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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

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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

    • Recognise signs and symptoms of Addison’s disease, confirm diagnosis and initiate immediate management of Addisonian crisis.

    • 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

    • Recognise the circumstances when hypopituiarism might occur, recognise possibility of hypopituitism with ‘non-specific’ symptoms, investigate causes.

    • Initiate investigation for posterior pituitary function in patients with polyuria.

    • 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

GHRH

TRH

Dopamine

CRH


Pituitary

Sphenoid sinus


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.


Classification


Clinical features

Over to you…


Symptoms

  • Depression

  • Confusion

  • Weight gain

  • Poor glucose control (diabetics)

  • Weakness rising from a chair (proximal myopathy)


Investigation

Bedside

Blood

Imaging


Not excluded

Abstinence

?EtOH excess


ACTH level?


Management

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

A

D

D

I

SO

N

– autoimmune (90% of cases)

– neoplasia (metastases)

– degenerative (amyloid)

– drugs (e.g. ketoconazole)

– infective (TB, HIV)

– secondary (ACTH, hypopituitism)

– other (e.g. adrenal bleeding)


Clinical Features

Over to you…


Investigations


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):

Plasma cortisol >460nmol/L at 30 minutes

Serum cortisol at 0 minutes

Serum cortisol at 30 minutes


Management

  • Glucocorticoid replacement

    • Hydrocortisone BD, usually 15mg on waking/5mg around 1800hrs

    • Excessive weight gain = over replacement

    • Educate patient – increase hydrocortisone when unwell

  • Mineralocorticoid replacement

    • Fludrocortisone 50-100µg daily

    • 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


Your turn!


Impress your examiner…

Hypopituitism


Investigations


Management

  • Conservative:

    • Patient education

  • Medical (second line):

    • Somatostatin analogues (octreotide, lanreotide)

    • Dopamine agonists

    • GH receptor antagonists (pegvisomant)

  • Surgery (first line):

    • Trans-sphenoidal surgical debulking of pituitary adenoma

  • Radiotherapy:

    • 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


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