Adrenal Flashcards
From superficial to deep, what are the layers of the adrenal cortex and what do they produce?
Zona glomerulosa - produces mineralocorticiods (aldosterone)
Zona fasciculata - produces glucocorticoids (cortisol)
Zona reticularis - produces androgens
Describe the steps of the renin-angiotensin-aldosterone-system (RAAS)
- Low sodium sensed by macula densa cells of the juxtaglomerular apparatus in the kidneys stimulated renal production of renin
- Renin converts angiotenisogen (produced by the liver) to angiotensin I
- Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II
- Angiotensin II vasoconstricts and releases aldosterone from the zona glomerulosa
- Aldosterone acts on the kidneys to increase sodium and water retention increasing blood pressure
What formation of glucocorticoids-glucocorticoid receptor activates transcription and which suppresses transcription?
Dimer activates transcription
Monomer suppresses transcription (by blocking NK kappa B)
How do glucocorticoids work?
Binding to intracellular receptors and altering DNA transcription
What cells are within the adrenal medulla and what do they do?
Chromaffin cells
Convert tyrosine to catecholamines
What is Addison’s disease?
Destruction of the adrenal cortex causing adrenal insufficiency (commonly autoimmune but can be infectious)
How does Addison’s disease present?
Non specific weight loss, fatigue
Dizziness
Skin pigmentation
What causes the skin pigmentation in Addison’s disease?
Excess ACTH acts on melanocytes
What do the stress hormones do to blood sugar levels?
Increase them
What blood results would you expect to see in Addison’s disease?
Hyponatraemia
Hyperkalaemia
(from loss of mineralocorticoid)
Hypoglycaemia
(from loss of cortisol)
How do you diagnose Addison’s disease?
Short Synatchen test
Measure cortisol before and after administering synthetic ACTH
If cortisol isn’t raised >550mmol/l, patient has Addison’s Disease
How is Addison’s disease treated?
Hydrocortisone replacement
Fludocortisone replacmeent
Patient presents with vomiting and abdominal pain. Blood results show hyponatreamia and hyperkalaemia.
What is the diagnosis?
Addisonian crisis
How is an Addisonian crisis managed?
Hydrocortisone IV
IV fluids
(IV glucose may also be needed)
What do patients with Addison’s disease do with their medications if they are ill?
Double doses
What should you consider if a child is diagnosed with a adrenocortical tumour?
Genetic condition (e.g.Li Fraumeni syndrome)
What features suggest a malignancy in an adrenocortical tumour?
Functional tumours
Large
Necrosis (present as fever)
What is a neuroblastoma?
Tumour of nervous tissue which often arises in adrenal medulla
Who tends to develop neuroblastomas?
Young children
What is a phaeochromocytoma?
Tumour of adrenal medulla chromaffin cells which secrete catecholamines causing symptoms
How do phaeochromocytoma present?
Episodes of
- Headache
- Hypertension
- Sweating
- Tachycardia
- Anxiety
- Tremor
How do you diagnose phaeochromocytoma?
Urine/plamsa catecholamine to confirm catecholamine excess
MRI abdomen to find source of excess
How do you treat phaeochromocytoma?
a-blocker (phenoxybenzamine) then ß-blocker
Then excision or chemotherapy if malignant
What is congenital adrenal hyperplasia (CAH)?
Group of conditions caused by deficiency of an enzyme involved in steroid synthesis resulting in steroid deficiencies
What enzyme is most commonly deficient in congenital adrenal hyperplasia (CAH)
21a-hydroxylase
What does a 21a-hydroxylase deficiency cause?
Loss of aldosterone and cortisol but excess androgen
What are the two classifications of congenital adrenal hyperplasia (CAH) and how do they present?
Classical:
severe enzyme deficiency presenting in infancy with
- adrenal insufficiency
- genital ambiguity
Non-Classical: milder enzyme deficinecy presenting with - precocious puberty - hirsutism - acne - oligomenorrhoea - infertility
How can congenital adrenal hyperplasia (CAH) be diagnosed?
Raised progesterone, 17-OH progesterone
Genetic mutation analysis
What is Cushing’s syndrome?
Collection of symptoms caused by excess cortisol
What is Cushing’s disease?
Excess cortisol caused by pituitary adenoma producing excess cortisol
How does Cushing’s syndrome present?
