- What is Cretinism?
- What is a Thyroid Gland?
- Cretinism Pathophysiology
- 1. Thyroid metabolism anomalies
- 2. Thyroid hormone resistance
- 3. Congenital TBG deficiency
- 4. Maternal thyroid hormone levels
- Causes of Cretinism
- 1. Hereditary in origin
- 2. Missing or misplaced thyroid gland
- 3. Maternal iodine levels
- 4. Maternal Thyroid condition and medications
- 5. Dysfunction of the pituitary gland/hypothalamus
- Prevalence of Cretinism
- 1. Race
- 2. Sex
- 3. Age
- Signs and Symptoms of Cretinism
- Cretinism Diagnosis
- 1. Newborn Screening Test
- 2. Measurement of TSH or thyroxine (T4)
- 3. Imaging studies
- Cretinism Treatment
- 1. L-thyroxine
- 2. Monitoring and Evaluation
- 3. Diet
- 4. Activity
- Cretinism Prognosis
- Points to Consider
Cretinism is a medical condition present at birth wherein there is a decreased or absent thyroid function and thyroid hormone production . When untreated, this could lead to severely stunted physical and mental growth of the newborn . This is also known as Congenital Hypothyroidism .
Picture 1: A Child with Cretinism
What is a Thyroid Gland?
This is a butterfly-shaped organ located at the lower portion of the neck. The main purpose of this gland is the thyroid hormone production. Thyroid hormone is also known as thyroxine or T4 . This hormone contains iodine which is responsible for growth regulation, body metabolism, and brain development .
Picture 2: Anatomy of the thyroid gland
At 4-10 weeks of gestation, the thyroid gland is formed as two-lobed organ located in the neck area which arises from the fourth branchial pouches. By 10-11 weeks of gestation, thyroid hormone is produced by the thyroid gland.
1. Thyroid metabolism anomalies
Cretinism or Congenital Hypothyroidism occurs when there are inborn anomalies in thyroid metabolism.
- For the production of thyroid hormones, T3 and T4, the thyroid gland uses tyrosine and iodine. The iodide is attached to the thyroid follicular cells through the active transport system.
- Iodide is oxidized by thyroid peroxidise and is converted to iodine.
- In Organification, iodine binds with tyrosine molecules. This forms monoiodotyrosine (MIT) and diiodotyrosine (DIT). When 2 molecules of DIT attach to each other, it will form tetraiodothyronine (T4). Also, when 1 molecule of MIT binds to 1 molecule of DIT, it results to formation of triidothyronine (T3).
- When there are errors in the metabolism of thyroid hormones, cretinism results.
2. Thyroid hormone resistance
- The primary hormone produced by the thyroid glands is T4.
- On the other hand, only 10-40% of T3 is released from the thyroid glands. The remainder of the T3 hormones are produced by the monodeiodination, a process involving the removal of one molecule of T4.
- Also, in order for T3 to facilitate its effects on the body, it interacts with a specific nuclear receptor. When there are abnormalities with the receptor in this process, thyroid hormone resistance can occur.
3. Congenital TBG deficiency
- The carrier proteins which are responsible for the circulation of thyroid hormones are thyroid-binding globulin (TBG), albumin, and thyroid-binding prealbumin (TBPA).
- Only 0.03% of the circulating T4 are unbound or free. These unbound T4 are metabolically active.
- In congenital TBG deficiency, infants have low levels of TBG. This can occur as a result of autosomal recessive or X-linked recessive condition.
4. Maternal thyroid hormone levels
- Maternal thyroid disease: This condition significantly affects the fetus’ thyroid function.
- Autoimmune thyroiditis: When the Immunoglobulin G (IgG) antibodies cross the placenta, it interferes with the fetal thyroid function.
- Maternal hyperthyroidism: This involves the medication called Thioamides. This treatment of maternal hyperthyroidism antagonizes the production of fetal thyroid hormones.
- Radioactive iodine: The use of this treatment to a pregnant woman can halt the thyroid gland proper functioning permanently. 
