus produces CRH which acts on anterior pituitary to stimulate ACTH
This stimulates adrenal gland to release cortisol
There is a short and long negative feedback loop
What enzyme is important in producing cortisol and aldosterone?
21-hydroxylase
What are 3 adrenal disorders leading to hypofunction?
Adrenal destruction - most common
Adrenal Dysgenesis
Impaired steroidogenesis
What disease causes primary adrenal insufficiency?
Addison’s disease - autoimmune destruction, invasion, infiltration, infection, iatrogenic
What causes adrenal enzyme defects?
Congenital adrenal hyperplasia - 21 hydroxylase deficiency
Describe autoimmune Addison’s disease
Positive adrenal autoantibodies
Lymphocytic infiltrate of adrenal cortex
Associated autoimmune diseases are common
More than 85% of adrenal failure
What are some common symptoms associated with primary adrenal failure?
Weakness, fatigue, weight loss
Skin pigmentation or vitiligo
Hypotension
Unexplained vomiting and diarrhoea
Salt craving
Postural symptoms
What are some possible clue to diagnosis of adrenal failure?
Disproportional between severity of illness and hypotension/ dehydration
Unexplained hypoglycaemia
Other endocrine features
Previous depression or weight loss
How is adrenal insufficiency diagnosed?
Bloods - U+E, glucose and FBC (low Na and high K)
Random cortisol (>450nmol/l adrenal status uncertain)
Synacthen test - 250mg of tetracosactin IM or IV (ACTH)
What tests should be done is adrenocortical insufficiency suspected?
Rapid ACTH stimulation test
If normal then excludes primary
If abnormal then Plasma ACTH
If elevated then primary
If supressed then secondary
Describe glucocorticoid replacement
Hydrocortisone (20-30mg), prednisolone and dexamethasone
Given in divided doses to mimic normal diurnal variation - more given in morning
Describe mineralocorticoid replacement
Synthetic steroid - fludrocortisone
Binds to mineralocorticoid (aldosterone) receptors
50-300 mg daily
Adjust dose according to clinical status, U+E and plasma renin level
Who needs special care when treating hypofunction?
Hypo-adrenal patients on replacement steroids
Patients on steroids
Patients who have received previous 18/12 treatment
What happens to treatment if minor short lived illness or stress?
Double glucocorticoid dose
What happens to treatment if major illness or operation?
100mg hydrocortisone IV stat
50-100 HC via IV every 8hrs
What are the 3 self acre rules for patients on steroids?
Never miss steroid dose
Double hydrocortisone dose in event of intercurrent illness
If severe vomiting or diarrhoea then call for help
What are some causes of primary hyperaldosteronism?
Unilateral adenoma and bilateral hyperplasia
What are some rarer endocrine causes for hypertension?
Pheochromocytoma, Cushing’s, acromegaly, hyperparathyroidism, hypothyroidism and congenital adrenal hyperplasia
What causes hypersecretion from cortex of adrenal gland?
Cushing’s syndrome - cortisol and androgens
Conn’s syndrome - aldosterone
What is a cause of hypersecretion from medulla of adrenal gland?
Pheochromocytoma - catecholamines
What are the side effects of Cushing’s syndrome?
Weakness of skin, muscle and bone
Hypertension and heart failure
Diabetes mellitus
Describe Cushing’s syndrome
Excess corticosteroids
Cortisol is a catabolic hormone so can cause tissue breakdown, sodium retention and insulin antagonism
Also immune system suppression
What are some signs of Cushing’s syndrome?
Central obesity, proximal weakness, easy bruising, hypertension, purple striae, oedema, thin skin, and moon face
What can cause ACTH dependant or independent Cushing’s disease?
Dependent - pituitary tumour or ectopic ACTH secretion
Independent - adrenal tumour
What is the approach to hypersortisolism?
Overnight Dex test or 24hr urine free cortisol to screen and confirm
To see if ACTH dependent - paired morn midnight ACTH cortisol
To see if pituitary or not then high Dex test
MRI and CT for localisation
What is the normal range for 24hr urinary free cortisol?
14-135 nmol/24hr
What is the treatment for Cushing’s syndrome?
Surgery to remove causative tumour
Medical
RT
Bilateral adrenalectomy
What is the medical treatment for Cushing’s syndrome?
Adrenal hormone synthesis inhibitors - ketoconazole and Metyrapone
Destroy adrenocortical cells - mitotane
Describe Conn’s syndrome
Aldosterone excess production
Adenoma or bilateral hyperplasia
Aldosterone - water and sodium retention and K excretion
Describe the pathophysiology of primary hyperaldosteronism
Aldosterone producing tumour increases blood volume, blood pressure and urine K+
Renin gives angiotensinogen then angiotensin I then II
So increased Aldosterone and decreased renin
What is the screening for hyperaldosteronism?
Plasma PA/PRA ration
Primary hyperaldosteronism - Ratio is over 20
Secondary or essential - Ratio is under 20
What are 2 signs of hyperaldosteronism?
Hypertension and hypokalaemia
What does decreased plasma renin activity and increased aldosterone conc. suggest?
Primary hyperaldosteronism
What does increased PRA and PAC suggest?
Secondary hyperaldosteronism
What does decreased PRA and PAC suggest?
Congenital adrenal hyperplasia
Cushing’s syndrome
DOC producing tumour
What is the conformation test for hyperaldosteronism?
24hr urine aldosterone . 12 ug/day
Urinary sodium >200mEq
During 4 days of salt loading
What tests help to establish aldosterone source?
CT scan of adrenal glands
Upright posture test
Plasma 18-hydroxycorticosterone
Describe pheochromocytoma
Rare tumour of adrenal glands producing too much catecholamines - norepinephrine and epinephrine
Get hypertension, headache, sweating, palpitations, tremor, pallor and anxiety (paroxysmal attacks)
What are some types of pheochromocytoma?
MEN II
MEN III
Von Hippel Landau Syndrome
How is a suspected pheochromocytoma investigated?
24 hr urine - total metanephrines and catecholamines
If normal then re check later
If 2 fold elevation then CT/MRI for localisation
Also consider 123-IMIBG scan
What is tested for in pheochromocytoma - genetic testing?
PHEOs/ PGLs - this leads to the metabolic problem giving tumour growth
What is the preoperative preparation for removal of pheochromocytoma?
Non selective alpha blocker
Beta blockers may also be needed
When trying to take tumour out - if touched could release large amounts of catecholamines into bloodstream
What test should be done if there is clinical suspicion of adrenal mass?
Free metanephrine in plasma or urine
1mg Dexamethasone suppression test
If hypertension then K and ALD/PRA ratio
How is an adrenal mass tested to see if malignant or benign?
Unenhanced CT
Chemical shift MRI
Then delayed enhanced CT
Surgery if malignant and if benign surgery depends on size (>6cm)
Why does a deficit in 21-hydroxylase cause adrenal hyperplasia?
Lack of enzyme inhibits synthesis of cortisol
So removes negative feedback on ACTH and CRH
Increased ACTH secretion is responsible for enlargement
Describe congenital adrenal hyperplasia
90% of cases are 21 hydroxylase deficiency
Severe cases - neonatal salt losing crisis and ambiguous genitalia
Incomplete - hirsutism and pseudo-precocious puberty
