adrenal gland disorders Flashcards
what part of the adrenal gland is highlighted red?
medulla
what part of the adrenal gland is highlighted red?
cortex
what is highlighted red?
right adrenal gland
what is highlighted red?
left adrenal gland
what are the 3 different layers of the adrenal gland?
- Capsule (most outer)
- Cortex
- Medulla (most inner)
what layers are in the cortex of the adrenal glands?
- zona glomerulosa
- zona fasciculata
- zona reticularis
what regulates the zona glomerulosa?
- Angiotensin II
- K+
what regulates the zona fasciculata?
ACTH
what regulates the zona reticularis?
ACTH and unknown factors
what does the zona glomerulosa layer of the adrenal gland secrete?
mineralocorticoids (e.g. aldosterone)
what does the zona fasciculata in adrenal glands secrete?
-glucocorticoids (e.g. cortisol and corticosterone)
what does the zona reticularis in adrenal glands secrete?
adrenal androgens (e.g. DHEA and DHEA-sulfate)
what makes up the medulla of the adrenal gland?
- chromaffin cells
- medullary veins
- splanchnic nerves
what does the medulla of the adrenal glands secrete?
-catecholamines (epinephrine and norepinephrine)
what regulates cortisol and androgen production?
-androgen and cortisol production is regulated by hormones produced in the hypothalamus and anterior pituitary gland
what regulates aldosterone?
-renin angiotensin system and plasma potassium
do steroid hormones bind extra or intracellularly?
intra cellularly
what are the 6 classes of steroid receptors?
- glucocorticoid
- mineralocorticoid
- progestin
- oestrogen
- androgen
- vitamin D
what effect does cortisol have on the CNS system?
- mood lability
- euphoria/ psychosis
- decrease in libido
what effect does cortisol have on the circulatory/renal system?
- increase in cardiac output
- increase in blood pressure
- increase in renal blood flow and GFR
what effect does cortisol have on the metabolic system?
- causes an increase in blood sugar
- increase in lipolysis
- increase in proteolysis
what effect does cortisol have on bone/ connective tissue?
- it accelerates osteopersosis
- decreases calcium
- decreases collagen formation
- decreases wound healing
what effect does cortisol have on immunology?
- decreases capillary dilatation/permeability
- decreases leucocyte migration
- decreases macrophage activty
- decreases inflammatory cytokine production
what are the 3 main principles of the clinical use of corticosteroids?
- suppress inflammation
- suppress immune system
- replacement treatment
what effect does aldosterone have on sodium/potassium balance?
- it promotes K+/H+ excretion
- increases Na+ reabsorption
what is aldosterone responsible for?
- sodium/potassium balance
- blood pressure regulation
- regulation of extracellular volume
where are mineralocorticoid receptors (MR) found?
- kidneys
- salivary glands
- gut
- sweat glands
what is the receptor for aldosterone?
-mineral corticoid receptor (MR)
what type of hormone is aldosterone?
steroid hormone
what is adrenal insufficiency?
-when there is inadequate adrenocortical function
what are some examples of primary adrenal insufficiency?
- Addison’s disease
- congenital adrenal hyperplasia (CAH)
- adrenal TB/malignancy
what are some examples of secondary adrenal insufficiency?
- lack of ACTH stimulation
- iatrogenic (excess exogenous steroid)
- pituitary/hypothalamic disorders
what is the most common cause of primary adrenal insufficiency?
Addison’s disease
what is Addison’s disease?
-the autoimmune destruction of the adrenal cortex
are autoantibodies commonly found in patients with Addison’s disease?
yes- autoantibodies are positive in 70% of cases
how much of the adrenal cortex is damages in addison’s before becoming symptomatic?
> 90%
what other diseases is Addison’s associated with?
-other autoimmune diseases (e.g. T1DM, autoimmune thyroid disease, pernicious anaemia)
How does Addison’s disease present?
