Dr J StorrowFY2

Cushings, Addisons and Acromegaly

ObjectivesBrief overview of the pituitary glandBrief overview of all three conditionsReview:

aetiologypresentationinvestigationscomplicationsprognosis

Brief case presentationsRevision tips

Pituitary glandAnterior and PosteriorAnterior hormones (FLAT-GP):

F – FSHL – LHA – ACTHT – TSHG – GHP – Prolactin

Posterior hormones (OA) :O – OxytocinA – ADH

HPA axis

DefinitionsCushings

Increased glucocorticoid exposureAddisons

Chronic primary adrenocortical insufficiencyAcromegaly

Increased growth hormone production

Cushings

Disease vs. SyndromeCushings Disease is the result of a pituitary tumour

secreting inappropriate ACTHCushings Syndrome causes the same symptoms, but is

caused by overproduction of adrenal hormones. It encompasses all other forms of Cushings

Basically:Disease = increased cortisol from pituitarySyndrome = all other sources

Harvey Cushing in 1932

Endogenous Causes:

65% = pituitary

25% = adrenals

10% = ectopic source (small cell lung ca), non-pituitary, ACTH producing tumour

Exogenous Causes:

Iatrogenic Steroids (Asthma, RA, palliative)

Higher incidence in people with: DM, HTN, Obesity and Osteoporosis

Aetiology

= Females 5:1 ratio and ages 25-40

S&S

SWEDISH

S – Spinal tenderness

W – Weight gain

E – Easily bruise

D – Diabetes

I – Intercapsular fat pad

S – Striae

H – HTN

Differential DiagnosisPseudo-Cushingoid:

Chronic severe anxiety and/or depressionProlonged excess alcohol consumptionObesityPoorly controlled diabetesHIV infection

Investigations Bedside?Bloods tests – which and why?

FBC – raised WCCU/E – low K

Special tests:Cortisol at midnight and 0900 (loss of diurnal variation

– should be low at midnight <550) – less reliable24 hour urinary cortisol – 3 collections24 hour salivary cortisol samplingDexamethasone Suppression Test

Dexamethasone Suppression Test Overnight Low dose = Baseline reading, Dex 1mg given at 11pm,

measure cortisol at 8am If cortisol low (<50nmol/L) = normal If cortisol high (>50nmol/L) = investigate further – Cushings syndrome

Localising the lesion:

Plasma ACTHif undetectable = adrenal cause (as adrenal cause independent of

ACTH)If detected – proceed to high dose dex suppression test

High dose if >90% suppression – pituitary if less/no suppression – ectopic source

InvestigationsIf any positive - imaging:CT of adrenalsMRI pituitary

If ?ectopic:CXRCT =/- MRI of neck, thorax, abdomen

ManagementAlways split in to:

ConservativeMedicalSurgical

ManagementDrug therapy remains very important for normalising cortisol

levels. Medical treatment can also be used in patients who are unwilling or unfit for surgery. Metyrapone, ketoconazole, and mitotane can all be used to lower

cortisol by directly inhibiting synthesis and secretion in the adrenal gland.

The treatment of choice in most patients is surgical but the metabolic consequences increase the risk of surgery:increased tissue fragilitypoor wound healingHTN and DM

Surgical TreatmentPituitary tumours:

trans-sphenoidal microsurgery. Radiation therapy may be used as an adjunct for patients who are not cured. Bilateral adrenalectomy may be necessary to control toxic cortisol levels.

Adrenocortical tumours: require surgical removal – can develop Nelsons Syndrome

Removal of neoplastic tissue is indicated for ectopic ACTH production. Metastatic spread makes a surgical cure unlikely or impossible. Bilateral adrenalectomy is indicated if necessary to control toxic cortisol levels.

PrognosisPatients with incompletely controlled Cushing's

syndrome have a five-fold excess mortality. Premature death in untreated Cushing's syndrome

are caused by vascular disease (MI/CVA), uncontrolled DM and infections.

The usual course is chronic, with cyclical exacerbations and rare remissions.

The prognosis is better with surgery. The rare adrenocortical carcinomas have a 5-year

survival rate of 30% or less.

