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