This document presents a case study of a 40-year-old man diagnosed with hypoadrenalism. He presented with nausea, vomiting, and weakness over several weeks. Initial lab results showed very low sodium and other electrolyte abnormalities. A short Synacthen test confirmed primary hypoadrenalism. He was started on hydrocortisone and fludrocortisone replacement. The document then reviews adrenal physiology, causes of hypoadrenalism including primary and secondary forms, clinical features such as adrenal crisis, and approaches to diagnosis and treatment including glucocorticoid and mineralocorticoid replacement therapy.

1. Hypoadrenalism – Case Presentation
Dr. Adam Stokes
ST4 in Anaesthesia & ICM
24th February 2015

2. Overview
1. Case Presentation
2. Adrenal Physiology
3. Hypoadrenalism
1. Causes
2. Clinical Features
3. Diagnosis
4. Treatment

3. Case Presentation -
Background
! 40 year old man
! PMH: Subclinical hypothyroidism (2008) – not on
replacement
! Admission Sept 2014 with right flank pain, no
cause found
! DH: Nil regular, NKDA.
! SH: Non-smoker, occasional alcohol, worked up
until last 2 weeks, living with parents.

4. Case Presentation
! Presentation
! 1/12 Hx of lethargy, weakness, muscular spasms
! 1/52 Hx of nausea and vomiting, hiccups
! 2-3/7 Hx of repeated vomiting, occasionally blood
tinged, patient reports feeling “slow”
! Saw GP 2/7 ago- plan for bloods and f/u, but
parents concerned and rang 111, who advised 999.

5. Case Presentation
! Assessment on admission
! Resp: RR 18, Sats 100% on air
! CVS: HR 80, BP 130/73, paramedics reported no
postural drop.
! Neuro: GCS 14/15, mild confusion/slowness in
speech, PERLA, BM 4.9, afebrile.
! GI: Abdo soft non-tender, BS active
! Tanned skin, but not obviously pigmented mucous
membranes.

6. Case Presentation
! Initial results/management in ED
! Lab- Na<100, K 5.7, Cl 67, Ur 6.1, Cr 74 CRP 36, Hb 17.5
WCC 4.1, Plt 166
! CXR: NAD
! ECG: NAD
! ABG: pH 7.44, pCO2 3, pO2 10.6, Lac 0.7, BE -8.6, Na
<100, Cl 69
! Random cortisol and TFTs sent
! Treatment:
! Metoclopramide
! Lansoprazole
! Saline 1000ml (commenced prior to Na result)
! Hydrocortisone 100mg

7. Case Presentation
! Next 24 hours in HDU
! Arterial line inserted for frequent ABGs
! Urine and plasma osmolalities sent, urinary Na
! Results: TFTs - T4 14.5 (N), TSH 29.7 (high), plasma
osmolality 212, urine 836, urine Na 71, random cortisol
110
! Slow Na correction with 1.8% NaCl
! CT head: Thrombosed cerebral artery aneurysm in
circle of Willis (?significance), nil else

8. Case Presentation
! Day 3
! Short synacthin test performed: 30min cortisol 290,
60min 275: positive test for primary hypoadrenalism
! Levothyroxine commenced, and after results of
synacthin test, fludrocortisone/hydrocortisone
replacement started
! Patient became more agitated/confused (required
DOLS)
! Renin/Aldosterone/ACTH and autoantibody screen
sent.

9. Case Presentation
! Days 4 -10
! Gradual improvement in mental condition and
weakness with Na up to 130
! CT head discussed with Neuro SGH- probably incidental
but will f/u in due course
! Discharged with f/u in Endo clinic in 2/52
! Results:
! ACTH high.
! Renin high.
! Aldosterone normal.
! Thyroid autoantibodies positive.
! Adrenal autoantibodies weakly positive.

10. Adrenal Physiology
Hypothalamus Pituitary
Adrenal
Cortex
(Glomerulosa)
Adrenal
Cortex
(Fasiculata)
Adrenal
Cortex
(Reticularis)
ACTRH
ACTH
Trauma
Temp
Hypoglycaemia
Exercise
Stress

11. Adrenal Physiology
Zona
glomerulosa Aldosterone
Na+ & water retention.
K+ secretion.
Zona fasiculata
Cortisol and
corticosterone
Gluconeogenesis
Proteolysis
Lipolysis
RBCs, plts, neuts.
Gastric acid & ulcers.
Reactivity to catecholeamines.
Reduced collagen & osteoporosis.
Anti-inflammatory.
Immunosuppression.
Zona reticularis
Androgens (&
small amount of
cortisol)
ACTH
K+
RAAS

12. Hypoadrenalism
! Causes
! Clinical features
! Diagnosis
! Treatment

13. Causes
! Secondary
! Mass lesions – pituitary adenomas
! Pituitary surgery / radiation
! Isolated ACTH deficiency
(autoimmune or genetic)
! Infiltrative lesions
! Infarction (Sheehans)
! TBI
! Tertiary
! Chronic high dose
glucocorticoid therapy
! Mass lesions
! Radiation
! Infiltrative lesions – e.g.
sarcoidosis
! TBI
! Infections
! Primary Adrenal Insufficiency
! Idiopathic / Autoimmune
! Infectious adrenalitis
! Bilateral adrenal infarct
! Metastatic disease
! Drugs

14. Clinical Features
! Depends on rate & extent of loss of adrenal
function, whether mineralocorticoid production is
preserved and degree of stress.
! Adrenal crisis
! Chronic primary adrenal insufficiency
! Secondary or tertiary adrenal insufficiency

15. Clinical Features
! Adrenal Crisis
! Occurs in:
! Undiagnosed primary adrenal insufficiency subject to
serious infection/stress.
! Known primary adrenal insufficiency who does not
take sufficient glucocorticoid during infection/stress.
! Bilateral adrenal infarct/haemorrhage.
! Less frequently with secondary/tertiary adrenal
insufficiency.
! Abrupt withdrawal of glucocorticoid therapy.