- anorexia/ weight loss
- fatigue
- dizziness and low BP
- abdominal pain, vomiting, diarrhoe
- skin pigmentation
how is adrenal insufficiency diagnosed?
Bloods test:
- decrease in Na, increase in K
- hypogylcamia
- ACTH levels raised (causes skin pigmentation)
- renin raised
- aldosterone lower
- adrenal autoantibodies
SHORT SYNACTHEN TEST
- measure plasma cortisol before and after 30 mins after iv/im ACTH injection
- normal: baseline > 250 nmol/L, post ACTH >550nmol/L
what is the management of adrenal insufficiency?
- hydrocortisone given as cortisol replacement
- fludrocortisone as aldosterone replacement
need to have a steroid treatment card!
how does secondary adrenal insufficiency due to exogenous steroid use present differently compared to Addison’s?
- in secondary adrenal insufficiency the skin is pale (as there is no increase in ACTH)
- aldosterone production is intact
what is the management for secondary adrenal insufficiency due to tumours?
-surgery/ radiotherapy
how do you treat secondary adrenal insufficiency due to exogenous steroid use?
-with hydrocortisone replacement
what is cushings syndrome?
-a disease that causes excess cortisol secretion
who is cushings syndrome more common in?
-women ages 20 to 40
what are some clinical features of cortisol excess?
- easy bruising
- facial plethora
- striae
- proximal myopathy
what are some ACTH dependant causes of Cushing’s syndrome?
- pituitary adenoma (cushings disease)
- ectopic ACTH
- ectopic CRH
what are some ACTH independant causes of Cushing’s syndrome?
- adrenal adenoma
- adrenal carcinoma
- nodular hyperplasia
what is the difference between cushings syndrome and cushings disease?
cushings disease is specifically cortisol excess due to a problem with the pituitary whereas cushings syndrome is cortisol excess with a problem outwith of the pituitary
how is cushing’s syndrome diagnosed?
- overnight dexamethasone suppression test
- 24 hour urinary free cortisol
- late night salivary cortisol
- low dose dexamethasone suppression test
repeat to confirm
what is the commonest cause of cortisol excess?
-iatrogenic cushing’s syndrome
what causes iatrogenic cushing’s syndrome?
-due to prolonged high dose steroid therapy
what is iatrogenic cushing’s syndrome?
-the chronic suppression of pituitary ACTH production and adrenal atrophy
what effect can long term steroid treatment have on ACTH?
- long term steroid treatment suppresses ACTH production
- this can lead to atrophy of adrenal cortex
can steroids be stopped suddenly?
no they cant be stopped suddenly there must be a gradual withdrawal of steroid therapy if >4-6 weeks
what are some endocrine causes of hypertension?
- acromegaly
- cushings syndrome
- prim
what would hypertension and hypokalaemia suggest?
-primary aldosteronism
what is primary aldosteronism?
-autonomous production of aldosterone independant of its regulators (angiotensin II/potassium)
what effects does aldosterona have?
- increase collagen
- increase in sympathetic outflow
- altered endothelial function and increase in pressor response
- increase in cardiac collagen
- sodium retention
- cytokines and ROS synthesis
what is the commonest secondary cause of hypertension?
primary aldosteronism (PA)
what are clinical features of primary aldosteronism (PA)?
- significant hypertension
- hypokalaemia
- alkalosis
what are subtypes of primary aldosteronism?
- adrenal adenoma
- bilateral adrenal hyperplasia (commonest cause)
- genetic mutations and unilateral hyperplasia (rare)
How is primary aldosteronism (PA) diagnosed?
Step 1: confirm aldosterone excess
- measure plasma aldosterone and renin and express a ration (ARR- aldosterone to renin ratio)
- if ratio raised then investigate further with saline suppression test
- failure of plasma aldosterone to suppress by >50% with 2 litres of normal saline confirms PA
Step 2: confirm subtype
- adrenal CT to demonstrate adenoma
- sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess
what is the management of primary aldosteronism if there is an adrenal adenoma?
