Adrenal insufficiency, also known as Addison's disease, is caused by destruction of the adrenal cortex leading to deficiencies in glucocorticoids and mineralocorticoids. It presents with non-specific symptoms like fatigue, weight loss, and low blood pressure. Diagnosis involves low cortisol levels in response to ACTH stimulation and high ACTH levels. Treatment is lifelong glucocorticoid and mineralocorticoid replacement. An adrenal crisis can result from infection or stress and requires immediate high dose glucocorticoid treatment in addition to intravenous fluids and glucose to prevent shock.

1. ADRENAL
INSUFFICIENCY
NUR FARRA NAJWA BINTI ABDUL AZIM
082015100035

2. LEARNING OBJECTIVES
• What is adrenal insufficiency
• Features/clinical findings
• Investigation
• Making diagnosis
• Treatment and follow-up
• Addisonian crisis

4. 1. Primary adrenocortical
insufficiency
2. Secondary adrenocortical
insufficiency

6. PRIMARY ADRENOCORTICAL
INSUFFICIENCY (ADDISON’S DISEASE)
• Rare (~0.8/100 000)
• Can be fatal
• Destruction of the adrenal cortex
– Glucocorticoid (cortisol)
– Mineralocorticoid (aldosterone) deficiency

7. Cont.
• It is ‘the unforgiving master of non-specificity
and disguise’.
• Suspected in : UNEXPLAINED FATIGUE,
HYPONATRAEMIA OR HYPOTENSION
• Misdiagnose a viral infection or anorexia
nervosa, chronic fatigue syndrome or
depression

8. Causes
• 80% are due to autoimmunity in the UK.
• Other causes:
– TB (commonest cause worldwide)
– Adrenal metastases (from lung, breast, renal cancer)
– Lymphoma
– Opportunistic infections in HIV (eg CMV, mycobacterium
avium)
– Adrenal haemorrhage (waterhouse–friderichsen
syndrome)
– Antiphospholipid syndrome
– SLE
– Congenital (late-onset congenital adrenal hyperplasia).

9. SECONDARY ADRENAL
INSUFFICIENCY
• Commonest cause
– Iatrogenic
– Due to long term steroid therapy leading to
suppression of the pituitary–adrenal axis.
• Symptoms apparent on withdrawal of the
steroids.
• Mineralocorticoid production remains intact, and there is
no hyperpigmentation as decreased ACTH
• Other causes are rare and include
– Hypothalamic–pituitary disease leading to decreased
ACTH production.

11. Symptoms (often diagnosed late)
1. Lean
2. Tanned
3. Tired
4. Tearful ± weakness
5. Anorexia
6. Dizzy
7. Faints
8. Flu-like
myalgias/arthralgias.
9. Mood: depression,
psychosis.
10. GI: nausea/ vomiting,
abdominal pain,
diarrhoea/constipation.
(Think of Addison’s in all
with unexplained
abdominal pain or
vomiting. )
11. Pigmented palmar
creases & buccal
mucosa.
12. Postural hypotension.
13. Vitiligo.

12. Signs of Critical Deterioration
• Addisonian crises
– Hypoglycaemia
– Hypercalcaemia.
– Muscle cramps
– Nausea
– Vomiting
– Diarrhoea
– Unexplained fever
High temperatureShock
Coma

13. TESTS
1. Low Na+ & high K+ (due to decreased
mineralocorticoid)
2. Low glucose (due to decreased cortisol)
3. Uraemia
4. High Ca2+
5. Eosinophilia
6. Anaemia.

14. ASSESSMENT OF GLUCOCORTICOIDS
• Random plasma cortisol is
– low in patients with adrenal insufficiency
– it may be within the reference range, yet
inappropriately low, for a seriously ill patient.
• Random measurement of plasma cortisol
– cannot therefore be used to confirm or refute the
diagnosis, unless the value is above 500 nmol/L (> 18
µg/dL), which effectively excludes adrenal
insufficiency.
• More useful is the short ACTH stimulation test

15. Short ACTH stimulation test
(Synacthen® test)
DO PLASMA CORTISOL ADDISON’S IS EXCLUDED
• Before and ½h after
tetracosactide (Synacthen®)
250mcg IM
• If 30min cortisol
>550nmol/L.