16. Clinical Features
! Adrenal Crisis:
! Features:
! Shock (predominant feature)
! Anorexia, N&V, weight loss.
! Weakness, fatigue, lethargy, confusion, coma.
! Abdo pain.
! Hypoglycaemia.
! Fever.
! Hyponatraemia, hyperkalaemia, hypercalcaemia,
eosinophilia.
! Hyperpigmentation or vitiligo.
! Autoimmune endocrine deficiencies e.g. hypothyroid

17. Clinical Features
! Chronic Primary Adrenal Insufficiency
! May have features of glucocorticoid,
mineralocorticoid and androgen deficiency.
! Insidious onset
! Non-specific features.
! Difficult to diagnose.

18. Clinical Features - CPAI
Symptom
Frequency
(%)
Weakness,
)redness,
fa)gue
100
Anorexia
100
GI
symptoms
92
Nausea
86
Vomi)ng
75
Cons)pa)on
33
Abdo
pain
31
Diarrhoea
16
Salt
craving
16
Postural
hypotension
12
Muscle/joint
pains
6-­‐13
Sign
Weight
loss
100
Hyperpigmenta)on
94
Hypotension
88-­‐94
Vi)ligo
10-­‐20
Auricular
calcifica)on
5
Laboratory
Abnormality
Electrolyte
disturbance
92
Hyponatraemia
88
Hyperkalaemia
64
Hypercalcaemia
6
Azotaemia
55
Anaemia
40
Eosinophilia
17

20. Clinical Features
! Secondary or Tertiary Adrenal Insufficiency
! Similar to chronic primary adrenal insufficiency with
the following exceptions:
! Hyperpigmentation not present as ACTH not
increased.
! Dehydration not present, and less hypotension.
! Hyperkalaemia not present, reflecting presence of
aldosterone.
! Less GI symptoms.
! Hypoglycaemia more common.
! Manifestations of pituitary/hypothalamic tumour.

21. Diagnosis
! Three stage process:
1. Demonstrating inappropriately low cortisol
2. Determine if cortisol deficiency is independent/
dependent of ACTH deficiency + evaluation of
mineralocorticoid secretion in pts without ACTH
deficiency.
3. Seeking treatable cause of the primary disorder.

22. Diagnosis – Low Cortisol
! Serum cortisol conc
! Morning serum cortisol conc
! Low is strongly suggestive of adrenal insufficiency
! Morning salivary cortisol conc
! For screening
! Afternoon/night serum cortisol
! No value
! Urinary cortisol
! Low in adrenal insufficiency, but can be low-normal in partial
insufficiency. Thus, unsuitable for screening.
! Short ACTH stimulation test

23. Diagnosis – Level of defect
! Need to measure basal plasma ACTH, renin and
aldosterone conc.
! If primary, ACTH high. Will have high renin, low
aldosterone, raised K+ and decreased Na+.
! If secondary/tertiary, ACTH low. Renin and
aldosterone usually unaffected.
! Prolonged ACTH test will help distinguish between
primary and secondary/tertiary.
! Differentiation between secondary and tertiary
by ACTRH – although not really important.

24. Diagnosis - Aetiology
! Pituitary CT or MRI.
! Abdominal CT.
! CXR, urine culture for TB.
! CT directed percutaneous fine needle aspiration
of enlarged adrenal glands.

25. Treatment – Adrenal Crisis
! Emergency Measures
! Large IV access
! Bloods – U&E, glucose, cortisol, ACTH.
! Saline 2000 – 3000ml
! Dexamethasone 4mg IV BD (does not affect cortisol measurement)
or hydrocortisone 100mg QDS.
! Supportive measures
! Subacute Measures
! Continue saline for 24 – 48 hours
! Treat precipitants
! Perform short ACTH stimulation test
! Determine type of insufficiency.
! Taper glucocorticoids over 1-3 days
! Begin mineralocorticoid replacement with fludrocortisone.

26. Treatment – Chronic Adrenal
Insufficiency
! Glucocorticoid Replacement
! Dexamethasone 0.25-0.75mg or prednisolone 2.5-7.5mg PO,
supplemented with hydrocortisone 5-10mg in afternoon PRN.
! Alternatively, hydrocortisone 15-20mg OM & 5-10mg in
afternoon.
! Monitor ACTH.
! Mineralocorticoid Replacement
! Fludrocortisone 0.05 – 0.2mg PO.
! Liberal salt intake.
! Monitor postural BPs, HR, oedema, K+, and renin.
! Androgen Replacement
! Dehydroepiandrosterone 25-50mg PO in women.
! Other
! Patient education
! Medic–alert bracelet

27. Thank you!