Cretinism

The word cretin is termed as the iodine deficiency disorder which is associated with insufficient intake of the thyroid hormone activity that occurs during the fetal, infant, or childhood phases. The word cretin is derived from the French word chrétien, literally meaning “Christian” or “Christ-like” as the diseased were mentally retarded and incapable of doing sin.

This medical condition affects humans differently according to the age it is being affected. In children, this condition is developed due to hypothyroidism which induces mental and physical retardation. During maternal hyperestrogenism, the TBG (Thyroxine binding globulin) may be elevated and therefore the total T4 (thyroxine or tetraiodothyronine) and T3 (triiodothyronine)may be normal. The lack of feedback will also give an elevated TSH level. Prompt diagnosis and treatment are important in cretinism since any delay in initial replacement may lead to irreversible damage.

Maternal hypothyroidism may also cause neonatal cretinism. Hypothyroidism may result from treatment of hyperthyroidism using antithyroid drugs or radioactive iodine. Replacement of the hormone will produce an immediate effect. This condition is developed due to the breakdown of thyroid development or a deficit in hormone synthesis which is known as sporadic cretinism or due to the extreme iodine deficiency known as endemic cretinism.

This is mainly differentiated between the infant period of childhood, and it is preferred to prevent this condition by screening the neonates. Everyday treatment with thyroxine (8-12 ug/kg) should be started as early as possible as mental retardation that has ensued already is only partially reversible. In this case, the response obtained is partial in which the physical development and growth are revived, and additional mental retardation is checked.

Facts About Thyroid Gland and Thyroid Hormone

• The most important endocrine gland of our body which is present in the neck region is known as the thyroid gland. This gland is responsible for the secretion of thyroid hormones such as triiodothyronine (T3) and tetraiodothyronine (T4). These hormones present inside the follicular cells are synthesized by iodinating tyrosine residues at various positions in the glycoprotein called thyroglobulin.

• Thyroid hormone plays an important role in maintaining basal metabolic rate, oxidation foodstuff, and growth and development at an early stage of life.

Synthesis of Thyroid Hormone

• The thyroglobulin is synthesized in the follicular cells and released into the follicular lumen.

• Transportation of iodine in anionic form into the follicular cell takes place with the help of active transport and it moves into the follicular lumen by facilitated diffusion. This process is called an Iodide trap.

• At the border of follicular cells oxidation of iodide into iodine takes place.

• In this step, binding of iodine with tyrosine which is catalyzed by the enzyme peroxidase to form the monoiodotyrosine and diiodotyrosine.

Types of Cretinism

The medical condition cretinism is distinguished into two types:

• Congenital Cretinism: The rate of incidence is 1:3000 to 1:4000 in an iodine-deficient endemic area. This is mainly due to the defect in the genes which is responsible for encoding the various enzymes involved in the thyroid hormone synthesis such as thyroglobulin, iodotyrosine deiodinase, and also a thyroid-stimulating hormone.  This type of hypothyroidism is also called congenital hypothyroidism, non-goitrous (CHNG). The types of congenital hypothyroidism genes are named CHNG1 to CHNG5. Non-Goitrous congenital hypothyroidism is treated as the most prevalent inborn endocrine disorder.

• Endemic Cretinism: In adults generally the required dietary intake of iodine is 150µg/ day. This type of cretinism majorly affects the children who live in geographical settings where iodine is deficient, and it is not corrected by either supplementing iodine or thyroid hormone to regain normal thyroid hormone levels during early life. In most cases, the mothers of endemic cretinism children have been affected with hypothyroidism during pregnancy (Maternal hypothyroidism).  Exposure to radioactive Iodine during pregnancy may also be the cause in some cases. Use of antithyroid drugs or sulphonamides during pregnancy. Iodine intake as low as 25 mcg/day during pregnancy would be a potential risk factor for giving birth to cretinism neonates.

• Neurological Cretinism: This type of cretinism shows features like retarded growth, deaf-mutism, motor spasticity, severe mental retardation with a squint.

