|Classification and external resources|
Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone (a mineralocorticoid), which regulates sodium conservation, potassium secretion, and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.
Addison's disease and congenital adrenal hyperplasia can manifest as adrenal insufficiency. If not treated, adrenal insufficiency may result in severe abdominal pains, vomiting, profound muscle weakness and fatigue, depression, extremely low blood pressure (hypotension), weight loss, kidney failure, changes in mood and personality, and shock (adrenal crisis). An adrenal crisis often occurs if the body is subjected to stress, such as an accident, injury, surgery, or severe infection; death may quickly follow.
Adrenal insufficiency can also occur when the hypothalamus or the pituitary gland does not make adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary or tertiary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH in the hypothalamus, respectively.
There are three major types of adrenal insufficiency.
- Primary adrenal insufficiency is due to impairment of the adrenal glands.
- Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus. The most common cause in the United States is exogenous steroid use. Other causes are a pituitary adenoma or microadenoma; a hypothalamic tumor (surgical removal of a pituitary tumor can also suppress production of ACTH and lead to adrenal deficiency); and Sheehan's syndrome, which is associated with impairment of only the pituitary gland.
- Tertiary adrenal insufficiency is due to hypothalamic disease and decrease in corticotropin releasing factor (CRF).
Signs and symptoms
Symptoms include: hypoglycemia, dehydration, weight loss, and disorientation. Symptoms may also include weakness, tiredness, dizziness, low blood pressure that falls further when standing (orthostatic hypotension), cardiovascular collapse, muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's disease can present with tanning of the skin that may be patchy or even all over the body. Characteristic sites of tanning are skin creases (e.g. of the hands) and the inside of the cheek (buccal mucosa). Goitre and vitiligo may also be present.
Causes of acute adrenal insufficiency are mainly Waterhouse-Friderichsen syndrome, sudden withdrawal of long-term corticosteroid therapy, and stress in patients with underlying chronic adrenal insufficiency. The latter is termed critical illness–related corticosteroid insufficiency.
For chronic adrenal insufficiency, the major contributors are autoimmune adrenalitis, tuberculosis, AIDS, and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis, and sarcoidosis.
Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome, which can include type 1 diabetes, hyperthyroidism, and autoimmune thyroid disease (also known as autoimmune thyroiditis, Hashimoto's thyroiditis, and Hashimoto's disease). Hypogonadism and pernicious anemia may also present with this syndrome.
Adrenal insufficiency can also result when a patient has a craniopharyngioma, which is a histologically benign tumor that can damage the pituitary gland and so cause the adrenal glands not to function. This would be an example of secondary adrenal insufficiency syndrome.
Hyponatremia can be caused by glucocorticoid deficiency. Low levels of glucocorticoids leads to systemic hypotension (one of the effects of cortisol is to increase peripheral resistance), which results in a decrease in stretch of the arterial baroreceptors of the carotid sinus and the aortic arch. This removes the tonic vagal and glossopharyngeal inhibition on the central release of ADH: high levels of ADH will ensue, which will subsequently lead to increase in water retention and hyponatremia.
Differently from mineralocorticoid deficiency, glucocorticoid deficiency does not cause a negative sodium balance (in fact a positive sodium balance may occur).
The best diagnostic tool to confirm adrenal insufficiency is the ACTH Stimulation test; however, if a patient is suspected to be suffering from an acute adrenal crisis immediate treatment with IV corticosteroids is imperative and should not be delayed for any testing, as the patients health can deteriorate rapidly and result in death without replacing the corticosteroids. Dexamethasone should be used as the corticosteroid if the plan is to do the ACTH stimulation test at a later time as it is the only corticosteroid that will not affect the test results.  If not in crisis then labs to be run should include: random cortisol, serum ACTH, aldosterone, renin, potassium and sodium. A CT of the adrenal glands can be used to check for structural abnormalities of the adrenal glands. An MRI of the pituitary can be used to check for structural abnormalities of the pituitary. However, in order to check the functionality of the Hypothalamic Pituitary Adrenal (HPA) Axis the entire axis must be tested by way of ACTH stimulation test, CRH stimulation test and perhaps an Insulin Tolerance Test (ITT). In order to check for Addison’s Disease, the auto-immune type of primary adrenal insufficiency, labs should be drawn to check 21-hydroxylase autoantibodies.
|Source of pathology||CRH||ACTH||DHEA||DHEA-S||cortisol||aldosterone||renin||Na||K||Causes5|
|low||low||low||low||low3||low||low||low||low||tumor of the hypothalamus (adenoma), antibodies, environment (i.e. toxins), head injury|
|high2||low||low||low||low3||low||low||low||low||tumor of the pituitary (adenoma), antibodies, environment, head injury,
surgical removal6, Sheehan's syndrome
|high||high||high||high||low4||low||high||low||high||tumor of the adrenal (adenoma), stress, antibodies, environment, Addison's Disease, trauma, surgical removal (resection), miliary tuberculosis of the adrenal|
|1||Automatically includes diagnosis of secondary (hypopituitarism)|
|2||Only if CRH production in the hypothalamus is intact|
|3||Value doubles or more in stimulation|
|4||Value less than doubles in stimulation|
|5||Most common, does not include all possible causes|
|6||Usually because of very large tumor (macroadenoma)|
|7||Includes Addison's disease|
- Adrenal crisis
- Cortisol deficiency (primary and secondary)
- Mineralocorticoid deficiency (low aldosterone)
- Fludrocortisone Acetate
(To balance sodium, potassium and increase water retention)
- Addison disease, primary adrenocortical insufficiency
- Cushing's syndrome, overproduction of cortisol
- Insulin tolerance test, another test used to identify sub-types of adrenal insufficiency
- Adrenal fatigue (hypoadrenia), a term used in alternative medicine to describe a believed exhaustion of the adrenal glands
- Eileen K. Corrigan (2007). "Adrenal Insufficiency (Secondary Addison's or Addison's Disease)". NIH Publication No. 90-3054.
- Adrenal Insufficiency at the US National Library of Medicine Medical Subject Headings (MeSH)
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- Ashley B. Grossman, MD (2007). "Addison's Disease". Adrenal Gland Disorders.
- Brender E, Lynm C, Glass RM (2005). "JAMA patient page. Adrenal insufficiency". JAMA 294 (19): 2528. doi:10.1001/jama.294.19.2528. PMID 16287965.
- "Dorlands Medical Dictionary:adrenal insufficiency".
- "Secondary Adrenal Insufficiency: Adrenal Disorders: Merck Manual Professional".
- "hypopituitary". 2006.
- Table 20-7 in: Mitchell, Richard Sheppard; Kumar, Vinay; Abbas, Abul K.; Fausto, Nelson. Robbins Basic Pathology. Philadelphia: Saunders. ISBN 1-4160-2973-7. 8th edition.
- Thomas A Wilson, MD (2007). "Adrenal Insufficiency". Adrenal Gland Disorders.
- Thomas A Wilson, MD (1999). Adrenoleukodystrophy.
- Robert W. Schrier, Body Water Homeostasis: Clinical Disorders of Urinary Dilution and Concentration, J Am Soc Nephrol 17: 1820–1832, 2006. doi: 10.1681/ASN.2006030240
- CAH - Congenital adrenal hyperplasia