ADDISON’S DISEASE

Addison’s disease is a primary adrenal insufficiency (i.e. disease affecting the adrenal gland while the hypothalamus & pituitary gland is normal) in which there is the destruction of the entire adrenal cortex resulting in a deficiency of adrenocortical hormones (glucocorticoid, mineral corticoids, and adrenal androgens).

Secondary adrenal insufficiency is due to pituitary failure as a result of atrophy, tumor, or necrosis

The mineralocorticoid production persists because it is under the control of the renin-angiotensin system.

ETIOLOGY

1 . Autoimmune

2. Tuberculosis

4. Bilateral adrenalectomy

5. HIV

Uncommon

1 . Metastatic carcinoma, lymphoma

2. Bilateral adrenal hemorrhage or infarction

3. Hemochromatosis

4. Amyloidosis

CLINICAL FEATURES

They result from glucocorticoids usually together with mineral corticoid insufficiency, loss of adrenal
androgen production and increased ACTH.

The presentation may be acute, chronic, or acute on chronic as following:

Chronic presentation

Symptoms

Weakness

Weight loss

Nausea, vomiting

Fever

Anorexia

Constipation

Abdominal pain

Impotence

Depression

Syncope due to postural hypotension

Myalgia

Mental irritability

On examination

Hyperpigmentation

Hyperpigmentation often raises suspicion. Hyperpigmentation is especially prominent over the knuckles,
elbows, knees, posterior neck, palmar creases, buccal cavity, and nail beds. New scars are also pigmented.

Hypotension and postural hypotension are almost invariably present.

Vitiligo

Hyperplasia of lymphoid tissue and scanty axillary and pubic hair.

Dehydration

Muscle wasting.

Acute presentation

Many patients are not diagnosed in the chronic phase and present with an acute adrenal crisis.

Intercurrent disease, infection, or surgery may be the precipitating factors.

Clinical features

Circulatory shock

Hyponatremia features

Hyperkalemia features

Hypoglycemia (in some cases)

Muscle cramps

Nausea, vomiting, diarrhea

Unexplained fever

INVESTIGATIONS

1. Blood urea & serum electrolytes

• Urea raised

• Sodium decreased

• Potassium increased

• Hypercalcemia

2. Blood sugar: low

3. Blood CP: neutropenia, lymphocytosis, eosinophilia

4. X-ray chest: may show tuberculosis, fungal infection, or cancer as a possible cause.

5. CT abdomen

Can show small non-calcified adrenals in autoimmune Addison’s disease, enlarged adrenals in metastatic disease

Calcification is also seen in adrenal hemorrhage, fungal infection, pheochromocytoma, and melanoma.

Serum cortisol: serum cortisol <5 mg/dl at 8 AM is diagnostic especially if there is
a simultaneous elevation of plasma ACTH

• ACTH stimulation test: failure of plasma cortisol to rise following administration of ACTH.

Measurement of plasma ACTH: a high level of ACTH with a low or normal level of cortisol confirms primary hypoadrenalism.

Anti-adrenal antibodies present in 50% of cases of autoimmune Addison’s disease.

Serum aldosterone: is reduced with high plasma renin activity.

MECHANISMS OF FEATURES OF ADRENAL INSUFFICIENCY

Features of glucocorticoid insufficiency

1 . Weakness, weight loss & malaise.

2. Anorexia, nausea, vomiting, diarrhea, or constipation.

3. Postural hypotension due to sodium loss.

4. Hypoglycemia.

Features of mineral corticoid insufficiency

Hypotension, hyponatremia, hyperkalemia

Features of increased ACTH secretion

Pigmentation of exposed areas & pressure areas e.g. elbow,/ knee, palmar creases, knuckles, mucous membrane, conjunctiva, and recent scars.

Mechanism

The cause of pigmentation is that the decreased level of cortisol in the blood has no feedback effect on ACTH. Therefore ACTH secretion continues from the anterior pituitary gland along with melanin stimulating hormone (MSH), which is also secreted by the same cells that secrete ACTH, the increased MSH stimulates more melanocytes which produce melanin in an excessive amount, resulting in pigmentation.

Features of adrenal androgen deficiency

Decreased body hair especially axillary and pubic hair.

Treatment

Glucocorticoid and mineralocorticoid replacement. Not discussed here as not within the scope of general practice