adrenal physiology and pathology Flashcards
where are the adrenal glands
on top of kidneys
histologically, what 3 parts make up the adrenal glands
capsule, cortex, medulla
what steroids does the cortex synthesise
Mineralocorticoids (aldosterone)/ glucocorticoids (cortisol)/ adrenal androgens(DHEA),
what steroids does the medulla synthesise
Catecholamines (epinephrine and norepinephrine)
what are steroids in the adrenal cortex made from
cholesterol
what causes cortisol (glucocorticoid) to be released from the adrenal cortex and what is the axis
stress response: hypothalamus releases CRH –> ant pit releases ACTH –> adrenals releases cortisol
which zona is cortisol released from
zona fasciculata
what causes aldosterone (mineralocorticoid) to be released
low blood pressure or high potassium (from RASAS system)
which zona is aldosterone released from
zona glomerulosa
what effect does aldosterone have on Na/K balance
Na reabsorption and K excretion
where are steroid receptors
nucleus
what effects do steroids have on the body
augment sympathetics, stress response, gluconeogenesis, proteinolysis, suppresses immune system, maintain BP, lower mood and libido
what medical uses are steroids for
suppress inflamm and immune system
what is adrenal insufficiency
inadequate adrenocortical function
what can cause primary adrenal insufficiency
Addison’s, congenital adrenal hyperplasia (CAH), adrenal malignancy
what can cause secondary adrenal insufficiency
lack of ACTH, iatrogenic (excess steroids), pit/ hypothalamic disorders
what is addisons disease
autoimmune destruction of adrenal cortex resulting in increased ACTH but decreased cortisol
what is addisons associated with
T1DM, thyroid disease, pernicious anaemia, TB, haemochromatosis
what are symptoms of Addison’s disease
anorexia and weight loss, hypotension, amenorrhoea, fatigue, dizziness and low BP, abdo pain, V+D. skin pigmentation
what blood test results would be seen in Addisons (biochem/ ACTH + cortisol / aldosterone/ antibodies)
biochem: increased Na, low K/ ACTH: high, cortisol: low / aldosterone: low / antibodies: 21 OH
what diagnostic test is used for adrenal insufficiency
synACTHen test: after injection will be no rise in cortisol if adrenal insufficiency
what is the most common cause of secondary adrenal insufficiency
exogenous steroid use - increases ACTH eg prednisolone, ICS, dexamethasone
what symptoms differ in primary and secondary adrenal insufficiency and why
no skin pigmentation (no ACTH increase), normal BP (normal aldosterone)
how do you treat adrenal insufficiency
DO NOT DELAY TREATMENT FOR RESULTS: hydrocortisone (cortisol), flucortisone - primary only (mineralocorticoid)
what is Cushing’s syndome
excess cortisol from adrenal overactivity
what is Cushing’s disease
excess cortisol and adrenal overactivity FROM a pit adenoma
who normal gets cushing’s syndrome
women aged 20-40
what are main symptoms of Cushing’s (9)
thin limbs fat body, striae, alopecia, myopathy, osteoporosis (fractures), think skin and bruising, oedema, acne
what effects do excess cortisol have in Cushings
protein loss:( myopathy, osteoporosis, thin skin). altered carb and lipid metabolism, T2DM, obesity, psychosis and depression
what effects do excess mineralocorticoids and androgens have in Cushings
mineralocorticoids: hypertension and oedema/
androgens: virilism, acne, amenorrhoea
what can cause Cushing’s (5)
pit adenoma (cushings DISEASE) / benign adrenal adenoma / exogenous meds eg steroids /ectopic ACTH production (thymus, lung, pancreas tumour)
what is pseudocushings and what can cause it
screening test is positive but definitive negative - severe depression and alcohol can cause
what is the screening test for Cushing’s
dexamethasone at night check cortisol 9 hours later - normal <50, abnormal 130
what is the definite Cushing’s diagnosis test
2mg of dexamethasone for 2 days, >50 = cushings
what surgical treatments are first line for Cushing’s
pituitary: hypophysectomy (transspehnoidal) + radio if needed/ adrenal: adrenalectomy / ectopic: remove souce
what drugs can be used in Cushing’s if surgery fails
metryapone and ketocanazole
how do chronic steroids cause adrenal atrophy
chronic suppression of ACTH production –> adrenal atrophy
what are the dangers of iatrogenic adrenal suppression
unable to initiate stress response, CANNOT STOP SUDDENLY
what is primary hyperaldosteronism (PA)
autonomous production of aldosterone independent of it’s regulators (angiotensin II and K)
what are causes of PA
adrenal adenoma eg CONNS SYNDROME, bilateral adrenal hyperplasia (most common), genetics eg KCNJ5 channel (rare)
what are symptoms of PA
HYPERTENSION, frequent, urination, weakness and fatigue, muscle cramps, hypokalaemia, hypernatremia, alkalosis
how do you diagnose PA (3)
plasma aldosterone and renin, saline suppression test (2L of saline should reduce aldosterone by 50%), adrenal CT
when would you treat PA surgically
adrenal adenoma (Conn’s) - unilateral adrenalectomy
when would you treat PA medically and with what
bilateral adrenal hyperplasia - mineralocorticoid antagonist eg spirnolocatone
what is congenital adrenal hyperplasia
rare condition that causes enzyme defect in steroid pathway of adrenal glands
what deficiency is most common in CAH and what does it result in
21a hydroxylase –> increased testosterone
what symptoms are seen
with CAH as babies (4)
adrenal insufficiency weeks 2/3, poor weight gain, increased K, decreased Na+ FEMALE genitalia ambiguity
what symptoms can be seen in later life with CAH
acne, hirsutism, infrequent periods
how do you treat CAH
steroid replacement and surgery
what is an adrenal medulla tumour cause and what does it cause excess of
Pheochromocytoma - excess epinephrine, norepinephrine
what classic triad is seen in Pheochromocytoma
hypertension, headache, sweating
what other symptoms are seen in Pheochromocytoma
hyperglycaemia, palpitations, SOB, constipation, anxiety, weight loss
what biochem can be seen in Pheochromocytoma (3)
hyperglycaemia, hypokalaemia, lactic acidosis
how do you diagnose Pheochromocytoma (its hard to do)
urine and plasma catecholamine, MRI, PET
what is Pheochromocytoma associated with
MEN2, neurofibromatosis, TB
how do you treat Pheochromocytoma (4)
alpha blockers first then beta blockers eg prazosin, doxazosin, propanolol/ fluids / surgical excisiion. chemo if malignant
