Cortisol crises

When Cushing and Addison walk into a

bar

Case 1: Bob, 45yo

Seen in A&E for Colles fracture after a
low impact fall
Previous problems with weight gain,
bruising, low mood
PMH: T2DM (insulin), refractory HTN,
CKD

Cushings syndrome

Cushings syndrome
Exposure to excess
glucocorticoids regardless of
cause
Often missed!
Insidious, symptoms attributed
to depression and menopause,
common conditions e.g. DM

5-year 50% mortality if

untreated usu from CV
events

Cushings syndrome
Causes
ACTH-dependent:
Pituitary tumour (Cushings disease)
Ectopic e.g. lung ca, neuroendocrine

ACTH-independent:
Adrenal adenomas, bilateral adrenal hyperplasia,
adrenal ca (rare)

Exogenous: Excess steroids (incl. nasal

spray, skin creams)

Recap: Cortisol
PHYSIOLOGICAL RESPONSE TO
STRESS

PATHOLOGICAL RESPONSE TO
STRESS

appetite

Central obesity, thin limbs, moon face

Protection against hypoglycaemia

Hyperglycaemia, glucosuria, polydipsia

protein catabolism

Muscle atrophy, proximal myopathy,

bruising, purple striae

Anti-inflammatory, immunosuppression Susceptibility to infection, ulcers

Acid secretion by stomach

Gastric ulcers

Na retention, redistribution of body

fluids

Hypertension

bone resorption by activating

osteoclasts

Osteoporosis

Baldness, hirsutism, menstrual

disturbance

Cushings syndrome
History
Weight gain,
depression,
weakness,
menstrual
irregularities
PMH of diabetes,
osteoporosis,
hypertension
DH of steroid
inhalers/creams

Cushings syndrome
Psych: depression, psychosis,
fatigue, insomnia
CV: HTN, VTE, MI
Skin: bruising, facial plethora,
purple striae, thin skin, poor
healing
MSK: proximal myopathy, OP +/fractures
Body: central obesity, moon face
(facial fullness), supraclavicular
fat pads
Repro: infertility, menstrual
irregularity
Metabolic: DM
Immune: Immunosuppression

Cushings syndrome
Diagnosis
1. Confirm Cushings
Late night salivary cortisol 2300

Cortisol is highest on waking,

decreases during day (with stress
activity spikes) and lowest in middle of
the night.
Rhythm is lost in disease states

1mg overnight dexamethasone suppression test (exclude if cortisol<50)

24h urinary free cortisol (>50mcg) *raised in pregnancy

2. ACTH-dependent or independent
48h low-dose (2mg) dexamethasone test
Plasma ACTH (low = adrenals, high = ectopic/pituitary)

3. Determine aetiology
ACTH-dependent:
48h high-dose (8mg) dexamethasone test
+/- Inferior petrosal sinus sampling

ACTH-independent:
CT adrenal

Cushings syndrome
Hypothalamus
Low dose dex
(2mg)

High dose dex

(8mg)

Normal

ACTH low, cortisol

low

ACTH low, cortisol

low

Adrenal

ACTH low, cortisol

high

ACTH low, cortisol

high

No effect on ACTH

No effect on ACTH

CRH

Pituitary
ACTH

Adrenal
Cortisol

Pituitary ACTH high, cortisol

high

ACTH low, cortisol

low
High doses can suppress

Ectopic

ACTH high, cortisol

high

ACTH high, cortisol

high

ACTH from tumour

High doses CANNOT

suppress

Cushings syndrome
Management
Treat the cause!
Surgical resection of underlying tumour
Reduce steroid dose if exogenous (do not stop
abruptly!)

Case 2: Brenda (51yo)

You are called to see lady with a high
NEWS score
Admitted 1 day ago for 5-day history of
vomiting
No diarrhoea, fever, abdo pain, recent
travel
PMH: recent depression, generalised
darkening of skin 2 years ago
O/E: HR 100, temp 37.9, BP 107/63,
dehydrated
Ix: Hb 118, WCC 2.8, Na 131, K 4.4, Ca

Case 2: Brenda
Overnight, she became more confused
and BP fell to 98/55

GCS 12
Brisk reflexes, bilateral extensor plantars
ABG: metabolic acidosis
BM: 1.1

What is going on?

Case 2: Brenda
Overnight, she
became more
confused and BP fell
to 98/55
GCS 12
Brisk reflexes,
bilateral extensor
plantars
ABG: metabolic
acidosis
BM: 1.1

Case 2: Brenda
You found her on Facebook
(which you shouldnt)

What is going on?

