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Excessive Synthesis (adrenocortical hyperfunction)
i. Cushing’s Syndrome
Definition(OH): the clinical state produced by chronic glucocorticoid excess and loss of the
normal feedback mechanisms of the hypothalamo-pituitary-adrenal axis and loss of
circadian rhythm of cortisol secretion (normally highest on waking).
Physiological Effects of
Increased mobilisation of
glucose and fatty acids
Mobilisation of protein from
Think about the physiological effects of cortisol and what symptoms/signs this might
Plethoric (red) moon face
Buffalo neck hump
Supraclavicular fat pads
Skin and muscle atrophy
Purple abdominal striae
Infection prone-poor healing.
Increase in weight
Mood change (depression, lethargy, irritability)
Facial hair growth (in females)
recurrent Achilles tendon rupture
What are the causes?
The commonest cause is oral steroid treatment (i.e. after long-term treatment with
prednisolone and dexamethasone)
The endogenous causes can be divided into:
-Adrenal origin (excess cortisol production by an adrenal cortical neoplasm, e.g. adrenal
-Pituitary origin (excess ACTH production by a pituitary neoplasm-Cushing’s disease)
-Ectopic origin (excess ACTH production by a non-pituitary neoplasm, especially small cell
lung cancer and carcinoid tumours).
How do you tell which is which?
• dexamethasone suppression test: in Cushing’s syndrome the cortisol does not fall as we
would expect it to.
• to work out where the lesion is-do a plasma ACTH; if it is undetectable, then the excess
cortisol must be coming from the Adrenals (as the pituitary is still responding to negative
feedback, resulting in the low/undetectable levels of ACTH, but the adrenals are out of
• if ACTH is detectable, to distinguish between a pituitary and an ectopic cause, we need
to do a high-dose dexamethasone suppression test; complete or partial suppression of
the cortisol levels indicates a pituitary cause as the pituitary retains some feedback
• Iatrogenic: Stop oral steroids if possible
• Endogenous: Selective removal of the offending neoplasm if possible; bilateral
adrenalectomy if source unlocatable, recurrence post-op, or adrenal adenoma/carcinoma
ii. Conn’s Syndrome
• Primary hyperaldosteronism (Conn Syndrome) is usually caused by an aldosterone-
secreting adrenal adenoma.
*Key thing to remember regarding Conn Syndrome: it causes hypertension,
neuromuscular symptoms and renal potassium wasting due to elevated levels of
aldosterone (if you think about what aldosterone does, it makes sense).
iii. Adrenogenital Syndromes
• Congenital adrenal hyperplasia-95% of cases are due to partial or complete deficiency in
• The deficiency in this enzyme involved in the biosynthesis of adrenal steroids (i.e.
cortisol) means that steroidogenesis is then channelled into other pathways, leading to
excess production of androgens.
*The 3 most common syndromes are characterised by virilism-the newborn female infant
may present with pseudohermaphrodism, while precocious puberty occurs in affected
*Some defects also affect aldosterone synthesis (i.e. low aldosterone as well as low
cortisol), causing salt wasting which can be life-threatening in the newborn.
Definition (OH): primary adrenocortical insufficiency; destruction of the adrenal cortex
leads to glucocorticoid (cortisol) and mineralocorticoid (aldosterone) deficiency.
What are the causes?
Surgical Sieve is helpful here:
• V vascular-perinatal haemorrhagic necrosis, adrenal haemorrhage (Waterhouse-
Friderichsen syndrome), post partum adrenal infarction
• I infection/inflammatory-chronic infections (T.B. is commonest cause worldwide),
• T trauma-traumatic necrosis
• A auto-immune-auto-immune adrenalitis (60-70%, now commonest cause in U.K.)
• M metabolic-amyloidosis (not really a metabolic condition but may help to remember it
here, or you can just remember it on it’s own)
• I iatrogenic-abrupt withdrawal of corticosteroid treatment
• N neoplastic-disseminated metastatic carcinoma (lung, breast)
• If it helps you can remember this slide and the 5 T’s:
Or this list:
• nausea & vomiting
• abdominal pain
• weight loss
• hyperpigmentation of the skin (check palmar creases) & mucous membranes
• hypotension-dizziness and faints.
Remember these electrolyte disturbances:
Hb 12.5 g/dL normal
Na+ 125 mmol/L (low)
K+ 6.5mmol/L (high)
Ur 10mmol/L (high)
Glucose 2.9 mmol/L (low)
• Short Synacthen Test-an injection of synacthen should cause a normal rise of cortisol in
30 minutes (cortisol measurement after 30 minutes should be >550nmol/L)
• Corticosteroid Replacement (hydrocortisone daily)
• Mineralocorticoid replacement may be needed as well (fludrocortisone daily)
• Warn against abruptly stopping steroids, and advise about need to increase doses in
• Give steroid card
Management of an Addisonian Crisis:
D-assess for danger
R-assess for a response (pt may be very weak and confused)
A-Airways-look, listen, feel.
B-Breathing-look, listen, feel, measure (O2 sats), treat (oxygen)
C-Circulation-look (pallor, oedema, bleeding), listen (heart sounds-may be soft), measure
(BP-they are likely to be hypotensive, HR-feeble rapid pulse, UO-may be oliguric, Temp-
pyrexia is common and may be due to underlying infection, Cap refill), treat (obtain iv
access, give bolus of normal saline, take bloods)
D-Disability-AVPU score, measure serum glucose
E-Exposure-hyperpigmentation/medic alert bracelet may give you some clues!
• If an Addisonian crisis is suspected, treat without waiting for biochemical results
• Take blood for cortisol and ACTH if possible
• Give Hydrocortisone sodium succinate 100mg stat.
• Glucose iv may be needed if hypoglycaemic
• Continue iv fluids to correct dehydration, as guided by clinical state. Correct electrolyte
• Continue hydrocortisone sodium succinate e.g. 100mg/6h iv.
• Change to oral steroids after 72 hrs if patient’s condition is good.
• Fludrocortisone may be needed as well.
• Search for and treat the underlying cause (Infection, trauma. abrupt withdrawal of
• In Cushing’s syndrome you have an excess of Cortisol
• To investigate this you do the dexamethasone suppression test (because you are
trying to see if the excess levels can be suppressed)
• In Addison’s disease you have Adrenal insufficiency
• This results in characteristic features including hyperpigmentation, nausea & vomiting,
weakness and hypotension.
• You get low sodium and low glucose
• You get high potassium and raised urea
• To investigate this you do the short synacthen test (because you are trying to see if
synthetic ACTH will stimulate cortisol release)