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Addison’s, Cushing’s & Acromegaly
Tom Collins
Objectives
Definitions Aetiology Presentation Investigations Complications Management Prognosis Clinical scenario
Addison’s DiseaseDefinition Autoimmune
destruction of the adrenal gland resulting in failure of adrenal steroid hormone production
Cortisol & Aldosterone
Lets take a step back…
Adrenal failure:1. Primary adrenal failure
› Atrophy/destruction of the adrenal gland
2. Secondary adrenal failure› Inadequate ACTH production
3. Tertiary adrenal failure› Failure of CRH production
Aetiology
1. Primary adrenal failure› Autoimmune› Infection (TB, HIV)› Invasion from mets (lymphoma, breast, lung)› Haemorrhage (anticoagulants, Waterhouse-
Friedrichsen Syndrome› Infiltration (amyloid, sarcoid,
haemochromatosis)› Congenital adrenal hyperplasia› Drugs (eg ketoconazole, phenytoin,
rifampicin)
ADDISON’S
Aetiology cont.
2. Secondary adrenal failure› Acute steroid withdrawal
3. Tertiary adrenal failure› Chronic high dose glucocorticoid therapy› Sarcoidosis› Tumour› Cranial irradiation
Presentation Non-specific symptoms:
› Abdominal pain› Nausea› Diarrhoea› Lassitude
Dizziness› Due to postural hypotension
Pigmentation› Buccal› Scars› Palmar creases› Generalised
Hypoglycaemia› Cortisol is one of the main insulin antagonists
Investigations 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)
ComplicationsAddisonian 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 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!
Management
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
Associated diseases
Hypothyroidism T1DM Pernicious anaemia Vitiligo Premature ovarian failure
Cushing’s
Cushing’s Syndrome or Disease?
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.
AetiologyCortisol
Endogenous
ACTH dependent
ACTH independent
Exogenous
Steroid use
• Pituitary adenoma• 70%• F>M
• Ectopic ACTH production• 14%• SCLC• Carcinoid tumour
• Adrenal adenoma • 10%
• Adrenal carcinoma • 5%
• Adrenal hyperplasia • 1%
Presentation
Use whatever helps you remember!
•Myopathy•Striae•Bruising•Osteoporosis
Catabolic effects
•Diabetes•Truncal obesity•Supraclavicular fat pad
Glucocorticoid effects
•Hypertension•Hypokalaemia
Mineralocorticoid effects
Acronyms
S – spinal tenderness W – weight (central obesity) E – easy bruising D – diabetes I – interscapular fat pad S – striae H –
hypertension/hypokalaemia
Investigations
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
Complications
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
Management
Treat the cause!
Conservative › Stop medications!› Exercise› Diet› Smoking cessation
Medical› 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) Surgical
› Trans-sphenoidal adenomectomy› Bilateral adrenalectomy (can’t locate tumour/recurrence post-surgery)› Removal of ACTH secreting tumour
Distinction:• Nelson’s syndrome – post-
adrenalectomy development of a locally aggressive pituitary tumour (corticotrophinoma) due to lack of negative feedback.
Prognosis
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
Acromegaly
Definition: A hormonal disorder
that develops when the pituitary gland produces too much growth hormone during adulthood
Aetiology
Pituitary adenoma (≈99%) Ectopic production (≈1%)
› Usually a carcinoid tumour Pancreas Lung Adrenals
PathophysiologyCause
Pituitary adenomaEctopic production
GH secretion
Insulin-like growth factors
Arteriolar muscle
hypertrophyHypertension
Anti-insulin effect
Diabetes
Soft tissue growth
Big tong
ueBig lips
Boggy
palms
Cardiomyopat
hyColorectal canc
er
Sweat gland
hypertrophyExcess sweating
Bone growt
hTypical facies
PresentationUsually a spot diagnosis Typical facies
› Prominent supra-orbital ridges› Big ears, nose, lips, tongue› Prognathism› Wide separation of teeth
May complain of:› Headache› Numbness/tingling in hands› Excessive sweating› Vision problems› Hoarse voice› Obstructive sleep apnoea› Muscle weakness
What should you do O/E?Observe: As previous slideHands: Size – compare with your own Thenar eminence – wasting Check median nerve sensation Sweaty? ‘Bogginess’ of palms Skinfold thickness – increased in active diseaseAsk for BPNeck Check for goitre JVPVisual fields and acuityStand from seated position
Investigations Bedside
› BP› Urine dip› BM› ECG› Echocardiogram
Bloods› IGF levels
Imaging› MRI head› Colonoscopy (if ≥50 years)
Special tests› Oral GTT with GH measurement
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
Management Conservative
› Exercise› Diet› Smoking cessation
Medical› Octreotide & Lanreotide (somatostatin analogues)› Bromocriptine & cabergoline (dopamine agonists)› Metformin › Pegvisomant (GH receptor antagonist)› Radiotherapy (as adjuvant/when surgery inappropriate)
Surgical› Trans-sphenoidal adenomectomy
Follow up:› Yearly GH & IGF-1 measurement + OGTT, visual fields, CV
assessment.
IGF
Insulin resistance
Complications 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
Clinical scenario
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?
Questions?
References
Medicine at a glance Ask Dr Clarke Patient.co.uk Oxford handbook of clinical medicine www.mayoclinic.com
Special thanks to Dr Thomas Marshall
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