Adrenal Flashcards
Adrenal Micro
Zones
- G - glomerulosa - salt - mineralocorticoid
- F - fasciculata - sugar - glucocorticoid
- R - reticularis - sex - sex hormones
- M - medulla - magic - eosinophilic chromaffin cells making catecholamines
Cortex from mesoderm 5-7th week gestation
- All hormones made from cholesterol through a series of pathways
Medulla from neuro ectoderm
Adrenal Hormones
Mineralocorticoids - mainly aldosterone
- Renin angiotensin aldosterone axis
- Renin - released from JGA due to low Na. Converts Ang to Ang I, cleaved by ACE in lungs to Angiotensin II
- Angiotensin II - vasoconstriction, aldosterone release from Adr
- Aldosterone - regulates circulating volume and electrolytes by acting on DCT - to increase Na and H20 resorption, at expense of K and H lost in urine
Glucocorticoids - Mainly cortisol and corticosterone
- Hypothalamus - Ant Pit - Adrenal
- Hypothalamus - Releases CRH in response to stress
- Ant Pit - stimulated by CRH, releases ACTH (circadian)
- Adrenal - ACTH stimulates glucocorticoids
- Glucocorticoids - broad range of effects, catabolic stress response - increase blood glucose, decrease glucose into tissues, protein catabolism and lipolysis of fats
Sex Steroids - DHEAS most important
- Weakly androgenic steroids under action of ACTH
- Converted in peripheral tissues - Via the aromatase system - Into dihydro-testosterone and estradiol
Catecholamines - Mainly noradrenaline and adrenaline
- Tyrosine - Dopamine - Norad - Adr
- SANS stimulation
- Catecholamines - bind alpha (Norad) and beta (Adr) receptors - flight or fight - HR, BP, CO, CNS up, splanchnic down
- Clearance under 1 min - broken into metanephrine and normetanephrine
Adrenal Insufficiency
Primary - Addisons - rare - weakness, fatigue, anorexia, N and V, weight loss, hyperpigmentation, HypoNa and HyperK
- Congenital adrenal hypoplasia, defective steroid formation or adrenal destruction
Secondary - Adrenal insufficiency due to low ACTH - often due to steroid withdrawal
- relatively common
- ACTH def - due to stopping steroids - 5 days of high dose or 3 weeks of low dose
- rare causes - pituitary disease, haemorrhage, infarction Sheehan syndrome post partum
Secondary - Critically Ill - Acute reversible dysfunction of the HPA axis
- seen in 30% critically ill patients - ACTH resistance or decreased organ response
- giving steroids - controversial
Adrenal crisis (Addisonian crisis) - Life threatening due to low adrenal function and stress
- Unable to respond to the adrenal demand - not enough mineralocorticoid
- Hypotensive shock, abdo P, N, V, fever,
- Rapidly fatal if not given steroids (100mg IV Hydrocort q6h) and large volume fluid and electrolyte resus
Adrenal Insuff work up - early am cortisol, if low do ACTH stimulation test - if cortisol doesn’t respond likely insufficiency
- Tx - Be aware of adrenal crisis and aggressive management - fluids and steroids
- Replace with pred and fludrocortisone - increase in stress
- Periop - need hydrocortisone - risk of adrenal critis
ACC
Rare tumour, most are functional
- 48% Cushings, 18% Cushing and virilization, 6% virilization (rare aldosterone)
- Build up of steroid hormones causes precursors to build up including DHEAS
- Non functioning - abdo discomfort or incidental
Incr in MEN1, Li Fraumeni
Work up - functional
Image - size over 4cm, over 6cm. CT heterogenous, necrosis, irregular margins
- Denser than 10U
- FDG PET very sens
Dx - no bx, tumour seeding risk
- difficult to tell if malig - invasion or mets
TNM - T stage - under 5cm, over 5cm, local invasion, invading other organs or vessels
- N any nodes, M any mets
- Stage I T1 82% 5y, Stage II T2 61%, Stage III - 50%
Tx - open adrenalectomy +/- en bloc resection of adjacent organs and regional lymphadenectomy
- Lap may increase recurrence. Complete resection needed. R side risk of IVC and heart invasion
