Adrenal Gland Flashcards
What does the zona glomerulosa produce and what is it regulated by?
Produces mineralocorticoids (aldosterone) Regulated by potassium
What does the zona fasciculata produce and what is it regulated by?
Glucocorticoids (cortisol and corticosterone)
Regulated by ACTH
What does the zona reticularis produce and what is it regulated by?
Adrenal androgens (DHEA, testosterone) Regulated by ACTH and other unknown factors
What can be found within the adrenal medulla and what do they produce?
Chromaffin cells
Medullary vein
Splanchnic nerve
Produce catecholamines (noradrenaline and adrenaline)
What system regulates the production of aldosterone?
Renin-antiogenin system and plasma potassium
What occurs in BP falls?
Sensed by kidneys, angiotensionogen is converted to angiotensin 1
This is converted to angiotensin 2 in the lungs by ACE which acts on the adrenal zona golmerulosa to produce aldosterone which acts to retain salt increasing BP
What is the action of angiotensin 2?
Direct vasoconstriction
Indirect aldosterone release
What are the 6 classes of steroid receptors?
Mineralocorticoid - aldosterone Progestin Oestrogen Androgen Vitamin D
What effect does cortisol have on the CNS?
Mood liability
Euophoria/psychosis
Decreased libido
What effect does cortisol have on bones/connective tissue?
Accelerates osteoporosis
Decreases serum calcium, collagen formation and wound healing
What effect does cortisol have on the immune system?
Decreases capillary dilation/permeability
Decreases leucocyte migration, macrophage activation and inflammatory cytokine production
What effect does cortisol have on metabolism?
Increases BG
Increases lipolysis
Increases proteolysis
What effect does cortisol have on the circulatory/renal system?
Increases cardiac output
Increases BP
Increases renal blood flow and eGFR
What are the 3 main principles of corticosteroid use?
Suppress inflammation
Suppress immune system
Replacement treatment
What diseases are corticosteroids particularly useful?
Allergic disease: asthma/anaphylaxis
Inflammatory disease: RA, UC, crohns
Malignant: improve appetite, suppress excess hormone production
What are the effects of aldosterone?
Sodium/potassium balance: K+/H+ excretion and Na+ reabsorption
BP regulation
Regulation of ECF
What can cause primary adrenal insufficiency?
Addison’s disease
Congenital adrenal hyperplasia
Adrenal TB
Adrenal malignancy
What can cause secondary primary adrenal insufficiency?
Due to lack of ACTH stimulation
Iatrogenic
Pituitary/hypothalamic disorders
Describe autoimmune polyglandular syndrome type 1 and 2
Type 1 = Addisons, hypoparathyroidism, mucosal candidiasis
Type 2 = hypothyroidism, addisons, T1DM
What is waterhouse friderichesen disease?
Bilateral haemorrhage into adrenal glands due to sepsis
What are the clinical features of addison disease?
Anorexia, wt loss Fatigue/lethary Dizziness/ low BP Abdo pain D+V Skin pigmentation (buccal mucosa)
What biochem is seen in addison/addisonian crisis?
Hyponatraemia
Hyperkalaemia
Hypotension
Hypoglycaemia
What is the short synacthen test?
250 micrograms of ACTh and do a cortisol level at 0 and 30 mins
Baseline should be above 250 and after 30 mins should rise to 500
Anything below that is abnormal
What will the ACTH levels be like in addisons?
Very high
What will the renin/aldosterone levels be like in addisons?
High renin
Reduced aldosterone
What will it suggest is there are high levels of 17-OH progesterone?
CAH
What should you do if there is a negative 21-Oh antibody?
CT adrenals: infiltrative disease, adrenal haemorrhage, infections, malignant tumours
What is adrenoleukodystrophy?
X-linked - breakdown of myelin which is the fatty covering of nerve cells, causes progressive dysfunction of the adrenal gland
Why is ACTH increased in addison’s if there is not cortisol?
Failure in the negative feedback loop- cortisol acts to suppress the hypothalamic (CRH) and anterior pituitary and therefore when there is no cortisol the levels of CRH and ACTH increase
How is an addisonian crisis managed?
IV hydrocortisone - 100mg IV/IM then 50mg every 6hr until well
0.9% saline - due to salt loss
Fludrocortisone for lack of mineralocoritoids
How is addison disease managed?
Give hydrocortisone to mimic physiological steroids - diurnal variation
Fludrocortisone - need to monitor BP and K
What are the sick rules in addison’s disease?
Double hydrocortisone for intercurrent illness until recovery - if unable to tolerate medication due to gastroenteritis need IM or SC hydrocortisone
Major surgery - 100mg IV pre op then continous infusion of 200mg/24hr
What can cause secondary adrenal insufficiency (lack of CRH/ACTH)?
Pituitary/hypothalamic disease tumours
Exogenous steroid use
What are the clinical features of secondary adrenal insufficiency?
Similar to addisons EXCEPT:
skin pale
Aldosterone production intact
Treat with hydrocortisone replacement
What are the clinical features of cortisol excess?
Easy bruising Facial plethora Striae Proximal myopathy Mental health: anxiety, fear, depression Interscapular fat pad Poor wound healing Central obesity Moon face Osteoporosis Increased appetitie T2DM
What is a common presentation of cushing’s?`
17 year old girl with a 3 year history of central weight gain, acne, amenorrhoea, hypertension, severe osteoporosis, proximal muscle weakness
What causes ACTH dependent cushing’s?
Pituitary adenoma - cushing’s disease
Ectopic ACTH
Ectopic CRH
What causes ACTH independent cushing’s syndrome?
Adrenal adenoma
Adrenal carcinoma
Nodular hyperplasia
What tumours commonly produce ACTH?
