Congenital adrenal hyperplasia: Pathogenesis, classification, symptoms

The article was written by a Doctor of Biochemistry - Laboratory Department - Vinmec Ha Long International Hospital

Congenital adrenal hyperplasia (CAH) is an inherited disease, the manifestation of which is a disorder in the synthesis of adrenal cortical hormones.

The adrenal gland consists of two small, flat-shaped glands, 2 -5 cm high, 3-5 cm wide, weighing about 4-6 grams, lying face down above the kidney.
Consists of 2 parts: the cortex (80%) and the medulla (20%)
There are about 50 steroids extracted from the adrenal cortex, but only 10 have hormonal activity divided into 3 main groups:
Metabolic hormones Sugar (Glucocorticoid): Including Cortisol, cortisone and corticosterone. These hormones are 21 carbon (C) and have oxygen at C11, so they are also called 11-oxysteroids. Water salt metabolism hormone (Mineralocorticoid): Including Aldosteron, 11-desoxycorticosterone (DOC). These hormones have 21C, are secreted from the glomerular layer of the adrenal cortex. Adrenal cortex sex hormones: Consists of dehydroepiandrogen (DHEA) androstendion, 17 cetoandrostendions (androstentrion) and 11 β-hydroxyandrostendions. This group has 19 carbons. All adrenocorticotropic hormones are steroid hormones, formed from cholesterol mediated by ∆5-pregnenolone according to the following metabolic scheme:

Congenital Adrenal Hyperplasia (CAH) is an inherited disease, the manifestation of which is a disorder of the adrenal cortex hormones.
Cause: The most common is inherited mutation of CYP21A2 gene leading to deficiency of 21-hydroxylase enzyme (accounting for 95% of cases), disrupting 2 metabolic pathways to form Cortisol (Sugar metabolism hormone) and Aldosteron in the biosynthesis of adrenocortical hormones.
May be caused by deficiency of the enzyme 11-beta-hydroxylase, which disrupts the metabolic pathway to form Cortisol (Sugar metabolism hormone) in the biosynthesis of adrenocortical hormone.
Disruption in the metabolic chain due to deficiency of the enzymes 21-hydroxylase and 11-beta-hydroxylase leads to deficiency of the hormone cortisol, lack or no deficiency of aldosterone, stagnation of the 17OH-Progesterone intermediate, excess androgens. a male hormone, a metabolic product of the adrenal cortex's sex hormone-forming pathway).

Classification of the Ho Chi Minh City Perinatal and Neonatal Association: the clinical type is divided into two types, classical and non-classical: Classical form: severe form, divided into two subgroups (salt loss and no loss). salt);
Non-classical form: mild and slow-onset.
Classification of the Vietnam Society of Endocrinology and Diabetes: divided into 2 main types, basic and non-basic. Congenital primary adrenal hyperplasia: is the more common form, divided into two subgroups, salt-depleted and virilized.
Non-basic congenital adrenal hyperplasia: when a child is born with normal health, symptoms of adrenal hyperplasia will appear later in life.
Frequency:
Severe classical (basic) form occurs in about 1/15,000 live births. The carrier (recessive gene) is about 1/60. The salt-losing body accounted for 67%, the salt-free body accounted for 33%.
The incidence of atypical (non-basic) disease is about 1 in 1,000 live births among Caucasians. The atypical form usually occurs in certain races, such as people of European ancestry.

3.1. For babies with classical/basic CAH, the baby's body will produce more androgens than usual before the baby is born. Androgen is a male sex hormone that stimulates the development of the gonads in men. In later life, they stimulate growth and puberty.
Women also have androgens but not as much as men. Overproduction of androgens causes anatomical abnormalities in both men and women.
Salt-depleting CAH: About 75% of children with basal (classical) CAH fall into this group. Salt-depleting CAH is a condition in which a child's body produces too much androgen but not enough cortisol and aldosterone. Cortisol is a hormone that helps maintain blood sugar levels, and it also helps the body fight disease and infection. Aldosterone is a hormone that helps balance salt and water in the body to keep blood pressure stable. If left untreated, children with salt-depleted CAH can become dehydrated leading to exhaustion and death. Babies born with salt-depleted CAH syndrome often have some of the following symptoms in the first few weeks after birth: Dehydration (baby crying, no sign of wet diapers for more than 6 hours, dark urine, sadness) sleep, fussiness), vomiting, refusal to eat, weight loss, diarrhea. In cases where a child with salt-depleting CAH is severely dehydrated and blood pressure is too low, the child may go into hypovolemic shock. If left untreated, the child can die. Symptoms of CAH-induced hypovolemic shock include tachycardia, loss of consciousness...
Congenital adrenal hyperplasia can occur in both boys and girls. Clinical severity depends on the degree of 21-hydroxylase deficiency. Children with this disease due to lack of enzymes necessary for the adrenal glands to produce the hormones cortisol and aldosterone, the body will produce more androgens, so male characteristics will appear dominant and early. Physically, the classical (basic) form at birth may have abnormalities of the external genitalia, such as:
Girls often have abnormalities of the external genitalia (large clitoris, urethral opening and normal vagina) and because of the abnormality of the external genitalia, the child is often detected early before the onset of hyperadrenocorticism in infancy;
Boys usually have no signs at birth, sometimes with subtle hyperpigmentation, large penises. The diagnosis depends on the level of aldosterone deficiency. Infants will have an adrenal crisis with dehydration present at 7-14 days of age.
Virilized CAH: Babies are born with normal levels of aldosterone, but produce too little cortisol and too much androgen. These children also often have high blood pressure. 3.2. Non-classical (non-primary) form Usually does not present in infancy but presents with precocious puberty between 2 and 4 years of age. Children with premature pubic hair, acne, excessive hair, low or amenorrhea with polycystic ovaries, infertility. Some girls and many boys have no clinical symptoms.

4.1. The 17-OH progesterone (17-OHP) biochemical test is the first test of choice to screen for congenital adrenal hyperplasia. There are two types of tests available (qualitative with blood taken from a child's heel or quantitative with blood taken from a vein). In it, a quantitative test will specifically indicate the level of 17-OHP, which can be performed immediately or after a qualitative test for high-risk results. Quantification of blood Aldosterone: decreased or normal depending on the body Cortisol measurement: decreased Testosterone: increased Electrolytes: decreased Na+, increased K+ Blood sugar (Glucose): decreased 21-hydroxylase deficiency is characterized by an increase in product intermediate metabolism 17-OH progesterone; The end products of the adrenal hormone synthesis pathways aldosterone and cortisol decrease, and androgens increase. In cases where the results of the above tests are not clear for diagnosis, the ACTH stimulation test can be used and is the gold standard for the diagnosis of the non-classical form.
4.2. X-ray imaging of long bones shows early calcification of the ends of the bones relative to age. Pelvic ultrasound to determine sex and urinary system abnormalities. 4.3. Karotype test Used when the external genitalia are not clear to determine the sex of the baby.
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