Indo American Journal of Pharmaceutical Research, 2015
ISSN NO: 2231-6876
A REVIEW ON ADDISON'S DISEASE
Sayyed Sarfaraz Ali Riyasat Ali*, Pentewar R. S, Shaikh F. E, Gholve S. B, Sugave R.V, Suryawanshi R.
N, Gapat S
Department of Pharmaceutics, Channabasweshwar Pharmacy College, Latur, Maharashtra, India.
ARTICLE INFO
Article history
Received 20/09/2015
Available online
30/09/2015
Keywords
Addison ’s Disease,
Autoimmune Adrenalitis,
Kidney, Cortisol.
ABSTRACT
Addison's disease is chronic, life threatening rare endocrinal disorder which affects 1 in
100,000 people. Both sex people equally affected by this disorder. Autoimmune adrenalitis is
most common cause of primary adrenal insufficiency. It's prevalence is about 140 per million.
Autoimmune adrenalitis disorder, the adrenal cortex is damaged causing the loss of
production of hormone such as glucocorticoid,mineralocorticoid. The fight and flight stress
hormone adrenaline produced by inner medulla. The cortisol and aldosterone are the
esssential steroid hormone produced by it. Function of the cortisol is to enable the body to
fight inflammation, stimulates liver to produce blood sugar, mobilises nutrients, helps to
balance the quantity of water in human body. While the salt & water level which have impact
on Blood Pressure is regulated by aldosterone. The main objective of this review article is to
create an awareness among the people concerning with the addison's disease & it's symptoms,
diagnosis, treatment. Rational utilization of drug therapy with patient compliance is
important.So that proper management of Addison's disease is achieved.
Copy right © 2015 This is an Open Access article distributed under the terms of the Indo American journal of Pharmaceutical
Research, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Please cite this article in press as Sayyed Sarfaraz Ali Riyasat Ali et al. A Review on Addison's Disease. Indo American Journal of
Pharmaceutical Research.2015:5(09).
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Corresponding author
Sayyed Sarfaraz Ali Riyasat Ali
M. Pharmacy,
Channabasweshwar Pharmacy College,
Latur-413512
[email protected]
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ISSN NO: 2231-6876
INTRODUCTION
In primary adrenal insufficiency condition the thomas addison detected group of patient with anaemia and disease adrenal
glands, almost 200 yrs ago.[1] In this disorder, adrenal cortex destroyed which result into inadequate secretion of adrenal cortical
hormone, cortisol and aldosterone.[2-3] In fact Addison's disease is progressive hypofunctioning of the adrenal cortex. The various
symptoms include loss of appetite, hyperpigmentation, hypotension and adrenal crisis. Diagnosis is clinical while treatment dependent
on the etiology but usually includes hydrocortisone, dexamethasone, prednisone, florinef etc. as per requirement. [4-5]
Adrenal disease is rare disorder which develops in 4/100,000 people anually. Both sex with all age group affected wchich tends to
become clinically apparent during stress. Various causes include Na loss, surgery & trauma. Slight increase in mortality rate of patient
suffering with addison's disease even when its treatment given. This happen particularly due to long term complications of inadvertent
over replacement.[7-8]
Fig no.1 Adrenal gland.
In hypoadrenocorticism the clinical features donot appear until 90% of the glandular tissue has been damaged.
Hyperpigmentation of eyes, mucous membrane and skin is associated with addison's disease. [9-11] Hyponatremia and hyperkalaemia
are usually realated with addison's disease patient complains of a peculiar craving of salt, adrenal calcification, anorexia, diarrhoea.[1214]
Addisonian crisis may occur due to an event of illness that can worsen the condition further. Symptoms of addisonian crisis
include penetrating pain in abdomen, legs and back region with diarrhoea which followed by low blood pressure and dehydration.[9-14]
There are two forms of Addison's disease as follows:
1.Primary adrenal insufficiency: It occurs when adrenal glands are destroyed and it fails to produce enough cortisol and aldosterone
hormone.[23]
2.Secondary adrenal insufficiency: It occurs when a bean size organ in brain unable to produce sufficient ACTH. Cortisol is produced
by adrenal gland which is stimulated by ACTH. Ultimately, there is decline in cortisol production. Lack of ACTH stimulation causes
adrenal glands to shrink.
Etiology
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Autoimmune disease almost accounts for about 80% of adrenal insufficiency. In this case body's immune system attack
adrenal glands which damages outer layer of the glands. [15] Deficiencies of glucocorticoid, mineralocorticoids which resulting from
damage of adrenal cortex caused by autoimmune adrenalitis. In men, adrenoleukodystrophy is important cause of rare endocrinal
disorder. It is resulting from accumulation of long chain fatty acid in adrenal gland. [16]
Cancer cells, fungal infections and long lasting infections such as TB & HIV can harm adrenal glands. Improper utilization of
steriodal hormone such as dexamethaone, prednisone leads to secondary adrenal insufficiency. Secondary adrenal insufficiency is
caused due to problems with hypothalamus located in the center of brain.ACTH is a pitituary hormone which stimulates the cortisol
production in adrenal gland. Another cause is due dysfunctioning of pitituary glands which is responsible for cortisol production in
adrenal glands.[17]
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ISSN NO: 2231-6876
Fig no:2 Adrenal tumor.
Fig no:3 Adrenocortical carcinoma.
Pathophysiology
The destruction of almost entire adrenal cortex result into adrenocortical insufficiency.Therefore, it causes the dysfunctioning
of steroidal hormone like mineralocorticoid and glucocorticoids. Disease onset occurs when nearly 90% of both the adrenal cortices
are dysfunctional.[18]
Epidemiology
Frequency:
It is found that about 50-60% cases per million population affected by this disorder.
