Addison’s Disease

Dr Shahjada SelimEndocrinologist

BIRDEM

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

MalaiseWeaknessAnorexiaNauseaVomitingGastrointestinal-diarrhoea or constipationPostural hypotensionShockHypoglycaemiaHyponatraemia (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