Addison's disease
Encyclopedia
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal gland
s do not produce sufficient steroid hormone
s (glucocorticoid
s and often mineralocorticoid
s). It is characterised by a number of relatively nonspecific symptoms, such as abdominal pain and weakness, but under certain circumstances these may progress to Addisonian crisis, a severe illness in which there may be very low blood pressure and coma
.
The condition arises from problems with the adrenal gland itself, a state referred to as "primary adrenal insufficiency" and can be caused by damage by the body's own immune system
, certain infections or various rarer causes. Addison's disease is also known as chronic primary adrenocortical insufficiency, to distinguish it from acute primary adrenocortical insufficiency, most often caused by Waterhouse-Friderichsen syndrome
. Addison's disease should also be distinguished from secondary and tertiary adrenal insufficiency which are caused by deficiency of ACTH
(produced by the pituitary gland
) and CRH
(produced by the hypothalamus
) respectively. Despite this distinction, Addisonian crisis can happen in all forms of adrenal insufficiency.
Addison's disease and other forms of hypoadrenalism are generally diagnosed via blood test
s and medical imaging
. Treatment involves replacing the absent hormones (oral hydrocortisone and fludrocortisone
). Lifelong, continuous treatment with steroid replacement therapy is required, with regular follow-up treatment and monitoring for other health problems.
Addison’s disease is named after Dr. Thomas Addison
, the British physician
who first described the condition in 1849. The adjective "Addisonian" is used to describe features of the condition, as well as patients suffering from Addison’s disease.
upon standing or while upright, muscle weakness
, fever
, weight loss, difficulty in standing up, anxiety, nausea
, vomiting
, diarrhea
, headache
, sweating
, changes in mood
and personality
, and joint
and muscle pains
. Some have marked cravings for salt or salty foods due to the urinary losses of sodium. Increased tanning
may be noted, particularly in sun-exposed areas, as well as darkening of the palmar creases, sites of friction, recent scars, the vermilion border of the lips, and genital skin. This is not encountered in secondary and tertiary hypoadrenalism.
On examination, the following may be noticed:
and potentially life-threatening situation requiring immediate emergency treatment.
Characteristic symptoms are:
transcription factor
, congenital adrenal hypoplasia
(AHC) due to DAX-1 gene mutations and mutations to the ACTH receptor
gene (or related genes, such as in the Triple A
or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase
deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.
, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith-Lemli-Opitz syndrome
and abetalipoproteinemia
.
Of the synthesis problems, congenital adrenal hyperplasia
is the most common (in various forms: 21-hydroxylase
, 17α-hydroxylase
, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase
), lipoid CAH
due to deficiency of StAR
and mitochondrial DNA
mutations. Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole
), while others accelerate the normal breakdown of hormones by the liver
(e.g. rifampicin
, phenytoin
).
destruction of the adrenal cortex
is caused by an immune reaction against the enzyme 21-hydroxylase
(a phenomenon first described in 1992). This may be isolated or in the context of autoimmune polyendocrine syndrome
(APS type 1 or 2), in which other hormone-producing organs such as the thyroid
and pancreas
may also be affected.
Adrenal destruction is also a feature of adrenoleukodystrophy
(ALD), and when the adrenal glands are involved in metastasis
(seeding of cancer
cells from elsewhere in the body, especially lung
), hemorrhage (e.g. in Waterhouse-Friderichsen syndrome
or antiphospholipid syndrome
), particular infection
s (tuberculosis
, histoplasmosis
, coccidioidomycosis
), deposition of abnormal protein in amyloidosis
.
In suspected cases of Addison's disease, one needs to demonstrate that adrenal hormone levels are low even after appropriate stimulation (called the ACTH stimulation test
) with synthetic pituitary ACTH hormone tetracosactide
. Two tests are performed, the short and the long test.
The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (IM/IV) is given. If, one hour later, plasma
cortisol exceeds 170 nmol/L and has risen by at least 330 nmol/L to at least 690 nmol/L, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal insufficiency and secondary adrenocortical insufficiency.
The long test uses 1 mg tetracosactide (IM). Blood is taken 1, 4, 8, and 24 hours later. Normal plasma cortisol level should reach 1000 nmol/L by 4 hours. In primary Addison's disease, the cortisol level is reduced at all stages whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.
Other tests that may be performed to distinguish between various causes of hypoadrenalism are renin
and adrenocorticotropic hormone
levels, as well as medical imaging
- usually in the form of ultrasound
, computed tomography
or magnetic resonance imaging
(MRI).
