What Is Congenital Adrenal Hyperplasia?

Congenital adrenal hyperplasia is also called adrenal genital syndrome or adrenal abnormality. Mainly due to the deficiency of the enzymes necessary for the adrenocortical hormone biosynthesis process, the corticosteroid synthesis is abnormal. In most cases, the adrenal glands secrete insufficient glucosamine and salt hormones and too much androgen, so clinically there are varying degrees of adrenal insufficiency, accompanied by virilization of girls, and boys with precocious puberty, and hyponatremia Or hypertension and other symptoms.

Congenital adrenal hyperplasia

Causes and pathophysiology of congenital adrenal hyperplasia

In the synthesis of normal adrenocortical hormones, the precursor cholesterol such as cortisol is converted to cortisol, aldosterone, sex hormones, etc. under the action of various enzymes. In patients with this disease, due to the lack of enzymes in different parts during the synthesis of the above hormones, the synthesis of cortisol and corticosterone has decreased, leading to an increase in secretion of adrenocorticotropic hormones in the anterior pituitary gland, and the adrenal cortex was stimulated by ACTH to proliferate, resulting in cortisol synthesis The amount can maintain the lowest level of life, but the reticular zone also produces a large amount of androgen, which causes virilization. Due to the deficiency of different enzymes, it can be accompanied by symptoms such as hyponatremia and hypertension. In the patient's body, various intermediate metabolites such as gestrinol, 17-hydroxypregnanolone, and tetrahydro compound S accumulate before the site of blockage can be detected in the patient's urine.

The disease is an autosomal recessive inheritance. It develops when two disease-causing genes are present at the same time (ie, homozygotes), and when only one disease-causing gene is present (ie, heterozygotes), it does not develop. A family member generally only has the same type of defects, and the most common clinical defects are 21 hydroxylase (about 90% of the total number of patients) and 11 hydroxylase (about 5% of the total number of patients). Other defects such as 17 hydroxylase, 3 steroid dehydrogenase, 18 oxidase, 20 and 22 carbon chain enzymes are rare. ^[1]

Clinical manifestations of congenital adrenal hyperplasia

The disease is more common in girls, with a male to female ratio of about 1: 4. Deficiency of any one enzyme (except 3-hydroxysteroid dehydrogenase) can have common symptoms caused by excessive secretion of adrenal androgens.

When a baby boy is born, the penis is slightly larger than normal, but it is often not noticeable. After half a year, the symptoms of precocious puberty gradually appear, and it is more obvious at the age of 4 to 5. The main manifestation is the rapid enlargement of the penis, the enlargement of the scrotum and the prostate, but the testicles do not increase relatively, are commensurate with age, and have no sperm formation. Pediatric hair and skin appear early

Acne, throat knots, low voice, muscular, hyper-physical development, body length over children of the same age, epiphysis growth far exceeds age. If the diagnosis and treatment are not timely, the epiphyseal fusion will be premature, and the body will become shorter when it is an adult. Intellectual development is generally normal.

A baby girl may have a clitoral hypertrophy at birth, and it will gradually grow like a boy's penis, but it will be thicker than a boy of the same age, and the labia majora will look like a boy's scrotum but no testicles. Due to the effects of excess androgen during the embryonic period, it can prevent the normal development of female reproductive organs. At the 12th week of the fetus, the female external genitals form, and the urethra and vaginal opening are separated.

If the 21hydroxylase deficiency is partial and the patient is less virilized, it is only manifested as clitoral hypertrophy. If the 21hydroxylase deficiency is more serious, androgen has an earlier and severe effect on the development of sexual organs during the embryonic period. The vagina does not separate, all open in the genitourinary sinus, and can even reach forward to the base of the clitoris, which looks like a boy's hypospadias. Therefore, the external genitalia can be manifested as three malformations, but the internal genitalia are completely female, so it is also called pseudo-hermaphroditism. Other virilization symptoms and physical development were similar to those of the boy patient mentioned above.

In addition, because ACTH and melanocyte stimulating hormones increase, patients often show skin and mucosal pigmentation. Generally speaking, the more severe the defect, the higher the incidence of pigmentation. In the newborn, only the areola is dark and the external genitalia is dark. If not treated, the pigmentation may develop rapidly.

Due to the defects of various enzymes, different types of clinical manifestations are possible:

First, the symptoms of purely virilized tadpoles are as described above, due to the incomplete lack of 21 hydroxylase, this type is the most common, accounting for more than 50% of the total number of patients.

Second, the salt-losing salamander accounts for about 1/3 of the total number of patients with this disease. When 21 hydroxylase is deficient, the progesterone and 17-hydroxyprogesterone of cortisol are secreted too much and the aldosterone synthesis is reduced, so that the distal renal tubules have excessive sodium excretion and potassium excretion. In addition to the above virilization manifestations, the patient began to vomit, anorexia, restlessness, weight loss and severe dehydration, electrolyte disorders such as hyperkalemia, hyponatremia, and metabolic acidosis soon after birth. Can die from circulatory failure. Some people think that this type of patients is more severe due to the lack of 21 hydroxylase than the purely masculine type, and some have speculated that 21 hydroxylase may have two isomerases. Girls have an appearance of sexual deformity at birth and are easier to diagnose. Boys are more difficult to diagnose. They are often misdiagnosed as pyloric stenosis or infant diarrhea and lose the chance of treatment, leading to early death. In some cases, there are no obvious symptoms of dehydration or peripheral circulation failure. Sudden death may be due to cardiac arrest caused by hyperkalemia. You should be vigilant.

