Adrenal insufficiency
Encyclopedia
Adrenal insufficiency is a condition in which the adrenal gland
s, located above the kidney
s, do not produce adequate amounts of steroid hormone
s (chemicals produced by the body that regulate organ function), primarily cortisol
, but may also include impaired aldosterone
production (a mineralocorticoid
) which regulates sodium
, potassium
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, diarrhea, 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
, both located at the base of the skull
, does not make adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH
in the hypothalamus.
, dehydration, weight loss, and disorientation. He or she may experience weakness, tiredness, dizziness, low blood pressure
that falls further when standing (orthostatic hypotension
), muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's 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.
, 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
, 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.
Adrenoleukodystrophy
can also cause adrenal insufficiency.
Adrenal Insufficiency can also be caused when a patient has a Craniopharyngioma
which is a benign tumor that can damage the Pituitary gland causing the Adrenal Glands not to function. This would be an example of Secondary Adrenal Insufficiency Syndrome.
may be given. If not in crisis, cortisol, ACTH, aldosterone, renin, potassium and sodium are tested from a blood sample before the decision is made if the ACTH stimulation test needs to be performed. X-rays or CT of the adrenals may also be done. The best test for adrenal insufficiency of autoimmune origin, representing more than ninety percent of all cases in a Western population, is measurement of 21-hydroxylase autoantibodies.
(To balance sodium, potassium and increase water retention)
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s, located above the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, do not produce adequate amounts of steroid hormone
Steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
s (chemicals produced by the body that regulate organ function), primarily cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
, but may also include impaired aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...
production (a mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
) which regulates sodium
Sodium
Sodium is a chemical element with the symbol Na and atomic number 11. It is a soft, silvery-white, highly reactive metal and is a member of the alkali metals; its only stable isotope is 23Na. It is an abundant element that exists in numerous minerals, most commonly as sodium chloride...
, potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
and water retention. Craving for salt or salty foods due to the urinary losses of sodium is common.
Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
and congenital adrenal hyperplasia
Congenital adrenal hyperplasia
Congenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
can manifest as adrenal insufficiency. If not treated, adrenal insufficiency may result in severe abdominal pains, diarrhea, vomiting, profound muscle weakness and fatigue, depression
Clinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, extremely low blood pressure (hypotension
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
), 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
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
or the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
, both located at the base of the skull
Human skull
The human skull is a bony structure, skeleton, that is in the human head and which supports the structures of the face and forms a cavity for the brain.In humans, the adult skull is normally made up of 22 bones...
, does not make adequate amounts of the hormones that assist in regulating adrenal function. This is called secondary adrenal insufficiency and is caused by lack of production of ACTH in the pituitary or lack of CRH
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
in the hypothalamus.
Types
There are two major types of adrenal insufficiency.- Primary adrenal insufficiency is due to impairment of the adrenal glands.
- One subtype is called idiopathicIdiopathicIdiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
or unknown cause of adrenal insufficiency. - 80% are due to an autoimmune diseaseAutoimmune diseaseAutoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
called Addison's diseaseAddison's diseaseAddison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
or autoimmune adrenalitis. - Other cases are due to congenital adrenal hyperplasiaCongenital adrenal hyperplasiaCongenital adrenal hyperplasia refers to any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands ....
or an adenomaAdenomaAn adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas...
(tumor) of the adrenal gland.
- One subtype is called idiopathic
- Secondary adrenal insufficiency is caused by impairment of the pituitary glandPituitary glandIn vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
or hypothalamusHypothalamusThe Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. These can be due to a form of cancer: a pituitary microadenoma, or a hypothalamic tumor; Sheehan's syndromeSheehan's syndromeSheehan syndrome, also known as Simmonds' syndrome or postpartum hypopituitarism or postpartum pituitary necrosis, is hypopituitarism , caused by necrosis due to blood loss and hypovolemic shock during and after childbirth...
