Cushing’s,
Addison’s and
Acromegaly
Dr Edward Hutchison FY1 (Geriatrics)
Phase II Objectives
• 3.21: Investigations –
o Request appropriately the more common tests of thyroid, adrenal and
pituitary gland function, seeking advice where necessary.
• 3.23: Adrenal gland hormones
o Recognise signs and symptoms of Addison’s disease, confirm diagnosis
and initiate immediate management of Addisonian crisis.
o Recognise symptoms and signs of Cushing’s syndrome, confirm diagnosis,
participat in management of Addison’s disease and Cushing’s syndrome.
• 3.24: Pituitary gland hormones
o Recognise the circumstances when hypopituiarism might occur,
recognise possibility of hypopituitism with ‘non-specific’ symptoms,
investigate causes.
o Initiate investigation for posterior pituitary function in patients with
polyuria.
o Recognise acromegaly, initiate investigation for acromegaly, outline to
patients the possible treatments for acromegaly.
Aims
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HPA Axis
Adrenal glands
Cushing’s syndrome/disease
Addison’s
Acromegaly
HPA Axis
Hypothalamus
GnRH
TRH Dopamine CRH
GHR
H
Pituitary
Sphenoid sinus
ACTH
GH
FSH
Anterior
Pituitary
Hormones
TSH
PRL
LH
ADH
Posterior
Pituitary
Hormones
Oxytocin
Adrenal Glands
Remember:
GFR!
Functions of Cortisol?
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Insulin resistance/gluconeogenesis
Protein catabolism
Immunosuppresion
CVS regulation – e.g. increasing BP
CNS actions – e.g. increased appetite,
impaired memory
Increased bone turnover
Gastric acid secretion
Reduced skin collagen
Fluid retention
Right, now onto the stuff
you actually want to
know…
Cushing’s…
Which is which?
Syndrome
• Excessive activation of
glucocorticoid
receptors.
Disease
• Excessive production of
ACTH caused by a
pituitary adenoma.
Classification
ACTH-dependent
Pituitary adenoma
Ectopic ACTH production – e.g. small cell lung cancer, neuroendocrine
tumours
Iatrogenic – ACTH therapy
ACTH-independent
Iatrogenic – steroid therapy
Adrenal adenoma/carcinoma
Pseudo-Cushing’s
EtOH excess
Major depressive disorder
Primary obesity
Clinical features
Symptoms
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Depression
Confusion
Weight gain
Poor glucose control (diabetics)
Weakness rising from a chair (proximal myopathy)
Investigation
Overnight dexamethasone
suppression test/
24hr urinary cortisol
Not excluded
48hr low-dose dexamethasone
suppression test
Confirmed
Abstinence
?EtOH excess
ACTH level?
ACTH level
High
Low/normal
CRH test/48hr
dexamethasone
suppression test
Adrenal cause
Suppressed
MRI
pituitary
Not
suppressed
Ectopic
source
CXR, CT
A/P,
tumour
markers
CT adrenals
±adrenal venous
sampling
Management
Conservative
Medical
Surgical
Patient education
Reduce oral steroid
therapy if possible
Inhibit biosynthesis of
corticosteroids – e.g.
ketoconazole and
metyrapone
Trans-sphenoidal
resection of pituitary
(requires lifelong
hormone
replacement).
Laparoscopic
resection of adrenal
tumour.
Ectopic ACTH: treat
underlying cause
±bilateral
adrenalectomy.
Untreated Cushing’s disease has a 50% 5 year mortality
Remember
• Not only oral corticosteroids can cause Cushing’s
syndrome, large amounts of topical and inhaled
steroid may be absorbed into the systemic
circulation.
• Patients on large amounts of oral corticosteroids will
require their dose to be tapered slowly to avoid an
Addisonian-like crisis.
• You also will need to manage the effect of longterm steroid therapy – e.g. diabetes, hypertension,
thin skin, osteporosis.
Addison’s disease
(Or adrenal insufficiency, to be more correct).
Definition?
A syndrome resulting from
inadequate secretion of
corticosteroid hormones from
progressive destruction of the
adrenal cortex.
Causes
– autoimmune (90% of cases)
– degenerative (amyloid)
– drugs (e.g. ketoconazole)
– infective (TB, HIV)
– secondary (ACTH, hypopituitism)
– other (e.g. adrenal bleeding)
– neoplasia (metastases)
Clinical Features
Investigations
Test
Bedside
Lying/standing BP
Bloods
U&Es – low Na+/high K+
Glucose – low
Random serum cortisol
Short synacthen test
Plasma renin
TFTs etc (?hypopituitism)
FBC (?perncious anaemia)
Gonadal function
HIV test
Plasma aldosterone
Imaging
AXR (?adrenal calcification
CT or MRI of adrenals
The short synacthen test
• Why do we do it?
• How do we do it?
• What result do we see in a positive
test? (Ruling out Addison’s)
250µg synacthen IM
Positive test (ruling out Addisons):
Serum
Plasma cortisol >460nmol/L
at cortisol
30 at
0 minutes
minutes
Serum cortisol at
30 minutes
Management
• Glucocorticoid replacement
o Hydrocortisone BD, usually 15mg on waking/5mg
around 1800hrs
o Excessive weight gain = over replacement
o Educate patient – increase hydrocortisone when
unwell
• Mineralocorticoid replacement
o Fludrocortisone 50-100µg daily
o Titrate according to symptoms and U&Es
Addisonian Crisis
Features:
• Severe shock – hypotension, tachycardia
• Fever, abdominal pain, nausea & vomiting
• Hyponatraemia/hyperkalaemia
±hypercalcaemia, hypoglycaemia
Management:
ABCDE assessment
• Correct volume depletion
• Replace glucocorticoids
• Correct metabolic abnormalities
• Treat underlying cause
Acromegaly
Definition?
• A condition caused by excessive secretion
of growth hormone
Most common cause?
• Pituitary macroadenoma
Impress your examiner…
Hypopituitism
Investigations
Bedside
Collateral Hx
Serial photographs
BP
ECG
Bloods
Serum GH (unreliable)
Oral glucose tolerance test
Serum IGF-1
TFTs/FSH/LH/PRL etc
Imaging
CT/MRI brain
Echo
Other
Colonoscopy
Management
• Conservative:
o Patient education
• Medical (second line):
o Somatostatin analogues (octreotide, lanreotide)
o Dopamine agonists
o GH receptor antagonists (pegvisomant)
• Surgery (first line):
o Trans-sphenoidal surgical debulking of pituitary adenoma
• Radiotherapy:
o Employed if acromegaly persists after surgery
References
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Walker, BR., Colledge, NR., Ralston, SH., “Davidson’s Principles of Clinical Medicine” 21st edition, Churchill
Livingstone, (2010).
Kumar, P., Clarke, M. “Clinical Medicine” 7th edition, Saunders, 2009.
Longmore, M. et al “Oxford Handbook of Clinical Medicine” 8th edition, Oxford University Press, 2010.
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