Primary Adrenal Insufficiency: Addison s Disease

Ashleigh Alderson, John Cossey, Neil Dodsworth, Timothy Down, Kayleigh Hughes

Adrenal Insufficiency

Adrenal Glands

Small, approximately 6 gram, glands located on top of the kidneys. Secrete hormones into circulation:

Adrenal Cortex (General divisions, in reality more complicated)

Glomerulosa: Mineralocorticoids Fasciculata: Glucocorticoids Reticularis: Glucocorticoids and androgens Chromaffin cells: Adrenaline and noradrenaline

Adrenal Medulla

Adrenal Function .

Addison's Disease Name refers to a condition brought on by adrenal insufficiency. Caused by destruction/dysfunction in the adrenal cortex or deficient ACTH secretion in the pituitary. Under some circumstances. . glucocorticoid and mineralocorticoid production can stop or decrease.

but diagnosis usually occurs around the time of a crisis. . Period of stress can increase symptoms.Addison's Disease: Pathophysiology Symptoms of adrenocortical insufficiency arises when less than 10% of cortex remains. Development can be quick or slow.

Pathophysiology: Mineralocorticoids Mineralocorticoids normally: Stimulate excretion of K Stimulate reabsorbtion of Na Deficiency in mineralocorticoids leads to low levels of Na and high levels of K: Dehydration Hypertonicity Acidosis Hypotension .

insulin sensitivity. Normally glucocorticoids: Stimulate carbohydrate. the body will be unable to produce glucocorticoids. altered metabolism. protein and fat metabolism. dehydration. Suppress inflammation and release of pituitary hormones. A lack of glucocorticoids leads to: . stress resistance lowered. weakness and increased pituitary function.Pathophysiology: Glucocorticoids With the adrenal glands failing. hypoglycemia. Hypotension.

Addison's Disease: Causes Primary: Autoimmune Adrenocortical Insufficiency Adrenal Hemorrhage Infection Adrenoleukodystrophy Metastatic Adrenal Disease AIDS Cortisol resistance Familial glucocorticoid deficiency. .

Signs and Symptoms } Common symptoms of } } } } } } } } Adrenal Insufficiency: Loss of Weight. Painful Muscles and Joints. Diarrhoea. Low Blood Pressure (Orthostatic Hypotension) Vomiting. } . Hyperglycaemia. Disorientation. Nausea. Unspecific Symptoms. } Not until an Addisonian Crisis occurs that Addison's Disease is Suspected.

Pinna Calcified. . Hyperkalaemia. Convulsions. Fever.Signs and Symptoms } Addisonian Crisis: } } } } } } } Sudden Pain. Syncope (Sudden Loss of Consciousness) Hypoglycaemia.Not usually apparent until over 90% of the adrenal cortex is destroyed.Legs/ Lower back or Abdomen. } Addison's Disease. (Primary Adrenal Sufficiency) } } } Salt Craving Skin Pigmentation. Dehydration.

.Hyperpigmentation Over production of Melanin in Skin: ACTH shares the same pre-cursor molecule (Pro-opiomelanocortin).

and orthostasis. ( Androgens in Women) } Patients show evidence of dehydration. for signs of excess fluid loss. hypotension. } Your blood pressure when you are lying down and sitting up. } Your skin and your weight. } Absence of axillary and pubic hair and decreased body hair.Physical Examination } Medical History. .Hyperpigmentation. } Skin Examination.

Auto Antibodies (21-hydroxlase autoantibodies) Immunofluorescence. } Autoimmune Addison s Disease: } } } . Additionally.Preliminary Blood Tests } Initially a blood sample will be taken from the patient and a number of parameters are measured: } } } } } } Potassium Levels (Hyperkalaemia) Sodium Levels (Hyponatremia) Cortisol Test. CRH Levels (Corticotrophin) ( ) ATCH (Adrenocorticotropic hormone) ( ) Metabolic Acidosis.Eosinophilia/ Lymphocytosis.

Aldosterone Levels ( ) Kidney function tests. } A BUN (Blood Urine Nitrogen) Test or Creatinine test is sometimes untaken to test kidney function which may be impaired during Addison s Disease.Preliminary Urine Tests } Along side blood testing a urine test is also undertaken to again check for certain parameters: } } } } Sodium Levels (Hypernatremia) Cortisol Test.Concentrated Urine. .

Stimulation Tests } If Addison's disease is suspected. } ACTH Stimulation Tests } Short ACTH Stimulation Tests: High-Dose } Low-Dose } } Prolonged ACTH Stimulation Tests: Eight-hour } Two-day } } CRH Stimulation Test . an additional test is necessary to confirm the diagnosis.

} The normal response after an ACTH injection is a rise in serum and urine cortisol levels. . 30 and 60 minutes.Short ACTH Stimulation Tests } Synthetic ACTH is administered intravenously: } } 250µg for the high dose test 1µg for the low dose test } Serum cortisol and urine cortisol is measured at 0. } People with Addison s disease or long-standing secondary adrenal insufficiency have little or no increase in cortisol levels.

} But if secondary adrenal insufficiency is mild or of recent onset. } The low dose seems more reliable because it can raise cortisol levels in healthy people but not in people with mild or recent secondary adrenal insufficiency.Short ACTH Stimulation Tests (Continued) } Whether a low or high dose ACTH stimulation test may be used is dependent on the suspected cause of the adrenal insufficiency. the adrenal glands may still respond to ACTH because they have not yet atrophied. . } The advantage of a high-dose is that it can also be injected intramuscularly.