, which is associated with impairment of only the pituitary gland; or a past head injury. - Tertiary adrenal insufficiency is due to hypothalamic disease and decrease in corticotropin releasing factor (CRF).
Signs and symptoms
Symptoms include: hypoglycemiaHypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
, dehydration, weight loss, and disorientation. He or she may experience weakness, tiredness, dizziness, low blood pressure
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
that falls further when standing (orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
), muscle aches, nausea, vomiting, and diarrhea. These problems may develop gradually and insidiously. Addison's 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
Goitre
A goitre or goiter , is a swelling in the thyroid gland, which can lead to a swelling of the neck or larynx...
and vitiligo
Vitiligo
Vitiligo is a condition that causes depigmentation of sections of skin. It occurs when melanocytes, the cells responsible for skin pigmentation, die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress,...
may also be present.
Causes
Causes of acute adrenal insufficiency are mainly Waterhouse-Friderichsen syndromeWaterhouse-Friderichsen syndrome
Waterhouse-Friderichsen syndrome or hemorrhagic adrenalitis or Fulminant meningococcemia, is a disease of the adrenal glands most commonly caused by the bacterium Neisseria meningitidis. The infection leads to massive hemorrhage into one or both adrenal glands...
, sudden withdrawal of long-term corticosteroid therapy and stress
Stress (biology)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
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
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
, AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
and metastatic disease. Minor causes of chronic adrenal insufficiency are systemic amyloidosis, fungal infections, hemochromatosis and sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...
.
Autoimmune adrenalitis may be part of Type 2 autoimmune polyglandular syndrome
Autoimmune polyendocrine syndrome type 2
Autoimmune polyendocrine syndrome type 2 is a form of autoimmune polyendocrine syndrome.Autoimmune polyendocrine syndrome, type 2 is the most common form of the polyglandular failure syndromes. It is more heterogeneous and has not been linked to one gene...
, which can include type 1 diabetes
Diabetes mellitus type 1
Diabetes mellitus type 1 is a form of diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose...
), hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
, autoimmune thyroid disease
Thyroid disease
-Hyper- and hypofunction:Imbalance in production of thyroid hormones arises from dysfunction of the thyroid gland itself, the pituitary gland, which produces thyroid-stimulating hormone , or the hypothalamus, which regulates the pituitary gland via thyrotropin-releasing hormone . Concentrations of...
(also known as autoimmune thyroiditis
Autoimmune thyroiditis
Autoimmune thyroiditis is a form of thyroiditis associated with an autoimmune disease where the body treats the thyroid gland and sometimes the hormones it produces as foreign bodies, therefore rejecting and attacking both.-Treatment:...
, Hashimoto's thyroiditis
Hashimoto's thyroiditis
Hashimoto's thyroiditis or chronic lymphocytic thyroiditis is an autoimmune disease in which the thyroid gland is gradually destroyed by a variety of cell- and antibody-mediated immune processes. It was the first disease to be recognized as an autoimmune disease...
and Hashimoto's disease). Hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...
and pernicious anemia
Pernicious anemia
Pernicious anemia is one of many types of the larger family of megaloblastic anemias...
may also present with this syndrome.
Adrenoleukodystrophy
Adrenoleukodystrophy
Adrenoleukodystrophy is a rare, inherited disorder that leads to progressive brain damage, failure of the adrenal glands and eventually death. ALD is a disease in a group of genetic disorders called leukodystrophies, whose chief feature is damage to myelin...
can also cause adrenal insufficiency.
Adrenal Insufficiency can also be caused when a patient has a Craniopharyngioma
Craniopharyngioma
Craniopharyngioma is a type of brain tumor derived from pituitary gland embryonic tissue, that occurs most commonly in children but also in men and women in their 50s and 60s....
which is a benign tumor that can damage the Pituitary gland causing the Adrenal Glands not to function. This would be an example of Secondary Adrenal Insufficiency Syndrome.
