Transient Hypothyroidism - Causes, Symptoms, and Treatment

What Is the Thyroid Gland and What Are Thyroid Diseases?

The thyroid gland is an endocrine gland responsible for producing the thyroid hormones thyroxine (T4), triiodothyronine (T3), and calcitonin. The thyroid is a tiny endocrine gland shaped like a butterfly, which is highly vascular and located in the neck. Several conditions can lead to dysfunctioning of the thyroid gland, which in turn causes an imbalance in the thyroid hormone levels. Thyroid hormones are essential to control the body's growth, development, and metabolism. An imbalance in thyroid hormone levels causes multiple thyroid conditions. Some of the most common thyroid diseases are hyperthyroidism (overactive thyroid), hypothyroidism (underactive thyroid), goiter (lump in the thyroid gland), thyroiditis (inflammation of the thyroid gland), etc.

What Is Hypothyroidism?

Hypothyroidism is also referred to as an underactive thyroid because it is a medical condition in which the thyroid gland does not synthesize enough thyroid hormones for the body to function efficiently. Hypothyroidism can cause several symptoms, including intolerance to cold temperatures, tiredness, fatigue, constipation, decreased heart rate, depression, and unusual weight gain. In some cases, the patient may also develop a swelling or lump in the neck known as goiter. Hypothyroidism can occur due to various reasons, but iodine deficiency remains the leading cause of hypothyroidism in developing countries. Moreover, Hashimoto’s thyroiditis is the prevalent cause of hypothyroidism in developed countries (countries with sufficient iodine supply in their daily diet).

What Is Transient Hypothyroidism?

Transient hypothyroidism or transient congenital hypothyroidism refers to a condition in which a newborn baby has abnormally low thyroid hormone levels at birth. However, this condition is temporary, and the thyroid hormone levels eventually stabilize. After birth, low thyroxine (T4) and increased thyrotropin (TSH or thyroid stimulating hormone) are signs of transient hypothyroidism. This condition later improves to better thyroxine production, usually in the initial months of infancy. Since transient hypothyroidism is a temporary and self-limiting condition, it may or may not require thyroid hormone replacement therapy.

Is Transient Hypothyroidism a Common Condition?

• According to newborn screening programs, 17 to 40 percent of children who were first diagnosed with congenital hypothyroidism actually had transient hypothyroidism.

• In North America, 5 to 10 percent of children who test positive for congenital hypothyroidism during mass screenings have transient congenital hypothyroidism.

• Transient congenital hypothyroidism is more common in certain geographic and racial groups than others.

Causes Transient Hypothyroidism

The causes of transient hypothyroidism include:

• Iodine Deficiency: The deficiency of iodine is a frequent cause of transient hypothyroidism reported globally. Iodine is crucial for producing thyroid hormones; therefore, iodine deficiency frequently leads to hypothyroidism. The mother's iodine status primarily influences iodine stores in the fetus and newborn during pregnancy and by the iodine concentration of breast milk or formula after birth. Due to low in-utero thyroidal iodine stores, immaturity of the hypothalamic-pituitary axis for producing thyroid hormones, and impaired capacity to convert thyroxine (T4) to metabolically active triiodothyronine (T3), preterm infants are notably vulnerable to the consequences of iodine deficiency.

• Thyrotropin Receptor Blocking Antibodies: Thyrotropin receptor blocking antibodies or TRBAbs develop in women affected by autoimmune thyroid disorders. These antibodies have the ability to pass through the placenta and stop the thyroid-stimulating hormone receptor in the developing baby's thyroid gland. After birth, transient hypothyroidism caused by TRBAbs can last for three to six months.

• Exposure to Anti-thyroid Drugs: Anti-thyroid medications, such as Propylthiouracil or Methimazole, might cross the placenta and reduce the fetus's ability to produce thyroid hormone for a few days to two weeks after delivery.

• Fetal Iodine Exposure: The use of Amiodarone during pregnancy may result in a transient hypothyroid condition in babies. This may subside in about five months, but there may be detrimental neurologic effects. It has been reported that pregnant women with increased intake of iodine or too much iodine from nutritional supplements will have babies with transient hypothyroidism. The kind and duration of exposure might be related to the risk of hypothyroidism.

