Definitions
 Aetiology
 Presentation
 Investigations
 Complications
 Management
 Prognosis
 Clinical scenario

Definition

Autoimmune
destruction of the
adrenal gland
resulting in failure
of adrenal steroid
hormone
production
Cortisol & Aldosterone
Adrenal failure:
1.
Primary adrenal failure
›
2.
Secondary adrenal failure
›
3.
Atrophy/destruction of the adrenal gland
Inadequate ACTH production
Tertiary adrenal failure
›
Failure of CRH production
1.
Primary adrenal failure
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Autoimmune
ADDISON’S
Infection (TB, HIV)
Invasion from mets (lymphoma, breast, lung)
Haemorrhage (anticoagulants, WaterhouseFriedrichsen Syndrome
Infiltration (amyloid, sarcoid,
haemochromatosis)
Congenital adrenal hyperplasia
Drugs (eg ketoconazole, phenytoin, rifampicin)
2. Secondary adrenal failure
›
3.
Acute steroid withdrawal
Tertiary adrenal failure
›
›
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Chronic high dose glucocorticoid therapy
Sarcoidosis
Tumour
Cranial irradiation

Non-specific symptoms:
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Abdominal pain
Nausea
Diarrhoea
Lassitude
Dizziness
› Due to postural hypotension

Pigmentation
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
Buccal
Scars
Palmar creases
Generalised
Hypoglycaemia
› Cortisol is one of the main insulin antagonists

Bed side
› Lying and standing BP
› ECG
› Blood glucose

Bloods
› U+Es
› Serum cortisol (best to be done in the morning)
› Adrenal autoantibodies

Imaging
› MRI head
› CT abdo

Special tests
› Short synacthen test (confirm the Dx)
› Long synacthen test (test response of adrenals)
Addisonian crisis

Occurs when the physiological demand for these
hormones exceeds the ability of adrenal glands to
produce them
› ie, patients with chronic adrenal insufficiency when
subject to an intercurrent illness or stress
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
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Major or minor infections
Injury
Surgery
Burns
Pregnancy
General anaesthesia
Abrupt withdrawal of steroids
Waterhouse-Friedrichsen syndrome
Present with hypovolaemic shock and profound
hypoglycaemia
MEDICAL EMERGENCY!
Chronic adrenal failure

Glucocorticoid replacement
› Hydrocortisone
› Double dose if intercurrent illness, infection or surgery

Mineralocorticoid replacement
› Fludrocortisone
Addisonian Crisis
IV fluids
High dose hydrocortisone
 Dopamine (if hypotension persists)
 Treat precipitant
 Monitor U+Es and glucose


Hypothyroidism
 T1DM
 Pernicious anaemia
 Vitiligo
 Premature ovarian failure

Cushing’s Syndrome definition:
 The clinical condition resulting from
prolonged exposure to glucocorticoids
from an exogenous or endogenous
cause.
Cushing’s Disease definition:
 The clinical condition resulting from
prolonged exposure to glucocorticoids
from a pituitary adenoma.
Cortisol
Endogenous
ACTH
dependent
•
•
Pituitary adenoma
• 70%
• F>M
Ectopic ACTH
production
• 14%
• SCLC
• Carcinoid tumour
Exogenous
ACTH
independent
•
•
•
Adrenal adenoma
• 10%
Adrenal carcinoma
• 5%
Adrenal hyperplasia
• 1%
Steroid use

Use whatever helps you remember!
Catabolic effects
Glucocorticoid
effects
Mineralocorticoid
effects
•Myopathy
•Striae
•Bruising
•Osteoporosis
•Diabetes
•Truncal obesity
•Supraclavicular fat pad
•Hypertension
•Hypokalaemia
S
– spinal tenderness
 W – weight (central obesity)
 E – easy bruising
 D – diabetes
 I – interscapular fat pad
 S – striae
 H – hypertension/hypokalaemia

Bedside
› 24 hour urinary free cortisol (to confirm
Cushing’s syndrome)

Bloods
› U+Es (<3.2 suggests ectopic ACTH
production)

Imaging
› MRI head (for pituitary adenoma)
› CT chest (for SCLC)

Special tests → to determine the
cause
› Serum ACTH
› Dexamethasone suppression test
 Distinguishes the ACTH dependent
causes
Same as complications of steroid use
 A common question in Finals!
 If struggling to remember don’t panic!

› What can they lead on to?
› Eg Diabetes and its complications,
cardiovascular disease, infections
Treat the cause!



