Operation of computed tomography

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https://en.wikipedia.org/wiki/Operation_of_computed_tomography 

 

CT scanner with cover removed to show internal components. Legend:
T: X-ray tube
D: X-ray detectors
X: X-ray beam
R: Gantry rotation

X-ray computed tomography operates by using an X-ray generator that rotates around the object; X-ray detectors are positioned on the opposite side of the circle from the X-ray source.

A sinogram (left) and an image sample (right).

 

Picture of a CT scout (scanogram or topogram) as used for planning every scan slice.

A visual representation of the raw data obtained is called a sinogram, yet it is not sufficient for interpretation. Once the scan data has been acquired, the data must be processed using a form of tomographic reconstruction, which produces a series of cross-sectional images. In terms of mathematics, the raw data acquired by the scanner consists of multiple "projections" of the object being scanned. These projections are effectively the Radon transformation of the structure of the object. Reconstruction essentially involves solving the inverse Radon transformation.

Structure

In conventional CT machines, an X-ray tube and detector are physically rotated behind a circular shroud (see the image above right). An alternative, short lived design, known as electron beam tomography (EBT), used electromagnetic deflection of an electron beam within a very large conical X-ray tube and a stationary array of detectors to achieve very high temporal resolution, for imaging of rapidly moving structures, for example the coronary arteries. Systems with a very large number of detector rows, such that the z-axis coverage is comparable to the xy-axis coverage are often termed cone beam CT, due to the shape of the X-ray beam (strictly, the beam is pyramidal in shape, rather than conical). Cone-beam CT is commonly found in medical fluoroscopy equipment; by rotating the fluoroscope around the patient, a geometry similar to CT can be obtained, and by treating the 2D X-ray detector in a manner similar to a CT detector with a massive number of rows, it is possible to reconstruct a 3D volume from a single rotation using suitable software.

Contrast media

Main article: Contrast CT

Contrast mediums used for X-ray CT, as well as for plain film X-ray, are called radiocontrasts. Radiocontrasts for X-ray CT are, in general, iodine-based. This is useful to highlight structures such as blood vessels that otherwise would be difficult to delineate from their surroundings. Using contrast material can also help to obtain functional information about tissues. Often, images are taken both with and without radiocontrast.

Schematic configuration and motion

In this section, the schematic configuration and motion of the parallel beam irradiation optical system configured to obtain the p(s,θ) of above-mentioned (eq. 5) will be explained. In this section, how to obtain the p(s,θ) of (eq.5) by utilizing parallel beam irradiation optical system will also be explained. Configuration and motions of parallel beam irradiation optical system, referring Fig. 3.

Statements

Numbers (1)–(7) shown in Fig. 3 (see the numbers within the parentheses) respectively indicate: (1) = an object; (2) = the parallel beam light source; (3) = the screen; (4) = transmission beam; (5) = the datum circle (a datum feature); (6) = the origin (a datum feature); and (7) = a fluoroscopic image (a one-dimensional image; p (s, θ)).

Two datum coordinate systems xy and ts are imagined in order to explain the positional relations and movements of features (0)–(7) in the figure. The xy and ts coordinate systems share the origin (6) and they are positioned on the same plane. That is, the xy plane and the ts plane are the same plane. Henceforth, this virtual plane will be called “the datum plane”. In addition, a virtual circle centered at the abovementioned origin (6) is set on the datum plane (it will be called “the datum circle” henceforth). This datum circle (5) will be represents the orbit of the parallel beam irradiation optical system. Naturally, the origin (6), the datum circle (5), and the datum coordinate systems are virtual features which are imagined for mathematical purposes.

The μ(x,y) is absorption coefficient of the object (3) at each (x,y), p(s,θ) (7) is the collection of fluoroscopic images.

Motion of parallel beam irradiation optical system

The parallel beam irradiation optical system is the key component of a CT scanner. It consists of a parallel beam X-ray source (2) and the screen (3). They are positioned so that they face each other in parallel with the origin (6) in between, both being in contact with the datum circle (6).

These two features ((2) and (3)) can rotate counterclockwise around the origin (6) together with the ts coordinate system while maintaining the relative positional relations between themselves and with the ts coordinate system (so, these two features ((2) and (3)) are always opposed each other). The ts plane is positioned so that the direction from a collimated X-ray source (2) to the screen (3) matches the positive direction of the t-axis while the s-axis parallels these two features. Henceforth, the angle between the x- and the s-axes will be indicated as θ. That is, parallel beam irradiation optical system where the angle between the object and the transmission beam equals θ. This datum circle (6) will be represents the orbit of the parallel beam irradiation optical system.