Adrenoleukodystrophy
, and the milder form, adrenomyeloneuropathy
, cause adrenal insufficiency combined with neurological symptoms. These diseases are estimated to be the cause of adrenal insufficiency in approximately 35% of male patients with idiopathic Addison’s disease and should be considered in the differential diagnosis of any male with adrenal insufficiency. Diagnosis is made by a blood test to detect very long chain fatty acid
s (VLCFA).
tablets in a dosing regimen that mimics the physiological concentrations of cortisol. Alternatively one quarter as much prednisolone
may be used for equal glucocorticoid effect as hydrocortisone. Treatment must usually be continued for life. In addition, many patients require fludrocortisone
as replacement for the missing aldosterone. Caution must be exercised when the person with Addison's disease becomes unwell with infection
, has surgery
or other trauma
, or becomes pregnant. In such instances, their replacement glucocorticoids, whether in the form of hydrocortisone, prednisone, prednisolone, or other equivalent, often need to be increased. Inability to take oral medication may prompt hospital attendance to receive steroids intravenously. People with Addison's are often advised to carry information on them (e.g. in the form of a MedicAlert
bracelet) for the attention of emergency medical services
personnel who might need to attend to their needs.
(Determining accurate numbers for Addison's is problematic at best and some incidence figures are thought to be underestimates.)
Addison's can afflict persons of any age, gender, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity.
A person with adrenal insufficiency should always carry identification stating their condition in case of an emergency. The card should alert emergency personnel about the need to inject 100 mg of cortisol if its bearer is found severely injured or unable to answer questions. The card should also include the doctor's name and telephone number and the name and telephone number of the nearest relative to be notified. When traveling, a needle, syringe, and an injectable form of cortisol should be carried for emergencies. A person with Addison's disease also should know how to increase medication during periods of stress or mild upper respiratory infections. Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A patient who is vomiting may require injections of hydrocortisone, since oral hydrocortisone supplements cannot be adequately metabolised.
, the British physician
who first described the condition in On the Constitutional and Local Effects of Disease of the Suprarenal Capsules (1849). All of Addison's six original patients had tuberculosis of the adrenal glands. While Addison's six patients in 1855 all had adrenal tuberculosis, the term "Addison's disease" does not imply an underlying disease process.
Hypoadrenocorticism is treated with fludrocortisone or a monthly injection called Percorten V (desoxycorticosterone pivlate (DOCP)) and prednisone. Routine blood work is necessary in the initial stages until a maintenance dose is established.
Most of the medications used in the therapy of hypoadrenocorticism cause excessive thirst and urination, making it important to provide enough drinking water.
If the owner knows about an upcoming stressful situation (shows, traveling etc.), patients generally need an increased dose of prednisone to help deal with the added stress. Avoidance of stress is important for dogs with hypoadrenocorticism.
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 do not produce sufficient 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 (glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
s and often mineralocorticoid
Mineralocorticoid
Mineralocorticoids are a class of steroid hormones characterised by their similarity to aldosterone and their influence on salt and water balances.-Physiology:...
s). It is characterised by a number of relatively nonspecific symptoms, such as abdominal pain and weakness, but under certain circumstances these may progress to Addisonian crisis, a severe illness in which there may be very low blood pressure and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
.
The condition arises from problems with the adrenal gland itself, a state referred to as "primary adrenal insufficiency" and can be caused by damage by the body's own immune system
Autoimmune disease
Autoimmune 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...
, certain infections or various rarer causes. Addison's disease is also known as chronic primary adrenocortical insufficiency, to distinguish it from acute primary adrenocortical insufficiency, most often caused by Waterhouse-Friderichsen syndrome
Waterhouse-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...
. Addison's disease should also be distinguished from secondary and tertiary adrenal insufficiency which are caused by deficiency of ACTH
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(produced by 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...
) and 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...
(produced by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
) respectively. Despite this distinction, Addisonian crisis can happen in all forms of adrenal insufficiency.
Addison's disease and other forms of hypoadrenalism are generally diagnosed via blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s and medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
. Treatment involves replacing the absent hormones (oral hydrocortisone and fludrocortisone
Fludrocortisone
Fludrocortisone is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. The brand name in the U.S. and Canada is Florinef.-Uses:...
). Lifelong, continuous treatment with steroid replacement therapy is required, with regular follow-up treatment and monitoring for other health problems.
