Adrenal Disease Flashcards
What differentiates Cushing Syndrome from Cushing Disease?
CS - hypercortisolaemia
CD - pituitary tumour
What are the zones of the adrenal cortex and what are their roles?
ZG - aldosterone (mineralocorticoids)
ZF - cortisol (glucocorticoids)
ZR - DHEA (androgens)
What does cortisol bind to in the bloodstream?
CBG (cortisol binding globulin)
What is the action of cortisol?
Stress
- gluconeogenesis
- lipolysis
- proteolysis
BP
- vasoconstriction (sensitivity to catecholamines)
Reduced immune response
- fewer PGs & ILKs
- inhibition of T-lymphocytes
Brain
- mood & memory
How does Cushing Syndrome present?
- severe muscle, bone & skin breakdown (easy bruising, thin skin)
- T2DM (hyperglycaemia)
- central obesity (high insulin, activation of lipoprotein lipase)
- HTN (catecholamine sensitivity = vasoconstriction ; ZG cross-activation = RAAS)
- reduced sexual function (GRH suppression)
- frequent infections
- impaired brain function
Causes of Cushing syndrome
- exogenous medications (steroids, oft for asthma/RA) = atrophy
- pituitary adenoma (CD = hyperplasia)
- SCC (LC - ectopic ACTH)
- adrenal adenoma/carcinoma (suppression of CRH, ACTH; contralateral atrophy)
Symptoms of Cushing disease
- muscle wasting
- thin extremities
- easy bruising
- striae
- fractures (osteoporosis)
- moon face
- buffalo hump
- truncal obesity
- DM
- HTN
- CVD risk
- vulnerable to infections
- poor wound healing
- amenorrhoea
- psychiatric (mental disorders)
Diagnosis of Cushing syndrome
- 24h urinary cortisol
- 9am serum cortisol
- LOW-DOSE overnight dexamethasone suppression test (+ increases; endogenous)
- plasma ACTH (low: 1ry INDEPT adrenal adenoma/carcinoma) (high: 2ry DEPENDENT Cushing disease & ectopic)
Treatment of Cushing syndrome
- treat ULC
- taper exogenous steroids (withdrawal = adrenal crisis)
- steroid inhibitors (metyrapone, ketoconazole)
- TSS (excision of pituitary adenoma) + RTx
- total adrenalectomy (supplemented with hydrocortisone/fludrocortisone)
Differentiate between Cushing disease & ectopic ACTH production
HIGH-DOSE DST injection - ectopic sites non-responsive
- CRH stimulation test = rise in CD
- Inf. petrosal sinus sampling (IPSS) - catheter in FV/JV, inject CRH, sample ACTH peripheral vein & petrosal sinus
Ix- pituitary MRI, CT TAP
Red flags of Cushing syndrome indicating adrenal carcinoma/adenoma
- UWL
- F: acne, deep voice, hirsutism
- CT: haemorrhage, necrosis, calcification
How would adrenal carcinoma be managed differently to an adenoma?
Adenoma - lap
Carcinoma - open (+LN resection +/- nearby organs)
Nelson syndrome
Pituitary hyperplasia post-bilateral adrenalectomy
- remove adrenals = no -ve feedback
Presents with: headache, visual impairment, hyperpigmentation (melanocytes)
Treat: TSS
What is the HPA axis?
CRH (hypothalamus) -> ACTH (ant. Pituitary) -> Cortisol (ZF adrenal cortex)
<— negative feedback
What are potential complication of prolonged systemic exogenous glucocorticoids?
- Cushing syndrome
- Posterior subcapsular cataracts (decreased night vision & glares)
What is the most common cause of Cushing’s syndrome?
Oral corticosteroid use
Pseudo-Cushing’s syndrome
- signs, symptoms & biochemical findings of Cushing’s syndrome
- no HPA abnormality
- diurnal variation retained
Cause: chronic alcoholism (repeat tests after 1m abstinence)
What is Addison’s disease?
Primary adrenal insufficiency due to bilateral adrenal cortex destruction
What mechanisms of compensation can mask Addison’s disease?
Low cortisol should = low adrenaline
- compensated by NAd
M: testicles 2ry supply of androgens
What are the causes of Addison’s disease?
- autoimmune destruction (polyglandular AIS T2)
- infection (TB, fungal)
- adrenal haemorrhage (WFS)
- adrenal vein thrombotic infarction
- mets
- cortisol synthesis inhibitors (ketoconazole, suramin)
What is an Addisonian crisis?
An adrenal crisis in Addison’s disease precipitated by physiologically stressful events:
- surgical procedures
- trauma
- infection
- dehydration
What are the characteristic symptoms of Addison’s disease?
- fatigue & weakness
- hypotension/syncope
- hyponatraemia & hypoglycaemia
- hyperkalaemia
- abdo pain, anorexia, N+V, WL
- intolerance of temp extremes
- hyperpigmentation (tanned palmar creases) / vitiligo
- reduced libido & hair (F)
- confusion / depression
Why does Addison’s disease cause hypotension?
Hypocortisolaemia - reduced vascular responsiveness to ATII & NAd (RAAS)
How does Addison’s disease cause hyponatraemia?
Hypoaldosteronism = Na+ loss
Low cortisol = high ADH = water loss
What causes the hyperkalaemia associated with Addison’s disease?
Hypoaldosteronism = mild hyperchloraemic acidosis
Why do Addison’s patients present with hyperpigmentation?
ACTH stimulation of melanocyte activity
What is vitiligo?
AI destruction of melanocytes.
How does an Addisonian crisis present?
- hypoglycaemia
- shock - vasomotor/circulatory collapse (unresponsive to vasopressors due to low cortisol)
- death?
How is Addison’s disease diagnosed?
Bedside - hx, exam findings
Bloods - LOW 9am cortisol, rapid ACTH (no cortisol), Na+
HIGH serum ACTH, plasma renin, K+, hyperchloraemic acidosis
Imaging - abdo CT (enlarged glands - TB/malignancy; small = AID/advanced TB; adrenal haemorrhage/thrombosis)
AXR - adrenal calcifications = infectious cause
What medications are used to manage Addison’s disease?
Life-long:
Glucocorticoid replacement
- hydrocortisone
Mineralocorticoid replacement
- fludrocortisone
Androgens (F)
- low dose DHEA
What drugs are used acutely in an Addisonian crisis?
- hydrocortisone etc.
- adrenaline
- glucose
- IV. 0.9% saline
What are ‘sick day rules’ for Addison’s disease?
- dose hydrocortisone during significant trauma/surgery
What is Waterhouse-Friderichsen syndrome?
Adrenal failure & crisis associated with overwhelming infection & adrenal gland haemorrhage = necrosis
- rare, severe