On the other hand, the object (1) will be scanned by CT scanner is fixed to xy coordination system. Hence, object (1) will not be moved while the parallel beam irradiation optical system are rotated around the object (1). The object (1) must be smaller than datum circle.

Increment/Table speed

The distance the table moves for every 360° rotation of the X-ray generator is called the increment or table feed for axial scan modes. For helical scan modes, it is called table speed. Setting an increment that is smaller than the slice thickness results in overlap between the slices. A beneficial effect of this is a smoother transition between images when scrolling through the stack.

Obtaining transmission image ‘s’

During the above-mentioned motion (that is pivoting around the object(1)) of parallel beam irradiation optical system, the collimated X-ray source (2) emits transmission beam (4) which are effectively “parallel rays” in a geometrical optical sense. The traveling direction of each ray of the transmission beam (4) is parallel to the t-axis. The transmission beam (4), emitted by the X-ray source (2), penetrates the object and reaches the screen (3) after attenuation due to absorption by the object.

Optical transmission can be presumed to occur ideally. That is, transmission beam penetrates without diffraction, diffusion, or reflection although it is absorbed by the object and its attenuation is assumed to occur in accordance with the Beer-Lambert law.

Consequently, a fluoroscopic image (7) is recorded on the screen as a one-dimensional image (one image is recorded for every θ corresponding to all s values). When the angle between the object and transmission beam is θ and if the intensity of transmission beam (4) having reached each "s" point on the screen is expressed as p(s, θ), it expresses a fluoroscopic image (7) corresponding to each θ.

Tomographic reconstruction

Further information: Tomographic reconstruction

The technique of filtered back projection is one of the most established algorithmic techniques for this problem. It is conceptually simple, tunable and deterministic. It is also computationally undemanding, with modern scanners requiring only a few milliseconds per image. However, this is not the only technique available: the original EMI scanner solved the tomographic reconstruction problem by linear algebra, but this approach was limited by its high computational complexity, especially given the computer technology available at the time. More recently, manufacturers have developed iterative physical model-based maximum likelihood expectation maximization techniques. These techniques are advantageous because they use an internal model of the scanner's physical properties and of the physical laws of X-ray interactions. Earlier methods, such as filtered back projection, assume a perfect scanner and highly simplified physics, which leads to a number of artifacts, high noise and impaired image resolution. Iterative techniques provide images with improved resolution, reduced noise and fewer artifacts, as well as the ability to greatly reduce the radiation dose in certain circumstances. The disadvantage is a very high computational requirement, but advances in computer technology and high-performance computing techniques, such as use of highly parallel GPU algorithms or use of specialized hardware such as FPGAs or ASICs, now allow practical use.

Basic principle

In this section, the basic principle of tomography in the case that especially uses tomography utilizing the parallel beam irradiation optical system will be explained.

Tomography is a technology that uses a tomographic optical system to obtain virtual 'slices' (a tomographic image) of specific cross section of a scanned object, allowing the user to see inside the object without cutting. There are several types of tomographic optical system including the parallel beam irradiation optical system. Parallel beam irradiation optical system may be the easiest and most practical example of a tomographic optical system therefore, in this article, explanation of "How to obtain the Tomographic image" will be based on "the parallel beam irradiation optical system". The resolution in tomography is typically described by the Crowther criterion.

Fig. 3: Considering a parallel beam irradiation optical system where the angle between the object and all transmission lights equals θ. Here, the numbers in the figure (see the numbers within the parentheses) respectively indicate: (1) = an object; (2) = the parallel beam light source; (3) = the screen; (4) = transmission beam; (5) = the datum circle; (6) = the origin; and (7) = a fluoroscopic image (a one-dimensional image; p_θ(s)). Two datum coordinate systems xy and ts are also imagined in order to explain the positional relations and movements of features (0)–(7) in the figure. In addition, a virtual circle centered at the above-mentioned origin (6) is set on the datum plane (it will be called “the datum circle” henceforth). This datum circle (6) represents the orbit of the parallel beam irradiation optical system. In the figure above, X-Y plane rotates around the point of origin in the plane in such a way “to keep mutual positional relationship between the light source (2) and screen (7) passing through the trajectory (5).” Rotation angle of this case is defined as θ. In the figure set out above, absorption coefficient at a cross-sectional coordinate (x, y) of the subject is modeled as μ(x, y).