Addison’s disease is named after Dr. Thomas Addison
Thomas Addison
Thomas Addison was a renowned 19th-century English physician and scientist. He is traditionally regarded as one of the "great men" of Guy's Hospital in London....
, the British physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
who first described the condition in 1849. The adjective "Addisonian" is used to describe features of the condition, as well as patients suffering from Addison’s disease.
Symptoms
The symptoms of Addison's disease develop insidiously, and it may take some time to be recognised. The most common symptoms are fatigue, lightheadednessLightheadedness
Light-headedness is a common and often unpleasant sensation of dizziness and/or feeling that one may be about to faint, which may be transient, recurrent, or occasionally chronic. In some cases, the individual may feel as though his or her head is weightless. The individual may also feel as...
upon standing or while upright, muscle weakness
Muscle weakness
Muscle weakness or myasthenia is a lack of muscle strength. The causes are many and can be divided into conditions that have true or perceived muscle weakness...
, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, weight loss, difficulty in standing up, anxiety, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
, diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
, sweating
Sweating
Perspiration is the production of a fluid consisting primarily of water as well as various dissolved solids , that is excreted by the sweat glands in the skin of mammals...
, changes in mood
Mood (psychology)
A mood is a relatively long lasting emotional state. Moods differ from emotions in that they are less specific, less intense, and less likely to be triggered by a particular stimulus or event....
and personality
Personality psychology
Personality psychology is a branch of psychology that studies personality and individual differences. Its areas of focus include:* Constructing a coherent picture of the individual and his or her major psychological processes...
, and joint
Arthralgia
Arthralgia literally means joint pain; it is a symptom of injury, infection, illnesses or an allergic reaction to medication....
and muscle pains
Myalgia
Myalgia means "muscle pain" and is a symptom of many diseases and disorders. The most common causes are the overuse or over-stretching of a muscle or group of muscles. Myalgia without a traumatic history is often due to viral infections...
. Some have marked cravings for salt or salty foods due to the urinary losses of sodium. Increased tanning
Sun tanning
Sun tanning or simply tanning is the process whereby skin color is darkened or tanned. The process is most often a result of exposure to ultraviolet radiation from the sun or from artificial sources, such as a tanning bed, but can also be a result of windburn or reflected light...
may be noted, particularly in sun-exposed areas, as well as darkening of the palmar creases, sites of friction, recent scars, the vermilion border of the lips, and genital skin. This is not encountered in secondary and tertiary hypoadrenalism.
Clinical signs
- Low blood pressureHypotensionIn 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 hypotensionOrthostatic hypotensionOrthostatic 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...
) - Most people with primary Addison's have darkening (hyperpigmentationHyperpigmentationIn dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
) of the skin, including areas not exposed to the sun; characteristic sites are skin creases (e.g. of the hands), nipple, and the inside of the cheek (buccal mucosa), also old scars may darken. This occurs because melanocyte-stimulating hormoneMelanocyte-stimulating hormoneThe melanocyte-stimulating hormones are a class of peptide hormones that are produced by cells in the intermediate lobe of the pituitary gland...
(MSH) and adrenocorticotropic hormoneAdrenocorticotropic hormoneAdrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH) share the same precursor molecule, Pro-opiomelanocortin (POMC). After production in anterior pituitary gland, POMC gets cleaved into Gamma-MSH, ACTH and Beta-lipotropin. The subunit ACTH undergoes further cleavage to produce Alpha-MSH, the most important MSH for skin pigmentation. In secondary and tertiary forms of Addison's, skin darkening does not occur. - Medical conditions such as type I diabetes, autoimmune thyroidThyroidThe thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
disease (Hashimoto's thyroiditisHashimoto's thyroiditisHashimoto'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 goiter) and vitiligoVitiligoVitiligo 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,...
often occur together with Addison's (often in the setting of Autoimmune polyendocrine syndromeAutoimmune polyendocrine syndromeIn medicine, autoimmune polyendocrine syndromes are a heterogeneous group of rare diseases characterised by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected....
). Hence, symptoms and signs of any of the former conditions may also be present in the individual with Addison's.- The occurrence of Addison's Disease in someone who also has Hashimoto's thyroiditis is called Schmidt syndrome.
Addisonian crisis
An "Addisonian crisis" or "adrenal crisis" is a constellation of symptoms that indicate severe adrenal insufficiency. This may be the result of either previously undiagnosed Addison's disease, a disease process suddenly affecting adrenal function (such as adrenal hemorrhage), or an intercurrent problem (e.g. infection, trauma) in someone known to have Addison's disease. It is a medical emergencyMedical emergency
A medical emergency is an injury or illness that is acute and poses an immediate risk to a person's life or long term health. These emergencies may require assistance from another person, who should ideally be suitably qualified to do so, although some of these emergencies can be dealt with by the...
and potentially life-threatening situation requiring immediate emergency treatment.