• Neonatal Iodine Exposure: Due to the Wolff-Chaikoff effect, neonatal exposure to excessive iodine levels can result in hypothyroidism. Premature babies are particularly susceptible to this.

• Genetic Mutations: Mutations that induce loss of function in the DUOX2 and DUOXA2 genes result in transient hypothyroidism. These genes are crucial for the production of hydrogen peroxide. This hydrogen peroxide is needed by thyroid peroxidase to produce thyroid hormones.

What Are the Symptoms of Transient Hypothyroidism?

Common signs and symptoms of transient hypothyroidism are:

• Typically, even in infants with thyroid agenesis, the clinical symptoms and signs of transient hypothyroidism do not appear during the neonatal period. Instead, they develop gradually over a few weeks.

• In neonates with some functional thyroid issues, the symptoms can appear after months or years.

• Reduced variability in fetal heart rate tracing patterns is markedly and independently correlated with transient hypothyroidism.

• Lethargy and tiredness.

• Inactive baby.

• Hypotonia or loss of muscle tone.

• Swelling around the eyes (periorbital edema).

• Bluish discoloration around the mouth (perioral cyanosis).

• Mottled skin.

• Hypothermia (extremely low body temperature).

• Pale skin.

• Difficulty in feeding.

• Prolonged jaundice.

• Constipation.

• Difficulty in breathing.

• Nasal stuffiness.

• Low blood pressure (hypotension).

• Anemia.

• Abdominal distension.

How to Differentiate Between Transient and Permanent Congenital Hypothyroidism?

• In the neonatal period, it is difficult to clinically distinguish between permanent and temporary forms of congenital hypothyroidism.

• The existence of an ectopic thyroid gland, the absence of the thyroid gland on ultrasonography, an initial thyroid-stimulating hormone level of greater than 100 mIU/ml, and various pituitary hormone deficits are the few clinical indicators that suggest congenital hypothyroidism is permanent.

• If these clinical symptoms are absent, then a diagnosis of transient congenital hypothyroidism can be proposed, especially if risk factors are present.

How Is Transient Hypothyroidism Diagnosed?

• Thyroid Function Test: Thyroid function testing, including TSH and free T4 levels, should be carried out for neonates with abnormal newborn screen results.

• Thyroid Imaging: This test can reveal the underlying cause, such as thyroid dysgenesis. In case of transient hypothyroidism due to lack of iodine, these tests will show increased radionuclide uptake in thyroid tissues.

• X-rays: Approximately 50 percent of newborns with primary hypothyroidism exhibit a delay in bone development. A neonate with absent proximal or distal femoral epiphyses may not have enough intrauterine thyroid hormone.

• Thyroid Antibodies: Useful for diagnosis in families where a previous sibling has been found to have congenital hypothyroidism and in newborns born to mothers with known autoimmune thyroid conditions.

How Is Transient Hypothyroidism Treated?

Transient hypothyroidism in newborns should be treated cautiously because untreated infants have serious repercussions. A population-specific strategy is beneficial when there is a higher frequency of autosomal recessive illnesses, a lack of iodine supplementation, or a lack of prenatal screening and testing.

• The baby should be started on thyroxine till age three if free thyroxine (FT4) is low or thyroid-stimulating hormone (TSH) remains higher than five milli-international unit per mililiter (mIU/ml) on repeated testing within the first month of life. This will protect the brain development of the baby. The development of the brain is negatively impacted by persistent TSH rise.

• Maintaining the serum thyroxine (T4) or free thyroxine (FT4) level in the upper half of the reference range during infancy, along with a serum TSH in the reference range therapy, helps in normal growth and brain development of the baby.

Conclusion

In neonates, thyroid function disorders should be evaluated cautiously. When dealing with a neonate suffering from abnormal thyroid function tests, the treating physician should be most concerned about the potential effects of undertreatment on brain development. However, the need for continuing thyroid hormone replacement medication in children being treated for congenital hypothyroidism at the age of three should constantly be reevaluated if treatment is initiated based on suspicion and there is no solid evidence of permanent congenital hypothyroidism.