• Myxedematous Cretinism: The conditions observed are Retarded growth, Incomplete maturation of facial expression, Thickened, and dry skin, Small and dry hair, eyelashes and eyebrows, Mental retardation of comparatively lesser intensity to neurological cretinism, Delayed sexual maturation, and other clinical manifestations of hypothyroidism.

Symptoms of Cretinism 

Like other diseases, one suffering from cretinism also exhibits few symptoms. 

Some of the common and identifiable symptoms of cretinism are as follow:-

• Delay of tendon reflexes

• Myxoedema

• Enlargement of tongue

• Protruded abdomen

• Hearing impairment and defect in speech

• Unable to maintain body balance and body posture with a characteristic walking style 

• Decreased intelligent quotient (IQ)

• Thickened skin

• Deep and hoarse voice 

• Enlargement of the thyroid gland, also known as the condition, goiter

•  Often characterized by mental retardation and stunted growth

• Umbilical hernia

• Retardation of sexual attributes in individuals

• The sparseness of nails and hair

• Dwarfism or short stature

• Reduced muscle tone and coordination with mild neurological impairment  

Causes of Cretinism

The major causes of cretinism are:

• Lack of thyroid gland and failure of the thyroid gland to produce thyroid hormone (congenital cretinism or congenital iodine deficiency syndrome).

• Iodine deficiency in diet (Endemic cretinism).

• The pathophysiological conditions state that an Optimal level of maternal thyroid status is required for normal growth of the fetus. The maternal thyroid hormone is the only source for the fetus that crosses the placenta for fetal brain development.

• Thyroid hormone plays a major role in the growth, branching, and myelination of neuronal cells of CNS at fetal and neonatal stages. So, the absence of thyroid hormone at these stages would severely affect the generalized nervous system development.

• Thyroid hormone also plays a critical role in skeletal muscle development than soft tissue development. During cretinism, this disproportionate rate of growth leads to excessive growth of soft tissue compared to skeletal tissues.

The cause of hypothyroidism in newborns can be caused by various factors. Some of these factors responsible for hypothyroidism are listed below: 

• Poor formation, absence, or abnormally small thyroid gland 

• Thyroid hormone production is affected by a genetic defect.

• Curation of thyroid cancer by radioactive iodine or antithyroid treatment during pregnancy

• Intake of medicines that can disrupt the thyroid hormone production such as sulfonamides, antithyroid drugs, or lithium during pregnancy

• Lack iodine in mother’s diet during the pregnancy period

Human bodies are not capable of building iodine in itself therefore it is necessary for us to get it from food sources. Iodine in food comes through the soil. However, in some parts of the world, the soil lacks the richness of iodine.

In the United States, iodine deficiency is not considered a health risk since the introduction of iodized salt in the country. Not a health risk, yet it is the most common preventable cause of impaired neurological function in the world.

Diagnosis of Cretinism

• Congenital cretinism with severe hypothyroidism can be identified by antenatal screening test in the first month of life.

• Technetium (Tc– 99m pertechnetate) thyroid scan.

• Radioactive Iodine (RAIU) test (to differentiate between the congenital absence of a defect in the organ formation process).

• Postnatal – Blood spot test such as Guthrie’s test.

• Elevated serum Thyroid binding globulin (TBG) and TSH level.

• Elevated serum T3 and low T4 level.

Treatment of Cretinism

• It is recommended that after diagnosis, treatment should be started within 1 -2 weeks of life.

• Treatment should be started before the onset of symptoms, if developmental abnormalities and mental retardation start to appear, will not reverse even on thyroid hormone replacement therapy.

• Recommended dose is 10 to 15ug per kg body weight. The dose should be increased as the age progresses.

• Treatment of thyroxine should be given every day as the mental retardation, which has already been in its initial stages, is only partially reversible. But with treatment within these initial stages of mental retardation, there is a chance for the revival of physical development and growth, and mental retardation can be checked.

To treat cretinism in newborns, doctors called pediatric endocrinologists to provide babies with thyroid hormone, also called levothyroxine. This thyroid hormone comes in the form of pills which parents can crush and add to their milk, formula, or water. While using formulas, parents should be cautious of the ingredients used. Formulas containing ingredients such as soy protein and concentrate can interfere with the absorption of thyroid hormone.