Characteristic symptoms are:
- Sudden penetrating pain in the legs, lower back or abdomen
- Severe vomitingVomitingVomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
and diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, resulting in dehydrationDehydrationIn physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism... - Low blood pressureHypotensionIn 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...
- SyncopeSyncope (medicine)Syncope , the medical term for fainting, is precisely defined as a transient loss of consciousness and postural tone characterized by rapid onset, short duration, and spontaneous recovery due to global cerebral hypoperfusion that most often results from hypotension.Many forms of syncope are...
(loss of consciousness and ability to stand) - HypoglycemiaHypoglycemiaHypoglycemia 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"...
(reduced level of blood glucose) - Confusion, psychosisPsychosisPsychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, slurred speech - Severe lethargy
- HyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
- HyperkalemiaHyperkalemiaHyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
(elevated potassium level in the blood) - Hypercalcemia (elevated calcium level in the blood)
- ConvulsionsSeizureAn epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
- FeverFeverFever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
Causes
Causes of adrenal insufficiency can be grouped by the way they cause the adrenals to produce insufficient cortisol. These are adrenal dysgenesis (the gland has not formed adequately during development), impaired steroidogenesis (the gland is present but is biochemically unable to produce cortisol) or adrenal destruction (disease processes leading to the gland being damaged).Adrenal dysgenesis
All causes in this category are genetic, and generally very rare. These include mutations to the SF1Steroidogenic factor 1
The steroidogenic factor 1 protein controls sexual development in the embryo and at puberty.SF1 is a member of the nuclear receptor family of intracellular transcription factors and is encoded by the NR5A1 gene .- Function :SF-1 is a critical regulator of reproduction, regulating the transcription...
transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
, congenital adrenal hypoplasia
X-linked adrenal hypoplasia congenita
X-linked adrenal hypoplasia congenita is a genetic disorder that mainly affects males. It involves many endocrine tissues in the body, especially the adrenal glands.-Presentation:...
(AHC) due to DAX-1 gene mutations and mutations to the ACTH receptor
ACTH receptor
The ACTH receptor is a type of melanocortin receptor , properly known as MC2, which is specific for ACTH.It is found in the zona fasciculata of the human adrenal cortex. Binding of the receptor by ACTH stimulates the production of cortisol...
gene (or related genes, such as in the Triple A
Triple A syndrome
Triple-A syndrome , also known as Achalasia-Addisonianism-Alacrimia syndrome or Allgrove Syndrome, is a rare autosomal recessive congenital disorder. In most cases, there is no family history of it. The syndrome was discovered by Jeremy Allgrove and colleagues in 1978. Triple A stands for...
or Allgrove syndrome). DAX-1 mutations may cluster in a syndrome with glycerol kinase
Glycerol kinase
Glycerol kinase is a phosphotransferase enzyme involved in triglycerides and glycerophospholipids synthesis.Glycerol kinase catalyzes the transfer of a phosphate from ATP to glycerol thus forming glycerol phosphate . Adipocytes lack glycerol kinase so they cannot metabolize the glycerol produced...
deficiency with a number of other symptoms when DAX-1 is deleted together with a number of other genes.
Impaired steroidogenesis
To form cortisol, the adrenal gland requires cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
, which is then converted biochemically into steroid hormones. Interruptions in the delivery of cholesterol include Smith-Lemli-Opitz syndrome
Smith-Lemli-Opitz syndrome
Smith-Lemli-Opitz syndrome is an autosomal recessive metabolic and developmental congenital disorder that causes the inability to correctly produce or synthesize cholesterol due to a low occurrence of the 7-DHC reductace enzyme.-Symptoms:The signs and symptoms of SLOS syndrome vary widely...
and abetalipoproteinemia
Abetalipoproteinemia
Abetalipoproteinemia, or Bassen-Kornzweig syndrome, is a rare autosomal recessive disorder that interferes with the normal absorption of fat and fat-soluble vitamins from food. It is caused by a deficiency of apolipoprotein B-48 and B-100, which are used in the synthesis and exportation of...
.
Of the synthesis problems, 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 ....
is the most common (in various forms: 21-hydroxylase
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency , in all its forms, accounts for over 95% of diagnosed cases of congenital adrenal hyperplasia, and "CAH" in most contexts refers to 21-hydroxylase deficiency...
