thyroid dyshormonogenesis 4

Thyroid Dyshormonogenesis: A Rare Condition

Thyroid dyshormonogenesis is a rare condition that affects the production of thyroid hormones in the body. It occurs when there are genetic defects in the synthesis of these hormones, leading to a deficiency or malfunctioning of the thyroid gland.

Causes and Symptoms

The condition can be caused by various genetic mutations, including those affecting the sodium-iodide symporter (NIS) gene, which is responsible for transporting iodine into the thyroid gland. This leads to a defect in the conversion of accumulated iodide to organically bound iodine, resulting in hypothyroidism.

Symptoms of thyroid dyshormonogenesis can be subtle and may include fatigue, physical or mental slowness, and difficulties in initiating or performing simple tasks. In some cases, goiter (enlargement of the thyroid gland) may also occur.

Inheritance Pattern

The mode of inheritance for all forms of thyroid dyshormonogenesis is autosomal recessive, except for DUOX2 mutations, which can be autosomal dominant. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Prevalence and Diagnosis

Thyroid dyshormonogenesis is a rare condition, with an estimated incidence of 1:67,000 in some populations. It can be diagnosed through genetic testing and measurement of thyroid hormone levels in the blood.

References

• [3] Congenital hypothyroidism is a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital).
• [5] Thyroid dyshormonogenesis continues to be a significant cause of congenital hypothyroidism.
• [6] Thyroid dyshormonogenesis-1 (TDH1) is caused by homozygous or compound heterozygous mutation in the sodium-iodide symporter (NIS) gene (SLC5A5; 601843).
• [7] A disorder due to defective conversion of accumulated iodide to organically bound iodine.
• [10] Defects in thyroid hormone synthesis (dyshormonogenesis) In about 15% of cases, the molecular mechanisms have been well defined.

Signs and Symptoms of Thyroid Dyshormonogenesis

Thyroid dyshormonogenesis, a rare condition due to genetic defects in the synthesis of thyroid hormones, can manifest in various ways. The primary signs and symptoms include:

• Hypothyroidism: A permanent thyroid hormone deficiency that is present from birth.
• Goiter: An enlargement of the thyroid gland, which can lead to difficulty swallowing or breathing.
• Poor growth and development: Affected individuals may experience delayed puberty, short stature, or other growth-related issues.

These symptoms can vary in severity and may not be immediately apparent. It's essential to note that thyroid dyshormonogenesis is a rare condition, and its signs and symptoms can be similar to those of other thyroid disorders.

Causes

Thyroid dyshormonogenesis is caused by genetic defects in the synthesis of thyroid hormones. This can result from:

• Deficiency of thyroid enzymes: A lack of essential enzymes necessary for thyroid hormone production.
• Inability to concentrate or ineffective binding: Issues with the concentration or binding of thyroid hormones, leading to a deficiency.

References

[4] Thyroid dyshormonogenesis is a rare condition due to genetic defects in the synthesis of thyroid hormones. [1] [2]

Note: The numbers in square brackets refer to the context numbers provided earlier.

Thyroid dyshormonogenesis, also known as congenital hypothyroidism due to thyroid hormone biosynthesis defects, can be diagnosed through various diagnostic tests.

• Thyroid imaging: Thyroid ultrasonography, thyroid scintigraphy or perchlorate discharge test can be used for etiological diagnosis. In thyroid dyshormonogenesis, thyroid ultrasonography shows eutopic thyroid and depending on the severity of hypothyroidism, the thyroid size may be normal or large [11].
• Thyroid radionuclide uptake and scan: This test can help pinpoint the underlying etiology, although treatment may be started without these tests. This is usually found in thyroid dyshormonogenesis where there is a defect in thyroid hormone production [12].
• Serum thyroglobulin determination: This test can also help identify the underlying cause of congenital hypothyroidism.
• Genetic testing: Genetic testing can help with making the diagnosis and can guide genetic counseling. All newborns with congenital hypothyroidism should be evaluated for birth defects such as cardiac defects and hearing loss [14].

It's worth noting that treatment with levothyroxine (L-T4) 10–15 mcg/kg should be started immediately after diagnosis without delaying for imaging purposes [13].

Treatment of Congenital Hypothyroidism

The treatment for congenital hypothyroidism, also known as thyroid dyshormonogenesis, involves administering synthetic thyroid hormone to replace the missing or defective thyroid hormone in the body.

• Levothyroxine: The most common form of thyroid hormone used for treatment is levothyroxine (T4), which is identical to the T4 produced by the thyroid gland. It is considered the best treatment option and should be started without delay.
• Starting Dose: The recommended starting dose of levothyroxine is 10-15 mcg/kg/day, with the goal of raising the serum T4 above 130 nmol/L (10 ug/dL) as rapidly as possible.

Early identification and treatment with high-dose levothyroxine have been shown to prevent irreversible developmental problems in children with congenital hypothyroidism. Treatment aims to detect the disease early and replace the thyroid hormone, preventing the development of complications such as growth retardation, hearing loss, and intellectual disability.

References:

• [4] Feb 1, 2022 - Treatment with levothyroxine (synthetic thyroid hormone, T4) should be started without delay. The dose is carefully calculated based on factors ...
• [9] Levothyroxine is the treatment of choice; the recommended starting dose is 10-15 mcg/kg/day. The immediate goals of treatment are to raise the serum T4 above ...

Differential Diagnosis of Thyroid Dyshormonogenesis

Thyroid dyshormonogenesis, a type of primary congenital hypothyroidism, can be challenging to diagnose due to its similarity with other conditions. The differential diagnosis for thyroid dyshormonogenesis includes:

• Aplastic or hypoplastic thyroid: This condition refers to the underdevelopment or absence of the thyroid gland, which can lead to congenital hypothyroidism.
• Autoimmune thyroiditis: In this condition, the immune system attacks the thyroid gland, leading to inflammation and potentially causing congenital hypothyroidism.

According to [7], these conditions should be considered in the differential diagnosis for congenital hypothyroidism. Additionally, [8] suggests that dyshormonogenesis may be suspected in an infant detected with congenital hypothyroidism and a goiter.

It's essential to note that thyroid dyshormonogenesis is a distinct condition from other forms of congenital hypothyroidism, such as thyroid dysgenesis, which accounts for the majority of cases [12]. A precise molecular diagnosis can help identify the underlying cause of congenital hypothyroidism and guide further management.

References:

[7] E Braham · 2013 · Cited by 11 [8] MV Rastogi · 2010 · Cited by 998