ADDISON'S DISEASE

ADDISON’S DISEASE:

Introduction:

·         One way the body keeps itself in balance is by using chemical messengers called hormones to regulate various functions. Just above each kidney is a small adrenal gland. These glands make hormones essential to a healthy life.

·         Addison’s disease is a disorder that occurs when the adrenal glands do not produce enough hormones.

·         Addison’s disease is a rare condition, only one in 100,000 people have this disease. It can happen at any age to either men or women. People with addison’s disease can lead normal lives as long as they take their medication. President John Kennedy had this condition.

·         Addison’s disease also called as primary adrenal insufficiency, the adrenal glands don’t make enough of a hormone named cortisol or less often a related hormone called aldosterone.

·         Cortisol’s most important function is to help the body respond to stress. It also helps regulate our body’s use of protein, carbohydrate and fat. It helps in maintaining blood pressure and cardiovascular function and controls inflammation.

·         Aldosterone helps kidney to regulate the amount of salt and water in the body. The main way is to regulate the blood volume and keeps our blood pressure under control when aldosterone level drops too low, kidneys cannot keep our salt and water levels in balance; this drops the blood pressure of the body.

·         Adrenal glands are composed of two sections. The internal medulla produces adrenaline like hormones. The outer layer (cortex) produce group of hormones called corticosteroids, which include glucocorticosteroids, mineralocorticosteroides and male sex hormones (androgens). Some of the hormones of cortex are essential for life like glucocorticoides and mineralocorticoides.

Structure of Adrenal glands:

·         Adrenal glands are small hormones releasing organs located on the top of each kidney. They are made up of an outer portion, called the cortex and the inner portion called medulla. These glands are located just above our kidneys. They produce hormones that give instructions to virtually every organ and tissues in our body.

                              

Cortex produces three hormones:

          i.            Glucocorticoides hormones (cortisol) maintain sugar (glucose) control, decrease or suppress immune response and help the body to respond to stress.

         ii.            Mineralocorticoides produces aldosterone hormones which regulate Na and K balance.

       iii.            Sex hormones are androgens (male sex hormone) and estrogens (female sex hormones) affect sexual development and sexes derive.

                 

Causes:

Addison’s disease results from the damaged adrenal gland which produces insufficient amounts of the hormones, cortisol and aldosterone. This damage is caused by following reasons:

Ø  Immune system mistakenly attacking adrenal glands (autoimmune disease).

Ø  Infections such as T.B., HIV or fungal infections.

Ø  Haemorrhage into the adrenal glands

Ø  Tumours

·         Risk factors for the autoimmune type of Addison disease includes:

Ø  Swelling (inflammation) of the thyroid gland that often results in reduced thyroid function. (Chronic thyroiditis).

Ø  Thyroid gland produces too much thyroid hormone.

·         Due to primary adrenal insufficiency autoimmune disease occurs for 70% of addison’s disease. This occurs when the body’s immune system mistakenly attacks the adrenal glands. This autoimmune assault destroys the outer layer of the glands.

·         Long lasting infections such as T.B., HIV and some fungal infections can harm the adrenal glands. Cancer cells that spread from other parts of the body to the adrenal glands also cause addison’s disease.

·         Adrenal glands can be injured as a result of bacterial infections.

·         Adrenal glands can be affected by secondary adrenal insufficiency which is caused by problem associated with the pituitary gland or hypothalamus; both are located in the centre of brain.

·         These glands produce hormones that act as a switch that can turn on or off the production of hormones in the rest of the body.

·         A primary pituitary hormone called ACTH is the switch that can turn on cortisol production in the adrenal glands. If ACTH levels are too low the adrenal glands stay in the off position.

·         Prolonged or improper use of steroid hormones such as prednisone.

·         Less common causes includes pituitary tumours and damage to the pituitary gland during surgery or radiation.

Symptoms of Addison’s disease:

The symptoms of Addison’s disease progress slowly, they may go unrecognized until a physically stressful event such as illness, surgery or an accident arises.  When this happens it is known as addisonian crisis. For one in four people with Addison’s disease they realize they are ill. An addisonian crisis is considered a medical emergency because it can be fatal.

·         Weakness in muscles and chronic fatigue.

·         Fatigue and tiredness

·         Darkening in the colour

·         Weight loss and decreased appetite

·         Decreased heart rate

·         Blood pressure get decreased

·         Low blood sugar level

·         Fainting spells

·         Sores are developed in the mouth

·         Craving for salt

·         Nausea, vomiting, irritability or depression

Symptoms of Addisonian crisis:

·         Shock, when the body does not get enough blood flow.

·         Sudden penetrating pain in the lower back, abdomen or legs.