Addisons

AetiologyDr Thomas Addison in 1855True Addisons:

Affects 1 in 10000 in UK – rareCommon presentation between 30 and 50Affects women more70-90% have autoimmune basis – cytotoxic T cellsClinical and biochemical insufficiency only occurs once

>90% of the gland is destroyed. Primary = adrenalsSecondary = pituitaryTertiary = hypothalamus

Aetiology continuedTB (most common worldwide)infections – AIDS, fungalAdrenal haemorrhage (caused by sepsis, meningitis) Metastatic spread to adrenalsAmyloidosis Adrenalectomy Genetic/congenital defects

Addsions = long term steroids leading to suppression of HPA axis

S&S

InvestigationsBedside?Blood tests:Low Na, low cortisolLow aldosterone causing high K, High adrenocorticotrophic hormone (ACTH) Low glucose High TSH – indicates what?Imaging?CXR – why?CT/MRI adrenals

Investigations - Synacthen Test Nightmare for busy house officer!How do you perform it?Measures cortisolShort – no cortisol produced (no response) Long allows differentiation

Primary – No cortisol produced (ACTH high) = adrenalSecondary – Cortisol produced (ACTH low) = pit

If initial cortisol is >140 nmol/L and second cortisol is >400-500 nmol/L, this excludes Addison's disease (most common finding!) The test can be performed at any time of day.

ManagementC, M, S (no surgical)Conservative = lifestyle

MedicAlert bracelet and steroid card.Importance of not missing steroids. Intercurrent illness - if tolerating oral medication then the dose

should be doubled until better

Medical = Replace steroidsGlucocorticoid replacement - hydrocortisone is the mainstay of

treatment; dose divided into two thirds in the morning and one third in the late afternoon (thus stimulating the normal diurnal adrenal rhythm).

Mineralocorticoid replacement - this is usually required in primary adrenal insufficiency – Fludrocortisone (what else used for – clue = elderly who fall)

Complications – Addisonian Crisissevere dehydrationpale, cold, clammy skin sweating rapid, shallow breathing dizziness severe vomiting and diarrhoeasevere muscle weakness headachesevere drowsiness or loss of consciousness coma and death

Treatment of crisisMedical emergencyBloods, large bore cannulaSeek help if you suspectIv HydrocortisoneIv fluidsIv glucose if needed

PrognosisDepends upon the underlying causeIn those patients in whom the prognosis is not

affected by the underlying pathology, replacement therapy should result in a return to health with a normal life expectancy.

Acromegaly

Aetiology Pituitary tumour >99% (very rarely ectopic (carcinoid)M:F = 1:130-50y old5% genetic association with MEN1

GH stimulates soft tissue and skeletal growth through increased secretion of IGF-1 and secretion inhibited by somatostatin

S&S A – Arthopathy B – BP high C – Carpal tunnel D – Diabetes & HF E – Enlarged tongue/heart F – Field defect - hemianopia

InvestigationsBedside?Bloods?

Random GH levels – not helpful (stress/sleep/pregnancy)IGF-1 increased in 75% people

Special tests:OGTT:

Measure glucose and GH at 0,30,60,90,120,150 minsNormally glucose causes GH suppressionIf Acromegaly – no GH suppressionFalse +ves – puberty, pregnancy, hepato-renal disease,

anorexia, DM

InvestigationsImaging:MRI pituitaryVisual fieds and acuityECG/Echo

Treatment – C,M,S Medical:

Somatostatin analogues - OctreotideInhibit GH secretionMonthly IM injectionControls GH and IGF1 in 60%

GH recpetor antagonists – PegvisomantSupresses IGF1 in 90% but GH levels riseCan cause tumour size to increase

SurgicalTrans-sphenoidal surgeryCures 80% microadenomas and 40% macroadenomas

Can try radiotherapy if surgery inappropriate – can take years to work

ComplicationsImpaired GT – 40%DM – 20% (GH counter regulates insulin)Vascular – HTN, LVH, IHD/CVAMalignancy – colonic polyps – controversialMortality 2-3 times (vascular risk)

Case presentations30 year old woman presents feeling unwell and dizzy,

loss of weight, decreased libido and darker skin but also some areas of very light skin. Treated for anorexia 2 years ago

50 year old man presents saying his rings are becoming tighter on his hands and he’s had to buy bigger shoes. Keeps walking into things

30 year old woman has noticed weight gain especially around face and abdomen, hair loss, bruises easily, urinating more often

Revision Tips Look at the patient and around the patient’s bedsideThink logically:

S&S lead to what investigations which leads to management which leads to complications which leads to prognosis

Management in to conservative, medical, surgical Investigations: start bedside then move to desk then walk to xray

etc:Obs, urine dip, ECG, BM, clinical examBloods, Iv fluids, VTE (anti-coag?), Kardex (meds)CXR, AXR, USS, CT/MRI

If endocrine – consider bloods for other pituitary hormonesHyperprolactinaemia is most common disorder

Tips for finals/FY1Be nice to nurses/pharmacists/physiosAlways ask if you don’t know what to do (inc exams – shows

safety and professionalism)Prioritise jobsTHINK LOGICALLY – start with basic things Learn sepsis six Learn medical emergencies – you might just save a life

HyperkalaemiaMassive UGI bleedAnaphylaxisDKAMeningitisSeizures + statusHypoglycaemia