, 17α-hydroxylase
Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency
Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene for the enzyme CYP17A1. It produces decreased synthesis of both cortisol and sex steroids, with resulting increase in mineralocorticoid production...
, 11β-hydroxylase and 3β-hydroxysteroid dehydrogenase
Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency
3β-Hydroxysteroid dehydrogenase II deficient congenital adrenal hyperplasia is an uncommon form of CAH resulting from a mutation in the gene for one of the key enzymes in cortisol synthesis by the adrenal gland, 3β-hydroxysteroid dehydrogenase type II...
), lipoid CAH
Lipoid congenital adrenal hyperplasia
Lipoid congenital adrenal hyperplasia is an endocrine disorder that is an uncommon and potentially lethal form of congenital adrenal hyperplasia...
due to deficiency of StAR
Steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR , is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones...
and mitochondrial DNA
Mitochondrial DNA
Mitochondrial DNA is the DNA located in organelles called mitochondria, structures within eukaryotic cells that convert the chemical energy from food into a form that cells can use, adenosine triphosphate...
mutations. Some medications interfere with steroid synthesis enzymes (e.g. ketoconazole
Ketoconazole
Ketoconazole is a synthetic antifungal drug used to prevent and treat fungal skin infections, especially in immunocompromised patients such as those with AIDS or those on chemotherapy. Ketoconazole is sold commercially as an anti-dandruff shampoo, topical cream, and oral tablet.Ketoconazole is...
), while others accelerate the normal breakdown of hormones by the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
(e.g. rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...
, phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
).
Adrenal destruction
Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialized world. AutoimmuneAutoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
destruction of the adrenal cortex
Adrenal cortex
Situated along the perimeter of the adrenal gland, the adrenal cortex mediates the stress response through the production of mineralocorticoids and glucocorticoids, including aldosterone and cortisol respectively. It is also a secondary site of androgen synthesis.-Layers:Notably, the reticularis in...
is caused by an immune reaction against the enzyme 21-hydroxylase
21-Hydroxylase
Steroid 21-hydroxylase is a cytochrome P450 enzyme that is involved with the biosynthesis of the steroid hormones aldosterone and cortisol.In humans, 21-Hydroxylase is encoded by the gene CYP21A2.-Names and classification:...
(a phenomenon first described in 1992). This may be isolated or in the context of autoimmune polyendocrine syndrome
Autoimmune polyendocrine syndrome
In medicine, autoimmune polyendocrine syndromes are a heterogeneous group of rare diseases characterised by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected....
(APS type 1 or 2), in which other hormone-producing organs such as the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
and pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
may also be affected.
Adrenal destruction is also a feature of 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...
(ALD), and when the adrenal glands are involved in metastasis
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
(seeding of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells from elsewhere in the body, especially lung
Lung cancer
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue and, eventually, into other parts of the body. Most cancers that start in lung, known as primary...
), hemorrhage (e.g. in Waterhouse-Friderichsen syndrome
Waterhouse-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...
or antiphospholipid syndrome
Antiphospholipid syndrome
Antiphospholipid syndrome or antiphospholipid antibody syndrome , often also Hughes syndrome, is an autoimmune, hypercoagulable state caused by antibodies against cell-membrane phospholipids that provokes blood clots in both arteries and veins as well as pregnancy-related complications such as...
), particular infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
s (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...
, histoplasmosis
Histoplasmosis
Histoplasmosis is a disease caused by the fungus Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease primarily affects the lungs...
, coccidioidomycosis
Coccidioidomycosis
Coccidioidomycosis is a fungal disease caused by Coccidioides immitis or C. posadasii. It is endemic in certain parts of Arizona, California, Nevada, New Mexico, Texas, Utah and northwestern Mexico.C...
), deposition of abnormal protein in amyloidosis
Amyloidosis
In medicine, amyloidosis refers to a variety of conditions whereby the body produces "bad proteins", denoted as amyloid proteins, which are abnormally deposited in organs and/or tissues and cause harm. A protein is described as being amyloid if, due to an alteration in its secondary structure, it...
.