Fig. 3 is intended to illustrate the mathematical model and to illustrate the principle of tomography. In Fig.3, absorption coefficient at a cross-sectional coordinate (x, y) of the subject is modeled as μ(x, y). Consideration based on the above assumptions may clarify the following items. Therefore, in this section, the explanation is advanced according to the order as follows:

• (1)Results of measurement, i.e. a series of images obtained by transmitted light are expressed (modeled) as a function p (s,θ) obtained by performing radon transform to μ(x, y), and
• (2)μ(x, y) is restored by performing inverse radon transform to measurement results.

(1) The Results of measurement of p(s,θ) in a parallel beam irradiation optical system

Consider the mathematical model where the absorption coefficient of the object at each point ${\displaystyle (x,y)}$ is represented by the function ${\displaystyle \mu (x,y)}$ and suppose that the transmission beam penetrates without diffraction, diffusion, or reflection. Also assume the beam is absorbed by the object and its attenuation occurs in accordance with the Beer-Lambert law. What we want to know then is the values of the function ${\displaystyle \mu }$. What we can measure will be the values of the function ${\displaystyle p(s,\theta )}$.

When the attenuation conforms to the Beer-Lambert law, the relation between ${\displaystyle I_0}$ and ${\displaystyle I}$ is given by equation (1) and the absorbance ${\displaystyle p_l}$ along the light beam path ${\displaystyle l(t)}$ is given by equation (2). Here ${\displaystyle I_0}$ is the intensity of the light beam before transmission, while ${\displaystyle I}$ is the beam intensity after transmission.

${\displaystyle \begin{array}{r}I=I_0\exp \left(-\int \mu (x,y)dl\right)=I_0\exp \left(-{\int }_{-\mathrm{\infty }}^{\mathrm{\infty }}\mu (l(t))|\dot{l}(t)|dt\right)\end{array}}$

(1)

${\displaystyle \begin{array}{r}{p}_l=\ln (I/I_0)=-\int \mu (x,y)dl=-{\int }_{-\mathrm{\infty }}^{\mathrm{\infty }}\mu (l(t))|\dot{l}(t)|dt\end{array}}$

(2)

Here, the direction from the light source toward the screen is defined as the ${\displaystyle t}$ direction and that perpendicular to the ${\displaystyle t}$ direction and parallel with the screen is defined as the ${\displaystyle s}$ direction. (Both the ${\displaystyle (t,s)}$ and ${\displaystyle (x,y)}$ coordinate systems are chosen such that they are reflections of each other without mirror-reflective transformation.)

By using a parallel beam irradiation optical system, one can experimentally obtain the series of fluoroscopic images (these are one-dimensional images ${\displaystyle p_{\theta }(s)}$ of a specific cross section of a scanned object) for each angle ${\displaystyle \theta }$ between the object and the transmitted light beam. In Fig.3, the ${\displaystyle (x,y)}$ plane rotates counter clockwise.  around the point of origin in the plane in such a way “to keep mutual positional relationship between the light source (2) and screen (7) passing through the trajectory (5).” Rotation angle of this case is same as above-mentioned θ.

The beam having an angle ${\displaystyle \theta }$ is the collection of lines ${\displaystyle l_{\theta ,s}(t)}$, represented by equation (3) below.

${\displaystyle l_{\theta ,s}(t)=t\left[\begin{array}{c}-\sin \theta \\ \cos \theta \end{array}\right]+\left[\begin{array}{c}s\cos \theta \\ s\sin \theta \end{array}\right]}$

(3)

The function ${\displaystyle p_{\theta }(s)}$ is defined by equation (4). That ${\displaystyle p_{\theta }(s)}$ is equal to the line integral of μ(x,y) along ${\displaystyle l_{[\theta ,s]}(t)}$ of (eq. 3) as the same manner of (eq.2). This means that, ${\displaystyle p(s,\theta )}$ of following (eq. 5) is a resultant of Radon transformation of μ(x,y).

${\displaystyle p_{\theta }(s)=-{\int }_{-\mathrm{\infty }}^{\mathrm{\infty }}\mu (s\cos \theta -t\sin \theta ,s\sin \theta +t\cos \theta )dt}$

(4)

One can define following function of two variables (5). In this article, ${\displaystyle p(s,\theta )}$ is the collection of fluoroscopic images.