Surgical
-unilateral laparoscopic adrenalectomy
what is the management of primary aldosteronism if there is bilateral adrenal hyperplasia?
MR antagonist (spironolactone or eplerenone)
what is congenital adrenal hyperplasia (CAH)?
-congenital adrenal hyperplasia is an inherited group of disorders characterised by a deficiency in one of the enzymes necessary for cortisol synthesis
what causes congenital adrenal hyperplasia?
- due to 21 alpha-hydroxylase deficiency
- autosomal recessive
what are the 2 types of congenital adrenal hyperplasia (CAH)?
- classic CAH
- non classic CAH
when is classic CAH normally diagnosed?
-in infancy
what is non- classic CAH due to?
a partial 21alpha- hydroxylase deficiency
who does non-classic CAH usually present in?
-in adolescence/ adulthood with hirsutism, mental disturbances, infertility due to anovulation
how does classic congenital adrenal hyperplasia present?
- salt wasting
- simple virilising
how does non classic congenital adrenal hyperplasia present?
-hyperandrogenaemia
what is the diagnosis of congenital adrenal hyperplasia?
- Basal (or stimulated) 17-OH progesterone
- increasingly supported by genetic mutation analysis
what is the presentation of classical CAH in male neonates?
adrenal insufficiency:
- often seen in the first 2 to 3 weeks
- poor weight gain
- biochemical pattern of Addison’s disease
what is the presentation of classical CAH in female neonates?
-genital ambiguity (virilisation)
what is the presentation of classical CAH in females?
- hirsute
- acne
- oligomenorrhoea
- precocious puberty
- infertility or sub fertility
what is the treatment for CAH in children?
- timely recognition
- glucocorticoid replacement
- mineralocorticoid replacement in some
- surgical correction
- achieve maximal growth potential
what is the treatment for CAH in adults?
- control androgen excess
- restore fertility
- avoid steroid over replacement
what is pheochromocytoma?
-a type of neuroendocrine tumor that grows from cells called chromaffin cells
what is a paraganglioma?
-a type of neuroendocrine tumor that forms near certain blood vessels and nerves outside of the adrenal glands
what effect does phaeochromocytoma have on blood pressure?
-it increases it causing hypertension
what is the presentation of phaeochromocytoma?
Classic triad (90% cases)
- hypertension
- headache
- sweating
- palpitations
- breathlessness
- constipation
- anxiety/fear
- weight loss
- flushing (uncommon)
what is the classical triad for phaeochromocytoma?
- hypertension
- headache
- sweating
what are the signs of phaeochromocytoma?
- hypertension
- postural hypotension
- pallor
- bradycardia and tachycardia
- pyrexia
what are some complications of phaeochromocytoma?
- left ventricular failure
- myocardial necrosis
- stroke
- shock
- paralytic ileus of bowel
how is phaeochromocytoma diagnosed?
confirm catecholamine excess by :
- uring (2 x 24 hour catecholamines or metanephrines)
- plasma
Then identify the source of catecholamine excess by doing:
- MRI scan of the abdomen and whole body
- MIBG scan
- PET scan
what is the treatment for phaeochromocytoma?
Laparoscopic surgery, long-term follow up and genetic testing= gold standard!!
(if malignant do chemo)
-to prepare patients for surgery they need to be put on medication:
Full alpha and beta-blockade (A before B)
-phenoxybenzamine (alpha blocker)
-propranolol, atenolol or metoprolol (beta blocker)
what are some clinical syndrome associations with phaeochromocytoma?
- multiple endocrine neoplasia 2 (MEN2)
- Von Hippel Lindau syndrome
- succinate dehydrogenase mutations
- neurofibromatosis
- tuberose sclerosis
what are some endocrine causes of hypertension that are curable?
- cushing’s syndrome
- conn’s syndrome
- phaeochromocytoma
