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Addison's disease

Addison's disease also known as chronic adrenal insufficiency is a hormonal disorder characterized by tissue necrosis and granulomatous appearance. Addison's disease occurs to people irrespective of age and gender. Addison's disease is also known as hypocortisolism as it is associated with insufficient production of cortisol from the adrenal glands.

Cortisol belongs to the class of glucocorticoid hormones. They are released from the cortex of the adrenal glands located on top of the kidneys. Cortisol has a significant function in the body and is associated with main organ system functions in maintaining the homeostasis in the body. Cortisol is essential in protein, carbohydrate and fat metabolism. It also helps in the regulation and release of insulin for blood sugar balance.

The other important functions of cortisol include maintenance of blood pressure, cardiovascular activity and inflammatory response process associated with the immune system. The level of cortisol in the body is used as a determination of stress management. Cortisol has precursors for its release such as the adrenocorticotropic hormone released due to the stimulus associated with the hypothalamus and pituitary gland.


Clinical manifestations

Addison's disease etiology is predominantly based upon the function of the adrenal gland and the release of cortisol regulated by the pituitary gland. Insufficient cortisol production may be due to impairment of adrenal glands which is categorized as the primary phase in Addison's disease occurrence. The secondary factors are associated with release of adrenocorticotropic hormone levels from the pituitary gland to stimulate the adrenal gland. The tertiary factors are associated with insufficient release of corticotrophin releasing hormone from the hypothalamus.


Significant clinical manifestations include anorexia, vomiting, hypoglycemia, weight loss, cutaneous and mucosal pigmentation, hypernatremia, hyperkalemia, hypotension caused due to extra cellular fluid loss. Excess melanin production is observed along with visible changes in the surfaces of lips and buccal mucosa. Addison's disease can also occur because of preexisting factors such as tuberculosis, histoplasmosis, coccidioiodomycosis , autoimmune diseases and conditions associated with bilateral metastases, hemorrhages, amyloidosis and adrenoleukodystrophy.


Diagnosis of Addison's disease

Addison's disease is diagnosed by clinical symptoms which are correlated with biochemical laboratory tests. The levels of sodium, potassium and other important parameters with respect to inflammatory response and hormonal levels can diagnose the presence of Addison's disease. One of the significant diagnostic tools used to detect the presence of Addison's disease is the ACTH (adrenocorticotropic hormone stimulation test). In this test, ACTH is given intravenously to the patient and the levels of cortisol in urine and blood are examined. This test determines adrenal insufficiency factor.


Addison's disease and pregnancy

Steroid hormone balance and support aids labor and fetal development. Insufficiency of steroid hormones can affect the pregnancy especially during a cesarian. Conditions associated with Addison's disease may increase under situations of emergency. This is because of lack of steroid production in the body. Symptoms such as colds, confusion, increased weakness and fatigue can occur; which may become fatal if untreated.


Diet for Addison's disease

Patients with Addison's disease express cravings for salty food or foods that have citrus flavor. Sufficient intake of proteins balanced with vitamins and minerals is advisable. Many patients suffer dehydration; hence increased fluid intake is advised. Diet patterns can be altered in patients having conditions such as diabetes, hypertension and osteoporosis.

Treatment for Addison's disease

Hydrocortisone and fludrocortisone are generally used to replace the cortisol and aldosterone hormones in cases of adrenal insufficiency. Other options used are prednisone, dexamethasone with slow and sustained release characteristics. The advisable dosage for these steroid hormones is thrice a day to meet with the energy demands and activity of the individual.

Adrenal Gland Tumor

The adrenal gland is located on the superior portion of the kidney. It produces some of the most important hormones associated with body metabolism. Many metabolic pathways depend upon the adrenal gland functionality through its hormone production. Some of the significant hormones produced by the adrenal gland include aldosterone, cortisol, sex hormones and adrenaline. The adrenal gland comprises two distinctive regions cortex and medulla respectively. Each region of the adrenal gland produces different kinds of hormones.

Adrenal Insufficiency

Adrenal insufficiency is a disorder predominantly associated with the dysfunction of the adrenal cortex region. The intensity of this disorder can be represented as primary or secondary depending upon the impaired adrenal cortex and its functionality. Studies imply that autoimmune diseases such as Addison's disease are the predominant cause for the adrenal sufficiency. In the secondary condition of this disorder, the production of adrenocortico tropic hormone is reduced to a greater extent. Although autoimmune disorders play a major role in the adrenal insufficiencies, other causes such as infectious diseases, vascular impairments, congenital disorders and also iatrogenic causes lead to adrenal insufficiencies. These factors predominantly influence the production of glucocorticoids.