${\displaystyle p(s,\theta )=p_{\theta }(s)}$

(5)

(2)μ(x, y) is restored by performing inverse radon transform to measurement results

“What we want to know (μ(x,y))” can be reconstructed from “What we measured ( p(s,θ))” by using inverse radon transformation . In the above-mentioned descriptions, “What we measured” is p(s,θ) . On the other hand, “What we want to know ” is μ(x,y). So, the next will be "How to reconstruct μ(x,y) from p(s,θ)".

Spiral CT

Spiral computed tomography
MeSH	D036542

Spiral computed tomography, or helical computed tomography, is a computed tomography (CT) technology in which the source and detector travel along a helical path relative to the object. Typical implementations involve moving the patient couch through the bore of the scanner whilst the gantry rotates. Spiral CT can achieve improved image resolution for a given radiation dose, compared to individual slice acquisition. Most modern hospitals currently use spiral CT scanners.

Willi Kalender is credited with invention of the technique, and uses the term spiral CT. Kalender argues that the terms spiral and helical are synonymous and equally acceptable.

There are a class of image artifacts specific to helical acquisition.

Single-slice and multi-slice Spiral CT

Since its invention by Kalender in the 1980s, helical scan CT machines have steadily increased the number of rows of detectors (slices) they deploy. The prototype 16 multi-slice scanner was introduced in 2001 and in 2004, 64 multislice scanners are on the market. These can produce an image in less than a second and thus can obtain images of the heart and its blood vessels (coronary vessels) as if frozen in time.

In order to illuminate multiple rows of detector elements in a multi-slice scanner, the x-ray source must emit a beam which is divergent along the axial direction (i.e. a cone beam instead of a fan beam).

Pitch

The field of view (FOV) multiplied by scan range creates a volume of voxels (abdominal CT pictured).

A helical CT beam trajectory is characterized by its pitch, which is equal to the table feed distance along the scan range over one gantry rotation divided by the section collimation. When pitch is greater than 1, the radiation dose for a given axial field of view (FOV) is decreased compared to conventional CT. At high pitches there is, however, a trade-off in terms of noise and longitudinal resolution.

Helical (or spiral) cone beam computed tomography

Further information: Cone beam computed tomography

In cone-beam computed tomography (commonly abbreviated CBCT), the X-ray beam is conical.

Helical (or spiral) cone beam computed tomography is a type of three-dimensional computed tomography (CT) in which the source (usually of X-rays) describes a helical trajectory relative to the object while a two-dimensional array of detectors measures the transmitted radiation on part of a cone of rays emanating from the source.

In practical helical cone beam X-ray CT machines, the source and array of detectors are mounted on a rotating gantry while the patient is moved axially at a uniform rate. Earlier X-ray CT scanners imaged one slice at a time by rotating source and one-dimensional array of detectors while the patient remained static. The helical scan method reduces the X-ray dose to the patient required for a given resolution while scanning more quickly. This is, however, at the cost of greater mathematical complexity in the reconstruction of the image from the measurements.

History

Further information: History of computed tomography

The earliest sensors were scintillation detectors, with photomultiplier tubes excited by (typically) cesium iodide crystals. Cesium iodide was replaced during the 1980s by ion chambers containing high-pressure xenon gas. These systems were in turn replaced by scintillation systems based on photodiodes instead of photomultipliers and modern scintillation materials (for example rare-earth garnet or rare-earth oxide ceramics) with more desirable characteristics.

Initial machines would rotate the X-ray source and detectors around a stationary object. Following a complete rotation, the object would be moved along its axis, and the next rotation started. Newer machines permitted continuous rotation with the object to be imaged slowly and smoothly slid through the X-ray ring. These are called helical or spiral CT machines. A subsequent development of helical CT was multi-slice (or multi-detector) CT; instead of a single row of detectors, multiple rows of detectors are used effectively capturing multiple cross-sections simultaneously.

