cushing’s, addison’s and acromegaly
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Cushing’s, Addison’s and Acromegaly. Dr Edward Hutchison FY1 (Geriatrics). Phase II Objectives. 3.21: Investigations – Request appropriately the more common tests of thyroid, adrenal and pituitary gland function, seeking advice where necessary. 3.23: Adrenal gland hormones - PowerPoint PPT PresentationTRANSCRIPT
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• HPA Axis• Adrenal glands• Cushing’s syndrome/disease• Addison’s• Acromegaly
HPA Axis
Hypothalamus
GnRH TRH Dopami
neCRH
GHRH
Pituitary
Sphenoid sinus
Anterior Pituitary
Hormones
ACTH
FSH
PRLLH
TSH
GH
Posterior Pituitary
Hormones
ADHOxytocin
Adrenal Glands
Remember:GFR!
Functions of Cortisol?• 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…
…disease or syndrome?
Which is which?Syndrome Disease
• Excessive activation of glucocorticoid receptors.
• Excessive production of ACTH caused by a pituitary adenoma.
ClassificationACTH-dependentPituitary adenomaEctopic ACTH production – e.g. small cell lung cancer, neuroendocrine tumoursIatrogenic – ACTH therapyACTH-independentIatrogenic – steroid therapyAdrenal adenoma/carcinomaPseudo-Cushing’sEtOH excessMajor depressive disorderPrimary obesity
Clinical featuresOver to you…
Symptoms• Depression• Confusion• Weight gain• Poor glucose control (diabetics)• Weakness rising from a chair (proximal
myopathy)
Investigation
BedsideBlood
Imaging
Overnight dexamethasone
suppression test/24hr urinary
cortisol48hr low-dose dexamethasone suppression
test
Confirmed
?EtOH excess
Not excluded
Abstinence
ACTH level?
ACTH levelHigh
CRH test/48hr dexamethasone suppression test
SuppressedMRI pituitary
Not suppressedEctopic
source
CXR, CT A/P, tumour markers
Low/normal
Adrenal causeCT adrenals
±adrenal venous
sampling
ManagementConservative Medical SurgicalPatient educationReduce 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 long-term 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
– neoplasia (metastases)
ADDISON
– autoimmune (90% of cases)– degenerative (amyloid)
– drugs (e.g. ketoconazole)
– infective (TB, HIV)
– secondary (ACTH, hypopituitism)
– other (e.g. adrenal bleeding)
Clinical Features
Over to you…
InvestigationsTest
Bedside Lying/standing BP
Bloods U&Es – low Na+/high K+
Glucose – low Random serum cortisolShort synacthen testPlasma reninTFTs etc (?hypopituitism)FBC (?perncious anaemia)Gonadal functionHIV testPlasma aldosterone
Imaging AXR (?adrenal calcificationCT 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
Serum cortisol at 0 minutes
Serum cortisol at 30 minutes
Positive test (ruling out Addisons):Plasma cortisol >460nmol/L at 30 minutes
Management• Glucocorticoid replacement
o Hydrocortisone BD, usually 15mg on waking/5mg around 1800hrs
o Excessive weight gain = over replacemento Educate patient – increase hydrocortisone
when unwell• Mineralocorticoid replacement
o Fludrocortisone 50-100µg dailyo Titrate according to symptoms and U&Es
Addisonian Crisis
Features:• Severe shock – hypotension,
tachycardia• Fever, abdominal pain, nausea &
vomiting• Hyponatraemia/hyperkalaemia
±hypercalcaemia, hypoglycaemiaManagement: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
Your turn!
Impress your examiner…
Hypopituitism
InvestigationsBedside Collateral Hx
Serial photographsBPECG
Bloods Serum GH (unreliable)Oral glucose tolerance testSerum IGF-1TFTs/FSH/LH/PRL etc
Imaging CT/MRI brainEcho
Other Colonoscopy
Management• Conservative:
o Patient education• Medical (second line):
o Somatostatin analogues (octreotide, lanreotide)o Dopamine agonistso GH receptor antagonists (pegvisomant)
• Surgery (first line):o Trans-sphenoidal surgical debulking of pituitary
adenoma• Radiotherapy:
o Employed if acromegaly persists after surgery
References• 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.• http://www.fipapatients.org/pictures/big/pituitary_normal.jpg• http://www.autismpedia.org/wiki/images/b/b9/Adrenal-core.gif• http://www.ghorayeb.com/files/Transsphenoid_Lateral_380x332.jpg• http://www.nosleeplessnights.com/wp-content/uploads/2013/03/dexamethasone.jpg• http://classconnection.s3.amazonaws.com/319/flashcards/1117319/jpg/addisons_disease1332524676283.jpg• http://upload.wikimedia.org/wikipedia/commons/2/2e/Addisons_hyperpigmentation.jpg• http://globalvoicesonline.org/wp-content/uploads/2012/05/syringe-drawing-320x300.jpg• https://lh5.googleusercontent.com/-qF8wwWfCtFI/TXRv47Ax4xI/AAAAAAAABR8/4jsTaDOngtc/s1600/
Synacthen.JPG• http://www.gloshospitals.org.uk/SharePoint11/Pathology%20Web%20Images/Specimen%20containers/
Gold_top_with_cap.jpg• http://www.sehha.com/diseases/endocrine/Addison12.gif• http://www.hdwallpapersinn.com/wp-content/uploads/2012/09/bigshow-img.jpg• http://www.examiner.com/images/blog/wysiwyg/image/andre-the-giant.jpg• http://upload.wikimedia.org/wikipedia/commons/1/15/Bitempvf.png• http://www.s2c8.co.uk/wp-content/uploads/2013/01/man-boob.jpg• http://www.physio-pedia.com/images/6/61/Moon_facies_in_Cushings.jpg• http://www.passpaces.com/images/acromegaly_MRCP.jpg