Congenital adrenal hyperplasia (CAH ) : definition, causes, symptoms , diagnosis, treatment

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH )

The term " adrenogenital syndrome ( AGS) " encompasses a group of genetic metabolic diseases in which the hormone is impaired in the formation of the adrenal cortex .

Cause of adrenogenital syndrome are different enzyme defects that are inherited as an autosomal recessive trait. This means that a child will inherit the disease only if both parents carry the defective gene . Affected parents give the AGS regardless of gender to the child further . The AGS therefore occurs in both sexes , but with different symptoms.

Depending on the type of defect, the conversion of cholesterol in the adrenal cortex hormone is blocked at a particular location . Thus, the hormones cortisol and aldosterone are no longer produced in sufficient quantities. To compensate for this deficiency, the adrenal cortex is overstimulated. Because the adrenal glands due to enzyme defects but not to "manufacture" can produce hormone , the precursors of cortisol and aldosterone accumulate.

To this pent-up hormone precursors to " dispose " , they are converted via a different pathway in male hormones (androgens ) . The clinical picture of the adrenogenital syndrome is therefore on the one hand determined by the hormone deficiency ( cortisol , aldosterone ) , on the other hand by an excess of male hormones . Depending on which enzyme is defective in the production chain, drop the adrenogenital syndrome at different hormone precursors.

In 90 percent of cases of adrenogenital syndrome , the enzyme 21- hydroxylase is defective. A adrenogenital syndrome with 21- hydroxylase defect occurs in different forms: as a classic adrenogenital syndrome or non - classical adrenogenital syndrome.

The classic AGS is already apparent at birth. The non-classical form is also referred to as "late- onset AGS " - the symptoms seen during the course of development, for example in puberty.

The treatment of adrenogenital syndrome consists of hormone replacement therapy. It is currently being tested , they perform even before birth . A masculinization of female external genitalia is corrected surgically in the first year of life .

Congenital adrenal hyperplasia (CAH ): Definition

The generic term " adrenogenital syndrome " (AGS ) summarizes various genetic metabolic diseases together . What they all have in common is that in the adrenal cortex , the formation of hormones is disrupted because an enzyme does not work properly .

The term " adrenogenital syndrome " derives from the words " adreno " ( adrenal gland ) and " genital " ( sex ) from . At the beginning of the 19th Century, the syndrome was first described ( 1802 through Bevern and Römhild , 1803 Telesius ) .

There are several enzyme defects that can cause a adrenogenital syndrome. In 90 percent of the enzyme 21- hydroxylase is not working properly . Through a defect in the 21- hydroxylase , the normal conversion of the starting material is disturbed cholesterol cortisol and aldosterone in the adrenal hormones. The result is a lack of cortisol and aldosterone in part , by a mechanism of control and regulation of the pituitary gland ( pituitary ) stimulates the adrenal glands.

The stimulated adrenal grow and work harder . If a adrenogenital syndrome , cholesterol may also be converted to the metabolic chain only up to the point where the enzyme is defective . The hormone precursors up to that date can no longer be converted to cortisol and collect itself. Some of these hormone precursors are directed to a different pathway and there to male sex hormones ( androgens ) converted .

Congenital adrenal hyperplasia (CAH ) : Hormones of the adrenal cortex

Cortisol is a glucocorticoid . It is also referred to as a stress hormone. Cortisol has important functions in energy metabolism and acts in carbohydrate, fat and protein metabolism. It can produce sugar from proteins. As a result, the blood sugar levels in the state of hunger remains largely constant . In addition, it has anti-inflammatory , it suppresses immune reactions of the body and regulates the water (similar to aldosterone ) .

Aldosterone is a mineralocorticoid called . It regulates the salt and water balance and prevents too much salt is excreted through the kidneys. Much salt is lost through the kidneys , it also means a loss of water , as the salt binds water . Through this relationship of salt and water balance aldosterone regulates blood pressure significantly . When the body produces too little aldosterone, it loses water and salt , the blood pressure falls and there is a so-called " salt-wasting syndrome." This makes , for example, by a low blood pressure ( hypotension), an excessively high potassium levels in the blood and nocturnal leg spasms .

Androgens are male hormones that cause increased hair growth , muscle growth and a deep voice . In women they cause a general masculinization .

Congenital adrenal hyperplasia

forms

A adrenogenital syndrome is divided by the course in two forms, classical and non-classical form . A classic adrenogitales hyperplasia (CAH ) causes already in the neonatal symptoms. For classic AGS include the "simple" AGS , in which only the cortisol is disturbed, and the " AGS with salt loss," in which not only the cortisol and aldosterone that is affected.

The non-classical AGS normally occurs in adolescence or adulthood in appearance and runs much milder . For non-classical AGS include the " late-onset " form ( the symptoms late on ) and the " cryptic form" ( without significant symptoms).

Congenital adrenal hyperplasia (CAH ) : Causes

A adrenogenital syndrome ( AGS) has different enzyme defects as causes : The adrenal glands require the affected enzymes to make the hormones cortisol and aldosterone.

It is an autosomal recessive hereditary enzyme defects , that is, when sick people are both copies of each gene - the paternal and the maternal copy - altered ( mutated ) . Both parents must therefore have changed the system and have passed on to their child. The inheritance is independent of the sex of the child .