} Patients with Addison s disease produce high levels of ACTH but no cortisol in response to the injection.CRH Stimulation Test } A CRH stimulation test can be used to determine the cause of adrenal insufficiency if the response to the ACTH test is abnormal. 90. synthetic CRH is intravenously injected. } Serum cortisol is measured before the injection and 30. 60. A delayed ACTH response indicates the cause could be the hypothalamus. } } An absent ACTH response indicates the cause could be the pituitary. and 120 minutes after the injection. } In the test. } Patients with secondary adrenal insufficiency have absent or delayed ACTH responses. .

salt. } The patient could have to wait for up to a month after the crisis has subsided and the treatment stopped before a reliable diagnosis can be made. } If the diagnosis still remains unclear then other laboratory tests should be performed. and glucocorticoid hormones. } The treatment makes the ACTH and CRH stimulation tests unreliable. the patient must undergo treatment immediately with glucosecontaining fluids. .Emergency Diagnosis } If an Addisonian crisis is suspected.

diseases with normal adrenal function or adrenal insufficiency. .Adrenal Imaging } The ability to use cross-sectional imaging has had a dramatic effect upon the examination of the adrenal glands } Diseases of the adrenal glands may come as a result of hormone deficiency or excess } Diseases may be considered hyperfunctional.

} The radiologic manifestations are dependant upon the cause of adrenal insufficiency.Adrenal Imaging } Primary adrenal insufficiency (Addisons disease) occurs only after at least 90% of the adrenal cortex has been destroyed. . } Normal radiography of the abdomen may reveal calcification commonly seen in tuberculosis or histoplasmosis.

The beam rotates around the area to be imaged and generates a 3D image of the internal structure .Adrenal Imaging A computerized tomography scan uses a thin X-ray beam to image a specific area of the body.

Figure 1 (left): normal adrenal glands as seen in a CT scan. .Adrenal Imaging } A CT scan of the abdomen is used to check for abnormalities of the adrenal glands and to measure the size of the glands. Figure 2 (right): Addisons disease. } This image may give some insight to the cause of the adrenal insufficiency. Adrenal glands appear small and densely calcified .

Radio waves are sent through the field enabling a 3D image to be constructed by computer . A tunnel like structure creates a magnetic field around a patient.Adrenal Imaging Magnetic Resonance Imaging (MRI) is used to image a patients internal structures.

Adrenal Imaging An MRI scan of the abdomen is used to check for abnormalities of the adrenal glands. Figure 4 (right): Addisons disease. In this frontal view a significant size increase of the adrenal glands due to Addisons disease. Figure 3 (left): normal adrenal glands as seen in a MRI scan. . Adrenal glands appear enlarged.

Turberculin skin Test Method Skin disinfected with alcohol TB protein antigen injected under the skin Firm red bump present after 2 days if previous exposure to TB bacteria .

Turberculin skin Test Why complete a tuberculin test? Tuberculosis can destroy the adrenal glands Less than 20% Mostly used in third world countries .

Plasma Renin activity Method Blood sample taken and analysed Aldosterone and renin ratio calculated Disease Addisons Disease Aldosterone Low Renin High Cortisol Low .

.Plasma Renin activity Why complete the test? Cortisol and Aldosterone low Renin activity elevated (increased renal sodium losses).

Thyroid Function Test Method Blood sample taken and analysed Thyroid stimulating hormone measured Why complete the test? Misdiagnosis of patients with Addisons diseasehypothyroidism (Hussein D et al. 2006) . frame13. (2003) Adrenal Insufficiency Endotext [online] Available at: [ Accessed: Monday 28th February 2011] } Charmandari. } Anon (2009) What is Hyperpigmentation? [Online] Available at: http://www.htm [accessed 15 Feb 2011]. available http://adam.P. & Chrousos G.References } ADAM (2009) Diagram of CT and MRI scan [image online].htm (Accessed 08/02/2011) . 64/ch164b. } Grossman al/sec12/ch153/ch153b. Available:http://www.html [Accessed Saturday 26th February 2011) .B. Hanson Lecture. R. (2007) Addison's Disease: (Primary or Chronic Adrenocortical Insufficiency)'.html [Accessed: Monday 28th February 2011] } Grossman. . Department of Radiology.References (cont. [Online] Available at: http://www. (2007) Addison s Disease. (1989) Adrenal Imaging: Current Status..) } Dunnick.merckmanuals.merckmanuals. North Carolina. A.

} Jeffcoate. (2003) Unique Adrenal Gland Imaging Features in Addison's Disease Caused by Paracoccidioidomycosis American Journal of Roentgenology. 1993.. V. A.becomehealthynow. available :http://www. F... 5th Ed. pp1433-1434. } ..htm [accessed 15 Feb 2011].References ( _glands1.) HealthyNow(2010) Diagram of Kidney and Adrenal Glands [image online]. Muglia. A. Bellucci. W. } Leal. and Lucchesi. Lecture Notes on Endocrinology. London: Blackwell Scientific Publications. Vol: 181.

org/cgi/reprint/149/2/79 [Accessed: 28 February 2011] .edu/ghaffar/tolerance2000.htm (Accessed 01/02/2011) Raffin-Sanson Ghaffar A.htm (Accessed on: Monday 28th February 2011) NIDDK (2009) Adrenal Insufficiency and Addison s Disease National Endocrine and Metabolic Diseases Information Service [online] Available at: http://endocrine.ejeonline. (2010) Immunology: Tolerance and Autoimmunity University of South Carolina [Online] Available at: http://pathmicro.nih. a polypeptide precursor with multiple functions: from physiology to pathological conditions. Keyzer Institut Cochin [Online] Available at: http://www.References (Continued) } } } Nagarkatti P .L. Bertagna X (2003)

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