Causes of Cretinism
Most cases of cretinism have no known cause. On the other hand, for the cases with determined causes, they are mostly caused by genetic mutations. These involve anomalies in the production of enzymes that are needed for the thyroid hormone synthesis . Here are some underlying causes of cretinism:
1. Hereditary in origin
- A small percentage of cretinism patients have inherited anomalous genes that cause the thyroid gland to produce less thyroid hormone. This happens though there is no detected abnormality in the size and shape of the thyroid gland. 
Picture 3: How Cretinism is inherited
2. Missing or misplaced thyroid gland
- In most babies born with cretinism, the thyroid is either absent or underdeveloped. For some, there are cases wherein the thyroid can be found on a different location such as under the tongue or side of the neck. Normally, the thyroid gland is at the center and front of the neck, and near at the top of the windpipe. Also, some patients with cretinism, thyroid is smaller than the normal size.
- If there are abnormalities like this on the thyroid gland, either less or no thyroid hormone will be produced. This kind of defect is not inherited. Also, the reason why this birth defect happens is unknown. 
Picture 4: What happens in Congenital Hypothyroidism
3. Maternal iodine levels
- When the mother of the baby has an iodine deficiency during her pregnancy, there will be insufficient amount of iodine for the production of thyroid hormones. This is a common cause of cretinism in people who do not have enough source of iodine in their countries.
- The thyroid of the fetus is also affected by too much iodine during pregnancy. [1, 3]
4. Maternal Thyroid condition and medications
- There are cases wherein the mother of the fetus is diagnosed with a thyroid problem.
- The treatment which involves anti-thyroid glands also contribute to the occurrence of cretinism. 
5. Dysfunction of the pituitary gland/hypothalamus
- Occurs in 5% of cretinism patients
- Thyroid gland is not stimulated by the pituitary gland
- Hypothalamic causes of cretinism include ischemic damage, congenital defects, and tumors. [5, 6]
Prevalence of Cretinism
The population of the patients that have severe thyroid function deficiency is 1 in 4000 newborn infants, while other cases have mild or partial degrees.
In countries such as North America, Japan, Australia, and Europe, cretinism occurs in 1 in 3000 to 4000 newborns. For some unknown reason, it is more common in females than in males.
- Cretinism affects all populations.
- There is a higher prevalence at birth for Hispanic females which is 1 in 1886 births.
- For Black infants, 11 are affected with cretinism which is one third of the prevalence rate in white infants.
- Female to male ratio of cretinism is 2:1.
- Cretinism occurs approximately 12 times more in twin births than singletons.
- According to the definition of cretinism, it is a condition which may be present before or after birth. For children aged 2 years or older who developed it, it is not referred to as cretinism but as primary hypothyroidism. 
Signs and Symptoms of Cretinism
The newborn screening test is usually used by the doctors to detect the presence of cretinism or congenital hypothyroidism. This is utilized since most newborns show mild or no symptoms at birth.
- Fontanelles: Larger anterior fontanel will be noticed. Also, there is persistence of posterior fontanel.
- Low hair line, dry brittle hair
- Face: The newborn’s face looks dull, puffy, and have slow reaction.
- Macroglossia: Large tongue, thick and protruding
Picture 5: A baby with macroglossia
- Protruded belly button
- Edema: periorbital (eyelids), extremities, genitalia
- Jaundice: Yellowish discoloration of the skin
- Hypothermia: low temperature
- Hypotonia: Decreased muscle tone; “floppy baby”
Picture 6: A baby with hypotonia (Floppy baby)
- Hoarse or low cry
- Dyspnea: Difficulty of Breathing
- Cardiac problems: Bradycardia (slow pulse), heart valve abnormality
- Short stature or poor growth
- Poor Weight gain [1, 7]
- Excessive sleeping
- Decreased activity
- Poor feeding patterns
- Constipation: less frequent bowel movement
- Choking [1, 7]
1. Newborn Screening Test
- This is a screening test is used to detect the newborn for metabolic and genetic disorders. The sample is collected by obtaining a few drops of blood using the heel-prick method.