The missing enzyme 21- hydroxylase (21- OH) is responsible for more than 90 percent of cases of adrenogenital syndrome. Rare enzyme defects that can cause a adrenogenital syndrome, such as the 11-beta - hydroxylase deficiency and the failure of 3 -beta -hydroxysteroid dehydrogenase. In addition, there are other , more rare enzyme deficiencies as possible causes of AGS .

Congenital adrenal hyperplasia (CAH ) : Symptoms

A adrenogenital syndrome ( AGS) is manifested by various symptoms - depending on the type of enzyme deficiency and sex of the person concerned .

A classic adrenogenital syndrome calls already from birth cause symptoms . The so-called " late-onset forms " of the AGS , however , the symptoms do not occur until later.

In the classical adrenogenital syndrome affected girls have been masculinized external genitalia at birth . The reason is that they are too much androgen in the womb - exposed - that male sex hormones. The masculinization ranges from mild clitoral enlargement to the formation of a pseudo- penis. The internal genitalia , however, are female. In affected boys adrenogenital syndrome first calls forth no outward symptoms : The external sex organs are developing normally .

Untreated growing girls and boys with a strong first adrenogenital syndrome . The kids are too big for her age. However, the epiphyseal plates ( cartilaginous growth plates of the bone) close quickly , so that the early victims no longer continue to grow. Adults in whom there is a adrenogenital syndrome, short stature , if not treated in time.

A adrenogenital syndrome often seen in boys only by symptoms of so-called " pseudo- puberty " . In this note puberty the boys get the high androgen levels pubic hair and the penis grows , but the testicles are still childlike. Even girl getting a premature pubic hair of the male type - for example, on the upper lip or on the chest (called hirsutism ) - and are generally more hairy than other girls . Some of the menstrual period (called amenorrhea ) remains and the breast does not develop .

A adrenogenital syndrome may also cause the following symptoms :

tiredness
susceptibility to stress
Blood sugar (hypoglycaemia )
increased susceptibility to infection

Congenital adrenal hyperplasia (CAH ) : Diagnosis

When a suspected adrenogenital syndrome (AGS ), the diagnosis by a physical examination and on the basis of symptoms :

at birth on the basis of masculinization of the external genitalia in girls
in the first weeks of life with life-threatening salt-wasting crisis
in child age at increased body size and sign of the effect of male sex hormones in both sexes
in adulthood with reduced body size
The suspicion of an adrenogenital syndrome is confirmed by blood tests in the diagnosis , in which certain hormone concentrations are measured . The hormones that are produced in the metabolic cascade of enzyme deficiency are increased in their concentrations by several times (particularly 17 -hydroxy- progesterone) . If a adrenogenital syndrome with salt loss , the doctor also a lack of sodium, potassium levels too high and acidification of the blood ( acidosis) can prove to the diagnosis in the blood. With a urine examination, the doctor may increase concentrations of degradation products detected in the urine of Vorhormone (eg pregnanetriol = degradation product of 17- hydroxy- progesterone) in the adrenogenital syndrome.

The so-called ACTH injects the test the doctor adrenocorticotropic hormone ( the adrenal cortex stimulating hormone), whereby the concentration of 17 -hydroxy- progesterone significantly increases. The ACTH test is particularly suitable carriers ( heterozygotes = only one of the two gene copies is changed ) to diagnose which themselves have no symptoms of the AGS , but can pass the system on to their children .

Through DNA testing on a blood sample to be detected gene mutations that lead to defects in the enzyme that can trigger an adrenogenital syndrome. This confirms the diagnosis .

Congenital adrenal hyperplasia

Congenital adrenal hyperplasia (CAH ) : Therapy

A adrenogenital syndrome ( AGS) requiring therapy . As this shape, depends on the shape occur . In classic AGS substitution therapy is necessary : sufferers have long live the missing hormones (ie the glucocorticoid cortisol ) take as drugs in pill form.

Since it is a stress hormone cortisol in , it is increasingly needed in stressful situations the body. Must therefore in stressful situations , for example in infections with fever , surgery, or a particularly strong physical exertion , the drug dose can be increased. When AGS with salt wasting the missing hormone aldosterone in addition to the cortisol must be replaced also . This is also done in the form of tablets .

In a masculinization of the external genitalia in girls ( clitoral hypertrophy and a reduced vaginal opening ) experienced specialists can correct this by surgery. This treatment is usually done in the first year of life .

Congenital adrenal hyperplasia (CAH ) : History

Depending on the enzyme defect causes a adrenogenital syndrome, course and prognosis are different. Thus, there are forms of AGS extending milder, and others, which have a rather poor prognosis .

A adrenogenital syndrome usually takes a good course , because the symptoms can be treated well . Prerequisite for a successful therapy is a good setting of the drug dose . It will be replaced as much hormone as is needed . This means that the medication is individual and must be checked regularly. If the medication well adapted to the individual requirements , adult women and men are normally capable of procreation .

Congenital adrenal hyperplasia (CAH ) : Prevention

A adrenogenital syndrome is an inherited disease that you can not directly prevent . Couples who already have a child with adrenogenital syndrome, or if it is known that one of the partners has the genetic predisposition can receive medical advice if they want more children.