Conservative
Distinction:
• Nelson’s syndrome – postadrenalectomy development
of a locally aggressive pituitary
tumour (corticotrophinoma)
due to lack of negative
feedback.
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Stop medications!
Exercise
Diet
Smoking cessation
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Metyrapone (blocks cortisol synthesis)
Ketoconazole (inhibits cytochrome P450)
Mitotane (adrenolytic agent) → adrenal carcinoma
Radiotherapy (adjuctive therapy/for relapse/if surgery inappropriate/in
children – when pituitary adenoma)
Medical
Surgical
›
›
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Trans-sphenoidal adenomectomy
Bilateral adrenalectomy (can’t locate tumour/recurrence post-surgery)
Removal of ACTH secreting tumour

If treated very good prognosis
› Resolution of physical features and
psychological disorders
› Follow up needed for osteoporosis, glucose
intolerance, DM, HTN, subtle mood changes,
obesity

Untreated = <5 years
› Cardiovascular disease
› Infection
Definition:
 A hormonal disorder
that develops when
the pituitary gland
produces too much
growth hormone
during adulthood
Pituitary adenoma (≈99%)
 Ectopic production (≈1%)

› Usually a carcinoid tumour
 Pancreas
 Lung
 Adrenals
Cause
Pituitary adenoma
Ectopic production
GH secretion
Insulin-like
growth factors
Arteriolar muscle
hypertrophy
Hypertension
Anti-insulin
effect
Diabetes
Soft tissue
growth
Big tongue
Big lips
Boggy palms
Cardiomyopathy
Colorectal cancer
Sweat gland
hypertrophy
Excess sweating
Bone growth
Typical facies
Usually a spot diagnosis
 Typical facies

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Prominent supra-orbital ridges
Big ears, nose, lips, tongue
Prognathism
Wide separation of teeth
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Headache
Numbness/tingling in hands
Excessive sweating
Vision problems
Hoarse voice
Obstructive sleep apnoea
Muscle weakness
May complain of:
Observe: As previous slide
Hands:
 Size – compare with your own
 Thenar eminence – wasting
 Check median nerve sensation
 Sweaty?
 ‘Bogginess’ of palms
 Skinfold thickness – increased in active disease
Ask for BP
Neck
 Check for goitre
 JVP
Visual fields and acuity
Stand from seated position

Bedside
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BP
Urine dip
BM
ECG
Echocardiogram
Bloods
› IGF levels

Imaging
Distinction:
• Random GH measurements
not helpful because GH
secreted in pulsatile manner.
• False positives for OGTT + GH
• Pregnancy
• Puberty
• Hepatic disease
• Renal disease
• Anorexia nervosa
• DM
› MRI head
› Colonoscopy (if ≥50 years)

Special tests
› Oral GTT with GH measurement

Conservative
› Exercise
› Diet
› Smoking cessation

Medical
›
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
Octreotide & Lanreotide (somatostatin analogues)
Bromocriptine & cabergoline (dopamine agonists)
Insulin
Metformin
resistance
Pegvisomant (GH receptor antagonist)
Radiotherapy (as adjuvant/when surgery inappropriate)
Surgical
› Trans-sphenoidal adenomectomy

IGF
Follow up:
› Yearly GH & IGF-1 measurement + OGTT, visual fields, CV
assessment.

Hypertension (increased risk of stroke & IHD)
Diabetes
Cardiomyopathy
LVH
Colorectal cancer

≈5% associated with MEN-1 → Remember ‘3Ps’




› Parathyroid hyperplasia/adenoma
› Pancreatic endocrine tumours
› Pituitary adenoma

Mortality increased 2-3x
28 year old woman is seen in outpatients. She has been
referred by her GP who has been unable to find a cause
for her symptoms. She has a 6 month history of
intermittent abdominal pain which varies in site and
intensity. She has also experienced some occasional
diarrhoea. She feels generally weak and off her food.
She has lost a stone over this period.
On examination she has pigmented palmar creases and
buccal mucosa but no other specific findings. Her BP is
100/70 lying down, you try to stand her to check it again
but she feels dizzy and light headed and has to sit down.
You check her BM and it is 2.9.
Addison’s disease
What are your differentials for this lady?
How would you investigate her?
How would you manage her?
What are the complications of Cushing’s
disease?
What is the difference between Cushing’s
syndrome and Cushing’s disease?
Medicine at a glance
 Ask Dr Clarke
 Patient.co.uk
 Oxford handbook of clinical medicine
 www.mayoclinic.com

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Special thanks to Dr Thomas Marshall