The adrenal insufficiencies associated with mineralocorticoids are caused because of underlying conditions such as corticosterone methyl oxidase deficiency, impairments in the Zona glomerulosa and treatments such as heparin therapy. The recommended treatment for adrenal insufficiency is usually through hormonal therapy. Care must be taken while administering hormones as it may induce side effects such as obesity. Hydrocortisone is administered to treat adrenal insufficiencies.


Adrenal Pheochromocytoma

Adrenal Pheochromocytoma is a condition in which tumors are formed on the adrenal gland. These tumors occur predominantly on one adrenal gland as an unilateral condition. The bilateral condition is found only in rare cases. These tumors occur together with other disorders such as endocrine neoplasia type 2. Majority of these pheochromocytomas are benign in origin and only a few cases develop malignancy.

The symptoms of adrenal Pheochromocytoma include headaches, palpitation, profuse sweating, glucose intolerance, heat sensitivity and decreased blood pressure. Since pheochromocytomas are associated with variations in blood pressure, the diagnosis of the respective underlying condition is done by the determination of products obtained from the breakdown of adrenaline and noradrenaline. Other tests include the glucagon stimulation test for monitoring the blood pressure and the clonidine suppression test to detect the presence of tumors which lower the catecholamines. Confirmatory tests are done using radiological determination through CT scan and MRI scans.

Pheochromocytoma is treated with blood pressure lowering drugs such as alpha adrenergic blockers and the tumors associated are surgically removed. Post-operative care such as transfusion of fluids is given to patients who experience weakness because of low blood pressure.


Adrenal tumors

Adrenal tumors are generally categorized into functional and nonfunctional depending upon their type. Tumors associated with the adrenal cortex fall into the functional category whereas the remaining part of the adrenal gland secreting mixed hormones such as sex hormones and aldosterone fall under the nonfunctional category. Metastases associated with adrenal gland are more prominent in the determination of preexisting neoplasms and underlying adrenal insufficiency. Adrenal tumors of the benign non-functional origin are also caused by other conditions such as amyloidosis and granuloma. The malignant nonfunctional tumors are caused by conditions such as neuroblastoma and lymphoma.

Adrenal tumors are identified by a careful examination of the patient history followed by biochemical and radiological investigations. Fine needle aspiration biopsy is advised for pathological determination of the existing tumor. Surgical procedures such as laparoscopic adrenalectomy have produced good results in the removal of adrenal tumors.



ACTH Test

ACTH also known as adrenocorticotropic hormone is a hormone produced by the pituitary gland. This hormone in turn regulates the production of another important hormone cortisol, made by adrenal glands. Cortisol, known as a 'stress hormone', controls varied reactions in our body that take place in response to stress. Cortisol regulates blood pressure and blood sugar levels in the body and helps in maintaining immune function and anti-inflammatory processes. ACTH travels through the bloodstream to the adrenal glands and stimulates the adrenals to release cortisol. An ACTH blood test is done to measure the level of the adrenocorticotropic hormone in the blood.


Too much or too little ACTH level reveals problems related to adrenal glands or pituitary glands. High level of ACTH points to problems with adrenal glands and low level of ACTH may imply defective pituitary glands. The results of ACTH test is extremely useful in diagnosing Cushing syndrome and adrenal insufficiency.

Higher values of ACTH test are associated with one of the following conditions:



Lower levels of ACTH could mean adrenal tumor, Exogenous Cushing syndrome or hypopituitarism, a pituitary dysfunction leading to little or no production of hormone.


Preparing for the test

Patient should not eat or drink for 10 hours prior to the test. It is advisable to take a diet low in carbohydrates for two to three days before the test. Exercise and alcohol should be avoided for 12 hours before the test. Few steroid medications result in low levels of ACTH, hence patient should share all the information regarding the current medication with the doctor. Patient should not have undergone any medical test that uses a radioactive tracer for a week before an ACTH test.


ACTH levels do not remain in the same range through the day. The plasma ACTH levels are highest in the morning and start to decline during the waking hours. Therefore, blood is usually collected in the morning hours or multiple blood samples are sought for accurate diagnosis.

The Normal reference range is as follows:

Morning: Less than 80 pg/mL or less than 18 pmol/L

Evening: Less than 50 pg/mL or less than 11 pmol/L

A significant deviation from the normal range could mean defective adrenal glands or pituitary gland and further investigation is ordered for the accurate diagnosis.

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Collection of Pages - Last revised Date: November 15, 2019