Third, the incidence of hypertension is relatively low, accounting for about 5% of the total number of patients with this disease. It is caused by 11 hydroxylase deficiency and excessive 11 deoxycorticosterone, which is less masculine and can cause high levels of virilization. Blood pressure, usually a moderate increase in blood pressure, sometimes as high as 160 to 200/100, 160 mm Hg. This type of hypertension is characterized by a decrease in corticosteroids and a rise in levels after discontinuation.

Diagnosis of congenital adrenal hyperplasia

Early diagnosis and early treatment of this disease can prevent the development of bisexual or precocious puberty, and children can maintain normal life and growth.

Diagnosis is mainly based on clinical manifestations and reference to family history. Suspicious cases can be measured for 24-hour urine l7 ketone steroid output. 17 ketosteroids are the final product of androgen metabolism in the body. In normal babies, the amount of 17 ketones excreted within three weeks after birth is up to 2.5 mg per day, which will be reduced later, less than 1 mg within 1 year, and 1-4 years old < 2 mg, 4 to 8 years old <3 mg, pre-puberty <5 mg. Patients can be as high as 5-30 mg and increase with age.

When 21 hydroxylase is deficient, a large amount of estriol may appear in the urine; when 11 hydroxylase is deficient, a large amount of tetrahydro compound S may be present in the urine, while estriol is only slightly increased.

When the diagnosis is difficult, a small-dose dexamethasone inhibition test can be performed. The urine 17 ketone steroid output is significantly reduced after administration, and then increased after stopping the treatment.

Differential diagnosis of congenital adrenal hyperplasia

1. Female children should be distinguished from true hermaphroditism. The latter is a gonad-ovarian and testicular tissue in a person, but it is underdeveloped, so its estrogen, androgen, and urinary 17-ketosteroid output Lower than normal.

Second, girls with urethral and vaginal openings in the genitourinary sinus, especially when the opening is at the base of the clitoris, should pay attention to distinguishing from the boy's hypospadias and cryptorchidism. Iodine oil can be used to observe the presence or absence of the uterus, and chromosome examination can be performed. Sexual chromatin is positive in patients with adrenal hyperplasia, and the sex chromosome is female.

3. When patients with salt-loss type suffer from vomiting, dehydration and other symptoms in the early postnatal period, they should be distinguished from gastrointestinal diseases such as pyloric stenosis and intestinal obstruction, especially in male children. Care should be taken with potassium that is not easily corrected.

Congenital Adrenal Hyperplasia

After the diagnosis is confirmed, early treatment with hydrocortisone or prednisone should be used. On the one hand, it can replace the lack of adrenocortical hormone synthesis, and it can also inhibit the release of pituitary corticotropin, thereby inhibiting the excessive production of adrenal androgen and stopping Male development. If applied properly, patients can maintain normal growth, development and life. The dose should be larger at the beginning, and can be reduced to the physiological dose when the steroid discharge in the urine has been controlled to a satisfactory level after 1 to 2 weeks: general prednisone infants 2.5 mg per day, children 2.5-5 mg, and adolescence 7.5 10 mg. The dose is adjusted according to the 17 ketosteroid excretion in urine. The daily dose is taken orally twice, and the last dose should be taken in the evening.

Should adhere to lifelong medication. Under stress, the hormone maintenance amount needs to be doubled. In case of severe stress or acute adrenocortical crisis, the hormone dose needs to be increased by 5-10 times. Water-soluble hydrocortisone Intravenous and supplemented with sodium chloride.

Patients with loss of salt should be rescued in the beginning. Hydrocortisone 25 100 mg / day is given intravenously at the beginning, supplemented with liquid and sodium chloride to correct dehydration and low salt, and can be applied with deoxycorticosterone acetate (DOCA) 0.5 l mg / day intramuscularly, or 250-300 g / m2 / day with the sodium natriuretic hormone 90-fluorohydrocorticoid, divided into three doses. Patients with mild salt loss can take prednisone orally, adding 2 to 5 grams of salt per day to maintain electrolyte balance.

Clitoral resection of children with pseudo-hermaphroditism should be performed 2 to 4 years after birth. The operation is too early to be successful. If it is too late, it will have adverse psychological and social effects. Patients with urethral and vaginal openings in the genitourinary sinus can perform urethral and vaginal separation after menstrual cramps to avoid ascending urinary tract infections. If the patient is definitely diagnosed during adolescence, and his external genitalia is basically like a male, it is not appropriate to change his original external genitalia, because changing the gender will often be a blow to the patient's psychology, and it will have a complex social impact. For hysterectomy and ovarian resection, to maintain the development of male secondary sexual characteristics, and adjust the amount of prednisone according to the urine 17 ketone steroid discharge to maintain it at the level of normal adult men.