16. ACTH
IN ADDISON’S (high) IN SECONDARY CAUSES (low)
• 9AM ACTH is high (>300ng/L:
inappropriately high).
• 21-Hydroxylase adrenal
autoantibodies: +ve in
autoimmune disease in
>80%
• Plasma renin &
aldosterone: to assess
mineralocortocoid
status.

17. AXR/CXR
• Any past TB,
– Upper zone fibrosis
• Adrenal calcification
• If no autoantibodies, consider further tests
– Adrenal CT
• TB, histoplasma, or metastatic disease.

18. Assessment of Mineralocorticoids
CANNOT BE ADEQUATELY ASSESSED BY
ELECTROLYTE MEASUREMENTS IS
• Since hyponatraemia occurs in both
aldosterone and cortisol deficiency
HYPERKALAEMIA MEASUREMENT • Finding is common, but not
universal
ALDOSTERONE DEFICIENCY. • Plasma renin and aldosterone
should be measured in the supine
position
MINERALOCORTICOID DEFICIENCY • Plasma renin activity is high, with
plasma aldosterone being either low
or in the lower part of the reference
range.

19. TREATMENT
Replace steroids
15–25mg hydrocortisone
daily, in 2 –3 doses,
10mg on waking,
5mg lunchtime.
Avoid giving late (may
cause insomnia).
Mineralocorticoids to
correct postural
hypotension, low Na+,
high K+
Fludrocortisone PO from
50–200mcg daily.

20. Steroid Use
1. Advise wearing a bracelet declaring steroid
use.
2. Add 5–10mg hydrocortisone to daily intake
before strenuous activity/exercise.
3. Double steroids in febrile illness, injury, or
stress.
4. Give out syringes and in-date IM
hydrocortisone, and show how to inject
100mg IM if vomiting prevents oral intake

21. Follow-up
• Yearly (BP, U&E)
• Watch for autoimmune diseases (pernicious
anaemia).

22. Prognosis
• (Treated) adrenal crises and infections do
cause excess deaths
• Mean age at death for
– Men is ~65yrs (11yrs <estimated life expectancy
– Women lose ~3yrs).

23. EXOGENOUS STEROID USE
• Replacement steroids are vital in those taking
long-term steroids when acutely unwell.
• Adrenal insufficiency may develop with deadly
hypovolaemic shock, if additional steroid is not
given.
• Warn against abruptly stopping steroids.
• Give steroid card.
• Emphasize that prescribing
doctors/dentists/surgeons must know of steroid
use

25. ADDISONIAN CRISIS

26. Signs and Symptoms
• Patients may present in shock (low HR;
vasoconstriction; postural hypotension;
oliguria; weak; confused; comatose)
High temperatureShock
Coma

27. Precipitating Factors
1. Infection, trauma, surgery, missed
medication
2. In a patient with known Addison’s
– oral steroid has not been increased to cover stress
such as pneumonia
3. Remember
– Bilateral adrenal haemorrhage (eg
meningococcaemia) hypoglycaemia.

28. Management
• If suspected, treat before biochemical results.
• Bloods for cortisol and ACTH (this needs to go straight to laboratory,
call ahead!)
• U&ES
– can have high K+ (check ECG and give calcium gluconate if needed)
– Low Na+ (salt depletion, should resolve with rehydration and steroids).
• Hydrocortisone 100mg IV stat.
• IV fluid bolus eg 500mL 0.9% saline to support BP, repeated as
necessary.
• Monitor blood glucose: the danger is hypoglycaemia.
• Blood, urine, sputum for culture, then antibiotics if concern about
infection

30. Continuing Treatment
HYPOGLYCAEMIC. • Glucose IV
CLINICAL STATE AND U&E IMBALANCE. • IV fluids
STEROIDS • Continue hydrocortisone, eg
100mg/8h IV or IM.
• Change to oral steroids after 72h if
patient’s condition good.
ADRENAL DISEASE: ASK AN EXPERT. • Fludrocortisone may well be needed
FIND UNDERLYING CAUSE. • Get endocrinological help
• Search for (and vigorously treat)

32. SUMMARY
• What is adrenal insufficiency
• Features/clinical findings
• Investigation
• Making diagnosis
• Treatment and follow-up
• Addisonian crisis, diagnosis,
investigation, management and follow-up

33. REFERENCES
• Clinical Medicine, Oxford Handbook
• Davidson, Medicine

34. • THANK YOU