Addison’s Disease
Case study:
• A patient of 40 years came to doctor with
the complaints of low grade fever for 3
months, haemoptysis and wt. loss. In
investigation- ESR 110 mm hr, x-ray
reveals-TB focus. Anti-TB drug started
but patient died suddenly after 3 days.
The doctor became confused whether
the patient died due to TB or anti-TB
drugs or some other causes.
???
• Addison's disease is a clinical condition
resulting from adrenocortical
insufficiency due to primary acquired
disease of adrenal gland. An English
physician, Thomas Addison, first
described this disease almost 150 years
ago.
These pictures are from Thomas
Addison's book in which he first
described Addison's Disease.
Incidence:
• Addison's disease is a rare endocrine or
hormonal disorder that affects about 1 in
100,000 people. It occurs in all age groups and
afflicts men and women equally.
Causes of Addison’s Disease:
Common causes:
• Autoimmune mechanism- 80% cases (more in female)
• Tuberculosis (of adrenal gland)-10%
• Secondary deposit in adrenals
• HIV infection
• Bilateral adrenalectomy
Other causes:
• Amyloidosis
• Sarcoidosis
• Haemochromatosis
• Bilateral adrenal haemorrhage- following meningococcal septicaemia
(Waterhouse- Friedrichson syndrome), trauma
• Lymphoma
Clinical features:
• Due to glucocorticoid insufficiency-
Weight loss
Malaise
Weakness
Anorexia
Nausea
Vomiting
Gastrointestinal-diarrhoea or constipation
Postural hypotension
Shock
Hypoglycaemia
Hyponatraemia (dilutional)
Hypercalcaemia
Clinical features(contd.)
• Due to mineralocorticoid insufficiency-
Hypotension
Shock
Hyponatraemia (depletional)
Hyperkalaemia
Clinical features(contd.)
• Due to ACTH excess-
Pigmentation:
Sun-exposed areas
Pressure areas, e.g. elbows, knees
Palmar creases
Knuckles
Mucous membranes
Conjunctivae
Recent scars
Clinical features(contd.)
• Due to adrenal androgen insufficiency:
Decreased body hair and loss of libido,
especially in female
Diagnostic criteria of Addison’s
Disease:
Triad of-
• Weakness or emaciation (100% cases)
• Pigmentation (90% cases)
• Hypotension
Investigation
• Random plasma cortisol level-
Usually low but may be within normal range.Refute the diagnosis if the
value is >460nmol/L
• Short ACTH stimulation test/Tetracosactide or short
synacthen test-250microgram ACTH by i.m at any time of day -0 and
30min for plasma cortisol-in addison’s disease plasma
cortisol<460nmol/L
• Long ACTH stimulation test-1mg depot ACTH i.m daily for 3 days-
plasma cortisol <700nmol/L at 8hrs after last injection
Investigation(contd):
• CBC-
For pernicious anaemia
• Blood glucose-
Low or lower limit, specially during
Addisonian crisis.
• Electrolytes-
a)Hyponatraemia.
b)Hyperkalaemia.
Only hyponatraemia is more important.
Investigation(contd):
• Tests to find out causes-
a)Chest X-ray (tuberculosis).
b)Plain X-ray of abdomen (to see adrenal calcification in
tuberculosis).
c)Adrenal auto-antibody.
d)Ultrasonography or CT scan of adrenals.
e)HIV test.
• Other tests-
Plasma calcium-high
Plasma renin activity-high
Plasma aldosterone-low
Treatment:
Replacement of hormones-
• Glucocorticoid (hydrocortisone-15 mg on waking and 5 mg at 6p.m)
• Mineralocorticoid (fludrocortisone 0.05 to 0.1mg daily)
Supportive treatment and treatment of cause:
e.g. if TB- antitubercular therapy
General advice to the patient-
• Good nutrition, regular meal, high carbohydrate and sufficient salt
• When oral therapy is not possible, injection hydrocortisone should
be taken
Complications:
The complications of untreated Addison's
disease include cardiovascular collapse, coma,
and death.
ADVICE TO PATIENTS ON
GLUCOCORTICOID REPLACEMENT:
Intercurrent stress
• e.g. Fever, cold, trauma-double dose of hydrocortisone.
During surgery
Minor operation-hydrocortisone 100 mg i.m. with pre-medication .
Major operation-hydrocortisone 100 mg 6-hourly for 24 hours, then 50 mg i.m. 6-
hourly until ready to take tablets .
Vomiting
Must have parenteral hydrocortisone if unable to take by mouth.
Bracelet and steroid card
patient should always carry this. Should have information regarding the diagnosis,
dose of steroid and doctor.
