Addison’s Disease (Primary Adrenal Insufficiency)

10 Adrenal Insufficiency-AD

- Destruction of adrenal cortex that leads to glucocorticoid (cortisol) and mireralocorticoid (aldosterone
deficiency) .

20 adrenal insufficiency

- Impairment of pituitary gland or hypothalamus.

Causes of AD

Common Less Common

 autoimmune adrenalitis - 80% IN UK 1. Infections-opportunistic infections
eg.HIV,CMV,Mycobacterium
 TB-worldwide avium;meningococcal infections→ waterhouse-
friderichsen’s syndrome.
 bilateral adrenalectomy for malignant disease
2. Antiphospolipid, SLE
 cessation of therapeutic corticosteroids or 3. Congenital-late onset congenital adrenal
failure to increase dose to cover stress hyperplasia.
4. infiltration:
o amyloidosis

o sarcoidosis

o haemochromatosis

5. Adrenal Metastasis (lung, breast, renal ca, etc)

6. drugs - rifampicin, etomidate, ketoconazole

ASSOCIATION OF AD

 Hashimoto's thyroiditis, Schmidt's syndrome (AD+Hypoparathyrodism)

 DMT1

 premature ovarian failure

 idiopathic hypoparathyroidism

 pernicious anaemia

 mucocutaneous candidiasis

 vitiligo

 alopecia

 Graves' disease

NB!!! primary and secondary adrenal insufficiency share many clinical features - differ in that only primary adrenal
insufficiency is characterized by mineralocorticoid deficiency and by hyperpigmentation.
 Common Less Common
 Muskuloskeletal-muscle weakness  impotence and amenorrhoea
,myalgia,arthralgia
 hypoglycaemia - reduced opposition to insulin-
 GI - anorexia, weight loss, nausea and vomiting, action
intermittent abdominal pain ,constipation.
 diarrhoea
 decrease axillary and pubic hair - common in
women

 Mood-depression, psychosis,low self esteem.

Signs

1. Hyperpigmentation-palmar crease, buccal mucosa

2. Postural HTN

Test

1. FBC-eosinophilia,anemia
2. U&E- ↓Na and ↑K (↓ mineralocorticoid), Uraemia, albumin ↑(dehydration),Ca 2+↑,

3. ↓Glucose-↓Cortisol

4. ↑ plasma ACTH (>300ng/L inappropriately high at 9am).ACTH↓ in secondary causes.

5. Synacthen test

The synacthen test is used to test adrenal reserve. Synacthen is tetracosactrin, the first 24 amino acids of ACTH.

Short synacthen test:

 take a basal sample for cortisol

 give 250 microgramme Synacthen i.v. or i.m.

 sample for cortisol are taken at 30 mins and 60 mins

Result :

 Normal- basal plasma cortisol should exceed 170 nmol/L and rise to at least 580 nmol/L
 The hypoadrenal patient is unable to raise their serum cortisol in response to synacthen.

A depot synacthen test/ long synacten test

Indication:May be performed if the short procedure is equivocal and Addison's disease is suspected:

 basal plasma cortisol is measured

  1 mg of synacthen is given intramuscularly

 samples for cortisol are taken at 1, 4, 8, and 24 hours

Result:

 Normal –plasma cortisol concentration reach 1000nmol/L in 4 H.

 Addisons disease -Plasma cortisol fails to exceed 580 nmol/L

 Secondary hypoadrenalism, a delayed but normal cortisol response may be observed.

6. Adreno-cortical antibodies (21-hydroxylase adrenal autoantibodies)- often present in autoimmune adrenalitis -

more common in women - 80% - than men - 10%
7. PFA - calcified adrenals of tuberculosis

8. CXR – TB, malignancy,calcification

9. Adrenal CT-may be considered.

10. Other autoimmune disease antibodies-thyroid,SLE

Treatment-Replace steroids BECLOMETHASONE: CUSHINGOID:

Buffalo hump Cataracts
Primary insufficiency: Easy bruising Ulcers
Cataracts Skin: striae, thinning, bruising
Larger appetite Hypertension/ Hirsutism/
1. 15-20 mg hydrocortisone/day in 2-3 divided doses,eg Obesity Hyperglycemia
o 10 mg in the morning Moonface Infections
Euphoria Necrosis, avascular necrosis of
o 5 mg at midday Thin arms & legs the femoral head
Hypertension/ Hyperglycaemia Glycosuria
Avascular necrosis of femoral Osteoporosis, obesity
Don’t give late in the day-----insomnia
head Immunosuppression
Skin thinning Diabetes
2. Mineralocorticoid (Fludrocortisone 50-200 microgramme/D)
Osteoporosis
Negative nitrogen balance
Indication:Postural HTN, ↓Na,↑K/↑plasma renin Emotional liability

o measure blood pressure and serum electrolytes to assess adequacy of mineralocorticoid therapy
o complications include hypokalaemia, hypertension, oedema and cardiac enlargement

o adjust doses of both drugs according to postural hypotension, plasma urea and electrolytes

NB:If Tx didn’t work→ check other autoimmune causes.

Steroids…..what pts need to know

NB: steroids card and medicalert bracelet

1. add 5-10 mg hydrocortisone to daily intake b4 strenuous activity

2. Double steroids-in illness, injury/stress
 3. Educate pts about injection---give syringe and IM hydrocortisone (use when PO route impossible)

4. Vomiting-take hydrocortisone 100mg IM, seek medical help,admit

Secondary insufficiency:As above ±mineralacorticoid±thyroxine (in case of ass. thyroid disease)

Folllow Up: Yearly BP and U&E

Prognosis:good with normal lifespan.

Emergency-Addison Crisis (cortisol inappropriately low)

S&S-usually as shock (tachy,vasoconstriction,postural HTN, oliguria, weak,confused,comatose).Typically happen in

known addison’s disease, but may happen in long term user of steroid who forget to take their tablet.

Precipitating Factor:Infection,trauma,Sx

Management-if suspected, treat B4 biochem result

Investigation

 Take blood for plasma cortisol and ACTH

 FBC,U&E,blood glucose,Cultures

Immediate

1. 100 mg IV Hydrocortisone (stat dose)

2. Use plasma expander for resuscitation/then 0.9 % saline, or straight away use saline eg.0.9% saline ,1L
over 30-60 mins.

3. 50 ml of 50% dextrose if hypoglycaemia

4. If suspect infections, prphylaxis antibiotics eg cefuroxime 1.5g/8HIV

Subsequent

1. Hydrocortisone 100 mg IM 6H
2. 0.9% saline 2-4L IV in 12-24H, Fluid replacement must be guided by clinical state.

3. Expect recovery with Normal BP, glucose and serum Na in 12-24H.

4. When stable, change to oral steroids, usually in 72H.

5. Fludrocortisone is needed only if hydrocortisone dose< 50mg/D and the condition is due to adrenal disease.

6. Search for the cause/s.