Adrenal Glands - Hyperfunction Flashcards
what does the zona glomerulosa produce
aldosterone
what do the zone fasciculata and zona reticularis produce
fasciculata - cortisol
reticularis - androgens
what does the medulla produce
noradrenaline and adrenaline
what activates the RAAS system
decrease in blood pressure
what are the effects of aldosterone
increased cardiac collagen
cytokines and ROS synthesis
sodium retention
increased sympathetic outflow
altered endothelial function - increased pressor
increased blood pressure, LVH and atheroma
synthesis of steroids
- They are synthesized from the same initial precursor cholesterol, and secreted on demand. They are lipid soluble (lipophilic) so when they are synthesized they are immediately capable of moving out of that cell (this is why they are secreted on demand).
- bind to intracellular receptors, and bind to nuclear DNA affecting transcription
- cholesterol - pregnenolone - progesterone (through the action of 3ßHSD)
what are the CNS actions of glucocorticoids
mood lability
euphoria/psychosis
decereased libido
what are the bone/connective tissue actions of glucocorticoids
accelerates osteoperosis by stimulating osteoclasts
decreased serum Ca, collagen formation and wound healing
what are the immunological actions of glucocorticoids
decreased:
- capillary dilatation/permeability
- leucocyte migration
- macrophage activity
- inflammatory cytokine production
suppress immune system to dampen pain response
what are the metabolic actions of glucocorticoids
carboydrate : inc blood sugar
lipid : inc lipolysis and central redistribution of it
inc proteolysis
what are the 3 main principles of use of glucocorticoids:
suppress inflammation
suppress immune system
replacement treatment
what are some causes of acquired adrenocortical hyperplasia
endogenous ACTH production: pituitary adenoma(Cushing’s disease) or ectopic ACTH (paraneoplastic syndrome - often SCLC)
bilateral adrenal enlargement as an inappropriate normal response
diffuse and nodular adrenocortical hyperplasia
diffuse - ACTH driven usually
nodular - usually ACTH independent
congenital adrenal hyperplasia syndromes
rare conditions associated with enzyme defects in the steroid pathway
most common form of CAH
the most common one is 21 hydroxylase deficiency (95% of cases), which affects one of the cytochrome p450 enzymes (p450c21)
results in reduced cortisol secretion, and this increases ACTH to maintain adequate cortisol, leading to adrenal hyperplasia
diversion of steroid pathway into androgenic pathway occurs
what is the result of the diversion of the steroid pathway into androgenic pathways in CAH
- 17-hydroxyprogesterone, androstenedione and testosterone levels are increased, leading to virilization and precocious puberty
- Aldosterone synthesis may be impaired with resultant salt wasting (low blood sodium concentration and dehydration).
- Non-classically, there can be hyperandrogenaemia.
diagnosis of CAH
basal (or stimulated with synACTHen test) 17 hydroxyprogesterone increased
increasingly suppported by genetic mutation analysis
basal ACTH levels raised
define salt wasting
low blood sodium concentration and dehydration
how can CAH present if severe
- if severe, can present with sexual ambiguity or adrenal failure (collapse, hypotension and hypoglycaemia), sometimes with a salt losing state (hypotension and hyponatraemia)
- eg Child may present with ambiguous genitalia, and then have severe vomiting, dehydration and weight loss
clinical features of CAH
female: clitoral hypertrophy, urogenital abnormalities and labioscrotal fusion
male: can be unrecognised, poor weight gain, adrenal insufficiency (starts at around 2-3 weeks), biochemical pattern
precocious puberty
hirsutism
acne
oligomenorrhoea
infertility/sub-fertility
what is the development of hirsutism before puberty suggestive of
CAH
treatment principles of CAH in paediatrics
timely recognition
glucorticoid (and mineralocorticoid) replacement
surgical correction
achieve maximal growth potential
treatment principles for adult physicians
control androgen excess
restore fertility
avoid steroid over replacement
who do adrenocortical tumours tend to occur in
adults, although can occur in younger patients (especially those with Li-Fraumeni syndrome
Li-Fraumeni syndrome
cancer predisposition syndrome caused by a germline mutation of p53 tumour suppressor gene
what can carcinomas with necrosis cause
fever
- pyrexia of unknown origin is a possible presentation
adrenocortical adenoma
well circumscribed, encapsulated lesions
usually small and have a yellow/brown surface - preponderance of lipid laden cells
they are well differentiated with small nuclei
adrenocortical carcinoma
rare
most of the lesions are clearly malignant at presentation with local spread (retroperitoneum/kidney) and/or metastases
what are tumours secreting androgens, oestrogens or precursor steroids more likely to be
malignant
what is the only definite criteria for malignancy
metastases
what are features suggestive of adrenocortical carcinoma
large (>50g >20cm)
haemorrhage and necrosis
frequent mitoses, atypical mitoses
lack of clear cells (not well differentiated)
capsular/vascular invasion
assimilation of evidence
Waterhouse Friderichen Sydnrome
- Adrenal failure due to bleeding into adrenal gland
- Commonly caused by severe bacterial infection, typically Neisseria Meningitidies
