Congenital hypothyroidism

The congenital ( congenital, also Connatal ) hypothyroidism is a special form of hypothyroidism; they do relates to the patient in a development phase in which their nervous system is especially sensitive and can be permanently damaged by the lack of thyroid hormones. If the fault is not detected immediately after birth and treated, it leads to the frame of cretinism.

Frequency

The screening report of the German Society for newborn screening has an overall prevalence of 1:3270 newborns for 2004. Within the individual screening centers varies between 1:2143 and 1:5239 frequency. These figures correspond approximately to those that are specified for North America, where a frequency of about 1:3000 to 1:4000 newborns with somewhat greater frequency among Spanish -born and lower values ​​in African American children is reported. Thus, the congenital hypothyroidism is about twice as common as phenylketonuria, the first congenital metabolic disorder for which screening has been introduced. Girls are about twice as often affected as boys.

Causes

In most cases, the underactive thyroid is caused by a disturbance in their organogenesis during embryonic development ( agenesis or dysgenesis ). This produces no or little functional thyroid tissue. The reason for these anomalies is not known. Only in rare cases, mutations in genes could be identified that play a role in the development of the thyroid gland, including the FOXE1 gene for the thyroidal transcription factor 2 ( TTF -2) encoding, and in the PAX8 gene for the Paired - box protein 8 (PAX -8) encoding.

There are also disorders of hormone formation in an otherwise downright applied thyroid. Congenital disorders of thyroxine synthesis follow an autosomal recessive inheritance, defects in the receptor for thyroid hormone are inherited as autosomal dominant. Overall, about 85 % of all congenital hypothyroidism functions are sporadic, the remaining 15 % are hereditary.

Rare is the sub-function of a temporary nature. This is the case when it is caused by the transfer of maternal medications or blocking antibodies through the placenta to the baby, by iodine deficiency or excessive Jodbelastung. Disorders of the hypothalamic- pituitary axis - so-called central, secondary or tertiary sub-functions - with reduced production of thyroid stimulating hormone (TSH ) or thyrotropin -releasing hormone (TRH ) are extremely rare, but missed the usual screening tests.

Clinical manifestations

Although the thyroid hormone in the development of almost all organ systems of the utmost importance, most children are at birth initially unremarkable. By maternal thyroid hormone, which is transmitted via the placenta, are even those fetuses, which is completely absent thyroid, at least partially protected. In cord blood of these children, the concentration of thyroxine ( T4) is about one third to one half that of healthy children. The approximately 5% most severely affected children can be noticed early on with large fontanelles, wide gaping cranial sutures, large tongue, distended abdominal wall and umbilical hernia. With increasing degradation of maternal thyroxine are in addition other symptoms. The babies drink bad, get a blockage, are listless and sleep a lot. Often they need to be woken up at mealtimes. The voice can be rough and hoarse, the skin feels cool, the tension of the muscles are flaccid (hypotension) and the reflexes are weak. A neonatal jaundice ( jaundice prolongatus ) is possibly extended due to delayed maturation of the liver. An enlargement of the thyroid gland ( goiter ) can be found in approximately 5-10 % of children, mostly in congenital disorder of thyroxine synthesis.

If the disease is not detected and treated, seen from the second to third month of life, growth retardation. The reduction of intelligence is also increasing, the later treatment is started. If it starts in the first three months, the average IQ is 89 (range 64-107 ), at the beginning between the fourth and sixth month of life was 71 (range 35-96 ) and inserts them after the first half year of life was 54 (range 25-80 ). Other long term consequences are disturbances in the gross and fine motor coordination, loss of balance ( ataxia ), muscle weakness and spasticity, speech disorders, attention disorders and strabismus.

Methods of investigation

Since early diagnosis is extremely important for normal development of the children as possible, the diagnosis in most developed countries over a series examination in the neonatal period ( neonatal screening ) will be provided. Here, in Germany, the content of thyrotropin (TSH ), which increases significantly in the absence of thyroid hormone, determined in so-called dry blood. However, while the rare cases where a central induced secondary or tertiary hypothyroidism be overlooked. In the United States of America, most screening programs measure first the T4 concentration and only at values ​​below the tenth percentile in addition thyrotropin. The sampling should necessarily take place already on the third day of life. If the newborn already fired or laid, it can also be done earlier, but then has to be repeated in the rule again. In the affirmative, then a confirmatory test with a determination of thyrotropin, free T4 and free T3 must be done immediately. If confirmed, the finding of an underactive thyroid, further investigation to determine the cause can be performed. In addition to the determination of thyroglobulin for the detection of thyroid tissue and hormone formation disorder mainly include imaging measures such as ultrasonography or thyroid scintigraphy. Since the results of these studies but have no influence on the treatment, they are not absolutely necessary. If there is evidence of a maternal thyroid disease, the determination of thyroid autoantibodies in the mother and child can discover those forms that are likely to be temporary in nature. There is suspicion of an iodine excess or iodine deficiency as a cause of hypothyroidism, this can be confirmed by a determination of the iodine excretion in the urine.

Treatment

Because of the possibly no longer irreversible damage to the nervous system, the treatment of congenital hypothyroidism must be done as early as possible. It must not be unnecessarily delayed by waiting for examination results and should be consumed immediately after blood collection for confirming diagnosis of positive screening results. Goal of treatment is as soon as possible normalization of T4 content with a subsequent normalization of the TSH content of the blood. To this end, the hormone deficit is compensated by administering levothyroxine in a relatively high initial dosage. After two weeks, the dose can be reduced in the blood depending on the result of a check of the values ​​of TSH and T4. According to the growth of the child, it must be adapted to the increased need in later life. If there is doubt about the diagnosis of permanent hypothyroidism, a Auslassversuch not earlier than after the first birthday, be made better only after the third birthday according to American sources. Otherwise, the substitution must be lifelong. Is iodine deficiency as a cause of underactive thyroid detected, it is treated with an iodine substitution.

Cure views

Depending on the time of diagnosis, the prognosis for affected children is very good. If the sub-function identified within the first two weeks of life and treated consistently find themselves in adulthood only slight differences in level of intelligence, school performance and neurophysiological tests compared with healthy classmates or siblings. However, the treatment does not begin until later, although the physical development can still normalize, intelligence, however, remains limited.