·         Severe vomiting and diarrhoea followed by dehydration

·         Fever

·         Weakness and Fatigue

·         Low blood pressure

·         Loss of consciousness

·         Multiple organ failure includes kidneys, if circulation of blood cannot be restart.

Diagnosis:

In its early stages, adrenal insufficiency can be difficult to diagnose. A review of patients medical history based on the symptoms especially the dark tanning of the skin will lead a doctor to suspect Addison’s disease. A diagnosis of addison’s disease is made by laboratory tests. The aim of these test is first to determine whether levels of cortisol are insufficient and then to establish the cause.  Hormonal blood and urine tests will be taken to check the cortisol levels and is they are too low, X- rays exams of the adrenal and pituitary glands also are useful for diagnosis.

There are two types of diagnostic test for Addison’s disease:

        I.            ACTH Stimulation test:

·         This is the most specific test for diagnosing addison’s disease. In this test, blood cortisol, urine cortisol or both are measured before and after a synthetic form of ACTH is given by injection. In ACTH test IV injections of the synthetic ACTH with samples of blood and urine taken before and after the injection. The measurement of blood is repeated 30-60 minutes after intravenous ACTH injections. The normal response after an injection of ACTH is a rise in blood and urine cortisol levels. Patients with either form of adrenal insufficiency respond poorly or do not respond at all.

      II.            CRH stimulation test:

·         When the response to the short ACTH test is abnormal a long CRH stimulation test is required to determine the cause of adrenal insufficiency. In this test, synthetic CRH is injected intravenously and blood cortisol is measured before and 30, 60, 90 and 120 minutes after the injection. Patients with primary adrenal insufficiency have high ACTHs but do not produce cortisol. Patients with secondary adrenal insufficiency have deficient cortisol responses but absent or delayed ACTH response. Absent ACTH response points to the pituitary as the cause; a delayed ACTH response points to the hypothalamus as the cause.

·         In patients suspected of having an addisonian crisis, the doctor must begin treatment with injections of salt, fluids and glucocorticoid hormones immediately. Although a reliable diagnosis is not possible with the patient’s being treated for the crisis, measurement of blood ACTH and cortisol during the crisis and before glucocorticoids are given is enough to make the diagnosis. Once the crisis is controlled and medication has been stopped, the doctor will delay further testing for one month to obtain an accurate diagnosis.

                                      

Other Diagnostic tests:

·         One a diagnosis of primary adrenal insufficiency has been made X-rays exams of the abdomen may be taken to see if the adrenals have any signs of calcium deposits. Calcium deposits may indicate TB; a tuberculin skin test may also be used.

·         If adrenal insufficiency is the cause, doctors may use different imaging tools to reveal the size and shape of the pituitary gland. The most common diagnostic test is the CT scan, which produces a series of X- ray pictures giving a cross- sectional image of a body part.

·         A diagnosis of Addison disease is made by biochemical laboratory tests.

·         Insulin induced hypoglycaemia test

Treatment:

        I.            Aldosterone Replacement therapy:

·         Treatment of Addison’s disease involves replacing or substituting the hormones that the adrenal glands are not making. Cortisol is replaced orally with hydrocortisone tablets, a synthetic glucocorticoid taken once and twice a day. If aldosterone is not deficient, it is replaced with oral doses of a mineralocorticoid called fludrocortisone acetate (Florinef), which is taken once a day.

·         Patients receiving aldosterone replacement therapy are usually advised by a doctor to increase their salt intake because patients with secondary adrenal insufficiency normally maintain aldosterone production; they do not require aldosterone replacement therapy. The doses of each of these medications are adjusted to meet the needs of individual patients.

·         During an addisonian crisis low blood pressure, low blood sugar and high levels of potassium can be life threatening. Standard therapy involves intravenous injections of the hydrocortisone, saline (salt water) and dextrose (sugar). This treatment usually brings rapid improvement when the patient can take fluid and medication by mouth, the amount of hydrocortisone is decreased until a maintenance dose is achieved. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.

      II.            Surgery:

·         Patients with chronic adrenal insufficiency who need surgery with general anaesthesia are treated with injections of hydrocortisone and saline. Injections given before the surgery and continue until the patients is fully awake and able to take medication by mouth. The dosage is adjusted until the maintenance dosage is given before surgery is reached.

    III.            Pregnancy:

·         Women with primary adrenal insufficiency who become pregnant are treated with standard replacement therapy. If nausea and vomiting in early pregnancy interfere with oral medications injections of the hormone may be necessary. During delivery treatment is similar to that of patients who need surgery; following delivery. The dose is gradually tapered and the usual maintenance doses of hydrocortisone and fludrocortisone acetate by mouth are reached by about 10 days after childbirth. 

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