EQUIVALENT DOSES OF
GLUCOCORTICOIDS:
• Hydrocortisone: 20 mg
• Cortisone acetate: 25 mg
• Prednisolone: 5 mg
• Dexamethasone: 0.5 mg
Side effects of glucocorticoid
Principle of glucocorticoid therapy
• Do not administer glucocorticoids unless
absolutely indicated or more conservative
measures have failed
• Keep dosage and duration of administration to
the minimum required for adequate
treatment
Checklist prior to glucocorticoid
treatment:
• Screen for tuberculosis with a PPD or CXR
• Evidence of IGT,H/O gestational diabetes,Strong family
H/O type II diabetes mellitus in first degree relative
Screen for DM by blood sugar measurement.
• Evidence of HTN,Cardiovascular disease or
hyperlipidaemia
• Evidence of pre-existing or high risk for
osteoporosis(Bone density assessment)
• Screen for glaucoma and cataracts before treatment
• H/O PUD, gastritis or oesophagitis
• H/O psychological disorders
Advise to the pt.
• Diet:
-monitor calorie intake to prevent weight gain
-diabetic diet if glucose intolerant
-restrict sodium intake to prevent oedema and
minimize HTN
-provide supplementary potassium if
necessary
• Administer glucocorticoids with meal to prevent
ulcer. Consider omeprazole 20-40 mg/day
Advise to the pt.(contd.)
• Minimize loss of bone mineral density
-Consider administering gonadal hormone
replacement therapy in post menopausal woman: 0.625-
1.25 mg conjugated estrogens given cyclically with
progesterone, unless the uterus is absent(Testosterone
replacement in hypogonadal men)
-Adequate calcium intake ~1200 mg/day elemental
calcium
-Administer a minimum of 800-1000 IU/day
supplemental vit D
-Consider administering biphosphonate
prophylactically, e.g. Alendronate 10 mg daily or 70 mg
weekly
Advise to the pt.(contd.)
• Prepare the pt. and family for possible adverse effect on
mood, memory and cognitive function
• Inform the pt. about side effects like wt. gain, osteoporosis
• Avoid prolonged bed rest that will accelerate muscle
weakness and bone mineral loss. Ambulate early after
fractures
• Avoid elective surgery, if possible. Vit A 20,000 U daily for 1
wk. may improve wound healing
• Avoid activities that could cause falls or other trauma
• Avoid smoking and alcohol
• Dose to be increased during stress according to advice of
doctor
Follow up:
History:
• About mood, memory and cognitive function
• Visual disturbance(cataract)
• Menstrual disturbance
• Wasting and weakness of proximal thigh
muscles
• About urine test result at home wkly for
glucose
Follow up(contd.)
Examination:
• Blood pressure
• Body wt
• Edema
• Cataract and glaucoma 3 months after Rx then
yearly
• Height(severe to document degree of axial
spine demineralization with compression)
Follow up(contd.)
Investigation:
• CBC
• Blood sugar
• Urine R/E
• ECG
• CXR
• Serum electrolytes
• Bone densitometry
• Serum creatinine
Addisonian Crisis
Definition:
It is a medical emergency due to acute
adrenocortical insufficiency
Causes:
• Sudden withdrawal of steroid(commonest cause, if pt.
on steroid for long time)
• Following stress e.g.intercurrent disease,trauma,
surgery, severe infection or prolonged fasting in a pt
with latent insufficiency
• Following sudden destruction of pituitary
gland(pituitary necrosis)or when thyroid hormone or
drugs which increase steroid metabolism(e.g.
phenytoin)given to a pt with hypoadrenalism
• Following bilateral adrenalectomy
• Following injury to both adrenals due to
trauma,adrenal vein thrombosis,adrenal haemorrhage
due to meningococcaemia or anticoagulant therapy
Clinical Features:
• Nausea, vomiting, diarrhoea
• Abdominal pain
• Diarrhoea
• Muscle cramps
• Unexplained fever
• Unconsciousness
• Severe hypotension
• Hyponatraemia, hyperkalaemia, hypoglycaemia,
hypercalcaemia
Treatment:
• I/V hydrocortisone 100 mg 6 hrly until GI
symptoms abate then oral therapy
• I/V fluid normal saline and 10% dextrose for
hypoglycaemia
• Precipitating factors should be find out and
treated
Why the patient died
in the case study
???
The patient may have subclinical
hypoadrenalism. After giving anti-TB
drugs due to Rifampicin induced
increased hepatic metabolism of
adrenocortical hormone, the patient
developed acute adrenocortical
insufficiency and died.
THANKS TO ALL