(breakdown)
Thin skin
Proximal myopathy
Osteoporosis
(altered lipid metabolism)
Central obesity
Moon face
Buffoon hump
(androgen excess)
Acne
Hirsutism
Amenorrhoea
What are 4 causes of Cushing’s syndrome?
Functional pituitary adenoma producing excess ACTH
Adrenal hyperplasia producing excess cortisol
Ectopic tissue producing excess ACTH
Excess exogenous steroids
What is the commonest cause of Cushing’s syndrome?
Excess exogenous steroids
What are the first line tests in the diagnosis of Cushing’s syndrome and how are they performed?
Overnight dexamethasone suppression test
- give 1mg PO dexamethasone at midnight and measure cortisol at 8am
- suppresses to <50nmol/l
- no suppression in Cushing’s
24h urinary cortsiol
- normal <280nmol/l
- raised in Cushing’s
What is the definitive diagnostic test for Cushing’s syndrome and when is it used?
Low dose dexamethasone suppression test
- give 0.5mg dexamethasone BD for 2 days and measure cortisol after last dose
- suppresses to <50nmol/l
- no suppression in Cushing’s
What test can distinguish pituitary Cushing’s disease from other causes of Cushing’s syndrome?
High dose dexamethasone test (2mg dexamethasone 6 hourly for 2 days)
- if this suppresses cortisol levels, suggests pituitary cause
- no suppression, ectopic/adrenal cause
What test can distinguish adrenal Cushing’s syndrome from other causes?
Measuring serum ACTH
ACTH is very low in adrenal Cushing’s
What results would you expect to see in high dose dexamethasone suppression test and by measuring serum ACTH in:
- Pituitary Cushing’s
- Adrenal Cushing’s
- Ectopic Cushing’s?
- Dexa - suppresion of cortisol ; ACTH - raised
- Dexa - no suppression ; ACTH - low
- Dexa - no suppression ; ACTH- raised
How is Cushing disease treated?
- Hypophysectomy (first line)
- Radiotherapy
- Bilateral adrenalectomy
How is adrenal Cushing’s treated?
Adrenalectomy
How is ectopic Cushing’s treated?
Remove ectopic tissue
Name 3 drugs which can be used to treat Cushing’s syndrome.
Metyrapone
Ketoconazole
Pasirotide
What is a common source of ectopic ACTH?
Small cell lung cancer
What produces aldosterone?
Zona glomerulosa of adrenal cortex
What produces cortisol?
Zona fasciculata of adrenal cortex
What produces androgens?
Zona reticularis of adrenal gland
What stimulates aldosterone release?
Low sodium (indirectly via RAAS)
High potassium (directly)
What does aldosterone do?
Acts on MR receptor on distal convulated tubule and collecting tubule to increase sodium reabsorption and potassium excretion
(keeps sodium, removes potassium)
What is primary aldosteronism?
Autonomous production of aldosterone causing hypertension, hypokalaemia and metabolic alkalosis
What is the biochemical presentation of hyperaldosteronism?
Hypernatreamia
Hypokalameia
Alkalosis
What is the clinical presentation of hyperaldosteronism?
Hypertension (sodium retention)
Weakness, cramps (hypokalaemia)
Confusion, vomiting, tetany (alkalosis)
Name 2 causes of primary aldosteronism.
Bilateral adrenal hyperplasia
Adrenal adenoma (Conn’s syndrome)
Name a gene mutation which may predispose to primary hyperaldosteronism.
KCNJ5
How do you diagnose primary hyperaldosteronism?
- Confirm aldosterone excess with
- raised aldosterone-renin-ratio
- saline suppression test (2l of saline don’t suppress aldosterone by 50%) - Confirm type with
- PET-CT overlay
- Adrenal vein sampling
How do you treat bilateral adrenal hyperplasia?
Spironolactone (MR antagonist)
How do you treat Conn’s syndrome?
Unilateral adrenalectomy
What is secondary adrenal insufficiency?
Adrenal failure from lack of ATCH stimulation due to pituitary tumour or exogenous steroids
How does secondary adrenal insufficiency present clinically?
Non specific weight loss, fatigue
Dizziness
Without skin pigmentation (lack of ACTH is the problem)
How is secondary adrenal insufficiency treated?
Hydrocortisone (replacement for cortisol)
no mineralocorticoid replacement needed
