ADDISON'S DISEASE

        ADDISON’S DISEASE

                                                           ( Synonym)ADRENAL INSUFFIENCY

CAUSES:

1.primary- Defect in adrenal gland itself

Secondary-secondary to pituitary defect

Primary

1.infection-TB

2.immunological-auto immune adrenalitis

3.infiltration-amyloid,fungal,malignant,hemochromatosis

4.infarction or hemorrhage-meningococcal

5.Abalation-surgical

6.secondaries in adrenal-metastatic invasion

7.syphilis

8.AIDS

Adrenalin insufficiency occurs when more than90% of the gland is destroyed

Secondary adrenal insufficiency

Hypopituitarism

Hypothalamic disease

Withdrawal of chronic steroid therapy causing suppression of hypothalamic pituitary axis

CLINICAL PICTURES

Due to 1.cortisol deficiency and 2.aldosterone deficiency both put together

3 main features of Adrenal dificiency

1.hypotension

2.hyperpigmentation of skin& mucosa

3.Severe asthenia

Asthenia or severe lassitude is a non specific symptom but is common  and marked.

Hypotension

Mechanism:

Loss of water and potassium(lack of aldosterone) +

Lack of cortisol which has vaso constrictor or pressor effect.

Hypotension-systolic BP is less than100mmof Hg

This is orthostatic hypotension-evident on standing postion not evident while lying down.

Patient c/o giddiness on standing.

Hyperpigmentation

Very characteristic.

It affects skin and buccal mucosa

Skin-over pressure points,creases,scars,knukles, elbow, knee, waist, over the exposed areas.

Already pigmented areas are more pigmented

Pigmentation is due to excess secretion of Melanocyte stimulating hormone by the pituitary

This along with ACTH

Pigmentation is absent in secondary adrenaline insufficiency

Mucosal pigmentation

Prominent over buccal mucosa and anterior aspect of gum.

Timing

In some cases pigmentation may preced other features by many years Hyperpigmentation may not be present in some cases..

Vitiligo may occur in some cases-usually associated with autoimmune adrenalitis.

Severe Asthenia

Other vague complaints are

1.G.I.Tract- nausea,vomiting,diahrrea,anorexia

2.loss of hair in axilla &pubis in females because of loss of adrenergic steroids.

3.Auto immune damage to ovaries/testis-impotence,loss of libido

4.Hypoglycemia related to reduced cortisol which coverts glycogen to glucose.

(cortisol is diabetogenic)

5.Mental symptoms like confusion, irritability, lethargy

6.Intolerence to stress;

In stress patient cannot increase the cortisol output.

So acute exacerbation of symptoms occur with life threatening vascular collapse.

Aldosterone deficiency

1.sodium loss- results from reduced aldosterone  mediated absorbtion of  Na &water consequence-hypovolemia,hypotension,fall in renal flow &uremia

2.Potassium retension- hyper kalemia and ecg chnges and arrhythmias.

Diagnostic features

1.Hypotension

Hyper pigmentation

Differentials for  hyperpigmentation

Pellagra

Malnutrition

Malignancy,irradiation

Drug induced

Thyrotoxicosis

Crohns disease

Ochronosis

Hemochromotosis

Acanthosis nigricans

Arsenic poisoning

Peutz jeghaers syndrome-(intestinal polyposis)

INVESTIGATIONS

Measure levels of Na,K,ACTH and cortisol

4 important investigations

1.low sodium and chloride levels in  blood and hyperkalemia

2.slow excretion of water load

3.low to absent 24 hrs 17 oh  ketosteroids

4. ACTH  stimulation test :poor response to IM injection of corticotrophin

(Tip- all low and slow except hyper kalemia)Water load

If water load is given there is failure to excretit.butdiagnostic value of this test is limited.

ACTH test

ACTH in dose of 25-50 mg is given IV over 8hrs 24 hr urinary excretion of 17-Oh ketosteroids is measured a) the day before the infusion b0 the day after infusion

Similarly serum cortisone level also is measured before and after infusion

Normal response is  3-5 fold rise in urinary corticosteroids

If level remains low throughout –primary

If cortisol is low initially but shows delayed rise-Pituitary cause.

5.Other investigations

ChestXray,(to detect evidence of TB)CT abdomen

Adrenalin antibodies 

TREATMENT

Gluco corticoid replacement is needed inall patients

Cortisol (Hydrocortisone) is given ,not cortisone,because cortisone is to be converted to active  cortisol in the body and its absorption is poor.

Minerelo corticoids need not be replaced in all.

Indication for replacement:

Low sodium,potassium,low BP.

Drug of choice –Fludrocortisone0.05to2mg.

NOTE:

Synthetic glucoteroids like predisolone,prednisone,dexamethasone triamcinalone are not substitute forCortisol because their salt retaining power is poor.

Acute addisonian crisis

Clinically:

Collapse with hypotension

Mental symptoms

Vomiting

Abdominal pain

Cause: untreated patient, stress like infection,trauma,surgerry

or if cortisol level is not raised in acute stress

Treatment of crisis:

IV cortisol

IV saline

Mineralo corticoids.

Mnemonics forAddison’s disease Clinical picture

A-Asthenia

D-dark skin-Hyper pigmentation

D-de pigmentation(vitiligo)Absent in secondary)

I-Intestinal symptoms

S-salt depletion(hyponatremia)

O-orthostatic hypotension

N-neuro psychiatric manifestation

MNEMONIC FOR CAUSES

IAS

I-infection,,infiltration,immunological,invasion,infarction,iotrogenic

A-ablation-surgical

S-syphilis,AIDS

===================