International:
In Denmark 50% cases per 1 million population while in Great Britain 40cases per 1 million population reported.
Mortality/Morbidity
Mortality & Morbidity occurs due to failure or delay in making diagnosis and failure to institute adequate necessary
hormone such as mineralocorticoid replacement. Failure to prompt treatment leads to addisonian crisis which eventually may cause
death. Risk of death is more than 2-fold high in patient with adrenal insufficiency even after clinical diagnosis and treatment.
Race
Adrenal insufficiency is not concern with racial predilection.
Sex
Woman and children are most susceptible to addison's disease than men.
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It can occur at any stage of life but usually occurs in adults in 35-50 yrs. It may be due to disorder of long chain fatty acid
metabolism, congenital adrenal hyperplasia.
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Age
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Sign and Symptoms
Sign
 Hyperpigmentation of skin and mucous membranes
 Low blood pressure
 Postural hypotension
Symptoms
 Fatigue
 Malaise
 Loss of appetite
 Nausea and vomiting
 Abdominal pain
 Weight loss
 Postural dizziness
 Myalgia
 Joint pain
 Salt craving
Addisonian crisis
If the patient with addison's disease faces extreme physical stress and trauma & does not get extra steroid to cover their body
needs to meet that trauma.Such circumstances resulting in the Addisonian crisis. This crisis needs quick emergency treatment as it is
potentially life threatening condition. If this situation is left untreated it may be fatal. The Addisonian crisis consist of symptoms
which include extreme weakness, fatigue, drop in blood pressure, dehydration etc. [18]
Diagnosis
Metabolic test
The main objective of laboratory testing is to document a low cortisol level and find out whether the insufficiency is due to
primary or secondary cause. It suggest adrenal insufficiency to low serum cortisol levels while hyponatraemia may be attributed to
mineralocorticoid deficiency.[19-20]
Immunogenic test
21-hydroxylase enzyme is essetial for synthesis of cortisol in adrenal cortex in adrenal cortex. Various antibodies directed
against the enzyme which are particularly for autoimmune adrenalitis and hence are detectable before the onset of symptoms. [1]
Imaging
Determination of the cause of Addison's disease by Radiographic imaging play's an important role in diagnostis. Before
radiographic imaging, it is necessary to make biochemical tests.
ACTH Stimulation test
The most significant test for diagnosing the addison's disease is ACTH test. In this diagnostic test both blood and urine
cortisol are measured before and after injection of ACTH is given. Measurement of cortisol in blood is repeated 30-50 min after IV
ACTH injected. Patient with adrenal insufficiency doesnot respond to this test. [21]
CRH stimulation test
This is the most specific test for diagnosing adrenal insufficiency. Determination of cause of addison's disease possible after
long CRH stimulation test. CRH is injected IV and blood cortisol is measured 30, 60, min before and after injection. High ACTH
found in primary adrenal insufficiency patient while deficient response in patient with secondary adrenal insufficiency. As patient is
being treated for crisis, reliable diagnosis is not possible at all. [21]
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Treatment[22-25]
Addison's disease treated by substituting, replacing hormones that adrenal glands are not producing. However, the cortisol is
replaced with the prednisone, dexamehasone, hydrocortisone which is taken orally thrice times a day. Deficiency of aldosterone is
overcome by replacement of oral doses of mineralocorticoid, florinef taken twice per day. It is usually advised by doctors to increase
salt intake in patient who is receiving aldosterone replacement therapy. In addisonian therapy low blood pressure, low glucose level,
high level of potassium which may be life threatening. Hence in such circumstances IV injection of glucocorticoid and large volume
IV saline solution with dextrose given.
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Other test
After diagnosis studies radiologic studies like x-ray, ultrasound of abdomen can be taken to observe if adrenal have any sign
of calcium deposits. Calcium deposit may be indicated by bleeding in adrenal cortex. Detection of antibodies concerned with
autoimmune disorder may be possible by blood test. [21]
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Surgery
Surgery carried out because cortisol is a stress hormone. IV glucocorticoids and saline given to patient with chronic adrenal
insufficiency who require general anaesthesia. The stress dosage is adjusted until patient recovers with presurgery maintainence dose.
Pregnancy
Those women suffering from addison's disease and at the same time who become pregnant are given treatment with standard
replacement therapy. Injection of hormone given when voitting occurs. Maintenance dose is given orally i.e. hydrocortisone acetate
post delivery.
Illness
Adjustment of oral dosing of mineralocoticoid to enhance the hormonal response of adrenal glands to this stress on patient's
body. Maintenance dose provide once the stress recovered.
Emergency
In the case of emergency patient must carry identification stating their condition. If a person found injured or unconsious in
such circumstances a medical alert tag must notify emergency health care providers the need to inject cortisol. The card must include
name, telephone no, address of both doctor and patient.While in journey patient must carry injectable cortisol for emergency purpose.
CONCLUSION
Addison's disease is a chronic endocrinal disorder which may be occur in both sex pople. It can be diagnosed, treated. But if
left untreated leads to Addisonian crisis & hence this may fatal. Therfore patient must follow the rational therapy.patient must carry
medical tag to notify the health care provider about their condition in emergency. Therefore, it is significant to study this life
threatening disorder and maje adequate precautions and follow essential guidelines to avoid any untoward incident.
Acknowledgement
The author wish to express his gratitude to the faculty members of Channabasweshwar Pharmacy college, Latur,India.
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Author's statements
competing interest
The author declare no conflict of interest.
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