Corticosteroid withdrawal
Use of high-dose steroids for more than a week begins to produce suppression of the patient's adrenal glands because the exogenous glucocorticoids suppress hypothalamic corticotropin-releasing hormone (CRH) and pituitary adrenocorticotropic hormone (ACTH). With prolonged suppression, the adrenal glands atrophy (physically shrink), and can take months to recover full function after discontinuation of the exogenous glucocorticoid. During this recovery time, the patient is vulnerable to adrenal insufficiency during times of stress, such as illness.Suggestive features
Routine investigations may show:- Hypercalcemia
- HypoglycemiaHypoglycemiaHypoglycemia 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"...
, low blood sugarBlood sugarThe blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
(worse in children due to loss of glucocorticoid's glucogenic effects) - HyponatremiaHyponatremiaHyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
(low blood sodium levels), due to the kidney's inability to excrete free water in the absence of sufficient cortisol, and also the effect of Corticotropin-releasing hormoneCorticotropin-releasing hormoneCorticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
to stimulate secretion of ADHVasopressinArginine vasopressin , also known as vasopressin, argipressin or antidiuretic hormone , is a neurohypophysial hormone found in most mammals, including humans. Vasopressin is a peptide hormone that controls the reabsorption of molecules in the tubules of the kidneys by affecting the tissue's...
. That hyponatremia occurs even in secondary adrenal insufficiency (i.e. due to pituitary disease), in which aldosterone deficiency is not a feature, underscores the fact that hyponatremia in Addison's disease is not due to lack of aldosterone. - HyperkalemiaHyperkalemiaHyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
(raised blood potassiumPotassiumPotassium 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...
levels), due to loss of production of the hormone aldosteroneAldosteroneAldosterone 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... - EosinophiliaEosinophiliaEosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 0.45×109/L . A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being...
and lymphocytosisLymphocytosisLymphocytosis is an increase in the number or proportion of lymphocytes in the blood, usually detected when a complete blood count is routinely obtained. Lymphocytes normally represent 20 to 40% of circulating white blood cells...
(increased number of eosinophils or lymphocyteLymphocyteA lymphocyte is a type of white blood cell in the vertebrate immune system.Under the microscope, lymphocytes can be divided into large lymphocytes and small lymphocytes. Large granular lymphocytes include natural killer cells...
s, two types of white blood cellWhite blood cellWhite blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
s) - Metabolic acidosisMetabolic acidosisIn medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
(increased blood acidity), also due to loss of the hormone aldosteroneAldosteroneAldosterone 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...
because sodium reabsorption in the distal tubule is linked with acid/hydrogen ion (H+) secretion. Low levels of aldosterone stimulation of the renal distal tubule leads to sodium wasting in the urine and H+ retention in the serum.
Testing
ACTH 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...
) with synthetic pituitary ACTH hormone tetracosactide
Tetracosactide
Tetracosactide is a synthetic analogue of the naturally occurring adrenocorticotrophic hormone .-Pharmacology:...
. Two tests are performed, the short and the long test.
The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (IM/IV) is given. If, one hour later, plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
cortisol exceeds 170 nmol/L and has risen by at least 330 nmol/L to at least 690 nmol/L, adrenal failure is excluded. If the short test is abnormal, the long test is used to differentiate between primary adrenal insufficiency and secondary adrenocortical insufficiency.
The long test uses 1 mg tetracosactide (IM). Blood is taken 1, 4, 8, and 24 hours later. Normal plasma cortisol level should reach 1000 nmol/L by 4 hours. In primary Addison's disease, the cortisol level is reduced at all stages whereas in secondary corticoadrenal insufficiency, a delayed but normal response is seen.
Other tests that may be performed to distinguish between various causes of hypoadrenalism are renin
Renin
Renin , also known as an angiotensinogenase, is an enzyme that participates in the body's renin-angiotensin system -- also known as the Renin-Angiotensin-Aldosterone Axis -- that mediates extracellular volume , and arterial vasoconstriction...
and adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
levels, as well as medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
- usually in the form of ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
, computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
or magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI).
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...
, and the milder form, adrenomyeloneuropathy
Adrenomyeloneuropathy
Adrenomyeloneuropathy is a rare inherited disorder. It is a milder form of X-linked adrenoleukodystrophy . In adrenoleukodystrophy, young children generally exhibit cerebral dysfunction, with rapid progression to dementia and quadriparesis. Adrenomyeloneuropathy progresses more slowly, with...
, cause adrenal insufficiency combined with neurological symptoms. These diseases are estimated to be the cause of adrenal insufficiency in approximately 35% of male patients with idiopathic Addison’s disease and should be considered in the differential diagnosis of any male with adrenal insufficiency. Diagnosis is made by a blood test to detect very long chain fatty acid
Very long chain fatty acid
A very long chain fatty acid is a fatty acid with aliphatic tails longer than 22 carbons.Unlike most fatty acids, VLCFAs are too long to be metabolized in the mitochondria, and must be metabolized in peroxisomes....
s (VLCFA).