Diagnosis
If the person is in adrenal crisis, the ACTH stimulation testACTH stimulation test
The ACTH stimulation test is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone...
may be given. If not in crisis, cortisol, ACTH, aldosterone, renin, potassium and sodium are tested from a blood sample before the decision is made if the ACTH stimulation test needs to be performed. X-rays or CT of the adrenals may also be done. The best test for adrenal insufficiency of autoimmune origin, representing more than ninety percent of all cases in a Western population, is measurement of 21-hydroxylase autoantibodies.
| Source of pathology | CRH | ACTH | DHEA | DHEA-S | cortisol | aldosterone | renin | Na | K | Causes5 |
| hypothalamus (tertiary)1 |
low | low | low | low | low3 | low | low | low | low | tumor of the hypothalamus (adenoma), antibodies, environment Environment (biophysical) The biophysical environment is the combined modeling of the physical environment and the biological life forms within the environment, and includes all variables, parameters as well as conditions and modes inside the Earth's biosphere. The biophysical environment can be divided into two categories:... (i.e. toxins), head injury Head injury Head injury refers to trauma of the head. This may or may not include injury to the brain. However, the terms traumatic brain injury and head injury are often used interchangeably in medical literature.... |
| pituitary (secondary) |
high2 | low | low | low | low3 | low | low | low | low | tumor of the pituitary (adenoma Adenoma An adenoma is a benign tumor of glandular origin. Adenomas can grow from many organs including the colon, adrenal glands, pituitary gland, thyroid, prostate, etc. Although these growths are benign, over time they may progress to become malignant, at which point they are called adenocarcinomas... ), antibodies, environment, head injury, surgical removal6, Sheehan's syndrome |
| adrenal glands (primary)7 |
high | high | high | high | low4 | low | high | low | high | tumor of the adrenal (adenoma), stress Stress (biology) Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance... , antibodies, environment, Addison's Disease Addison's disease Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones... , trauma Physical trauma Trauma refers to "a body wound or shock produced by sudden physical injury, as from violence or accident." It can also be described as "a physical wound or injury, such as a fracture or blow." Major trauma can result in secondary complications such as circulatory shock, respiratory failure and death... , surgical removal (resection Segmental resection Segmental resection is a surgical procedure to remove part of an organ or gland. It may also be used to remove a tumor and normal tissue around it. In lung cancer surgery, segmental resection refers to removing a section of a lobe of the lung.- External links :* entry in the public domain NCI... ), miliary tuberculosis Tuberculosis Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body... 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 |
Treatment
-
- Adrenal crisis
- Intravenous fluids
- Intravenous steroid (Solu-Cortef/injectable hydrocortisone) later hydrocortisone, prednisone or methylpredisolone tablets
- Rest
-
- Cortisol deficiency (primary and secondary)
- Hydrocortisone (Cortef)
-
- PrednisonePrednisonePrednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
(Deltasone) - PrednisolonePrednisolonePrednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
(Delta-Cortef) - MethylprednisoloneMethylprednisoloneMethylprednisolone is a synthetic glucocorticoid or corticosteroid drug. It is marketed in the USA and Canada under the brand names Medrol and Solu-Medrol. It is also available as a generic drug....
(Medrol) - DexamethasoneDexamethasoneDexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...
(Decadron)
- Prednisone
-
- Mineralocorticoid deficiency (low aldosterone)
- Fludrocortisone Acetate
(To balance sodium, potassium and increase water retention)
See also
- Addison disease, primary adrenocortical insufficiency
- Cushing's syndromeCushing's syndromeCushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
, overproduction of cortisol - Insulin tolerance testInsulin tolerance testAn insulin tolerance test is a medical diagnostic procedure during which insulin is injected into a patient's vein to assess pituitary function, adrenal function, and sometimes for other purposes. An ITT is usually ordered and interpreted by endocrinologists.Insulin injections are intended to...
, another test used to identify sub-types of adrenal insufficiency - Hypoadrenia (adrenal fatigue), the precursor to adrenal insufficiency.
External links
- CAH - Congenital adrenal hyperplasia