 Addisonian crisis
Precipitated by viral infection
On background of undiagnosed Addisons
disease

Addisons disease
Primary adrenal insufficiency
Usually secondary to autoimmune
destruction of adrenal cortex
Clinical manifestations occur once 90%
adrenal cortex is destroyed
Symptom progression varies from weeks to
years
Non-specific symptoms

Recap: Adrenal gland

Anatomy of the adrenal gland
Outer cortex (90%): steroid hormones
Inner medulla (10%): catecholamines

Whats produced by the adrenal gland?

Glucocorticoids: effects on carbohydrate metabolism
Mineralocorticoids: extracellular balance of Na/K in
distal tubule of kidney (mostly aldosterone)
Androgens: precursors of testosterone (peripherally
metabolised)

Addisons disease
Symptoms
Lethargy, dizziness, LOA, LOW
GI symptoms
Hyperpigmentation
Skin and mucosal (esp scars, flexures, palmar creases)
Melanocyte stimulating hormone is produced in producing
ACTH
Not always present e.g. abrupt withdrawal of long-term
steroids

Craving for salt, soy sauce, liquorice

Postural hypotension
Crisis: hypotension, hypovolaemic shock, acute
abdominal pain, low-grade fever, and vomiting

Addisons disease
Biochemical findings

Low Na, high K

Metabolic acidosis
Hypoglycaemia
Moderate neutropenia
Hyper/HypoCa
Complex interaction between glucocorticoid,
parathyroid and glcuose homeostasis

Raised TSH
Glucocorticoid regulation of hypothalamic secretion
of TRH

Addisons disease
Primary adrenal dysfunction (Addisons disease)
Autoimmune 80%
TB (commonest cause worldwide), AIDS
Mets
Infiltration e.g. sarcoid, amyloid
Haemorrhage
Infarct

Adrenal insufficiency can be caused by long-term steroids but this is

not Addisons disease!
Secondary adrenal dysfunction
Pituitary tumour

Precipitants: Sepsis, trauma, surgery, MI, sudden steroid withdrawal

Clues: lap adenectomy scars, steroid card, medical alert bracelet

Addisons disease
Request U&Es and random cortisol
Random cortisol: <100 = admit to hospital

Diagnosis
9am cortisol
>550nmol/L excludes Addisons
<100nmol/L suggests adrenal dysfunction

9am ACTH
Short synACTHen test

9am cortisol, 9am ACTH

Give 250ug Synacthen
30min cortisol, 60min cortisol
Primary adrenal insufficiency if cortisol<550

Addisons disease
Other tests
Consider CT adrenals for TB/infiltration/mets
Consider long synACTHen test, insulin
tolerance test for secondary adrenal failure
Atrophy of adrenal gland takes 6wk from onset of
ACTH deficiency, during which response to short
synACTHen may be normal

Addisons disease
Management of adrenal crisis
Pre-hospital
IM/IV hydrocortisone before transfer

Hospital
IV fluids
IV/IM hydrocortisone 100mg (bloods before
replacement!)
Continue at 100mg/6h until stable, taper after
Perform short synACTHen test by delaying previous
evenings hydrocortisone and delaying morning dose
until after test

Addisons disease
Long-term management
Lifelong hydrocortisone and flucortisone
replacement
Hydrocortisone tds waking, 12pm, 5pm
In hypopituitarism, replace thyroid AFTER hydrocortisone to
prevent precipitating crisis
Double doses during sick days
Wear steroid card / medical bracelet
Emergency IM hydrocortisone should be available at home
ideally
Seek medical help if sick / vomiting

Dehydroepiandrosterone (unlicensed) may be prescribed

by some specialists for androgen replacement.

Addisons disease
Associated conditions (50% develop
them)

Autoimmune hypothyroidism
Pernicious anaemia
Premature gonadal failure
Vitiligo
Alopecia
T1DM
Autoimmune polyendocrine syndromes

Brendas happy ending

After treatment
Her hypotension, hyponatraemia, metabolic acidosis,
and cognitive function improved completely.
Her depressive symptoms resolved and she no longer
required citalopram.

When investigating hypoCa, she was also found

to have significant hypophosphataemia and
severe vitamin D deficiency.
Possibly due to avoidance of sun exposure for fear of
further exacerbating her pigmentation.
For more info: http://www.bmj.com/content/339/bmj.b2384

Thank you!