Maintenance
Treatment for Addison's disease involves replacing the missing cortisol, sometimes in the form of hydrocortisone tablets, or prednisonePrednisone
Prednisone 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...
tablets in a dosing regimen that mimics the physiological concentrations of cortisol. Alternatively one quarter as much prednisolone
Prednisolone
Prednisolone 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...
may be used for equal glucocorticoid effect as hydrocortisone. Treatment must usually be continued for life. In addition, many patients require fludrocortisone
Fludrocortisone
Fludrocortisone is a synthetic corticosteroid with moderate glucocorticoid potency and much greater mineralocorticoid potency. The brand name in the U.S. and Canada is Florinef.-Uses:...
as replacement for the missing aldosterone. Caution must be exercised when the person with Addison's disease becomes unwell with infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
, has surgery
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
or other 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...
, or becomes pregnant. In such instances, their replacement glucocorticoids, whether in the form of hydrocortisone, prednisone, prednisolone, or other equivalent, often need to be increased. Inability to take oral medication may prompt hospital attendance to receive steroids intravenously. People with Addison's are often advised to carry information on them (e.g. in the form of a MedicAlert
MedicAlert
The MedicAlert Foundation, a non-profit company founded in 1956 and headquartered in Turlock, California, maintains a database of members' medical information that is made available to medical authorities in the event of an emergency. Members supply critical medical data to the organization and...
bracelet) for the attention of emergency medical services
Emergency medical services
Emergency medical services are a type of emergency service dedicated to providing out-of-hospital acute medical care and/or transport to definitive care, to patients with illnesses and injuries which the patient, or the medical practitioner, believes constitutes a medical emergency...
personnel who might need to attend to their needs.
Crisis
Standard therapy involves intravenous injections of glucocorticoids and large volumes of intravenous saline solution with dextrose (glucose), a type of sugar. This treatment usually brings rapid improvement. When the patient can take fluids and medications by mouth, the amount of glucocorticoids is decreased until a maintenance dose is reached. If aldosterone is deficient, maintenance therapy also includes oral doses of fludrocortisone acetate.Epidemiology
The frequency rate of Addison's disease in the human population is sometimes estimated at roughly 1 in 100,000. Some research and information sites put the number closer to 40-60 cases per 1 million population. (1/25,000-1/16,600)(Determining accurate numbers for Addison's is problematic at best and some incidence figures are thought to be underestimates.)
Addison's can afflict persons of any age, gender, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity.
Prognosis
With proper medication, patients can expect to live a healthy and normal life.A person with adrenal insufficiency should always carry identification stating their condition in case of an emergency. The card should alert emergency personnel about the need to inject 100 mg of cortisol if its bearer is found severely injured or unable to answer questions. The card should also include the doctor's name and telephone number and the name and telephone number of the nearest relative to be notified. When traveling, a needle, syringe, and an injectable form of cortisol should be carried for emergencies. A person with Addison's disease also should know how to increase medication during periods of stress or mild upper respiratory infections. Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A patient who is vomiting may require injections of hydrocortisone, since oral hydrocortisone supplements cannot be adequately metabolised.
Discovery and development
Addison’s disease is named after Dr. Thomas AddisonThomas Addison
Thomas Addison was a renowned 19th-century English physician and scientist. He is traditionally regarded as one of the "great men" of Guy's Hospital in London....
, the British physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
who first described the condition in On the Constitutional and Local Effects of Disease of the Suprarenal Capsules (1849). All of Addison's six original patients had tuberculosis of the adrenal glands. While Addison's six patients in 1855 all had adrenal tuberculosis, the term "Addison's disease" does not imply an underlying disease process.
Famous Addisonians
- United States President John F. KennedyJohn F. KennedyJohn Fitzgerald "Jack" Kennedy , often referred to by his initials JFK, was the 35th President of the United States, serving from 1961 until his assassination in 1963....
was one of the best-known Addison's disease sufferers. He was possibly one of the first Addisonians to survive major surgery. There was substantial secrecy surrounding his health during his years as president. - Eunice Kennedy ShriverEunice Kennedy ShriverEunice Kennedy Shriver, DSG a member of the Kennedy family, sister to President John F. Kennedy and Senators Robert F. Kennedy and Edward Kennedy, was the founder in 1962 of Camp Shriver, and in 1968, the Special Olympics...