Addison's disease

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Addison%27s_disease

 

Addison's disease
Other names	Addison disease, primary adrenal insufficiency, primary adrenocortical insufficiency, chronic adrenal insufficiency, chronic adrenocortical insufficiency, primary hypocorticalism, primary hypocortisolism, primary hypoadrenocorticism, primary hypocorticism, primary hypoadrenalism
Darkening of the skin seen on the legs of a patient with an excess of melanin.
Specialty	Endocrinology
Symptoms	Abdominal pain, weakness, weight loss, darkening of the skin
Complications	Adrenal crisis
Usual onset	Middle-aged females
Causes	Problems with the adrenal gland
Diagnostic method	Blood tests, urine tests, medical imaging
Treatment	Synthetic Corticosteroid such as hydrocortisone and fludrocortisone
Frequency	0.9–1.4 per 10,000 people (developed world)
Deaths	Doubles risk of death

Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal glands (adrenal cortex), causing adrenal insufficiency. Symptoms generally come on slowly and insidiously and may include abdominal pain and gastrointestinal abnormalities, weakness, and weight loss. Darkening of the skin in certain areas may also occur. Under certain circumstances, an adrenal crisis may occur with low blood pressure, vomiting, lower back pain, and loss of consciousness. Mood changes may also occur. Rapid onset of symptoms indicates acute adrenal failure, which is a clinical emergency. An adrenal crisis can be triggered by stress, such as from an injury, surgery, or infection.

Addison's disease arises from problems with the adrenal gland such that not enough of the steroid hormone cortisol and possibly aldosterone are produced. It is an autoimmune disease which affects some genetically predisposed people in whom the body's own immune system has started to target the adrenal gland. While it can follow tuberculosis, in many adult cases it is unclear what has triggered onset of the disease. Causes can include certain medications, sepsis, and bleeding into both adrenal glands. Addison's disease is generally diagnosed by blood tests, urine tests, and medical imaging.

Treatment involves replacing the absent hormones. This involves taking a synthetic corticosteroid, such as hydrocortisone or fludrocortisone. These medications are usually taken by mouth. Lifelong, continuous steroid replacement therapy is required, with regular follow-up treatment and monitoring for other health problems. A high-salt diet may also be useful in some people. If symptoms worsen, an injection of corticosteroid is recommended (people need to carry a dose with them). Often, large amounts of intravenous fluids with the sugar dextrose are also required. With appropriate treatment, long-term outcomes are typically favorable, and most people are able to lead a reasonably normal life. Without treatment, an adrenal crisis can result in death.

Addison's disease affects about 9 to 14 per 100,000 people in the developed world. It occurs most frequently in middle-aged females. Secondary adrenal insufficiency is more prevalent. The disease is named after Thomas Addison, a graduate of the University of Edinburgh Medical School, who first described the condition in 1855.

Signs and symptoms

Hyperpigmentation as seen in a woman with Addison's disease

The symptoms of Addison's disease generally develop gradually. Symptoms may include fatigue, muscle weakness, weight loss, nausea, vomiting, loss of appetite, lightheadedness upon standing, irritability, depression, and diarrhea. Some people have cravings for salty foods due to the loss of sodium through their urine. Hyperpigmentation of the skin may be seen, particularly when the person lives in a sunny area, as well as darkening of the palmar crease, sites of friction, recent scars, the vermilion border of the lips, and genital skin. These skin changes are not encountered in secondary and tertiary hypoadrenalism.

• Skin changes
  • Hyperpigmentation of the skin (sometimes termed an "Addisonian tan")
• Gastrointestinal changes
  • Nausea and vomiting
  • Weight loss
  • Abdominal pain
  • Less common but still occurring: malnutrition and muscle wasting
• Behavioral disorders
  • Anxiety
  • Depression
  • Irritability
  • Poor concentration
• Changes in females
  • Loss or irregularity of menstrual cycle
  • Loss of body hair
  • Decreased sexual drive

On physical examination, these clinical signs may be noticed:

• Low blood pressure with or without orthostatic hypotension (blood pressure that decreases with standing)
• Darkening (hyperpigmentation) of the skin, including areas not exposed to the sun – characteristic sites of darkening 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 hormone (MSH) and ACTH share the same precursor molecule, pro-opiomelanocortin (POMC). After production in the 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 adrenal insufficiency, skin darkening does not occur, as ACTH is not overproduced.

Addison's disease is associated with the development of other autoimmune diseases, such as type I diabetes, thyroid disease (Hashimoto's thyroiditis), celiac disease, or vitiligo. Addison's disease may be the only manifestation of undiagnosed celiac disease. Both diseases share the same genetic risk factors (HLA-DQ2 and HLA-DQ8 haplotypes).

