Sandbox:Aditya

Epidemiology

Incidence

United States The prevalence of Addison disease is 40-60 cases per 1 million population.

Mortality/Morbidity

Morbidity and mortality associated with Addison disease usually are due to failure or delay in making the diagnosis or a failure to institute adequate glucocorticoid and mineralocorticoid replacement. [6] If not treated promptly, acute addisonian crisis may result in death. This may be provoked either de novo, such as by adrenal hemorrhage, or in the setting of an acute event superimposed on chronic or inadequately treated adrenocortical insufficiency. With slow-onset chronic Addison disease, significant low-level, nonspecific, but debilitating, symptomatology may occur. Even after diagnosis and treatment, the risk of death is more than 2-fold higher in patients with Addison disease. Cardiovascular, malignant, and infectious diseases are responsible for the higher mortality rate. [7] White and Arlt examined the prevalence of and risk factors for adrenal crisis in patients with Addison disease, utilizing a survey of Addison patients in the United Kingdom, Canada, Australia, and New Zealand. The authors' results indicated that approximately 8% of patients diagnosed with Addison disease require annual hospital treatment for adrenal crisis. In addition, the investigators concluded that exposure to gastric infection is the most important risk factor for adrenal crisis in the presence of Addison disease; diabetes and/or asthma [8] concomitant with Addison disease also increase the risk, according to White and Arlt. [9] A study by Chantzichristos et al indicated that in patients with type 1 or 2 diabetes, those who also have Addison disease have a higher mortality rate than do those with diabetes alone. Over a median follow-up period of 5.9 years, the mortality rate for diabetes patients with Addison disease was 28%, compared with 10% for those without Addison disease. The increase in the estimated relative overall mortality risk was 3.89 for the Addison disease patients compared with the other group. Although cardiovascular deaths accounted for the highest mortality rate in both groups, the death rate from diabetes complications, infectious diseases, and unknown causes was greater in the patients with Addison disease than in those with diabetes alone. [10]

Race

Addison disease is not associated with a racial predilection.

Sex

Idiopathic autoimmune Addison disease tends to be more common in females and children.

Age

The most common age at presentation in adults is 30-50 years, but the disease could present earlier in patients with any of the polyglandular autoimmune syndromes, congenital adrenal hyperplasia (CAH), or if onset is due to a disorder of long-chain fatty acid metabolism.

Historical perspective

• In 1563, Bartholomeus Eustachius (1520-1574), an anatomy professor at the Collegio della Sapienza in Rome gave a detailed description of the human adrenal glands in his publication "glandulae renibus incumbentes"
• In 1586, Piccolomini, named the glands the suprarenals.
• In 1651, Highmore suggested that the suprarenals act to absorb exudates from the large vessels, and Thomas Wharton in 1656 suggested that the adrenals took something from the nerves and secreted it into the circulation which mirrors the current concept of the neuroendocrine function of the adrenal medulla today.
• In 1716, The Academy of Sciences in Bordeaux conducted an essay competition to determine the function of the adrenal glands, but none of the entries were considered worthy of the prize.
• In 1805, Cuvier defined the medulla and cortex of the adrenal gland,
• In 1852, Albert von Kölliker (1817-1905), gave the first complete description of the microscopic anatomy of the adrenal gland.
• In 1849, Thomas Addison identified the physiological role of the glands and presented a paper on the clinical features of patients with adrenal disease.
• In 1856, Charles Brown-Séquard provided experimental proof of the vital role of the adrenals by performing adrenalectomies (the removal of adrenals) from several animal species.

Classification

Adrenal insufficiency disorders may be classified into acute and chronic forms, depending on the timing of presentation and duration and into primary and secondary, depending on the etiology of adrenal insufficiency.

Based on the duration of symptoms

Acute adrenal insufficiency

• Adrenal crisis

Chronic adrenal insufficiency

• Chronic primary adrenal insufficiency
• Chronic secondary adrenal insufficiency

Based on etiology

Primary adrenal insufficiency(Addisons disease)

• Anatomic destruction of the adrenal gland
• Infection (TB)
• Congenital adrenal hyperplasia

Secondary adrenal insufficiency

• Hypothalamic-pituitary axis suppression

Pathology

Cortisol is normally produced by the adrenal glands, which are located just above the kidneys. It belongs to a class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. Scientists think that cortisol possibly has hundreds of effects in the body. Cortisol's most important job is to help the body respond to stress. Among its other vital tasks, cortisol;

Helps maintain blood pressure and cardiovascular function Helps slow the immune system's inflammatory response Helps balance the effects of insulin in breaking down sugar for energy Helps regulate the metabolism of proteins, carbohydrates, and fats Helps maintain proper arousal and sense of well-being Because cortisol is so vital to health, the amount of cortisol produced by the adrenals is precisely balanced. Like many other hormones, cortisol is regulated by the brain's hypothalamus and the pituitary gland, a bean-sized organ at the base of the brain. First, the hypothalamus sends "releasing hormones" to the pituitary gland. The pituitary responds by secreting hormones that regulate growth, thyroid function, adrenal function, and sex hormones such as estrogen and testosterone. One of the pituitary's main functions is to secrete ACTH (adrenocorticotropin), a hormone that stimulates the adrenal glands. When the adrenals receive the pituitary's signal in the form of ACTH, they respond by producing cortisol. Completing the cycle, cortisol then signals the pituitary to lower secretion of ACTH.

Aldosterone Aldosterone belongs to a class of hormones called mineralocorticoids, also produced by the adrenal glands. It helps maintain blood pressure and water and salt balance in the body by helping the kidney retain sodium and excrete potassium. When aldosterone production falls too low, the kidneys are not able to regulate salt and water balance, causing blood volume and blood pressure to drop.

Laboratory

8 am cortisol

>15Ug/dL

3-15Ug/dL

<3Ug/dL

30 min cortisol during cosyntropin stimulation test

>18Ug/dL

<18Ug/dL

Adrenal insufficiency confirmed

Measure ACTH