Congenital adrenal hyperplasia is a genetic defect consisting in a genetic mutation that results in the elimination of one of the key enzymes involved in the synthesis of adrenal hormones. Several forms of the disease have been identified, the most severe of which is manifested by a deficiency of cortisol, mineralocorticoids, and an excess of androgens. What are the symptoms of congenital adrenal hyperplasia and how is it treated?

Congenital adrenal hyperplasia,CAH ) Is a hereditary genetic defect consisting in a deficiency of enzymes involved in the adrenal hormone synthesis pathway. Several forms of the disease have been identified, the most severe of which is manifested by a deficiency of cortisol, mineralocorticoids, and an excess of androgens. It manifests itself already in the neonatal period. It has a violent course and can be life-threatening. The body becomes dehydrated, which translates into severe electrolyte metabolic disturbances that require immediate medical attention. In order to supplement the deficiencies of hormones, it is recommended to substitute them, and then the clinical symptoms gradually disappear.

The most common type of disease is based on a mutation in 21-hydroxylase, which is responsible for up to 90% of cases. There are two varieties within CAH: classical and non-classical forms. The first of them is characterized by a significant androgenization of the body, which translates into masculinization of the female genital organs. Statistics show that the disease affects 1/14000 births and as many as ¾ of patients present symptoms associated with fluctuations in aldosterone concentration, mainly in the form of excessive s alt loss.

What is the pathomechanism of CAH

The synthesis of cortisol, one of the adrenal hormones, takes place within the adrenal cortex and involves an enzymatic pathway. The deficiency of enzymes playing a key role at each stage of transformation manifests itself in a variety of clinical pictures. By blocking the formation of cortisol, 21-hydroxylase stimulates the hypothalamus and the pituitary gland, i.e. two superior structures for the secretion of, among others, ACTH - an adrenocorticotropic hormone that stimulates the adrenal glands, leading to organ hypertrophy.

Symptoms of congenital adrenal hyperplasia

In many cases, symptoms of congenital adrenal hyperplasia are noticed right after the baby is born. The most significant are:

  • masculinization of female genital organs - girls are born with zwitterionic genitalia, boys may develop hyperpigmentation of the external genitalia, i.e. darker discoloration, caused by increasing ACTH concentration
  • premature development of pubic hair
  • characteristic axillary odor
  • acne
  • high growth in childhood combined with advanced bone age in the future may eventually result in short stature
  • scanty or complete amenorrhea
  • coexistence of polycystic ovary syndrome
  • hirsutism, i.e. the presence of hair in places unusual for women
  • infertility
  • male pattern of baldness

Diagnosis and differentiation of congenital adrenal hyperplasia

In the classic form, almost all symptoms appear immediately after birth and are so characteristic that the clinical picture alone is sufficient to make a diagnosis. An additional factor facilitating diagnosis is family history. Unfortunately, the incomplete spectrum of symptoms makes the task difficult for the doctor, which is why patients are referred to a series of tests to rule out other causes of the reported ailments.

  • hormone diagnostics - in order to prove the deficiency of 21-hydroxylase, the concentration of 17-hydroxyprogesterone, which is a substrate for the enzyme, should be measured, and its concentration in CAH is increased. In many countries, the test is classified as a newborn screening test for many diseases that can be detected as early as neonatal age. The gold standard is the iv corticotropin loading test, in which the concentration of 17-hydroxyprogesterone and androstenedione is determined initially and after 60 minutes. The obtained results should be compared with specially prepared normograms to assess the severity of the disease. The greatest usefulness of the test is the ability to recognize a non-classical form
  • molecular diagnostics - involves the assessment of mutations in the gene encoding the 21-hydroxylase enzyme, located on the short arm of chromosome 6. It is believed that the classic form of congenital adrenal hyperplasia occurs in people with identified strong mutations.

Treatment of congenital adrenal hyperplasia

The aim of therapeutic treatment is to replenish hormonal deficiencies as soon as possible. A well-chosen therapy with glucocorticosteroids (hydrocortisone, prednisone) allows for a quick inhibition of excessive synthesisandrogens, which prevents masculinization. The dose should be adjusted to age and gender, but you need to remember about the possibility of overdosing on drugs, which results not only in growth inhibition, but also in the development of iatrogenic Cushing's syndrome ("buffalo neck", face like "full moon", weight increase, hyperglycemia, abnormalities in a blood smear, depressive disorders).

Children suffering from CAH with excessive s alt loss should be supplemented with sodium at a dose of 8-10 meq / kg / day. The daily sodium requirement should be dissolved in water, divided into four portions and given to the child mixed with milk as part of their meals. In older children, the problem resolves itself, because s alt is present in almost every food product.

There is an increasing effort to develop novel treatments, mainly to increase the final height of CAH patients. Growth hormone and LH releasing hormone analogue (LHRH) are administered simultaneously, which ultimately increases patients' height by up to 8 cm in adulthood.

Treatment should be holistic and also include the effects of excessive androgenization, such as the treatment of infertility in CAH patients or treatments that eliminate cosmetic defects in the form of hirsutism. This improves the mental state of patients and thus reduces the risk of depression.

Category:

Genetic diseases