The presence of Addison's in addition to mucocutaneous candidiasis, hypoparathyroidism, or both, is called autoimmune polyendocrine syndrome type 1. The presence of Addison's in addition to autoimmune thyroid disease, type 1 diabetes, or both, is called autoimmune polyendocrine syndrome type 2.

Adrenal crisis

Main article: Adrenal crisis

An "adrenal crisis" or "addisonian crisis" is a constellation of symptoms that indicates 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 emergency and potentially life-threatening situation requiring immediate emergency treatment.

Characteristic symptoms are:

• Sudden penetrating pain in the legs, lower back, or abdomen
• Severe vomiting and diarrhea, resulting in dehydration
• Low blood pressure
• Syncope (loss of consciousness and ability to stand)
• Hypoglycemia (reduced level of blood glucose)
• Confusion, psychosis, slurred speech
• Severe lethargy
• Hyponatremia (low sodium level in the blood)
• Hyperkalemia (elevated potassium level in the blood)
• Hypercalcemia (elevated calcium level in the blood)
• Convulsions
• Fever

Causes

The negative feedback loop for glucocorticoids

Causes of adrenal insufficiency can be categorized by the mechanism through which they cause the adrenal glands to produce insufficient cortisol. This can be due to damage or destruction of the adrenal cortex. These deficiencies include glucocorticoid and mineralocorticoid hormones as well. 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 glandular damage).

Adrenal destruction

Autoimmune adrenalitis is the most common cause of Addison's disease in the industrialized world as it represents between 68% and 94% of cases. Autoimmune 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, 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 infections (tuberculosis, histoplasmosis, coccidioidomycosis), or the deposition of abnormal protein in amyloidosis.

Adrenal dysgenesis

All causes in this category are genetic, and generally very rare. These include mutations to the SF1 transcription factor, congenital adrenal hypoplasia 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.

Impaired steroidogenesis

To form cortisol, the adrenal gland requires cholesterol, 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).

Diagnosis

Suggestive features

Routine laboratory investigations may show:

• Low blood sugar (worse in children due to loss of glucocorticoid's glucogenic effects)
• Low blood sodium, due to loss of production of the hormone aldosterone, to the kidney's inability to excrete free water in the absence of sufficient cortisol, and also the effect of corticotropin-releasing hormone to stimulate secretion of ADH.
• High blood potassium, due to loss of production of the hormone aldosterone.
• Eosinophilia and lymphocytosis (increased number of eosinophils or lymphocytes, two types of white blood cells)
• Metabolic acidosis (increased blood acidity), also is due to loss of the hormone aldosterone because sodium reabsorption in the distal tubule is linked with acid/hydrogen ion (H⁺) secretion. Absent or insufficient levels of aldosterone stimulation of the renal distal tubule lead to sodium wasting in the urine and H⁺ retention in the serum.

Testing

Cortisol

Aldosterone

In suspected cases of Addison's disease, demonstration of low adrenal hormone levels even after appropriate stimulation (called the ACTH stimulation test or synacthen test) with synthetic pituitary ACTH hormone tetracosactide is needed for the diagnosis. Two tests are performed, the short and the long test. Dexamethasone does not cross-react with the assay and can be administered concomitantly during testing.

The short test compares blood cortisol levels before and after 250 micrograms of tetracosactide (intramuscular or intravenous) 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 1mg tetracosactide (intramuscular). Blood is taken 1, 4, 8, and 24 hours later. Normal plasma cortisol level should reach 1,000 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 may be performed to distinguish between various causes of hypoadrenalism, including renin and adrenocorticotropic hormone levels, as well as medical imaging – usually in the form of ultrasound, computed tomography or magnetic resonance imaging.

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 about 35% of diagnosed males 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 acids.

Treatment

Maintenance

Treatment for Addison's disease involves replacing the missing cortisol, sometimes in the form of hydrocortisone tablets, or prednisone 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 is usually lifelong. In addition, many people require fludrocortisone as a replacement for the missing aldosterone.

People with Addison's are often advised to carry information on them (e.g., in the form of a MedicAlert bracelet or information card) for the attention of emergency medical services personnel who might need to attend to their needs. A needle, syringe, and injectable form of cortisol are also recommended to be carried for emergencies. People with Addison's disease are advised to increase their medication during periods of illness or when undergoing surgery or dental treatment. Immediate medical attention is needed when severe infections, vomiting, or diarrhea occur, as these conditions can precipitate an Addisonian crisis. A person who is vomiting may require injections of hydrocortisone, instead.

