Endo - Adrenals Flashcards
Hormone produced by Adrenal Medulla?
Adrenaline
Hormone produced by zona glomerulosa and mediated by?
Aldosterone
Mediated by K+ level and angiotensin II
Hormone produced by zona fasciculata and mediated by?
Cortisol
ACTH
Hormone produced by zona reticularis and mediated by?
DHEAS (androgens)
ACTH
Cortisol peak and trough?
Highest on waking Lowest asleep (midnight)
Functions of cortisol?
Hyperglycaemia Increased gluconeogenesis and resistance to insulin Decreased lymph/mono/eos and B & T cells Decreased growth Decreased Ca+ Increased bone resorption Increased androgens
Aldosterone stimulated by?
Angiotensin II
Hyperkalameia
ACTH
Aldosterone inhibited by?
Atrial Naturietic Peptide
Function of aldosterone?
Maintain intravascular volume
Increases Na channel expression in renal collecting ducts which increases Na+ resorption (bringing H20) and increases K+ excretion
Function of adrenaline and noradrenaline?
Raise MAP
Adrenaline increases cardiac output
1mg pred =?hydrocort
1mg Methylpred = ?hydrocort
1mg dexamethasone = ?hydrocort
1mg pred =4mg hydrocort
1mg Methylpred = 5mg hydrocort
1mg dexamethasone = 25mg hydrocort
Physiological requirement of hydrocortisone?
10mg/m2/day
Primary adrenal insufficiency due to what?
Inadequate adrenal function
Deficit in glucocorticoids and mineralocorticoids
Central adrenal insufficiency due to what?
Secondary - pituitary defect (ACTH)
Tertiary - hypothalamic defect (corticotrophin releasing hormone)
Deficit in glucocorticoids only
Signs of primary adrenal insufficiency?
Low cortisol High ACTH Hyponatremia Hyperkalaemia HTN Hyperpigmentation of skin (bronze) Fasting hypoglycaemia
Signs of secondary adrenal insufficiency?
Low cortisol Low ACTH Fasting hypoglycaemia Increased insulin sensitivity FTT, GIT upset, fatigue, weakness
Most common cause of primary adrenal insufficiency?
Congenital Adrenal Hyperplasia
Signs of over replacement of glucocorticoids?
Excess hydrocortisone dose = weight gain, cushingoid features
Sign of under replacement of glucocorticoids?
Insufficient hydrocortisone dose = hyperpigmentation, hypoglycaemia, FTT, high ACTH
Signs of over replacement of mineralocorticoids?
Excess fludrocortisone = HTN and low renin
Signs of under replacement of mineralocorticoids?
Insufficient fludrocortisone = salt craving, hyponatremia, hyperkalaemia, hypotension, high renin
Most common form of CAH?
21 hydroxylase deficiency
Second most common cause of CAH?
11-beta-hydroxylase deficiency
Signs of 21 hydroxylase deficiency (classic) CAH?
Glucocorticoid deficiency
Mineralocorticoid deficiency
(typically adrenal crisis by D10-14 of life)
Ambiguous genitalia in females
Early virilisation - pubic/axillary hair, early skeletal maturation
How is height affected in classic CAH?
Final height 8-10cm shorter
Signs non-classic CAH?
Normal glucocorticoid and mineralocorticoid function
Isolated hyperandrogenism without adrenal insufficiency
Premature pubarche, BO, hisutism, pubic hair
Advanced bone age, reduced adult height
Why does 11 beta hydroxylase deficiency have some mineralocorticoid function?
Blocks conversion of DOC to corticosterone and 11-DOC to cortisol however there is an adjacent pathway that is unaffected allowing aldosterone synthase production
DOC has mineralocorticoid function
Clinical manifestation of 11 beta hydroxylase deficiency?
Excess androgens (but milder than CAH)
Excess mineralocorticoids (via DOC)
Cortisol insufficiency
-> HTN, hyperkalaemia, ambiguous female genitalia/increased penis size
Treatment of 11 beta hydroxylase deficiency?
Hydrocortisone
Don’t give fludrocortisone usually - sometimes even need Spiro as mineralocorticoid antagonist
Cushing syndrome vs Cushing disease?
Syndrome = prolonged glucocorticoid excess Disease = specifically ACTH secreting pit adenoma
Cushing syndrome + precocious puberty, fibrous dysplasia and cafe au lait?
McCune Albright
Causes of ectopic ACTH production?
Islet cell ca neuroblastoma Ganglioneuroblastoma Wilms Thymic carcinoid
How does 2 step Dex suppression test differentiate ACTH dependant and independent cushing syndrome?
ACTH-independant (secondary) causes not suppressed with smaller or larger dose of cortisol
ACTH-dependant (central) causes will be suppressed with larger dose
What is Conn’s Syndrome?
Excess aldosterone secretion (independent of RAAS)
Child with hypernatremia, hypokalaemia, hypertension and high aldosterone and decreased renin activity?
Conn’s Syndrome
Causes of Conn’s?
Aldosterone secreting adenoma
Bilateral nodular adrenocortical hyperplasia
Unilateral hyperplasia
Cancer syndromes assoc w adrenocortical tumours?
Li Fraumeni (p53) MEN1 Familial adenomatous polyposis PRKAR1A Beckwith-Wiedemann
Child presents with HTN, tachycardia, sweating, headache. Progresses to hypertensive encephalopathy. Good appetite but failing to thrive. Dx?
Phaechromocytoma
What is a phaechromocytoma?
Catecholamine secreting tumour arising from chromatin cells -> produced adrenaline, noradrenaline and dopamine
In adrenal medulla 90%
10% elsewhere in sympathetic chain
80% of phaeos related to familial disorders - what are these?
Von Hippel-Lindau MEN2A and 2B (bilat adrenalectomy req due to risk) NF1 TS Sturge Weber Ataxia-Telangiectasia
How to differentiate catecholamine secreting phaeo vs neuroblastoma?
Urine catechols higher in phaeo
Dopamine and homovanillic acid higher in neuroblastoma
Retinal and CNA haemangioblastomas, phaechromocytoma what tumour suppressor defect?
Von Hippel-Lindau (VHL tumour suppressor mutation)
