Addison’s, Cushing’s & Acromegaly - PowerPoint Presentation

Slide1

Addison’s, Cushing’s & Acromegaly

Tom CollinsSlide2

Objectives

Definitions

Aetiology

PresentationInvestigationsComplicationsManagementPrognosisClinical scenarioSlide3

Addison’s Disease

Definition

Autoimmune destruction of the adrenal gland resulting in failure of adrenal steroid hormone production

Cortisol & AldosteroneSlide4

Lets take a step back…

Adrenal failure:

Primary adrenal failure

Atrophy/destruction of the adrenal glandSecondary adrenal failure

Inadequate ACTH production

Tertiary adrenal failure

Failure of CRH productionSlide5

Aetiology

Primary adrenal failure

Autoimmune

Infection (TB, HIV)Invasion from mets

(lymphoma, breast, lung)

Haemorrhage (anticoagulants, Waterhouse-

Friedrichsen

Syndrome

Infiltration (amyloid, sarcoid, haemochromatosis)

Congenital adrenal hyperplasiaDrugs (eg ketoconazole, phenytoin, rifampicin)

ADDISON’SSlide6

Aetiology cont.

2. Secondary adrenal failure

Acute steroid withdrawal

Tertiary adrenal failureChronic high dose glucocorticoid therapy

Sarcoidosis

Tumour

Cranial irradiationSlide7

Presentation

Non-specific symptoms:

Abdominal pain

NauseaDiarrhoeaLassitude Dizziness

Due to postural hypotension

Pigmentation

Buccal

Scars

Palmar creasesGeneralised HypoglycaemiaCortisol is one of the main insulin antagonistsSlide8

Investigations

Bed side

Lying and standing BP

ECGBlood glucoseBloodsU+Es

Serum cortisol (best to be done in the morning)

Adrenal autoantibodies

Imaging

MRI head

CT abdoSpecial testsShort

synacthen test (confirm the Dx)Long synacthen test (test response of adrenals)Slide9

Complications

Addisonian

crisis

Occurs when the physiological demand for these hormones exceeds the ability of adrenal glands to produce themi

e

, patients with chronic adrenal insufficiency when subject to an

intercurrent

illness or stress

Major or minor infectionsInjury Surgery

Burns Pregnancy General anaesthesiaAbrupt withdrawal of steroidsWaterhouse-

Friedrichsen

syndrome

Present with

hypovolaemic

shock and profound hypoglycaemia

MEDICAL EMERGENCY!Slide10

Management

Chronic adrenal failure

Glucocorticoid replacement

HydrocortisoneDouble dose if intercurrent illness, infection or surgery

Mineralocorticoid replacement

Fludrocortisone

Addisonian

Crisis

IV fluidsHigh dose hydrocortisoneDopamine (if hypotension persists)

Treat precipitantMonitor U+Es and glucoseSlide11

Associated diseases

Hypothyroidism

T1DM

Pernicious anaemiaVitiligoPremature ovarian failureSlide12

Cushing’sSlide13

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

.Slide14

Aetiology

Pituitary adenoma

70%

F>M

Ectopic ACTH production

14%

SCLC

Carcinoid tumour

Adrenal adenoma

10%

Adrenal carcinoma

5%

Adrenal hyperplasia

1%Slide15

Presentation

Use whatever helps you remember!Slide16

Acronyms

S – spinal tenderness

W – weight (central obesity)

E – easy bruisingD – diabetesI – interscapular

fat pad

S –

striae

H – hypertension/hypokalaemiaSlide17

Investigations

Bedside

24 hour urinary free cortisol

(to confirm Cushing’s syndrome)BloodsU+Es (<3.2 suggests ectopic ACTH production)Imaging

MRI head (for pituitary adenoma)

CT chest (for SCLC)

Special tests →

to determine the cause

Serum ACTHDexamethasone suppression testDistinguishes the ACTH dependent causesSlide18

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, infectionsSlide19

Management

Treat the cause!

Conservative

Stop medications!ExerciseDiet

Smoking cessation

Medical

Metyrapone

(blocks cortisol synthesis)

Ketoconazole (inhibits cytochrome P450)Mitotane (adrenolytic agent) → adrenal carcinomaRadiotherapy (

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.Slide20

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, obesityUntreated = <5 yearsCardiovascular diseaseInfection Slide21

Acromegaly

Definition:

A hormonal disorder that develops when

the

pituitary gland produces too much growth hormone during adulthoodSlide22

Aetiology

Pituitary adenoma (≈99%)

Ectopic production (≈1%)

Usually a carcinoid tumourPancreasLungAdrenalsSlide23

PathophysiologySlide24

Presentation

Usually a spot diagnosis

Typical

faciesProminent supra-orbital ridgesBig ears, nose, lips, tongue

Prognathism

Wide separation of teeth

May complain of:

Headache

Numbness/tingling in handsExcessive sweatingVision problems

Hoarse voiceObstructive sleep apnoeaMuscle weaknessSlide25

What should you do O/E?

Observe: As previous slide

Hands:

Size – compare with your ownThenar eminence – wasting

Check median nerve sensation

Sweaty?

‘Bogginess’ of palms

Skinfold thickness – increased in active disease

Ask for BPNeckCheck for goitre

JVPVisual fields and acuityStand from seated positionSlide26

Investigations

Bedside

BP

Urine dipBMECGEchocardiogram

Bloods

IGF levels

Imaging

MRI head

Colonoscopy (if ≥50 years)Special testsOral 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

DMSlide27

Management

Conservative

Exercise

DietSmoking cessationMedicalOctreotide

&

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 resistanceSlide28

Complications

Hypertension (increased risk of stroke & IHD)

Diabetes

CardiomyopathyLVHColorectal cancer≈5% associated with MEN-1 → Remember ‘3Ps’

Parathyroid hyperplasia/adenoma

Pancreatic endocrine tumours

Pituitary adenoma

Mortality increased 2-3xSlide29

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

diseaseSlide30

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 C

ushing’s

disease?Slide31

Questions?Slide32

References

Medicine at a glance

Ask Dr Clarke

Patient.co.ukOxford handbook of clinical medicinewww.mayoclinic.comSpecial thanks to Dr Thomas Marshall