Those with low aldosterone levels may also benefit from a high-sodium diet. It may also be beneficial for the people with Addison's disease to increase their dietary intake of calcium and vitamin D. High dosages of corticosteroids are linked to osteoporosis so these may be necessary for bone health. Sources of calcium include dairy products, leafy greens, and fortified flours among many others. Vitamin D can be obtained through the sun, oily fish, red meat, and egg yolks among many others. Though there are many sources to obtain vitamin D through diet, supplements are also an option.

Crisis

Standard therapy involves intravenous injections of glucocorticoids and large volumes of intravenous saline solution with dextrose (glucose). This treatment usually brings rapid improvement. If intravenous access is not immediately available, intramuscular injection of glucocorticoids can be used. When the person 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.

Prognosis

Outcomes are typically good when treated. Most people can expect to live relatively normal lives. Someone with the disease should be observant of symptoms of an "Addison's crisis" while the body is strained, as in rigorous exercise or being sick, the latter often needing emergency treatment with intravenous injections to treat the crisis.

Individuals with Addison's disease have more than a doubled mortality rate. Furthermore, individuals with Addison's disease and diabetes mellitus have an almost four-fold increase in mortality compared to individuals with only diabetes. The risk ratio for cause mortality in males and females is 2.19 and 2.86, respectively.

Death from individuals with Addison's disease often occurs due to cardiovascular disease, infectious disease, and malignant tumors, among other possibilities.

Epidemiology

The frequency rate of Addison's disease in the human population is sometimes estimated at one in 100,000. Some put the number closer to 40–144 cases per million population (1/25,000–1/7,000). Addison's can affect persons of any age, sex, or ethnicity, but it typically presents in adults between 30 and 50 years of age. Research has shown no significant predispositions based on ethnicity. About 70% of Addison's disease diagnoses occur due to autoimmune reactions, which cause damage to the adrenal cortex.

History

Addison's disease is named after Thomas Addison, the British physician who first described the condition in On the Constitutional and Local Effects of Disease of the Suprarenal Capsules (1855). He originally described it as "melasma suprarenale", but later physicians gave it the medical eponym "Addison's disease" in recognition of Addison's discovery.

While the six under Addison in 1855 all had adrenal tuberculosis, the term "Addison's disease" does not imply an underlying disease process.

The condition was initially considered a form of anemia associated with the adrenal glands. Because little was known at the time about the adrenal glands (then called "Supra-Renal Capsules"), Addison's monograph describing the condition was an isolated insight. As the adrenal function became better known, Addison's monograph became known as an important medical contribution and a classic example of careful medical observation. Tuberculosis used to be a major cause of Addison's disease and acute adrenal failure worldwide. It remains a leading cause in developing countries today.

US president John F. Kennedy suffered from complications of Addison's Disease throughout his life, including during his presidency, resulting in fatigue and hyperpigmentation of the face.

Other animals

Main article: Hypoadrenocorticism in dogs

Hypoadrenocorticism is uncommon in dogs, and rare in cats, with less than 40 known feline cases worldwide, since first documented in 1983. Individual cases have been reported in a grey seal, a red panda, a flying fox, and a sloth.

In dogs, hypoadrenocorticism has been diagnosed in many breeds. Vague symptoms, which wax and wane, can cause delay in recognition of the presence of the disease. Female dogs appear more affected than male dogs, though this may not be the case in all breeds. The disease is most often diagnosed in dogs that are young to middle-aged, but it can occur at any age from 4 months to 14 years. Treatment of hypoadrenocorticism must replace the hormones (cortisol and aldosterone) which the dog cannot produce itself. This is achieved either by daily treatment with fludrocortisone, or monthly injections with desoxycorticosterone pivalate (DOCP) and daily treatment with a glucocorticoid, such as prednisone. Several follow-up blood tests are required so the dose can be adjusted until the dog is receiving the correct amount of treatment, because the medications used in the therapy of hypoadrenocorticism can cause excessive thirst and urination if not prescribed at the lowest effective dose. In anticipation of stressful situations, such as staying in a boarding kennel, dogs require an increased dose of prednisone. Lifelong treatment is required, but the prognosis for dogs with hypoadrenocorticism is very good.