1. Addison’s, Cushing’s & Acromegaly
Tom Collins

2. Objectives Definitions Aetiology Presentation Investigations
Complications
Management
Prognosis
Clinical scenario

3. Addison’s Disease Definition Cortisol & Aldosterone
Autoimmune destruction of the adrenal gland resulting in failure of adrenal steroid hormone production
Cortisol & Aldosterone

4. Lets take a step back… Adrenal failure: Primary adrenal failure
Atrophy/destruction of the adrenal gland
Secondary adrenal failure
Inadequate ACTH production
Tertiary adrenal failure
Failure of CRH production

5. Aetiology Primary adrenal failure ADDISON’S Autoimmune
Infection (TB, HIV)
Invasion from mets (lymphoma, breast, lung)
Haemorrhage (anticoagulants, Waterhouse-Friedrichsen Syndrome
Infiltration (amyloid, sarcoid, haemochromatosis)
Congenital adrenal hyperplasia
Drugs (eg ketoconazole, phenytoin, rifampicin)
ADDISON’S

6. Aetiology cont. 2. Secondary adrenal failure Tertiary adrenal failure
Acute steroid withdrawal
Tertiary adrenal failure
Chronic high dose glucocorticoid therapy
Sarcoidosis
Tumour
Cranial irradiation

7. Presentation Non-specific symptoms: Dizziness Pigmentation
Abdominal pain
Nausea
Diarrhoea
Lassitude
Dizziness
Due to postural hypotension
Pigmentation
Buccal
Scars
Palmar creases
Generalised
Hypoglycaemia
Cortisol is one of the main insulin antagonists

8. Investigations Bed side Bloods Imaging Special tests
Lying and standing BP
ECG
Blood glucose
Bloods
U+Es
Serum cortisol (best to be done in the morning)
Adrenal autoantibodies
Imaging
MRI head
CT abdo
Special tests
Short synacthen test (confirm the Dx)
Long synacthen test (test response of adrenals)

9. Complications Addisonian crisis
Occurs when the physiological demand for these hormones exceeds the ability of adrenal glands to produce them
ie, patients with chronic adrenal insufficiency when subject to an intercurrent illness or stress
Major or minor infections
Injury
Surgery
Burns
Pregnancy
General anaesthesia
Abrupt withdrawal of steroids
Waterhouse-Friedrichsen syndrome
Present with hypovolaemic shock and profound hypoglycaemia
MEDICAL EMERGENCY!

10. Management Chronic adrenal failure Addisonian Crisis
Glucocorticoid replacement
Hydrocortisone
Double dose if intercurrent illness, infection or surgery
Mineralocorticoid replacement
Fludrocortisone
Addisonian Crisis
IV fluids
High dose hydrocortisone
Dopamine (if hypotension persists)
Treat precipitant
Monitor U+Es and glucose

11. Associated diseases Hypothyroidism T1DM Pernicious anaemia Vitiligo
Premature ovarian failure

12. Cushing’s

13. 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.

14. Aetiology Pituitary adenoma 70% F>M Ectopic ACTH production 14%
Cortisol
Endogenous
ACTH dependent
ACTH independent
Exogenous
Steroid use
Pituitary adenoma
70%
F>M
Ectopic ACTH production
14%
SCLC
Carcinoid tumour
Adrenal adenoma
10%
Adrenal carcinoma 5%
Adrenal hyperplasia 1%

15. Presentation Use whatever helps you remember! Catabolic effects
Myopathy
Striae
Bruising
Osteoporosis
Glucocorticoid effects
Diabetes
Truncal obesity
Supraclavicular fat pad
Mineralocorticoid effects
Hypertension
Hypokalaemia

16. Acronyms S – spinal tenderness W – weight (central obesity)
E – easy bruising
D – diabetes
I – interscapular fat pad
S – striae
H – hypertension/hypokalaemia

17. Investigations Bedside Bloods Imaging
24 hour urinary free cortisol (to confirm Cushing’s syndrome)
Bloods
U+Es (<3.2 suggests ectopic ACTH production)
Imaging
MRI head (for pituitary adenoma)
CT chest (for SCLC)
Special tests → to determine the cause
Serum ACTH
Dexamethasone suppression test
Distinguishes the ACTH dependent causes

18. 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, infections

19. Management Treat the cause! Conservative Medical Surgical Distinction:
Stop medications!
Exercise
Diet
Smoking cessation
Medical
Metyrapone (blocks cortisol synthesis)
Ketoconazole (inhibits cytochrome P450)
Mitotane (adrenolytic agent) → adrenal carcinoma
Radiotherapy (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.

20. Prognosis If treated very good prognosis Untreated = <5 years
Resolution of physical features and psychological disorders
Follow up needed for osteoporosis, glucose intolerance, DM, HTN, subtle mood changes, obesity
Untreated = <5 years
Cardiovascular disease
Infection

21. Acromegaly Definition:
A hormonal disorder that develops when the pituitary gland produces too much growth hormone during adulthood

22. Aetiology Pituitary adenoma (≈99%) Ectopic production (≈1%)
Usually a carcinoid tumour
Pancreas
Lung
Adrenals

23. Pathophysiology Cause Big tongue Big lips Boggy palms Cardiomyopathy
Ectopic production
Pituitary adenoma
GH secretion
Insulin-like growth factors
Arteriolar muscle hypertrophy
Hypertension
Anti-insulin effect
Diabetes
Soft tissue growth
Big tongue
Big lips
Boggy palms
Cardiomyopathy
Colorectal cancer
Sweat gland hypertrophy
Excess sweating
Bone growth
Typical facies

24. Presentation Usually a spot diagnosis Typical facies May complain of:
Prominent supra-orbital ridges
Big ears, nose, lips, tongue
Prognathism
Wide separation of teeth
May complain of:
Headache
Numbness/tingling in hands
Excessive sweating
Vision problems
Hoarse voice
Obstructive sleep apnoea
Muscle weakness

25. What should you do O/E? Observe: As previous slide Hands:
Size – compare with your own
Thenar eminence – wasting
Check median nerve sensation
Sweaty?
‘Bogginess’ of palms
Skinfold thickness – increased in active disease
Ask for BP
Neck
Check for goitre
JVP
Visual fields and acuity
Stand from seated position

26. Investigations Bedside Bloods Imaging Special tests BP Urine dip BM
ECG
Echocardiogram
Bloods
IGF levels
Imaging
MRI head
Colonoscopy (if ≥50 years)
Special tests
Oral 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 DM

27. Management Conservative Medical Surgical Follow up: Exercise Diet
Smoking cessation
Medical
Octreotide & 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 resistance

28. Complications Hypertension (increased risk of stroke & IHD) Diabetes
Cardiomyopathy
LVH
Colorectal cancer
≈5% associated with MEN-1 → Remember ‘3Ps’
Parathyroid hyperplasia/adenoma
Pancreatic endocrine tumours
Pituitary adenoma
Mortality increased 2-3x

29. 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 disease

30. What are your differentials for this lady
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 Cushing’s disease?

31. Questions?

32. References Medicine at a glance Ask Dr Clarke Patient.co.uk
Oxford handbook of clinical medicine
Special thanks to Dr Thomas Marshall