- Chemo - mitotane - adrenocorticol toxic, steroidogenesis inhibitor
Congenital adrenal hyperplasia
Rare AR disorders with deficiency of steroids due to over production of intermediates, due to defects in the synthetic pathways
Lack of negative feedback leads to adrenal hyperplasia
Types
- 21 hydroxylase def - most common - def gluco/mineralo - too much androgen
- 17 hydroxylase def - loss of cortisol and sex hormones, aldo up
- 11 beta hydroxylase def - loss of cortisol - androgen and aldo up
Adrenal Lesion Imaging
Incidental adrenal mass over 1cm
- Common
- Functional or non functional, benign or malignant (primary or mets)
Benign vs malig
- Size - over 4cm
- Image - non con - under 10 HU benign
- CT adrenal protocol - fine slices, washout
- Malig high attenuation on CT with slow washout - less than 60% total or 40% relative
Lesions
- Benign adenoma - smooth round homogenous, unilateral, under 4cm, rapid washout, isointense liver on MR
- ACC - irregular, heterogenous, calc, over 4cm, hypointense to liver on MRI, high PET uptake
- Phaeo - variable size, can be bilateral, increased attenuatation and vascular, delayed washout, high MRI
- Adrenal mets - irregular, heterogenous, can be bilat, high attenuatation, delayed washout, isointense liver MRI, raised FDG PET
FNA / Bx - only for mets, rarely needed, rule out phaeo first, 3% complication rate
Phaeo WU
Tumour from the chromaffin cells of neural crest origin, from the adrenal medulla
- Includes phaeo and paraganglioma
Rare, most middle aged
10% rule - bilateral, extra adrenal, familial, malignant
Symptoms - incidental asyx
- Syx - Headache, diaphoresis and palpitations
- Hypertensive
Phaeo crisis - ppt by anaesthesia, trauma, bx, haemorrhage
- massive release, arrythmias, multi organ failure or sudden death
Aetio - most sporadic
- Genetic - MEN2A, MEN2B, VHL (30%), NF1 (5%), SDH mutations
- Family history - higher if young, multiple, bilateral, extra adrenal
Biochem
- Plasma metanephrines - breakdown products
- 24 hour urinary metanephrines catecholamines
- (stop meds - paracetamol, phenoxybenzamine, sympathomimetics, psychotropics)
- Clonidine suppression test
Localization - cross section - MRI (sens) or CT (vasc / op planning
- MIBG - for multifocal or no tumour found
- FDG PET (or dotatate) very sens
Phaeo Management
Preop - Phenoxybenzamine - alpha adrenergic receptor blocker - start low and increase (or doxazosin)
- Beta blockers for tachycardia and arrythmias - only after alpha blockade
Path - vascular tone a balance of alpha 1 contraction and beta 2 relaxation
- Alpha 1 receptors - Sm musc contraction and vasoconstriction
- Beta 1 receptors - increases cardiac conduction, HR and contractility
- Beta 2 receptors - Sm muscle relaxation
- Unopposed alpha action (due to B blocker) precipitates a crisis
- Increased alpha 1 contraction without beta 2 relaxation or B1 cardiac contractility
- Acute HTN and coronary vasoconstriction
Intraop
- Arterial line and central line - Detect and correct any HTN episodes - sodium nitroprusside, nicardipine, phentolamine, beta blockers
- Avoid handling of the tumour
Post operative
- Loss of catecholamines can lead to peripheral vasodilation - large increase in venous capacitance - cardiovascular collapse
- Aggressive volume replacement, inotropes, ICU, monitor BSLs for drop
Operative
- Laparoscopic adrenalectomy -Contraindicated for local invasion
- Open for paraganglioma - Tumours tend to be highly vascular and adhere to other structures
Malignant Phaeo
Risk higher if larger, paraganglioma, SDH mutation
Prognosis OS 30% at 5y
Can’t tell on histo - dx is based on metastatic disease
- Axial skeleton, LN, liver, lung, kidney
Tx - Alpha and beta blockade, nil curative, debulking can help, chemo/rad/RFA/TACE can help, therapeutic MIBG
