Cretinism

Bookmark added to your notes.
View Notes
×

Introduction

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 the 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 infant period or 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 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 food stuffs 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 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 thyroid-stimulating hormone.  This type of hypothyroidism is also called congenital hypothyroidism, non-goitrous (CHNG). The types of congenital hypothyroidism genes are named as 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 the 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 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.

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 states that 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 stage. So, 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.

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 congenital absence or a defect in 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 starts 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.

FAQ (Frequently Asked Questions)

1. How Can Cretinism be Prevented?

About one billion people worldwide risk the consequences of iodine deficiency, all of which can be prevented by adequate maternal and infant iodine nutrition. Iodized salt is usually the preferred prophylactic vehicle, but iodized vegetable oil, iodized water, and iodine tablets are also occasionally used.

2. Why does Cretinism Cause Mental Retardation?

Iodine deficiency is the single most common cause of preventable mental retardation in the world. This view implies that anyone who is iodine deficient may be at risk of sub-optimal cognitive and psychomotor function.