, one of John F. Kennedy's sisters, was believed to have Addison's disease as well. - Popular singer Helen ReddyHelen ReddyHelen Reddy , often referred to as "The Queen of 70s Pop", is an Australian-American singer and actress. In the 1970s, she enjoyed international success, especially in the United States, where she placed fifteen singles in the Top 40 of the Billboard Hot 100. Six of those 15 songs made the Top 10...
. - Scientist Eugene Merle ShoemakerEugene Merle ShoemakerEugene Merle Shoemaker , American geologist, was one of the founders of the fields of planetary science....
, co-discoverer of the Comet Shoemaker-Levy 9Comet Shoemaker-Levy 9Comet Shoemaker–Levy 9 was a comet that broke apart and collided with Jupiter in July 1994, providing the first direct observation of an extraterrestrial collision of solar system objects. This generated a large amount of coverage in the popular media, and the comet was closely observed by...
. - French Carmelite nun and religious writer Blessed Elizabeth of the Trinity
- American artist Ferdinand Louis Schlemmer died from Addison's disease.
- Some have suggested that Jane AustenJane AustenJane Austen was an English novelist whose works of romantic fiction, set among the landed gentry, earned her a place as one of the most widely read writers in English literature, her realism and biting social commentary cementing her historical importance among scholars and critics.Austen lived...
was an avant la lettre case, but others have disputed this. - According to Dr. Carl Abbott, a Canadian medical researcher, Charles DickensCharles DickensCharles John Huffam Dickens was an English novelist, generally considered the greatest of the Victorian period. Dickens enjoyed a wider popularity and fame than had any previous author during his lifetime, and he remains popular, having been responsible for some of English literature's most iconic...
may also have been affected. - Osama bin LadenOsama bin LadenOsama bin Mohammed bin Awad bin Laden was the founder of the militant Islamist organization Al-Qaeda, the jihadist organization responsible for the September 11 attacks on the United States and numerous other mass-casualty attacks against civilian and military targets...
may have been an Addisonian. Lawrence WrightLawrence WrightLawrence Wright is a Pulitzer Prize-winning American author, screenwriter, staff writer for The New Yorker magazine, and fellow at the Center for Law and Security at the New York University School of Law...
noted that bin Laden manifested all the key symptoms, such as "low blood pressure, weight loss, muscle fatigue, stomach irritability, sharp back pains, dehydration, and an abnormal craving for salt". Bin Laden was known to have consumed large amounts of the drug SulbutiamineSulbutiamineSulbutiamine is a synthetic derivative of thiamine . As a dimer of two modified thiamine molecules, it is a lipophilic compound that crosses the blood-brain barrier more readily than thiamine and increases the levels of thiamine and thiamine phosphate esters in the brain...
to treat his symptoms. - Basque nationalist and founder of the Basque Nationalist PartyBasque Nationalist PartyThe Basque National Party is the largest and oldest Basque nationalist party. It is currently the largest political party in the Basque Autonomous Community also with a minor presence in Navarre and a marginal one in the French Basque Country...
(PNV), Sabino AranaSabino AranaSabino Arana Goiri, self-styled as Arana ta Goiri'taŕ Sabin, , was a Spanish and Basque writer. He was the founder of the Basque Nationalist Party and father of Basque nationalism....
died in SukarrietaSukarrietaSukarrieta is a town and municipality located in the province of Biscay, in the Autonomous Community of Basque Country, northern Spain.-External links:*...
at the age of 38 after falling ill with Addison's disease during time spent in prison.
In other animals
The condition has been diagnosed in all breeds of dogs. In general, it is underdiagnosed, and one must clinically suspect it as an underlying disorder for many presenting complaints. Females are overrepresented, and the disease often appears in middle age (4–7 years), although any age or gender may be affected. Genetic continuity between dogs and humans helps to explain the occurrence of Addison's disease in both species.Hypoadrenocorticism is treated with fludrocortisone or a monthly injection called Percorten V (desoxycorticosterone pivlate (DOCP)) and prednisone. Routine blood work is necessary in the initial stages until a maintenance dose is established.
Most of the medications used in the therapy of hypoadrenocorticism cause excessive thirst and urination, making it important to provide enough drinking water.
If the owner knows about an upcoming stressful situation (shows, traveling etc.), patients generally need an increased dose of prednisone to help deal with the added stress. Avoidance of stress is important for dogs with hypoadrenocorticism.