Small cell lung carcinoma Bronchial carcinoid tumour Thymic carcinoid Pancreatic islet cell tumour Pheochromocytoma Medullary carcinoma
How is cushing’s diagnosed?
Establish cortisol excess: overnight dexamethasone suppression test
24 urinary free cortisol
Late nigh salivary cortisol
What occurs in the low dose dexamethasone suppression test?
0.5mg every 6hrs for 48hrs - 2mg overall
If dexamethasone suppresses cortisol levels then you don’t have cushing’s
What is the commonest cause of cushing’s syndrome?
Prolonged high dose steroid therapy - asthma, RA, IBD, transplants
Chronic suppression of pituitary ACTH production and adrenal atrophy
What are the implications of long term steroid use?
Unable to respond to stress
Need extra doses when ill/surgical procedure
Cannot stop suddenly
Gradual withdrawal of steroid therapy if >4-6 weeks
What are the endocrine causes of hypertension?
Conn’s syndrome
Pheochromocytoma
Cushing’s
Acromegaly
What does hypertension, hypokalemia and alkalosis suggest?
Primary aldosteronism
What is primary aldosteronism?
Autonomous production of aldosterone independent of its regulators (angiotensin 2/potassium)
What is conn’s syndrome?
Aldosterone adenoma in the adrenal cortex
What occurs are the apical membrane?
Retention of sodium and excreting potassium
How does spironolactone work?
mineralocorticoid receptor antagonists - can cause hyperkalaemia
What are the CV actions of aldosterone?
Increases symp flow Increased cardiac collagen Altered endothelial function BP Sodium retention LVH Increased production of free radicals
What can cause primary aldosteronism?
Conn’s syndrome
Bilateral adrenal hyperplasia
Genetic mutations
Unilateral hyperplasia
What is step 1 in the diagnosis of primary aldosteronism?
Measure plasma aldosterone and renin and express as ratio
If raised, then investigate further with saline suppression test
Failure of plasma aldosterone to suppress by more than 50% with 2 litres of normal saline confirms PA
What is step 2 in the diagnosis of primary aldosteronism?
Adrenal CT to demonstrate adenoma
Adrenal vein sampling to confirm adrenoa is true source of aldosterone excess
At a cellular level, what causes conns?
Mutation in the potassium channel of adrenocorticoid cells
How is PA treated?
Surgical onlyif adrenal adenoma and excess confirmed in adrenal vein sampling
Medical in bilateral adrenal hyperplasia
Use MR antagonists - spirnoloacton
What will surgery cure in PA?
Hypokalaemia
Hypertension in 30-70% of cases
What is CAH?
Disorder resulting in malfunction in steroid production due to mutations int he enzyme 21-alpha hydroxylase
Very high levels of testosterone
What is the mode of inheritance of CAH?
Autosomal recessive inheritance in consanguineous parents
Can be sporadic
What are the classical symptoms of CAH?
Salt-wasting
Hypotension
Adrenal crisis
Simple virilising of females
How is CAH diagnosed?
Basal 17-OH progesterone levels
How will CAH present in males?
Adrenal insufficiency within first 2/3 weeks
Poor weight gain
Biochemical pattern of addisons
Percocious puberty
How will CAH present in females?
Genital ambiguity
Hirsutism
Acne
Oligomenorrhea
How is CAH treated in children?
Glucocorticoid replacement
Surgical correction
Achieve maximal growth potential
How is CAH treated in adults?
Control androgen excess
Restore fertility
Avoid steroid over-replacement
What are the precursors of adrenaline and noradrenaline?
Tyrosine to L-dope to dopamine which converts to noradrenaline which then converts to adrenaline
What is a paraganglioma?
Extra-adrenal pheochromocytoma that can occur anywhere in the symp chain
What is a MIBG scan?
Scan that shows the ability of a phaeo to take up a radio-isotope linked to the MIBG tracer
What cells does the phaeo originate from?
Neuroendocrine tumour of the medulla originating from the chromaffin cells
What are clinical clues to phaeochromocytoma?
Labile hypertension (see-sawing hypertension) Postural hypotension Paroxysmal sweating Headache Pallor Tachycardia
What is the rule of 10s in a phaeo?
10% malignant 10% bilateral 10% extra-adrenal 10% familial 10% associated with hyperglycaemia 10% children
What colour will a phaeo turn the adrenal gland?
Reduces chrome salts to metal chromium resulting in a brown colour reaction
What is included in the differential of a phaeo?
Angina Anxiety Carcinoid Thyrotoxicosis Insulinoma Menopause Arrhythmia e.g. SVT Migraine Drug toxicity Alcohol withdrawal Pregnancy Hypoglycaemia
What is the classic symptoms in a phaeo?
Hypertension Headache Sweating Palipatations Breathlessness Constipation Wt loss Anxiety/fear FHx
What are signs of complications in a phaeo?
LVF Myocardial necrosis Stroke Shock Paralytic ileus of bowel
What biochemical abnormalities are present in a phaeo?
Hyperglycaemia Hypokalaemia High haematocrit Mild hypercalcaemia Lactic acidosi
Who should be investigated for a phaeo?
Family members with syndromes Resistant hypertension Young (under 50) with hypertension Classical symptoms Consider with hypertension and hyperglycaemia
How are catecholamines excess confirmed?
Urine - 2x24h4 catecholamines
Plasma - ideally at time of symptoms
How is a phaeochromocytoma diagnosed?
MRI scan: abdomen, whole body
MIBG
PET scan
How is a phaeo treated?
Always A before B Alpha blockage Beta blocker Fluid/ blood replacement Careful anaesthetic assessment Surgery Chemo is malignant
What clinical syndromes is a pheochromocytoma associated with?
MEN2 VHL SDH - B and D Neurofibromatosis Tuberous sclerosis