- This is done to detect the possible occurrence of these disorders to prevent physical disabilities, mental retardation, and death.
- This test is usually done in the first 24 to 72 hours of life. [7, 8]
Picture 7: How Newborn Screening Test is done
2. Measurement of TSH or thyroxine (T4)
- The sample is obtained on the second or third day of life.
- High levels of TSH and low levels of T4 confirm congenital hypothyroidism or cretinism.
- When this is the result of the test, the parents of the newborn are referred to a pediatric endocrinologist. This is for the confirmation of the diagnosis and initiation of treatment. [5, 7]
3. Imaging studies
- Technetium (Tc-99 pertechnetate) thyroid scan: This is ordered by the doctor to examine if there is the presence of structural abnormalities of the thyroid gland. This procedure will aid in differentiation if the cause is congenital absence or organification defect. Organification is the process needed to facilitate thyroid hormone production.
- X-rays: Usually, the x-rays of the baby’s legs are used. This is to show the bone ends at the knee joints. Also, from the x-ray images, the doctor can see if there are immature appearances in babies with hypothyroidism. Lastly, it aids in the diagnosis confirmation. 
The main goal of the treatment is early detection and early initiation of treatment . When the diagnosis is made early, within the first two weeks of life, the effects of this condition to the brain and nervous system can be prevented by the thyroid hormone replacement. This is because they are not yet fully developed .
- The thyroid hormone replacement involves the administration of L-thyroxine. This is a synthetic thyroid hormone which comes in tablet forms. The amount and frequency of this medication is determined by the doctor and endocrinologist. As the child grows up, the dose is gradually increased. This is to be given daily to the baby throughout his life.
- L-thyroxine is in the form of small tablets. They are crushed and added into the milk formula of the baby.
- This is also given 30 minutes prior to feeding. [1, 3]
Picture 8: L-thyroxine (Thyroid Hormone Replacement)
2. Monitoring and Evaluation
- Regular visits to the doctor are essential to examine the child’s weight, height, development, and general health. Also, it is expected that the child will be having regular blood test every one to three months until age one. This is performed to detect the thyroid hormone levels. Then, the frequency of blood tests decrease as the child reaches age three.
- Mental development monitoring: These include 4 areas to be evaluated. These are communication and personality behaviour, motor ability, adaptive behaviour, and language ability.
- Developmental growth evaluation: Formal evaluation of the child’s developmental growth is monitored continuously to provide early intervention programs. If the child shows any delays in areas of learning or speech, these programs can be arranged to provide help to the child before school age. [3, 5]
- Dietary iodide supplementation: This is particularly useful for people who are in iodine-deficient areas. Dietary iodine contributes to the prevention of brain damage in cretinism endemic areas.
- Soy-based formulas and iron medication: These can reduce the absorption of the synthetic L-thyroxine being given to the baby. [3, 4]
- This should be encouraged in children with cretinism . This is to help them in developing their motor skills.
- Early diagnosis of the disease leads to better prognosis. The newborns that are diagnosed and treated within their first month of life usually have normal intelligence.
- On the other hand, newborns which are not treated immediately or not treated at all, suffer from intellectual disability and delayed growth.
- According to some studies, some of the patients with cretinism have been found to have slight decreased performance in their IQ as well as in verbal and math. They have memory and attention deficits due to delayed diagnosis and treatment. [6, 7]
Points to Consider
Cretinism or Congenital hypothyroidism, generally, is a preventable disease. For the pregnant women who have been having treatments for their thyroid gland problems, they must be monitored closely. Also, sufficient amount of nutritional iodine should be consumed by pregnant mothers.
Keep in mind that it is very beneficial to allow the newborn to be screened using the Newborn Screening Test. Early detection and initiation of treatment can make a great difference to the baby’s future. With appropriate treatment and monitoring, mental and growth retardation can be totally prevented.
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